The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9)
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Established cell cultures that have the potential to propagate indefinitely.
Elements of limited time intervals, contributing to particular results or situations.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
Conceptual response of the person to the various aspects of death, which are based on individual psychosocial and cultural experience.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The process by which chemical compounds provide protection to cells against harmful agents.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Transport proteins that carry specific substances in the blood or across cell membranes.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Glycoproteins found on the membrane or surface of cells.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
All deaths reported in a given population.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Postmortem examination of the body.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
Diseases of plants.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A condition of decreased oxygen content at the cellular level.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The action of a drug in promoting or enhancing the effectiveness of another drug.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Refers to animals in the period of time just after birth.
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
Proteins prepared by recombinant DNA technology.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
An infant during the first month after birth.
An inhibitory T-lymphocyte receptor that has specificity for CD274 ANTIGEN and PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN. Signaling by the receptor limits T cell proliferation and INTERFERON GAMMA synthesis. The receptor also may play an essential role in the regulatory pathway that induces PERIPHERAL TOLERANCE.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed)
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A diazo-naphthalene sulfonate that is widely used as a stain.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A compound obtained from the bark of the white willow and wintergreen leaves. It has bacteriostatic, fungicidal, and keratolytic actions.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.

Low resting potential and postnatal upregulation of NMDA receptors may cause Cajal-Retzius cell death. (1/11751)

Using in situ patch-clamp techniques in rat telencephalic slices, we have followed resting potential (RP) properties and the functional expression of NMDA receptors in neocortical Cajal-Retzius (CR) cells from embryonic day 18 to postnatal day 13, the time around which these cells normally disappear. We find that throughout their lives CR cells have a relatively depolarized RP (approximately -50 mV), which can be made more hyperpolarized (approximately -70 mV) by stimulation of the Na/K pump with intracellular ATP. The NMDA receptors of CR cells are subjected to intense postnatal upregulation, but their similar properties (EC50, Hill number, sensitivity to antagonists, conductance, and kinetics) throughout development suggest that their subunit composition remains relatively homogeneous. The low RP of CR cells is within a range that allows for the relief of NMDA channels from Mg2+ blockade. Our findings are consistent with the hypothesis that CR cells may degenerate and die subsequent to uncontrolled overload of intracellular Ca2+ via NMDA receptor activation by ambient glutamate. In support of this hypothesis we have obtained evidence showing the protection of CR cells via in vivo blockade of NMDA receptors with dizocilpine.  (+info)

Ischemic tolerance in murine cortical cell culture: critical role for NMDA receptors. (2/11751)

Murine cortical cultures containing both neurons and glia (days in vitro 13-15) were exposed to periods of oxygen-glucose deprivation (5-30 min) too brief to induce neuronal death. Cultures "preconditioned" by sublethal oxygen-glucose deprivation exhibited 30-50% less neuronal death than controls when exposed to a 45-55 min period of oxygen-glucose deprivation 24 hr later. This preconditioning-induced neuroprotection was specific in that neuronal death induced by exposure to excitotoxins or to staurosporine was not attenuated. Neuroprotection was lost if the time between the preconditioning and severe insult were decreased to 7 hr or increased to 72 hr and was blocked if the NMDA antagonist 100 microM 3-((D)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid was applied during the preconditioning insult. This was true even if the duration of preconditioning was increased as far as possible (while still remaining sublethal). A similar preconditioning effect was also produced by sublethal exposure to high K+, glutamate, or NMDA but not to kainate or trans-1-aminocyclopentane-1, 3-dicarboxylic acid.  (+info)

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB. (3/11751)

The developing cerebral cortex undergoes a period of substantial cell death. The present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in cerebral cortical development. Fas mRNA and protein are transiently expressed in subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE-inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD, RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-kappaB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL-expressing) cells and that Fas may have functions in addition to suicide in the developing brain.  (+info)

Microvessels from Alzheimer's disease brains kill neurons in vitro. (4/11751)

Understanding the pathogenesis of Alzheimer's disease is of widespread interest because it is an increasingly prevalent disorder that is progressive, fatal, and currently untreatable. The dementia of Alzheimer's disease is caused by neuronal cell death. We demonstrate for the first time that blood vessels isolated from the brains of Alzheimer's disease patients can directly kill neurons in vitro. Either direct co-culture of Alzheimer's disease microvessels with neurons or incubation of cultured neurons with conditioned medium from microvessels results in neuronal cell death. In contrast, vessels from elderly nondemented donors are significantly (P<0.001) less lethal and brain vessels from younger donors are not neurotoxic. Neuronal killing by either direct co-culture with Alzheimer's disease microvessels or conditioned medium is dose- and time-dependent. Neuronal death can occur by either apoptotic or necrotic mechanisms. The microvessel factor is neurospecific, killing primary cortical neurons, cerebellar granule neurons, and differentiated PC-12 cells, but not non-neuronal cell types or undifferentiated PC-12 cells. Appearance of the neurotoxic factor is decreased by blocking microvessel protein synthesis with cycloheximide. The neurotoxic factor is soluble and likely a protein, because its activity is heat labile and trypsin sensitive. These findings implicate a novel mechanism of vascular-mediated neuronal cell death in Alzheimer's disease.  (+info)

Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome. (5/11751)

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (6/11751)

We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability.  (+info)

Elevated expression of the CD4 receptor and cell cycle arrest are induced in Jurkat cells by treatment with the novel cyclic dinucleotide 3',5'-cyclic diguanylic acid. (7/11751)

The effect of the novel, naturally occurring nucleotide cyclic diguanylic acid (c-di-GMP) on the lymphoblastoid CD4+ Jurkat cell line was studied. When exposed to 50 microM c-di-GMP, Jurkat cells exhibited a markedly elevated expression of the CD4 receptor of up to 6.3-fold over controls. C-di-GMP also causes blockage of the cell cycle at the S-phase, characterized by increased cellular thymidine uptake, reduction in G2/M-phase cells, increase in S-phase cells and decreased cell division. Additionally c-di-GMP naturally enters these cells and binds irreversibly to the P21ras protein. The effects described appear to be unique for c-di-GMP.  (+info)

Glutamate receptor signaling interplay modulates stress-sensitive mitogen-activated protein kinases and neuronal cell death. (8/11751)

Glutamate receptors modulate multiple signaling pathways, several of which involve mitogen-activated protein (MAP) kinases, with subsequent physiological or pathological consequences. Here we report that stimulation of the N-methyl-D-aspartate (NMDA) receptor, using platelet-activating factor (PAF) as a messenger, activates MAP kinases, including c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated kinase, in primary cultures of hippocampal neurons. Activation of the metabotropic glutamate receptor (mGluR) blocks this NMDA-signaling through PAF and MAP kinases, and the resultant cell death. Recombinant PAF-acetylhydrolase degrades PAF generated by NMDA-receptor activation; the hetrazepine BN50730 (an intracellular PAF receptor antagonist) also inhibits both NMDA-stimulated MAP kinases and neuronal cell death. The finding that the NMDA receptor-PAF-MAP kinase signaling pathway is attenuated by mGluR activation highlights the exquisite interplay between glutamate receptors in the decision making process between neuronal survival and death.  (+info)

