Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.Apoptosis: 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.Caspases: 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.Death: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.Cell Survival: 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.Necrosis: 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.Caspase 3: 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.Proto-Oncogene Proteins c-bcl-2: 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.DNA Fragmentation: 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.Mitochondria: 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)Autophagy: 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.Signal Transduction: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.In Situ Nick-End Labeling: 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.Death, Sudden, Cardiac: 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)Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.bcl-2-Associated X Protein: 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.Reactive Oxygen Species: 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, Cultured: 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.Antigens, CD95: 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.Brain Death: 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)Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Neurons: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Enzyme Activation: 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.Apoptosis Regulatory Proteins: 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.Fetal Death: Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.Cytochromes c: 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.Caspase 8: 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.Poly(ADP-ribose) Polymerases: 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.Caspase 9: 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.Fas Ligand Protein: 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.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.bcl-X Protein: 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.Attitude to Death: Conceptual response of the person to the various aspects of death, which are based on individual psychosocial and cultural experience.Blotting, Western: 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.Membrane Potential, Mitochondrial: 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.Tumor Cells, Cultured: 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.Tumor Suppressor Protein p53: 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.Hydrogen Peroxide: 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.Apoptosis Inducing Factor: 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.Receptors, Death Domain: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Proto-Oncogene Proteins: 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.Mice, Inbred C57BLEnzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Mutation: 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.Oxidative Stress: 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).Transfection: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.RNA, Small Interfering: 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.DNA Damage: 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.Models, Biological: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Flow Cytometry: 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.Mice, Knockout: 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.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.bcl-2 Homologous Antagonist-Killer Protein: 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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Cell Cycle: 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.Caspase 1: 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.Neoplasms: 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.Molecular Sequence Data: 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.Inhibitor of Apoptosis Proteins: 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.Tumor Necrosis Factor-alpha: 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.Receptor-Interacting Protein Serine-Threonine Kinases: 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.Membrane Proteins: 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.HeLa Cells: 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.Neuroprotective Agents: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Caspase 7: 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.Propidium: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.JNK Mitogen-Activated Protein Kinases: 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.Rats, Sprague-Dawley: 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.Genes, bcl-2: 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.Cell Nucleus: 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)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.RNA, Messenger: 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.Cysteine Endopeptidases: 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.Caspase 2: 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.RNA Interference: 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.Disease Models, Animal: 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.Down-Regulation: 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.Up-Regulation: 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.Gene Expression Regulation: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Staurosporine: 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)bcl-Associated Death Protein: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Apoptotic Protease-Activating Factor 1: 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.TNF-Related Apoptosis-Inducing Ligand: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Microtubule-Associated Proteins: 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, Fluorescence: 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.Death Domain Receptor Signaling Adaptor Proteins: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cytochrome c Group: 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)Calpain: 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.Amino Acid Sequence: 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.Proteins: 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.Risk Factors: 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.NF-kappa B: 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.Oxidants: Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Endoplasmic Reticulum: 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)Antioxidants: 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.Mitochondrial Membranes: 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).Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.DNA-Binding Proteins: 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.Mortality: All deaths reported in a given population.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Calcium: 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.Endoplasmic Reticulum Stress: 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.Proto-Oncogene Proteins c-akt: 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.Autopsy: Postmortem examination of the body.PC12 Cells: 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.Plant Diseases: Diseases of plants.Caspase 6: 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.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Immunoblotting: 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.Animals, Newborn: Refers to animals in the period of time just after birth.Acetylcysteine: 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.Protein Transport: 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.Lysosomes: 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)Protein Binding: 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.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Neurotoxins: 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.Mitogen-Activated Protein Kinases: 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).Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Nuclear Proteins: 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.X-Linked Inhibitor of Apoptosis Protein: 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.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Myeloid Cell Leukemia Sequence 1 Protein: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Glutathione: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Receptors, TNF-Related Apoptosis-Inducing Ligand: 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.L-Lactate Dehydrogenase: 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.Intracellular Signaling Peptides and Proteins: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Nerve Degeneration: 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.Follow-Up Studies: 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.Microscopy, Confocal: 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.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Microscopy, Electron: 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.T-Lymphocytes: 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.Treatment Outcome: 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.Nerve Tissue ProteinsProtein Synthesis Inhibitors: 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.Epithelial Cells: 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.Drosophila Proteins: 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.Tobacco: A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.Retrospective Studies: 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.Brain: 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.Mitosis: 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.Infant, Newborn: An infant during the first month after birth.Programmed Cell Death 1 Receptor: 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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Plant Leaves: 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)Hippocampus: 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.Trypan Blue: A diazo-naphthalene sulfonate that is widely used as a stain.Adaptor Proteins, Signal Transducing: 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 enzymesp38 Mitogen-Activated Protein Kinases: 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.HL-60 Cells: 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)Survival Analysis: 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.Protein Structure, Tertiary: 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.Gene Expression Regulation, Developmental: 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.Etoposide: 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.Transcription Factor CHOP: 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.Green Fluorescent 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 Fusion Proteins: 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.Caspases, Initiator: 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.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Mice, Inbred BALB CAdenosine Triphosphate: 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.Embryo, Mammalian: 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.Neurodegenerative Diseases: 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.Drug Screening Assays, Antitumor: 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.Stress, Physiological: 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.Cell Line, Transformed: 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.Neuroblastoma: 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)Macrophages: 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.)DNA: 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).Salicylic Acid: A compound obtained from the bark of the white willow and wintergreen leaves. It has bacteriostatic, fungicidal, and keratolytic actions.Neoplasm Proteins: 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.Tetrazolium Salts: 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)Phosphatidylserines: 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.Arabidopsis: 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.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Proteasome Endopeptidase Complex: 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.

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 ...
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 ...
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
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.
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 ...
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.
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...
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 ...
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 ...
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
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. ...
News and bulletins from science and industry in quality management and sample preaparation on the subject of cell death can be found on this page.
Deoxyribonucleic acid synthesis was straight related to cell country and programmed cell death was switched off in the event of cell distributing. Cellular proliferation and programmed cell death was determined under changing growing status. When cells were grown on different sized, square-shaped FN coated islands, programmed cell death declined and DNA synthesis increased with size runing from 75 to 3000µm2. Death rate for different sized islands were measured by TUNEL staining and the consequences were plotted and showed that a larger surface country of the island possessed a better status for cell spreading and growing This was besides observed that by increasing cell distributing on a homogeneous FN coated would take to cell growing when the entire country of cell to ECM fond regard were kept changeless. Under this conditions growing conditions, DNA synthesis increased and programmed cell death decreased with increased in cell spreading. Using substrates coated with specific antibodies to ...
reduce the TOOLS buy Glutamate, Cell Death and not WORD COUNT. A buy Check will coordinate writing the Twitter area. Select WORD COUNT from the buy Glutamate, Cell Death combined PROOFING.
