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 184.108.40.206.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)
Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. (1/149)Calpains and caspases are two cysteine protease families that play important roles in regulating pathological cell death. Here, we report that m-calpain may be responsible for cleaving procaspase-12, a caspase localized in the ER, to generate active caspase-12. In addition, calpain may be responsible for cleaving the loop region in Bcl-xL and, therefore, turning an antiapoptotic molecule into a proapoptotic molecule. We propose that disturbance to intracellular calcium storage as a result of ischemic injury or amyloid beta peptide cytotoxicity may induce apoptosis through calpain- mediated caspase-12 activation and Bcl-xL inactivation. These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families. (+info)
Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. (2/149)When accumulation of a malfolded protein in the endoplastic reticulum (ER) is induced by various adverse conditions, such as hypoxia, glucose starvation, and perturbation of calcium homeostasis, cells respond to the stress by increasing transcription of genes encoding ER molecular chaperones, a process known as unfolded protein response. The signaling is initiated by IRE1s, ER stress sensors. Alternatively, excessive stress to the ER results in apoptosis. Caspase-12 is known to be essential for this ER stress-induced apoptosis. In this study, we analyzed the detailed regulatory mechanisms of IRE1s during ER stress. We identified c-Jun N-terminal inhibitory kinase (JIK) as a binding partner of IRE1alpha, and JIK was seen to modulate IRE1alpha-TRAF2 (tumor necrosis factor receptor-associated factor 2) complex formation and the resultant alteration to c-Jun N-terminal kinase signaling from IRE1s in response to ER stress. We also demonstrated that TRAF2 interacts with procaspase-12 and promotes the clustering of procaspase-12 and its activation by cleavage in response to ER stress. These results indicate that TRAF2 plays crucial roles not only in the signaling of the c-Jun N-terminal kinase pathway but also in activation of caspase-12 to transduce signals from IRE1s. Thus, we provide a missing link in the ER stress-induced apoptosis-signaling pathway, one which connects the stress sensor molecule IRE1 and the activation of caspase-12. (+info)
Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. (3/149)The endoplasmic reticulum (ER) is the site of assembly of polypeptide chains destined for secretion or routing into various subcellular compartments. It also regulates cellular responses to stress and intracellular Ca(2+) levels. A variety of toxic insults can result in ER stress that ultimately leads to apoptosis. Apoptosis is initiated by the activation of members of the caspase family and serves as a central mechanism in the cell death process. The present study was carried out to determine the role of caspases in triggering ER stress-induced cell death. Treatment of cells with ER stress inducers such as brefeldin-A or thapsigargin induces the expression of caspase-12 protein and also leads to translocation of cytosolic caspase-7 to the ER surface. Caspase-12, like most other members of the caspase family, requires cleavage of the prodomain to activate its proapoptotic form. Caspase-7 associates with caspase-12 and cleaves the prodomain to generate active caspase-12, resulting in increased cell death. We propose that any cellular insult that causes prolonged ER stress may induce apoptosis through caspase-7-mediated caspase-12 activation. The data underscore the involvement of ER and caspases associated with it in the ER stress-induced apoptotic process. (+info)
Endoplasmic reticulum stress-induced cysteine protease activation in cortical neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation. (4/149)Endoplasmic reticulum (ER) stress elicits protective responses of chaperone induction and translational suppression and, when unimpeded, leads to caspase-mediated apoptosis. Alzheimer's disease-linked mutations in presenilin-1 (PS-1) reportedly impair ER stress-mediated protective responses and enhance vulnerability to degeneration. We used cleavage site-specific antibodies to characterize the cysteine protease activation responses of primary mouse cortical neurons to ER stress and evaluate the influence of a PS-1 knock-in mutation on these and other stress responses. Two different ER stressors lead to processing of the ER-resident protease procaspase-12, activation of calpain, caspase-3, and caspase-6, and degradation of ER and non-ER protein