Initiating discussions about fungal cell death is challenged by the lack of a vocabulary with generally agreed-upon definitions. The definition of programmed cell death also holds layers of complexity. The concept of physiological cell death arose in the 19th and 20th centuries when investigators observed the systematic disappearance of cells in various developing animal models (8). With the discovery of lysosomes in 1955 (9), some researchers in the cell death field became occupied with the idea that leakage of hydrolases from these suicide bags was to blame, while others argued that unleashed hydrolases were a consequence rather than a cause of cell death (10). These ideas have been revisited and extended more recently both in human disease (11) and in yeast cell death (12).. In pursuit of the components that control developmental cell death, Richard Lockshin and his PhD adviser Carroll Williams at Harvard published a series of papers in 1964 to 1965 applying the term programmed cell ...
Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferropto …
TY - JOUR. T1 - Nitric oxide-GAPDH-Siah. T2 - a novel cell death cascade.. AU - Hara, Makoto R.. AU - Snyder, Solomon H. PY - 2006/7. Y1 - 2006/7. N2 - 1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extremely abundant glycolytic enzyme, and exemplifies the class of proteins with multiple, seemingly unrelated functions. Recent studies indicate that it is a major intracellular messenger mediating apoptotic cell death. This paper reviews the GAPDH cell death cascade and discusses its clinical relevance. 2. A wide range of apoptotic stimuli activate NO formation, which S-nitrosylates GAPDH. The S-nitrosylation abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah, an E3-ubiquitin-ligase, which translocates GAPDH to the nucleus. In the nucleus, GAPDH stabilizes the rapidly turning over Siah, enabling it to degrade selected target proteins and affect apoptosis. 3. The cytotoxicity of mutant Huntingtin (mHtt) requires nuclear translocation which appears to be ...
The concept of programmed cell death has evolved over the years to include both apoptotic and non-apoptotic death mechanisms. This study describes a novel form of non-apoptotic cell death induced as a result of dysregulated macropinocytosis. We have named this cell death methuosis. Methuosis is observed when the activated form of Ras GTPase is over-expressed in glioblastoma cells. It is accompanied by the accumulation of large phase-lucent cytoplasmic vacuoles, followed by rounding up, detachment, and disintegration of the cells. The vacuoles quickly take up extracellular fluid-phase tracers, a hallmark of macropinosomes. Our studies also show that the Ras-induced vacuoles are not acidic and are negative for LC3-II (a marker for autophagosomes), transferrin and EEA1 (endosomal markers). These observations rule out the vacuoles originating from autophagosomal, endosomal or lysosomal compartments. Even though caspase activation is observed in dying cells, death is not prevented by zVAD-fmk, a ...
In the context of pulmonary infection, both hosts and pathogens have evolved a multitude of mechanisms to regulate the process of host cell death. The host aims to rapidly induce an inflammatory response at the site of infection, promote pathogen clearance, quickly resolve inflammation, and return to tissue homeostasis. The appropriate modulation of cell death in respiratory epithelial cells and pulmonary immune cells is central in the execution of all these processes. Cell death can be either inflammatory or anti-inflammatory depending on regulated cell death (RCD) modality triggered and the infection context. In addition, diverse bacterial pathogens have evolved many means to manipulate host cell death to increase bacterial survival and spread. The multitude of ways that hosts and bacteria engage in a molecular tug of war to modulate cell death dynamics during infection emphasizes its relevance in host responses and pathogen virulence at the host pathogen interface. This narrative review outlines
Animals and plants diverged over one billion years ago and evolved unique mechanisms for many cellular processes, including cell death. One of the most well-studied cell death programmes in animals, apoptosis, involves gradual cell dismantling and engulfment of cellular fragments, apoptotic bodies, through phagocytosis. However, rigid cell walls prevent plant cell fragmentation and thus apoptosis is not applicable for executing cell death in plants. Furthermore, plants are devoid of the key components of apoptotic machinery, including phagocytosis as well as caspases and Bcl-2 family proteins. Nevertheless, the concept of plant
It has been described that in mammalian cells, growth and integrity are directly influenced by changes in cell membrane composition occurring when PtdCho biosynthesis has been perturbed by mutations, inhibition, or nutrient deficiency (Cui et al., 1996). We also found that the reduced primary root growth in XPL1 Arabidopsis mutants is related to a 50% reduction in cell elongation. Because PEAMT plays a pivotal role in the PtdCho biosynthetic pathway in plants, reduced root growth and epidermal cell death in xipotl could also be because of perturbation in the synthesis of PtdCho in the root meristem. However, the observation that PA can alleviate cell death suggests that some of cellular phenotypes observed in xipotl are not because of a direct effect in the reduction of PtdCho levels (Figure 9).. Cell death has been classified into physiological cell death and nonphysiological cell death (Vaux and Korsmeyer, 1999). Physiological cell death refers to the process of programmed cell death, in which ...
TY - JOUR. T1 - Programmed cell death in fission yeast. AU - Rodriguez-Menocal, Luis. AU - DUrso, Gennaro. N1 - Funding Information: We would like to thank Bill Burhans and Frank Madeo for valuable discussions. G.D. is supported by NIH1R01CA099034-01. L.R.M is supported by a post-doctoral fellowship from the American Heart Association.. PY - 2004/11. Y1 - 2004/11. N2 - Recently a metacaspase, encoded by YCA1, has been implicated in a primitive form of apoptosis or programmed cell death in yeast. Previously it had been shown that over-expression of mammalian pro-apoptotic proteins can induce cell death in yeast, but the mechanism of how cell death occurred was not clearly established. More recently, it has been shown that DNA or oxidative damage, or other cell cycle blocks, can result in cell death that mimics apoptosis in higher cells. Also, in fission yeast deletion of genes required for triacylglycerol synthesis leads to cell death and expression of apoptotic markers. A metacaspase sharing ...
Different cell-death mechanisms control many physiological and pathological processes in humans. Mitochondria play important roles in cell death through the release of pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor (AIF), which activate caspase-dependent and caspase-independent cell death, respectively. Poly(ADP-ribose) polymerase 1 (PARP-1) is emerging as an important activator of caspase-independent cell death. PARP-1 generates the majority of long, branched poly(ADP-ribose) (PAR) polymers following DNA damage. Overactivation of PARP-1 initiates a nuclear signal that propagates to mitochondria and triggers the release of AIF. AIF then shuttles from mitochondria to the nucleus and induces peripheral chromatin condensation, large-scale fragmentation of DNA and, ultimately, cytotoxicity. Identification of the pro-death and pro-survival signals in the PARP-1-mediated cell-death program might provide novel therapeutic targets in human diseases.
bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic cell death was evident in postmitotic immature neurons of the developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells in the liver were also apoptotic. Analyses of bcl-x double-knockout chimeric mice showed that the maturation of Bcl-x-deficient lymphocytes was diminished. The life-span of immature lymphocytes, but not mature lymphocytes, was shortened. Thus, Bcl-x functions to support the viability of immature cells during the development of the nervous and hematopoietic systems. ...
TY - JOUR. T1 - Activation of caspase-8 and Erk-1/2 in domes regulates cell death induced by confluence in MDCK cells. AU - Chang, Yung Heng. AU - Lin, Hsi Hui. AU - Wang, Yang Kao. AU - Chiu, Wen Tai. AU - Su, Hsiao Wen. AU - Tang, Ming Jer. PY - 2007/4/1. Y1 - 2007/4/1. N2 - Under normal culture conditions, cells adhere to culture dish, spread out, proliferate, and finally cover all areas and reach confluence. During the confluent stage, cell proliferation ceases and differentiation is enhanced. Meanwhile, cell death also appears as the monolayer confluence proceeds. To delineate the mechanism of cell death induced by the confluent process, we employed Madin-Darby canine kidney (MDCK) cells. When approaching confluence, MDCK cells exhibited increase the levels of caspase-2 and enhanced the activity of caspase-8. Using various caspase inhibitors to block apoptosis, we found that only z-VAD-fmk and z-IETD-fmk can inhibit confluent cell death, indicating that confluent cell death is mediated by ...
BACKGROUND: High levels of ex vivo CD4 T-cell death and the accumulation of highly differentiated and/or immunosenescent T cells have been associated with poor CD4 T-cell recovery in treated HIV-infected individuals. However, the relationship between cell death and T-cell differentiation is still unclear. METHODS: We have analyzed cell death, immunosenescence and differentiation parameters in HAART-treated subjects (VL |50 copies/mL for more than 2 years) with CD4 T-cell count |350 cells/μL (immunodiscordant, n = 23) or |400 cells/μL (immunoconcordant, n = 33). We included 11 healthy individuals as reference. RESULTS: As expected, suboptimal CD4 T-cell recovery was associated with low frequencies of naïve cells, high frequencies of transitional and effector memory cells and a subsequent low ratio of central/transitional memory cells in the CD4 compartment. These alterations correlated with spontaneous CD4 T-cell death. A deeper analysis of cell death in CD4 T-cell subsets showed increased cell death
The life/death decisions in the cell are controlled by the balance between apoptotic and anti-apoptotic signaling pathways such as DNA repair. Despite the fact these pathways have been studied relatively well, their quantitative regulation until recently has been poorly understood. This situation has dramatically changed in the last years. Creation of mathematical models of apoptotic and non-apoptotic signaling pathways led to an enormous progress in the quantitative understanding of the network regulation and provided fascinating insights into the mechanisms of life/death control. Moreover, it led to the identification of targets within the cell death networks followed by the drug discovery. In this Research topic, the computational models of apoptotic and non-apoptotic signaling and their biological implications will be addressed. Central attention will be given to the cross-talk between cell death and DNA repair pathways defining cell fate. Additionally, we also welcome methodology-related
Bax inhibitor-1 (BI-1) was initially identified for its ability to inhibit BAX-induced apoptosis in yeast cells and is the founding member of a family of highly hydrophobic proteins localized in diverse cellular membranes. It is evolutionarily conserved and orthologues from plants can substitute for …
Programmed Cell Death Pcd Plays Pivotal Roles In Tumor Progression Cancer Therapeutics And Resistance Of Tumor Cells To Therapy With The Discovery Of Key Mechanisms That Are Involved In Mediating Pcd And In Promoting Resistance To Therapy Design Of Therapeutic Approaches For Promoting Tumor Selective Cell Death Has Risen Dramatically
Cell death and differentiation is a monthly research journal focused on the exciting field of programmed cell death and apoptosis. It provides a single accessible source of information for both scientists and clinicians, keeping them up-to-date with advances in the field. It encompasses programmed cell death, cell death induced by toxic agents, differentiation and the interrelation of these with cell proliferation.
Cel-lu-lar deci-sions to live or die are fun-da-men-tal to devel-op-ment and adult home-osta-sis, play-ing roles in a wide vari-ety of phys-i-o-log-i-cal and patho-log-i-cal processes. These include can-cer, degen-er-a-tive dis-ease, innate and adap-tive immu-nity, ischemia-​reperfusion injury, and infec-tious disease. Over the past decades, the fun-da-men-tal mol-e-c-u-lar mech-a-nisms under-ly-ing one form of cell death, apop-to-sis, have been largely defined. Other forms of cell death, such as pro-grammed necro-sis or autophagic cell death, are not as well understood. In this meet-ing, the path-ways that impact on a cells deci-sion to live or die will be pre-sented in the con-text of phys-i-ol-ogy and dis-ease, and ways to influ-ence that deci-sion ther-a-peu-ti-cally will be explored. The con-se-quence of cell death for the body is also of great inter-est, as the clear-ance of dying cells impacts on other phys-i-o-log-i-cal processes. ...
Ferroptosis is a non-apoptotic form of regulated cell death. It is distinct from other regulated cell death phenotypes, such as apoptosis and necroptosis. Ferroptosis is characterized by extensive lipid peroxidation, which can be suppressed by iron chelators or lipophilic antioxidants. Mechanistically, Ferroptosis inducers are divided into two classes: (1) inhibitors of cystine import via system xc− (e.g., Erastin), which subsequently causes depletion of glutathione (GSH), and (2) covalent inhibitors (e.g., (1S, 3R)-RSL3) of glutathione peroxidase 4 (GPX4). Since GPX4 reduces lipid hydroperoxides using GSH as a co-substrate, both compound classes ultimately result in loss of GPX4 activity, followed by elevated levels of lipid reactive oxygen species (ROS) and consequent cell death. Ferroptosis is an iron- and ROS-dependent form of regulated cell death (RCD). Misregulated Ferroptosis has been implicated in multiple physiological and pathological processes, including cancer cell death, ...
Cell death has been recognized in the cardiovascular system for centuries. In Virchows 1858 lectures, he described atherosclerosis as producing new tissue, followed by cell death: Thus, we have here an active process which really produces new tissues, but then hurries on to destruction in consequence of its own development.1 Degraded and dying cells are found in both myocardial infarction and in atherosclerosis, and until the last 20 years were classified as necrosis. Death was considered a passive phenomenon due to ischemic or other insult, resulting in cell membrane dissolution and leakage of proinflammatory contents. The consequences of cell death resulted from loss of the function of the live cells and subsequent inflammation.. This scenario changed with the description of apoptosis in the 1970s,2 and the subsequent detailed description of the mechanisms underlying this form of programmed cell death. The presence of apoptosis in atherosclerotic plaques has been confirmed by a number of ...
The robust and rapid induction of innate immune signaling is a hallmark of the host response to microbial infection. Successful pathogens subvert, thwart, or dismantle these defensive measures. Growing evidence suggests that the host recognizes these disruptive efforts, eliciting effective backup measures. Cell death processes, including apoptosis and pyroptosis, are integral components of the host response to infection. Multiprotein inflammasome complexes sense the presence of pathogens and activate inflammatory caspases, typically caspase-1 or caspase-11, leading to pyroptotic cell death and maturation of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Pyroptosis is an inflammasome-driven cytotoxic process that occurs in macrophages after limited proteolysis of gasdermin D (GSDMD). The generation of an N-terminally cleaved fragment then creates large oligomeric membrane pores and causes lytic cell death (1-7). At present, caspase-1 and caspase-11 are the only known regulators of ...
SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinsons disease. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Sortilin (∼95 kDa) is a member of the recently discovered family of Vps10p-domain receptors, and is expressed in a variety of tissues, notably brain, spinal cord and muscle. It acts as a receptor for neurotensin, but predominates in regions of the nervous system that neither synthesize nor respond to this neuropeptide, suggesting that sortilin has additional roles. Sortilin is expressed during embryogenesis in areas where nerve growth factor (NGF) and its precursor, proNGF, have well-characterized effects. These neurotrophins can be released by neuronal tissues, and they regulate neuronal development through cell survival and cell death signalling. NGF regulates cell survival and cell death via binding to two different receptors, TrkA and p75NTR (ref. 10). In contrast, proNGF selectively induces apoptosis through p75NTR but not TrkA. However, not all p75NTR-expressing cells respond to proNGF, suggesting that additional membrane proteins are required for the induction of cell death. Here we report that
TY - JOUR. T1 - Role of apoptosis in pancreatic β-cell death in diabetes. AU - Chandra, Joya. AU - Zhivotovsky, Boris. AU - Zaitsev, Sergei. AU - Juntti-Berggren, Lisa. AU - Berggren, Per Olof. AU - Orrenius, Sten. PY - 2001. Y1 - 2001. N2 - Apoptosis is a physiological form of cell death that occurs during normal development, and critical mediators of this process include caspases, reactive oxygen species, and Ca2+. Excessive apoptosis of the pancreatic β-cell has been associated with diabetes. Consequently, apoptosis research has focused on how infiltrating macrophages or cytotoxic T-cells might kill pancreatic β-cells using cytokines or death receptor triggering. Meanwhile, the intracellular events in the target β-cell have been largely ignored. Elucidation of such targets might help develop improved treatment strategies for diabetes. This article will outline recent developments in apoptosis research, with emphasis on mechanisms that may be relevant to β-cell death in type 1 and type 2 ...
Near East University Experimental Health Sciences Research Center (DESAM) board members and doctoral students represented our country in collaboration with the Marmara University, Genetic and Metabolic Diseases Research and Application Center (GEMHAM) and Cell Death Research Association (HÖAD) at...
BOC lecture - 7 Cell Death 1. The Biology of Cancer Chapter 9: p53 and Apoptosis: Master Guardian and Executioner Cell Death 2. Apoptosis Autophagy Necrosis Programmed cell death. Death cycle is programmed by the cell itself Self-eating Catabolic process involving lysosomes.
DESCRIPTION (provided by applicant): The reduction of oxygen occurring as a result of advanced vascular diseases poses severe clinical problems including massive cell death and resultant tissue loss. Compared to pharmacological methods of therapeutic angiogenesis, cell-based strategies represent a direct approach to generate a capillary network. Endothelial colony forming cells (ECFCs) are a subpopulation of endothelial progenitor cells that exhibit robust angiogenic potential under hypoxic conditions and can form functional vascular networks in vivo. Adipose- derived stem cells (ASCs) are a promising cell population for promoting angiogenesis and potentially stabilizing new vessels. However, the success of cell-based therapies is limited by rapid cell death due to apoptosis upon implanting cells into ischemic tissue environments, dramatically reducing the number of cells available to participate in vasculogenesis. Additionally, recent data suggest that cells derived from older donors are more ...
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nunez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G (2012). Molecular definitions of cell death subroutines: recommendations of the Nomencla- ture Committee on Cell Death 2012.Cell Death Differ 19, 107-120. ...
Although the antitumor properties of cannabinoids were first observed more than 30 years ago, when Munson et al (27) demonstrated that Δ9-tetrahydrocannabinoid (THC) inhibits lung adenocarcinoma cell growth in vivo, the elucidation of mechanisms employed by cannabinoids for influencing cancer cell proliferation and death was developed in the last two decades. However, there are still many obscure sides on death pathways activated by these compounds and, in particular, on the different contribution of apoptosis and autophagy in cell death.. The anticancer potential of this class of compounds can be very different in the various tumor systems. This depends on the mechanism used by cannabinoids to interact with the cells, i.e. the class of receptors to which they bind or on the specific intracellular activated pathways.. Regarding the interaction with the target cell, it has been demonstrated that cannabinoids can interact with the specific type 1 or 2 cannabinoid receptors (CB1 and CB2), which ...
Ren, Y.; Lv, Q.; Yue, W.; Liu, B.; Zou, Z., 2019: The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases
Cell death and Differentiation provides an accessible source of up-to-date information for scientists and clinicians. It covers programmed cell death, cell death induced by toxic agents, differentiation and their relation to cell proliferation.
Death receptors are activated, for example, in the case of infections when white blood cells that have combatted a virus are to be removed. It was previously known that death receptors in the blood can be measured, but not whether an elevated level was linked to increased cell death in type 2 diabetes and arteriosclerosis. The aim of the study was therefore to investigate whether death receptors could be used as a marker that could be linked to ongoing tissue damage and if this could be used to predict the risk of developing diseases. The results show that increased cell death can be linked to increased levels in the blood of three different members of the same death receptor family (TNFR-1, TRAILR-2 and Fas). Increased cell death is seen in type 2 diabetes as well as arteriosclerosis. High blood sugar and blood fats (low levels of HDL, the good cholesterol) subject the bodys blood vessels and insulin-producing beta cells to stress. Long-term stress damages the cells and can cause the ...
Cell Death and Immunity symposium will provide a unique opportunity to bring together researchers in the cell death and immunology communities, as well as scientists studying host-pathogen interactions, who are focused on understanding the molecular and cellular mechanisms that link cell death and the immune response.. Visit the website to know more.
Cell Death and Immunity symposium will provide a unique opportunity to bring together researchers in the cell death and immunology communities, as well as scientists studying host-pathogen interactions, who are focused on understanding the molecular and cellular mechanisms that link cell death and the immune response.. Visit the website to know more.
BioAssay record AID 729817 submitted by ChEMBL: Induction of apoptosis in human DG75 cells assessed as cell death at 2.5 uM after 24 hrs by flow cytometry (Rvb = 0.8 +/- 0.25%).
Billions of cells in our body die every day. Damaged, infected or superfluous cells are thus disposed of to keep our bodies healthy. It is thought that most of these cells die by a process called apoptosis. However, we have shown that cells in the breast, following lactation, do not die by apoptosis but by a novel mechanism that requires organelles called lysosomes. These tend to be thought of as cellular waste bins since they digest cellular components and recycle them. However, we have discovered that during regression of the breast, enzymes called cathepsins leak out of the lysosomes into the cell and induce a process that we call lysosomal-mediated programmed cell death (LM-PCD). This is the first time that this type of cell death has been shown to occur in a normal mammalian organism. Furthermore, we have shown that a transcription factor, Stat3, that is often associated with breast cancer, is responsible for executing LM-PCD as it induces high levels of cathepsins while suppressing ...
Originally aired: Wednesday, December 6, 2017. The mechanisms of cell death play a fundamental role in neurodegenerative disorders such as Alzheimers disease, Parkinsons disease, and Huntingtons disease. Caspase activity, cathepsin activity, and oxidative stress all contribute to cell death in the forms of apoptosis, pyroptosis, and necrosis. ICT offers a reliable and accurate line of fluorescent reagents to help neuroscience researchers detect cell death in their samples using flow cytometry, fluorescence microscopy, or a fluorescence plate reader. In this webinar, we will discuss different types of cell death, the role of cell death in neurodegenerative diseases, and methods to assess cell death in cell cultures.. ...
Big Pharma has been accused of selling drugs that are so dangerous they cause death and drugs that cause the. some direct toxicity that causes death or
My lab is interested in understanding the mechanisms by which normal and malignant cells regulate programmed cell death. Multicellular organisms have devised a tightly regulated, genetically programmed mechanism of cell suicide to maintain homeostasis and to prevent propagation of genetically damaged cells. The discovery of the BCL-2 family of genes uncovered the underlying genetic mechanism of this regulation, as well as a class of oncogenes that governs cell death rather than cell proliferation. There are two major pathways that regulation programmed cell death: apoptosis and programmed necrosis. Simply, apoptotic cells implode in a relatively immune silent manner. Necrotic cells explode, releasing cellular contents and inciting an immune response- beneficial in settings of infection, but detrimental in settings of chronic damage, where the inflammation elicited by necrotic cell death amplifies cellular damage. Current studies focus on how programmed cell death regulates homeostasis in
Purpose: TUNEL assay is widely used to evaluate cell death. Quantification of TUNEL-positive (TUNEL+) cells in tissue sections is usually performed manually, ideally by two masked observers. This process is time consuming, prone to measurement errors, and not entirely reproducible. In this paper, we describe an automated quantification approach to address these difficulties. Methods: We developed an ImageJ macro to quantitate cell death by TUNEL assay in retinal cross-section images. The script was coded using IJ1 programming language. To validate this tool, we selected a dataset of TUNEL assay digital images, calculated layer area and cell count manually (done by two observers), and compared measurements between observers and macro results. Results: The automated macro segmented outer nuclear layer (ONL) and inner nuclear layer (INL) successfully. Automated TUNEL+ cell counts were in-between counts of inexperienced and experienced observers. The intraobserver coefficient of variation (COV) ...
