One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A 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.
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.
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.
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.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
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.
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.
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.
A cell line derived from cultured tumor cells.
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.
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.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A 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.
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)
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.
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.
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.
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.
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.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A 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.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A 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.
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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
Glycoproteins found on the membrane or surface of cells.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A 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)
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.
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.
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.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A 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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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.
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.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The action of a drug in promoting or enhancing the effectiveness of another drug.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
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.
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.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
A 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.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Proteins 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.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
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.
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)
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
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.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A 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.
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.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
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.
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.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
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.
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.
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.
CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A 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.
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.
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.
Proteins prepared by recombinant DNA technology.
The process by which chemical compounds provide protection to cells against harmful agents.
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).
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
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.
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.
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.
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.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Peptides composed of between two and twelve amino acids.
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.
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.
Tumors or cancer of the COLON.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
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.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
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.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.
Tumors or cancer of the PROSTATE.
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.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
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.
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.
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.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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)
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.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
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).
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
Tumors or cancer of the human BREAST.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
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)
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A group of phenyl benzopyrans named for having structures like FLAVONES.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
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.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Compounds that inhibit cell production of DNA or RNA.
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.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides.
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.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC
Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).
Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Inorganic or organic compounds that contain arsenic.

Inducible NO synthase: role in cellular signalling. (1/71063)

The discovery of endothelium-derived relaxing factor and its identification as nitric oxide (NO) was one of the most exciting discoveries of biomedical research in the 1980s. Besides its potent vasodilatory effects, NO was found under certain circumstances to be responsible for the killing of microorganisms and tumour cells by activated macrophages and to act as a novel, unconventional type of neurotransmitter. In 1992, Science picked NO as the 'Molecule of the Year', and over the past years NO has become established as a universal intercellular messenger that acutely affects important signalling pathways and, on a more long-term scale, modulates gene expression in target cells. These actions will form the focus of the present review.  (+info)

VEGF is required for growth and survival in neonatal mice. (2/71063)

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.  (+info)

A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates. (3/71063)

The Drosophila doublesex (dsx) gene encodes a transcription factor that mediates sex determination. We describe the characterization of a novel zebrafish zinc-finger gene, terra, which contains a DNA binding domain similar to that of the Drosophila dsx gene. However, unlike dsx, terra is transiently expressed in the presomitic mesoderm and newly formed somites. Expression of terra in presomitic mesoderm is restricted to cells that lack expression of MyoD. In vivo, terra expression is reduced by hedgehog but enhanced by BMP signals. Overexpression of terra induces rapid apoptosis both in vitro and in vivo, suggesting that a tight regulation of terra expression is required during embryogenesis. Terra has both human and mouse homologs and is specifically expressed in mouse somites. Taken together, our findings suggest that terra is a highly conserved protein that plays specific roles in early somitogenesis of vertebrates.  (+info)

Alzheimer's disease: clues from flies and worms. (4/71063)

Presenilin mutations give rise to familial Alzheimer's disease and result in elevated production of amyloid beta peptide. Recent evidence that presenilins act in developmental signalling pathways may be the key to understanding how senile plaques, neurofibrillary tangles and apoptosis are all biochemically linked.  (+info)

Cell-mediated immunity: dealing a direct blow to pathogens. (5/71063)

Cytotoxic T lymphocytes are essential for defence against viral infections. Recent data demonstrating direct killing of intracellular bacteria by granulysin, a protein released from the granules of cytotoxic T lymphocytes, emphasize the contribution of these lymphocytes to the control of tuberculosis.  (+info)

JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. (6/71063)

BACKGROUND: The Jun N-terminal kinase (JNK) signaling pathway has been implicated in cell proliferation and apoptosis, but its function seems to depend on the cell type and inducing signal. In T cells, JNK has been implicated in both antigen-induced activation and apoptosis. RESULTS: We generated mice lacking the JNK2 isozymes. The mutant mice were healthy and fertile but defective in peripheral T-cell activation induced by antibody to the CD3 component of the T-cell receptor (TCR) complex - proliferation and production of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) were reduced. The proliferation defect was restored by exogenous IL-2. B-cell activation was normal in the absence of JNK2. Activation-induced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+) CD8(+)) thymocytes lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3 antibody in vivo. The lack of JNK2 also resulted in partial resistance of thymocytes to anti-CD3 antibody in vitro, but had little or no effect on apoptosis induced by anti-Fas antibody, dexamethasone or ultraviolet-C (UVC) radiation. CONCLUSIONS: JNK2 is essential for efficient activation of peripheral T cells but not B cells. Peripheral T-cell activation is probably required indirectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stimulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-Fas antibody, UVC or dexamethasone. JNK2 is not required for activation-induced cell death of mature T cells.  (+info)

Bcl-2 regulates amplification of caspase activation by cytochrome c. (7/71063)

Caspases, a family of specific proteases, have central roles in apoptosis [1]. Caspase activation in response to diverse apoptotic stimuli involves the relocalisation of cytochrome c from mitochondria to the cytoplasm where it stimulates the proteolytic processing of caspase precursors. Cytochrome c release is controlled by members of the Bcl-2 family of apoptosis regulators [2] [3]. The anti-apoptotic members Bcl-2 and Bcl-xL may also control caspase activation independently of cytochrome c relocalisation or may inhibit a positive feedback mechanism [4] [5] [6] [7]. Here, we investigate the role of Bcl-2 family proteins in the regulation of caspase activation using a model cell-free system. We found that Bcl-2 and Bcl-xL set a threshold in the amount of cytochrome c required to activate caspases, even in soluble extracts lacking mitochondria. Addition of dATP (which stimulates the procaspase-processing factor Apaf-1 [8] [9]) overcame inhibition of caspase activation by Bcl-2, but did not prevent the control of cytochrome c release from mitochondria by Bcl-2. Cytochrome c release was accelerated by active caspase-3 and this positive feedback was negatively regulated by Bcl-2. These results provide evidence for a mechanism to amplify caspase activation that is suppressed at several distinct steps by Bcl-2, even after cytochrome c is released from mitochondria.  (+info)

Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. (8/71063)

To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-XL protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-XL inhibits activation of NF-kappaB and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappaB in EC occurs upstream of IkappaBalpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappaB inhibitory function of Bcl-2 was mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-XL belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappaB without sensitizing the cells (as with IkappaBalpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-XL are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.  (+info)