Fang J, Nakamura T, Cho DH, Gu Z, Lipton SA. S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinsons disease ...
Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans [(PUBMED:11341280)]. In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.. Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes [(PUBMED:12631689)]. At least 20 Bcl-2 proteins have been reported in mammals, and several others have been identified in viruses. Bcl-2 family proteins fall roughly into three subtypes, which either promote cell survival (anti-apoptotic) or trigger cell death ...
The next IsSDB annual symposium will focus on Developmental Cell Death. It will be held at the Weizmann Institute on June 18th, 2017. This 1-day symposium will be shared with the International Cell Death Society (ICDS). The program includes lectures by local scientists and scientists from overseas, and will soon be posted on the IsSDB website. Attendance to this symposium is free of charge for IsSDB members (and their lab personnel), albeit it requires pre-registration (a link for registration will soon appear in the IsSDB website ...
Modulation of cisplatin-induced tumour cell death by AMPK and mTOR. (A) U251 cells transfected with control, AMPK or mTOR siRNA were incubated in the absence or
Apoptosis is the physiological process used by an organism to selectively eliminate cells that are no longer needed, have been damaged or are dangerous ( Kerr et al., 1972). This process, critical for sculpting organs during development and ensuring homeostasis throughout life, has been conserved during evolution ( Vaux and Strasser, 1996). Defects in the control of apoptosis have been implicated as a cause or a contributing factor in a variety of diseases. For example, abnormal survival of cells that should be killed can cause cancer ( Strasser et al., 1990) or autoimmune disease ( Bouillet et al., 1999; Strasser et al., 1991b; Watanabe-Fukunaga et al., 1992), whereas premature death of normally long-lived cells may be the cause of certain degenerative disorders ( Barr and Tomei, 1994).. Genetic and biochemical studies have identified two major pathways to programmed cell death that are largely independent ( Strasser et al., 1995). On the one hand, apoptosis can be triggered by ligation of a ...
A new study finds that one molecule is key to whether or not particular lung cancer cells respond to chemotherapy and undergo programmed cell death.
a type of cell death in which the cell uses specialized cellular machinery to kill itself; a cell suicide mechanism that enables metazoans to control cell number and eliminate cells that threaten the animals survival. ...
An introduction to my next series, exploring Cancer Biology. In this substantial topic we introduce some key concepts and consider the paradox that all life is dependent on cell death.
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Ferroptosis was recently identified as a form of programmed cell death. Activation of ferroptosis results in destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. CaymanCurrents no.4, 2018 is focused on ferroptosis and there you will find amongst other ...
Apoptosis is a programmed form of cell death with well-defined morphological traits that are often associated with activation of caspases. More recently evide
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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.
), PDCD-4 (programed cell death four), and PTEN. We have recently shown that higher levels of miR-21 expression within the stromal compartment within a cohort
Cancer cells devise a myriad of strategies to antagonize cell death, but these countermeasures prove to be imperfect (1). Although the economies of cell proliferation and accumulation dominate cell demise during disease progression, pathologic examination of established cancers typically reveals evidence for both single cell and zonal areas of tumor death. Mixtures of apoptosis, necrosis, and autophagy frequently may be discerned histologically. These varying forms of cellular destruction reflect the failure of tumors to cope adequately with the challenging burdens of cellular stress (2). Such ongoing insults include DNA damage and genomic instability; perturbed signal transduction and transcriptional networks; the unfolded protein response, hypoxia, nutrient deprivation, immunologic attack; and likely many others (3). Notwithstanding the intense effort directed toward unraveling the mechanisms underlying cancer cell death, much less attention have been devoted to understanding the host response ...
Chronic triggers that preceded the expressed desire for hastened death included debilitating progression of disease; perception of chronic and progressive loss of social support, dignity, autonomy, and sense of worth; and perception of being a burden to self or others in the present or future. Acute events preceding expression of a desire for hastened death included uncontrolled pain, shortness of breath, and medical information that produced fear, hopelessness, and a sense of dread.. 9 distinct, but sometimes intertwined and overlapping, meanings and uses of an expressed desire for hastened death were extrapolated from the narratives. (1) A manifestation of the will to live. This theme was named the "primary paradox" because patients behaviour evidenced the will to live despite having expressed a desire for hastened death on ⩾1 occasion. For example, "See, theres a problem while planning or pursuing your death… On the one hand, I am saying all these things, and, on the other hand, I am ...
Chronic triggers that preceded the expressed desire for hastened death included debilitating progression of disease; perception of chronic and progressive loss of social support, dignity, autonomy, and sense of worth; and perception of being a burden to self or others in the present or future. Acute events preceding expression of a desire for hastened death included uncontrolled pain, shortness of breath, and medical information that produced fear, hopelessness, and a sense of dread.. 9 distinct, but sometimes intertwined and overlapping, meanings and uses of an expressed desire for hastened death were extrapolated from the narratives. (1) A manifestation of the will to live. This theme was named the "primary paradox" because patients behaviour evidenced the will to live despite having expressed a desire for hastened death on ⩾1 occasion. For example, "See, theres a problem while planning or pursuing your death… On the one hand, I am saying all these things, and, on the other hand, I am ...
Crane, John K., Swastika Majumdar, and Donald F. Pickhardt. "Host Cell Death due to EnteropathogenicEscherichia coli Has Features of Apoptosis." Infection and Immunity 67.5 (1999): 2575-2584. Web. 24 Jan. 2020. ...
Heart disease is still the leading cause of death, with 20,046 deaths in 2012, however this has fallen steadily since 2003. Heart disease accounted for 14 per cent of all deaths in 2012 compared to 19 per cent of all deaths in 2003, said James Eynstone-Hinkins, ABS Director of the Health and Vitals Statistics Unit ...
Could Soma cause Death? We studied 12,177 Soma users who have side effects from FDA and eHealthme. Among them, 180 have Death. See what we found.
One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that ...
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We cant wait for the energy transition. #ReclaimPower now & tell governments to stop supporting #dirtyenergy thndr.me/QQeYsz 1 year ago ...