Of all the Hallmarks of Cancer defined by Hanahan and Weinberg, the ability to proliferate indefinitely is often considered to be the most central to cancers core features. Sustaining Growth and Resisting Cell Death enable cancer cells to override signaling that ensures normal tissues homeostasis of numbers and size. Previous chapters in our mini-series on Hypoxia and the Hallmarks of Cancer have showcased Avoiding Immune Destruction and Tumor Promoting Inflammation and Genome Instability and Mutation and Enabling Replicative Immortality as well as Inducing Angiogenesis and Activating Invasion and Metastasis.. In part four of our mini-series describing Hypoxia and the Hallmarks of Cancer, we look more closely at how researchers are using the HypOxystation to delineate the Hallmarks Sustaining Growth and Resisting Cell Death. The HypOxystation creates a cell culture environment that mimics authentic conditions for cancer research with regard to oxygen, CO2, temperature, and humidity. ...
TY - JOUR. T1 - Connexin 43 channels protect osteocytes against oxidative stress-induced cell death. AU - Kar, Rekha. AU - Riquelme, Manuel A.. AU - Werner, Sherry. AU - Jiang, Jean X.. PY - 2013/7. Y1 - 2013/7. N2 - The increased osteocyte death by oxidative stress (OS) during aging is a major cause contributing to the impairment of bone quality and bone loss. However, the underlying molecular mechanism is largely unknown. Here, we show that H2O2 induced cell death of primary osteocytes and osteocytic MLO-Y4 cells, and also caused dose-dependent decreased expression of gap junction and hemichannel-forming connexin 43 (Cx43). The decrease of Cx43 expression was also demonstrated with the treatment of other oxidants, rotenone and menadione. Antioxidant reversed the effects of oxidants on Cx43 expression and osteocyte cell death. Cx43 protein was also much lower in the osteocytes from 20-month-old as opposed to the 5-week-old or 20-week old mice. Dye transfer assay showed that H2O2 reduced the gap ...
(−)-Epigallocatechin-3-gallate (EGCG) is the most extensive studied tea polyphenol for its anti-cancer function. In this study, we report a novel mechanism of action for EGCG-mediated cell death by identifying the critical role of lysosomal membrane permeabilization (LMP). First, EGCG-induced cell death in human cancer cells (both HepG2 and HeLa) was found to be caspase-independent and accompanied by evident cytosolic vacuolization, only observable when cells were treated in serum-free medium. The cytosolic vacuolization observed in EGCG-treated cells was most probably caused by lysosomal dilation. Interestingly, EGCG was able to disrupt autophagic flux at the degradation stage by impairment of lysosomal function, and EGCG-induced cell death was independent of Atg5 or autophagy. The key finding of this study is that EGCG is able to trigger LMP, as evidenced by Lyso-Tracker Red staining, cathepsin D cytosolic translocation and cytosolic acidification. Consistently, a lysosomotropic agent, chloroquine,
TY - JOUR. T1 - How Do Cardiomyocytes Die? Apoptosis and Autophagic Cell Death in Cardiac Myocytes. AU - Kunapuli, Sanjay. AU - Rosanio, Salvatore. AU - Schwarz, Ernst R.. PY - 2006/6/1. Y1 - 2006/6/1. N2 - Background: Cell death constitutes one of the key events in biology. Historically, apoptosis and necrosis have been considered to represent the 2 fundamental forms of cell death. Apoptosis is a tightly regulated, energy-dependent process in which cell death follows a programmed set of events. Necrosis refers to the sum of degenerative changes that follow any type of cell death. Methods and Results: The role of apoptosis in development of ischemic heart disease, hypertensive heart disease, and end-stage heart failure has been well documented. Recent evidence suggests the potential role of a third mechanism of cell death, autophagy, in loss of cardiac myocytes. Autophagic cell death has been recently documented in myocardial cells from hypertrophied, failing, and hibernating myocardium. ...
P2X7 is an ATP-gated ion channel that is highly expressed by leukocytes, such as macrophages. Here, it has been demonstrated to be involved in the regulation of various cell death pathways; including apoptosis, pyroptosis, necrosis, and autophagy. However, cell death induction via P2X7 is complex and is reliant upon the nature of the stimulus, the duration of the stimulus, and the cell type investigated. Previous reports state that high extracellular ATP concentrations promote osmotic lysis, but whether positive allosteric modulation of P2X7 in the presence of lower concentrations of ATP condemns cells to the same fate is unknown. In this study, we compared cell death induced by high ATP concentrations, to cell death induced by compound K, a recently identified and potent positive allosteric modulator of P2X7. Based on our observations, we propose that high ATP concentrations induce early cell swelling, loss of mitochondrial membrane potential, plasma membrane rupture, and LDH release. ...
Programmed cell death (or apoptosis) is usually an evolutionarily conserved, genetically controlled suicide mechanism for cells that, when deregulated, can lead to developmental defects, cancers, and degenerative diseases [1, 2]. for germ cell death. We confirmed this initial observation by performing a dose-response analysis of the deletion mutant. In contrast to wild-type animals, deletion mutants did not exhibit an increase in germ cell apoptosis after exposure to increasing doses of IR (Physique?1C; see also Figure?S1 available online). This was reminiscent of loss-of-function (lf) mutants that are also resistant to IR-induced apoptosis. Therefore, we examined whether regulates germ cell death specifically, like and mutants. We found that developmental cell death was unaffected in mutants, suggesting that the rules of cell death by is usually specific to germ cells, like (Physique?1D). Finally, to determine whether the allele is usually a null, we performed a deficiency analysis by crossing ...
Programmed cell death (PCD) is a deliberate cellular suicide process. Dysfunction of PCD is implicated in various human diseases, including developmental and neurodegenerative disorders, cancer and autoimmune diseases [1]. PCD can be categorized by morphological criteria [2]. Type I cell death, known as apoptosis, is characterized by cell shrinkage, nuclear condensation, membrane blebbing, mitochondria dysfunction, loss of selectivity in membrane permeabilization, and nuclear DNA fragmentation. Lastly, cells are rapidly eliminated by phagocytosis [3]. Type II PCD refers to autophagic cell death (ACD). Autophagy is a catabolic process that disposes of various cytoplasmic components, including protein aggregates and organelles [4]. The components are sequestered by autophagosomes, which fuse with lysosomes for degradation. This process usually occurs in response to cellular stress to protect the cells. However, prolonged autophagy can cause ACD [5]. Type III cell death, called necrosis, is best ...
Hot pepper is one of the economically important crops in Asia. A large number of gene sequences, including expressed sequence tag (EST) and genomic sequences are publicly available. However, it is still a daunting task to determine gene function due to difficulties in genetic modification of a pepper plants. Here, we show the application of the virus-induced gene silencing (VIGS) repression for the study of 459 pepper ESTs selected as non-host pathogen-induced cell death responsive genes from pepper microarray experiments in Nicotiana benthamiana. Developmental abnormalities in N. benthamiana plants are observed in the 32 (7%) pepper ESTs-silenced plants. Aberrant morphological phenotypes largely comprised of three groups: stunted, abnormal leaf, and dead. In addition, by employing the combination of VIGS and Agrobacterium-mediated transient assays, we identified novel pepper ESTs that involved in Bax or INF1-mediated cell death responses. Silencing of seven pepper ESTs homologs suppressed Bax or INF1
The p38 mitogen-activated protein kinase (p38 MAPK) family, which is comprised of four protein isoforms, p38α, p38β, p38γ and p38δ, forms one of the key MAPK pathways. The p38 MAPKs are implicated in many cellular processes including inflammation, differentiation, cell growth, cell cycle and cell death. The function of p38 MAPKs in mitotic entry has been well established, but their role in mitotic progression has remained controversial. We identify p38γ MAPK as a modulator of mitotic progression and mitotic cell death. In HeLa cells, loss of p38γ results in multipolar spindle formation and chromosome misalignment, which induce a transient M phase arrest. The majority of p38γ-depleted cells die at mitotic arrest or soon after abnormal exit from M-phase. We show that p38 MAPKs are activated at the kinetochores and spindle poles throughout mitosis by kinase(s) that are stably bound to these structures. Finally, p38γ is required for the normal kinetochore localization of polo-like kinase 1 ...
Molecular deletion of transglutaminase 2 (TG2) has been shown to improve function and survival in a host of neurological conditions including stroke, Huntingtons disease, and Parkinsons disease. However, unifying schemes by which these cross-linking or polyaminating enzymes participate broadly in neuronal death have yet to be presented. Unexpectedly, we found that in addition to TG2, TG1 gene expression level is significantly induced following stroke in vivo or due to oxidative stress in vitro. Forced expression of TG1 or TG2 proteins is sufficient to induce neuronal death in Rattus norvegicus cortical neurons in vitro. Accordingly, molecular deletion of TG2 alone is insufficient to protect Mus musculus neurons from oxidative death. By contrast, structurally diverse inhibitors used at concentrations that inhibit TG1 and TG2 simultaneously are neuroprotective. These small molecules inhibit increases in neuronal transamidating activity induced by oxidative stress; they also protect neurons ...
Autophagy is a process in which cells digest their own organelles and proteins in response to nutritional starvation. Yu et al. describe a form of cell death that bears similarities to autophagy. Unlike apoptosis, which depends on activation of proteases in the caspase family, autophagic cell death in a mouse cell line was actually inhibited by caspase-8. Inhibition of expression of two genes known to function in autophagy, ATG7 and beclin 1, reduced cell death caused by inhibition of caspase-8. These findings could impact strategies for combating unwanted apoptosis that use caspase inhibitors to prevent cell death.. L. Yu, A. Alva, H. Su, P. Dutt, E. Freundt, S. Welsh, E. H. Baehrecke, M. J. Lenardo, Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304, 1500-1502 (2004). [Abstract] [Full Text]. ...
TY - JOUR. T1 - Therapeutic implications of disorders of cell death signalling. T2 - membranes, micro-environment, and eicosanoid and docosanoid metabolism. AU - Davidson, Jillian. AU - Rotondo, D. AU - Rizzo, Maria. AU - Leaver, Anne. PY - 2012/6/6. Y1 - 2012/6/6. N2 - Disruptions of cell death signalling occur in pathological processes, such as cancer and degenerative disease. Increased knowledge of cell death signalling has opened new areas of therapeutic research, and identifying key mediators of cell death has become increasingly important. Early triggering events in cell death may provide potential therapeutic targets, whereas agents affecting later signals may be more palliative in nature. A group of primary mediators are derivatives of the highly unsaturated fatty acids (HUFAs), particularly oxygenated metabolites such as prostaglandins. HUFAs, esterified in cell membranes, act as critical signalling molecules in many pathological processes. Currently, agents affecting HUFA metabolism ...
TY - JOUR. T1 - The wound response in fresh-cut lettuce involves programmed cell death events. AU - Iakimova, Elena T.. AU - Woltering, Ernst J.. PY - 2018/7. Y1 - 2018/7. N2 - In this work, the involvement of programmed cell death (PCD) in the wound-induced postharvest browning disorder and senescence in butterhead lettuce (Lactuca sativa L.) fresh-cuts was studied. At the wounded (cut, bruised) sites, rapid browning, loss of chlorophyll and massive cell death, accompanied with accumulation of reactive oxygen species and increased electrolyte leakage occurred in a narrow strip of tissue adjacent the injury. The dead cell morphology (protoplast and nuclei shrinkage) together with the biochemical and physiological changes resembled necrotic PCD type. With a slight delay post-wounding, senescence associated with similar cell death features was initiated in distant non-wounded sites. In addition to necrotic PCD, both in wounded and senescing tissue, the appearance of empty cell corpses was ...
At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis. Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs. Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C.) diluted with normal saline at E12. To analyze the cell death, we
Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces profound oxidative injury and neuronal cell death. It mimics ischemia-reperfusion neuronal injury. CPI-1189 is a novel tumor necrosis factor alpha-inhibiting compound with potential neuroprotective function. Here in SH-SY5Y neuronal cells and primary murine cortical neurons, CPI-1189 pretreatment potently inhibited OGDR-induced viability reduction and cell death. In OGDR-stimulated neuronal cells, p38 phosphorylation was blocked by CPI-1189. In addition, CPI-1189 alleviated OGDR-induced reactive oxygen species production, lipid peroxidation, and glutathione consumption. OGDR-induced neuronal cell apoptosis was also inhibited by CPI-1189 pretreatment. Furthermore, in SH-SY5Y cells and cortical neurons, CPI-1189 alleviated OGDR-induced programmed necrosis by inhibiting mitochondrial p53-cyclophilin D-adenine nucleotide translocase 1 association, mitochondrial depolarization, and lactate dehydrogenase release to the medium. In summary, CPI-1189
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, or may result from such factors as disease, localized injury, or the death of the organism of which the cells are part. Kinds of cell death include the following: Programmed cell death (or PCD) is cell death mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organisms life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and metazoa (multicellular animals) tissue development. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or ...
Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1. CAMK1 and the demethylase PPME1 were required for the subsequent demethylation and inactivation of the catalytic subunit of the phosphatase PP2A (PP2Ac) and the phosphorylation of RIPK1. Plasma membrane depolarization, PP2Ac demethylation, and cell death were prevented by glucose and, unexpectedly, by its nonmetabolizable analog 2-deoxy-d-glucose (2-DG), a glycolytic inhibitor. These findings reveal a previously unknown function of glucose as a ...
Most schemes for TGs role in acute and chronic neurodegeneration have centered around the ability of these enzymes to cross-link mutated and/or accumulated proteins in a host of diseases, including AD, HD, and PD (Caccamo et al., 2010). And while this model unifies diseases associated with proteotoxicity, it fails to account for the benefits of molecular or pharmacological TG deletion in ischemic (Hwang et al., 2009; Colak et al., 2011) or hemorrhagic stroke (Okauchi et al., 2009). Indeed, exciting new data on the role of TG in autophagosome formation (DEletto et al., 2009), in inhibiting axonal transport of growth factors such as BDNF (Borrell-Pagès et al., 2006), in repressing adaptive gene expression (McConoughey et al., 2010), and on influencing nuclear actin dynamics (Munsie et al., 2011) have focused attention on biological roles of these fascinating enzymes other than cross-linking. Here, we demonstrate that TG is a necessary component of oxidative stress-induced death signaling in ...
During development, large numbers of cells die by a nonpathological process referred to as programmed cell death. In many tissues, dying cells display similar changes in morphology and chromosomal DNA organization, which has been termed apoptosis. Apoptosis is such a widely documented phenomenon that many authors have assumed all programmed cell deaths occur by this process. Two well-characterized model systems for programmed cell death are (i) the death of T cells during negative selection in the mouse thymus and (ii) the loss of intersegmental muscles of the moth Manduca sexta at the end of metamorphosis. In this report we compare the patterns of cell death displayed by T cells and the intersegmental muscles and find that they differ in terms of cell-surface morphology, nuclear ultrastructure, DNA fragmentation, and polyubiquitin gene expression. Unlike the T cells, which are known to die via apoptosis, we find that the intersegmental muscles display few of the features that characterize ...
BNIP3 is a cell death-inducing mitochondrial protein that is part of a Bcl-2 subfamily with NIX and ceBNIP3. BNIP3-induced cell death morphologically resembles necrosis that is characterized by rapid plasma membrane damage and mitochondrial dysfunction in the early stages, followed by DNA fragmentation and chromatin condensation characteristic of apoptotic cell death in the later stages. DNA fragmentation during most types of apoptosis is predominantly due to caspase-3 activation. However, BNIP3-induced cell death is independent of caspase-3 activity, thus the mechanism of BNIP3-induced DNA fragmentation remains unknown. Co-immunoprecipitation analysis revealed an interaction between BNIP3, NIX, and caspase-2. The interaction is unique in that it is not mediated through the caspase-2 prodomain. Caspases-1, -8, and -9, which have homologous prodomains to caspase-2, do not bind BNIP3 or NIX, indicating specificity for caspase-2. Further structural analysis indicated that the transmembrane domain ...
Cell death can occur through 3 mechanisms: apoptosis, autophagy, and necrosis. Apoptosis, or programmed cell death, results in controlled cell shrinkage and nuclear fragmentation via the action of caspases, as well as an anti-inflammatory cytokine release. In contrast, necrosis signals via RIPK1 (RIP1), leading to cell swelling, lysis, and a pro-inflammatory cytokine release. Autophagy destroys the cells damaged proteins and organelles via an intracellular catabolic process in the lysosome. Multiple physiological processes require the removal of specific cells by a controlled cell-death program. For example, tissue remodeling activates apoptosis, whereas energy metabolism and growth regulation responses rely on autophagy. Developmental processes often activate apoptosis, while bodily injuries or infection more commonly induce necrosis. The molecular mechanisms behind these cell death pathways overlap, and can be co-activated during some cellular functions. Apoptosis and necrosis both signal ...
FIG. 2. Dose- and time-dependent effects of SERCA inhibition on CHOP expression, caspase-3 activation, and cell death. Cell death was assayed in real-time by propidium iodide incorporation in MIN6 cells. A: Images illustrating the progressive propidium iodide incorporation in a field of MIN6 cells exposed to 1 μmol/l thapsigargin (Tg). B: Representative time course of cell death in response to various concentrations of thapsigargin. ○, Control; ▪, 0.01 μmol/l thapsigargin; ▴, 0.1 μmol/l thapsigargin; •, 1 μmol/l thapsigargin. C: Dose dependence of the thapsigargin-induced MIN6 cell death, quantified as the area under the curves (IAUC) of the first 24 h of the propidium iodide incorporation profiles (n = 3). D: Induction of CHOP (∼31-kDa band) and cleaved caspase-3 (∼17- to 19-kDa band) in MIN6 cells cultured for 24 h in DMEM containing 25 mmol/l glucose and increasing concentrations of thapsigargin (n = 3). E: Representative real-time imaging of caspase-3 activation in living ...
The present study aimed to investigate anti-proliferative and apoptotic effects of quercetin on human leukemia cells and effects of quercetin-induced cell death on a nov..
Programmed cell death (or PCD) is the death of a cell in any form, mediated by an intracellular program. PCD is carried out in a biological process, which usually confers advantage during an organisms life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development. Apoptosis and autophagy are both forms of programmed cell death, but necrosis was long seen as a non-physiological process that occurs as a result of infection or injury. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Recently a form of programmed necrosis, called necroptosis, has been recognized as an alternate form of programmed cell death. It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is ...
Excitotoxic cell death, the end for many cells after ischemic brain injury and in some neurodegenerative diseases, is triggered by glutamate-induced calcium influx. Downstream, activation of the p38α map kinase leads to apoptosis, but just how calcium and p38 connect has been an open question. New results from Michael Courtneys lab at the University of Kuopio in Finland show that the small GTPase Rho is the missing link. Their work, published in the March 18 online edition of Nature Neuroscience, establishes Rho activation by calcium influx as a necessary and sufficient event to turn on p38 and cause cell death in primary neurons.. Their results open up a potential new target for drugs to block excitotoxicity, and may have some additional relevance to Alzheimer disease. Inhibitors of Rho and its downstream kinase Rock can modulate amyloid-β (Aβ) peptide production (Zhou et al., 2003; Leuchtenberger et al., 2006). In addition, Rho is farnesylated, and changes in Rho/Rock pathway activity have ...
Cell death is not only an essential phenomenon in normal development and homeostasis, but also crucial in various pathologies. It is now clear that many types of cell death can be regulated by pharmacological or genetic interventions. These were largely achieved by identifying the molecular mechanisms underlying the regulated cell death (RCD). While in the immune system, RCD needs to be facilitated to help the clearance of pathogens and tumors, in healthy cells, especially the terminally differentiated neurons in the nervous system, it is more desirable to protect cells from dying due to stress under pathological conditions. Thus, understating the inhibitory and the activating signals for RCD in different systems is important. In this thesis, I will discuss the study of two key molecules involved in RCD: programmed death 1 (PD-1, as inhibitor for RCD) and serine/threonine kinase receptor interaction protein 3 (RIP3, as promoter for RCD) in two different systems. First, I studied the role of PD-1
Dive into the research topics of Neuronal death in amyotrophic lateral sclerosis is apoptosis: Possible contribution of a programmed cell death mechanism. Together they form a unique fingerprint. ...
Although it is well established that IFNγ causes cell death in a variety of cell types (Deiss et al., 1995; Ossina et al., 1997; Wen et al., 1997; Ruiz-Ruiz et al., 2000; Trautmann et al., 2000; Horiuchi et al., 2006), the signal transduction downstream of STAT1 remains largely unknown (Barber, 2000). Unraveling the role of IFNγ in apoptosis remains a challenge because IFNγ may prime cells to apoptosis and through induction of many genes can concomitantly elicit an antiproliferative and a proliferative state (Xiang et al., 2008). The decision between life and death may depend on possible costimuli or the cell type. Enhanced expression and translocation of Diablo into the cytosol play a critical role in the promotion of IFNγ-induced apoptosis of IFNγ-sensitive B cells (Yoshikawa et al., 2001). Th1 cells that secrete high levels of IFNγ are more susceptible to activation-induced cell death than Th2 cells because Th2 cells express Fas-associated phosphatase, FAP-1 (Zhang et al., 1997). In ...
03.05.2016 The Gutenberg Research College (GRC) of Johannes Gutenberg University Mainz (JGU) has chosen to give the 2016 Gutenberg Research Award to American biomedical researcher Dr. Vishva Dixit for his groundbreaking work in the field of programmed cell death. His findings have contributed significantly to the understanding of the actual mechanisms involved in the crucial process that is also known as apoptosis. At the same time, Dixit is also helping to convert the information obtained into a form that can be employed in clinical applications. In the person of Dr. Vishva Dixit, the Gutenberg Research College is bestowing the Gutenberg Research Award on an internationally acclaimed top-level researcher. His groundbreaking findings on cell death have provided important clues that help us understand in much more detail the processes associated with the immune system, emphasized the Director of the Gutenberg Research College, Professor Matthias Neubert. Programmed cell death is actually a ...
TY - JOUR. T1 - Comparative analysis of the role of small G proteins in cell migration and cell death. T2 - Cytoprotective and promigratory effects of RalA. AU - Jeon, Hyejin. AU - Zheng, Long Tai. AU - Lee, Shinrye. AU - Lee, Won Ha. AU - Park, Nammi. AU - Park, Jae-Yong. AU - Heo, Won Do. AU - Lee, Myung Shik. AU - Suk, Kyoungho. PY - 2011/1/1. Y1 - 2011/1/1. N2 - Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with ...
Balakireva A. V., Zamyatnin Jr A. A. Cutting out the gaps between proteases and programmed cell death // Frontiers in plant science. - 2019. - Vol. 10. - P. 704. To date, many animal models for programmed cell death (PCD) have been extensively characterized and classified while such efforts in plant types of PCD still remain poorly understood. However, despite a wide range of functional differences between PCD types in animals and plants, it is certain that all of them are regulated through the recruitment of proteases. Most importantly, proteases are able to perform proteolysis that results in a gain or loss of protein function. This principle relies on the presence of proteolytic cascades where proteases are activated upon various upstream stimuli and which lead to repetitive cell death. While protease activation, proteolytic cascades and targeted substrates are described in detail mainly for nematode, human, and mice models of apoptosis, for plants, only fragmentary knowledge of protease ...
Finland Deaths Stats, NationMaster. Retrieved from Finland Deaths Stats, NationMaster. 1948-2012. ,,.. Finland Deaths Stats, NationMaster, ,, [assessed 1948-2012]. Finland Deaths Stats, NationMaster [Internet]. 1948-2012. Avaliable from: ,,.. Finland Deaths Stats, NationMaster. Avaliable at: Assessed 1948-2012.. Finland Deaths Stats, NationMaster, (assessed 1948-2012). Finland Deaths Stats, NationMaster, (last visited 1948-2012). Finland Deaths Stats, NationMaster, (as ...
Scale?bars denote 50 m. Open in a separate window Figure 7 Correlation among cell death, nitric oxide (NO) and autophagy in tobacco BY-2 cells after 24 h of toxin (AaT) exposure. After 24 h, AaT facilitated Ca2+ influx with an accumulation of reactive oxidant intermediates and NO, to manifest necrotic cell death. Inhibition of NO accumulation by 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) decreased the level of necrotic cell death, and induced autophagy, which suggests NO accumulation represses autophagy and facilitates necrotic cell death at 24 h. Application of N-acetyl-L-cysteine at 3 h, 666-15 confirmed ROS to be the key initiator of autophagy, and together with cPTIO for 24 h, revealed the combined effects of NO and ROS is required for necrotic HR cell death. and plants with silenced or knocked-out (Fr.) Keissler causes a serious worldwide depletion of economic yield30. In (tobacco), the pathogen has been reported to inculcate lethal symptoms like anthracnose, ...
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Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstream signaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. ...