METHODS: The cytotoxic effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 50% inhibitory concentration (IC50) value was determined. The self-renewal and proliferating potential of A549 cells after treatment with deoxyelephantopin were examined by colony formation assay. Cellular morphology of deoxyelephantopin-treated cells was observed using phase-contrast microscopy. The induction of apoptosis was evaluated using acridine orange and ethidium bromide staining, Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) assay, DNA fragmentation analysis and Annexin V-fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow cytometric analysis. The total cellular DNA content and expression of cleaved poly (ADP-ribose) polymerase was ...
Read independent reviews on CardioTACS™ In Situ Apoptosis Detection Kits from AMS Biotechnology (Archived Products) on SelectScience
Anti-apoptotic action of polyphenols derived from red wine and green tea against beta-amyloid in hippocampal cells Author: Stéphane Bastianetto and Slavica Krantic and Rémi Quirion Background: It has been suggested that accumulation of amyloid-beta (Aß) peptides into senile plaques plays a pivotal role in neuronal cell
BioAssay record AID 541028 submitted by ChEMBL: Induction of apoptosis in bovine BL3 cells assessed as early apoptotic cells after 24 hrs by annexin V/propidium iodide staining-based FACS analysis.
During apoptosis, phosphatidylserine (PS) is translocated from the cytoplasmic face of the plasma membrane to the cell surface. Annexin V has a strong, Ca2+-dependent affinity for PS and therefore is used as a probe for detecting apoptosis., Annexin V-FITC Apoptosis Detection Reagent, GTX14082, Applications: FACS; Flow cytometry/FACS; CrossReactivity:
The Annexin V-Biotin Apoptosis Detection Kit is based on the observation that soon after initiating apoptosis, most cell types translocate the membrane phospholipid phosphatidylserine (PS) from the inner face of the plasma membrane to the cell surface. Once on the cell surface, PS can easily bind to Biotin-conjugated Annexin V, a protein that has a strong natural affinity for PS. Annexin V-Biotin can be detected in conjunction with conventional dye-staining using any streptavidine- or avidin-dye reagents, such as (strept)avidine-fluorescein, -peroxidase, -alkaline phosphatase (AP), and -β-gal, etc. |p>‧ Detection method- Flow cytometry (Ex = 488 nm; Em = 530 nm) using and fluorescence microscopy |br>‧ Sample type- Living cells (suspension and adherant)|br>‧ Species reactivity- Mammalian |br>‧ Applications- Detect early/middle stages of apoptosis; differentiate apoptosis from necrosis.|p>|b>Features and Benefits|/b>|br>‧ Simple one step staining procedure in 30 minutes|br>‧ Fast and
TransDetect® Annexin V-EGFP/PI Cell Apoptosis Detection Kit,Cell Detection,Cell Culture and Detection,Products,Beijing TransGen Biotech Co.Ltd,OverviewContents& storageCitations & referencesRelated ImagesDownloadOverviewDescriptionThe Annexin V
Invitrogen™ eBioscience™ Annexin V Apoptosis Detection Kit PerCP-eFluor™ 710 200 tests Invitrogen™ eBioscience™ Annexin V...
Antibodies for proteins involved in negative regulation of cardiac muscle cell apoptotic process pathways, according to their Panther/Gene Ontology Classification
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TY - JOUR. T1 - Formosanin C-induced apoptosis requires activation of caspase-2 and change of mitochondrial membrane potential. AU - Lee, Jenq Chang. AU - Su, Chun Li. AU - Chen, Lin Lin. AU - Won, Shen Jeu. PY - 2009/4/30. Y1 - 2009/4/30. N2 - Formosanin C is a pure compound isolated from Paris formosana Hayata (Liliaceae). The antitumor efficacy of formosanin C has been observed in cultured cells and animal systems. However, the molecular mechanisms of formosanin C remain unknown. The results of the present study indicate that formosanin C induced apoptosis of HT-29 cells characterized by exposure of phosphatidylserine, accumulation of cells at the sub-G1 phase, fragmentation of DNA, and change of nuclear morphology in a time- and dose-related manner. The apoptotic signaling cascades may proceed via proteolytic activation of caspase-2, change of mitochondrial membrane potential (Δεm), release of cytochrome c and second mitochondria-derived activator of caspase/direct IAP binding protein with ...
This kit is designed for histochemical detection of fragmented DNA using the TUNEL method. It allows quick and easy detection of single cells at the primary stage of apoptosis. Tissue sections and fixed cells may be used for samples.
Tumor Necrosis Apoptosis Inducing Ligand (TRAIL) is a death ligand with some specificity for transformed cells. However, some cancer cells develop resistance to TRAIL allowing escape from immune surveillance. Re-sensitization of these cells to TRAIL depends on identifying the mechanism of resistance and applying a targeted corrective. We studied several possible mechanisms of TRAIL resistance beginning with FLICE-Like Inhibitory Protein (FLIP). The short isoform of FLIP (FLIPshort) is an effective inhibitor of caspase 8 activation and therefore overexpression of FLIPshort may be a mechanism of TRAIL resistance. We found that downregulation of FLIP short was sufficient to re-sensitize some prostate carcinoma cells to TRAIL. Another mechanism we investigated is mediated by Elongation Factor 2 (EF2) which acilitates ribosomal translocation along mRNA strands. EF2 can be inactivated by phosphorylation or by ADP-ribosylation, thereby inhibiting protein synthesis. During inhibition of protein ...
TY - JOUR. T1 - Reversibility of apoptosis in cancer cells. AU - Tang, H. L.. AU - Yuen, K. L.. AU - Tang, H. M.. AU - Fung, M. C.. PY - 2009/1/13. Y1 - 2009/1/13. N2 - Apoptosis is a cell suicide programme characterised by unique cellular events such as mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of apoptotic protease caspases, and these serve as the noticeable apoptotic markers for the commitment of cell demise. Here, we show that, however, the characterised apoptotic dying cancer cells can regain their normal morphology and proliferate after removal of apoptotic inducers. In addition, we demonstrate that reversibility of apoptosis occurs in various cancer cell lines, and in different apoptotic stimuli. Our findings show that cancer cells can survive after initiation of apoptosis, thereby revealing an unexpected potential escape mechanism of cancer cells from chemotherapy.. AB - Apoptosis is a cell suicide programme characterised by ...
Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-a
세포 죽음의 평가에 대한 정확한 방법을 설명합니다. 프로토콜은 세포 라인과 동물 모델의 광범위한 범위에서 기본 세포 40 % 허위 - 긍정적인 이벤트까지 표시 기존 Annexin V / propidium 요오드화물 (PI) 프로토콜에 따라이...
The fourth meeting on dependence receptors featured descriptions of previously unknown dependence receptors. New mechanistic data were presented on the switch between the trophic, antiapoptotic response with the proapoptotic response that occurs with loss of trophic support. The possibility that the loss of trophic support may also involve the binding of an active antitrophin was also discussed. New in vivo data were presented on the roles of dependence receptors in development, angiogenesis, oncogenesis, and neurodegeneration, as well as new therapeutic approaches based on dependence receptor function. The next meeting on dependence receptors is scheduled for 2012.. ...
As soon as Peripheral Blood Mononuclear Cells (PBMC) are isolated from whole blood, some cells begin dying. The rate of apoptotic cell death is increased when PBMC are shipped, cryopreserved, or stored under suboptimal conditions. Apoptotic cells secrete cytokines that suppress inflammation while promoting phagocytosis. Increased numbers of apoptotic cells in PBMC may modulate T cell functions in antigen-triggered T cell assays. We assessed the effect of apoptotic bystander cells on a T cell ELISPOT assay by selectively inducing B cell apoptosis using α-CD20 mAbs. The presence of large numbers of apoptotic B cells did not affect T cell functionality. In contrast, when PBMC were stored under unfavorable conditions, leading to damage and apoptosis in the T cells as well as bystander cells, T cell functionality was greatly impaired. We observed that measuring the number of apoptotic cells before plating the PBMC into an ELISPOT assay did not reflect the extent of PBMC injury, but measuring apoptotic cell
Few things can be considered to be more important to a cell than its threshold for apoptotic cell death, which can be modulated up or down, but rarely in both directions, by a single enzyme. Therefore, it came as quite a surprise to find that one enzyme, glycogen synthase kinase-3 (GSK3), has the pe …
Apoptosis is a genetically regulated form of cell death that occurs when the cell is exposed to physiological, pathogenic, or cytotoxic stimuli. Unregulated apoptosis (too much or too little apoptosis) at any time from embryogenesis to adulthood, can result in a variety of disease states, such as neurodegenerative disorders, autoimmunity, cardiovascular disease, liver and kidney problems, and cancer. A reasonable estimation is that either too little or too much cell death contributes to half of the main medical illnesses for which adequate therapy or prevention is lacking. The apoptotic pathways can be initiated by reactive oxygen species (ROS) and inflammatory molecules, both of which are believed to be up-regulated in a state of obesity. In addition, multiple studies have shown that the risk of developing cardiovascular disease, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and certain types of cancers increase with increasing degree of obesity in both men and women. Despite the ...
AAD positive means late apoptosis? - posted in Flow Cytometry: We have a discussion in the lab about apoptosis detection by annexin V/AAD labeling. Many people say that Annexin V+/AAD+ cells must not be considered apoptotic but necrotic. I agree, provided that the apoptotic stimulus was rather short (for example 2 hours-staurosporine). However, when the stimulus lasts for 24 hours (serum starvation for instance) I think that cells which started the apoptotic process shortly after the start...
Photodynamic therapy (PDT) is considered to be an advancing antitumor technology. PDT using hydrophilic/lipophilic tetra‑α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn-PDT) has exhibited antitumor activity in Bel-7402 hepatocellular cancer cells. However, the manner in which p38 MAPK and caspase-9 are involved in the regulation of mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo human colon carcinoma cells remains unclear. Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase‑9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the TαPcZn-PDT‑treated LoVo cells. The findings revealed that the TαPcZn-PDT treatment of LoVo cells resulted in the induction of apoptosis, the formation of p38 MAPK/caspase-9 complexes, the activation of p38 MAPK, caspase-9, caspase-3 and Bid, the downregulation of Bcl-2, the reduction of mitochondrial membrane ...
