Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.Caspase 7: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.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.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Caspase 10: 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.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Caspase 12: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Caspase 14: A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.DNA Fragmentation: Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Cytochrome c Group: A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Apoptotic Protease-Activating Factor 1: A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Inhibitor of Apoptosis Proteins: A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Caspases, Initiator: A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Apoptosis Regulatory Proteins: A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Oligopeptides: Peptides composed of between two and twelve amino acids.Fas-Associated Death Domain Protein: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cell Line: Established cell cultures that have the potential to propagate indefinitely.bcl-X Protein: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.Apoptosis Inducing Factor: A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.CASP8 and FADD-Like Apoptosis Regulating Protein: 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.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Caspases, Effector: A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.Apoptosomes: Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.CRADD Signaling Adaptor Protein: A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Death Domain Receptor Signaling Adaptor Proteins: Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.CARD Signaling Adaptor Proteins: A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.bcl-2 Homologous Antagonist-Killer Protein: A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 18.104.22.168.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Receptor-Interacting Protein Serine-Threonine Kinases: A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Receptors, TNF-Related Apoptosis-Inducing Ligand: Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.bcl-Associated Death Protein: A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.U937 Cells: 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.Genes, bcl-2: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Mice, Inbred C57BLCeramides: 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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Receptor-Interacting Protein Serine-Threonine Kinase 2: A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Myeloid Cell Leukemia Sequence 1 Protein: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Receptors, Tumor Necrosis Factor, Type I: 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.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Acetylcysteine: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Viral Proteins: Proteins found in any species of virus.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Endoplasmic Reticulum Stress: Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Deoxyadenine Nucleotides: Adenine nucleotides which contain deoxyribose as the sugar moiety.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Insect Proteins: Proteins found in any species of insect.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Gene Knockdown Techniques: 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.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.DNA Primers: 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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.FlavoproteinsCathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Bongkrekic Acid: An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.Pentanoic AcidsHepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Lamin Type B: A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.Isatin: An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.Keratin-18: A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.MAP Kinase Signaling System: 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.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Xenograft Model Antitumor Assays: 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.Mitogen-Activated Protein Kinase 8: 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.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Bcl-2 regulates amplification of caspase activation by cytochrome c. (1/8107)Caspases, a family of specific proteases, have central roles in apoptosis . 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  . 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    . 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  ) 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)
Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. (2/8107)The cyclin-dependent kinase inhibitor p21waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells. (+info)
Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. (3/8107)The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery. Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site. Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death. (+info)
Activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 kinase in calphostin C-induced apoptosis requires caspase-3-like proteases but is dispensable for cell death. (4/8107)Apoptosis was induced in human glioma cell lines by exposure to 100 nM calphostin C, a specific inhibitor of protein kinase C. Calphostin C-induced apoptosis was associated with synchronous down-regulation of Bcl-2 and Bcl-xL as well as activation of caspase-3 but not caspase-1. The exposure to calphostin C led to activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 kinase and concurrent inhibition of extracellular signal-regulated kinase (ERK). Upstream of ERK, Shc was shown to be activated, but its downstream Raf1 and ERK were inhibited. The pretreatment with acetyl-Tyr-Val-Ala-Asp-aldehyde, a relatively selective inhibitor of caspase-3, or benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk), a broad spectrum caspase inhibitor, similarly inhibited calphostin C-induced activation of SAPK/JNK and p38 kinase as well as apoptotic nuclear damages (chromatin condensation and DNA fragmentation) and cell shrinkage, suggesting that caspase-3 functions upstream of SAPK/JNK and p38 kinase, but did not block calphostin C-induced surface blebbing and cell death. On the other hand, the inhibition of SAPK/JNK by transfection of dominant negative SAPK/JNK and that of p38 kinase by SB203580 induced similar effects on the calphostin C-induced apoptotic phenotypes and cell death as did z-VAD.fmk and acetyl-Tyr-Val-Ala-Asp-aldehyde, but the calphostin C-induced PARP cleavage was not changed, suggesting that SAPK/JNK and p38 kinase are involved in the DNA fragmentation pathway downstream of caspase-3. The present findings suggest, therefore, that the activation of SAPK/JNK and p38 kinase is dispensable for calphostin C-mediated and z-VAD.fmk-resistant cell death. (+info)
Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (5/8107)We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability. (+info)
Phosphatidylinositol 3-kinase and protein kinase C are required for the inhibition of caspase activity by epidermal growth factor. (6/8107)The mechanism by which growth factors exert an anti-apoptotic function on many cell types is not well understood. This issue is addressed in relation to epidermal growth factor (EGF) which inhibits apoptosis induced by staurosporine or wortmannin in an epithelial tumour cell line (CNE-2). The presence of EGF substantially reduced the in vitro Ac-DEVD-AMC hydrolytic activity and almost completely suppressed the intracellular cleavage of poly(ADP-ribose) polymerase in staurosporine- or wortmannin-treated cells. Staurosporine but not wortmannin caused the intracellular proteolytic processing of pro-caspase-3 and this event was transiently inhibited by EGF. Staurosporine-induced apoptosis was not inhibited by EGF in the presence of wortmannin or LY294002. Similarly, EGF failed to inhibit wortmannin-induced apoptosis in the presence of staurosporine, chelerythrine chloride or Go6850. These results suggest that phosphatidylinositol 3-kinase and protein kinase C play a role in the survival function of EGF but the reduction of cellular caspase activity cannot be satisfactorily explained by a lack of pro-caspase-3 activation. (+info)
p27Kip1 induces drug resistance by preventing apoptosis upstream of cytochrome c release and procaspase-3 activation in leukemic cells. (7/8107)The cyclin-dependent kinase inhibitor p27Kip1 has been implicated as a drug resistance factor in tumor cells grown as spheroids or confluent monolayers. Here, we show that p27Kip1 overexpression also induces resistance to drug-induced apoptosis and cytotoxicity in human leukemic cells growing in suspension. The anti-apoptotic effect of p27Kip1 is not restricted to DNA-damaging agents but extends to the tubulin poison vinblastin, agonistic anti-Fas antibodies and macromolecule synthesis inhibitors. To further identify at which level this protein interferes with the cell death pathway, we investigated its influence on caspase activation and mitochondrial changes. Exposure of mock-transfected U937 cells to 50 microm etoposide activates procaspase-3 and the long isoform of procaspase-2 and induces mitochondrial potential decrease and cytochrome c release from mitochondria to the cytosol. All these events are prevented by p27Kip1 overexpression. p27Kip1 does not modulate Bcl-2, Bcl-X(L), Mcl-1 and Bax protein level in leukemic cells but suppresses Mcl-1 expression decrease observed in mock-transfected U937 cells undergoing etoposide-induced cell death. We conclude that p27Kip1 prevents cell death upstream of the final pathway common to many apoptotic stimuli that involves cytochrome c release from mitochondria and activation of downstream caspases. (+info)
MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (8/8107)Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited. (+info)
BioAssay record AID 666968 submitted by ChEMBL: Inhibition of human recombinant caspase-3 catalytic domain using Ac-DEVD-pNA as substrate at 20 ug/ml preincubated for 30 mins before substrate addition measured after 3 mins.
Flow cytometry is used to detect the fragmented DNA. Conofocal microscopy to assesses the morphological features of apoptosis such as apoptotic blebs. DNA marker to detect the DNA fragmentation. The fragmented DNA, from the apoptic cell, will present a DNA ladder in comparison to the unfragmented live cell. Hoecht staining of apoptotic nuclei (with Hoescht 33342 as a blue stain) to determine the condensation and fragmentation of the nuclei. Hoechst 33342 binds preferentially to adenine-thymine (A-T) regions of DNA. This stain binds into the minor groove of DNA and exhibits distinct fluorescence emission spectra that are dependent on dye:base pair ratios. FLICA (flourochrome inhibitor of caspase) is a simple yet accurate method to measure apoptosis via caspase activity in whole cells. It applies the green fluorescent inhibitor probe FAM-VAD-FMK to label active caspase enzymes in the cell samples. FLICA probes are comprised of an inhibitor peptide sequence that binds to active caspase enzymes, a ...
Active Caspase 2 FITC Staining Kit (ab65612). Active caspase 2 detection in living cells by flow, microscopy or fluorescent plate reader.
Active Caspase 3 FITC Staining Kit(Caspase 3FITC染色试剂盒)(ab65613)在活细胞中检测激活型caspase 3，基于流式、显微镜或荧光读板仪。
The IUPHAR/BPS Guide to Pharmacology. Caspase 1 - C14: Caspase. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
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The intracellular redox position is intently connected to the levels of professional-inflammatory cytokines, IL-1β, IL-23 and TNF-α which are the major factors of inflammatory responses. IFN-γ has also been shown to be linked with swelling although TNF-α has been researched thoroughly for its function in the inflammatory method and generation of ROS.Maintaining the earlier mentioned information into thought, we evaluated the level of IL-1β and IL-seventeen employing ELISA even though IFN-γ, IL-23 and TNF-α mRNA expression fold transform was identified utilizing qRT-PCR. We located that IL-1β ranges had been considerably larger in the two diabetic teams as in MEDChem Express 415903-37-6 contrast to the wholesome handle topics. The IL-1β is typically expressed by in-filtering macrophages, once activated they synthesize larger volume of nitric oxide as well. Curiously, there have been outstanding discrepancies in both NO and cytokine levels in the patients of higher age teams with glucose ...
The importance of the presented study lies in several key findings. First, our mechanistic knowledge of how the alternative splicing of caspase 9 is regulated has been expanded by our identification of a novel RNA cis-element via which SRSF1 (ASF/SF2) enhances the inclusion of the exon 3,4,5,6 cassette. Furthermore, SRSF1 was shown to specifically interact with this RNA cis-element, and regulate the alternative splicing of caspase 9 via this novel RNA cis-element. Second, we showed that the alternative splicing of caspase 9 is a relevant therapeutic target as shown by direct manipulation of this splicing cascade having significant effect on the sensitivity NSCLC cells to clinically relevant chemotherapeutics. Finally, one of the major findings of the report is our data showing that the synergism of erlotinib combination therapy is in part via modulation of the alternative splicing of caspase 9.. In regard to the RNA cis-element that specifically interacts with SRSF1, a purine-rich RNA ...