substrates. Immunocytochemical localization of activated caspase-3 and a cleaved substrate of caspase-6 confirms that caspase activation extends into the cytosol and nucleus. ER stress-induced proteolysis is unchanged in cortical neurons derived from the PS-1 P264L knock-in mouse. Furthermore, the PS-1 genotype does not influence stress-induced increases in chaperones Grp78/BiP and Grp94 or apoptotic neurodegeneration. A similar lack of effect of the PS-1 P264L mutation on the activation of caspases and induction of chaperones is observed in fibroblasts. Finally, the PS-1 knock-in mutation does not alter activation of the protein kinase PKR-like ER kinase (PERK), a trigger for stress-induced translational suppression. These data demonstrate that ER stress in cortical neurons leads to activation of several cysteine proteases within diverse neuronal compartments and indicate that Alzheimer's disease-linked PS-1 mutations do not invariably alter the proteolytic, chaperone induction, translational suppression, and apoptotic responses to ER stress. (+info)
Wild-type, mitochondrial and ER-restricted Bcl-2 inhibit DNA damage-induced apoptosis but do not affect death receptor-induced apoptosis. (5/149)The proto-oncogene Bcl-2 is expressed in membranes of mitochondria and endoplasmic reticulum and mediates resistance against a broad range of apoptotic stimuli. Although several mechanisms of Bcl-2 action have been proposed, its role in different cellular organelles remains elusive. Here, we analyzed the function of Bcl-2 targeted specifically to certain subcellular compartments in Jurkat cells. Bcl-2 expression was restricted to the outer mitochondrial membrane by replacing its membrane anchor with the mitochondrial insertion sequence of ActA (Bcl-2/MT) or the ER-specific sequence of cytochrome b5 (Bcl-2/ER). Additionally, cells expressing wild-type Bcl-2 (Bcl-2/WT) or a transmembrane domain-lacking mutant (Bcl-2/DeltaTM) were employed. Apoptosis induced by ionizing radiation or by the death receptors for CD95L or TRAIL was analyzed by determination of the mitochondrial membrane potential (DeltaPsi(m)) and activation of different caspases. Bcl-2/WT and Bcl-2/MT strongly inhibited radiation-induced apoptosis and caspase activation, whereas Bcl-2/DeltaTM had completely lost its anti-apoptotic effect. Interestingly, Bcl-2/ER conferred protection against radiation-induced mitochondrial damage and apoptosis similarly to Bcl-2/MT. The finding that ER-targeted Bcl-2 interfered with mitochondrial DeltaPsi(m) breakdown and caspase-9 activation indicates the presence of a crosstalk between both organelles in radiation-induced apoptosis. By contrast, Bcl-2 in either subcellular position did not influence CD95- or TRAIL-mediated apoptosis. (+info)
Formation of noncanonical high molecular weight caspase-3 and -6 complexes and activation of caspase-12 during serum starvation induced apoptosis in AKR-2B mouse fibroblasts. (6/149)Apoptosis is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. In mammals, different complexes like the DISC complex or the apoptosome complexes have been delineated leading to the cleavage and thus activation of the executioner caspases. Although caspase-3 is the main executioner caspase in apoptosis induced by serum starvation in AKR-2B fibroblasts as demonstrated by affinity labeling with YVK(-bio)D.aomk and partial purification of cytosolic extracts by high performance ion exchange chromatography, its activation is apparently caused by a noncanonical pathway: (1) Expression of CrmA, an inhibitor of caspase-8, failed to suppress apoptosis; (2) There was no formation of high molecular weight complexes of Apaf-1 indicative for its activation. Furthermore no cleavage of caspase-9 was observed. But surprisingly, gelfiltration experiments revealed the distribution of caspase-3 and -6 into differently sized high molecular weight complexes during apoptosis. Though the apparent molecular weights of the complexes containing caspase-3 (600 kD for apoptosome and 250 kD for microapoptosome) are in accordance with recently published data, the activity profiles differ strikingly. In AKR-2B cells caspase-3 is mainly recovered as uncomplexed enzyme and in much lower levels in the apoptosomes. Remarkably, the 600 kD and 250 kD complexes containing activated caspase-3 were devoid of Apaf-1 and cytochrome c. In addition a new 450 kD complex containing activated caspase-6 was found that is clearly separated from the caspase-3 containing complexes. Furthermore, we disclose for the first time the activation of caspase-12 in response to serum starvation. Activated caspase-12 is detectable as non-complexed free enzyme in the cytosol. (+info)
Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway. (7/149)Accumulation of misfolded proteins and alterations in Ca2+ homeostasis in the endoplasmic reticulum (ER) causes ER stress and leads to cell death. However, the signal-transducing events that connect ER stress to cell death pathways are incompletely understood. To discern the pathway by which ER stress-induced cell death proceeds, we performed studies on Apaf-1(-/-) (null) fibroblasts that are known to be relatively resistant to apoptotic insults that induce the intrinsic apoptotic pathway. While these cells were resistant to cell death initiated by proapoptotic stimuli such as tamoxifen, they were susceptible to apoptosis induced by thapsigargin and brefeldin-A, both of which induce ER stress. This pathway was inhibited by catalytic mutants of caspase-12 and caspase-9 and by a peptide inhibitor of caspase-9 but not by caspase-8 inhibitors. Cleavage of caspases and poly(ADP-ribose) polymerase was observed in cell-free extracts lacking cytochrome c that were isolated from thapsigargin or brefeldin-treated cells. To define the molecular requirements for this Apaf-1 and cytochrome c-independent apoptosis pathway further, we developed a cell-free system of ER stress-induced apoptosis; the addition of microsomes prepared from ER stress-induced cells to a normal cell extract lacking mitochondria or cytochrome c resulted in processing of caspases. Immunodepletion experiments suggested that caspase-12 was one of the microsomal components required to activate downstream caspases. Thus, ER stress-induced programmed cell death defines a novel, mitochondrial and Apaf-1-independent, intrinsic apoptotic pathway. (+info)
Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. (8/149)Alterations in Ca(2+) homeostasis and accumulation of unfolded proteins in the endoplasmic reticulum (ER) lead to an ER stress response. Prolonged ER stress may lead to cell death. Glucose-regulated protein (GRP) 78 (Bip) is an ER lumen protein whose expression is induced during ER stress. GRP78 is involved in polypeptide translocation across the ER membrane, and also acts as an apoptotic regulator by protecting the host cell against ER stress-induced cell death, although the mechanism by which GRP78 exerts its cytoprotective effect is not understood. The present study was carried out to determine whether one of the mechanisms of cell death inhibition by GRP78 involves inhibition of caspase activation. Our studies indicate that treatment of cells with ER stress inducers causes GRP78 to redistribute from the ER lumen with subpopulations existing in the cytosol and as an ER transmembrane protein. GRP78 inhibits cytochrome c-mediated caspase activation in a cell-free system, and expression of GRP78 blocks both caspase activation and caspase-mediated cell death. GRP78 forms a complex with caspase-7 and -12 and prevents release of caspase-12 from the ER. Addition of (d)ATP dissociates this complex and may facilitate movement of caspase-12 into the cytoplasm to set in motion the cytosolic component of the ER stress-induced apoptotic cascade. These results define a novel protective role for GRP78 in preventing ER stress-induced cell death. (+info)
It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and ... Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal ... "Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection". The American Journal of Human Genetics ... It is found on chromosome 11 in humans in a locus with other inflammatory caspases. CASP12 orthologs have been identified in ...
Human evolutionary genetics
CASPASE12, a cysteinyl aspartate proteinase. The loss of this gene is speculated to have reduced the lethality of bacterial ... Of these 12 supported the Homo-Pan clade, 3 the Homo-Gorilla clade, 4 the Pan-Gorilla clade and 16 gave no resolution. ... Retrieved 2010-12-31. Tishkoff, SA.; Reed, FA.; Friedlaender, FR.; Ehret, C.; Ranciaro, A.; Froment, A.; Hirbo, JB.; Awomoyi, ... Usually the molecular clock is calibrated assuming that the orangutan split from the African apes (including humans) 12-16 MYA ...
Another more recent example of a disabled gene links the deactivation of the caspase 12 gene (through a nonsense mutation) to ... "Spread of an inactive form of caspase-12 in humans is due to recent positive selection". American Journal of Human Genetics. 78 ... 12 (4): 246-58. doi:10.1038/nrm3089. PMID 21427766. Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Léopold V, Sjoberg M, ... 12 (1): 109-20. doi:10.1016/0092-8674(77)90189-1. PMID 561661. Zheng D, Frankish A, Baertsch R, Kapranov P, Reymond A, Choo SW ...
"Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes ... Retrieved 12 September 2011. "'Man flu and other health myths'". 2007-10-01. "Boots advert should not have been made". Men's ... Alleyne, Richard (2009-05-12). "Men succumb to manflu because women have stronger immune systems, claim scientists". The Daily ...
Involvement of Apoptosis Inducing Factor and Caspase-12". Journal of Medicinal Chemistry. 52: 5176-5187. doi:10.1021/jm900365v ... compound induces the death of cancer cells by an original mechanism that involves the apoptosis-inducing factor and caspase 12 ...
Chimpanzee genome project
Humans appear to have lost a functional caspase-12 gene, which in other primates codes for an enzyme that may protect against ... 12, 15, 16, 17, and 18. After the completion of the Human genome project, a common chimpanzee genome project was initiated. In ...
2001). "Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor- ... 8 (12): 982-9. doi:10.1038/nchembio.1094. PMC 3508346 . PMID 23086298. Katayama T, Imaizumi K, Sato N, et al. (2000). " ... 12 (12): 1812-24. doi:10.1101/gad.12.12.1812. PMC 316900 . PMID 9637683. "Entrez Gene: ERN1 endoplasmic reticulum to nucleus ...
2001). "Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor- ...
... 2, Caspase 8, Caspase-9, Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro- ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... Pyroptosis by Caspase -4 and Caspase-5 in humans and Caspase-11 in mice These caspases have the ability to induce direct ...
... has been shown to interact with Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000138794 - ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene ... "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase". Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct ...
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis ... Wang, J; Chun H J; Wong W; Spencer D M; Lenardo M J (November 2001). "Caspase-10 is an initiator caspase in death receptor ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1998). "Identification and characterization of murine caspase-14, a new member of the caspase family". Cancer Res. 58 (22): ... 2004). "Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin ...
Instead, it is thought to inhibit Caspase-1 activation by interfering with the interaction of Caspase-1 with other important ... and a caspase, in this case Caspase-1. In some cases, where the signaling proteins contain their own CARDs, like in NLRP1 and ... Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the ... Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both ...
Caspase-8 has been shown to interact with: BCAP31, BID, Bcl-2, CFLAR, Caspase-10, Caspase-2, Caspase-3, Caspase-6, Caspase-7, ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase ...
Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other ... Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating ... Different protein isoforms of caspase-9 are produced due to alternative splicing. Similar to other caspases, caspase-9 has ... Previously activated caspases can cleave caspase-9, causing its dimerization. Caspase-9 has a preferred cleavage sequence of ...
CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ... Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ, Megeney LA (March 2010). "Caspase 3/caspase-activated DNase promote ... "Entrez Gene: DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)". Davidson College. "Caspase ... Caspase-activated DNase, and Inhibitor of Caspase-activated DNase to the Nuclear Phenotype and DNA Degradation during Apoptosis ...
CEDS is caused by homozygous mutations in caspase-8. Caspase-8 is a 51 kb gene with 13 exons encoding for a 496 amino acid ... For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase ... The mutations lead to functional caspase-8 deficiency by destabilizing the caspase-8 protein and inactivating its enzymatic ... Caspase-8 deficiency (CEDS) is a very rare genetic disorder of the immune system. It is caused by mutations in the CASP8 gene ...
"Effects of galactomyces ferment filtrate on epidermal barrier marker caspase-14 in human skin cells". Journal of the American ... Retrieved 2017-12-03. "The Effects of Essence-Formed Cosmetic Ingredients Containing the Galactomyces Ferment Filtrate on Skin ...
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 ...
McDonald ER, El-Deiry WS (2004). "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ... 2005). "Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2". Structure. 12 (12): 2257-63. doi ...