This kit is designed for histochemical detection of fragmented DNA using the TUNEL method. It allows quick and easy detection of single cells at the primary stage of apoptosis. Tissue sections and fixed cells may be used for samples.
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today ...
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today ...
SMAC/DIABLO (second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI) is a proapoptotic mitochondrial protein that is released in response to various apoptotic stimuli. Molecular mimetics of SMAC are being investigated for use in cancer treatment, but their activities in vivo have not been fully characterized.. In a recent study, Emeagi and colleagues from Vrije Universiteit Brussel, Belgium, showed that SMAC mimetics induce cancer cell death via a proinflammatory effect that is accompanied by an adaptive antitumor immune response. Transduction with lentiviral vectors encoding a cytosolic form of a SMAC mimetic (LV-tSMAC) resulted in apoptosis of cancer cells of different histologic origins, and treatment of tumor-bearing mice with the SMAC mimetic resulted in induction of apoptosis, activation of antitumor immunity, and prolonged survival.. Immune Response. The antitumor immune response included increased levels of tumor-infiltrating ...
Hochwertige Annexin V FITC Kits für Apoptose Detektion mit Flow Cytometry. ✅ Namhafte Top-Hersteller im Vergleich. ✅ Top-Support bei Fragen.
Albany, New York, Dec 1, 2017: Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) - Apoptosis regulator BAX or bcl-2-like protein 4 is a protein is encoded by the BAX gene. It accelerates programmed cell death by antagonizing the apoptosis repressor BCL2. It promotes activation of CASP3, and thereby apoptosis. It undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis under stress conditions.. Request For Free Sample - Apoptosis Regulator BAX (Bcl 2 Like Protein 4 or BCL2L4 or BAX) pipeline Target constitutes close to 7 molecules. Out of which approximately 3 molecules are developed by companies and remaining by the universities/institutes. The molecules developed by companies in Phase III, Phase II and Preclinical stages are 1, 1 and 1 respectively. Similarly, the universities portfolio in Preclinical and Discovery ...
Heart ischemia can rapidly induce apoptosis and mitochondrial dysfunction via mitochondrial permeability transition-induced cytochrome c release. We tested whether nitric oxide (NO) can block this damage in isolated rat heart, and, if so, by what mechanisms. Hearts were perfused with 50 μM DETA/NO (NO donor), then subjected to 30 min stop-flow ischemia or ischemia/reperfusion. Isolated heart mitochondria were used to measure the rate of mitochondrial oxygen consumption and membrane potential using oxygen and tetraphenylphosphonium-selective electrodes. Mitochondrial and cytosolic cytochrome c levels were measured spectrophotometrically and by ELISA. The calcium retention capacity of isolated mitochondria was measured using the fluorescent dye Calcium Green-5N. Apoptosis and necrosis were evaluated by measuring the activity of caspase-3 in cytosolic extracts and the activity of lactate dehydrogenase in perfusate, respectively. 30 min ischemia caused release of mitochondrial cytochrome c to the cytoplasm
Evidence suggests that the signalling events which occur after apoptotic stimulation, define two basic mechanisms for the induction of apoptosis. The first is dependent on signalling via the mitochondria and the second is dependent upon signalling directly from the death receptors. After induction of apoptosis, there is a convergence in signalling at the level of caspase activation and subsequent biochemical and morphological changes. Therefore the efficacy of various inhibitors of apoptosis is dependent upon the initiating signal. In order to understand the apoptotic pathway, the mechanisms by which these inhibitors regulate chemical- and receptor-mediated apoptosis must be understood. The anti-apoptotic oncoprotein, Bcl-2, was shown to inhibit both staurosporine and Fas-mediated apoptosis in a manner which was partially dependent upon the level of Bcl-2 protein expressed. During both staurosporine and Fas-induced apoptosis Bcl-2 acted downstream of caspase-8 activation. High levels of Bcl-2 ...
The influence of diabetes enhanced inflammation on cell apoptosis and periodontitis. . 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.
Drug resistance has been mostly explained by molecular changes, such as overexpression of p-glycoprotein or O6-methylguanine-DNA-methyltransferase, which interfere with drug actions on the targets (1 , 2) . Because most anticancer agents, regardless of their diverse targets, exert effects by inducing apoptosis via activation of apoptotic pathways common to many cellular stresses, any antiapoptotic changes disrupting the common intrinsic pathways to execute physiological cell death can also make malignant cells resistant to chemotherapy (3) . Such alterations opposing apoptosis are routinely observed in malignant tumors, including both the functional loss of tumor suppressors p53, Bax, or PTEN and deregulated hyperfunction of oncogenic proteins, such as Ras, Bcl-2, and PI3K 2 ,(3) .. In tumor cells with an aberrantly activated PI3K/Akt survival pathway, the increased antiapoptotic signals overcome apoptotic signals of anticancer drugs, confer drug resistance on the tumor cells, and result in a ...
New York - September 19, 2019 - BOC Sciences, a New York-based supplier of various bio-chemicals such as inhibitors, APIs, metabolites and impurities, announced earlier this month to launch cell apoptosis assay service for scientists engaged in drug discovery research. With expertise and well-published cell based assays from BOC Sciences, researchers now dont need to worry about apoptosis detection anymore.. Apoptosis, or alternatively referred to as programmed cell death, plays an important role in many human diseases. Controlled by multiple signaling and effector pathways, apoptosis is found to be closely linked with caspase related apoptotic enzyme cascades, mitochondrial depolarization, DNA fragmentation and ultimately cell blebbing and destruction. This offers new insights for scientists who are seeking new treatment for various diseases: through approaches of genetically modulating these apoptosis-associated pathways, new therapies might be discovered. Many human conditions like ...
Apoptosis is characterized by a series of well defined morphological and biochemical features that allow cells to initiate self-destruction in response to a variety of stimuli. CD4⁺CD8⁺ is a sub-population of immature thymocytes that are especially prone to the action of apoptosis-inducing agents and are sensitive to glucocorticoid-induced apoptosis, an event that plays a critical role in eliciting the antigen-specific thymocyte repertoire. Glucocorticoids induce apoptosis through activation of the GR, a ligand-induced transcription factor that transduces the hormonal signals into the regulated expression of target genes. While much is known about the structure and function of GR, key steroid-regulated genes believed to be required for thymocyte apoptosis have not been found. Based on the transcriptional-regulation of apoptosis by ecdysone-mediated induction of reaper gene expression in Drosophila, and p53-mediated transcriptional-activation of Bax gene expression in mammalian cells, our ...
Zeng L., Li T., Xu D.C., Liu J., Mao G., Cui M.Z., Fu X., Xu X.. Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). These two pathways can be linked by caspase-8-activated truncated Bid formation. Very recently, death receptor 6 (DR6) was shown to be involved in the neurodegeneration observed in Alzheimer disease. DR6, also known as TNFRSF21, is a relatively new member of the death receptor family, and it was found that DR6 induces apoptosis when it is overexpressed. However, how the death signal mediated by DR6 is transduced intracellularly is not known. To this end, we have examined the roles of caspases, apoptogenic mitochondrial factor cytochrome c, and the Bcl-2 family proteins in DR6-induced apoptosis. Our data demonstrated that Bax translocation is absolutely required for DR6-induced apoptosis. On the other hand, inhibition of caspase-8 and knockdown of Bid have no effect on DR6-induced ...
As one of the cellular death mechanisms, apoptosis, also known as programmed cell death, can be defined as the process of a proper death of any cell under certain or necessary conditions. Apoptosis is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body.. Many biochemical events and a series of morphological changes occur at the early stage and increasingly continue till the end of apoptosis process. Morphological event cascade including cytoplasmic filament aggregation, nuclear condensation, cellular fragmentation, and plasma membrane blebbing finally results in the formation of apoptotic bodies. Several biochemical changes such as protein modifications/degradations, DNA and chromatin deteriorations, and synthesis of cell surface markers form morphological process during apoptosis.. Apoptosis can be stimulated by two different pathways: (1) intrinsic pathway (or mitochondria pathway) that mainly occurs via release of ...
Explore EarlyTox Caspase-3/7 NucView 488 Assay Kits that enables detection of apoptosis within intact cell populations through the use of NucView 488 Caspase-3 substrate.
Annexin V-Biotin Apoptosis Reagent (ab14165). Quick and reliable detection of phosphatidylserine exposure by flow cytometry or microscopy.
The molecular nature of calcium (Ca(2+))-dependent mechanisms and the ion channels having a major role in the apoptosis of cancer cells remain a subject of debate. Here, we show that the recently identified Orai1 protein represents the major molecular component of endogenous store-operated Ca(2+) entry (SOCE) in human prostate cancer (PCa) cells, and constitutes the principal source of Ca(2+) influx used by the cell to trigger apoptosis. The downregulation of Orai1, and consequently SOCE, protects the cells from diverse apoptosis-inducing pathways, such as those induced by thapsigargin (Tg), tumor necrosis factor α, and cisplatin/oxaliplatin. The transfection of functional Orai1 mutants, such as R91W, a selectivity mutant, and L273S, a coiled-coil mutant, into the cells significantly decreased both SOCE and the rate of Tg-induced apoptosis. This suggests that the functional coupling of STIM1 to Orai1, as well as Orai1 Ca(2+)-selectivity as a channel, is required for its pro-apoptotic effects. We have