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Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
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Effects of ponicidin on the activity of caspase-3 in MKN28 cells. After treatment, the activity of caspase-3 in MKN28 cells was analyzed by the caspase-3 assay
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Assay Kits , Caspase Assay Kits , SensoLyte AFC Caspase Profiling Kit *Fluorimetric*; Caspases play important roles in apoptosis and cell signaling. They are also identified as drug-screening targets. AFC-based substrates yield blue fluorescence upon protease cleavage. They are widely used to monitor caspase activity. The SensoLyte Caspase Profiling Kit contains a series of AFC-based peptide substrates (Ex/Em=380 nm/500 nm) as fluorogenic indicators for assaying caspase protease activities. The kit contains a well-designed plate in which a series of AFC-based caspase substrates are coated with both positive and negative controls. It provides the best solution for profiling caspases or caspase inhibitors. The kit contains: A 96-well plate coated with a series of AFC-based caspase substrates along with various controls* Cell lysis buffer Assay buffer AFC (fluorescence reference standard for calibration) A detailed protocol A detailed protocol
Silibinin, a natural flavonolignan, induces apoptosis in human bladder transitional-cell papilloma RT4 cells both in vitro and in vivo; however, mechanisms of such efficacy are not completely identified. Here, we studied the mechanisms involved in silibinin-induced apoptosis of RT4 cells having intact p53. Silibinin increased p53 protein level together with its increased phosphorylation at serine 15, activated caspase cascade and caused Bid cleavage for apoptosis. Silibinin-caused p53 activation was mediated via ATM-Chk2 pathway, which in turn induced caspase 2-mediated apoptosis. Pifithrin-α, a p53 inhibitor, reversed silibinin-induced caspase activation including caspase 2; however, caspase 2 inhibitor also reversed p53 phosphorylation suggesting a bidirectional regulation between them. Further, silibinin caused a rapid translocation of p53 and Bid into mitochondria leading to increased permeabilization of mitochondrial membrane and cytochrome c release into the cytosol. JNK1/2 activation was ...
Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein (XIAP) against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by ...
Caspase inhibition is effective in minimizing nucleosome accumulation in key cortical cultures stimulated by TNF and thrombin. In contrast, the exact same effect is simply not observed in differentiated PC12 cells. In PC12 cells TNF induced LDH release is decreased by caspase inhibition. For the reason that TNF remedy induces both LDH release and nucleosome accumulation in PC12 cells, caspase inhibition could possibly enrich cell survival below disorders that induce a mixed apoptotic necrotic response. Pytlowany and colleagues demonstrate that In PC12 cells NO released from SNP decreases cell viability inside a time and concentration dependent method, with a increased concentration of NO leading to immediate and sustained lower in cell survival with no evoking a corresponding immediate activation of caspase three . In the recent review we locate that NO created by 0.5 mM SNP activates caspase three inside a longer time frame ...
Purpose: To model the time evolution of active caspase-3 protein expression in a healthy lens, and in a lens exposed to UVR-300 nm (UVR-B). To develop an automated method to classify the fluorescent signal of biomarkers in the lens epithelial cells.. Methods: Six-week old Sprague-Dawley rats were used. Firstly, expression of active caspase-3 was studied in the lens epithelium of healthy rats. Secondly, rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-B for 15 minutes. At 0.5, 8, 16, and 24 hours after the UVR-B exposure, the exposed and the contralateral non-exposed lenses were removed. Immunohistochemistry was done on three mid-sagittal sections from each lens. The florescent labelling for active caspase-3 in each lens section was counted three times. The time evolution of active caspase-3 expression in response to UVR-B exposure was modelled as a function of cell position in the lens epithelium. An automated objective method was developed to quantify the lens epithelial cells and to ...
Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegenration in Huntingtons and Alzheimers disease. This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative ...
[50 Pages Report] Check for Discount on Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 22.214.171.124) - Pipeline Review, H2 2016 report by Global Markets Direct. Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC...
Fluorescent Dyes , Enzyme Detection Reagents , Caspase 3 (Apopain) Substrate 1r-z, fluorogenic; Rh110 (rhodamine 110)-derived caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase activities. Cleavage of Rh110 peptides by caspases generates strongly fluorescent Rh110 that is monitored fluorimetrically at 510-530 nm with excitation of 488 nm, the most common excitation light source used in fluorescence instruments.; Caspase-3 substrate and caspase-7 substrate; (Z-DEVD)2-Rh110; z-(Asp-Glu-Val-Asp)2-Rh110
Caspase Substrate Assay Kit (Colorimetric) is used for assaying activities of members of caspase 1/2/3/5/6/8/9. (KA3698) - Products - Abnova
Caspase 3 antibody LS-C88630 is a biotin-conjugated rabbit polyclonal that binds human, mouse, rat, bovine, dog, hamster, pig, rabbit, and sheep caspase 3 (also known as CASP3). Caspase 3 antibody is validated for use in IHC-paraffin, immunoprecipitation, and western blot.
... evolutionarily, provides been suggested as a factor in maintenance of chromosomal tumour and balance reductions. can either arise from different structural lesions, such simply because mutations, chromosomal translocations or deletions, or can result from statistical changes where cells lose or gain copies of entire chromosomes (aneuploidy).3 NVP-BEP800 As the most common chromosome abnormality in individuals, aneuploidy is the most common chromosome abnormality in individuals, is the trigger of many congenital delivery flaws and is found in the majority of good tumours.4 It is also regarded a key underlying factor to tumor onset and treatment. Aneuploidy occurs from extravagant mitotic occasions, including problems in centrosome quantity, kinetochore-microtubule accessories, spindle-assembly gate (SAC), chromosome telomeres or cohesion. 4 Aberrant mitotic police arrest systems normally result in cell loss of life by apoptosis, ...
Consistent with the reported role for the NLRP3 inflammasome in LPS plus Dox-induced IL-1β production by bone marrow-derived macrophages (14), we observed reduced IL-1β release at the early (≤8-h) stages of LPS plus Dox stimulation in BMDC lacking caspase-1 (Fig. 2A, 2B), ASC (Fig. 2C), or NLRP3 (Fig. 2C). However, when Dox stimulation was sustained, the relative contribution of this NLRP3/caspase-1 cascade to IL-1β accumulation was superseded by an alternative pathway that was attenuated in the absence of caspase-8 or TRIF (Figs. 2, 4, 5). Robust proteolytic maturation of caspase-1 per se was invariably observed in WT BMDC treated with LPS plus Dox (Figs. 1, 2, 4) or LPS plus STS (Fig. 6), despite the fact that caspase-1 was dispensable for maximal IL-1β processing. We initially expected that the activation of caspase-1 and caspase-8 in response to Dox or STS comprised independent IL-1β-processing pathways operating in parallel. However, our observations and recent studies by others ...
BioAssay record AID 364025 submitted by ChEMBL: Induction of apoptosis in mouse TLT cells assessed as effect on caspase 3 activity at 100 ug/ml after 24 hrs by fluorometric assay in presence of 2 mM vitamin C.
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by caspase- 3 or -8.
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by caspase- 3 or -8.
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 ...
Kumar, A.P., Chang, M.K.X., Clement, M.-V., Fliegel, L., Pervaiz, S. (2007). Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death and Differentiation 14 (10) : 1733-1746. [email protected] Repository. https://doi.org/10.1038/sj.cdd. ...
Click to launch & play an online audio visual presentation by Prof. Guy Salvesen on Natural caspase inhibitors, part of a collection of online lectures.
We observed previously that cisplatin-resistant HeLa cells were cross-resistant to UV light due to accumulation of DDB2, a protein implicated in DNA repair. More recently, we found that cFLIP, which represents an anti-apoptotic protein whose level is induced by DDB2, was implicated in preventing apoptosis induced by deathreceptor signaling. In the present study, we investigated whether DDB2 has a protective role against UV irradiation and whether cFLIP is also involved in this process. Methods: We explored the role of DDB2 in mediating UV resistance in both human cells and Drosophila. ...
This video will show you how to perform an apoptosis assay using adherent cells on the Celigo image cytometer using caspase 3/7 and Hoechst reagents.
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013 ...
Fig: Stem cell treatment after MCAO procedure reduces caspase-dependent apoptosis and brain damage. a Green fluorescence indicates cleaved caspase 3 protein expression. Representative cleaved caspase3 images were merged with respective DAPI images. Scale bar 100 lm. b Quantification of cleaved caspase-3 protein expression in the ipsilateral hemisphere of untreated  and hUCBSCs-treated animals. n C 3. Values are expressed as mean ± SEM; *p\0.05 compared to untreated MCAO subjected animals. c Representative hematoxylin and eosin stained paraffinembedded tissue sections from rat brains. Higher magnification images from the ischemic cortex and striatal regions of MCAOsubjected and untreated animals show interstitial edema and damaged neurons that have a condensed, irregular shaped and darkly stained nuclei which are absent or less frequent in control/hUCBSCs-treated brain sections. Each group consisted of a minimum of three animals. Scale bar value for the magnified images = 100 lm ...
|strong|Rabbit anti caspase-9 p10 antibody|/strong| recognizes caspase-9, a member of the cysteine-aspartic acid protease family. The active form of caspase-9 is generated by cleavage of the pro-caspa…
Caspase-1 Inhibitor I - CAS 143313-51-3 - Calbiochem The Caspase-1 Inhibitor I, also referenced under CAS 143313-51-3, controls the biological activity of Caspase-1. This small molecule/inhibitor is primarily used for Cancer applications. - Find MSDS or SDS, a COA, data sheets and more information.
Rabbit polyclonal active Caspase-3 antibody validated for WB, ICC/IF and tested in Human, Mouse and Rat. Referenced in 2 publications and 3 independent…
Research tested and proven Caspase-10/b-Flice 2 antibody. Antibody is guaranteed to work in western blot applications and is reactive in human and mouse.
The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event. . 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.
Ac-IETD-AFC is a fluorogenic substrate for caspase-8/caspase-3 processing enzyme and granzyme B. It is also a substrate for caspase-10. The IETD sequence is based on casp
TY - JOUR. T1 - Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts. AU - Ulakcsai, Zsófia. AU - Bagaméry, Fruzsina. AU - Vincze, István. AU - Szöko, Éva. AU - Tábi, Tamás. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Aim: To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results: Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 μM. It also reduced ...
Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 126.96.36.199) - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at Researchmoz.us
Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18. It is found on chromosome 11 in humans in a locus with other inflammatory caspases. CASP12 orthologs have been identified in numerous mammals for which complete genome data are available. The CASP12 gene is subject to polymorphism, which can generate a full length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS). A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block ...
PTK787 2HCl and -7 (Lakhani et al. 2006 offers contributed to your knowledge of the physiological tasks of the caspases significantly. Oddly enough C57BL/6 mice deficient for both caspase-3 and -7 perish shortly after delivery while mice missing only caspase-3 or -7 have a normal life span and display a limited apoptotic phenotype in this genetic background (Lakhani et al. 2006 Leonard et al. 2002 This points to the functional redundancy between caspase-3 and -7 during embryogenesis. However several observations suggest that this overlap is not complete and that caspase-3 and -7 also fulfill non-redundant roles in apoptosis. For instance eye lenses of caspase-7 knockout mice are grossly normal whereas those of caspase-3 deficient mice display marked cataracts at the anterior lens pole (Zandy et al. 2005 Further support for this notion stems from biochemical studies demonstrating that caspase-3 and -7 exhibit differential activities toward multiple protein substrates with caspase-7 being more ...