Caspase 13: caspase 13, apoptosis-related cysteine peptidase  ICEBERG: caspase 1 inhibitor iceberg  Pseudo-ICE:Caspase-1 ... Caspase 1: caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase; ICE)  Caspase 2: caspase 2, ... caspase 4, apoptosis-related cysteine peptidase  Caspase 5: caspase 5, apoptosis-related cysteine peptidase  Caspase 9: ... caspase recruitment domain family, member 8  CARD9: caspase recruitment domain family, member 9  CARD10: caspase ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs ... As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after ... Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ... During the caspase cascade, however, caspase-3 functions to inhibit XIAP activity by cleaving caspase-9 at a specific site, ...
Envelope glycoprotein GP120
gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading ... "Tubular cell HIV-1 gp120 expression induces caspase 8 activation and apoptosis". Ren Fail. 31 (4): 303-12. doi:10.1080/ ... "Tubular Cell HIV-1 gp120 Expression Induces Caspase 8 Activation and Apoptosis". Renal Failure. 31 (4): 303-312. doi:10.1080/ ... 14 (12): 1229-46. doi:10.1093/glycob/cwh106. PMID 15175256. Liu Y, Curlin ME, Diem K, Zhao H, Ghosh AK, Zhu H, Woodward AS, ...
Once active, the inflammasome binds to pro-caspase-1 (the precursor molecule of caspase-1), either homotypically via its own ... The inflammasome is a multiprotein oligomer consisting of caspase 1, PYCARD, NALP and sometimes caspase 5 (also known as ... Caspase-1 then assembles into its active form consisting of two heterodimers with a p20 and p10 subunit each. Once active, it ... Caspase-1 activates maturation of proinflammatory cytokines (IL-1b, IL-18). AIM2 is activated by viral dsDNA, bacterial dsDNA ...
... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspases Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn activates the effector caspase-3. MAC ( ... There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ...
Proto-oncogene tyrosine-protein kinase Src
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 5 (12): 1347-55. PMID 7696183. Lee J, Wang Z, Luoh SM, Wood WI, Scadden DT (January 1994). "Cloning of FRK, a novel human ... 244 (4905): 707-12. Bibcode:1989Sci...244..707S. doi:10.1126/science.2470152. PMID 2470152. Nam S, Kim D, Cheng JQ, Zhang S, ...
Although caspase-12 is a proximal caspase and is an important mediator of apoptosis triggered by ER stress, we believe its accumulation may not, itself, be sufficient to induce cell death. When we overexpressed caspase-12 in various cell types, including fibroblasts and neuronal cells, it was much less effective in inducing cell death than other proximal caspases, such as caspase-8, -9, and -10 (unpublished data). To be effective, apparently, caspase-12 needs to interact with one or more activators. In our study, E2-25K/Hip-2 was able to induce both calpainlike activity and efficient proteolytic processing of caspase-12. One possible explanation is that the inhibition of proteasome activity by E2-25K/Hip-2 leads to an accumulation of misfolded proteins within cells, which in turn induces ER stress, including the activation of calpain. Consistent with that idea, it has been shown that the inhibition of proteasome activity by aggregation-prone proteins or proteasome inhibitors does indeed induce ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Aβ-induced cell death | JCB
It has been known that apoptotic morphological changes are observed in cell death caused by ER stress (Imaizumi et al., 2001). Caspases are activated to transmit apoptotic signals transcending the difference in species (Alnemri et al., 1996). In rodents, caspase-12 mediates apoptosis specifically in response to ER stress (Nakagawa et al., 2000). Although human caspase-12 gene is transcribed into mRNA, mature caspase-12 protein would not be produced, because the gene is interrupted by frame shift and premature stop codon (Fischer et al., 2002). Furthermore, it contains amino acid substitution in the critical site, which leads to loss of function in several caspases (Fischer et al., 2002). Thus, human caspase-12 does not seem to function in ER stress-induced apoptosis, and some other caspases with similar structure might substitute functionally for caspase-12 in humans. The caspase-12 gene is located within a region where caspase-1/ICE subfamily genes cluster (caspases 1, 4, 5, 12 in human and ...
Heme Oxygenase (HO)-1 Induction Prevents Endoplasmic Reticulum Stress-Mediated Endothelial Cell Death and Dysfunction |...