Bullacta exarata was hydrolyzed with trypsin to prepare peptides; Hydrolysates were isolated by ultrafiltration and purified using G-25 gel filtration. The purity of the Bullacta exarata was demonstrated by HPLC and its peptide sequence analysis was detected. The effects of BEPT II and BEPT II-1 on the proliferation of PC-3 cells were examined using a MTT assay. BEPT II and BEPT II-1 significantly inhibited the proliferation of PC-3 cells in a time- and dose-dependent manner. Annexin V/PI double staining studies showed exposing PC-3 cells to 5, or 15 mg/mL BEPT II-1 for 24 h increased the percentage of the early stage of apoptotic cells from 11.22% to 22.09%. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. These data support that BEPT II-1 has anticancer properties and merits further investigation to understand the mechanisms of BEPT II-1-induced apoptosis in PC-3 cells.
The BCL-2 family of proteins forms a complex interaction network that regulates cellular life and death decisions and contributes to cancer development, maintenance, and chemoresistance. BH3 only member proteins (e.g. BIM) serve as cellular stress sentinels and, when triggered, signal irreversible activation of apoptosis through their α-helical BH3 death domains. These pro-apoptotic signals are normally held in check by the multidomain anti-apoptotic proteins (e.g. BCL-XL, MCL-1) but when they are unable to do so the multidomain pro-apoptotic proteins BAX and BAK induce cell death through pore formation in the mitochondrial outer membrane. Therapeutic manipulation of the BCL-2 family with BH3 mimetics (including small molecules and synthetic peptides) is an emerging paradigm in cancer treatment and immune modulation. The design of next-generation therapeutics based on the BIM BH3 helix offers the unique advantage of recapitulating BIMs natural capacity to directly target the full complement of ...
transgene mice still have some protective effect. We propose that exogenous TNF-α results in robust induction of antiapoptotic genes, particularly through NF-κB activation, that is sufficient itself to prevent hepatocytes apoptosis in vivo. In contrast, the antiapoptotic gene response to Fas/CD95 activation alone is insufficient to prevent apoptosis but could act synergistically with Bcl-2. Although this antiapoptotic transcriptional response may be permissive for the Bcl-2 action, Bcl-xL could still have some antiapoptotic activity when transcription is blocked.. The major antiapoptotic role of NF-κB in the liver has now been extended to numerous models (4, 34).1) Embryonic lethal apoptotic liver destruction has been described in p65 and IκB kinase 2-deficient mice (6, 25). 2) Murine hepatocytes treated with NF-κB inhibitors also became apoptotic (7).3) NF-κB downregulation is required for TGF-β-induced apoptosis in hepatic cell lines (2).4) Finally, blocking NF-κB posthepatectomy ...
The major findings of this study are that ET-1 prevents apoptosis induced by serum deprivation in a dose-dependent manner via an ETA receptor in H9c2 cardiomyocytes and that the antiapoptotic effect of ET-1 is mediated through a c-Src/Bcl-xL pathway. Evidence for this proposal includes the following: (1) ET-1, but not AII, prevented mitochondrial cytochrome c release and apoptosis induced by serum deprivation in a dose-dependent manner, and this antiapoptotic effect was inhibited by an ETA receptor antagonist (BQ123) but not by an ETB receptor antagonist (BQ788); (2) the inhibitory effects of ET-1 on apoptosis were inhibited by tyrosine kinase inhibitors and adenovirus-mediated overexpression of KI-c-Src; (3) ET-1 stimulated c-Src activation; and (4) ET-1 upregulated an antiapoptotic molecule, Bcl-xL, and this upregulation was inhibited by tyrosine kinase inhibitors or cotransfection with KI-c-Src.. Recent evidence suggests that apoptosis of cardiac myocytes is a feature in cardiovascular ...
The present study examined levels of various components of the cell death machinery and drug sensitivity of 60 human cancer cell lines to anticancer drugs. With the exception of procaspase-3, which was undetectable in MCF-7 cells, caspases-2, -3, -6, -7, -8, and -9, as well as Apaf-1, were detectable in all 60 cell lines. Although these components of the cell death machinery varied widely in abundance, strong correlations between levels of Apaf-1 or procaspase-2, -3, -6, -8, or -9 and sensitivity to any class of antineoplastic agent were not observed. These results, although negative, have several important implications.. The attempt to correlate drug sensitivity with levels of various components of the cell death machinery was prompted by previous studies indicating that drug-induced apoptosis is markedly diminished when certain key components of the core cell-death machinery, particularly Apaf-1, procaspase-9, or procaspase-3, are genetically or functionally deleted (36, 37, 38 , 58 , 88 , 99) ...
Tomato extracts can inhibit the growth and malignant cloning of stomach cancer cells, according to a new study that paves the way for novel therapies to treat the deadly disease. Researchers analysed whole tomato extracts for their ability to tackle gastric cancercell lines.. Their antitumoral effect seem not related to specific components, such as lycopene, but rather suggest that tomatoes should be considered in their entirety, said Daniela Barone, researcher at the Oncology Research Centre of Mercogliano (CROM) in Italy.. Extracts of San Marzano and Corbarino tomato varieties were able to inhibit the growth and cloning behaviour of malignant cells. Treatment with the whole tomato extracts affected key processes within the cells hindering their migration ability, arresting cell cycle through the modulation of retinoblastoma family proteins and specific cell cycle inhibitors, and ultimately inducing cancer cell death through apoptosis.. Our results prompt further assessment of the potential ...
The relationship between apoptotic progression and cell cycle perturbation induced by microtubule-destabilising (vinblastine, Colcemid) and -stabilising (taxol) drugs was studied in two mesenchyme-derived neoplastic cell lines, growing as suspension (Jurkat) and monolayer (SGS/3A) culture, by morphocytochemical and biochemical approaches. The same kind of drug induced different effects on the cell kinetics (proliferation, polyploidisation, death) of the two cell lines. In floating cells, the drugs appeared more effective during the S phase, while in adherent cells they were more effective during the G2/M phase. Moreover two distinct neoplasia-associated apoptotic phenotypes emerged: the first pattern was the typical one and was found in cells with a low transition through the S/G2 phase (Jurkat), and the second one was mainly characterised by a cell death derived from micronucleated and mitotic cells, as a consequence of a low transition through the M/G1 phase (SGS/3A). Our data show that the ...
Apoptosis is a major form of cell death that is dependent on wild-type p53 after DNA damage for certain normal cells, such as those of the early embryo and those of lymphoid origin (3 , 4) . There are also several examples in the literature where apoptosis clearly contributes to the overall sensitivity of cells to treatment with radiation or chemotherapeutic agents as assessed either by in vivo treatments (15 , 72) or by clonogenic assays in vitro (69 , 72 , 73) . However, a major difference between these studies and ones that have failed to find a link between apoptosis and overall sensitivity has been the choice of the cells used in the study. For cells of nonlymphoid origin, the cases in which apoptosis does contribute to overall sensitivity have in large part been those that used cells derived from normal tissues genetically engineered to express dominant oncogenes. Introduction of viral or cellular oncogenes such as E1A (74 , 75) , myc (72 , 76) , or human papillomavirus E7 (77) renders ...
Objective - Pro-inflammatory cytokines are cytotoxic to β-cells and have been implicated in the pathogenesis of type 1 diabetes and islet graft failure. The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced β-cell death is unclear. Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two pro-apoptotic Bcl-2 proteins, Bad and Bax were examined in β-cells.. Research Design and Methods - Human islets, rat islets, and INS-1 cells were exposed to a combination of pro-inflammatory cytokines: interleukin (IL)-1β, interferon (IFN)γ and/or tumor necrosis factor (TNF)α. Activation of Bad was determined by Ser136 dephosphorylation; mitochondrial stress by changes in mitochondrial metabolic activity and cytochrome c release; and downstream apoptotic signalling by activation of caspase-9 and -3, and DNA fragmentation. The inhibitors FK506 and V5 were used to investigate the role of Bad and Bax activation, respectively.. Results - We found that ...
Mice and primary neuronal cultures. Hq, Apaf1-/-, and Bax-/- mice were maintained and genotyped as described previously (Fortin et al., 2001; Klein et al., 2002). Cortical neurons and cerebellar granule neurons (CGNs) were cultured from cortices of E15.5 mice and cerebellums of postnatal day 7 mice, respectively, as described previously (Fortin et al., 2001). Recombinant adenoviral vectors carrying human AIF or LacZ expression cassettes were prepared and used at 50 multiplicity of infection as described previously (Cregan et al., 2002).. Camptothecin treatment and cell viability assays. Neurons were treated with 10 μm camptothecin with or without 10 μm Boc-aspartyl (Ome)-fluoromethylketone (BAF) (Enzyme System Products, Livermore, CA) after 2 d in vitro (DIV). Cell survival was measured by the following: live/dead staining (Molecular Probes, Eugene, OR), Hoechst staining, MTT assay (Cell Titer kit; Promega, Madison, WI), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end ...
The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to undergo apoptotic changes that can reproduce the damage of intestinal epithelia exposed to inflammatory cytokines. In this model, we measured the effect of curcumin (curcuminoid from Curcuma Longa) added as a pre-treatment at different time intervals before stimulation with IFNγ. Curcumin administration to HT29 culture before the inflammatory stimulus IFNγ reduced the cell apoptosis rate. This effect gradually declined with the reduction of the curcumin pre-incubation time. This anti-apoptotic action by curcumin pre-treatment was paralleled by a reduction of secreted IL7 in the HT29 culture media, while there was no relevant change in the other cytokine levels. Even though curcumin pre-administration did not impact the activation of the