Im preparing a Caspase 3 preparation today, in fact. The tissue is paraffin embedded rat ethmoturbinate. I boil the slides in 10 mM Na Citrate pH 6.0 20. Im using Sigmas rabbit polyclonal and Vectors DAB kit. John Carroll Dennis Anatomy, Physiology, and Pharmacology 109 Greene Hall Auburn University, AL 36849 On Wed, 1 Feb 2006, Yu, Jian wrote: > Thanks to several of you who have given me a lot of great suggestions on > how to get good cross sections of mouse small intestine One of you > mentioned that you do Caspase 3 staining routinely with the small > intestine, sorry that I could not find your email anyone. I have been > using the CAM1 Ab from BD, which works well for IF on frozen sections > but have a lot of background for IHC. Unfortunately the frozen sections > do not have the greatest structures. I would very much appreciate that > if you could share your experience with paraffin sections. > > > > Thanks again! > > ******************************************************** > > Jian ...
Caspase-3 is a cysteine protease that hydrolyzes diverse intracellular proteins during programmed cell death (known as apoptosis). It has been a popular target for drug design against abnormal cell death for more than a decade. No approved caspase based drug, however, is available so far. Therefore, structural insights about the substrate recognition of caspase-3 are needed for the future development of caspase-3 based inhibitors and drugs. In this study, crystal structures of recombinant caspase-3 in complex with seven substrate analog inhibitors, including acetyl (Ac)-DEVD-aldehyde (Cho), Ac-DMQD-Cho, Ac-IEPD-Cho, Ac-YVAD-Cho, Ac-WEHD-Cho, Ac-VDVAD-Cho, and tert-butoxycarbonyl (Boc)-D-fluoromethylketone (Fmk), have been analyzed in combination with enzyme kinetic data and computational models. Seven crystal structures were determined at resolutions of 1.7-2.6Å. The binding conformation of each inhibitor residue at P1-P4 position was analyzed. The negative P1 aspartic acid side chain is exclusively
The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimers and Parkinsons diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in ...
Severn Biotech, Limited SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde - SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde MW: 492.5 Ac-Tyr-Val-Ala-Asp-CHO A specific reversible inhibitor of caspase 1 (ICE, Interleukin 1ß Converting Enzyme) Thornberry N.A. et al. (1992) Nature 356, 768; Molineaux S.M. et al. (1993) Proc. Natl. Acad. Sci. USA 90, 1809; Walker N.P.C. et al. (1994) Cell 78, 343; Wilson K.P. et al. (1994) Nature 370, 270;
Zheng, T. , Rakic, P. and Flavell, R A. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1996, 384, 368-72. , Soengas, M. , Duncan, G. , Kaufman, S. , Lowe, S. W. and Mak, T. W. Essential contribution of caspase-3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev 1998, 12, 806-19. , Braun, M. , Denis, F. and Sekaly, R. P. Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus. J Exp Med 1997, 186, 1503-12. The route leading from ER stress to caspase-12 activation, however, remains unclear. There is evidence, however, suggesting that release of intracellular calcium stores associated with ER stress activates the protease calpain, which in turn can activate caspase-12 and lead to apoptosis . 10 Compensatory Caspase Activation: A Caveat to Knockout Analysis Although the generation of knockout animals has vastly increased our knowledge of the cellular apoptotic machinery, one difficulty in ...
Caspases, aspartate-specific cysteine proteases, have fate-determining roles in many cellular processes including apoptosis, differentiation, neuronal remodeling, and inflammation (for review, see Yuan & Kroemer, 2010). There are a dozen caspases in humans alone, yet their individual contributions toward these phenotypes are not well understood. Thus, there has been considerable interest in activating individual caspases or using their activity to drive these processes in cells and animals. We envision that such experimental control of caspase activity can not only afford novel insights into fundamental biological problems but may also enable new models for disease and suggest possible routes to therapeutic intervention. In particular, localized, genetic, and small-molecule-controlled caspase activation has the potential to target the desired cell type in a tissue. Suppression of caspase activation is one of the hallmarks of cancer and thus there has been significant enthusiasm for generating ...
Read independent reviews on Caspase Fluorometric Substrate Set II Plus from AMS Biotechnology (Archived Products) on SelectScience
F CD8+ T lymphocytes before operation, but this difference was not statistically BI 78D3 Significant (P.0.05). The percentages of CD8+ T lymphocytes in the
Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene. CASP7 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.
Induction of apoptosis and NF-kB activation by Apaf-1/Nod1 family members and DD proteins (Inohara et al., 2000). The more recent study suggested that IKKgamma binds to the site in C-terminal regulatory region of IKKbeta which is located after the HLH motif. Images ...
Pendedahan sel Jurkat kepada ekstrak biji anggur - GSE mengakibatkan peningkatan dose- dan masa yang bergantung kepada di apoptosis dan pengaktifan caspase,
Detail záznamu - Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells - Detail záznamu - Knihovna Akademie věd České republiky
Caspase 9 (cleaved Asp353) antibody (caspase 9, apoptosis-related cysteine peptidase) for ELISA, IHC-P, WB. Anti-Caspase 9 (cleaved Asp353) pAb (GTX86912) is tested in Mouse, Rat samples. 100% Ab-Assurance.
Caspase 8 antibody (caspase 8, apoptosis-related cysteine peptidase) for WB. Anti-Caspase 8 pAb (GTX50675) is tested in Human samples. 100% Ab-Assurance.
Polyclonal antibody for CASPASE 6/CASP6 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Human. CASPASE 6/CASP6 information: Molecular Weight: 33310 MW; Subcellular Localization: Cytoplasm.
As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues,...
Plasmid pcDNA-Caspase 12 from Dr. Junying Yuans lab contains the insert Caspase 12 and is published in Nature. 2000 Jan 6. 403(6765):98-103. This plasmid is available through Addgene.
Characterize the expression of caspase-4 and -5 in by measuring the production of cytokines: IL-1β concentrations and IL-1α will determined by ELISA in the cell supernatant will be collected from monocytes stimulated or ...
Protein and mRNA expression of Sirt1 is significantly reduced by I/R. Cardiac-specific Sirt1-/- mice exhibited a significant increase (44±5% versus 15±5%; P=0.01) in the size of myocardial infarction/area at risk. In transgenic mice with cardiac-specific overexpression of Sirt1, both myocardial infarction/area at risk (15±4% versus 36±8%; P=0.004) and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nuclei (4±3% versus 10±1%; P,0.003) were significantly reduced compared with nontransgenic mice. In Langendorff-perfused hearts, the functional recovery during reperfusion was significantly greater in transgenic mice with cardiac-specific overexpression of Sirt1 than in nontransgenic mice. Sirt1 positively regulates expression of prosurvival molecules, including manganese superoxide dismutase, thioredoxin-1, and Bcl-xL, whereas it negatively regulates the proapoptotic molecules Bax and cleaved caspase-3. The level of oxidative stress after I/R, as evaluated by ...
In this study, we define a critical role for Grx in TNF-α-mediated caspase-3 activation through regulation of caspase-3 cleavage and glutathiolation. Data to support this notion include (1) caspase-3 cleavage by TNF-α inversely correlated with glutathiolation; (2) TNF-α activated Grx. In Grx knock-down cells, TNF-α-induced apoptosis was attenuated and caspase-3 cleavage was significantly reduced, concomitant with increased caspase-3 glutathiolation; (3) enhanced caspase-3 cleavage by Grx overexpression was reversed by a thioltransferase inactive Grx (C22S); (4) in vitro glutathiolation experiments showed that caspase-3 cleavage by caspase-8 was inversely correlated with caspase-3 glutathiolation; (5) mutations of cysteines (C184 and C220) in caspase-3 show significant increase in cleavage; and (6) Grx binds caspase-3. Our data suggest a model in which TNF-α activates Grx, Grx deglutathiolates caspase-3, and then Grx dissociates from caspase-3, leading to caspase-3 activation. The present ...
Caspase-3 plays a key role in initiation of cellular events during the apoptotic process. PromoKines Caspase-3 and Caspase-7 Immunoassay Kits allow quantification of the specific activity of caspase-3 and -7, respectively. Since caspase-3 and -7 share the same target substrate sequence (DEVD), it is difficult to differentiate the cleavage activity attributed by these two caspases in vitro. Thus, the assays utilize caspase-3 or -7 specific antibodies to capture the activated caspase-3 or -7 in cell lysate. Specific activity of caspase-3 or -7 can then be analyzed using the common caspase-3/7 substrate DEVD-AFC. The assay system ensures absolute specific detection of only caspase-3 or caspase-7 activity in apoptotic samples. Other caspases and non-specific proteases are not detected.. ...
Caspase 3/7 Glo assay from Promega - posted in Apoptosis, Necrosis and Autophagy: Hello all, I recently purchased a Caspase 3/7 Glo assay kit from Promega for apoptosis detection.My assay was done with HEK293 cells which were stimulated with Etoposide.I performed the assay exactly described in the protocol,and detected the luminescence with our Luminoskan Ascent luminometer. Unfortunately, in my assay I observed no induction of caspase activity and that the highest reading was equal to the...
Apoptosis is a process of fundamental importance to multicellular organisms that enables control of cell populations and the removal of damaged or potentially harmful cells (Arends and Wyllie 1991). Apoptosis occurs in two phases: an initial commitment phase followed by an execution phase involving cytoskeletal disruption, membrane blebbing, condensation and fragmentation of chromatin, and the formation of apoptotic bodies (Earnshaw 1995). Caspases, a family of aspartate-specific cysteine proteases, play a critical role in the execution phase of apoptosis and are the key effectors responsible for many of the dramatic morphological and biochemical changes of apoptosis (for reviews see Cohen 1997; Thornberry and Lazebnik 1998). Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. Caspases can be divided into two classes: (1) initiator caspases, with long prodomains, such as caspases-8 and -9, which either ...
Caspase-1, originally called ICE, was the first mammalian analogue of the Caenorhabditis elegans death genes to be identified.11 Like all caspases, it is expressed as a proform, which is activated through proteolytic cleavage of an amino-terminal 11-kDa prodomain to release p20 and p10 subunits. Active caspase-1/ICE consists of a (p20/p10)2 tetramer, which is sufficient to process precursor IL-1β9,12-14 and, in at least some cell types, to induce apoptosis.16 Additionally, the prodomain has been postulated to have independent proapoptotic activity by enhancing death receptor-mediated caspase-8 activation.39 Although caspase-1 has conventionally been regarded as a proinflammatory, not a proapoptotic, caspase,10-12 it has been observed to induce or amplify apoptosis in tissue culture models.15,16. Regulated expression of caspase-1 in cardiac hypertrophy,17 the dilated cardiomyopathy of TNF-α overexpression,19 ischemia/infarction,21 and endotoxin-induced myocardial dysfunction18 prompted our ...