Diabetes is intimately associated with cardiovascular complications. Much evidence highlighted the complex interplay between Endoplasmic Reticulum (ER) stress and oxidative stress in the pathogenesis of diabetes. Hemeoxygenase-1 (HO-1) induction was shown to protect against oxidative stress in diabetes; however the underlying molecular mechanisms have not yet been fully elucidated. We aim in this project to test the hypothesis that HO-1 induction will protect against high glucose-mediated ER stress and oxidative stress in endothelial cells and will enhance cell survival. Endothelial cells were cultured in physiological or high concentrations of glucose in the presence of cobalt protoporphyrin 1X (CoPP, HO-1 inducer), 4-phenylbutyrate (PBA, chemical chaperone to inhibit ER stress) or vehicle. Then, ER stress response was assessed (PCR, western blot). The productions of ROS (flow cytometer) and NO (Griess assay) were analysed. Also, apoptosis and caspase 3/7 activity were assessed. High glucose treatment
ER stress-induced processing and nuclear translocation of GFP-ATF6. (a) Twenty-four hours after transfection with pCMVshort-EGFP-ATF6 (WT), 293T cells were left
Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice ...
Maamoun, Hatem, Agouni, Abdelali and McVey, John (2017) Heme oxygenase (HO)-1 induction prevents endoplasmic reticulum stress-mediated endothelial cell death and impaired angiogenic capacity induced by high glucose. Doctoral thesis, University of Surrey. Mac Crosain, Alison (2017) Evaluating RE-ID : an acceptance and commitment therapy group intervention exploring identity after acquired brain injury. Doctoral thesis, University of Surrey. Maheshwarappa, Mamatha R. (2017) Software defined radio (SDR) architecture for concurrent multi-satellite communications. Doctoral thesis, University of Surrey. Mai, Anna (2017) Oxidative stress in high fat diet-induced metabolic syndrome, hypertension and endothelial dysfunction. Doctoral thesis, University of Surrey. Maldonado, Elaina Marie (2017) An investigation of the role of glucose and fructose in non-alcoholic fatty liver disease using systems approaches. Doctoral thesis, University of Surrey. Mallikarachchi, Thanuja (2017) HEVC encoder optimization ...
Acts as a positive regulator of T-cell maturation and inflammatory function. Required for several functions of T-cells, in both the CD4(+) and the CD8(+) compartments and this includes expression of cell surface markers of activation, proliferation, and cytokine production in response to specific or non-specific stimulation (By similarity). Enhances NK cell cytotoxicity by positively regulating polarization of microtubule-organizing center (MTOC) to cytotoxic synapse, lytic granule transport along microtubules, and dynein-mediated clustering to MTOC (PubMed:25762780). Interacts with HSPA5 and stabilizes the interaction between HSPA5 and ERN1, leading to suppression of ERN1-induced JNK activation and endoplasmic reticulum stress-induced apoptosis (PubMed:21289099).
AID 513048 - Inhibition of human caspase-3-mediated apoptosis assessed as Ac-DEVD-7-amino-4-methylcoumarin cleavage product at...
BioAssay record AID 513048 submitted by ChEMBL: Inhibition of human caspase-3-mediated apoptosis assessed as Ac-DEVD-7-amino-4-methylcoumarin cleavage product at 100 uM by fluorescence assay.
Endoplasmic reticulum (ER) stress is an ancient conserved mechanism that allows cells, especially those with significant secretory function such as intestinal e...