TY - JOUR. T1 - Mifepristone regulates expression of apoptosis related genes Fas and FasL in mouse endometrium. AU - Gao, F.. AU - Xu, F. H.. AU - Zhou, X. C.. AU - Han, X. B.. AU - Liu, Y. X.. PY - 2001/7/3. Y1 - 2001/7/3. N2 - AIM: To investigate the anti-implantation mechanism of mifepriston. METHODS: In situ hybridization and immunohistochemistry were applied to determine mRNA and protein. RESULTS: After mifepriston injection, the number of implantation sites were obviously reduced, mifepriston could inhibit the embryo implantation in mouse. The expression of apoptosis related genes, Fas and FasL, in mouse endometrium was also decreased after mifepriston treatment. CONCLUSION: The expression of apoptosis related genes Fas and FasL is regulated by mifepriston and the inhibitory effect of mifepriston on the embryo implantation may be mediated by action on the Fas/FasL system.. AB - AIM: To investigate the anti-implantation mechanism of mifepriston. METHODS: In situ hybridization and ...
title: Galpha12 Protects Vascular Endothelial Cells from Serum Withdrawal-Induced Apoptosis through Regulation of miR-155, doi: 10.3349/ymj.2016.57.1.247, category: Article
High-density lipoproteins (HDL) levels have been shown to be inversely correlated with coronary heart disease, but the mechanisms of the direct protective effect of HDL on endothelial cells are not fully understood. The apoptosis of endothelial cells induced by cytokines and/or oxidized low-density …
Vascular Endothelial Growth Inhibitor (VEGI) is an endothelial cell autocrine factor and a member of the tumor necrosis family of ligands. VEGI is able to specifically inhibit endothelial cell growth and is an efficient inhibitor of angiogenesis. The molecular mechanisms of VEGI activity on endothelial cells remain undefined. Here we focused on two important steps in the signal transduction of VEGI. We first determined a role of NF-κB in VEGI-induced apoptosis. We found that inhibition of the NF-κB pathway resulted in an increased apoptotic potential of VEGI. We conclude that the NF-κB pathway plays a role in suppressing the apoptotic potential of VEGI. We next investigated the receptor responsible for VEGI-induced endothelial cell apoptosis. DR3 is a receptor for VEGI and thus we first focused on confirming if DR3 is the receptor responsible for VEGI-mediated endothelial cell death. We determined VEGI had diminished apoptotic activity in endothelial cells that are depleted of DR3 by siRNA. ...
HOTAIR was known to enhance radioresistance in several cancers. However, the function of HOTAIR on radioresistance involving the regulation of HIF-1α in cervical cancer has not been reported. BALB/c nude mice were injected subcutaneously with HeLa cells and irradiated by X-ray. The tumor volume was measured and the expression of HOTAIR in tumors was detected by quantitative real-time PCR. Western blot was performed to detect the protein level of HIF-1α. MTT (3-(4,5-Dimethylthiazol-2-yl) 22,5-diphenyltetrazolium bromide) assay and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to examine the cell viability and cell apoptosis of HeLa cells and C33A cells exposed to radiation. Radiotherapy inhibited the tumor growth in mice bearing HeLa cells. Radiotherapy reduced the expression of HOTAIR and HIF-1α in tumor tissues and HeLa cells or C33A cells. HOTAIR overexpression abrogated the effect of radiation on the cell viability and cell apoptosis of HeLa and C33A cells
Pure ginsenoside standards (saponins Rh2, PD, and PT), along with an Rh2-enhanced North American ginseng (Panax quinquefolius) leaf extract (LFRh2), were tested for cytotoxic activity in cultured THP-1 leukemia cells. Thermal treatment of ginseng leaf resulted in production of both Rh2 and Rg3 content that was confirmed by liquid chromatography-mass spectrometry (LC-MS). Flow cytometry of cells stained with annexin V-fluorescein isothiocyanate and propidium iodide showed that the LFRh2 significantly (p ≤ 0.05) increased apoptosis (18% ± 0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50 (72 h) = 52 μmg/mL. In comparison, a similar significant (p ≤ 0.05) increase in apoptotic cell numbers occurred at 41 h of exposure for pure ginsenoside standards, PD (LC50 (72 h) = 13 μg/mL), PT (LC50 (72 h) = 19 μg/mL), and Rh2 (LC 50 (72 h) = 15 μg/mL). Although no further increase in apoptosis was observed in THP-1 cells after exposure to increasing concentrations of LFRh2 ...
TY - JOUR. T1 - FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. AU - Chinnaiyan, Arul M.. AU - Tepper, Clifford G. AU - Seldin, Michael F. AU - ORourke, Karen. AU - Kischkel, Frank C.. AU - Hellbardt, Stefan. AU - Krammer, Peter H.. AU - Peter, Marcus E.. AU - Dixit, Vishva M.. PY - 1996/3/1. Y1 - 1996/3/1. N2 - CD95 (Fas/APO-1) and tumor necrosis factor receptor-1 (TNFR-1) are related molecules that signal apoptosis. Recently, a number of novel binding proteins have been proposed to mediate the signaling of these death receptors. Here we report that an N-terminal truncation of one of these candidate signal transducers, FADD/MORT1, abrogates CD95-induced apoptosis, ceramide generation, and activation of the cell death protease Yama/CPP32. In addition, this dominant-negative derivative of FADD (FADD-DN) blocked TNF- induced apoptosis while not affecting NF-κB activation. FADD-DN bound both receptors, and in the case of CD95, it disrupted ...
In this paper, the use of (123)I-Annexin V for the detection of farnesyltransferase inhibitor (FTI)-induced apoptosis in tumour-bearing athymic mice is described. In vitro binding assays on LoVo cells show time- and dosage-dependent (125)I-Annexin V binding upon treatment with Tipifarnib (Zarnestra,
Objectives : We investigated the effect of Haein-tang(Hairen-tang) on short-term memory and apoptosis in dentate gyrus of the gerbils with transient global ischemia. Methods : For the induction of cerebral ischemia model in mice, common carotid arteries of gerbils were occluded with aneurysm clips for 5 min. One day after operation, Haein-tang(Hairen-tang) was administrated orally injected once a day for 15 consecutive days. Gerbils were randomly divided into four group(n=10 in each group): sham-operation group, ischemia-induction group, ischemia-induction and 50 mg/kg Haein-tang(Hairen-tang)-treated group, ischemia-induction and 100 mg/kg Haein-tang(Hairen-tang)-treated group, and ischemia-induction and 200 mg/kg Haein-tang(Hairen-tang)-treated group. The effect of Haein-tang(Hairen-tang) on memory function was investigated by using step-down avoidance task. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining and immunohistochemistry ...
We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...
In previous study we showed that caspase-2 plays the role of an apical caspase in cell death induction by taxanes in breast cancer cells. This study deals with the role of other caspases. We tested breast cancer cell lines SK-BR-3 (functional caspase-3) and MCF-7 (nonfunctional caspase-3). Using western blot analysis we demonstrated the activation of initiator caspase-8 and -9 as well as executioner caspase-6 and -7 in both tested cell lines after application of taxanes (paclitaxel, SB-T-1216) at death-inducing concentrations. Caspase-3 activation was also found in SK-BR-3 cells. Employing specific siRNAs after taxane application, suppression of caspase-3 expression significantly increased the number of surviving SK-BR-3 cells. Inhibition of caspase-7 expression also increased the number of surviving SK-BR-3 and MCF-7 cells. On the other hand, suppression of caspase-8 and caspase-9 expression had no significant effect on cell survival. However, caspase-9 seemed to be involved in the activation of
TY - JOUR. T1 - Nitrite generation and antioxidant effects during neutrophil apoptosis. AU - Misso, Neil L.A.. AU - Peacock, Craig D.. AU - Neil Watkins, D.. AU - Thompson, Philip J.. PY - 2000/3/15. Y1 - 2000/3/15. N2 - Neutrophil apoptosis is important for the resolution of airway inflammation in a number of lung diseases. Inflammatory mediators, endogenous reactive oxygen and nitrogen species, and intracellular and extracellular antioxidants may all influence neutrophil apoptosis. This study investigated the involvement of these factors during apoptosis of neutrophils cultured in vitro. Neutrophils undergoing spontaneous apoptosis in culture as assessed by annexin V binding generated significant amounts of nitrite. Incubation with agonistic anti-Fas monoclonal antibody or tumor necrosis factor-α (TNF-α) enhanced neutrophil apoptosis at 6 h, although it decreased nitrite accumulation. Although granulocyte-macrophage colony-stimulating factor significantly reduced neutrophil apoptosis, this ...
Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.
TY - JOUR. T1 - Pretreatment with low nitric oxide protects osteoblasts from high nitric oxide-induced apoptotic insults through regulation of c-Jun N-terminal kinase/c-Jun-mediated Bcl-2 gene expression and protein translocation. AU - Tai, Yu-Ting. AU - Cherng, Yih-Giun. AU - Chang, Chia Chen. AU - Hwang, Yi Ping. AU - Chen, Jui Tai. AU - Chen, Ruei-Ming. PY - 2007/5. Y1 - 2007/5. N2 - Nitric oxide (NO) can regulate osteoblast activity. In this study, we evaluated the effects of pretreatment with a low concentration of NO on osteoblast injuries induced by a high level of NO and its possible molecular mechanisms. Exposure of osteoblasts to 0.3 mM sodium nitroprusside (SNP), an NO donor, slightly increased cellular NO levels without affecting cell viability. SNP at 2 mM greatly increased the levels of cellular NO and reactive oxygen species, and induced osteoblast death. Thus, osteoblasts were treated with 0.3 and 2 mM SNP as the sources of low and high NO, respectively. Exposure of osteoblasts ...
Because defects in apoptosis programs, for example, high expression of antiapoptotic molecules, can cause resistance to treatment regimens including radiotherapy (8), current attempts to improve the outcome of glioblastoma patients depend on strategies to increase apoptosis sensitivity. In this study, we identify a new proapoptotic role of NF-κB in γ-irradiation-mediated apoptosis of glioblastoma cells by showing, for the first time, that NF-κB is critically required for Smac mimetic-triggered radiosensitization. This conclusion is supported by several independent pieces of evidence. First, BV6 and γ-irradiation cooperate to trigger apoptosis in glioblastoma cells. This interaction is highly synergistic in A172 glioblastoma cells (CI , 0.3). Second, BV6 stimulates NF-κB activation, which is required for the potentiation of γ-irradiation-induced apoptosis because genetic inhibition of NF-κB by overexpression of the dominant-negative superrepressor IκBα-SR significantly reduces BV6- and ...
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 ...