Neurodegenerative diseases pose one of the most pressing unmet medical needs today. It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently no disease-modifying therapies. Thus it is a potential target for neurodegenerative drug development. In the present study we report on the biochemistry and structure of caspase-6. As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free structure shows caspase-6 in a partially mature but latent conformation. The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase ...
The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 (Golgi reassembly and stacking protein of 65 kD) as a novel caspase substrate. GRASP65 is cleaved specifically by caspase-3 at conserved sites in its membrane distal COOH terminus at an early stage of the execution phase. Expression of a caspase-resistant form of GRASP65 partially preserved cisternal stacking and inhibited breakdown of the Golgi ribbon in apoptotic cells. Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity.
Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of caspase activation and tyrosine kinase/adaptor protein signaling to forge a unique approach for selectively killing leukemic cells through the forcible induction of apoptosis. We have engineered caspase variants that can directly be activated in response to BCR-ABL. Because we ...
Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...
The invention relates to an isolated nucleic acid molecule encoding a caspase-14 polypeptide or functional fragment thereof, a vector that contains the nucleic acid molecule and a host cell that contains the vector. The invention also relates to an isolated gene encoding caspase-14, as well as functional fragments thereof. The gene or nucleic acid molecule can include single or double stranded nucleic acids corresponding to coding or non-coding strands of the caspase-14 nucleotide sequence. Isolated caspase-14 polypeptides or functional fragments thereof are also provided, as are antibodies that specifically bind thereto. In addition, the invention relates to methods of identifying compounds that modulate caspase-14 activity.
In eukaryotic cells, there are 2 different forms of cell death: necrosis and apoptosis.19 Necrosis is considered to be a nonphysiological cell death. Necrosis is characterized as an uncoordinated collapse of cellular homeostasis, resulting in early damage of the plasma membrane and consequently the loss of the integrity of the cell. In contrast, apoptosis is a process of programmed cell death in which unnecessary cells are eliminated from multicellular organism. In apoptotic changes, condensation of the nucleus chromatin and fragmentation of the DNA are manifested. The cell shrinks as a result of cytoplasmic condensation, and organelles preserve their normal ultrastructure. The plasma membrane becomes ruffled and blebbed, which eventually separates the cell into a number of membrane-bound fragments of different sizes. The fragments are known as "apoptotic bodies."20 Besides its normal role in the development and maintenance of proliferating mature tissue, apoptosis is also involved in abnormal ...
Lee Ann, I asked a similar question months ago and got no help other than a hearty good luck! :-) So I did some investigating and can offer two IHC suggestions: Anti-activated Caspase-3. Cleavage (activation) of procaspase-3 (CPP32, apopain, YAMA) irreversibly commits the cell to the caspase cascade and cell death via apoptosis. Antibodies are available that react only with the Caspase-3 cleavage fragment(s) and not procaspase-3. Similarly, anti-PARP p85 fragment. PARP (poly ADP-ribose) is the nuclear substrate for activated Caspase-3 which cleaves PARP into the 25kDa and 85kDa fragments. Antibodies are available that react specifically with the PARP 85kDa fragment. Neither of these should stain necrotic cells as far as I know. As you point out TUNEL labeling of fragmented DNA doesnt discriminate between the two processes. I wish someone would find a protein expressed only by necrotic cells. Regards, Brett Brett M. Connolly, Ph.D. Merck Research Laboratories Department of Pharmacology ...
Looking for online definition of Caspase-1 in the Medical Dictionary? Caspase-1 explanation free. What is Caspase-1? Meaning of Caspase-1 medical term. What does Caspase-1 mean?
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 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 ...
Human caspase 2 ELISA kit can be used for detecting in vitro quantitative levels of caspase-2 (CASP2) in human serum, cell culture supernatant, plasma, tissue
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Apoptosis Protocol - posted in Apoptosis, Necrosis and Autophagy: Introduction to apoptosishttp://www.abcam.com...g...e&rid=11367Annexin V detection protocolhttp://www.abcam.com...g...e&rid=11369Apoptosis induction protocolhttp://www.abcam.com...g...e&rid=11368Caspase detection protocolhttp://www.abcam.com...g...e&rid=11370DNA fragmentation analysis protocolhttp://www.abcam.com...g...e&rid=11371
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Myc-DDK-tagged ORF clone of Homo sapiens caspase 8 associated protein 2 (CASP8AP2), transcript variant 2 as transfection-ready DNA - 10 µg - OriGene - cdna clones
In Figure 3, they added the DRACOs to these cells, either with, or without the inhibitor. They also included a product which makes cells which have just self destructed glow in the dark. The first four sections on the graph are simply controls, to pick up the background levels of cell death. Since the main function of caspases is to cause cell death to occur, you can guess what would happen if we were to add caspase inhibitors to a normal set of cells. The blue and red bars are both lower than the green bar , because they have the caspase inhibitors added. The next three sections show what happens when DRACOs are added to the mix, and they show that they kill off a lot of cells. And importantly, you can tell that its performed using caspases, because in the presence of inhibitor, the cells do not die as much. In fact, the levels of death seen is more or less the same as the other controls with inhibitors ...
Chemical-registry-number] 0 / Antigens, CD95; 0 / BH3 Interacting Domain Death Agonist Protein; 0 / BID protein, human; 0 / Carrier Proteins; 9007-43-6 / Cytochromes c; EC 3.4.22.- / CASP3 protein, human; EC 3.4.22.- / CASP8 protein, human; EC 3.4.22.- / CASP9 protein, human; EC 3.4.22.- / Caspase 3; EC 3.4.22.- / Caspase 8; EC 3.4.22.- / Caspase 9; EC 3.4.22.- / ...
Caspase-3 Assay Kit (Colorimetric) is used for detecting the activity of caspases that recognize the sequence DEVD using colorimetric method. (KA0740) - Products - Abnova
Progression of the cell cycle and control of apoptosis are crucial and intimately linked processes that occur in all multicellular organisms during development, normal cellular differentiation and tissue homeostasis. Survivin (TIAP, BIRC5), a 16 kDa protein, is a member of the inhibitors of apoptosis (IAP)/BIRP gene family, which includes XIAP, c-IAP-1, c-IAP-2, ILP-2, NAIP, Livin and Apollon.
Gabriel Gil has directed the Apoptotic Signalling research group of the IMIM since 2000. Apoptosis, or programmed cell death, is a physiological process with an essential role both during development and in the adult organism.
Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor, blocks all features of apoptosis in THP.1 and Jurkat T-cells.
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Incheol Shin heeft geschreven in bericht ,8o0up8$9qn$1 at green.kreonet.re.kr,... ,Also, if you know the best apoptosis assay system ,for the adherent cells. I would like to avoid ,the system with microscopic observations since ,I need to include the floating (apoptotic) cells ,in my assay. Cant you just collect the medium with floating cells, and then trypsinize your adherent cells and do your thing? Regards, Bas ...
New, license-free DNA ladders will allow researchers to estimate the size of fragments of DNA for a fraction of the cost of currently available methods.
Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been ... Apoptosis & Caspase 8-The Proteolysis Map (animation). *Caspase 8 at the US National Library of Medicine Medical Subject ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1f9e: CASPASE-8 SPECIFICITY PROBED AT SUBSITE S4: CRYSTAL STRUCTURE OF THE CASPASE-8-Z-DEVD-CHO ...
Datta R, Kojima H, Yoshida K, Kufe D (1997). "Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis ... 275 (3): 1902-9. doi:10.1074/jbc.275.3.1902. PMID 10636891.. *^ Hehner SP, Li-Weber M, Giaisi M, Dröge W, Krammer PH, Schmitz ... 70 (3): 1384-9. PMC 189957 . PMID 8627654.. *. Smith BL, Krushelnycky BW, Mochly-Rosen D, Berg P (1996). "The HIV nef protein ... 16 (3): 178-92. doi:10.1002/stem.160178. PMID 9617893.. *. Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M ( ...
Charvet C, Alberti I, Luciano F, et al., Proteolytic regulation of Forkhead transcription factor FOXO3a by caspase-3-like ... The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 ... The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 ... 21, nº 3, 2001, pp. 952-65, DOI:10.1128/MCB.21.3.952-965.2001, PMC 86685, PMID 11154281. ...
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ...
... which resembles that of the animal caspases. Similarly to the animal caspases, the phytaspase is a cell death promoting ... In contrast with the animal caspases, that exist in the cytoplasm in a form of pre-synthesized precursors, the activation of ... Porter, A. G.; Jänicke, R. U. (1999-02-01). "Emerging roles of caspase-3 in apoptosis". Cell Death and Differentiation. 6 (2): ... The phytaspase displays a strict substrate specificity, which resembles that of the animal caspase-3. It recognizes a ...
2003 nomenclature IA - Fas IB - Fas ligand IIA - Caspase 10 IIB - Caspase 8 III - unknown IV - Neuroblastoma RAS viral oncogene ... Caspase 10. Germline CASP10 mutation. 2% of patients ALPS-U: Undefined. 20% of patients CEDS: Caspase 8 deficiency state. No ... Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... 9 (3): 233-5. PMID 21475130. Archived from the original on 2012-04-26. [unreliable medical source?] Van Der Werff Ten Bosch, ...
Mishra MK, Basu A (June 2008). "Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and ... 133 (3): 866-74. doi:10.1016/j.foodchem.2012.01.106.. *^ Dutta K, Ghosh D, Basu A (May 2009). "Curcumin Protects Neuronal Cells ... 13 (3): 393-403. doi:10.1038/sj.cdd.4401833. PMID 16397582. Archived from the original on 29 September 2007.. ... 61 (3): 679-88. doi:10.1093/jac/dkm503. PMID 18230688. Archived from the original on 4 February 2010.. ...
Lo SS, Lo SH, Lo SH (2005). "Cleavage of cten by caspase-3 during apoptosis". Oncogene. 24 (26): 4311-4. doi:10.1038/sj.onc. ... 2007). "A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration". Nat. Cell Biol. 9 (8): 961-9. doi: ... 2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Mol. Cell. Proteomics. 4 (6 ...
In caspase-3 the 'hook' and 'sinker' attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. ... This is done through the binding to caspases directly. Similar to the functionality of NAIP, the BIR3 domain of XAIP binds to ... This is unexpected because in nerve growth factor withdrawal, caspase-3 and -9 are activated, causing cell death, which are the ... When overexpressed, XAIP is able to block caspases extremely well and prevents cell death of sympathetic neurons when nerve ...