During development of the nervous system, as many as half of all neurons generated are ultimately eliminated by a process known as programmed cell death. Much of this cell death occurs as newly differentiated neurons compete for limiting amounts of survival-promoting neurotrophic factors. Though counterintuitive, the selective death of neurons at specific times during development is critical for sculpting a properly wired nervous system. While programmed cell death is essential for normal development, too much or too little cell death later in life is a confounding factor in diseases ranging from Alzheimers disease and stroke to brain cancer. Research in the Freeman laboratory is aimed at characterizing the mechanisms that regulate cell death in the mammalian nervous system. More specifically, we aim to identify and understand the critical cell signaling events that, if left unchecked, commit a neuron to die ...
JUPITER, FL - January 27, 2015 - In a pair of related studies, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown their drug candidates can target biological...
1. Lipid-induced cell death - Investigation of the mechanism leading to lipotoxicity. 2. Meiotic Processes within the regulation of aging - characterization of the mechanism leading to longevity in yeast and mammalian cells. 3. Autophagy (self-eating) in dying cells - Interconnection of apoptosis and autophagy via a new Bcl-2 family-protein. 4. Identification of a novel yeast caspase - Functional analysis of the raptor- protein regarding the regulation of autophagy and apoptosis. 5. Yeast as a model for neurodegeneration - Parkinson´s, Alzheimer`s, and Huntington`s disease. 6. Caspase independent regulation of cell death - implications of apoptosis-inducing factor AIF1 and its interactom in aging and apoptosis. Contact: Prof. Dr. Frank Madeo. ...
Drug resistance has been mostly explained by molecular changes, such as overexpression of p-glycoprotein or O6-methylguanine-DNA-methyltransferase, which interfere with drug actions on the targets (1 , 2) . Because most anticancer agents, regardless of their diverse targets, exert effects by inducing apoptosis via activation of apoptotic pathways common to many cellular stresses, any antiapoptotic changes disrupting the common intrinsic pathways to execute physiological cell death can also make malignant cells resistant to chemotherapy (3) . Such alterations opposing apoptosis are routinely observed in malignant tumors, including both the functional loss of tumor suppressors p53, Bax, or PTEN and deregulated hyperfunction of oncogenic proteins, such as Ras, Bcl-2, and PI3K 2 ,(3) .. In tumor cells with an aberrantly activated PI3K/Akt survival pathway, the increased antiapoptotic signals overcome apoptotic signals of anticancer drugs, confer drug resistance on the tumor cells, and result in a ...
Cells of the Monocyte / Macrophage lineage are key players in innate and adaptive immunity. They eliminate pathogens through their phagocytic and antimicrobial properties, secretion of inflammatory and immunoregulatory cytokines, as well as their capacity to present foreign antigens to T lymphocytes in lymphoid tissues. The importance of M/Ms in the immune response require them to undergo strict regulation, which occurs, at least in part, through the control of monocytic cell survival. Autophagy is a ubiquitous cellular process by which cells degrade intracellular, cytoplasmic components via a network of interconnected vacuoles to carry out a variety of functions. Autophagy typically functions in maintaining cellular homeostasis and mitigating stresses. However, more recent studies have shown that autophagy may play a role in cell death. Our laboratory has previously found that the cytokine IFNγ can induce cell death in human monocytes in an autophagy-dependent manner. Conversely, IL-10 ...
Inflammasome Lab researchers, Associate Professor Kate Schroder and Dr Dave Boucher, are looking forward to the 2nd Japan Australia Meeting on Cell Death, in Tokyo 22-23 May 2018.
Roscoff, May 17th, 2021. SeaBeLife, a pharmaceutical company focused on identifying a new class of drug candidates able to deprogram regulated cell death, announces its second seed money fundraising with several Business Angels networks.. The companys disruptive technology is based on inhibiting simultaneously two kinds of necrotic cell deaths. The therapeutic potential is major because simultaneous activation has been recently pointed as an explanation for acute pathologies, which have limited therapeutic options and are notoriously hard to treat.. In particular SeaBeLife has confirmed the promising in vivo preliminary results obtained in 2020 for two indications: acute renal failure and liver failure. Beyond acute pathologies, SeaBeLife is also looking into chronical diseases such as Parkinsons, Alzheimers, or AMD (retinal degeneration). Encouraging preliminary results were generated in vitro for all these three chronic indications. The team is presently performing in vivo ...
Extensive programmed cell death (PCD) occurs in the developing nervous system. Neuronal death occurs, at least in part, because neurons are produced in excess during development and compete with each other for the limited amounts of the survival-promoting trophic factors secreted by target tissues. Neuronal death is apoptotic and utilizes components that are conserved in other PCD pathways. In this review, we discuss the mechanism of trophic factor-dependent neuronal cell death by focusing on the pathway of nerve growth factor (NGF) deprivation-induced sympathetic neuronal death. We describe the biochemical and genetic events that occur in NGF-deprived sympathetic neurons undergoing PCD. Participation of the Bcl-2 family of proteins and the interleukin-1β-converting enzyme family of proteases (caspases) in this and other models of neuronal death is also examined. The order and importance of these components during NGF deprivation-induced sympathetic neuronal death are discussed.. ...
The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues.[3]. Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis. These forms of cell death are important for protecting an organism from stress signals and pathogenic attack. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. These are signalling molecules that allow recruitment of immune cells to an infected cell or tissue. There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon ...
Mitochondrial regulation of cell death: a phylogenetically conserved control - Mitochondria are fundamental for eukaryotic cells as they participate in critical catabolic and anabolic pathways. Moreover, mitochondria play a key role in the signal transduction cascades that precipitate many (but not all) regulated variants of cellular demise. In this short review, we discuss the differential implication of mitochondria in the major forms of regulate cell death.
Cellular decisions to live or die are fundamental to development and adult homeostasis, playing roles in a wide variety of physiological and pathological processes. These include cancer, degenerative disease, innate and adaptive immunity, ischemia-reperfusion injury, and infectious disease. As the study of cell death moves beyond the central mechanisms of apoptosis to wider issues of regulation and other forms of cell death, this vibrant area of research widens its influence and importance for human health and disease.
The MAP kinase p38 is activated by noncanonical BMP signaling, and also by cellular stress, with p38 activity providing a second readout of intrinsic and extrinsic function. If Gdf6a promotes apoptosis by increasing cell stress, upregulated p38 activity would be observed in mutants, while the converse would occur if p38 is a mediator of Gdf6a signaling. Compared with gdf6a+/+ siblings (Fig. 4A), gdf6a−/− embryos exhibit markedly increased ocular p38 MAP kinase phosphorylation assessed with whole-mount IHC using phospho-specific (Thr180/Tyr182) p38 MAP kinase antibodies (Fig. 4B). If such increased levels of phosphorylated-p38 MAP kinases activate apoptosis, inhibition of this kinase would be expected to rescue the gdf6a −/− cell death phenotype. To test this, we applied a pharmacologic inhibitor of p38 MAP kinase (SB203580 [60 μM]) to zebrafish embryos and examined apoptosis using caspase-3 IHC. Treatment with SB203580 partially inhibits the increased ocular caspase-3 activation of ...
Introduction. Sydney Brenner, Robert Horvitz and John Sulstons discoveries concerning the genetic regulation of organ development and programmed cell death have truly opened new avenues for biological and medical research. We have all begun our lives in a seemingly modest way - as the fertilized egg cell, a tenth of a millimeter in size. From this small cell, the adult human being develops, with its hundred thousand billion cells, through cell division, cell differentiation and by formation of the various organs. To only make new cells is however not sufficient, certain cells must also die at specific time points as a natural part of the growth process. Think for example about how we for a short period during fetal life have web between our fingers and toes, and how this is removed by cell death.. The importance of cell differentiation and organ development was understood by many, but progress was slow. This was largely an effect of our complexity, with the large number of cells and many cell ...
A method of detection and quantification of miRNA free of specific cells of cells, tissue and / or organs in the body fluid for the evaluation of cell death in vivo in different tissues and organs, where in vivo cell death is associated with a disorder of a specific tissue and / or organ comprising: the analysis of a sample of body fluid selected from blood, serum and urine obtained from a subject to determine one or more specific miRNA sequences, wherein said analysis comprises the step of detecting said miRNA with a primer and / or probe that is substantially complementary to a portion of said specific miRNA sequences.
Intra-cellular processes: cell motility and division; cell death; intra-cellular transport; secretion. Extra-cellular processes ... Metabolism: Anabolic and catabolic processes; cell maintenance and homeostasis; secondary metabolism. ... inter-, extr-cellular processes like cell adhesion; organismal process like blood clotting or the immune system. General: ...
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... age Oxidative stress Phenoptosis Plant senescence Programmed cell death Regenerative medicine Rejuvenation SAGE KE Stem cell ... In many organisms, there is asymmetric cell division, e.g. a stem cell dividing to produce one stem cell and one non-stem cell ... cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated. There is negligible ... activation of oncogenes and cell-cell fusion, independent of telomere length. Senescent cells within a multicellular organism ...
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Ceramide mediates many cell-stress responses, including the regulation of programmed cell death (apoptosis) and cell aging ( ... whereby the cells differentiated into white blood cells called macrophages. Treatment of the same cells by exogenous Sph caused ... This results in a substantial decrease in insulin responsiveness (i.e. to glucose) and in the death of insulin-producing cells ... Obeid, L. M., Linardic, C. M., Karolak, L. A. & Hannun, Y. A. (1993) Programmed cell death induced by ceramide. Science. 259, ...
Cell Death & Disease. 2 (4): e140. doi:10.1038/cddis.2011.22. PMC 3122055. PMID 21472003. Lawson AP, Long MJ, Coffey RT, Qian Y ... "Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated ... Diindolylmethane is a strong androgen antagonist in human prostate cancer cells". The Journal of Biological Chemistry. 278 (23 ...
... virus replication and protection from cell death require ER stress (PERK) pathway activation". Cell Death & Disease. 7 (e2127 ... PERK dimerizes with BiP in resting cells and oligomerizes in ER-stressed cells. Although this is traditionally the accepted ... This also produces translational attenuation of the protein machinery involved in running the cell cycle, producing cell cycle ... Cell. 75 (4): 717-28. doi:10.1016/0092-8674(93)90492-9. PMID 7902213. Brewer JW, Diehl JA (November 2000). "PERK mediates cell- ...
Cell Death & Differentiation. 18 (6): 1057-70. doi:10.1038/cdd.2010.181. PMC 3131941. PMID 21252914. Liotta LA, Mandler R, ... In addition, GPI is secreted exclusively by tumor cells and not normal cells. For these reasons, GPI inhibitors may be a safer ... Neuroleukin also acts as a lymphokine secreted by T cells stimulated by lectin. It induces immunoglobulin secretion in B cells ... "Autocrine motility factor/phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release". ...
"Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure". Cell Cycle. 10 (22): 3938-47. doi: ... Cell Death Differ. 18 (6): 974-84. doi:10.1038/cdd.2010.164. PMC 3131937. PMID 21233845. Huang X, Xu S, Gao J, Liu F, Yue J, ... Chen T, Wu B (October 2011). "miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells". Int. J. Mol ... "MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and ...
January 2009). "Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009". Cell Death ... The maturing neutrophil will condense its nucleus into several connected lobes that stay in the cell until the end of its cell ... a red blood cell) and the neutrophil (a type of white blood cell). The maturing metarubricyte (a stage in RBC maturation) will ... Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or ...
"The role of phosphatidylserine in recognition of apoptotic cells by phagocytes". Cell Death Differ. 5 (7): 551-62. doi:10.1038/ ... During programmed cell death a protein called a scramblase equilibrates this distribution, displaying phosphatidylserine on the ... These vesicles fuse with the cell membrane at the pre-synaptic terminal and release its contents to the exterior of the cell. ... These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and ...
Cell Death Differ. 17 (1): 68-77. doi:10.1038/cdd.2009.84. PMC 2818775. PMID 19557014. Rotin D, Kumar S (Jun 2009). " ... "Patch-clamp studies on epithelial sodium channels in salivary duct cells". Cell Biochem. Biophys. 36 (2-3): 105-13. doi:10.1385 ... "Androgens differentially regulate the expression of NEDD4L transcripts in LNCaP human prostate cancer cells". Mol. Cell. ... Cell. 36 (3): 457-68. doi:10.1016/j.molcel.2009.09.043. PMC 2796330. PMID 19917253. Zhang Y, Ding Y, Chen YG, Tao Q (Aug 1, ...
Cell Death Differ. 18 (11): 1702-10. doi:10.1038/cdd.2011.28. PMC 3190106. PMID 21455217. Kulkarni S, Savan R, Qi Y, Gao X, ... Haflidadóttir BS, Bergsteinsdóttir K, Praetorius C, Steingrímsson E (2010). "miR-148 regulates Mitf in melanoma cells". PLOS ... "Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control human mesenchymal stem cell phenotype via EPAS1 ... "miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression ...
... an essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death". Cell Death ... Huang G, Chen Y, Lu H, Cao X (2007). "Coupling mitochondrial respiratory chain to cell death: ... Cytogenet Cell Genet. 82 (1-2): 115-9. doi:10.1159/000015082. PMID 9763677. S2CID 46818955. Mao M, Fu G, Wu JS, Zhang QH, Zhou ... hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning". Proc Natl Acad Sci U S ...
Cell Death Dis. 5 (3): e1153. doi:10.1038/cddis.2014.118. PMC 3973230. PMID 24675471. v t e. ... Cell. 25 (6): 917-31. doi:10.1016/j.molcel.2007.02.017. PMID 17386267. Rizvi F, Shukla S, Kakkar P (2014). "Essential role of ...
Cell Death Dis. 6 (3): e1697. doi:10.1038/cddis.2015.58. PMC 4385936. PMID 25789972. Liang L, Deng L, Chen Y, Li GC, Shao C, ... "Replication protein A stimulates proliferating cell nuclear antigen-dependent repair of abasic sites in DNA by human cell ... Cell. 7 (6): 1221-31. doi:10.1016/s1097-2765(01)00272-6. PMID 11430825. Chai Q, Zheng L, Zhou M, Turchi JJ, Shen B (Dec 2003 ... Cell. 4 (6): 1079-85. doi:10.1016/S1097-2765(00)80236-1. PMID 10635332. Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, ...
Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R (May 2009). "Mitochondria, calcium and cell death: a deadly ... Filadi R, Pendin D, Pizzo P (February 2018). "Mitofusin 2: from functions to disease". Cell Death & Disease. 9 (3): 330. doi: ... Among different cell types, neurons are particularly sensitive to MFN2 defects: to work properly, these cells need functional ... Vyas S, Zaganjor E, Haigis MC (July 2016). "Mitochondria and Cancer". Cell. 166 (3): 555-566. doi:10.1016/j.cell.2016.07.002. ...
Cell Death Dis. 5 (5): e1226. doi:10.1038/cddis.2014.168. PMC 4047874. PMID 24832598. Lu H, Shamanna RA, Keijzers G, Anand R, ... "Werner protein protects nonproliferating cells from oxidative DNA damage". Mol. Cell. Biol. 25 (23): 10492-506. doi:10.1128/MCB ... Cell. 46 (1): 43-53. doi:10.1016/j.molcel.2012.02.020. PMC 3328772. PMID 22500736. Séguéla-Arnaud M, Crismani W, Larchevêque C ... So S, Adachi N, Lieber MR, Koyama H (2004). "Genetic interactions between BLM and DNA ligase IV in human cells". J. Biol. Chem ...
Cell Death & Disease. 1 (10): e82. doi:10.1038/cddis.2010.59. PMC 3035901. PMID 21368855. Rabouille C, Linstedt AD (2016). " ... Yoshimura S, Yoshioka K, Barr FA, Lowe M, Nakayama K, Ohkuma S, Nakamura N (June 2005). "Convergence of cell cycle regulation ... The Journal of Cell Biology. 155 (4): 557-70. doi:10.1083/jcb.200107045. PMC 2198855. PMID 11706049. Lane JD, Lucocq J, Pryde J ... The Journal of Cell Biology. 156 (3): 495-509. doi:10.1083/jcb.200110007. PMC 2173349. PMID 11815631. Cheng JP, Betin VM, Weir ...
"FKHRL1-mediated expression of Noxa and Bim induces apoptosis via the mitochondria in neuroblastoma cells". Cell Death Differ. ... Kim JY, Ahn HJ, Ryu JH, Suk K, Park JH (2004). "BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia- ... "The molecular mechanism of Noxa-induced mitochondrial dysfunction in p53-mediated cell death". J. Biol. Chem. 278 (48): 48292-9 ... "Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa". J. ...
Cell Death Dis. 7 (6): e2262. doi:10.1038/cddis.2016.168. PMC 5143396. PMID 27277684. "BRAIN CYTOPLASMIC RNA 1; BCYRN1." "Alu ... It was also discovered to be overexpressed in tumor cells of colorectal cancer where the transcript is located just next to a ... The biosynthesis of BC200 RNA occurs at the cell body of a neuron and requires upstream promoter elements, downstream internal ... Although they evolved separately, both are not usually expressed in non-neural somatic cells, with the exception of tumors. The ...
... cell death) of lymphocytes further worsens the immunosuppression. Neutrophils, monocytes, macrophages, dendritic cells, CD4+ T ... It is the second-leading cause of death in non-coronary intensive care unit (ICU) and the tenth-most-common cause of death ... Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized ... cells, and B cells all undergo apoptosis, whereas regulatory T cells are more apoptosis resistant. Subsequently, multiple organ ...
T Cells to protect tumour cells. Nature Communications. March 2018, 9 (1): 948. PMC 5838096. PMID 29507342. doi:10.1038/s41467- ... The late phase of sepsis is characterized by an increased microbiological burden and death rate. Critical Care. July 2011, 15 ( ... 细胞毒性T细胞(CTLs, killer T cells)负责杀伤被病毒感染的细胞和癌细胞,在对器官移植的免疫排斥中也有参与。其特点在于细胞表面的CD8蛋白质。它通过识别所有有核细胞表
Sun T, Han X (2019). "Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes". ... a type 2 diabetic will have lost about half of their beta cells.[52] Fatty acids in the beta cells activate FOXO1, resulting in ... Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.[13] Insulin ... In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for ...
... premature shedding of leaves and particularly in the death of the top of the crown.[27] Below the bark, necrotic lesions ... perforating the middle lamella but damage to either the plasmalemma or cell walls was not observed.[29] The disease is often ...
1156 patients with a mean of 87 CD4 cell counts and mean viral load of 100,000 copies/ml were randomized to one of the two ... The end point of the study was death or development of opportunistic infections.[13] ... Viral resistance to the drug leads to the drug becoming useless since the virus evolves to have cells that are able to resist ... There were higher CD4 cell counts and less viral load in patients assigned to the three-drug group, proving that a three-drug ...
The cells met to read Marxist texts and hold self-criticism sessions.[51] Sâr joined a cell that met on the rue Lacepède; his ... Heuveline's central estimate is 2.52 million excess deaths, of which 1.4 million were the direct result of violence.[313][315] ... Pol Pot had grown suspicious of Son Sen and in June 1997 ordered his death. Khmer Rouge cadres subsequently killed Son and 13 ... The idea that the deaths which occurred under Pol Pot's government should be considered genocide was first put forward by the ...
Cells at Work! Code Black (2018). *Gurazeni: Pa League-hen (2018). *Cells at Work! Baby (2019) ... Death Billiards (2013). *Hunter × Hunter: The Last Mission (2013). *No Game No Life: Zero (2017) ...
The nerve cells responsible for reflexes are not always in the brain, but often in the spinal cord. This way, reflexes are ... Reflexes may take place even after death. The bite of a poisonous snake can be triggered up to several hours after it has died. ... Nerve cells in the brain still get feedback that the reflex action occurred. And, of course, reflex actions involving sight and ...
Invasins, such as pneumolysin, an antiphagocytic capsule, various adhesins, and immunogenic cell wall components are all major ... Sepsis is caused by overwhelming response to an infection and leads to tissue damage, organ failure, and even death. The ... and white blood cells to fill the alveoli. This condition is called pneumonia.[20] It is susceptible to clindamycin.[21] ...
... and this infection results in programmed cell death.[49] Other types of white blood cells, such as lymphocytes, also undergo ... dendritic cells and other cells including liver cells, fibroblasts, and adrenal gland cells.[93] Viral replication triggers ... doi:10.1016/j.cell.2014.10.006. PMC 4243531. PMID 25417101.. *^ a b c d e f g h Kühl A, Pöhlmann S (September 2012). "How Ebola ... liver cells, and several types of immune cells such as macrophages, monocytes, and dendritic cells are the main targets of ...
... excess secretion from the acidophil cells) caused acromegaly, then an excess of basophil cells must be involved in another ... The reason behind this survival remains a mystery, since an autopsy of Minnie was refused after her death.[3] However, the most ... Given this conviction, and his knowledge of the three anterior pituitary cell types, Cushing hypothesized that if acidophil ... In a patient with Cushing's disease, the tumor cells will be stimulated to release corticotropin and elevated plasma ...
It also contains pacemaker cells and nonpacemaker cells that initiate spontaneous breathing. Research is being conducted on the ... it has been used as a model to study pathological conditions such as apnea of prematurity and sudden infant death syndrome. The ... It is one of the four cell groups of the Ventral Respiratory Group (VRG). It is hypothesized that the pre-Bötzinger complex is ... which helps cell regenerate its bursts. The ratio between inward and outward currents helps determine the activity of pacemaker ...
T-cell count drops below 200).[76] The Medicaid eligibility policy contrasts with the Journal of the American Medical ... sickle cell anemia; sepsis; congestive heart failure; chronic obstructive pulmonary disease; and complications of devices, ... or in certain patients commencing at an even higher T-cell count. Due to the high costs associated with HIV medications, many ... Association (JAMA) guidelines which recommend therapy for all patients with T-cell counts of 350 or less, ...
... and Th1 cells.[45] IL-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development.[45 ... and cases of death in women taking even low doses of the medication to treat androgen-dependent skin and hair conditions have ... and accumulation of skin cells in the hair follicle.[1] In healthy skin, the skin cells that have died come up to the surface ... the increased production of oily sebum causes the dead skin cells to stick together.[10] The accumulation of dead skin cell ...
... which is primarily found on the surface of immune system B cells.[6] When it binds to this protein it triggers cell death.[2] ... cells in destroying these B cells. When an NK cell latched onto the cap, it had an 80% success rate at killing the cell. In ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... It induces apoptosis of CD20+ cells.. The combined effect results in the elimination of B cells (including the cancerous ones) ...
"The cell was hot. I couldn't sleep at night. The pillow was soaked with my sweat. There was a small opening in the cell wall; I ... Deaths in custody. *Dilawar. *Jamal Nasser. *Abdul Wahid. *Habibullah. *Abed Hamed Mowhoush ...
If these cells do not get this chance to recover, they are vulnerable to death. ... Outer hair cells serve as acoustic amplifiers for stimulation of the inner hair cells. Outer hair cells respond primarily to ... "J. Cell Biol. 164 (6): 887-97. doi:10.1083/jcb.200310055. PMC 2172292. PMID 15024034.. ... The stereocilia (hair cells) of the inner ear can become subjected to bending from loud noises. Because they are not ...
It is the major source of late treatment-related complications, although it less often results in death. In addition to ... who have lost their stem cells after birth. Other conditions[13] treated with stem cell transplants include sickle-cell disease ... Peripheral blood stem cells[26] are now the most common source of stem cells for HSCT. They are collected from the blood ... Sources and storage of cells[edit]. To limit the risks of transplanted stem cell rejection or of severe graft-versus-host ...
doi:10.1016/j.cell.2021.06.02: Convalescent serum (i.e. antibodies in blood from people previously infected) of people who had ... risk of death, risk of sequelae after infection resolves, (decrease in) viral load, "transmissibility", and many more. This is ...
Depending on cell width, the links show above or next to the diamond. While technically possible to enter plain text, this is ... Health code 4: Very short exposure could cause death or major residual injury. E.g. VX gas ...
The skin consists of a thin outer epidermis with mucous cells and sensory cells, and a connective tissue dermis consisting ... This causes death by respiratory failure leading to cerebral anoxia. No antidote is known, but if breathing can be kept going ... Other colour-changing cells are reflective iridophores and white leucophores.[93] This colour-changing ability is also used to ... The lens is suspended behind the pupil and photoreceptive retinal cells cover the back of the eye. The pupil can be adjusted in ...
Role of the swarmer cell stageEdit. The Caulobacter stalked cell stage provides a fitness advantage by anchoring the cell to ... "Aging and Death in an Organism That Reproduces by Morphologically Symmetric Division". PLOS Biology. 3 (2): e45. doi:10.1371/ ... Swarmer cells differentiate into stalked cells after a short period of motility. Chromosome replication and cell division only ... What is the offsetting fitness advantage of this motile cell stage? The swarmer cell is thought to provide cell dispersal, so ...