3H]Thymidine Incorporation Studies. Thymidine incorporation studies were performed with cells grown in 35-mm culture dishes. The cells were labeled by the addition of methyl-[3H]thymidine (1 μCi/ml) to the medium, and the reactions were stopped after 1 h. The medium was drawn off, and the cells were rinsed twice with ice-cold phosphate-buffered saline (PBS). The cultures were then fixed with ice-cold 5% trichloracetic acid overnight at 4°C, after which the cells were extracted as previously described (Guo and Reiners, 2000). A second replicate set of nonfixed dishes was treated with 0.25% trypsin-EDTA to estimate cell numbers. [3H]Thymidine was detected by scintillation counting and expressed as disintegration per minute per 103 cells.. Assessment of Apoptosis. The effects of HET0016 to induced apoptosis in 9L cells were examined by fluorescence-activated cell sorting analysis after the cells were labeled with an annexin V-fluorescein isothiocyanate (FITC) antibody (Sigma Chemical, St. Louis, ...
Previous studies suggested that dithio-carbamates are potent apoptosis and anti-apoptosis inducing agents in various cancer cells. Here, the anti-proliferative and apoptosis inducing effects of a new derivative (2-NDC) from the dithio-carbamate family was examined in human leukemia K562 cells. We use thiazolyl blue tetrazolium bromide (MTT) to measure viability and cell growth inhibition. The 2-NDC showed effects on viability in a dose and time-dependent manner, inhibiting proliferation at concentrations of 10-30 M after 24-48 hours of treatment and increasing values after 72 hours at 40-120 M. The cytotoxic effect of the compound was calculated with an IC50 of 30 M after 24-hour. Apoptosis induction was confirmed by acridine orange-ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, flow cytometric assessment and also caspase-3 activation assay. Furthermore, enzymes level such as superoxide dismutase (SOD) and catalase (CAT) involved in oxidative stress were evaluated. The results of this
Our results uncovered an unexpected role for MPO to influence the fate of neutrophils and consequently the duration of inflammation. By suppressing the constitutive cell death program, MPO prolonged the life span of neutrophils, thereby delaying the resolution of inflammation. These actions were specific for MPO, because other azurophilic granule constituents lactoferrin and elastase failed to affect neutrophil apoptosis.. Consistent with the commitment of neutrophils to apoptosis, MPO at clinically relevant concentrations delayed, rather than blocked apoptosis, resulting in prolonged survival of human neutrophils in vitro. We confirmed that increasing plasma concentrations of MPO in rats to levels comparable to those detected in patients with inflammatory vascular diseases20,21 was sufficient to retard the apoptotic machinery in neutrophils as assayed ex vivo. Furthermore, MPO also suppressed apoptosis in neutrophils that had emigrated into the airways and delayed resolution of inflammation in ...
The effects of the acute phase proteins AGP and AAT on early (2-hour) and late (24-hour) apoptosis and inflammation after renal I/R were investigated. Both AGP and AAT administered at reperfusion decrease early as well as late apoptosis, as reflected by renal internucleosomal DNA cleavage, TUNEL histology, and caspase-like activities. In line, we previously demonstrated that abrogating acute early apoptosis with selective antiapoptotic agents prevents subsequent inflammation as well as secondary apoptosis caused by inflammation, whereas antiapoptotic treatment that is initiated after the onset of apoptosis does not reduce I/R-induced inflammation.1 In contrast, in the present study, treatment after 2 hours of reperfusion inhibited inflammation, which is supported by reports of anti-inflammatory effects mediated by AGP and AAT.12 13 Early primary19 20 as well as late secondary2 21 apoptosis after I/R has been reported to be caused by various means. The present results, showing that AGP and (to a ...
TY - JOUR. T1 - Response of Apoptosis Related Proteins to Running in Fluoride-Exposed Mice. AU - Canning, M.. AU - Zohoori, Fatemeh. AU - Valentine, Ruth. AU - Khan, Z.. AU - Ahmed, A.. AU - Amaral, A.. AU - Azevedo, Liane. AU - Buzalaf, Maria. AU - Fabricio, M.. AU - Fernandes, M.. AU - Maguire, Anne. PY - 2017. Y1 - 2017. M3 - Meeting Abstract. VL - 96A. JO - Journal of Dental Research. JF - Journal of Dental Research. SN - 0022-0345. ER - ...
An in vitro ischemia model was established and the effect of the metabolic inhibitors cycloheximide (CHX) and actinomycin D (ActD) on apoptosis in astrocytes under ischemia studied. CHX decreased by 75% the number of cells dying after 6 hr of ischemia compared with control cultures. TdT-mediated dUTP nick end labelling (TUNEL) staining of comparable cultures was reduced by 40%. ActD decreased cell death by 60% compared with controls. The number of TUNEL-positive cells was reduced by 38%. The nuclear shrinkage in TUNEL-positive astrocytes in control cultures did not occur in ActD-treated astrocytes, indicating that nuclear shrinkage and DNA fragmentation during apoptosis are two unrelated processes. Expression of bcl-2 (alpha and beta), bax, and Ice in astrocytes under similar ischemic conditions, as measured by quantitative reverse transcription-polymerase chain reaction, indicated that ischemia down-regulated bcl-2 (alpha and beta) and bax. Ice was initially down-regulated from 0 to 4 hr, ...
AIMS--To compare in situ end-labelling (ISEL) of apoptosis in lung carcinoma with quantitative and semiquantitative light microscopic assessment and ultrastructural observations. METHODS--ISEL of apoptosis was evaluated in 42 lung carcinomas (24 squamous cell carcinomas, 12 adenocarcinomas and six small cell carcinomas). Results were correlated semiquantitatively with the extent of apoptosis in haematoxylin and eosin stained sections, with apoptotic indices and with ultrastructural observations (nine cases). RESULTS--In each tumour type the extent of apoptosis identified by ISEL correlated with that observed on light and electron microscopy. Tumour cells undergoing apoptosis showed either uniform nuclear staining with a surrounding halo or peripheral nuclear membrane staining. The latter pattern was more prominent in small cell carcinoma and correlated ultrastructurally with early apoptosis. A variable proportion of apoptotic cells and apoptotic bodies were unlabelled. Necrotic tumour cells ...
TY - JOUR. T1 - Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. AU - Condorelli, Gianluigi. AU - Morisco, Carmine. AU - Stassi, Giorgio. AU - Notte, Antonella. AU - Farina, Felicia. AU - Sgaramella, Giuseppe. AU - De Rienzo, Assunta. AU - Roncarati, Roberta. AU - Trimarco, Bruno. AU - Lembo, Giuseppe. PY - 1999/6/15. Y1 - 1999/6/15. N2 - Background - Left ventricular hypertrophy (LVH) represents both an adaptive response to increased cardiac work load and a precursor state of heart failure. Recent evidence linked cardiac myocyte death by apoptosis with LVH and heart failure. It remained unclear, however, whether apoptosis participated in the transition from LVH to left ventricular dysfunction (LVD). Methods and Results - Cardiac myocyte apoptotic events and changes in apoptosis-specific genes were studied in a rat model of chronic pressure overload induced by ...
When hypertonicity is imposed with sufficient intensity and acuteness, cells die. Here we investigated the cellular pathways involved in death using a cell line derived from renal epithelium. We found that hypertonicity rapidly induced activation of an intrinsic cell death pathway- release of cytochrome c and activation of caspase-3 and caspase-9-and an extrinsic pathway-activation of caspase-8. Likewise, a lysosomal pathway of cell death characterized by partial lysosomal rupture and release of cathepsin B from lysosomes to the cytosol was also activated. Relationships among the pathways were examined using specific inhibitors. Caspase inhibitors did not affect cathepsin B release into the cytosol by hypertonicity. In addition, cathepsin B inhibitors and caspase inhibitors did not affect hyper-tonicity-induced cytochrome c release, suggesting that the three pathways were independently activated. Combined inhibition of caspases and cathepsin B conferred significantly more protection from ...
Differentiation refers to the ability of cancer cells to revert to their normal counterparts, and its induction represents an important noncytotoxic therapy for leukemia, and also breast, prostate, and other solid malignancies. Flavonoids are a group of differentiation-inducing chemicals with a potentially lower toxicology profile than retinoids. Flavonoid-rich polyphenol fractions from the pomegranate (Punica granatum) fruit exert anti-proliferative, anti-invasive, anti-eicosanoid, and pro-apoptotic actions in breast and prostate cancer cells and anti-angiogenic activities in vitro and in vivo.. The results highlight an important, previously unknown, mechanism of the cancer preventive and suppressive potential of pomegranate fermented juice and pericarp extracts.. Journal of Medicinal Food, Volume: 7 Issue 1: July 7, 2004 ...
TY - JOUR. T1 - Reduced wall compliance suppresses Akt-dependent apoptosis protection stimulated by pulse perfusion. AU - Li, Manxiang. AU - Chiou, Kuan Rau. AU - Bugayenko, Artem. AU - Irani, Kaikobad. AU - Kass, David A.. PY - 2005/9/16. Y1 - 2005/9/16. N2 - Reduced arterial compliance and increased pulse pressure are common and major risk factors for cardiovascular disease. Here, we reveal a novel mechanism whereby loss of wall distensibility blunts endothelial cell protection to oxidant stress-induced apoptosis. Bovine aortic endothelial cells cultured in compliant or stiff silastic tubes were pulse perfused by arterial pressure/flow waveforms generated by a servo-pump. Pulse perfusion induced time-dependent Akt activation peaking ,6-fold after 2 hours in compliant tubes and a similar time course but half the magnitude in stiff tubes. This was accompanied by quantitatively similar disparities in phosphoinositide-3 kinase activation and in Akt-stimulated suppressors of apoptosis: glycogen ...
Worldwide Market Reports added Latest Research Report titled Global Apoptosis Assays Market Is Expected To Reach Around USD 6.96 Billion By 2025″ to its Large Report database. The report, the global Apoptosis Assays Market, demonstrates an all-encompassing investigation of the global Apoptosis Assays Market that appraises the market magnitude and evaluates the market assessment above the predicted time. The ruling players of the Apoptosis Assays Market are visible inside the report in company with thorough details referring to their revenue break-up, synopsis of the business, latest developments, product segmentation, and so on. The operative market players in the global Apoptosis Assays Market are further discussed in the report.. This Research will help you grow your Business: [Download free Sample PDF of This Research Report]. Some of the Major Apoptosis Assays Market Players Are:. Merck KGaA, Thermo Fischer Scientific, Bio-Rad Laboratories, GE Healthcare, Geno Technology, BioTek ...