Rho inactivation can activate caspase-3 and caspase-9; two key components of the apoptotic pathway. TcdA has been linked to ... 56 (3): 582-8. PMC 259330 . PMID 3343050. Lyras D, O'Connor JR, Howarth PM, Sambol SP, Carter GP, Phumoonna T, Poon R, Adams V ... 467 (7316): 711-3. doi:10.1038/nature09397. PMID 20844489. Dove CH, Wang SZ, Price SB, Phelps CJ, Lyerly DM, Wilkins TD, ... 35 (3): 1032-40. PMC 351151 . PMID 7068210. von Eichel-Streiber C, Laufenberg-Feldmann R, Sartingen S, Schulze J, Sauerborn M ( ...
Chen, Y R; Kori R; John B; Tan T H (Nov 2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins ... Chen YR, Kori R, John B, Tan TH (2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins ... HCLS1 has been shown to interact with Caspase 3. GRCh38: Ensembl release 89: ENSG00000180353 - Ensembl, May 2017 GRCm38: ... induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells". ...
This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 ... 978-3-319-11730-0. . PMID 25487014.. *^ Wegele H, Müller L, Buchner J (2004). Hsp70 and Hsp90 - a relay team for protein ... 978-3-540-22096-1. . PMID 14740253.. *^ Cvoro A, Dundjerski J, Trajković D, Matić G (1999-04-01). "The level and ... The Hsp70s are an important part of the cell's machinery for protein folding, and help to protect cells from stress. ...
2000). "Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8 and caspase-3 in human lymphomas". J. ... 1998). "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD". Nature. 391 (6662): 43-50. doi: ... Liu X, Zou H, Slaughter C, Wang X (May 1997). "DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger ... DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in ...
Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... This allows normal caspase activity to proceed. The binding process of Smac/DIABLO to XIAP and caspase release requires a ... 2 region that is thought to contain the only element that comes into contact with the caspase molecule to form the XIAP/Caspase ... Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1, MAP3K2, MAP3K7IP1, and XAF1. GRCm38: Ensembl release 89: ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases. TRAIL ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
... accompanied by activations of nuclear factor kappaB and caspase-3.. „Life Sci". 77 (7), s. 824-836, 2005-07-01. PMID: 15936354. ... Fitoterapia". 75 (3-4), s. 261-6, 2004-06. PMID: 15158982. *↑ Moon PD, Lee BH, Jeong HJ, An HJ, Park SJ, Kim HR, Ko SG, Um JY, ... ISBN 978-3-00-028747-3. *↑ Alexandra Dittmar. Morinda citrifolia L: Use in Indigenous Samoan Medicine. „Journal of Herbs and ... Głównymi mikronutrientami są witamina C, niacyna (witamina B3), żelazo i potas. Ilość potasu w noni jest porównywalna z ilością ...
Caspase 3 is reported to be involved in the proteolytic processing of this protein. Two alternatively spliced transcript ... This cytokine is produced as a precursor peptide (pro-IL-16) that requires processing by an enzyme called caspase-3 to become ... 1998). "Processing and activation of pro-interleukin-16 by caspase-3". J. Biol. Chem. 273 (2): 1144-9. doi:10.1074/jbc.273.2. ... doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Zhang Y, Center DM, Wu DM, et al. ( ...
CARD: Caspase recruitment domain, retrieved 3 November 2016 Bouchier-Hayes, L; Martin, SJ (2002). "CARD games in apoptosis and ... DD's can also be found with other types of domains including Ankyrin repeats, caspase-like folds, kinase domains, leucine ... Protein modules containing the CARD domain are associated with apoptosis, through the regulation of caspases that they are ... There are four types of death domain subfamilies: death effector domain (DED), caspase recruitment domain (CARD), pyrin domain ...
Swanton E, Bishop N, Woodman P (Dec 1999). "Human rabaptin-5 is selectively cleaved by caspase-3 during apoptosis". The Journal ... 346 (3): 593-601. doi:10.1042/0264-6021:3460593. PMC 1220890 . PMID 10698684. Hirst J, Lui WW, Bright NA, Totty N, Seaman MN, ... 83 (3): 423-32. doi:10.1016/0092-8674(95)90120-5. PMID 8521472. "Entrez Gene: RABEP1 rabaptin, RAB GTPase binding effector ... 508 (2): 201-9. doi:10.1016/s0014-5793(01)02993-3. PMID 11718716. Xiao GH, Shoarinejad F, Jin F, Golemis EA, Yeung RS (Mar 1997 ...
Affar, E. B.; Germain, M.; Winstall, E.; Vodenicharov, M.; Shah, R. G.; Salvesen, G. S.; Poirier, G. G. (2000). "Caspase-3- ... 392 (3): 499-509. doi:10.1042/BJ20050792. PMC 1316289 . PMID 16117724. This article incorporates text from the United States ...
2002). "Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis". J. ... 127 (3): 635-48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping ... 572 (1-3): 41-5. doi:10.1016/j.febslet.2004.07.007. PMID 15304321. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The ... 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948 . PMID 17353931. Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, ...
... increases caspase 3 activity in radiodamaged tumor cells and, therefore, increases radiation-induced apoptosis. It is ... Nasu, S; Milas, L; Kawabe, S; Raju, U; Newman, R (2002). "Enhancement of radiotherapy by oleandrin is a caspase-3 dependent ... 14 (4): 350-3. doi:10.1016/S0196-0644(85)80103-7. PMID 4039113. Bandara, V; Weinstein, SA; White, J; Eddleston, M (2010). "A ... 179 (2-3): e31-6. doi:10.1016/j.forsciint.2008.05.002. PMID 18602779. "Nerium oleander L.(PIM 366)". IPCS Inchem. 2005. . ...
... is able to suppress caspase-3 through MAPK and PKCalpha. Apoptosis as a result of anoxia/reoxygenation and H(2)O(2) ... "The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha". Biochimica et ... 284 (3): 1082-1094. PMID 9495870. Dong, J.; De Montigny, C.; Blier, P. (1998). "Full agonistic properties of BAY x 3702 on ... 3 (6): 924-7. PMID 12137415. Teal, P; Davis, S; Hacke, W; Kaste, M; Lyden, PD; Modified Randomized Exposure Controlled Trial ...
The main factors could be DNA fragmentation and caspase-3 activation. FB1 has also immunotoxic effects, but much more research ... 301 (1-3): 21-32. doi:10.1016/j.tox.2012.06.012. PMID 22749975. Riley, R.T.; Voss, K.A. (2006). "Differential sensitivity of ... The proposed mechanism of action is depicted in figure 3. Fumonisin B1 occupies the space and electrostatic interactions of ... 3): 83-84. PMID 6346521. Wild CP, Gong YY (29 October 2009). "Mycotoxins and human disease: a largely ignored global health ...
Mitchell DA, Marletta MA (August 2005). "Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine". Nat. ... Nitrosylated thioredoxin, via directed protein-protein interaction, trans-nitrosylates the active site cysteine of caspase-3 ... 129 (3): 511-22. doi:10.1016/j.cell.2007.02.046. PMID 17482545. Que LG, Liu L, Yan Y, Whitehead GS, Gavett SH, Schwartz DA, ... thus inactivating caspase-3 and preventing induction of apoptosis. As might be expected of an enzyme involved in regulating NO ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 18 (3): 914-22. PMC 2042137. PMID 9437013.. *^ Nielsen AL, Holm IE, Johansen M, Bonven B, Jørgensen P, Jørgensen AL (August ... 10 (3): 563-8. doi:10.1097/00001756-199902250-00022. PMID 10208590.. *^ Zhang W, Han SW, McKeel DW, Goate A, Wu JY (February ... doi:10.1016/S0896-6273(00)80291-3. PMID 8755489.. *^ Ratovitski T, Slunt HH, Thinakaran G, Price DL, Sisodia SS, Borchelt DR ( ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Molecular Docking Analysis of Caspase-3 Activators as Potential Anticancer Agents.. Kashaw SK, Agarwal S, Mishra M, Sau S, Iyer ... Pharmacophore Modeling, Docking and Molecular Dynamics Studies on Caspase-3 Activators Binding at β-Tubulin Site. Bhunia SS et ... Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinsons Disease. Yuan J et al. PLoS ... Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. Sharma S et al. Biomed Res Int. (2013 ...
Caspases are crucial mediators of programmed cell death (apoptosis). Among them, caspase-3 is a frequently activated death ... Caspase-3 is essential for normal brain development and is important or essential in other apoptotic scenarios in a remarkable ... Thus, caspase-3 is essential for certain processes associated with the dismantling of the cell and the formation of apoptotic ... Pathways to caspase-3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c ...
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... homogeneous fluorescent apoptosis assay for use in cultured cells and with purified caspase. Just add-mix-read. ... Caspase-Glo® 8 Assay Systems. Measure caspase-8 activity with this homogeneous, luminescent assay. ... Caspase-Glo® 9 Assay Systems. Measure caspase-9 activity with this homogeneous, luminescent assay. ... A fluorescent pan-caspase inhibitor to detect caspase activity in live cells. ...
Cancer gene therapy using a pro-apoptotic gene, caspase-3.. Yamabe K1, Shimizu S, Ito T, Yoshioka Y, Nomura M, Narita M, Saito ... Caspase-3 is a member of the cysteine protease family, which plays a crucial role in apoptosis. We applied the human caspase-3 ... Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, but apoptosis was markedly enhanced by ... In conclusion, caspase-3 gene transduction accompanied by an additional death stimulus may be a useful method of anticancer ...
... which regulates the initiator caspase-9, and the executioner caspases-3 and -7. We report the crystal structure of the second ... Structural basis for the inhibition of caspase-3 by XIAP.. Riedl SJ1, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW, ... The inhibitor makes limited contacts through its BIR domain to the surface of the enzyme, and most contacts to caspase-3 ... The molecular mechanism(s) that regulate apoptosis by caspase inhibition remain poorly understood. The main endogenous ...
Rabbit polyclonal Caspase-3 antibody. Validated in WB, IP, IHC, ICC/IF and tested in Mouse, Rat, Rabbit, Human, Monkey. Cited ... Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the ... Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice ... associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the ...
Caspase-7 Activation , Caspase-9 Activation, Chemopreventive. Additional Keywords : Beet, Benzo(a)pyrene, Betaine, lung cancer ... Caspase-8 activation, Caspase-9 Activation, Tumor Suppressor Protein p53 Upregulation ... Caspase-8 activation, Caspase-9 Activation, Cell cycle arrest, Chemotherapeutic ... Baicalein could increase caspase-3 and Bax expression and decrease survivin and Bcl-2 to induce apoptosis.Aug 31, 2017. ...
Cleaved caspase-3 product listings, product citations, comparison tables and educational resources for apoptosis signaling from ... Caspases, a family of cysteine proteases, are the central regulators of apoptosis. Initiator caspases (including caspase-2, -8 ... Once activated, initiation caspases cleave and activate downstream effector caspases (including caspase-3, -6, and -7), which ... Caspase-3 Western Blotting Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664. Western blot analysis of extracts from C6 (rat ...
Rabbit polyclonal Caspase-3 antibody validated for WB, IHC and tested in Human, Mouse, Rat and Rabbit. Referenced in 16 ... Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the ... Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice ... associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the ...