In his speech he used words such as "cell" and "metabolism" in relation to urban design. The Metabolist movement grew out of ... Tange continued to practice until three years before his death in 2005. He disliked postmodernism in the 1980s and considered ... he and his family returned to Japan after learning of the death of one of his uncles. In contrast to the green lawns and red ...
... cell-death-inducing DFFA-like effector B). Six types (1-6) have been described. Types 1-5 are inherited in an autosomal ...
General gene knock out of the TGF-β resulted in death. Conditional inactivation of TGF-βr2 of osteochondroprogenitor cells in ... Osteochondroprogenitor cells are progenitor cells that arise from mesenchymal stem cells (MSC) in the bone marrow. They have ... Sox9 blocked osteochondroprogenitor cells were found to express osteoblast marker genes, reprogramming the cells into the ... McBride, SH; Falls T; Knothe Tate ML (2008). "Modulation of stem cell shape and fate B: mechanical modulation of cell shape and ...
"Prisoner's death". The Age. Melbourne. 10 May 1972.. *^ Dunn, Alan (2 February 1973). "Axe murderer escapes from Pentridge gaol ... Cells of Pentridge Prison. The prison was split into many divisions, named using letters of the alphabet. ... Ryan was hanged in "D" Division at 8.00 on 3 February 1967 after being convicted of the shooting death of a prison officer ... amidst controversy after the deaths of five prisoners in 1987.[11] ...
Michael W. Dols (1977). The Black Death in the Middle East. Princeton. pp. 119, 285-290. OCLC 2296964.. ). ... discovered by Paul Ehrlich in 1908 after he observed that bacteria took up toxic dyes that human cells did not. The first major ... Forensic medicine deals with medical questions in legal context, such as determination of the time and cause of death, type of ... The major shift in medical thinking was the gradual rejection, especially during the Black Death in the 14th and 15th centuries ...
Landmark papers in cell biology. Bethesda MD and Cold Spring Harbor NY: The American Society for Cell Biology and Cold Spring ... The birth of the cell. Yale University Press, New Haven. *↑ Schwann, Theodor 1847 [1839]. Microscopic investigations on the ... The nucleus is the core element of the cell.. The key works of Schwann and Schleiden were published in 1838 and 1839.[2] These ... Every cell comes from another cell that lived before it.. * ... 1881 deaths. *German botanists. *People from Hamburg. *German ...
One study, however, did make use of human neural stem cells grown into a network to control a robotic actuator. These cells ... and continuing until culture death. They gathered network burst profiles (BPs) through a mathematical observation of array-wide ... Harvesting neural stem cells requires sacrificing the developing fetus, a process considered too costly to perform on many ... Like most cell cultures, neuron cultures are highly susceptible to infection. They are also susceptible to hyperosmolality from ...
Multiple tornadoes produced by the same storm cell are referred to as a "tornado family".[21] Several tornadoes are sometimes ... "Overpasses are tornado death traps". USA Today. Archived from the original on 2005-04-08. Retrieved 2007-02-28 ... Tornadic storms do not contain more lightning than other storms and some tornadic cells never produce lightning at all. More ...
"The Resurrection of Cell and Frieza" / "The Villains Of Hell!! The Revival of Cell and Frieza". Transcription: "Jigoku no ... With no other way out, Baby hits Goku with his Revenge Death Ball. Goku is enveloped by the blast, but refuses to give up. He ... Cell and Frieza show up, and now that he's trapped in hell, he has no choice but to fight them. ... He says that there is a single cell on the chest of the robot, and that hitting it with simultaneous blasts from the inside and ...
Cell Death and Disease is an online journal in the field of translational cell death. It seeks to promote diverse and ... Cell Death and Differentiation, Cell Death & Disease, and Cell Death Discovery. ... Welcome to Cell Death & Disease A peer-reviewed online journal in the field of translational cell death, promoting diverse and ... 10 Years of Cell Death & Disease This special issue celebrates the 10th Anniversary of Cell Death & Disease. Read on to hear ...
It covers programmed cell death, cell death induced by toxic agents, differentiation and their relation to cell proliferation. ... Cell death and Differentiation provides an accessible source of up-to-date information for scientists and clinicians. ... Welcome to Cell Death & Differentiation Devoted to the cell biology, molecular biology and biochemistry of cell death and ... the latest web focus which highlights some of the latest research from China covered by the three journals in the Cell Death ...
Programmed cell death (or PCD) is the death of a cell in any form, mediated by an intracellular program. PCD is carried out in ... Cell death in arthropods occurs first in the nervous system when ectoderm cells differentiate and one daughter cell becomes a ... Apoptosis and Cell Death Labs International Cell Death Society The Bcl-2 Family Database. ... "Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death". Cell. 149 (5): 1060-1072. doi:10.1016/j.cell.2012.03.042. Lang ...
Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is ... "non-apoptotic programmed cell-death" (or "caspase-independent programmed cell-death"), these alternative routes to death are as ... Ischemic cell death, or oncosis, is a form of accidental, or passive cell death that is often considered a lethal injury. The ... Programmed cell death (or PCD) is cell death mediated by an intracellular program. PCD is carried out in a regulated process, ...
... Research Group. Research focus. Research in the Walczak Laboratory is focused on cell death ... therapies by specifically inducing cancer cell death and by therapeutically directing the type of death induced in cancer cells ... Cell Death, Cancer and Inflammation The Henning Walczak Lab. Professor Henning Walczak, PhD. Scientific Director of the Cancer ... HOIP deficiency caused embryonic lethality by aberrant TNFR1-mediated endothelial cell death. Cell Reports 9(1): 153-165, 2014 ...
Source for information on Cellular Aging: Cell Death: Encyclopedia of Aging dictionary. ... and it is important to understand what cell death is, and what it is not, as there are several phenomena that use similar ... CELL DEATH Cell death during aging is an important issue, ... CELLULAR AGING: CELL DEATH. Cell death during aging is an ... Cell death: programmed, apoptosis, and necrosis. Cell senescence is distinct from what is properly called cell death. Cells can ...
Nahle Z, Polakoff J, Davuluri RV et al (2002) Direct coupling of the cell cycle and cell death machinery by E2F. Nat Cell Biol ... and caspase-dependent cell death pathway. Cell Death Differ 10:850-852. doi: 10.1038/sj.cdd.4401245 PubMedCrossRefGoogle ... Candi E, Schmidt R, Melino G (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6:328-340 ... The keratinocytes are the major cell type in the epidermis and undergo a specialized form of programmed cell death, called ...
An antibody that blocks the "programmed cell death" pathway may help the immune system fight off sepsis-related fungal ... Cell Counting Without Slides to Reduce Waste and Cost. Daniel Schieffer. Until recently, cells were typically counted on a ... This is because these cells, called peripheral T helper cells, are found to circulate at a higher rate in children with type 1 ... CRISPR and human organoids to dissect beta cell defects and create a human cell model of type 1 diabetes aimed at identifying ...
Apoptosis, also known as programmed cell death or cell suicide, is a tidy death.. The cell manages its own destruction and ... Cell debris lingers and can trigger an inflammatory response. The. dying myocardial cell died by necrosis; its death was not ... Broadly speaking, death. comes in two forms, that which is meant to happen and that which is not. At the. cell level, this is ... Clark takes us aboard a cell that is dying this way: its death will help to. form a gap between the fingers of a developing ...
Organisms that carry disease can travel through the blood stream into the liver and form an abscess, a collection of infected tissue and pus.
A new study finds that one molecule is key to whether or not particular lung cancer cells respond to chemotherapy and undergo ... Cancerous mesenchymal-like cells are very often resilient and typically resist programmed cell death after exposure to ... Researchers have identified a molecule that determines whether or not a type of lung cancer cell will undergo cancer cell death ... determines programmed cell death in cells that have gone through the epithelial-to-mesenchymal transformation. ...
50 billion cells in our bodies die and are replaced by new cells. Most of the time, there are no side effects - but things can ... But cell death pathways do not happen in isolation, and activating one type of cell death does not guarantee that a cell does ... When programmed cell death goes wrong. Cancer cells are masters at evading our immune system and avoiding death. When a cancer ... Cancer: Novel cell death technique may be better than chemo A study suggests that a new cell death method - called caspase- ...
T cell differentiation in the thymus generates a repertoire of mature T cells that is tailored to tolerate self antigens but ... Cell traffic in the adult thymus: Cell entry and exit, cell birth and death. in: "Recognition and Regulation in Cell Mediated ... Does T-cell tolerance require a dedicated antigen-presenting cell? Nature 338: 74 (1989).PubMedCrossRefGoogle Scholar ... T cell tolerance by clonal elimination in the thymus. Cell 49: 273 (1987).PubMedCrossRefGoogle Scholar ...
Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites Apoptosis-like programmed cell death (PCD ... Protozoan parasites and cell death. A key component of the life history of metazoans is the ability of their cells to undergo ... Impact of protozoan cell death on parasite-host interactions and pathogenesis PCD in protozoan parasites has emerged as a ... Spliced leader RNA silencing (SLS) - a programmed cell death pathway in Trypanosoma brucei that is induced upon ER stress ...
The concept of cell death used to be simple as there were just two or three types, so we just had to work out whic … ... Neuronal cell death occurs extensively during development and pathology, where it is especially important because of the ... that blocking a particular mechanism of cell death may not prevent the cell from dying, and that non-neuronal cells also ... The concept of cell death used to be simple as there were just two or three types, so we just had to work out which type was ...
... often leading to cell death. Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major ... ER stress-induced cell death mechanisms.. Sano R1, Reed JC2. ... ER stress-induced cell death mechanisms. Biochim Biophys Acta ... CHOP can induce transcriptional activation of genes that contribute to cell death, including Ero1α (hyperoxidizes the ER and ... This article is part of a Special Section entitled: Cell Death Pathways. ...
... probably due to cell death, positively correlates to performances. Rats with the highest newly born cell number were less able ... Depending on their birth date, newly born cell number is increased or decreased. Reduction in neurogenesis, ... rats with the lowest cell death were less able to acquire and use spatial information than those with the highest cell death. ... This learning-induced decrease in the number of newly generated cells results most probably from the death of the cells. ...
Many of the signals that elicit cell death converge on mitochondria, which regulate cell death by a pivotal process called ... Under certain circumstances, however, a cell can survive cell death; its survival may have pathophysiological consequences ... He studies programmed cell death and how defects in apoptosis cause cancer or autoimmune disease and impair the response of ... Deciphering cancer: Investigating cell death mechanisms. This webinar is brought to you by the Science/AAAS Custom Publishing ...
Injured cells release danger signals that alert the host to cell death. Some of these molecules are recognized by cellular ... Responses to different forms of cell death. Cells undergoing necrosis lose membrane integrity and leak their intracellular ... The inflammatory response to cell death.. Rock KL1, Kono H.. Author information. 1. Department of Pathology, University of ... Acute inflammation induced by cell death. (A) Normal myocardium showing the expected absence of leukocytes. (B) Infarcted ...
... they are usually forced to undergo programmed cell death, or apoptosis. However, cancer cells often ignore these signals, ... When cells suffer too much DNA damage, they are usually forced to undergo programmed cell death, or apoptosis. However, cancer ... cells often ignore these signals, flourishing even after chemotherapy drugs have ravaged their DNA.. ... When cells suffer too much DNA damage, ...
... Mike Herron herro001 at Thu Nov 14 07:51:43 EST 1996 *Previous message: CELL DEATH IN ... I seed HeLa - cells on standard 6-well cell culture plates (Costar) in 1 ml , , DMEM plus 5 % FCS , let them attach to the ... while in number 4 and 6 most of the cells , , were dead , altough an equal amount of cells had been attached to the bottom , , ... For example: If I number the wells from left to right 1 to 3 in , , the upper row and 4 to 6 in the lower , the cells in number ...
of Technology The ICE family of genes and mammalian programmed cell death. 4. Mechanisms of Cell Death in the CNS Tue July 4, ... First Gordon Conference on Cell Death Colby-Sawyer North, Lebanon NH July 2-7, 1995 The first Gordon Conference on Cell Death ... Center & Queens Coll of CUNY Regulation of cell death in mammalian embryogenesis P. K. Donahoe Mass General Hospital Cell death ... Cell Death Gordon Conference. LOCKSHIN, RICHARD A YPRLBIO at STJOHNS.EDU Wed Mar 22 01:25:13 EST 1995 *Previous message: ...
All posts tagged with cell death. * TCM medicines confirmed to accelerate cell death of breast cancer tumors. ... presented a novel cell death pathway through introducing how depriving cancer cells of sugar can trigger a reaction that causes ... Cancer cells use sugar to divide; starving them of sugar can slow their progression. ... Natural News) Researchers have discovered a mechanism that explains how reducing sugar can cause cancer cells to die. The study ...
"One thing we cannot reverse is the death of these cells, but maybe we can reverse those epigenic alterations that are ... Alcohol, pregnancy and brain cell death NIH $3.5 million award enables Rutgers researcher to continue exploring the damaging ... The genes themselves become abnormal and, while they may be producing some cells, the cells do not produce endorphin. ... These neurons also have connections with the lymphatic system, which is engaged in transporting immune cells to and from the ...
Cancer cells are characterized by genetic mutations that deregulate cell proliferation and suppress cell death. To arrest the ... In cultured human cancer cells (glioblastoma, prostate carcinoma, Ewings sarcoma), HCR transduction mediates cell death with ... to induce cell death via an innate immune response if and only if a cognate mRNA cancer marker is detected within a cell. The ... Selective cell death mediated by small conditional RNAs. Suvir Venkataraman, Robert M. Dirks, Christine T. Ueda, Niles A. ...
... a process known as T cell receptor activation-induced cell death (TCR-AICD). Their research revealed that T cells lacking ... Furthermore, it appears that the two tumor suppressors work together to induce cell death. Building on Kaelins findings, ... Failure to do so can lead to an accumulation of excess cells, each of which has the potential to mutate into a cancerous cell. ... Washington University pathologist Steven F. Dowdy and his colleagues focused on suicide in immune system cells called T cells, ...
... between cell life and death. In a paper published in the journal Cell, they reveal RIPK1 is essential for a cells decision to ... Institute researchers Associate Professor John Silke from the Cell Signalling and Cell Death division, Dr Motti Gerlic from the ... However when this cell death pathway begins to spiral out of control, it can lead to inflammatory disease. Necroptosis has also ... "We also found that it played a role in another type of programmed cell death called apoptosis. Our research highlighted that ...
David Dungay Hills death began with him eating a Tim Tam in his prison cell. A few hours later he would be dead, after he was ... Inside the cell, he was again held in a face down position on the mattress. Shortly after a nurse gave him a shot of the ... During the cell extraction, guards twice placed Dungay Hill in a face-down position, potentially restricting his breathing. ... One year after his death, the grief still devastates his family. His father, David Hill, had lost contact with his son while he ...
Pharmacological manipulation of cell death * Pharmacological manipulation of Bcl-2 family members to control cell death Anthony ... Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 1999. 6:1028-1042. View ... pharmacological manipulation of cell death Lisa Bouchier-Hayes et al. * Pharmacological manipulation of cell death: clinical ... Autophagy in cell death: an innocent convict? Beth Levine et al. * Death versus survival: functional interaction between the ...
  • Apoptosis and autophagy are both forms of programmed cell death, but necrosis was long seen as a non-physiological process that occurs as a result of infection or injury. (
  • It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is blocked by endogenous or exogenous factors such as viruses or mutations. (
  • The concept of "programmed cell-death" was used by Lockshin & Williams in 1964 in relation to insect tissue development, around eight years before "apoptosis" was coined. (
  • Apoptosis or Type I cell-death. (
  • Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. (
  • There is some evidence that certain symptoms of "apoptosis" such as endonuclease activation can be spuriously induced without engaging a genetic cascade, however, presumably true apoptosis and programmed cell death must be genetically mediated. (
  • However, apoptosis does not necessarily require protein synthesis and is usually not programmed (meaning that the sequence of death is coded in the genes) except in the generic sense that it was preprogrammed into the cell and simply required release or activation. (
  • The keratinocytes are the major cell type in the epidermis and undergo a specialized form of programmed cell death, called cornification, which is different from classical apoptosis. (
  • Lippens S, Denecker G, Ovaere P, Vandenabeele P, Declercq W (2005) Death penalty for keratinocytes: apoptosis versus cornification. (
  • At the cell level, this is manifest as death either by apoptosis or by necrosis. (
  • Apoptosis, also known as programmed cell death or cell suicide, is a tidy death. (
  • Apoptosis is the most common form of cell death and is referred to as programmed cell suicide. (
  • During apoptosis, a cell is broken up and packaged into small, self-contained pieces, which are easily recycled by phagocytes. (
  • T-cell apoptosis detected in situ during positive and negative selection in the thymus. (
  • Phagocyte recognition of cells undergoing apoptosis. (
  • Apoptosis-like programmed cell death (PCD) has recently been described in multiple taxa of unicellular protists, including the protozoan parasites Plasmodium, Trypanosoma and Leishmania . (
  • Fatalities caused by parasitic infections often occur as a result of tissue injury that results from a form of host-cell death known as apoptosis. (
  • Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. (
  • Cell death, including autophagy, necroptosis, and apoptosis, is a physiological process critical for normal development and function of multicellular organisms. (
  • In apoptosis, MOMP is tightly regulated by the Bcl-2 family of proteins, composed of both proapoptotic (Bax, Bak, Bid, Bim) and antiapoptotic (Bcl-2, Bcl-xL, Bcl-W) members, which act in part by governing mitochondrial death signaling through cytochrome C release and subsequent activation of caspases. (
  • He studies programmed cell death and how defects in apoptosis cause cancer or autoimmune disease and impair the response of tumor cells to anticancer therapy. (
  • They also found that BCL-2 and death receptors regulate distinct pathways to apoptosis, and have studied how the individual and overlapping roles of these two apoptotic pathways function in the immune system. (
  • Dr. Strasser discovered BIM and BMF, and was the first to show that BH3-only proteins are essential for the initiation of programmed cell death and stress-induced apoptosis. (
  • His laboratory studies how apoptosis can be evaded, particularly in cancer cells, and how this evasion may be detected and targeted. (
  • When cells suffer too much DNA damage, they are usually forced to undergo programmed cell death, or apoptosis. (
  • For more complete details see announcement on web page, or reply to this announcement. (
  • We also found that it played a role in another type of programmed cell death called apoptosis. (
  • When mitochondrial fusion goes awry, cells are targeted for programmed cell death, or apoptosis. (
  • Apoptosis is a normal process in healthy individuals, but if mitochondrial fusion doesn't work, the wrong cells die, causing disease. (
  • DNA methylation of DAPK1 gene, which encodes a serine/threonine kinase implicated in promoting apoptosis in response to Fas, interferon-γ, and TNF-α, was increased in peripheral blood mononuclear cells and CD19+ B cells from people with CLL compared with that in cells from healthy volunteers. (
  • Depletion of tryptophan and the accumulation of tryptophan metabolites mediated by the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1), trigger immune cells to undergo apoptosis. (
  • Investigators at St. Jude Children's Research Hospital have discovered a dance of proteins that protects certain cells from undergoing apoptosis, also known as programmed cell death. (
  • In a series of experiments, St. Jude researchers found that if any one of three molecules is missing, certain cells lose the ability to protect themselves from apoptosis. (
  • Many developmental processes involve programmed cell death, or apoptosis, to control cell number and ensure normal size, shape, and pattern development of tissues. (
  • Drosophila were engineered to express the caspase inhibitor, p35, in the posterior (P) compartment of the wing disc to uncouple apoptosis initiation (from x-ray exposure) from cell death. (
  • The excess cell proliferation, observed in the background of inhibited cell death, suggests that tissues that have initiated apoptosis could compensate for cell loss by providing proliferative signals. (
  • In the absence of completed apoptosis, secreted Wg and Dpp could stimulate cell proliferation and also affect cells in neighboring compartments. (
  • Intense research into the mechanism of p53‐induced apoptosis revealed an involvement of p53 in the extrinsic and intrinsic cell death pathways, reactive oxygen species signalling and antisurvival responses. (
  • Apoptosis (programmed cell death) is a fundamental cellular process during development, maintenance of tissue homeostasis, and in cellular response to stress. (
  • P53 tumour suppressor protein responds to diverse intarcellular (e.g. oncogene activation) and extracellular stimuli (e.g. nutrients deprivation) through activation of relevant downstream mechanisms (e.g. apoptosis) that act to protect cells from oncogenic transformation. (
  • Two complementary techniques were used to detect apoptosis-specific internucleosomal DNA fragmentation: agarose gel electrophoresis and in situ labeling of apoptotic cells by terminal dUTP nick end labeling. (
  • Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. (
  • Apoptosis * ('programmed cell death') is a biologically ubiquitous phenomenon that deserves to be much more widely known among non-biologists and laypeople. (
  • Cell death can occur through 3 mechanisms: apoptosis, autophagy, and necrosis. (
  • Apoptosis, or programmed cell death, results in controlled cell shrinkage and nuclear fragmentation via the action of caspases, as well as an anti-inflammatory cytokine release. (
  • Apoptosis and necrosis both signal through the death domain receptors FAS, TNFRSF1A (TNFR1), and TNFRSF10A (TRAIL-R), while autophagy and apoptosis share BCL2 family members as key players. (
  • The Human Apoptosis RT² Profiler PCR Array profiles the expression of 84 key genes involved in programmed cell death. (
  • Apoptosis plays a critical role in normal biological processes requiring cell. (
  • The Human Cell Death PathwayFinder RT² Profiler PCR Array profiles the expression of 84 key genes important for the central mechanisms of cellular death: apoptosis, autophagy, and necrosis. (
  • To answer these questions, the scientists engineered a mouse model where they could turn on apoptosis and catch phagocytes in the act of sampling dying cells. (
  • The results showed Cur-NPs induced apoptosis in CAR cells but exhibited low cytotoxicity to normal human gingival fibroblasts (HGFs) and normal human oral keratinocytes (OKs). (
  • Called "non-apoptotic programmed cell-death" (or "caspase-independent programmed cell-death"), these alternative routes to death are as efficient as apoptosis and can function as either backup mechanisms or the main type of PCD. (
  • Immunogenic cell death or immunogenic apoptosis is a form of cell death caused by some cytostatic agents such as anthracyclines, oxaliplatin and bortezomib, or radiotherapy and photodynamic therapy (PDT). (
  • In response to stress or as a natural part of aging, many cells undergo programmed suicide, also known as apoptosis. (
  • Cancer cells often become immortal and dangerous by developing the ability to suppress apoptosis. (
  • A decade ago apoptosis was thought to be directed solely by the nucleus and mitochondria of cells. (
  • In earlier research, Dr. Shields' group demonstrated that the Golgi's p115 protein splits into two pieces early in apoptosis and that the smaller of these protein fragments-205 amino acids in length-helps to maintain the cell-suicide process. (
  • His efforts to uncover fundamental mechanisms governing how cells work has led to new ways of thinking about apoptosis, in particular, how the Golgi regulates this process. (
  • Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. (
  • Local disruption of ECM by pharmacologic or genetic means results in selective programmed cell death (apoptosis) within adjacent cells ( 2 , 6 , 7 ). (
  • Soluble integrin α V β 3 antagonists also induce apoptosis in cultured endothelial cells and promote capillary involution in vivo ( 8 ). (
  • We first measured apoptosis rates in suspended human capillary endothelial cells attached to a range of different-sized beads coated with fibronectin (FN). (
  • Effect of cell spreading on apoptosis. (
  • B ) Apoptosis in cells attached to different-sized beads, in suspension, or attached to a dish. (
  • Despite this, genetic control of β-cell apoptosis is only poorly understood. (
  • We report that inhibition of gene transcription sensitized β-cells to tumor necrosis factor (TNF)-α-induced apoptosis, indicating the presence of a regulated antiapoptotic response. (
  • Finally, A20 expression was sufficient to protect β-cells from TNF-induced apoptosis. (
  • Apoptosis or programmed cell death is a genetically controlled response of the cell to commit suicide ( 1 , 2 ). (