The basal machinery controlling PCD appears to have been substantially conserved throughout metazoan evolution. The mammalian bcl‐2 gene family encodes cell death regulator proteins that exhibit structural and functional homology with the product of the death‐suppressing ced‐9 gene of C.elegans. Likewise, the ced‐3 killer gene of C.elegans encodes a member of the conserved caspase family of cysteine proteases, members of which play critical proapoptotic roles in mammalian apoptosis.. However, despite this conservation of the basal machinery between the nematode and mammals, neither ced‐9/bcl‐2 nor caspase homologues has yet been identified in the fruit fly, D.melanogaster. Indeed, the proapoptotic machinery so far defined in Drosophila via genetic screening comprises three genes, rpr, hid and grim that share little if any homology with known components of the mammalian death machinery and none at all with the nematode. The only clear link thus far between the apoptotic machinery in ...
In this paper we used a multiparametric approach to analyze extensively the events occurring during apoptotic cell death of thymocytes, and furthermore, we asked whether alterations in mitochondrial structure and function are occurring in early stages of apoptosis. A multiparametric quantitative analysis was performed on normal or apoptotic thymocytes emerging from a few-hour culture performed in culture medium or in the presence of dexamethasone. Simultaneous detection of light scattering properties, integrity of plasma membrane (trypan blue exclusion), chromatin condensation (AO/EB staining of entire cells or PI staining of nuclei), and DNA fragmentation (in situ nick-translation in apoptotic cells) allowed a precise analysis of the preapoptotic and apoptotic stages. Moreover a thorough study of mitochondrial transmembrane potential (delta psi m) assessed following in a time course study the uptake by apoptotic cells of the cationic lipophilic dye DiOC6(3) or the J-aggregate-forming cation ...
Successful wound closure is mainly the result of two cellular processes: migration and proliferation. Apoptosis has also been suggested to play a role in the mechanisms of wound healing. The fast calcium wave (FCW), triggered immediately after a wound is produced, has been proposed to be involved in determining healing responses in epithelia. We have explored the effects of the reversible inhibition of FCW on the apoptotic and proliferative responses of healing bovine corneal endothelial (BCE) cells in culture. The most important findings of this study are that caspase-dependent apoptosis occurs during the healing process, that the amount of apoptosis has a linear dependence on the migrated distance, and that FCW inhibition greatly increases the apoptotic index. We have further been able to establish that FCW plays a role in the control of cell proliferation during BCE wound healing. These results indicate that one of the main roles of the wave is to inhibit an excessive apoptotic response of the
CCAR1; cell division cycle and apoptosis regulator 1; cell division cycle and apoptosis regulator protein 1; CARP 1; CARP1; FLJ10590; death inducer with SAP domain; cell cycle and apoptosis regulatory protein 1; MGC44628; RP11-437A18.1; novel protein similar to vertebrate cell division cycle and apoptosis regulator 1 (CCAR1 ...
Cell apoptosis assay PaTu8988 cell apoptosis was Inhibitors,Modulators,Libraries detected by the Annexin V Apoptosis Detection Kit in accordance on the producers protocol. Briefly, 1 million cells with indicated therapies were stained with FITC Annexin V and PI. Each early and late apoptotic cells had been sorted by fluorescence activated cell sorting. Cell morphologic examination A total of 4 104 PaTu8988 cells were seeded on glass cover slips during the six very well plate and taken care of using the indicated concentration of SAHA for 48 h. Cells were fixed and stained with Wright Giemsa stain. The slides had been photographed using oil microscopy. In vitro tube formation assay or vasculogenic mimicry assay The tumor cell formation of capillary structure in vitro was examined as we previously described.. Cellular immuno fluorescence staining PaTu8988 cells were seeded on glass cover slips in merely six nicely plates and taken care of with described dosage of SAHA for 48 h. Cells about the ...
The development and growth of aneurysms involve the complex events of arterial wall cells remodeling (38). Previous studies have demonstrated that apoptosis is involved in the pathogenesis of aneurysms (6,7). However, the molecular mechanisms underlying the stimulation of apoptosis in the mouse IA model remains unknown.. To investigate the apoptotic events of IA mice model, the present study investigated the mRNA expression of caspases associated with the mitochondrial apoptotic pathway, including caspase-3, −8 and −9. The activation of caspases serves an essential role during the process of apoptosis (39), which may be caused by an extrinsic or intrinsic pathway, which lead to a terminal common pathway (40). Caspase-8 activation is involved in the extrinsic pathway and caspase-9 is involved in the intrinsic pathway. In the mitochondrial pathway, the release of Cyt-c constitutes an apoptotic complex, which subsequently results in the activation of caspase-9. The activation of caspase-8 and ...
The nuoG gene of Mycobacterium tuberculosis (Mtb) has the ability to inhibit host cell apoptosis. This ability is a virulence factor and does not exist in facultative pathogenic and non-pathogenic mycobacterial species. NuoG is part of the NDH-1 complex, and this study addressed the potential link between the role of NuoG in apoptosis inhibition and the biochemical activity of the NDH-1 complex. Different mycobacterial species were tested for their NDH-1 activities. Among the bacteria tested were bacteria transformed with the Mtb nuoG plasmid, or with the almost entire NDH-1 coding region. Surprisingly, the levels of NDH-1 activity did not correlate with apoptosis levels, suggesting a potential independent, novel mechanism by which NuoG inhibits host cell apoptosis. ...
Abstract: PURPOSE: The clinical use of the zoledronic acid has been increasing recently, and especially for the treatment of bone metastases. The synergistic effects of zoledronic acid with other chemotherapeutic agents have been shown. However it is not known whether a similar synergistic apoptotic effects exist for a combination therapy of zoledronic acid with radiation. METHODS: The MCF-7 human breast cancer cell lines were treated with 10 micrometer, 50 micrometer or 100 micrometer of zoledronic acid, irradiated with 5 Gy, and they were also treated with a combination of both treatments. The results of the synergistic effect on apoptosis were identified by performing XTT assay, DNA fragmentation assay, FACS analysis and western blot analysis at 24, 48, 72 hours after treatment. RESULTS: Zoledronic acid afftects anti-proliferative and apoptotic effects on MCF-7 breast cancer cell line in a dose-dependent manner. The synergistic cytotoxic effect of zoledronic acid and radiation was noted. The ...
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TY - JOUR. T1 - Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. AU - Thress, Kenneth. AU - Song, Jaewhan. AU - Morimoto, Richard I.. AU - Kornbluth, Sally. PY - 2001/3/1. Y1 - 2001/3/1. N2 - Protein folding mediated by the Hsp70 family of molecular chaperones requires both ATP and the cochaperone Hdj-1. BAG-1 was recently identified as a bcl-2-interacting, anti-apoptotic protein that binds to the ATPase domain of Hsp70 and prevents the release of the substrate. While this suggested that cells had the potential to modulate Hsp70-mediated protein folding, physiological regulators of BAG-1 have yet to be identified. We report here that the apoptotic regulator Scythe, originally isolated through binding to the potent apoptotic inducer Reaper, shares limited sequence identity with BAG-1 and inhibits Hsp70-mediated protein refolding. Scythe-mediated inhibition of Hsp70 is reversed by Reaper, providing evidence for the regulated reversible inhibition of chaperone activity. As ...
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 ...
B36 Lantadene A (LA, 22β-angeloyloxy-3-oxoolean-12-en-28-oic acid) a pentacyclic triterpenoid isolated from leaves of obnoxious weed Lantana camara L. was evaluated for apoptosis induction in human leukemia HL-60 cell line. The effect of LA on cell proliferation of HL-60 cancer cells were determined by MTT assay. The morphological effects of LA treated HL-60 cancer cells were observed under a fluorescence microscope. DNA fragmentation was observed using gel electrophoresis. Flow cytometry was carried out to observe changes in cell-cycle distribution of the cells. The expression of Bcl-2 and Bax proteins in HL-60 cells were visualized by means of immunohistochemical assay and cell viability was determined upon treatment with DEVD-CHO and LA. Typical morphological changes including cell shrinkage, chromatin condensation and characteristic DNA ladder formation in agarose gel electrophoresis were observed. LA induced marked concentration and time dependant inhibition of cancer cell proliferation ...
Systems Biology of Apoptosis summarizes all current achievements in this emerging field. Apoptosis is a process common to all multicellular organisms. Apoptosis leads to the elimination of cells via a complex but highly defined cellular programme. Defects in the regulation of apoptosis result in serious diseases such as cancer, autoimmunity, AIDS and neurodegeneration. Recently, a substantial step forward in understanding the complex apoptotic pathways has been made by utilising systems biology approaches. Systems biology combines rigorous mathematical modelling with experimental approaches in a closed loop cycle for advancing our knowledge about complex biological processes. In this book, the editor describes the contemporary systems biology studies devoted to apoptotic signaling and focuses on the question how systems biology helps to understand life/death decisions made in the cell and to develop new approaches to rational treatment strategies ...
Vasicinone, a quinazoline alkaloid from Adhatoda vasica Nees. is well known for its bronchodilator activity. However its anti-proliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, 70 μM) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. The Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells. Moreover vasicinone treatment also lead to down regulation of Bcl-2, Fas death receptor and up regulation of PARP, BAD and cytochrome c, suggesting the anti-proliferative nature of vasicinone which mediated apoptosis through both Fas death receptors as well as Bcl-2 regulated signaling. ...