Effector caspases-3, -6 and -7 are responsible for producing the morphological features associated with apoptosis, such as DNA ... Inhibition of caspase-7 activity reduced the extent of apoptosis induced, indicating that activation of caspase-7 is involved ... Apoptosis was accompanied by DNA fragmentation and the activation of caspase-7, but not caspases-3 and -6. ... Caspase-3 is not essential for DNA fragmentation in MCF-7 cells during apoptosis induced by the pyrrolo-1,5-benzoxazepine, PBOX ...
Rabbit polyclonal active Caspase-3 antibody validated for WB, ICC/IF and tested in Human, Mouse and Rat. Referenced in 2 ... Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the ... Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice ... associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the ...
Anti-active Caspase-3 antibody (ab2302) has been cited in 150 publications. References for Human, Mouse, Rat, Rabbit in ICC/IF ... Han X et al. Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice. ASN Neuro 7 ... Huang H et al. Microcystin-LR Induced Apoptosis in Rat Sertoli Cells via the Mitochondrial Caspase-Dependent Pathway: Role of ... Bulosan M et al. Inflammatory caspases are critical for enhanced cell death in the target tissue of Sjögrens syndrome before ...
Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage (By similarity). ... Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it ... PS01122 CASPASE_CYS, 1 hit. PS01121 CASPASE_HIS, 1 hit. PS50207 CASPASE_P10, 1 hit. PS50208 CASPASE_P20, 1 hit. ... PS01122 CASPASE_CYS, 1 hit. PS01121 CASPASE_HIS, 1 hit. PS50207 CASPASE_P10, 1 hit. PS50208 CASPASE_P20, 1 hit. ...
The cleaved caspase 3 assay utilizes the Caspase-3 inhibitor… ... Cleaved Caspase-3 Staining Kit (FITC) ab65613 provides a ... convenient means for sensitive detection of activated Caspase-3 in living cells. ... The caspase family of cysteine proteases play a key role in apoptosis. Caspase 3 (also known as CPP32, YAMA and apopain) is the ... Caspases 8, 9 and 10). The processed form of Caspase 3 consists of large (17kD) and small (12kD) subunits which associate to ...
Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ... caspase activity would kill cells indiscriminately. As an executioner caspase, the caspase-3 zymogen has virtually no activity ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10 ...
MilliporeSigma Calbiochem Caspase-3 Substrate IV, Fluorogenic 5mg Life Sciences:Protein Biology:Protein Extraction and ...
Ethanol-induced caspase-3 activation in the in vivo developing mouse brain.. Olney JW1, Tenkova T, Dikranian K, Muglia LJ, ... we document that ethanol intoxication of 7-day-old infant mice causes a widespread pattern of caspase-3 activation ...
Cleavage of Rh110 peptides by caspases generates strongly fluorescent Rh110 that is monitored fluorimetrically at 510-530 nm ... caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase ... Caspase-3 substrate and caspase-7 substrate; (Z-DEVD)2-Rh110; z-(Asp-Glu-Val-Asp)2-Rh110 ... Caspase 3 (Apopain) Substrate 1r-z, fluorogenic; Rh110 (rhodamine 110)-derived ...
caspase-3-like Symbol and Name status set to provisional. 70820. PROVISIONAL. ... 3. 0.0001. tibia size trait (VT:0100001). tibia midshaft cross-sectional area (CMO:0001717). 8. 33558660. 89058369. Rat. ... Hepatocarcinoma resistance QTL 3. 2.9. 0.0005. liver integrity trait (VT:0010547). volume of individual liver tumorous lesion ( ... 3. blood glucose amount (VT:0000188). blood glucose level (CMO:0000046). 8. 30144800. 75144800. Rat. ...
It has been widely accepted that the activation of effector caspases, such as caspase-3, will eventually lead to apoptosis of a ... The cleavage of PARP by caspases (such as caspase-3) facilitates cellular disassembly and serves as a marker of cells ... I: Quantitation of caspase-3 labeled neurons. *P ≤ 0.05. Bar = 50 μm in A-C, F, and G; 100 μm in D and E; and 7.4 μm in H. ... with Apaf-1 and caspase-9, forms the apoptosome, which then generates a downstream cascade of caspase activation. Other ...
Knockout Tested Rabbit recombinant monoclonal Caspase-3 antibody [E87]. Validated in WB, IP, IHC, Flow Cyt, ICC/IF and tested ... Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the ... Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice ... associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the ...
Invitrogen Anti-Caspase 3 Polyclonal, Catalog # PA5-96077. Tested in Western Blot (WB), Immunofluorescence (IF), ... Cite Caspase 3 Polyclonal Antibody. The following antibody was used in this experiment: Caspase 3 Polyclonal Antibody from ... Caspase-3; Caspase-3 subunit p12; Caspase-3 subunit p17; CPP-32; CPP32beta; Cysteine protease CPP32; IRP; LICE; PARP cleavage ... Caspase 3 apoptosis related cysteine protease (ICE-like cysteine protease); caspase 3, apoptosis related cysteine protease; ...
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by ... Caspase Colorimetric Assay Kits & Caspase Fluorescent Assay Kits. The Caspase-3 Colorimetric Assays measure the proteolytic ... Caspase Colorimetric and Fluorescent Assay Kits. The ApoAlert Caspase Assay Kits provide a simple and convenient way to detect ... Simultaneously profile multiple caspases *Perform the assay directly on cell lysates *Fast and easy: caspase colorimetric ...
- Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. (wikipedia.org)
- The inhibitor makes limited contacts through its BIR domain to the surface of the enzyme, and most contacts to caspase-3 originate from the N-terminal extension. (nih.gov)
- C2C12 cells were treated with Staurosporine, a PKC inhibitor that induces apoptosis (1 μM for 3 hours). (cellsignal.com)
- The cleaved caspase 3 assay utilizes the Caspase-3 inhibitor, DEVD-FMK, conjugated to FITC (FITC-DEVD-FMK) as a marker. (abcam.com)
- A ) Autoradiogram of [ 35 S]methionine-labeled proteins treated with purified active (-) or inactivated [by addition of a caspase-3 inhibitor, DEVD-fmk (+)] recombinant caspase-3. (sciencemag.org)
- Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. (sigmaaldrich.com)
- In this study, we used cellular models to mimic such blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression. (springer.com)
- The GSDME-NT production and lytic cell death induced by ATP were diminished by caspase-3 inhibitor. (springer.com)
- Moreover, we show that, in contrast to the human enzymes, mouse caspase-7 is as efficient as caspase-3 at cleaving and thus inactivating ICAD (inhibitor of caspase-activated DNase), the inhibitor of apoptotic DNA fragmentation. (jneurosci.org)
- Caspase-3 inhibitor (Z-DEVD-FMK ) is a cell-permeable, potent, and irreversible inhibitor of caspase-3, caspase-6, caspase-7, caspase-8 and caspase-10. (scbt.com)
- See how others have used Caspase-3 Inhibitor. (scbt.com)
- EGCG-mediated induction of apoptosis was significantly blocked by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-FMK), and moderately blocked by the specific caspase-3 inhibitor Z-DEVD-FMK. (nih.gov)
- Caspase-1 Inhibitor I (Ac-YVAD-CHO, also designated L-709049) is a potent, specific, reversible inhibitor of caspase-1 (K i = 200 pM for human recombinant caspase-1), caspase-4, and caspase-5. (scbt.com)
- We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. (nih.gov)
- Furthermore, the above stated signaling steps were prevented by Z-DEVD-FMK, a known inhibitor of caspase-3. (biomedsearch.com)
- A synthetic peptide inhibitor that irreversibly inhibits caspase-3 and related protease/caspase activity and blocks apoptosis. (creative-enzymes.com)
- Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex which were crucial for the induction of nuclear translocation of NF-κB. (wikipedia.org)
- Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
- Akt acts as an allosteric inhibitor of caspase-9 because the site of phosphorylation of serine-196 is far from the catalytic site. (wikipedia.org)
- The inhibitor affects the dimerization of caspase-9 and causes a conformational change that affects the substrate-binding cleft of caspase-9. (wikipedia.org)
- DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in humans is encoded by the DFFA gene. (wikipedia.org)
- X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. (wikipedia.org)
- It was identified as the target of the baculoviral caspase inhibitor protein P35, which it cleaves and by which it is inhibited. (wikipedia.org)
- Caspase activity and apoptosis inhibitor 1 is a protein that in humans is encoded by the CAAP1 gene. (wikipedia.org)
- CAD is normally inhibited by another protein, the Inhibitor of Caspase Activated DNase (ICAD). (wikipedia.org)
- PUMA levels are downregulated through the activation of caspase-3 and a protease inhibited by the serpase inhibitor N-tosyl-L-phenylalanine chloromethyl ketone, in response to signals such as the cytokine TGFβ, the death effector TRAIL or chemical drugs such as anisomycin. (wikipedia.org)
- A covalent inhibitor of aspartate proteases, 1,2-epoxy-3-(p-nitrophenoxy)propane or EPNP, completely blocks toxin B function on cultured cells and has been used to identify the catalytically active protease site. (wikipedia.org)
- Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. (wikipedia.org)
- The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
- and the protein itself is processed and activated by caspases 8, 9, and 10. (wikipedia.org)
- Recombinant full length protein corresponding to Human Caspase-3. (abcam.com)
- Caspase 3 (also known as CPP32, YAMA and apopain) is the most extensively studied apoptotic protein among caspase family members. (abcam.com)
- Gene for Caspase 3 also known as Yama, CPP32, and apopain codes for a 32-kDa protein. (abcam.com)
- Protein corresponds to full length Caspase 3, subunit p12 (NP_116786). (abcam.com)
- We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. (hindawi.com)
- A recombinant full-length human Caspase-3 protein was used as the immunogen for this antibody. (novusbio.com)
- Although multiple protein substrates of caspases have been found, the functional significance of the substrates is poorly understood ( 3 ). (sciencemag.org)
- We used an amount sufficient to cleave 80% of a known substrate of caspase-3, baculovirus protein p35 (Fig. 1 A) ( 5 ). (sciencemag.org)
- The arrows indicate a caspase-3-sensitive protein that is cleaved from an apparent size of 65 kD to 48 kD. (sciencemag.org)
- The human caspase-3 gene encodes a cytoplasmic protein that is highly expressed in lung, spleen, heart, liver, kidney and cells of the immune system. (scbt.com)
- Recombinant protein encompassing a sequence within the center region of human Caspase 3. (genetex.com)
- Caspase 3 antibody detects Caspase 3 protein by western blot analysis. (genetex.com)
- Caspase 3 antibody detects CASP3 protein at Cytoplasm by immunofluorescent analysis. (genetex.com)
- Green: CASP3 protein stained by Caspase 3 antibody (GTX110543) diluted at 1:500. (genetex.com)
- The discovery that caspase-3 also cleaves α-helices contradicts a current dogma and offers new insights into protein signaling pathways. (phys.org)
- Taken together, caspase 2 and caspase 3 protein levels obtained at diagnosis may constitute a reliable prognostic factor in AML. (bloodjournal.org)
- Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-κB signal. (nih.gov)
- Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-κB signaling. (nih.gov)