  • Apoptosis is the physiological process for cell deletion in normal, reorganizing, or involuting tissue and is required for shaping of the endocrine pancreas ( 3 , 4 ). (
  • Aside from its role in normal cell biology, β-cell apoptosis has been implicated in the pathophysiology of type 1 diabetes, both at its initiation phase and as the final effector mechanism ( 5 , 6 ). (
  • Despite the importance of apoptosis in the pathophysiology of β-cell death, the genetic control of apoptosis in islets is poorly understood. (
  • Determining the molecular basis of β-cell susceptibility to apoptosis would increase our understanding of the mechanisms underscoring β-cell loss, as well as reveal potential gene therapy candidates for the creation of "death-defying" islets ( 13 ), capable of resisting immune and nonimmune insults. (
  • Significantly, we demonstrate that A20 is regulated at the level of gene transcription in pancreatic β-cells by the proinflammatory transcription factor nuclear factor-κB (NF-κB), thus linking islet inflammatory gene responses with protection from apoptosis. (
  • Since the Cell Death Detection ELISA PLUS assay does not require prelabeling of cells, it can detect internucleosomal degradation of genomic DNA during apoptosis even in cells that do not proliferate in vitro (for example, freshly isolated tumor cells). (
  • Use this kit for relative quantification of histone-complexed DNA fragments (mono- and oligonucleosomes) in the cytoplasm of cells after the induction of apoptosis (requires cell lysis) or released from necrotic cells into the cell culture supernatant or into serum/plasma. (
  • Centrifugation at 200 x g is necessary before using the supernatant for detection of apoptosis in order to separate DNA fragments from other cell components ( e.g., cell walls and cell nuclei which contain non-fragmented DNA). (
  • The beneficial side of cell death - known as apoptosis - occurs when it kills cells at appropriate times, as is the case, for example, when it removes the webbing from the fingers of an embryo or shapes a developing brain. (
  • Dr. Wang said that while there are many possible routes a cell may take toward apoptosis, this interaction serves as one of the "master switches" controlling whether or not those other pathways are triggered. (
  • Normally, Mcl-1 keeps cells alive by protecting them against apoptosis. (
  • Scientists have found that after a severe infection or injury, cells in the intestinal lining die off in a process called apoptosis. (
  • Researchers now suspect that blocking apoptosis in the intestines of critically ill patients may help prevent death from sepsis. (
  • This study suggests that minimizing apoptosis in intestinal cells may prevent death in people with sepsis. (
  • However, phylogenetically conserved PCD types other than apoptosis exist i n animal and non-animal cells. (
  • Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem-like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. (
  • The 'death program' called apoptosis is common to all cells throughout the body. (
  • sometimes referred to as cellular suicide) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. (
  • Apoptosis and autophagy are both forms of programmed cell death. (
  • A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified. (
  • The DNA encompassed by the deletion was cloned and the reaper gene was identified on the basis of the ability of cloned DNA to restore apoptosis to cell death defective embryos in germ line transformation experiments. (
  • The reaper gene appears to encode a small peptide that shows no homology to known proteins, and reaper messenger RNA is expressed in cells destined to undergo apoptosis. (
  • This is exciting - if the proteasome-mediated degradation of Bax could be inhibited specifically in cancer cells, it could cause the harmful cancer cells to go through apoptosis," Dr. Victor Yu said. (
  • In apoptosis, unwanted, damaged and infected cells are eliminated. (
  • One programmed response to such trajectories causes the cell to commit suicide, a process known as apoptosis. (
  • Apoptosis can also be brought to bear on otherwise-healthy cells that the organism no longer needs. (
  • The animal kingdom provides an excellent example of this: the cells of a tadpole's tail die through apoptosis when it transforms into a frog, and the tail simply disappears. (
  • Another kind of programming provides an alternative to apoptosis in dealing with damaged or unwanted cells. (
  • To elucidate molecular mechanisms regulating the development of apoptosis resistance, a panel of 15 BL cell lines was investigated for apoptosis induction upon treatment with microtubule inhibitors taxol, nocodazole and vincristine. (
  • Significant differences were observed in the extent of apoptosis induction among BL cell lines examined. (
  • Further, in sensitive cell lines taxol-induced apoptosis was accompanied by caspase activation, Bid cleavage and Mcl-1 down-regulation. (
  • Remarkably, inhibition of apoptosis in sensitive cell lines by caspase inhibition promoted polyploidy confirming the inverse relationship between apoptosis and polyploidization. (
  • In the June 30 issue of the journal Cell, the research team found that a natural "brake" exists in a cell to prevent it from undergoing apoptosis, or programmed cell death, and they say that optimal anti-cancer therapies should take a two-pronged approach to overriding this brake in order to force a tumor cell to die. (
  • Apoptosis can occur when a cell has reached its lifespan, and so is "programmed" to die, or is initiated when a cell is damaged beyond repair or infected by a virus. (
  • Apoptosis is rare in cancer because tumor cells have adapted biological pathways to circumvent cell death, so many anti-cancer therapies focus on inducing apoptosis in these cells, Tang says. (
  • But what they also believed is that a cell needs extra energy from ATP to undergo apoptosis, and that this extra energy was produced from the "pools" of free nucleotides that exist in the cell cytoplasm. (
  • However, through a series of biological and biochemical experiments, Tang and his research team found that adding ATP to a cancer cell could potentially impede apoptosis. (
  • Many cancer drugs focus on pushing the mitochondria to release CC, and not on reducing the nucleotide pool, and our new model suggests that decreasing this pool is essential to produce sensitivity in cancer cells to apoptosis," Tang says. (
  • The healthy organism needs "programmed cell death" - apoptosis . (
  • How apoptosis is triggered in glial cells is not fully understood yet. (
  • Another approach pursues the idea of preventing apoptosis in glial cells. (
  • Although in vivo apoptosis did not require the Fas death receptor, B cells were protected by interleukin (IL)-4 or CD40L, or overexpression of Bcl-2. (
  • Billions of cells in our bodies die every day in an important process called apoptosis. (
  • Fas antigen (Fas) is a cell surface receptor that triggers apoptosis in sensitive cells when bound to the Fas ligand (Fas L). The present study was undertaken to identify the presence of a Fas-Fas L system in bovine corpus luteum (CL) and to evaluate the regulation of Fas-mediated luteal cell death by leukocyte-derived cytokines. (
  • In isolated cells, propidium iodide and Hoechst 33342 staining showed a cold-storage, time-dependent increase in necrosis, whereas apoptosis was minimal even after 48h of hypothermia. (
  • James Ferrell found that trigger waves help guide a widespread form of cell death known as apoptosis. (
  • A new study out of the Stanford University School of Medicine has found that this phenomenon guides one of the most well-known and widespread forms of cell death: apoptosis. (
  • One of the better-understood forms of cell death, apoptosis still manages to mystify scientists. (
  • It doesn't get any lower in amplitude because every step of the way it's generating its own impetus by converting more inactive molecules to active molecules, until apoptosis has spread to every nook and cranny of the cell. (
  • To start, the two scientists took fluid from the egg and inserted it into Teflon tubes, which were several millimeters long, and initiated apoptosis through a molecular "death signal. (
  • The question was, did apoptosis also spread like that in cells as they naturally occur? (
  • Apoptosis and other cell death mechanisms are complex and carefully controlled. (
  • In addition, this issue also includes several reviews on tangential topics, such as viral hijacking of host caspases, metacaspase functions, non-lethal functions of BCL-2 family proteins, and alternative, caspase-independent developmental cell death pathways. (
  • Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. (
  • This article is part of a Special Section entitled: Cell Death Pathways. (
  • In the event of amino acid starvation, the cell activates two main protective pathways: Amino Acid starvation Response (AAR), to inhibit global translation, and autophagy, to recover the essential substrates f. (
  • P53 activates the extrinsic and intrinsic cell death pathways. (
  • In skeletal muscle, progressive loss of myofibers associated with muscular dystrophy is also regulated by specific molecular pathways that mediate apoptotic and / or necrotic cell death. (
  • Thus, inhibition of nodal cell death pathways could have a significant implication in combating diseases of striated muscle. (
  • The molecular mechanisms behind these cell death pathways overlap, and can be co-activated during some cellular functions. (
  • Other pathways of programmed cell death have been discovered. (
  • The symposium aimed to bring together expertise from a broad scientific background focused on understanding the distinct mechanisms and signalling pathways that cell death can occur through. (
  • This gave me a great opportunity to put into context the significance of my work in relation to cell death and the numerous underlying pathways. (
  • In the early 1990s, Dixit was not only able to identify the molecular components of the cell death signal pathways, such as the so-called caspases, i.e., enzymes involved in the initiation and implementation of cell death, but was also able to uncover the mechanisms that underlie this fundamental cellular process. (
  • On the other hand, PCD can sometimes proceed in the absence of caspase activity, through alternative cell death pathways. (
  • Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. (
  • Recently a form of programmed necrosis, called necroptosis, has been recognized as an alternate form of programmed cell death. (
  • Necrosis, by contrast, is a messy death. (
  • Some of these damaged cells will die by necrosis. (
  • Scientists call this the passive form of necrosis, as it does not require any specific activity by the cell. (
  • However, there are two forms of necrosis - necroptosis and pyroptosis - which are actively regulated by the cell and are now recognized as specialized forms of programmed cell death. (
  • Cells undergoing necrosis lose membrane integrity and leak their intracellular components some of which serve as danger signals that stimulate inflammation. (
  • However, if the apoptotic cells are not cleared rapidly they release danger signals when they proceed into secondary necrosis. (
  • In contrast, necrosis signals via RIPK1 (RIP1), leading to cell swelling, lysis, and a pro-inflammatory cytokine release. (
  • Necrosis is cell death where a cell has been badly damaged through external forces such as trauma or infection and occurs in several different forms. (
  • Necrosis was long seen as a non-physiological process that occurs as a result of infection or injury, but in the 2000s, a form of programmed necrosis, called necroptosis, was recognized as an alternative form of programmed cell death. (
  • In contrast to necrosis, which is a form of cell-death that results from acute tissue injury and provokes an inflammatory response, PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle. (
  • More dangerous is a morbid, uncontrolled cell death - a so-called necrosis . (
  • Because programmed cell death does not create a toxic environment that would provoke further necrosis. (
  • But Hans-Joachim Anders and his colleagues have now shown that the different types of crystals all initiate an active process that leads to cell necrosis. (
  • The lab is particularly interested in unravelling the mechanisms on how different death receptor-ligand systems such as the TNF and TRAIL systems are regulated and how they impact cancer cell survival, cancer-related inflammation and immunity. (
  • Deregulation of cell death mechanisms in the skin can lead to diseases such as cancer, necrolysis and graft-versus-host disease. (
  • Understanding the mechanisms that are associated with phenotypic heterogeneity in lung cancer cells - specifically differences between epithelial and mesenchymal-like cells - allows these differences to be exploited to develop more selective therapeutic agents. (
  • Mechanisms concerning life or death decisions in protozoan parasites are still imperfectly understood. (
  • We next explore the mechanisms of neuronal death during development, and those induced by axotomy, aberrant cell-cycle reentry, glutamate (excitoxicity and oxytosis), loss of connected neurons, aggregated proteins and the unfolded protein response, oxidants, inflammation, and microglia. (
  • ER stress-induced cell death mechanisms. (
  • This webinar will examine how identification of dysregulated cell-death mechanisms underpinning various pathologies can be exploited to develop novel treatments for cancer and neurodegenerative diseases that directly activate the cell-death machinery. (
  • Cells contain a number of different danger signals that can potentially stimulate inflammation through different mechanisms. (
  • Autophagy and ER stress are involved in maintaining some well-orchestrated mechanisms aimed at either restoring cellular homeostasis or performing cell death. (
  • Despite this, adult flies emerge from the treatment with normal wing morphology, which indicates that mechanisms are in place to compensate for cell loss. (
  • Although mutations in the rhodopsin, peripherin, and cGMP phosphodiesterase genes have been identified in some forms of RP, it remains to be determined whether these mutations lead to photoreceptor cell death through necrotic or apoptotic mechanisms. (
  • We also show that apoptotic death occurs in the retina during normal development, suggesting that different mechanisms can cause photoreceptor death by activating an intrinsic death program in these cells. (
  • F. Ballarini, S. Bortolussi, A. M. Clerici, C. Ferrari, N. Protti, and S. Altieri, "From radiation-induced chromosome damage to cell death: modelling basic mechanisms and applications to Boron neutron capture therapy," submitted to Radiation Protection Dosimetry . (
  • Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. (
  • For example, the XY chromosome cells found in males have different mechanisms for triggering cell death than the XX chromosome cells found in females. (
  • We are investigating the molecular mechanisms that underlie cell death, and are exploring the potential medical benefits that might arise from inhibition of death in certain disease states. (
  • However, multiple obstacles are faced in islet transplants, including cellular rejection akin to the mechanisms involved in autoimmune destruction of β-cells, and also primary nonfunction, a phenomena related to lack of nutrients, hypoxia, and nonspecific inflammatory mediators ( 10 - 12 ). (
  • Many of the targets of the compounds we have been studying have been associated with cell death mechanisms and so my work really fitted nicely into the theme of the meeting. (
  • Programmed cell death occurs throughout life in essentially all tissues in the human body as part of the normal process of development and death, and the human body has innate mechanisms to clean up these fragments of dead cells. (
  • Specialised white blood cells called professional phagocytes are essential to this clean-up and we hope that by better understanding the mechanics of this, scientists can better harness the human body's own defence and healing mechanisms, leading to better health treatments and outcomes in the future. (
  • Dixit and his team laid the foundations for decoding the mechanisms underlying programmed cell death in the early 1990s. (
  • Developmental control of cell death through apoptotic mechanisms is a common mechanism for influencing cell number in a variety of brain regions that is actively regulated by both genetic and environmental factors. (
  • It is the intention of this review to provide an overview of viral gene products that are able to promote or inhibit apoptotic death of the host cell and to discuss their mechanisms of action. (
  • Cold ischemia - warm reperfusion (CI/WR) injury of liver transplantation involves hepatocyte cell death, the nature and underlying mechanisms of which remain unclear. (
  • Contributors describe in detail the molecular mechanisms of cell death signaling, including death receptor-ligand systems, BCL-2 family proteins, mitochondrial permeabilization, the endocytic pathway, caspases, and signals that trigger the clearance of dying cells. (
  • Survival mechanisms and proteins such as IAPs that antagonize cell death are also described. (
  • European researchers investigated the molecular mechanisms that drive stress-related responses that cause aging and death in plants. (
  • Cells can, of course, encounter violent situations in which proteins precipitate, membranes are ruptured, or their access to energy sources is destroyed. (
  • In developmental situations, death frequently, if surprisingly, requires the synthesis of new proteins, perhaps including those involved in killing the cell. (
  • Eukaryotic cells have developed an evolutionarily conserved adaptive mechanism, the unfolded protein response (UPR), which aims to clear unfolded proteins and restore ER homeostasis. (
  • Earlier work had indicated that a number of proteins that activate p53 do not affect p73, but by employing tumor cells that lacked p53, the team found that E2F-1 does, in fact, activate p73. (
  • Netosis is a recently described type of neutrophil death occurring with the release to the extracellular milieu of a lattice composed of DNA associated with histones and granular and cytoplasmic proteins. (
  • The protein, ALKBH7, is one of several proteins that can trigger cell death in both mice and humans. (
  • And if so, are there ways to selectively re-introduce the ALKBH7 protein-or other proteins that trigger cell death-into cancer cells but not in the normal cells? (
  • The Golgi package proteins and other substances made by cells and direct them to their destination within the cell. (
  • This is the first enzymatic step that regulates the degradation of proteins that control cell death. (
  • Downstream of this activational cascade, caspases cleave a variety of regulatory and structural proteins and important enzymes, targeting the cell for destruction by disassembling its contents. (
  • In a researcher article in the journal Molecular Cell, the researchers describe proteasomes as "protein-digesting machines" that regulate cellular levels of various proteins, including that of the lethal Bax , by breaking them into smaller components within the cell. (
  • Senescent cells secrete large amounts of proteins that cause inflammation in the immune system and degradation in supportive tissue. (
  • The negative effects of these proteins are negligible in younger people because they have only a few senescent cells in their tissues, but these as senescent cells accumulate over the decades the secreted proteins wreak havoc on nearby healthy tissue in older individuals. (
  • Nucleotides are the primary structural chemical units that make up DNA, RNA and proteins, and they combine to play a variety of roles in the cell, such as formation of ATP. (
  • Events that happen inside our cells are often controlled by interactions between proteins and modifications of proteins that change how they can interact with each other. (
  • This theory receives support from immunocytochemical evidence for the reexpression of several cell cycle-related proteins. (
  • cell cycle-related proteins appear in neurons at risk for death. (
  • For example, testosterone exposure reduces loss of neurons in the rat spinal cord and BSTp by reducing the incidence of cell death mediated by apoptotic proteins of the Bcl-2 family ( Forger 2009 ). (
  • Yet, viruses have the potential to initiate or stay the onset of programmed cell death through the manipulation of a variety of key apoptotic proteins. (
  • Once cell death is initiated, by way of disease or something else, specific killer proteins in the cell, called caspases, activate. (
  • Allombert-Blaise C, Tamiji S, Mortier L et al (2003) Terminal differentiation of human epidermal keratinocytes involves mitochondria- and caspase-dependent cell death pathway. (
  • An antibody that blocks the "programmed cell death" pathway may help the immune system fight off sepsis-related fungal infections, according to animal studies reported in SHOCK: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches, Official Journal of the Shock Society. (
  • The study, which was published in the online journal Science Signaling, presented a novel cell death pathway through introducing how depriving cancer cells of sugar can trigger a reaction that causes them to die. (
  • However when this cell death pathway begins to spiral out of control, it can lead to inflammatory disease. (
  • Associate Professor Silke said the institute was already capitalising on its expertise in necroptotic cell death with a drug discovery program to identify small molecules that could target molecules downstream of RIPK1 in the necroptotic pathway, such as MLKL (mixed lineage kinase domain-like). (
  • Likewise, tumorigenesis may result in part from the initiation of the apoptotic pathway coupled with inhibition of cell death, producing abnormal signaling of factors that cause cell proliferation. (
  • This is because the pathway only functions in primary neurons, and not in cultured cell lines, they found. (
  • The results fill in one more piece of the puzzle of excitotoxic cell death, and open up the possibility of a new target for inhibiting the pathway. (
  • P53 activates the extrinsic pathway by directly inducing the expression of death receptors, such as Fas/CD95 or DR‐5 as well as caspases 8 and 6. (
  • We are currently focusing most of our efforts on elucidating the mitochondrial (intrinsic) cell death pathway, with a specific emphasis on the process of mitochondrial permeability pore formation. (
  • QIAGEN provides a broad range of assay technologies for cell death research that enable analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. (
  • Our results suggest that Cur-NPs triggered the intrinsic apoptotic pathway through regulating the function of multiple drug resistance protein 1 (MDR1) and the production of reactive oxygen species (ROS) in CAR cells. (
  • Once the cells start down paths to become specific body parts, they deactivate their instant-suicide pathway. (
  • These studies define a pathway for BCR-mediated programmed cell death that is V H region targeted by a superantigen. (
  • In all cases, the researchers found that the crystals activated the same signal transduction pathway in the cells. (
  • Together, these data suggest that an intrinsic cell death pathway is activated by estrogen to regulate TH-ir cell number. (
  • It is counter-intuitive that such simple organisms would be efficient at regulating this the most crucial pathway within the host, given the relative complexity of the host cells. (
  • In cell-death-related treatments such as chemotherapy, the mitochondrial pathway is activated. (
  • This causes leaks in the membranes of mitochondria, which are the powerhouses that convert oxygen into energy in the cell. (
  • Once mitochondria are damaged, a cell is well and truly on its way to becoming a corpse. (
  • Many of the signals that elicit cell death converge on mitochondria, which regulate cell death by a pivotal process called mitochondrial outer membrane permeabilization (MOMP). (
  • New methods to measure death signaling in mitochondria that provide clues to how an individual's tumor cells will respond to therapy. (
  • In healthy cells, mitochondria (tiny energy substations that churn out each cell's power supply) continually fuse together and split in two. (
  • When we induced some cell stress and damage, the low levels of CC that came out from the mitochondria were ineffective because they are sequestered by an ocean of free nucleotides and ATP," he says. (
  • They found that cell mitochondria needed to release a large and sustained volume of CC to overcome this nucleotide barrier, and they also found evidence that as soon as the release of CC increases, another mechanism kicks in that simultaneously begins to reduce the size of the nucleotide pool to allow CC to bind to Apaf-1, Tang says. (
  • The researchers say this kind of strategy makes sense for the cell, because it acts like a biological fail-safe system to protect against the errant release of CC from malfunctioning mitochondria. (
  • Published in eLife , the study focuses on the protein IRBIT and how its action near mitochondria in our cells can set off a chain reaction that leads to programmed cell death. (
  • The key factor in this process is the flow of calcium ions between two organelles within a cell-the ER and mitochondria. (
  • When this happens, the team saw that without Bcl2l10, calcium flow into the mitochondria increased, which led to cell death. (
  • In physiological condition, in WT cells, IRBIT promotes ER-mitochondria contact rendering Ca 2+ transfer easier between the two organelles. (
  • In IRBIT KO cells, although Ca 2+ released through IP3R is increased due to absence of IRBIT, Ca 2+ transfer to the mitochondria is reduced because of the great reduction of ER-mitochondria contact. (
  • In WT cells, IRBIT dephosphorylation induces its translocation together with Bcl2l10 allowing a massive Ca 2+ transfer from ER to mitochondria. (
  • T cell receptor antagonist peptides induce positive selection. (
  • Here, we describe small conditional RNAs that undergo hybridization chain reactions (HCR) to induce cell death via an innate immune response if and only if a cognate mRNA cancer marker is detected within a cell. (
  • Furthermore, it appears that the two tumor suppressors work together to induce cell death. (
  • However, exposure to x-rays can induce substantial cell death in the larval wing. (
  • They injected into the intestinal walls of these mice a carefully titrated dose of toxin to induce cell death. (
  • Curcumin-loaded nanoparticles induce apoptotic cell death through. (
  • It has been shown to induce cell death in a variety of cancer cells, however, its effect on CAL27cisplatin-resistant human oral cancer cells (CAR cells) has not been elucidated to date. (
  • Through recent research published in Cancer Research , Faber and his collaborators have determined that the MYCN gene creates a vulnerability to drugs that induce ferroptosis because MYCN uses a lot of iron to help power the cancer cell and grow uncontrollably. (
  • Using preclinical tumor models, Faber's team will use the grant funding to test the ability of sulfasalazine and auronofin - drugs FDA-approved for rheumatoid arthritis - to induce ferroptosis and tumor responses in neuroblastoma cells with high levels of MYCN. (