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"Insights into male germ cell apoptosis due to depletion of gonadotropins caused by GnRH antagonists". Apoptosis. 12 (6): 1085- ... However, increasing the levels of FSH will increase the production of spermatozoa by preventing the apoptosis of type A ...
Apoptosis, or Type I programmed cell death, is essential for the maintenance of normal cellular homeostasis and is an important ... Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the "tumor suppressor lipid". Several ... However, owing to the conflicting and variable nature of studies into the role of ceramide in apoptosis, the mechanism by which ... There has been research suggesting that when ionizing radiation causes apoptosis in some cells, the radiation leads to the ...
... apoptosis, etc.). This is due to the fact that each remodeler complex has unique protein domains (Helicase, bromodomain, etc.) ... apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are ...
The second target gene, protein tyrosine phosphatase-1B (Ptp1b) is involved in the induction of apoptosis. Ptp1b gene protein ... Song H, Zhang Z, Wang L (March 2008). "Small interference RNA against PTP-1B reduces hypoxia/reoxygenation induced apoptosis of ... which are genes which endogenously regulate angiogenesis and apoptosis, respectively. Ephrin-A3 (Efna3) is a gene that is ... rat cardiomyocytes". Apoptosis. 13 (3): 383-393. doi:10.1007/s10495-008-0181-1. PMID 18278556. Szabó DR, Luconi M, Szabó PM, ...
Therefore, paraptosis was concluded to differ from apoptosis (cell death type 1) in being unaffected by inhibitors of apoptosis ... Like apoptosis and other types of programmed cell death, the cell is involved in causing its own death, and gene expression is ... In apoptosis, HMGB1, a chromatin protein, is retained within the nucleus to result in formations of apoptotic bodies, while in ... Similar to apoptosis, staining techniques can be used to identify paraptotic cells by highlighting the translocation of ...
Increased apoptosis will result. But, activity can be rescued by re-addition of the DUE-B's, even from a different species. ...
Shu HB, Halpin DR, Goeddel DV (1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751-63. ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1997). "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30 ... Cohen GM (1997). "Caspases: the executioners of apoptosis". Biochem. J. 326 (Pt 1): 1-16. doi:10.1042/bj3260001. PMC 1218630. ...
And secondly, to raise the threshold for apoptosis, therefore nonspecific leakage of cytochrome c would not result in apoptosis ... The inhibition of apoptosis is one of the key features of cancer so finding ways to manipulate and overcome this inhibition to ... In animals, apoptosis can be catalyzed in one of two ways; the extrinsic pathway involves binding of extracellular ligands to ... Mutated apoptosis pathways causing disease are plentiful and have a wide range from cancer, due to lack of apoptosome activity ...
Apoptosis and the cell cycle. McShea et al., 2007. Biochim Biophys Acta. 2007 Apr;1772(4):467-72. Epub 2006 Oct 3.Neuronal cell ... AD neurons which exit G0 and enter G1 do not activate the full set of caspases required for neuronal apoptosis (Raina et al. ... Since the cell is unable to complete the cell cycle, it dies via apoptosis (Meikrantz et al., 1995). In the past decade, ... Apoptosis and the cell cycle. Vincent et al., 1997. A Conformation- and Phosphorylation-Dependent Antibody Recognizing the ...
Analogy to apoptosis of somatic cells". Exp Cell Res. 207 (1): 202-205. doi:10.1006/excr.1993.1182. PMID 8391465. Lozano GM, ... It may also label cells having DNA damaged by other means than in the course of apoptosis. The fluorochrome-based TUNEL assay ... Detection of apoptosis and cell proliferation". Cell Proliferation. 28 (11): 571-579. doi:10.1111/j.1365-2184.1995.tb00045.x. ... Negoescu A, Guillermet C, Lorimier P, Brambilla E, Labat-Moleur F (1998). "Importance of DNA fragmentation in apoptosis with ...
doi:10.1016/S1471-4906(01)01941-X. Ashkenazi, Avi; Dixit, Vishva M. (April 1999). "Apoptosis control by death and decoy ... inhibiting the ability of the cytokines to signal for cell death or apoptosis. VEGFR-1 is a kinase-defective receptor tyrosine ...
Bates S; Vousden KH (February 1996). "p53 in signaling checkpoint arrest or apoptosis". Curr. Opin. Genet. Dev. 6 (1): 12-8. ...
Role in apoptosis[edit]. Cytochrome c also has an intermediate role in apoptosis, a controlled form of cell death used to kill ... Inhibition of apoptosis[edit]. One of the ways cell apoptosis is activated is by release of cytochrome c from the mitochondria ... Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation. *UMich Orientation of Proteins in Membranes families/superfamily-78 ... Cytochrome c is known to play a role in the electron transport chain and cell apoptosis. However, a recent study has shown that ...
However p21 may inhibit apoptosis and does not induce cell death on its own.[23] The ability of p21 to inhibit apoptosis in ... Apoptosis inhibition[edit]. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a ... "Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress". Mol. Biol. Cell. 17 (1): 402-12. doi:10.1091/ ... dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. ...
Apoptosis[edit]. Apoptosis is the programmed cell death of superfluous or potentially harmful cells in the body. It is an ... In the average adult between 50 and 70 billion cells die each day due to apoptosis. Inhibition of apoptosis can result in a ... In multicellular organisms, cell death in response to DNA damage may occur by a programmed process, apoptosis.[15] ... Hyperactive apoptosis can lead to neurodegenerative diseases, hematologic diseases, and tissue damage. ...
... inducing either apoptosis or osmotic cell lysis. The distinction between apoptosis and cell lysis is important in immunology: ... Cytolytic granule mediated cell apoptosis[edit]. NK cells are cytotoxic; small granules in their cytoplasm contain proteins ... Natural cytotoxicity receptors directly induce apoptosis after binding to Fas ligand that directly indicate infection of a cell ... The MHC-dependent receptors (described above) use an alternate pathway to induce apoptosis in infected cells. Natural killer ...
In fact, amphibian frog Xenopus laevis serves as an ideal model system for the study of the mechanisms of apoptosis.[40][41][42 ... Thyroxine and iodine stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibian ... Tamura K, Takayama S, Ishii T, Mawaribuchi S, Takamatsu N, Ito M (2015). "Apoptosis and differentiation of Xenopus tail-derived ... "Optogenetic Control of Apoptosis in Targeted Tissues of Xenopus laevis Embryos". Journal of Cell Death. 7: 25-31. doi:10.4137/ ...
DNA binding and apoptosis[edit]. The c-Abl gene in wild-type cells is implicated in DNA binding, which affects such processes ... The BCR-ABL fusion, in contrast, has been shown to inhibit apoptosis, but its effect on DNA binding in particular is unclear.[ ... The function of these pro-apoptotic proteins, however, is impaired, and apoptosis is not carried out in these cells. BCR-ABL ... Dan, S.; Naito, M.; Tsuruo, T. (1998). "Selective induction of apoptosis in Philadelphia chromosome-positive chronic ...
... MiniCOPE Dictionary-list of apoptosis terms and acronyms. *Apoptosis (Programmed Cell Death) - The Virtual Library of ... Hyperactive apoptosis[edit]. On the other hand, loss of control of cell death (resulting in excess apoptosis) can lead to ... Apoptosis Interest Group (1999). "About apoptosis". Archived from the original on 28 December 2006. Retrieved 2006-12-15.. ... The study of apoptosis brought on by Bunyaviridae was initiated in 1996, when it was observed that apoptosis was induced by the ...
Impaired developmental apoptosis[edit]. Paraganglionic tissue is derived from the neural crest cells present in an embryo. ... The induced glycolytic enzymes could potentially block cell apoptosis. RNA editing[edit]. The mRNA transcripts of the SDHB gene ... "Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer". ...
In animals apoptosis is induced by caspases and in fungi and plants, apoptosis is induced by arginine and lysine-specific ... The Mechanisms of Apoptosis Kimball's Biology Pages. Simple explanation of the mechanisms of apoptosis triggered by internal ... Apoptosis[edit]. Initiator caspases are activated by intrinsic and extrinsic apoptopic pathways. This leads to the activation ... Examples of caspase cascade during apoptosis: *Intrinsic apoptopic pathway: During times of cellular stress, mitochondrial ...
Apoptosis (type I)[edit]. Apoptosis is a form of programmed cell death in multicellular organisms. It is one of the main types ... It is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis.[3 ... the combination of apoptosis and necrosis, when in higher concentrations. ...
Humanin can protect brain cells by inhibiting apoptosis. Despite its name, versions of humanin also exist in other animals, ...
... or apoptosis.[2] It is followed by karyorrhexis, or fragmentation of the nucleus. Pyknosis (from Greek pyknono meaning "to ...
Tavassoly, Iman (2015). Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells. ... R. Kang, H. J. Zeh, M. T. Lotze, and D. Tang, 'The Beclin 1 Network Regulates Autophagy and Apoptosis', Cell Death Differ, 18 ( ... Cells that undergo an extreme amount of stress experience cell death either through apoptosis or necrosis. Prolonged autophagy ... Tavassoly Iman, Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells: ...
Tavassoly I (2015). Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells. ... Cells that undergo an extreme amount of stress experience cell death either through apoptosis or necrosis. Prolonged autophagy ... Tavassoly Iman, Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells: ... The second strategy is to inhibit autophagy and thus induce apoptosis.[94] ...
Apoptosis. *see apoptosis signaling pathway. GTP-binding protein regulators. *see GTP-binding protein regulators ...
In apoptosis, the cleavage of DNA is done by Ca2+ and Mg2+ -dependent endonucleases. ... Zamzami N, Kroemer G (1999). "Apoptosis: Condensed matter in cell death". Nature. 401 (127): 127-8. doi:10.1038/43591. PMID ...
Lippens, S; Hoste, E; Vandenabeele, P; Agostinis, P; Declercq, W (April 2009). "Cell death in the skin". Apoptosis. 14 (4): 549 ...
hCG - Promotes cellular differentiation, and is potentially involved in apoptosis.[citation needed] ...