- Insulin-like growth factor-binding protein-3 (IGFBP-3) is a potent tumor suppressor and is significantly suppressed in a variety of cancers. (nih.gov)
- These changes probably led to the activation of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell lines upon 24 h treatment with PEs and PMA. (mdpi.com)
- Caspases orchestrate the organized death of the cell by cleaving a small but specific complement of protein substrates. (jneurosci.org)
- EGCG treatment of cells also resulted in significant activation of caspases, as shown by the dose- and time-dependent increase in DEVDase activity, and protein expression of caspase-3, -8 and -9. (nih.gov)
- Immunoblot analysis revealed that the expression of p53, caspase-7 and -9 as well as the ratio of Bax/Bcl-2 protein increased significantly with higher EGCG concentrations and longer incubation times. (nih.gov)
- In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels. (frontiersin.org)
- Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. (frontiersin.org)
- Caspase-8 is a caspase protein, encoded by the CASP8 gene. (wikipedia.org)
- For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase heterotetramer whereas for the activation pathway, the zymogen appears to remain intact perhaps to limit its proteolytic function but enhance its capability as an adapter protein. (wikipedia.org)
- Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (wikipedia.org)
- Caspase 3 is responsible for cellular differentiation, although it is unclear how this kind of protein can promote the cell apoptosis. (wikipedia.org)
- Caspase-7, apoptosis-related cysteine peptidase, also known as CASP7, is a human protein encoded by the CASP7 gene. (wikipedia.org)
- They are named caspases due to their specific cysteine protease activity - a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. (wikipedia.org)
- Different protein isoforms of caspase-9 are produced due to alternative splicing. (wikipedia.org)
- This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. (wikipedia.org)
- Caspase-11 was subsequently shown to be a cytosolic protein that responds solely to intracellular, cytosolic LPS. (wikipedia.org)
- This mechanism contrasts to that of the canonical inflammasome, in which a bacterial ligand activates caspase-1 through an upstream sensor protein, and this is the reason why caspase-11 is often referred to as the non-canonical inflammasome. (wikipedia.org)
- The inflammasome complex is a ring complex composed of trimers of a signal specific sensor protein such as those of the NLR family and the AIM-1 (Absent in Melanoma) like receptors, an adaptor protein such as ASC, and a caspase, in this case Caspase-1. (wikipedia.org)
- This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. (wikipedia.org)
- When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking access of the normal protein substrate that would result in apoptosis. (wikipedia.org)
- Smac/DIABLO, a mitochondrial protein and negative regulator of XIAP, can enhance apoptosis by binding to XIAP and preventing it from binding to caspases. (wikipedia.org)
- It is produced as a zymogen, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain. (wikipedia.org)
- Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD), caspase 2 has been shown to form the so-called PIDDosome, which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD. (wikipedia.org)
- Caspase 3 is reported to be involved in the proteolytic processing of this protein. (wikipedia.org)
- Protein modules containing the CARD domain are associated with apoptosis, through the regulation of caspases that they are interacting with, as well in inflammation processes through its participation in NF-kappaB signaling pathways. (wikipedia.org)
- Nitrosylated thioredoxin, via directed protein-protein interaction, trans-nitrosylates the active site cysteine of caspase-3 thus inactivating caspase-3 and preventing induction of apoptosis. (wikipedia.org)
- The 3-phosphoinositide dependent protein kinase-1 (PDPK1/PDK1) is reported to phosphorylate this kinase, which may mediate insulin signals to the actin cytoskeleton. (wikipedia.org)
- Serine/threonine-protein kinase WNK3, also known as protein kinase lysine-deficient 3, is a protein that in humans is encoded by the WNK3 gene. (wikipedia.org)
- This protein can be cleaved by caspase-3 during the induction of apoptosis. (wikipedia.org)
- The protein Sf caspase-1 is the insect ortholog of the human effector caspases CASP3 (CPP32) and CASP7 (MCH3) in the species Spodoptera frugiperda (Fall armyworm). (wikipedia.org)
- Matrin-3 is a protein that in humans is encoded by the MATR3 gene. (wikipedia.org)
- Ced-3 is one of the major protein components of the programmed cell death (PCD) pathway for Caenorhabditis elegans. (wikipedia.org)
- One of the main roles of the ced-3 protein in C. elegans is to help the development and growth of the organism. (wikipedia.org)
- Afterwards, ced-3 indirectly releases another protein, WAH-1, that can cause signals on the surface of the cell to be released so that the cell can be phagocytosed by a neighbouring cell. (wikipedia.org)
- The survivin protein functions to inhibit caspase activation, thereby leading to negative regulation of apoptosis or programmed cell death. (wikipedia.org)
- The typical DCC protein has one signal peptide motif and eleven domains, including multiple immunoglobulin-like domains, a transmembrane domain, and several fibronectin type 3 domains. (wikipedia.org)
- This molecule, when delivered to cancer cells, signals the cells to self-destruct by activating an "executioner" protein, procaspase-3. (wikipedia.org)
- It is caused by mutations in the CASP8 gene that encodes the protein caspase-8. (wikipedia.org)
- Caspase-8 is a 51 kb gene with 13 exons encoding for a 496 amino acid protein that maps to 2q33.1. (wikipedia.org)
- The mutations lead to functional caspase-8 deficiency by destabilizing the caspase-8 protein and inactivating its enzymatic capacity. (wikipedia.org)
- Specific proteolysis of the kinase protein kinase C-related kinase 2 by caspase-3 during apoptosis. (wikipedia.org)
- ced-9 encodes a protein that is structurally similar to Bcl-2 that binds to another protein ced-4, a homolog of APAF-1 in humans, and prevents it from activating caspase ced-3, which is necessary for killing of the cell. (wikipedia.org)
- Caspase recruitment domain-containing protein 8 is an protein that in humans is encoded by the CARD8 gene. (wikipedia.org)
- It has additionally been found to target the (CASP3) gene responsible for encoding the protein caspase 3. (wikipedia.org)
- The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein, member of the Bcl-2 protein family. (wikipedia.org)
- In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene. (wikipedia.org)
- During apoptosis, this protein is cleaved in a caspase-dependent way. (wikipedia.org)
- Eosinophil Cationic Protein (ECP) also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. (wikipedia.org)
- Furthermore, αBC may confer stress resistance to cells by inhibiting the processing of the pro-apoptotic protein caspase-3. (wikipedia.org)
- The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. (wikipedia.org)
- Immunohistochemical analysis of frozen H1650 xenograft section, using Cleaved Caspase-3 (Asp175) Antibody #9661 . (cellsignal.com)
- Company 1 cleaved caspase-3 rabbit polyclonal antibody shows high background and does not detect distinct bands in the expected 19/17 kDa range. (cellsignal.com)
- Company 2 active caspase-3 rabbit polyclonal antibody detects multiple non-specific bands at various molecular weights but weakly detects the bands of interest in the 19/17 kDa and 12 kDa range. (cellsignal.com)
- Company 1 active caspase-3 rabbit monoclonal antibody detects multiple non specific bands at various molecular weights. (cellsignal.com)
- The antibody recognizes only the 17 kDa band corresponding to one form of the large fragment of cleaved caspase-3. (cellsignal.com)
- This antibody is specific for the pro form and the p17 cleaved form of human Caspase-3. (abcam.com)
- Rat reactivity: We have preliminary internal testing data indicating this antibody does not react with mouse caspase 3. (abcam.com)
- The following antibody was used in this experiment: Caspase 3 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-96077. (thermofisher.com)
- The antibody only recognizes the pro-form of Caspase-3. (abcam.com)
- We are unable to >get good results using an rabbit anti-mouse anti-caspase-3 antibody. (histosearch.com)
- The 5A1E antibody reacts with the active cleaved form of caspase-3. (fluidigm.com)
- There are currently no images for Caspase-3 Antibody (NB100-56709R). (novusbio.com)
- Immunoblots of spinal cord extracts from G37R ( a ) and G85R ( b ) mice probed with a polyclonal antibody against both the inactive (p45) pro-enzyme and the active (p20) caspase-1. (nih.gov)
- Caspase-3 antibody was raised against a 17 amino acid synthetic peptide near the center of human Caspase-3.The immunogen is located within amino acids 70 - 120 of Caspase-3. (genetex.com)
- IHC-P analysis of human tonsil tissue using GTX31698 Caspase 3 antibody. (genetex.com)
- Western blotting using polyclonal anti-caspase-3 antibody and mouse anti-human poly(ADP-ribose) polymerase (PARP) monoclonal antibody was performed to investigate caspase-3 and PARP activity. (fluoridealert.org)
- Non-transfected (-) and transfected (+) HeLa whole cell extracts (30 μg) were separated by 12% SDS-PAGE, and the membrane was blotted with Caspase 3 antibody (GTX110543) diluted at 1:4000. (genetex.com)
- Wild-type (WT) and Caspase 3 knockout (KO) HeLa cell extracts (30 μg) were separated by 12% SDS-PAGE, and the membrane was blotted with Caspase 3 antibody (GTX110543) diluted at 1:4000. (genetex.com)
- Immunohistochemistry-Paraffin: Caspase-3 Antibody [ABIN- Human tonsil. (antikoerper-online.de)
- Fresh PBMCs (To) were cultured with medium alone (NS), anti-CD3 and IL-2 (CD3), or SAC for 4 d, and whole PBMCs (lane 1-3) or sorted CD19+ B lymphocytes (lane 4) were lysed in Laemmli buffer and subjected to Western blot analysis using the anti-caspase-3 antibody. (nih.gov)
- This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. (wikipedia.org)
- Caspases, a family of cysteine proteases, are the central regulators of apoptosis. (cellsignal.com)
- The caspase family of cysteine proteases play a key role in apoptosis. (abcam.com)
- Caspases are a family of cysteine proteases that are key mediators of programmed cell death or apoptosis. (abcam.com)
- The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. (sciencemag.org)
- A conserved family of aspartate-specific cysteinyl proteases (caspases) has been identified as critical mediators of apoptosis in Caenorhabditis elegans and mammals ( 1 , 2 ). (sciencemag.org)
- Most signals that lead to apoptosis do so by activating interleukin-1β converting enzyme (ICE)-like proteases termed caspases. (bloodjournal.org)
- The caspases are a family of cysteine proteases that are key regulators of apoptosis and their activity may thus serve as a good marker to monitor cell death. (rsc.org)
- Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. (nih.gov)
- Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signalling. (wikipedia.org)
- Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by TLR4 and TLR3 signaling during the innate immune response. (wikipedia.org)