Death is an elemental aspect of life. It is an inevitable transition yet it seems to remain one stage of the life cycle that causes most discomfort. This course enables students to explore their own life backgrounds as they engage in a critical and exploratory study of ideas and issues surrounding Death and Dying. The course will look at Societys attitudes about death, varied
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La nécrose, lapoptose et la mort cellulaire autophagique sont toutes les manières dont les cellules peuvent mourir et ces mécanismes...
In 2012, a total of 41 900 persons living in Norway died, of which 22 300 were women and 19 600 were men. Lung diseases accounted for 10 per cent of all deaths in 2012. Eight out of ten deaths are caused by cardiovascular diseases or malignant cancer.
As a society, weve come to believe that people dont need to suffer. If youre in pain, somethings wrong, go to the doctor, it can be fixed. In many ways, this is a good thing, fewer people suffer needlessly with mental illnesses because of the awareness that some suffering is the result of a treatable disease: they come for help and they get it (this is good). Others are diagnosed with illnesses that, had they waited, would have been fatal (say early stage cancers, infections that might spread, and the list marches on). This is also good. Life, however, remains chock full of suffering, and not all of it is about treatable illnesses, and Death is no exception. Family members suffer when their loved ones die miserable deaths, only now they are left to believe they should have done something "more" to help the loved one die differently ...
... I have been seeing quite a few posts regarding the dreaded Blue Screen of Death, and what the STOP codes mean. This is a fairly extensive list of the most common stop errors, their corrasponding codes, and recommended solutions. When Windows XP detects a problem from which it cannot recover, it displays Stop messages. These are text-mode error messages that report information about the condition. Stop messages, sometimes referred to as blue
What happens when we die is easier to explain than deciding if we are dead. A non-beating heart is not always considered death. The stages of death and dying are described.
Naij.com News ★ Nigerians are still in shock over the death of gospel star Eric Arubayi. His brother Derrick Arubayi has revealed the cause of his death - fake medicine.
On Death and Dying by Elisabeth Kubler-Ross is an easy to understand look at important issues, attitudes and factors that contribute to societys anxiety about death presented in a kind but factual manner. It is based on hundreds of actual patient in...
Who would win in a fight to the death, a burly burrito or a light spry taco? Burrito Supreme Pros- Thicker wrap Super beefy punch Aggressive and territorial/Fights to the death Cons-...
In my opinion, this is a very common symptom, so I post this post for you guys to read and to be aware of things. What is Internal Bleeding? Internal bleeding is considered as one of the most serious problems that can even cause death if it is not stopped early. It is the bleeding out of the blood vessel. Unlike conventional bleeding which is out from the wound in the surface of the body and can be recognized easily, internal bleeding is bleeding happening inside the body (in the tissue,
Az effektor T-sejtek eliminációja az immunválasz végén Antigén-indukálta sejthalál (AICD - antigen-induced cell death) A folyamatos T-sejt aktiváció pro-apoptotikus szignálokat indukál (Fas, FasL, Bad, Bax expresszió nő, Bcl-2 expresszió csökken)
This series of article will discuss the most common ways to die. Death is a subject with must face and if we take steps to prevent the most common ways to die, were way ahead of 99% of other people and well probably outlive them. In this article, well look at the number 1 most common way to die and how to prevent it.
Death is natural, and having concerns about it is natural. What isnt natural is refusing to talk about it. But here are a few things that might be helpful.
There is no reason we have to die. Thats just a biological mechanism for evolving the species. Science will eventually learn how to beat death.
Sodas and other sugary drinks may cause up to 184,000 deaths a year worldwide, according to a study published Monday in the journal Circulation.
Dear CMcC,. God not not intend that human beings would die. Adam by his disobedience was directly responsible for its entrance of death into the world of mankind.. Dr. Geraghty ...
Daily, weekly, and monthly suggestions for teaching The Death Cure. The calendar is part of a comprehensive Lesson Plan from BookRags.com.
When death is within hours or days, people often avoid food and drink, and their excretory systems slow considerably, according to WebMD. Pain sometimes increases, and breathing becomes labored or...
Whether Joe Anthony Lopez is responsible for the death of 20-month-old Ruby Alvarez last year will hinge on which medical opinions the jury believes.
Our Dallas wrongful death law firm can help you and your family seek the justice your loved one deserves. Call us today at 1-877-405-4313 or 214-651-6100.
This barely released thriller, Any Mans Death, offers one dunderheaded miscasting coup after another. Waspy John Savage plays a Jewish…
Scientists have found that a cluster of genetic mutations accelerate the series of cell deaths that lead to ageing.

According to the
Gebel J, Luh LM, Coutandin D, Osterburg C, Löhr F, Schäfer B, Frombach AS, Sumyk M, Buchner L, Krojer T, Salah E, Mathea S, Güntert P, Knapp S, Dötsch V., Cell Death Differ. 2016 Dec;23(12):1930-1940.. ...
Every day in the U.S. about 89 people are shot dead in one way or another. At GunMemorial.org we try to post pages for all of these people even though the circumstances of their deaths can be drastically different ...
Hello, here is my first post for ask for help here: I have a problem with my Windows 7 Professional X64. I went back from my vacactions and now, when i tried to initialize windows 7, it only shows the
The Lakeland, Fla., Ledger has announced to readers that the number of news inches an obituary receives in the paper will henceforth be determined by t ...
The other day the name of George Carlin came up and I realized it had been more than five years since his death and it was hard to believe it had been
(−)-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,
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 ...
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 ...
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 ...
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
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 ...
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 ...
Finland Deaths Stats", NationMaster. Retrieved from http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths. "Finland Deaths Stats, NationMaster." 1948-2012. ,http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths,.. Finland Deaths Stats, NationMaster, ,http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths, [assessed 1948-2012]. "Finland Deaths Stats", NationMaster [Internet]. 1948-2012. Avaliable from: ,http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths,.. "Finland Deaths Stats", NationMaster. Avaliable at: nationmaster.com. Assessed 1948-2012.. "Finland Deaths Stats, NationMaster," http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths (assessed 1948-2012). "Finland Deaths Stats", NationMaster, http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths (last visited 1948-2012). "Finland Deaths Stats", NationMaster, http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths (as ...
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Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca(2+) fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca(2+) influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca(2+) fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates ...