  • LMU researchers led by Hans-Joachim Anders have now elucidated how the insoluble deposits induce cell death. (
  • In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not ident. (
  • if activated briefly, it stimulates proliferation of pre-malignant and cancerous tumor cells,' said Karin. (
  • Tumor cells also don't want to decrease their nucleotide pool, because they need ATP for continued functioning, he says. (
  • According to our in vitro results, we assume that this is how the tumor cells located in the center of a tumor -- the so-called necrotic core -- die, because there are never enough nutrients in those areas", adds the IDIBELL researcher. (
  • The team, from the Cancer Research UK Centre at the UCL Cancer Institute, found that mutations in the KRAS gene interferes with protective self-destruct switches, known as TRAIL receptors, which usually help to kill potentially cancerous cells. (
  • These activate so-called death receptors on the cell. (
  • Examples of cellular receptors that sense infection and cell death. (
  • 2004). These authors showed evidence for a different mechanism to activate p38 by NMDA receptors-one that could explain a caspase-independent programmed cell death that is sensitive to Bcl-2. (
  • It occurs as a result of repeated stimulation of specific T-cell receptors (TCR) and it helps to maintain the periphery immune tolerance. (
  • To understand how a B cell superantigen affects the host immune system, we infused protein A of Staphylococcus aureus (SpA) and followed the fate of peripheral B cells expressing B cell receptors (BCRs) with V H regions capable of binding SpA. (
  • It is generally believed that sex steroids act via steroid receptors to promote neuronal survival by reducing the incidence of cell death. (
  • Instead, when starved, cells activate the so-called "death receptors" on their membrane, which are normally used by the lymphocytes of the immune system to attack and destroy infected cells. (
  • Feeling the stress produced by the lack of nutrients, the reticulum send an alarm signal that triggers the appearance of death receptors in the membrane", says Dr. Muñoz-Pinedo. (
  • Research in the Walczak Laboratory is focused on cell death and ubiquitin in inflammation, cancer and immunity. (
  • The research aims are to develop novel cancer therapies by specifically inducing cancer cell death and by therapeutically directing the type of death induced in cancer cells to convert cancer-related inflammation from being immune-regulatory to enabling the immune system to recognise and kill cancer cells. (
  • Necrotic cells, generated in an uncontrolled manner, create many problems for an organism because of inflammation and because of the leakage of potentially dangerous chemicals or enzymes. (
  • When cells burst and die, their contents are released, causing inflammation. (
  • They are also the gatekeepers of inflammation , and cell death can either be pro- or anti-inflammatory, leading to different outcomes. (
  • Acute inflammation induced by cell death. (
  • Apoptotic cells may not stimulate inflammation if they are ingested by phagocytes before they release their intracellular contents. (
  • Some of these signal are intracellular molecules that trigger inflammation by directly stimulating cells to make proinflammatory cytokines. (
  • Institute researchers Associate Professor John Silke from the Cell Signalling and Cell Death division, Dr Motti Gerlic from the Inflammation division and Dr Ben Croker led the project, working with PhD students Mr James Richard, Ms Joanne O'Donnell and Mr Joseph Evans. (
  • Upon inflammation, neutrophils are the first cells to be recruited to the inflammatory site, in a process orchestrated by chemokines, a series of attractive molecules produced locally. (
  • The inability to clear dying cells has been linked to inflammation and autoimmunity. (
  • Dying epithelial cells are shed into the gut lumen, so their active clearance is not necessary and they were thought to have no role in intestinal inflammation. (
  • We know there is excessive cell death, inflammation and microbial imbalance in IBD, so the prediction is that the immunosuppressive program in phagocytes, associated with natural cell death in the gut epithelium, would be disrupted," Blander said. (
  • With funding from SENS Research Foundation and working in Dr. Judith Campisi's laboratory at the Buck Institute for Research on Aging, PhD candidate Kevin Perrott is investigating how molecules affect one type of senescent skin cell to understand its role in inflammation and the immune system. (
  • SENS Research Foundation funding also supports research performed by Nick Schaum in the Campisi lab, which has shed light on the link between the two hallmarks of cell senescence, identifying a key driver of inflammation and halted cell division. (
  • This special issue brings a comprehensive collection of reviews highlighting diverse non-lethal functions of caspases in a variety of organisms, cell types, and cellular processes, such as signaling, proliferation, differentiation, remodeling and neuronal plasticity. (
  • Unlike other cancer genes, which promote cancer by stimulating cell proliferation, BCL2 promoted cancer by stopping lymphoma cells from being able to kill themselves. (
  • Under culture conditions, or in conditions of excessive proliferation, such as chronic challenge to the immune system, the cells eventually use up their telomeres and cease proliferation. (
  • Although evidence suggest that neurogenesis play a role in spatial learning, the effect of learning on cell proliferation remains unclear. (
  • The authors generated and tested the hypothesis that different phases of spatial learning measured in the Morris water maze have distinct actions on cell proliferation. (
  • Strikingly, cell death and not proliferation was positively correlated with performance in the water-maze. (
  • The results reveal a complex modulation of learning on brain plasticity, which induces death and proliferation of different populations of cells. (
  • Cancer cells are characterized by genetic mutations that deregulate cell proliferation and suppress cell death. (
  • and cell proliferation and death. (
  • The research, appearing online the week of June 19 in advance of publication in the journal Proceedings of the National Academy of Sciences , underscores the importance of JNK1-mediated cell death and compensatory proliferation. (
  • Since we previously knew that JNK activity is required for normal liver cell proliferation, we wondered if the same activity is required for production of liver cancer in carcinogen-exposed mice. (
  • Within hours, a sequence of events was initiated in SpA-binding splenic B cells, with rapid down-regulation of BCRs and coreceptors, CD19 and CD21, the induction of an activation phenotype, and limited rounds of proliferation. (
  • Cell Death and Differentiation 21: 491-502, 2014. (
  • Through the combined effects of positive and negative selection, T cell differentiation in the thymus generates a repertoire of mature T cells that is tailored to tolerate self antigens but mount strong responses to foreign antigens 1,2 . (
  • The researchers found that a molecule called mIR-124 , which is involved in the regulation of gene expression, determines programmed cell death in cells that have gone through the epithelial-to-mesenchymal transformation. (
  • in: "Recognition and Regulation in Cell Mediated Immunity," J. D. Watson and J. Marbrook, eds. (
  • Seeking to address this shortcoming, we pursue therapeutic regulation that is conditional, activating selectively in cancer cells. (
  • Our results indicate that programmable mechanical transduction with small conditional RNAs represents a fundamental principle for exploring therapeutic conditional regulation in living cells. (
  • Inhibition of Rho has proven to be beneficial in models of axonal regeneration, and regulation of the release of amyloidogenic Aβ42 peptide from neuroblastoma cells,' the authors write. (
  • Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment. (
  • Regulation of A20 was nuclear factor-κB (NF-κB)-dependent, two NF-κB sites within the A20 promoter were found to be necessary and sufficient for A20 expression in β-cells. (
  • It is a recurring theme in cell regulation. (
  • The term programmed cell death derived originally from developmental and embryonic observations, and it emphasizes the idea that specific genes regulate the death of cells. (
  • It can help the cancer grow and survive, but it also creates these toxic molecules within the cell called reactive oxygen species,' said Faber, Natalie N. and John R. Congdon Chair in Cancer Research and co-leader of the Developmental Therapeutics research program at Massey and associate professor in the Philips Institute for Oral Health Research at the VCU School of Dentistry. (
  • These observations suggest that the same prohibitions against cell division that followed a neuron from the ventricular zone through the developmental process remain in effect until the end of life. (
  • It is an essential reference for cell and developmental biologists, cancer biologists, and all who want to understand when and how cell death is required for life. (
  • Evidence that programmed cell death also occurs in unicellular organisms, including parasitic protozoans, is rapidly growing. (
  • Neuronal cell death occurs extensively during development and pathology, where it is especially important because of the limited capacity of adult neurons to proliferate or be replaced. (
  • In this paper, we report a test of the hypothesis that photoreceptor cell death occurs by an apoptotic mechanism in three mouse models of RP: retinal degeneration slow (rds) caused by a peripherin mutation, retinal degeneration (rd) caused by a defect in cGMP phosphodiesterase, and transgenic mice carrying a rhodopsin Q344ter mutation responsible for autosomal dominant RP. (
  • Pyroptosis is a highly inflammatory form of programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response in myeloid cells. (
  • In an accompanying News and Views letter, Nathaniel Heintz of the Rockefeller University in New York applauds the study, but notes that, 'In some well-characterized animal models of neurological disease, obvious histological abnormalities appear and deterioration of neuronal function occurs well in advance of cell loss. (
  • Virtually all programmed cell death that normally occurs during Drosophila embryogenesis was blocked in embryos homozygous for a small deletion that includes the reaper gene. (
  • Sickle cell disease is a genetic disease that occurs predominantly in people of African descent. (
  • The more widespread cell death occurs, the more severe the loss of function in spinal cord injury could be. (
  • Inside a cell, death often occurs like the wave at a baseball game. (
  • The mechanism for cell senescence is not completely understood. (
  • These are not random events, but part of a finely tuned biological mechanism called programmed cell death. (
  • It is also a crucial mechanism of defense against pathogens, as cells that are infected with bacteria or viruses are removed this way. (
  • But unfortunately, programmed cell death is not a foolproof mechanism. (
  • However, we now know that there are at least a dozen ways for neurons to die, that blocking a particular mechanism of cell death may not prevent the cell from dying, and that non-neuronal cells also contribute to neuronal death. (
  • We also discuss why it has been so difficult to pinpoint the type of neuronal death involved, if and why the mechanism of neuronal death matters, the molecular overlap and interplay between death subroutines, and the therapeutic implications of these multiple overlapping forms of neuronal death. (
  • Natural News) Researchers have discovered a mechanism that explains how reducing sugar can cause cancer cells to die. (
  • The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. (
  • Programmed cell death is actually a genetically predetermined mechanism that takes more or less the same form in almost all multi-cellular organisms. (
  • Now a team of researchers headed by LMU's Professor Hans-Joachim Anders at the Department of General Medicine and Nephrology (Medical Clinic IV, Downtown Medical Campus) has uncovered the mechanism by which such crystals set off the train of events that leads to cell death. (
  • Thus, in contrast to the more widespread neuroprotective actions of sex steroids in the mammalian nervous system, in the AVPV estrogen regulates dopaminergic neuron number through a caspase-dependent mechanism of apoptotic cell death. (
  • This special issue celebrates the 10th Anniversary of Cell Death & Disease. (
  • This Collection features our best recent content from CDDpress, which publishes forefront, innovative and international research covering the cell biology, molecular biology, and biochemistry of cell death and disease. (
  • University of California San Diego School of Medicine researchers have been awarded nearly $9 million to fund two multi-institutional research projects that use human pluripotent stem cells, CRISPR and human organoids to dissect beta cell defects and create a human cell model of type 1 diabetes aimed at identifying the elusive cellular actions leading to disease onset. (
  • According to data from the Centers for Disease Control and Prevention (CDC), lung cancer is the leading cause of cancer-related death in the United States. (
  • We then reassess which forms of cell death occur in stroke and Alzheimer's disease, two of the most important pathologies involving neuronal cell death. (
  • Dr. Strasser and colleagues were the first to discover that abnormalities in cell death can cause cancer and autoimmune disease, including the discovery that BCL-2 collaborates with the MYC oncogene in tumorigenesis. (
  • A team of Melbourne researchers has shown a recently discovered type of cell death called necroptosis could be the underlying cause of inflammatory disease. (
  • This study estimated death rates among people with sickle cell disease (SCD) by matching up data from studies that monitor all people with SCD in a population with state death records. (
  • Read more about the sickle cell disease mortality study here external icon . (
  • Sickle Cell Disease is a group of genetic (inherited) red blood cell disorders. (
  • How many deaths occur among children with sickle cell disease detected through newborn screening? (
  • Despite recent progress in reducing death among young children with Sickle Cell Disease (SCD), some children with sickle cell anemia continue to die of health problems related to SCD. (
  • Children with a milder form of sickle cell disease known as sickle-hemoglobin C disease were not more likely to die than New York children who did not have SCD. (
  • To learn more about CDC's activities related to sickle cell disease and sickle cell trait check out the About Us section of our Web site. (
  • To learn more about sickle cell disease and sickle cell trait, please visit our sickle cell disease homepage . (
  • To obtain free resources on sickle cell disease and sickle cell trait, please visit the free materials section of our website. (
  • Mortality of New York Children with Sickle Cell Disease Identified Through Newborn Screening. (
  • In the study, published in Cell Death & Disease , the researchers show that healthy photoreceptor cells and cerebellar granule neuron cells were significantly more likely to survive chemotherapy in mice that had been genetically engineered to lack ALKBH7, as opposed to control mice that still had ALKBH7. (
  • For example, inhibition of cell death in the heart could potentially rescue an individual from death or serious disease following myocardial infarction injury. (
  • The next phase of Blander's research will be to investigate how the inflammatory conditions of IBD alter cell death and the homeostatic immunosuppressive functions of intestinal phagocytes, in both mouse models and different groups of IBD patients undergoing anti-TNF therapy at the Jill Roberts Center for Inflammatory Bowel Disease at New York-Presbyterian and Weill Cornell Medicine. (
  • This may be the result of the natural process of old cells dying and being replaced by new ones, or may result from such factors as disease, localized injury, or the death of the organism of which the cells are part. (
  • A study published in tomorrow's Nature suggests that a 'one-hit' hypothesis better explains the temporal pattern of cell death in a number of neurodegenerative disease models. (
  • But in their current paper, Roderick McInnes, Geoff Clarke, and colleagues at the University of Toronto present evidence supporting a model in which neurons in inherited disease exist in an abnormal steady state in which a rare catastrophic event will lead to cell death. (
  • The authors examined experimental models of inherited neurodegenerative disease (including 12 different models of photoreceptor degeneration, as well as models of cerebellar degeneration, Parkinson's disease, and hippocampal neurons undergoing excitotoxic death), as well as an indirect measure of cell loss in living Huntington's disease patients. (
  • It could be that we've identified the mechanics of how dying white blood cells go about alerting neighbouring cells to the presence of disease or infection. (
  • The clinic claims its technique for stem cell transplantation has had success in treating 17 different diseases including cerebral palsy, multiple sclerosis, autism, Parkinson's, Alzheimer's, heart disease, diabetes and spinal cord injuries. (
  • This cell suicide is critical not only for development (without it, we wouldn't have normal fingers and toes), but also to help stop the spread of disease. (
  • A new study pinpoints a major complication in adults with sickle cell disease that can often lead to death. (
  • The research shows nearly one-third of adults with sickle cell disease develop high blood pressure in their lungs and that the condition increases their risk of death. (
  • For the study researchers followed 195 sickle cell disease patients for two years. (
  • Thus researchers say the Doppler echocardiography is a reasonably priced, non-invasive test that should be offered to adults with sickle cell disease. (
  • Researchers say this study gives doctors an opportunity to address a major cause of disability and death in the adult sickle cell disease population and move forward with clinical trials to investigate therapies. (
  • Sickle cell anemia is the most common form of sickle cell disease. (
  • Alzheimer's disease (AD) is a devastating dementia of late life that is correlated with a region-specific neuronal cell loss. (
  • Despite progress in uncovering many of the factors that contribute to the etiology of the disease, the cause of the nerve cell death remains unknown. (
  • Quantitative analysis indicates that the genetic imbalance persists for many months before the cells die, and we propose that this imbalance is the direct cause of the neuronal loss in Alzheimer's disease. (
  • The present invention relates to a method of reducing cell death in a warm-blood animal wherein said cell death associated with a neurodegenerative disorder, an immune disease, a neoplastic disorder, an inflammatory disorder, or a viral disease. (
  • 1. A method of reducing cell death in a warm-blooded animal, said cell death associated with a neurodegenerative disorder, an immune disease, a neoplastic disorder, an inflammatory disorder, or a viral disease, said method comprising administering to said animal a therapeutically effective amount of a peptide comprising the amino acid sequence Val-Asp-Val such that cell death is reduced. (
  • For years, scientists suspected that E. histolytica caused disease by poisoning and killing human cells before gobbling up the cellular corpses. (
  • In studies in mice, Johns Hopkins Medicine researchers report they have found that bilirubin, a bile pigment most commonly known for yellowing the skin of people with jaundice, may play an unexpected role in protecting brain cells from damage from oxidative stress. (
  • Researchers have identified a molecule that determines whether or not a type of lung cancer cell will undergo cancer cell death. (
  • The researchers, from the Walter and Eliza Hall Institute, also discovered that the 'survival' molecule RIPK1 acts as the 'gatekeeper' between cell life and death. (
  • The researchers found higher death rates among people with SCD than previous estimates that used other methods. (
  • The researchers then compared these death rates to those of African Americans and to the general population in the corresponding states. (
  • By using multiple diverse sources of data, the researchers were able to gather information about people who may not have been included in previous studies, such as those who received care outside of sickle cell care centers or those who may have had limited or no access to regular medical care. (
  • Many challenges exist for researchers that work to accurately estimate the number of deaths among people with SCD. (
  • Because the researchers who conducted the study described here used multiple sources of information, they were able to gain a more accurate picture of age at death among people with SCD. (
  • Researchers at the University of Rochester, collaborating with colleagues at MIT, Harvard, and the University of Oslo, have identified a protein that is required for cell death after undergoing chemotherapy-at least, it appears, in male mice. (
  • The researchers used mice that were engineered to lack a protein they suspected would otherwise cause normal cells to self-destruct after exposure to chemotherapy or other stresses-a "regulated" death aimed at heading off the risk of mutation. (
  • RxPG] Researchers at UT Southwestern Medical Center have found an enzyme vital for controlling the early stages of cell death - a beneficial and normal process when it works right, but malignant in a variety of cancers when it malfunctions. (
  • The newly discovered enzyme, which the researchers have named Mule, destroys a key molecule at the top of the pyramid, thus leading to the cascading disintegration of the cell. (
  • The key to the researchers' finding was the interaction between the Mule enzyme and a major player in cell death, the protein Mcl-1. (
  • Using human cell extracts, the researchers found that Mule caused a protein called ubiquitin to bind to several sites on Mcl-1. (
  • Lead researchers, Dr Ivan Poon and Georgia Atkin-Smith said until now scientists had thought the breakdown of dying cells was a random process. (
  • Anthony Faber, Ph.D., and a team of researchers at VCU Massey Cancer Center were awarded a grant from the American Cancer Society to study how MYCN and an abundance of iron can drive cancer cell death in neuroblastoma and potentially be targeted with novel treatments. (
  • The researchers found that blocking these detoxifying systems with available drugs makes MYCN-amplified cells sick and die. (
  • Learning more about these cells could help researchers make specific cell types . (
  • Most research on embryonic stem cells has focused on how to grow them into different cell types in the lab, with studies of the cells themselves lacking, the researchers said. (
  • The embryonic cells keep this molecular kill switch, called Bax waiting, around for this very purpose, the researchers found. (
  • The researchers also hope to bolster the immune system by increasing the body's ability to produce new killer T-cells. (
  • Additionally, these researchers are testing a library of compounds to identify any that are capable of selectively targeting senescent cells. (
  • Researchers at The University of Texas M. D. Anderson Cancer Center have significantly refined the scientific understanding of how a cell begins the process of self-destruction - an advance they say may help in the design of more targeted cancer therapies. (
  • In a collaborative study carried out by an international team of researchers, which appears in the journal Nature, he and his colleagues focus on the role of cells known as neutrophils, which form a large part of the innate immune system. (
  • The researchers next paired amoebae with human red blood cells, since a hallmark of amoebiasis is finding traces of these cells inside amoebae. (
  • Researchers from the Cell death group of the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr. Cristina Muñoz-Pinedo, have characterized the cell death process due to starvation, in which the endoplasmic reticulum plays a leading role. (
  • Australian researchers have made a surprise discovery that could rewrite our understanding of the role programmed cell death plays in embryonic development and congenital birth defects. (
  • MDA-MB-231 cells were transfected with indicated plasmids along with a green fluorescent protein-encoding plasmid (GFP) using Lipofectamine. (
  • Previous research had shown that a protein dubbed p53 instructs cells with faulty DNA to commit suicide. (
  • Associate Professor Silke said the team had shown for the first time that RIPK1 (receptor interacting protein kinase 1) was a master controller of cell life and death. (
  • performed quantitative high-throughput analysis to investigate DNA methylation in the CpG island of DAPK1 ( death-associated protein kinase 1 ). (
  • The same effect was elicited with a dominant negative Rho mutant, suggesting that the protein was necessary for cell death. (
  • In their experiments, the scientists expressed a green fluorescent protein fused to the diphtheria toxin receptor within intestinal epithelial cells of mice, which made them visible under a microscope and sensitive to diphtheria toxin. (
  • Scientists at Albert Einstein College of Medicine of Yeshiva University have identified a small intracellular protein that helps cells commit suicide. (
  • Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. (
  • Another conserved flu protein that is strongly expressed in virus-infected cells is a nonstructural protein 1 (NS1). (
  • Dr. Craig Coopersmith of Washington University in St. Louis genetically engineered laboratory mice to produce large amounts of a cell death-blocking protein called bcl-2 in their intestines. (
  • This is a significantly important field of study that may have far-reaching implications in cancers beyond neuroblastoma, including some small cell lung cancers and triple negative breast cancer, which rely on a similar protein (c-MYC) to drive their growth. (
  • This is an image depicting active quick-kill molecule Bax (red) located in the protein-modifying compartment of the cell, the Golgi Apparatus, where it's kept safe so it doesn't accidentally kill the cell. (
  • An autonomous institute of the Agency for Science, Technology and Research in Singapore has announced the discovery of a human protein called Bax-beta (Bax ), which can potentially cause the death of cancer cells and lead to new approaches in cancer treatment. (
  • Our research findings reveal that Bax protein levels are normally kept at essentially undetectable levels in healthy cells by the protein degradation machine in cells known as proteasomes," said Dr. Victor Yu, who led the Institute of Molecular and Cell Biology (IMCB) research team. (
  • Before the discovery of Bax , only one single protein called Bax-alpha (Baxa) had been extensively studied in cells. (
  • These molecules then bind to another protein called Apaf-1 in the cell cytoplasm, and together they form a scaffolding "death wheel" to activate enzymes called caspases that shred a cell apart. (