- The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal transduction related to apoptosis. (wikipedia.org)
- It is known that intracellular proteases called caspases degrade the cellular contents of the cell by proteolysis upon activation of the death pathway. (wikipedia.org)
- His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic cell death pathway. (wikipedia.org)
- Many of these inhibitors act to block caspases, a family of cysteine proteases that play an integral role in apoptosis. (wikipedia.org)
- Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. (nih.gov)
- The main endogenous inhibitors are members of the IAP family and are exemplified by XIAP, which regulates the initiator caspase-9, and the executioner caspases-3 and -7. (nih.gov)
- The active forms of caspases are generated by several stimuli including ligand-receptor interactions, growth factor deprivation and inhibitors of cellular functions. (abcam.com)
- The α-santalol-induced apoptotic cell death and activation of caspase-3 was significantly attenuated in the presence of pharmacological inhibitors of caspase-8 and caspase-9. (nih.gov)
- Caspase inhibitors play an important role in investigating biological processes. (scbt.com)
- Owing to the importance of CARD-CARD interactions in inflammasome formation, many COPs are known inhibitors of Caspase activation. (wikipedia.org)
- When these T lymphocytes were pretreated with caspase inhibitors, DNA fragmentation (an indicator of apoptosis) was prevented. (wikipedia.org)
- Caspase-3, in particular, (also known as CPP32/Yama/apopain) is formed from a 32 kDa zymogen that is cleaved into 17 kDa and 12 kDa subunits. (wikipedia.org)
- Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. (hindawi.com)
- Adenovirus-mediated delivery of p53 to cerebellar granule neurons resulted in caspase-3 (CPP32) activation followed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining and loss of viability as determined by an MTT survival assay. (jneurosci.org)
- 2-4 Consistent with this scheme, caspase 3 (CPP32, prICE, or Yama) 6-8 has been found to be involved in leukemia-cell apoptosis induced by cytotoxic agents such as ara-C, 9 10 etoposide, mitoxantrone, 10 and CPT-11. (bloodjournal.org)
- This assay has high sensitivity and excellent specificity for detection of Caspase 3 (CASP3). (antibodies-online.com)
- No significant cross-reactivity or interference between Caspase 3 (CASP3) and analogues was observed. (antibodies-online.com)
- Low levels of caspase-7 expression and activation correlate with lack of DNA fragmentation in 129- Casp3 -/- apoptotic precursor neurons, whereas B6- Casp3 -/- cells, which can fragment their DNA, show higher levels of caspase-7 expression and activation. (jneurosci.org)
- Together, our findings demonstrate for the first time a strong correlation between caspase-7 activity, normal brain development, and apoptotic DNA fragmentation in Casp3 -/- mice. (jneurosci.org)
- Bcl2L12 directly neutralizes caspase-7 (CASP7) and indirectly neutralizes caspase-3 (CASP3) by an indirect mechanism. (wikipedia.org)
- Under normal circumstances, caspases recognize tetra-peptide sequences on their substrates and hydrolyze peptide bonds after aspartic acid residues. (wikipedia.org)
- Rh110 (rhodamine 110)-derived caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase activities. (anaspec.com)
- One thousand cDNA pools, each containing 100 cDNA clones (100,000 cDNA clones total), were screened to identify substrates of caspase-3. (sciencemag.org)
- NucView® Caspase-3 Substrates are novel, fluorogenic peptide caspase 3 & 7 substrates invented by Biotium. (biotium.com)
- The NucView® substrates come in 3 color options: blue (405), green (488) and orange (530). (biotium.com)
- In addition, researchers found that caspase-3 and the substrates it binds to co-evolved. (phys.org)
- Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
- These data show that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase 3 pathways. (aacrjournals.org)
- Activation of pro-caspase-3 is a central event in the execution phase of apoptosis and appears to serve as the convergence point of different apoptotic signaling pathways. (uniprot.org)
- Moreover, the biochemical form of caspase-8 differed in the two pathways. (wikipedia.org)
- A study indicates that it may be at the mitochondria where the various processes (ligan-dependent receptor activation and cytosolic signaling) pathways are activated by the production of reactive oxygen species (ROS) that may direct the destruction of keratinocytes through apoptosis by activating caspase. (wikipedia.org)
- The amount of caspase-7 activation in apoptotic precursor neurons is independent of the presence of caspase-3. (jneurosci.org)
- The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. (wikipedia.org)
- Activation occurs when caspase-9 dimerizes, and there are two different ways for which this can occur: Caspase-9 is auto-activated when it binds to apaf-1(apoptosome), as apaf-1 oligomerizes the precursor molecules of pro-caspase-9. (wikipedia.org)
- TRIF activation is necessary for the upregulation of pro-caspase-11 (an inactive precursor to active caspase-11) expression and caspase-11-mediated pyroptosis. (wikipedia.org)
- The CellEvent™ Caspase-3/7 Green Flow Cytometry Assay Kit enables the flow cytometric detection of activated caspase-3 and caspase-7 in apoptotic cells. (thermofisher.com)
- Hello all, I recently purchased a Caspase 3/7 Glo assay kit from Promega for apoptosis detection.My assay was done with HEK293 cells which were stimulated with Etoposide.I performed the assay exactly described in the protocol,and detected the luminescence with our Luminoskan Ascent luminometer. (protocol-online.org)
- I used etoposide to treat my cells for different time,and i also use different concentration.I also use the caspase 3/7 glo assay kit from promega. (protocol-online.org)
- The EarlyTox ™ Caspase-3/7 R110 Assay Kit provides a single-step, homogenous assay that is specifically designed for microplate readers. (moleculardevices.com)
- In this application note we report the use of the EarlyTox Caspase-3/7 R110 Assay Kit in combination with SpectraMax ® fluorescence microplate readers . (moleculardevices.com)
- Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, but apoptosis was markedly enhanced by the addition of etoposide. (nih.gov)
- In an AH130 liver tumor model, transduction of human caspase- 3, but not the empty vector, induced extensive apoptosis and reduced tumor volume when combined with etoposide administration. (nih.gov)
- Synthetic peptide within Human Caspase-3 aa 50-150. (abcam.com)
- Finally intratumoral administration of IGFBP-3 resulted in significant tumor suppression as well as sensitization of antitumor effect of doxorubicin. (nih.gov)
- Voxel-based spatiotemporal analysis of tumor-intrinsic heterogeneity suggested that discrete pockets of caspase-3 activation could be detected by [ 18 F]ICMT-11. (aacrjournals.org)
- Increased tumor [ 18 F]ICMT-11 uptake was associated with caspase-3 activation measured ex vivo , and early radiotracer uptake predicted apoptosis, distinct from the glucose metabolism with [ 18 F]fluorodeoxyglucose-PET, which depicted continuous loss of cell viability. (aacrjournals.org)
- Previously, we reported that caspase-8 promotes cell migration, cell adhesion, and Rac activation in normal and tumor cell lines ( 2 ). (aacrjournals.org)
- Although the genesis of certain tumor types such as neuroblastoma and small-cell lung cancer involves the loss of caspase-8 expression, which suppresses anoikis in neuroblastomas ( 4 ), expression is maintained or increased in most tumor types (Supplementary Fig. S1). (aacrjournals.org)
- Thus, caspase-8 may contribute to metastasis in the more typical anoikis-resistant tumor cell context. (aacrjournals.org)
- Furthermore, Grx association with caspase-3 was decreased by tumor necrosis factor-α. (ahajournals.org)
- These findings demonstrate a novel mechanism of caspase-3 regulation by Grx in tumor necrosis factor-α-induced apoptosis. (ahajournals.org)
- 3-azidoWA acts as a tumor suppressor by inducing Par-4, TIMP-1 and by reducing the levels of pAkt and pERK that are activated in various cancers. (wikipedia.org)
- An early event in the mechanism of toxicity from such mutants is now demonstrated to be activation of caspase-1. (nih.gov)
- Our findings indicate that IGFBP-3 exerts antitumor effects via IGF-independent mechanisms which involve activation of caspase-dependent apoptosis and cross-talk with NF-κB signaling. (nih.gov)
- Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia-reperfusion. (sigmaaldrich.com)
- The abnormalities in the fetal thyroid gland seemed to depend on the activation of caspase-3, Bcl-2, BAX, Cox2, and NF-κB mRNA expression. (rsc.org)
- drugs blocking the activation of Caspase-1 have been used to improve the health of patients. (wikipedia.org)
- Both 2A(pro) and 3C(pro) induce caspase-8-mediated by activation of caspase-3. (wikipedia.org)
- DFFA is encoded by an alternatively encrypted mRNAs originating two distinct forms: short (ICAD-S) and long (ICAD-L), which act like a specific chaperone ensuring the correct CAD's folding Besides, it contains two aspartic acid residues (Asp117 and Asp224) where CAD is identified and, consequently, it stays bounded until Caspase-3 splits this union. (wikipedia.org)
- ICAD has two caspase recognition sites at Asp117 and Asp224. (wikipedia.org)
- The caspase-3 His-237 stabilizes the target Aspartate causing the break of the association of ICAD and CAD leaving the endonuclease CAD active allowing it to degrade chromosomal DNA. (wikipedia.org)
- During apoptosis, the apoptotic effector caspase, caspase 3, cleaves ICAD and thus causes CAD to become activated. (wikipedia.org)
- The use of IGFBP-3 as a cancer therapeutic with this distinctive suppression mechanism may offer alternate means to treat chemotherapy resistant tumors. (nih.gov)
- Using a biochemical approach to investigate the molecular mechanism responsible for the resistance of the B6 strain to the loss of caspase-3, we identified caspase-7 as having similar properties to caspase-3 in the mouse. (jneurosci.org)
- We present a common allosteric mechanism for control of inflammatory and apoptotic caspases. (rcsb.org)
- We investigated whether the dynamic temporal and spatial evolution of apoptosis in response to cytotoxic and mechanism-based therapeutics could be detected noninvasively by the caspase-3 radiotracer [ 18 F]ICMT-11 and positron emission tomography (PET). (aacrjournals.org)
- In the present study, we identify a novel regulatory mechanism for caspase-3 activation. (ahajournals.org)
- Caspase-11 activation by direct binding to LPS represents a novel and unprecedented mechanism for caspase activation. (wikipedia.org)
- The mechanism linking caspase-11 to NLRP3 is not currently known. (wikipedia.org)
- Following infection, the inflammatory response increases expression of Caspase-1, by a positive feedback mechanism that amplifies the response. (wikipedia.org)
- Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
- Those studies also demonstrated that the expressed Bax activated caspase-3, indirectly inhibited Bcl-2 expression, formed Bax-Bcl-2 heterodimers and initiated cell apoptosis following cerebral ischemia/reperfusion injury. (spandidos-publications.com)