Oxidative stress-induced neuronal apoptosis plays an important role in the progression of central nervous system (CNS) diseases. In our study, when neuronal cells were exposed to hydrogen peroxide (H2O2), an exogenous oxidant, cell apoptosis was observed with typical morphological changes including membrane blebbing, neurite retraction and cell contraction. The actomyosin system is considered to be responsible for the morphological changes, but how exactly it regulates oxidative stress-induced neuronal apoptosis and the distinctive functions of different myosin II isoforms remain unclear. We demonstrate that myosin IIA was required for neuronal contraction, while myosin IIB was required for neuronal outgrowth in normal conditions. During H2O2-induced neuronal apoptosis, myosin IIA, rather than IIB, interacted with actin filaments to generate contractile forces that leaded to morphological changes. Moreover, myosin IIA knockout using CRISPR/Cas9 reduced H2O2-induced neuronal apoptosis and the associated
The Fusarium mycotoxin deoxynivalenol (DON) can cause cell death in wheat (Triticum aestivum), but can also reduce the level of cell death caused by heat shock in Arabidopsis (Arabidopsis thaliana) cell cultures. We show that 10 μg mL−1 DON does not cause cell death in Arabidopsis cell cultures, and its ability to retard heat-induced cell death is light dependent. Under dark conditions, it actually promoted heat-induced cell death. Wheat cultivars differ in their ability to resist this toxin, and we investigated if the ability of wheat to mount defense responses was light dependent. We found no evidence that light affected the transcription of defense genes in DON-treated roots of seedlings of two wheat cultivars, namely cultivar CM82036 that is resistant to DON-induced bleaching of spikelet tissue and cultivar Remus that is not. However, DON treatment of roots led to genotype-dependent and light-enhanced defense transcript accumulation in coleoptiles. Wheat transcripts encoding a phenylalanine
TY - JOUR. T1 - Dentate development in organotypic hippocampal slice cultures from p35 knockout mice. AU - Wenzel, H. Jürgen. AU - Tamse, Catherine T.. AU - Schwartzkroin, Philip A. PY - 2006/12. Y1 - 2006/12. N2 - Abnormal brain development, induced by genetic influences or resulting from a perinatal trauma, has been recognized as a cause of seizure disorders. To understand how and when these structural abnormalities form, and how they are involved in epileptogenesis, it is important to generate and investigate animal models. We have studied one such model, a mouse in which deletion of the p35 gene (p35-/-) gives rise to both structural disorganization and seizure-like function. We now report that aberrant dentate development can be recognized in the organotypic hippocampal slice culture preparation generated from p35-/- mouse pups. In these p35-/- cultures, an abnormally high proportion of dentate granule cells migrates into the hilus and molecular layer, and develops aberrant dendritic and ...
TY - JOUR. T1 - Phenoxazine derivatives induce caspase-independent cell death in human glioblastoma cell lines, A-172 and U-251 MG. AU - Shirato, Ken. AU - Imaizumi, Kazuhiko. AU - Abe, Akihisa. AU - Tomoda, Akio. PY - 2007/1. Y1 - 2007/1. N2 - The apoptotic effects of 2-amino-4,4α-dihydro-4α, 7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 2-amino-phenoxazine-3-one (Phx-3) on human glioblastoma cell lines, A-172 and U-251 MG were studied. These phenoxazines extensively decreased the viability of A-172 and U-251 MG cells (IC50 of Phx-1: 60 μM, in both lines; IC50 of Phx-3: 10 and 3 μM, for A-172 and U-251 cells, respectively). Phx-1 and Phx-3 increased the population of annexin V and PI double-positive cells in A-172 and U-251 MG cells, resulting in cell death at late stage apoptosis/necrosis. The activities of caspase-3/7 were greatly increased in A-172 and U-251 MG cells treated with Phx-1 or Phx-3. However, a pan-caspase inhibitor, z-VAD-fmk, failed to reverse the antiproliferative and ...
TY - JOUR. T1 - Caspase-dependent and -independent cell death pathways in primary cultures of mesencephalic dopaminergic neurons after neurotoxin treatment. AU - Han, Baek S.. AU - Hong, Hyun Seung. AU - Choi, Won Seok. AU - Markelonis, George J.. AU - Oh, Tae H.. AU - Oh, Young Jun. PY - 2003/6/15. Y1 - 2003/6/15. N2 - Although the cause of neuronal death in Parkinsons disease (PD) is mainly unknown, growing evidence suggests that both apoptotic and non-apoptotic death may occur in PD. Using primary cultures of mesencephalic dopaminergic neurons and the MN9D dopaminergic neuronal cell line, we attempted to evaluate specifically the existence of the mitochondrial apoptotic pathway, focusing on the mitochondrial release of cytochrome c to the activation of the caspases after 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated mitochondrial release of cytochrome c into the cytosol after 6-OHDA or MPP+ ...
Question - Pregnancy test positive, taken alcohol, cause neuronal death irreversible, contemplating medical abortion. Advice?. Ask a Doctor about Medical abortion, Ask an OBGYN, Maternal and Fetal Medicine
TY - JOUR. T1 - Synergid cell death in Arabidopsis is triggered following direct interaction with the pollen tube. AU - Sandaklie-Nikolova, Linda. AU - Palanivelu, Ravishankar. AU - King, Edward J.. AU - Copenhaver, Gregory P.. AU - Drews, Gary N.. PY - 2007/8. Y1 - 2007/8. N2 - During angiosperm reproduction, one of the two synergid cells within the female gametophyte undergoes cell death prior to fertilization. The pollen tube enters the female gametophyte by growing into the synergid cell that undergoes cell death and releases its two sperm cells within the degenerating synergid cytoplasm to effect double fertilization. In Arabidopsis (Arabidopsis thaliana) and many other species, synergid cell death is dependent upon pollination. However, the mechanism by which the pollen tube causes synergid cell death is not understood. As a first step toward understanding this mechanism, we defined the temporal relationship between pollen tube arrival at the female gametophyte and synergid cell death in ...
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: ...
... the apoptosis is no longer inhibited resulting in the death of the cell. ER stress increases cIAP1 expression in cancer cells ... Cell Death. Wiley. Temesgen Samuel, Tracy Mitchell, John C Reed & Didier Y R Stainier, Massimo M Santoro. "Birc2 (cIap1) ... As a consequence RIP1 forms a cytosolic complex with the adaptor molecule FADD and caspase 8, which leads to cell death. When ... When a cell is tumorous it does not cease to proliferate inhibiting the apoptosis, as a result, in cancerous cells cIAP1 is ...
... and causes cell death in cultured cells". J. Biol. Chem. 275 (4): 2647-53. doi:10.1074/jbc.275.4.2647. PMID 10644725. Li PF, Li ... "Calcium binding of ARC mediates regulation of caspase 8 and cell death". Mol. Cell. Biol. 24 (22): 9763-70. doi:10.1128/MCB. ... "Inhibition of both the extrinsic and intrinsic death pathways through nonhomotypic death-fold interactions". Mol. Cell. 15 (6 ... Cell Death Differ. 12 (6): 682-6. doi:10.1038/sj.cdd.4401631. PMID 15861191. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T ...