  • In recent studies, we have shown that protein A of Staphylococcus aureus (SpA) has the properties of a B cell superantigen by virtue of interactions with a large supraclonal B cell set via high affinity framework-mediated interactions with soluble and cell-associated BCR ( 1 ). (
  • The reason for this prediction was that IRBIT has been primarily described as a protein that reduces cellular calcium levels, a phenomenon that can lead to cell death. (
  • Surviving de novo produced cells develop into granule neurons and integrate into the functional circuitry. (
  • The number of newly born cells increased contingently with the late phase and a large proportion of these cells survived for at least 4 weeks and differentiated into neurons. (
  • These neurons also have connections with the lymphatic system, which is engaged in transporting immune cells to and from the lymph nodes and can stimulate an immune response. (
  • Their work, published in the March 18 online edition of Nature Neuroscience, establishes Rho activation by calcium influx as a necessary and sufficient event to turn on p38 and cause cell death in primary neurons. (
  • They found a similar role for Rho in p38 activation and cell death after glutamate stimulation in cortical and hippocampal neurons in culture. (
  • Despite the obvious biochemical differences in the etiology of various neurodegenerative disorders, it is has been suggested that common principles may apply in the death of neurons in these diseases. (
  • At the point of injury, there is an immediate destruction of neurons, glial cells and blood vessels. (
  • One promising theory is that the neurons degenerate because they reenter a lethal cell cycle. (
  • We conclude that the AD neurons complete a nearly full S phase, but because mitosis is not initiated, the cells remain tetraploid. (
  • The loss of neurons during adult life, however, is a pathological process that produces behavioral disorders and potentially the death of the organism. (
  • Using mutant models of target-related cell death, Herrup and Busser (1995) showed that target-deprived neurons initiated the synthesis of cell cycle enzymes [cyclin D and proliferating cell nuclear antigen (PCNA)] and incorporated bromodeoxyuridine (BrdU) into high molecular weight DNA just before dying. (
  • There are fewer dopaminergic neurons labeled with tyrosine hydroxylase (TH) in the male AVPV than the female, and sex steroids determine this sex difference, yet the role of cell death in specifying numbers of dopaminergic neurons in the AVPV is unknown. (
  • The number of neurons that reside in brain nuclei are determined by a variety of factors that regulate production and death of neurons during development. (
  • Molecular Cell 36: 831-844, 2009. (
  • We are extending these and other key observations in an attempt to better characterize the molecular underpinnings of cell death in mammalian tissues. (
  • This TransDeath project will focus on cellular and molecular events in these less well known cell death types. (
  • Scientists based at the La Trobe Institute of Molecular Science have discovered that some molecules which are central to the body's defence and immune system are ejected from inside the decomposing cell to form long beaded strings that can break off and are distributed through the body. (
  • In this context, he was able to show which molecular processes are involved in ubiquitin-based signal transductions in cells and their relevance to carcinogenic processes, inflammatory reactions, autoimmune diseases, and diabetes. (
  • The study was published today (May 3) in the journal Molecular Cell. (
  • A fundamental characteristic of multicellular organisms is the ability to activate a gene-encoded cell suicide program called programmed cell death (PCD). (
  • First identified in the late 1960s by Leonard Hayflick and his collaborators, the term cellular senescence refers to the fact that normal, nonmalignant cells of vertebrates do not divide indefinitely in culture, but in time terminally differentiate and enter a prolonged postmitotic phase, eventually dying in the culture dish. (
  • In cases where ER stress cannot be reversed, cellular functions deteriorate, often leading to cell death. (
  • A fundamental cellular event related to programmed cell death has been decoded by cell biologists. (
  • This programmed cell death enables the body to maintain a state of equilibrium known as cellular homeostasis. (
  • By ramping up the systems that remove toxins on a cellular level, MYCN generates so much iron that it also initiates a weakness to drugs that block the ability of the cell to eliminate ROS, as discovered by Konstantinos Floros, Ph.D., postdoctoral fellow at Massey and the Philips Institute for Oral Health Research whose extensive background in cell death effectively advanced this research project. (
  • In these situations, cells typically lose the ability to maintain their volumes against osmotic forces, and they swell and rupture (technically, lyse), spilling their contents and provoking an inflammatory response. (
  • Cell debris lingers and can trigger an inflammatory response. (
  • The inflammatory response to cell death. (
  • When cells die in vivo, they trigger an inflammatory response. (
  • Moreover, during this process apoptotic cells can stimulate phagocytes to produce anti-inflammatory cytokines. (
  • Necroptosis is a type of 'controlled' death that instructs a cell to die while stimulating an inflammatory reaction to let the immune system know something has gone wrong. (
  • Though later changes in islet gene expression after cytokine activation have been mapped in a number of studies ( 14 , 15 ), we focused only on the immediate early response, as it is this response that determines cell fate after inflammatory insult ( 16 - 19 ). (
  • However, the surprising outcome of those studies was the finding that while NF-kB activation in hepatocytes (liver cells) prevents liver cancer, its activation in inflammatory cells, such as tissue macrophages, promotes tumor development. (
  • In these and other similar cases, exposure to crystalline microparticles not only provokes an immune reaction that initiates a chronic inflammatory process, but also results in cell death. (
  • Every inflammatory reaction results in some collateral damage, because neutrophils also attack healthy cells," he explains. (
  • They enter the underlying tissue by infiltrating between endothelial cells, while releasing compounds that attract still more immune cells, until at some point the inflammatory reaction becomes chronic. (
  • Associate Professor Silke said necroptosis was a newly discovered type of cell death that had only really been studied in the past five years. (
  • Why this matters: Cancer cells avoid destruction by inhibiting a process (which is called necroptosis). (
  • Strikingly, this signal relay is known to trigger a specific, injury-induced form of cell death, referred to as necroptosis. (
  • But cancer cells swerve away from this suicide path and become immortal. (
  • These forms of death are a sort of cell suicide, in which cells self-destruct in a controlled and contained manner. (
  • Building on Kaelin's findings, Washington University pathologist Steven F. Dowdy and his colleagues focused on suicide in immune system cells called T cells, a process known as T cell receptor activation-induced cell death (TCR-AICD). (
  • How, exactly, do damaged or diseased cells "commit suicide" to protect the body? (
  • Almost all of the cells committed suicide within five hours, suggesting these types of cells are more sensitive to damage than other cell types, which usually take 24 hours to die once they get damaged. (
  • With time winding down until the state planned to put Slagle to death for the fatal stabbing of a neighbor, he committed suicide inside his jail cell. (
  • Thymic selection is associated with extensive cell death, and only a very small proportion of thymocytes are selected for survival and export to the extrathymic environment. (
  • These authors and others have shown previously that high KCl is necessary for cerebellar granule cell survival. (
  • Other reports indicate that glutamate itself is a survival factor for these cells. (
  • Cell survival experiments in mixed alpha-particle and gamma-ray fields," Applied Radiation and Isotopes , vol. 67, no. 7-8, pp. (
  • But surprisingly, the improvement in brain cell survival rates occurred only in male mice, and was far more pronounced in males for photoreceptor cells as well. (
  • Thus, we have to weigh the cost/benefit of increasing the survival rate of normal cells with the increased risk of mutation and cancer," he says. (
  • UCL scientists have discovered that a vital self-destruct switch in cells is hijacked - making some pancreatic and non small cell lung cancers more aggressive, according to research published in Cancer Cell. (
  • But the darker side of this complex process manifests itself in cancers when cells don't die when they're supposed to. (
  • Too much, and cells stay alive when they shouldn't, leading to cancers such as lymphomas. (
  • If cell death does not occur when it should, cancer and other diseases may develop. (
  • Cancer Research UK scientists have found a drug combination that can trigger the self-destruct process in lung cancer cells - paving the way for new treatments, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference. (
  • Nanoparticles trigger cell death? (
  • The cell cycle, a cornerstone of cell biology in which cells divide to make new cells, regulates production via trigger waves, too. (
  • Trigger waves in an apoptotic cell are governed by that same phenomenon. (
  • The genes themselves become abnormal and, while they may be producing some cells, the cells do not produce endorphin. (
  • Their research revealed that T cells lacking either E2F-1 or p73 genes fail to undergo TCR-AICD. (
  • Direct phosphorylation by PKB results in cytoplasmic retention and inactivation, inhibiting the expression of FOXO-regulated genes, which control the cell cycle, cell death, cell metabolism and oxidative stress. (
  • Specifically, the study tried to ascertain which genes are expressed by phagocytes after the uptake of dead cells. (
  • Through a series of experiments, they found that several of the genes modulated up or down in phagocytes bearing dead cells overlapped with the same genes that have been associated with susceptibility to IBD. (
  • Macrophages, one kind of phagocyte, expressed genes that help process the increased lipid and cholesterol load they acquired from dying cells. (
  • Dendritic cells, another type of phagocyte, activated genes responsible for instructing the development of regulatory CD4 T cells, a class of suppressive white blood cells. (
  • Because the same genes that confer susceptibility to IBD were modulated in response to apoptotic cell sampling, the research indicates that a disruption of the phagocytes' immunosuppressive response would have consequences for homeostasis - or stable conditions - in the gut. (
  • Reactive oxygen species (ROS) are highly unstable chemical molecules that react with other molecules within a cell and cause damage to genes and cell death (ferroptosis). (
  • In the mouse, Fab-mediated SpA-binding interactions are commonly displayed by 5-10% of mature B cells, which express genes from the clan III set of related V H families, the murine homologues of human V H 3 genes ( 4 , 5 ). (
  • Genes must be expressed in precise levels and at the exact moment if the complex balance regulating cell activity is to be maintained. (
  • A ) Combined phase contrast-fluorescence micrographs of capillary endothelial cells cultured in suspension in the absence or presence of different-sized microbeads or attached to a planar culture dish coated with FN for 24 hours ( 28 ). (
  • Atherosclerosis is characterized by the build-up of fat-rich deposits known as plaques under the endothelial cell layer that forms the blood-vessel wall. (
  • A collaboration between WEHI (including the Strasser group), Genentech, and AbbVie led to development of the BCL-2 inhibitor venetoclax, approved for treatment of refractory chronic lymphocytic leukemia, while a similar collaboration with Servier yielded the first potent and selective inhibitor of cell-death inhibitor MCL-1, currently in clinical trials. (
  • Cyclosporin A, an inhibitor of cell death dependent on the opening of a mitochondrial permeability transition pore also blocked TH-ir cell loss. (
  • similar results were obtained by analyzing changes in nuclear condensation and fragmentation in cells stained with DAPI at 24 hours (gray bars). (
  • It is the first time we have ever seen this take place and we now need to better understand the reasons behind this and the implications of this process of cell fragmentation. (
  • The main hallmark of necrotic cell death is swelling leading to rupture of the cell membrane. (
  • In NSCLC, some epithelial cells - which form part of the lung tissue lining and normally align neatly with each other - transform into mesenchymal-like cells. (
  • In the study, published Nov. 9 in Nature, the scientists investigated the healthy turnover of epithelial cells, which are born and die every four to five days, to better understand how the gut maintains a healthy equilibrium. (
  • The investigators sought to understand whether phagocytes can take up dying epithelial cells in the gut and, if so, how these phagocytes respond. (
  • Irrespective of caspase activity, MOMP can lead to cell death by causing a progressive decline in mitochondrial function. (
  • We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (
  • Both the activity and the expression levels of caspase-3 and caspase-9 were elevated in the treated CAR cells. (
  • To test for caspase dependent TH-ir cell loss, the pancaspase inhibitor ZVAD ( N -benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone) was used to rescue TH-ir cells from estradiol-mediated reduction in number. (
  • In the context of NSCLC, they have the potential to become cancerous cells, invading healthy tissue and forming tumors. (
  • Whatever is at the root of cell death, the corpse lodged in the tissue cannot stick around forever. (
  • Embryonic stem cells are special because they can give rise to any tissue in the body. (
  • Such "senescent" are relatively harmless when they few in number, but these cells can accumulate over time, eventually reaching levels that are harmful to human tissue. (
  • This programming prevents skin cells from continuing down a path that leads to the development of cancer, for example, or halt uncontrolled growth of scar tissue cells and fibrous connective tissue after an injury. (
  • In the study, a number of cell types, including kidney-tubule cells and the fibroblast cells responsible for the production of connective tissue, were exposed to a variety of crystals. (
  • They then nibbled and killed the cells, penetrating deeper into the tissue. (
  • The findings suggest that amoebae might invade and destroy host intestinal tissue by nibbling alive the cells that line the gut," Ralston says. (
  • Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion. (
  • Cancerous mesenchymal-like cells are very often resilient and typically resist programmed cell death after exposure to chemotherapy. (
  • Then, when they compared the biochemical profiles of the cancerous cells, they were able to establish that miR-124 was key to determining whether or not the type of cell aforementioned would respond to chemotherapy agents. (
  • Failure to do so can lead to an accumulation of excess cells, each of which has the potential to mutate into a cancerous cell. (
  • Embryonic stem cells - those revered cells that give rise to every cell type in the body - will swiftly fall on their metaphorical swords for the greater good if they are injured, new research suggests. (
  • Limitations on government funding of human embryonic stem cell labs have also hampered work in this area. (
  • Deshmukh and colleagues treated human embryonic stem cells with DNA-damaging drugs to see what happened. (
  • Instead of activating Bax at the end of a long chain reaction, the embryonic stem cells have it ready and waiting in case of DNA damage. (
  • In this way, a damaged cell is dangerous to its fellow embryonic cells. (
  • Fig.1 Human cancer cells undergoing TRAIL-induced cell death. (
  • a new study led by Dr. Anurag Singh - from the Boston University School of Medicine in Massachusetts - has found that one molecule indicates whether or not some of the more resilient cancer cells die following chemotherapy . (
  • First, they confirmed the profiles of different types of lung cancer cells. (
  • He adds that better understanding the differences between how various cancer cells function will be a key element in this process. (
  • However, cancer cells often ignore these signals, flourishing even after chemotherapy drugs have ravaged their DNA. (
  • The sequences of the small conditional RNAs can be designed to accept different mRNA markers as inputs to HCR transduction, providing a programmable framework for selective killing of diverse cancer cells. (
  • In cultured human cancer cells (glioblastoma, prostate carcinoma, Ewing's sarcoma), HCR transduction mediates cell death with striking efficacy and selectivity, yielding a 20- to 100-fold reduction in population for cells containing a cognate marker, and no measurable reduction otherwise. (
  • Importantly, more than 20 years of intense research has paved the way for a rational design of selective anticancer therapies aimed at restoration of p53 functionality in cancer cells. (
  • Strategies for activation of p53 in cancer cells. (
  • By gaining a better understanding of how cells respond to chemotherapy, we are hoping to make these therapies more targeted for certain kinds of cells, such as a cancer cells-and also, importantly, to lessen the affects they have on our normal cells," Fu says. (
  • It is the most common mode of cell death in cancer cells exposed to ionizing radiation and many other anti-cancer treatments. (
  • Oncologists already use this type of approach when treating some types of cancer with the intent of shutting down the cancer cells' growth with drugs or by stimulating the immune system to do the job. (
  • But the notion of how to push cancer cells to die has been flawed, Tang says. (
  • This volume includes discussion of tumor suppression, the altered metabolism of cancer cells, and the development of therapeutic drugs. (
  • All cells carry within themselves the capacity to self-destruct, but are normally restrained from doing so. (
  • If this restraint is removed when a cell is challenged, it will default to the self-destruct mode and, assuming that the challenge is not so severe that the cell becomes necrotic, it will undergo this physiological form of death. (
  • A large pool of free nucleotides along with complete ATP molecules normally exists in a healthy cell so that just a little CC could not mistakenly push the cell to self destruct, Tang says. (
  • Multicellular organisms, including humans, need to keep a tight lid on the number of cells in their bodies. (
  • A new Finnish study suggests that type 1 diabetes may in part be caused by a novel subset of immune cells. (
  • Using SENS Research Foundation funding, scientists from University of Arizona are investigating ways to restore a healthy immune system in aging mice by purging unhealthy immune cells known as "anergic T-cells" to free up space for new and healthy killer T-cells. (
  • Immune cells migrate to sites of plaque formation via the bloodstream in response to specific biochemical signals. (
  • The scientists fluorescently labeled the membranes of human immune cells. (
  • Trogocytosis had been seen before in immune cells, which use the process to exchange pieces of molecules that might be targeted in an immune attack. (
  • But this nibbling activity doesn't destroy the immune cells. (
  • Excitotoxic cell death, the end for many cells after ischemic brain injury and in some neurodegenerative diseases, is triggered by glutamate-induced calcium influx. (
  • A Common Principle of Neurodegenerative Cell Death? (
  • If the genetically controlled death program is in any way defective, this can have serious consequences and can result, for example, in the promotion of tumor growth and neurodegenerative disorders. (
  • Sometimes our cells die when we really don't want them to - say, in neurodegenerative diseases. (
  • Phagocytes patrol our tissues on the lookout for "find-me" signals released by dying cells, and then engulf them when they encounter "eat-me" signals. (
  • Because cells, called phagocytes, can clear dying cells so quickly in the body, it had been difficult to study this process in tissues. (
  • The local differentials in cell growth and viability that drive morphogenesis in complex tissues, such as branching capillary networks ( 1 , 2 ), are controlled through modulation of cell binding to extracellular matrix (ECM) ( 3-6 ). (
  • Tissues that contain large numbers of senescent cells are at greater risk for developing cancer, becoming inflamed and negatively affecting the immune system. (
  • The new report describes how neutrophils damage tissues by initiating a previously unrecognized type of induced cell death. (
  • Both diseases kill nerve cells. (
  • The finding, reported as the "paper of the week" in the January 16th print issue of the Journal of Biological Chemistry, could lead to drugs for combating cancer and other diseases characterized by overproduction of cells. (
  • Programmed cell death (PCD) is normally invoked during development and immunity, but inappropriate PCD is associated with pathologies including cancer and degenerative diseases. (
  • Autophagic or Type II cell-death. (
  • Plant cells undergo particular processes of PCD similar to autophagic cell death. (
  • Cytokine induction of A20 mRNA in primary islets and insulinoma cells was rapid and observed within 1 h, consistent with A20 being an immediate early response gene in β-cells. (
  • Mutations that develop in these cells could be catastrophic for the developing organism, so it would make sense for these cells to be rapidly eliminated," Deshmukh said. (
  • Injured" cells with damaged DNA can lead to mutations that could kill an organism. (
  • If the organism dies, so do all of its cells. (
  • Of significant clinical relevance is the increasing evidence that neuronal degeneration in the adult organism is also accompanied by apparent cell cycle involvement. (
  • We initially expected that IRBIT would function to suppress cell death. (
  • PCD has become the general terms that refers to all the different types of cell death that have a genetic component. (
  • Sickle cell anemia (SCA) is a genetic blood disorder caused by abnormal inherited hemoglobin. (
  • Dead cells also release danger signals that activate dendritic cells and promote the generation of immune responses to antigens. (
  • 100-μm diameter) microcarrier beads ( 4 ), whereas they rapidly die when bound to small (4.5 μm) ECM-coated beads ( 10 ) that cluster integrins and activate signaling but do not support cell extension ( 11 ). (
  • ANYONE who reckons that science writing is dry stuff may find their outlook broadened by this little book about the biology of death. (
  • RBE-LET relationships for cell inactivation and mutation induced by low energy protons in V79 cells: further results at the LNL facility," International Journal of Radiation Biology , vol. 74, no. 4, pp. 501-509, 1998. (
  • Much of my work has been in the development of the chemical proteomic technology itself and it is only until recently that we are beginning to show the significance of cell death targets within our datasets and gain functional insight into the biology. (
  • Death on foot: Distracted driving, cell phones factor in pedestrian deaths U.S. emergency room visits blamed on cellphone use spiked 83.5 percent from 17,851 in 2007 - the year Apple introduced the iPhone - to 32,755 in 2016. (
  • The Governors Highway Safety Association has noted that the number of active cell phones in use in the U.S. between 2010 and 2016 increased by 236 percent. (
  • The Gutenberg Research College (GRC) of Johannes Gutenberg University Mainz (JGU) has chosen to give the 2016 Gutenberg Research Award to American biomedical researcher Dr. Vishva Dixit for his groundbreaking work in the field of programmed cell death. (
  • Access the latest web focus which highlights some of the latest research from China covered by the three journals in the Cell Death portfolio. (
  • Our research highlighted that RIPK1 is the gatekeeper that controls whether a cell lives or dies, and the decision it makes on how to die. (
  • As part of the research we found that RIPK1 was essential for keeping blood stem cells alive after bone marrow transplant," he said. (
  • Our research has shown that permeability transition, as regulated by cyclophilin D in the inner mitochondrial matrix, serves a nodal function in controlling cell death in response to oxidative injury and calcium overload. (
  • The natural life cycle of cells that line the intestine is critical to preserving stable conditions in the gut, according to new research led by a Weill Cornell Medicine investigator. (
  • Dr. Xiaodong Wang, professor of biochemistry at UT Southwestern and a researcher with the Howard Hughes Medical Institute, said the discovery of Mule will open up a whole field of research to study the enzyme's role in normal cell death and cancer. (
  • We think this gene will really be a hot spot in research," said Dr. Qing Zhong, postdoctoral researcher in biochemistry at UT Southwestern and lead author of a paper to be published in the July 1 issue of the journal Cell. (
  • This GRS will be held in conjunction with the "Cell Death" Gordon Research Conference (GRC). (
  • World-first research has captured the complex stages of the death of a human white blood cell using time-lapse microscopy - a unique phenomenon never seen before. (
  • His groundbreaking findings on cell death have provided important clues that help us understand in much more detail the processes associated with the immune system,' emphasized the Director of the Gutenberg Research College, Professor Matthias Neubert. (
  • In addition to his academic career, he contributes his extensive expertise as a top specialist in cell death research to the US biotech company Genentech. (
  • The ICDS is a nonprofit organization attempting to promulgate basic research and translational studies on the broad topic of cell death. (
  • Research at the University of California, San Diego (UCSD) School of Medicine shows that liver cancer is likely caused by cycles of liver cell death and renewal. (
  • In research published in the journal Cell in 2005, Karin and his colleagues at UCSD implicated the pathway's activator, IKK, in chemically induced liver cancer. (
  • It emerged from the research that certain cell cultures are not affect. (
  • The research teams of Professor Ilpo Vattulainen (Department of Physics, Tampere University of Technology, Finland) and academy researcher Emppu Salonen (Department of Applied Physics, Helsinki University of Technology, Finland) have together with Professor Pu-Chun Ke's (Clemson University, SC, USA) team researched how carbon-based nanoparticles interact with cells. (
  • It emerged from the research that certain cell cultures are not affected when exposed to fullerenes, i.e. nano-sized molecules that consist of spherical, ellipsoid, or cylindrical arrangement of carbon atoms. (
  • This book is a collection of selected and relevant research, concerning the developments within the Cell Death field of study. (