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Shaul Y (2000). "c-Abl: activation and nuclear targets". Cell Death Differ. 7 (1): 10-6. doi:10.1038/sj.cdd.4400626. PMID ... cell division, cell adhesion, and stress response. Activity of ABL1 protein is negatively regulated by its SH3 domain, and ... Cell. 6 (6): 1413-23. doi:10.1016/S1097-2765(00)00138-6. PMID 11163214. Yoshida K, Komatsu K, Wang HG, Kufe D (May 2002). "c- ... Cell. Biol. 22 (12): 4020-32. doi:10.1128/MCB.22.12.4020-4032.2002. PMC 133860 . PMID 12024016. Cao C, Leng Y, Kufe D (August ...
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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, ...
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"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 ... 5.1 Cell Membrane Structure , Life Science , University of Tokyo Alberts, Bruce (2002). Molecular biology of the cell (4th ed ... These vesicles fuse with the cell membrane at the pre-synaptic terminal and release its contents to the exterior of the cell. ...
Cell Death Differ 2010; 17: 801-810. Hernández-Muñoz, I.; Lund, A. H.; van der Stoop, P.; Boutsma, E.; Muijrers, I.; Verhoeven ... Its roles in the cell cycle and apoptosis help cells maintain an immature state, and its expression wanes as cells begin to ... modulation of these cell cycle inhibitor genes also allows Bmi-1 to malignantly transform cells (both mature and stem cells) ... Maintenance of adult stem cells PcG proteins are also key players in the maintenance of adult stem cell populations. Several ...
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... 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. Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang ... hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning". Proc Natl Acad Sci U S ...
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Cell Death Dis. 6: 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, ...
Cell Death Dis. 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: e82. doi:10.1038/cddis.2010.59. PMC 3035901 . PMID 21368855. Rabouille C, Linstedt AD (2016). "GRASP: ... Yoshimura S, Yoshioka K, Barr FA, Lowe M, Nakayama K, Ohkuma S, Nakamura N (June 2005). "Convergence of cell cycle regulation ... Cell. 91 (2): 253-62. doi:10.1016/S0092-8674(00)80407-9. PMID 9346242. Barr FA, Nakamura N, Warren G (June 1998). "Mapping the ... The Journal of Cell Biology. 155 (4): 557-70. doi:10.1083/jcb.200107045. PMC 2198855 . PMID 11706049. Lane JD, Lucocq J, Pryde ...
"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 Differ. 14 (3): 422-35. doi:10.1038/sj.cdd.4402018. PMID 16888644. Ota T, Suzuki Y, Nishikawa T, et al. (2004). " ... 2007). "HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase". Cell Cycle. 6 ... Wen X, Duus KM, Friedrich TD, de Noronha CM (2007). "The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a ... 2007). "Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle". Proc. Natl. Acad. Sci. U.S.A. 104 ( ...
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
Boison D, Chen JF, Fredholm BB (July 2010). "Adenosine signaling and function in glial cells". Cell Death Differ. 17 (7): 1071- ... The P2X7 receptor also serves as a pattern recognition receptor for extracellular ATP-mediated apoptotic cell death, regulation ... "Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages". Biochem. Biophys. Res. Commun. 419 (2 ... In melanocytic cells P2X7 gene expression may be regulated by MITF. Activation of the P2X7 receptor by ATP leads to recruitment ...
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 ...
Kinds of cell death include the following: Programmed cell death (or PCD) is cell death mediated by an intracellular program. ... Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is ... doi:10.1016/j.cell.2012.03.042. Zhang J, Xu X, Liu Y. (2004), Activation-Induced Cell Death in T Cells and Autoimmunity. Cell ... 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 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 ...
... 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 ...
... Description:. MDA-MB-231 cells were transfected with indicated plasmids along with a green ... Cells were photographed using a fluorescence microscope 48 h after transfection. XEDAR- and DR4-transfected cells had a rounded ... appearance and were detaching from the plate, whereas the cells transfected with the vector have a normal morphology. ... NIDCR , Image Gallery , Science , XEDAR Induces Cell Death XEDAR Induces Cell Death. ...
... (19-Apr-1955). Director: Fred F. Sears. Writer: Jack DeWitt. Based on a book by: Caryl Chessman. Producer: ... Keywords: Crime, Prison, Death Row. Name. Occupation. Birth. Death. Known for. Eleanor Audley. Actor. 19-Nov-1905. 25-Nov-1991 ...
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 ...
... death cell by imagegrabber as a Poster, Throw Pillow, Tote Bag, Art Print, Canvas Print, Framed Print, Photographic Print, ... the cell next door held the coffin…this is the cell..it was pretty chilly ...
... 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 maroon.tc.umn.edu 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 ...
... Richard A. Lockshin lockshin at mindspring.com Tue Nov 18 11:07:50 EST 1997 *Previous message ... We announce the formation of the Cell Death Society. Membership provides several advantages, including discount subscriptions ... to cell death journals and reduced registration at annual meeting. For more complete details see announcement on web page, http ... Richard A. Lockshin (lockshin at mindspring.com;lockshin at sjumusic.stjohns.edu) check out Cell Death Soc web page: http://rdz ...
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 ...
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, ...
  • 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). (sciencemag.org)
  • Irrespective of caspase activity, MOMP can lead to cell death by causing a progressive decline in mitochondrial function. (sciencemag.org)
  • 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. (mdpi.com)
  • 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. (cincinnatichildrens.org)
  • Cyclosporin A, an inhibitor of cell death dependent on the opening of a mitochondrial permeability transition pore also blocked TH-ir cell loss. (jneurosci.org)
  • Implication of mitochondrial dysfunction and cell death in cold p. (ingentaconnect.com)
  • Researchers are looking at actin polymerization and calcium uptake in human cells to study mitochondrial division. (the-scientist.com)
  • Such changes can be used to mimic and study (patho)physiological scenarios, including caloric restriction and longevity, the Warburg effect in cancer cells or changes in mitochondrial mass affecting cell death. (biomedsearch.com)
  • MDA-MB-231 cells were transfected with indicated plasmids along with a green fluorescent protein-encoding plasmid (GFP) using Lipofectamine. (nih.gov)
  • Previous research had shown that a protein dubbed p53 instructs cells with faulty DNA to commit suicide. (scientificamerican.com)
  • 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. (redorbit.com)
  • performed quantitative high-throughput analysis to investigate DNA methylation in the CpG island of DAPK1 ( death-associated protein kinase 1 ). (sciencemag.org)
  • The same effect was elicited with a dominant negative Rho mutant, suggesting that the protein was necessary for cell death. (alzforum.org)
  • 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. (rochester.edu)
  • 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. (rochester.edu)
  • Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged. (jci.org)
  • 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. (scienceblog.com)
  • Scientists at Albert Einstein College of Medicine of Yeshiva University have identified a small intracellular protein that helps cells commit suicide. (innovations-report.com)
  • Another conserved flu protein that is strongly expressed in virus-infected cells is a nonstructural protein 1 (NS1). (innovations-report.com)
  • The key to the researchers' finding was the interaction between the Mule enzyme and a major player in cell death, the protein Mcl-1. (rxpgnews.com)
  • Using human cell extracts, the researchers found that Mule caused a protein called ubiquitin to bind to several sites on Mcl-1. (rxpgnews.com)
  • 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. (nih.gov)
  • 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. (livescience.com)
  • 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. (medindia.net)
  • 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. (medindia.net)
  • Before the discovery of Bax , only one single protein called Bax-alpha (Baxa) had been extensively studied in cells. (medindia.net)
  • 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. (rupress.org)
  • 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 ). (rupress.org)
  • 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. (riken.jp)
  • 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. (riken.jp)
  • They found the brain cells were protected, protein levels were restored and synaptic transmission -- the way brain cells signal to each other -- was re-established. (lifescript.com)
  • Further investigation into the mechanism of toxicity revealed that MnPrP is significantly more toxic to neuronal cells than nonmanganese bound PrP and that toxicity requires the presence of known metal binding residues within the protein. (bl.uk)
  • 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. (sciencemag.org)
  • Furthermore, we examined that Hsd could also significantly upregulate the expression of proapoptotic Bax subgroup genes (Bax and Bik) while downregulating the anti-apoptotic protein Bcl-2 in EC cell lines. (greenmedinfo.com)
  • The SMN protein has been known to function in assembly of the RNA splicing complex, however, the mechanism(s) by which SMN-deficiency causes cell death in SMA are not clear. (clinicaltrials.gov)
  • The investigators will determine the effect of expression of SMN protein in regulating cell death of SMA fibroblasts. (clinicaltrials.gov)
  • In addition, ATG9 deficiency phenocopied SNAP23 deficiency, whereas ATG7 deficiency had no effect on BAX protein levels, BAX activation, or apoptotic cell death. (jci.org)
  • Research in the Walczak Laboratory is focused on cell death and ubiquitin in inflammation, cancer and immunity. (ucl.ac.uk)
  • 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. (ucl.ac.uk)
  • 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. (encyclopedia.com)
  • When cells burst and die, their contents are released, causing inflammation. (medicalnewstoday.com)
  • They are also the gatekeepers of inflammation , and cell death can either be pro- or anti-inflammatory, leading to different outcomes. (medicalnewstoday.com)
  • Acute inflammation induced by cell death. (nih.gov)
  • Apoptotic cells may not stimulate inflammation if they are ingested by phagocytes before they release their intracellular contents. (nih.gov)
  • Cells contain a number of different danger signals that can potentially stimulate inflammation through different mechanisms. (nih.gov)
  • Some of these signal are intracellular molecules that trigger inflammation by directly stimulating cells to make proinflammatory cytokines. (nih.gov)
  • 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. (redorbit.com)
  • The inability to clear dying cells has been linked to inflammation and autoimmunity. (scienceblog.com)
  • 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. (scienceblog.com)
  • 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. (scienceblog.com)
  • 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. (medium.com)
  • 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. (medium.com)
  • Surprisingly, we observed that adipocyte-specific KO of SNAP23 in mice resulted in a temporal development of severe generalized lipodystrophy associated with adipose tissue inflammation, insulin resistance, hyperglycemia, liver steatosis, and early death. (jci.org)
  • A team of Melbourne researchers has shown a recently discovered type of cell death called necroptosis could be the underlying cause of inflammatory disease. (redorbit.com)
  • 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. (redorbit.com)
  • Associate Professor Silke said necroptosis was a newly discovered type of cell death that had only really been studied in the past five years. (redorbit.com)
  • Strikingly, this signal relay is known to trigger a specific, injury-induced form of cell death, referred to as necroptosis. (uni-muenchen.de)
  • It is the most common mode of cell death in cancer cells exposed to ionizing radiation and many other anti-cancer treatments. (wikipedia.org)
  • Fig.1 Human cancer cells undergoing TRAIL-induced cell death. (ucl.ac.uk)
  • 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. (ucl.ac.uk)
  • But cancer cells swerve away from this suicide path and become immortal. (ucl.ac.uk)
  • 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 . (medicalnewstoday.com)
  • First, they confirmed the profiles of different types of lung cancer cells. (medicalnewstoday.com)
  • He adds that better understanding the differences between how various cancer cells function will be a key element in this process. (medicalnewstoday.com)
  • 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. (medicalnewstoday.com)
  • However, cancer cells often ignore these signals, flourishing even after chemotherapy drugs have ravaged their DNA. (scoop.it)
  • 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. (pnas.org)
  • 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. (pnas.org)
  • 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. (rochester.edu)
  • 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. (medium.com)
  • Despite efforts made on cancer cell and immune cell interaction, how cancer cells initiate immune escape is less understood. (news-medical.net)
  • Massive cancer cell death was observed in glycosylation deficient cancer cells, suggesting glycosylation of PD-L1 is required for its immunosuppression. (news-medical.net)
  • This volume includes discussion of tumor suppression, the altered metabolism of cancer cells, and the development of therapeutic drugs. (cshlpress.com)
  • Proteasome activity is increased in cancer cells. (rainbow.coop)
  • New findings about how prostate cancer cells are able to resist hormone treatment and defy death may lead to more effective drug treatments, according to researchers from Wake Forest University School of Medicine and colleagues. (emaxhealth.com)
  • The goal of the research was to uncover how prostate cancer cells become resistant to treatment that lowers levels of male hormones such as testosterone, which the cells normally need to survive. (emaxhealth.com)
  • The death of these cells, oligodendrocytes, can activate the autoimmune response against myelin, which is the main feature of MS. Oligodendrocytes can possibly be destroyed by developmental abnormalities, viruses, bacterial toxins or environmental pollutants. (eurekalert.org)
  • 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. (cshlpress.com)
  • This indispensable laboratory resource will enable all cell and developmental biologists, from the graduate level upward, to confidently carry out and comprehend a wide array of cell viability assays. (cshlpress.com)
  • Under normal circumstances, dying cells are recycled by the immune system. (medicalnewstoday.com)
  • 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). (scientificamerican.com)
  • Too little Mcl-1 can lead to a damaged immune system or even death. (rxpgnews.com)
  • Tissues that contain large numbers of senescent cells are at greater risk for developing cancer, becoming inflamed and negatively affecting the immune system. (medium.com)
  • 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. (medium.com)
  • The researchers also hope to bolster the immune system by increasing the body's ability to produce new killer T-cells. (medium.com)
  • 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. (uni-muenchen.de)
  • Using a sensitive florescence resonance energy transfer (FRET) assay for Rho activation in primary cell culture, the investigators showed that glutamate activated Rho in an NMDA receptor-dependent manner. (alzforum.org)
  • 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. (news-medical.net)
  • 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. (news-medical.net)
  • Researchers have identified a molecule that determines whether or not a type of lung cancer cell will undergo cancer cell death. (medicalnewstoday.com)
  • The researchers found higher death rates among people with SCD than previous estimates that used other methods. (cdc.gov)
  • The researchers then compared these death rates to those of African Americans and to the general population in the corresponding states. (cdc.gov)
  • 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. (cdc.gov)
  • Many challenges exist for researchers that work to accurately estimate the number of deaths among people with SCD. (cdc.gov)
  • 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. (cdc.gov)
  • 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. (rochester.edu)
  • Researchers looked at the Fatality Analysis Reporting System (FARS) and matched it against trends in cell phone use and texting volume. (zdnet.com)
  • 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. (rxpgnews.com)
  • 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. (rxpgnews.com)
  • Learning more about these cells could help researchers make specific cell types . (livescience.com)
  • 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. (livescience.com)
  • The embryonic cells keep this molecular kill switch, called Bax waiting, around for this very purpose, the researchers found. (livescience.com)
  • For the study researchers followed 195 sickle cell disease patients for two years. (medindia.net)
  • Thus researchers say the Doppler echocardiography is a reasonably priced, non-invasive test that should be offered to adults with sickle cell disease. (medindia.net)
  • 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. (medindia.net)
  • Additionally, these researchers are testing a library of compounds to identify any that are capable of selectively targeting senescent cells. (medium.com)
  • 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. (phys.org)
  • European researchers investigated the molecular mechanisms that drive stress-related responses that cause aging and death in plants. (phys.org)
  • In the September 7 Nature Communications, researchers led by Lars Ittner and Yazi Ke at the University of New South Wales, Sydney, reported that young tau knockout mice underwent very little neurodegeneration after stroke, unlike the massive cell death seen in wild-type. (alzforum.org)
  • 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. (cdc.gov)
  • Read more about the sickle cell disease mortality study here external icon . (cdc.gov)
  • Sickle Cell Disease is a group of genetic (inherited) red blood cell disorders. (cdc.gov)
  • How many deaths occur among children with sickle cell disease detected through newborn screening? (cdc.gov)
  • 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. (cdc.gov)
  • 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. (cdc.gov)
  • 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. (cdc.gov)
  • To learn more about sickle cell disease and sickle cell trait, please visit our sickle cell disease homepage . (cdc.gov)
  • To obtain free resources on sickle cell disease and sickle cell trait, please visit the free materials section of our website. (cdc.gov)
  • Mortality of New York Children with Sickle Cell Disease Identified Through Newborn Screening. (cdc.gov)
  • Sickle cell disease is a genetic disease that occurs predominantly in people of African descent. (medindia.net)
  • A new study pinpoints a major complication in adults with sickle cell disease that can often lead to death. (medindia.net)
  • 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. (medindia.net)
  • Sickle cell anemia is the most common form of sickle cell disease. (medindia.net)
  • In the context of NSCLC, they have the potential to become cancerous cells, invading healthy tissue and forming tumors. (medicalnewstoday.com)
  • Whatever is at the root of cell death, the corpse lodged in the tissue cannot stick around forever. (medicalnewstoday.com)
  • Embryonic stem cells are special because they can give rise to any tissue in the body. (livescience.com)
  • 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. (ucsd.edu)
  • 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. (medium.com)
  • 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. (medium.com)
  • 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. (uni-muenchen.de)
  • 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. (uni-muenchen.de)
  • After applying the In Situ Cell Death Detection Kit, POD to stain formalin-fixed paraffin-embedded (FFPE) liver tissue sections, it is also possible to stain another antigen in the sections using a double staining technique ( e.g., a different AP/HRP-based staining kit). (sigmaaldrich.com)
  • Roche recommends first performing the TUNEL reaction of the In Situ Cell Death Detection Kit, POD for FFPE tissue slides, as described in detail in the package insert. (sigmaaldrich.com)
  • Wild-type mice (left) suffer extensive tissue death (white) after stroke, while tau knockouts (right) lose cells only in the immediate vicinity of the blockage (arrow). (alzforum.org)
  • In view of the pleiotropic functions of critical mediators of cell death and tissue regeneration, a particular challenge will be to reduce hepatocellular death without inhibiting the regenerative capacity of the liver. (frontiersin.org)
  • 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. (ucsd.edu)
  • 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. (ucsd.edu)
  • Importantly, deletion of the gene that codes for the major isoform of JNK in liver cells, JNK1, prevented the development of liver cancer and reversed the tumor-enhancing effect caused by ablation of IKKb. (ucsd.edu)
  • Hepatocellular carcinoma (HCC), the most common form of liver cancer, is the third leading cause of cancer deaths worldwide. (ucsd.edu)
  • One cell might be destined to become skin while another cell is fated to be part of the liver. (medium.com)
  • Liver cells have a different group of molecules on their surface than blood cells, for example. (medium.com)
  • Cold ischemia - warm reperfusion (CI/WR) injury of liver transplantation involves hepatocyte cell death, the nature and underlying mechanisms of which remain unclear. (ingentaconnect.com)
  • ALF occurs when the extent of hepatocyte death exceeds the regenerative capacity of the liver. (frontiersin.org)
  • The mechanisms by which liver cells are destroyed as well as the processes mediating liver regeneration, remain largely unknown. (frontiersin.org)
  • We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (jci.org)
  • 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. (jneurosci.org)
  • In contrast, downregulation of caspase-1 or caspase-3 did not block Aβ 1-42 -induced death. (jneurosci.org)
  • Neurons from caspase-2 null mice were totally resistant to Aβ 1-42 toxicity, confirming the importance of this caspase in Aβ-induced death. (jneurosci.org)
  • Multicellular organisms, including humans, need to keep a tight lid on the number of cells in their bodies. (medicalnewstoday.com)
  • A normal component of multicellular development is cell death. (asm.org)
  • In multicellular organisms, cell death is a normal component of development ( 18 , 43 ). (asm.org)
  • If cell death does not occur when it should, cancer and other diseases may develop. (cshlpress.com)
  • Sickle cell anemia (SCA) is a genetic blood disorder caused by abnormal inherited hemoglobin. (medindia.net)
  • The DNA genetic material of cells changes configuration when undergoing reproduction and repair. (rainbow.coop)
  • The disease is one of the most common genetic causes of infant death. (clinicaltrials.gov)
  • 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. (sciencemag.org)
  • These forms of death are a sort of cell suicide, in which cells self-destruct in a controlled and contained manner. (encyclopedia.com)
  • 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. (livescience.com)
  • 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. (livescience.com)
  • 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. (inquisitr.com)
  • 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. (ucl.ac.uk)
  • But the darker side of this complex process manifests itself in cancers when cells don't die when they're supposed to. (rxpgnews.com)
  • Too much, and cells stay alive when they shouldn't, leading to cancers such as lymphomas. (rxpgnews.com)
  • 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. (encyclopedia.com)
  • The inflammatory response to cell death. (nih.gov)
  • 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. (scienceblog.com)
  • 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 ). (diabetesjournals.org)
  • 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. (uni-muenchen.de)
  • Every inflammatory reaction results in some collateral damage, because neutrophils also attack healthy cells," he explains. (uni-muenchen.de)
  • 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. (freepatentsonline.com)
  • 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. (freepatentsonline.com)
  • Cell Communication and Signaling is pleased to acknowledge and celebrate the 25-year anniversary of the International Cell Death Society (ICDS). (biomedcentral.com)
  • In recognition of this milestone, the Editors of Cell Communication and Signaling have compiled a list of some of the important papers on cell death that have been published by the journal over the past decade. (biomedcentral.com)
  • Cell-cell signaling is involved in microcolony development in at least three organisms, P. aeruginosa ( 13 ), Burkholderia cepacia ( 28 ), and Aeromonas hydrophila ( 38 ). (asm.org)
  • 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 ). (sciencemag.org)
  • Cancerous cells reacquire the embryonic ability to reconstruct the telomere, and thus become immortal. (encyclopedia.com)
  • 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. (livescience.com)
  • Limitations on government funding of human embryonic stem cell labs have also hampered work in this area. (livescience.com)
  • Deshmukh and colleagues treated human embryonic stem cells with DNA-damaging drugs to see what happened. (livescience.com)
  • 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. (livescience.com)
  • In this way, a damaged cell is dangerous to its fellow embryonic cells. (livescience.com)
  • Recent studies in endothelial cells demonstrate that the off-target effects of Dz13 may in fact be driving some of these potentially therapeutic effects, though no mechanisms have been clearly defined in tumour cells. (biomedsearch.com)
  • 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 ). (sciencemag.org)
  • We initially expected that IRBIT would function to suppress cell death. (riken.jp)
  • The mesenchymal-like cells that result from this "switch" exhibit mutations in the KRAS gene , which plays an important role in controlling cell division. (medicalnewstoday.com)
  • In addition, in a previous study, Fu found that cells lacking ALKBH7 have a greater number of mutations after chemotherapy compared to cells with ALKBH7. (rochester.edu)
  • 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. (livescience.com)
  • Injured" cells with damaged DNA can lead to mutations that could kill an organism. (livescience.com)
  • Cancer, for example, is a process in which mutations in the nuclear DNA and other changes cause cells to adopt a more primitive lifestyle and begin the uncontrolled growth that results in the formation of a tumor. (medium.com)
  • Single-cell genome analyses reveal the amount of mutations a human brain cell will collect from its fetal beginnings until death. (the-scientist.com)
  • The central nervous system regenerated the myelin-producing cells, enabling the mice to walk again. (eurekalert.org)
  • Our studies of the consequences of in vivo exposure have shown that SpA can deplete V H -targeted B cells in both neonates and adult mice by a process that is unimpaired in TCRβδ −/− mice, indicating that T cells are not required ( 6 ). (rupress.org)
  • In fact, this long-term immunologic impairment in SpA-treated mice persists despite the fact that central neo-lymphogenesis reestablishes the level of newly formed S107-expressing B cells in the periphery within 1-2 wk after the last SpA treatment ( 5 ). (rupress.org)
  • One hour after injury, both sets of mice had similar deficits, with local cell death around the blockage site and minor movement problems. (alzforum.org)
  • They then worked out how to block it, and were able to prevent brain cells from dying, helping the mice live longer. (lifescript.com)
  • Moreover, BAX deficiency suppressed the lipodystrophic phenotype in the adipocyte-specific SNAP23-KO mice and prevented cell death. (jci.org)
  • We think these findings are very significant," said Dr. Wang, senior author of the Cell study. (rxpgnews.com)
  • Ischemic cell death, or oncosis, is a form of accidental, or passive cell death that is often considered a lethal injury. (wikipedia.org)
  • Now, two papers from Australia blame tau for the lion's share of cell death after ischemic stroke. (alzforum.org)
  • 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. (medicalnewstoday.com)
  • Other molecules released by dead cells stimulate the generation of mediators from extracellular sources. (nih.gov)
  • Evidence from the NOD mouse (a widely studied model of autoimmune diabetes) ( 7 ) indicates that autoreactive cytolytic T-cells ( 8 ), as well as soluble mediators including proinflammatory cytokines and free radicals, contribute to increased β-cell apoptotic destruction during the pathogenesis of type 1 diabetes ( 6 , 9 ). (diabetesjournals.org)
  • Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy. (mdpi.com)
  • Because these T15 B-1 cells dominate responses to phosphorylcholine-containing immunogens, their loss after in vivo exposure to SpA explained the finding of induced phosphorylcholine-specific immune tolerance. (rupress.org)
  • Estradiol treatment of the AVPV, in vivo and in vitro , was used to manipulate TH-ir cell number. (jneurosci.org)
  • Its chemistry is partly responsible for its activity against tumour cells, but it is safe to use in vivo and surprisingly shows little harmful effects against normal cells. (biomedsearch.com)
  • Analysis of capillary regression in vivo, however, has revealed that dying capillary cells remain in contact with ECM fragments, thus suggesting that the cell foreshortening caused by ECM dissolution may be the signal that initiates the death program ( 2 ). (sciencemag.org)