Frontiers | Endoplasmic reticulum stress-induced PCD and caspase-like activities involved | Plant Science
Plant cells, like cells from other kingdoms, have the ability to self-destruct in a genetically controlled manner. This process is defined as Programmed Cell Death (PCD). PCD can be triggered by various stimuli in plants including by endoplasmic reticulum (ER) stress. Research in the past two decades discovered that disruption of protein homeostasis in the endoplasmic reticulum (ER) could cause ER stress, which when prolonged/unresolved leads cells into PCD. ER stress-induced PCD is part of several plant processes, for instance, drought and heat stress have been found to elicit ER stress-induced PCD. Despite the importance of ER stress-induced PCD in plants, its regulation remains largely unknown, when compared with its counterpart in animal cells. In mammalian cells, several pro-apoptotic proteases called caspases were found to play a crucial role in ER stress-induced PCD. Over the past decade, several key proteases with caspase-like enzymatic activity have been discovered in plants and implicated in
Several studies have correlated ER stress with myocardial damage. For example, the ER stress response is activated in the hearts of transgenic mice that overexpress monocyte chemoattractant protein-1 and develop heart failure,36 suggesting that in this model, the proapoptotic phase of ER stress contributes to the loss of myocardium associated with failure. In further support of a role for ER stress in heart failure is the finding that transgenic overexpression of a mutant KDEL receptor, an ER protein that facilitates ER protein targeting, activates the ER stress response in mouse hearts and causes dilated cardiomyopathy.69 Also, overexpression of the ER stress response gene product p53-upregulated modulator of apoptosis (PUMA) contributes to ER stress-mediated apoptosis in cultured cardiomyocytes70 and targeted deletion of PUMA in mouse hearts attenuates cardiomyocyte death during ex vivo I/R.71. In contrast to the studies cited above, other studies suggest that ER stress might protect the ...
Endoplasmic Reticulum Stress-Induced Resistance to Doxorubicin Is Reversed by Mulberry Leaf Polyphenol Extract in...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Endoplasmic reticulum stress with low-dose cyclosporine in frequently relapsing nephrotic syndrome.: An unfolded protein response due to ER stress induced by Cs
Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells | Stem Cells Portal - Stem...
Association of Prx II with cancer stem cell in HCC cells. (A): Representative image of EpCAM(+)/K19(+) HCC showing Prx II expression in contrast to EpCAM(−)/K19(−) HCC without expression of Prx II (magnification, × 200). (B): Comparison of proportions of Prx II expressing in EpCAM(+)/K19(+) HCCs and EpCAM(−)/K19(−) HCCs. (C): Expression levels of Sox2 in Huh7 cells transfected with siPrx II.
Caspase recruitment domain-containing protein 16
Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 ... Protective role of Cop in Rip2/caspase-1/caspase-4-mediated HeLa cell death.. ... Caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop; alterations of this balance may ... results from its interference with the activation of caspase-1 and caspase-4.. ...https://pharos.nih.gov/idg/targets/Q5EG05
Caspase 12 - Wikipedia
It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and ... Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal ... "Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection". The American Journal of Human Genetics ... It is found on chromosome 11 in humans in a locus with other inflammatory caspases. CASP12 orthologs have been identified in ...https://en.wikipedia.org/wiki/Caspase_12
Caspase 12 Antibody
Caspase 12 Polyclonal Antibody from Invitrogen for Western Blot, Immunofluorescence, Immunocytochemistry and ... Cite Caspase 12 Polyclonal Antibody. The following antibody was used in this experiment: Caspase 12 Polyclonal Antibody from ... Caspase-12 is localized to the ER but not to cytoplasm or mitochondrion. Caspase-12 is activated by ER stress, including ... Caspase-12 is co-localized to the ER with several proteins that are involved in Alzheimers disease including -gamma-secretase ...https://www.thermofisher.com/antibody/product/Caspase-12-Antibody-Polyclonal/PA5-19963
Mouse Caspase-12 peptide (ab8374) | Abcam
Buy our Mouse Caspase-12 peptide. Ab8374 is a blocking peptide and has been validated in BL. Abcam provides free protocols, ...http://www.abcam.com/mouse-caspase-12-peptide-ab8374.html
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.https://www.biovision.com/products/apoptosis-related-products/caspases/caspase-12/caspase-12-antibodies.html
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.https://www.biovision.com/products/cancer-research/apoptosis-related-products/caspases/caspase-12/caspase-12-antibodies.html
anti-Caspase 12 antibody | GeneTex
Anti-Caspase 12 pAb (GTX28117) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance. ... caspase 12. Background. Three distinct signaling pathways lead to programmed cell death (apoptosis). The death receptor and ... Caspase-12 is colocalized to the ER with several proteins that are involved in Alzheimers disease including g-secretase ... Caspase-12 is activated by ER stress, including disruption of ER calcium homeostasis, and mediates ER stress-induced apoptosis ...http://www.genetex.com/Caspase-12-antibody-GTX28117.html
caspase-12 Activators | SCBT - Santa Cruz Biotechnology
These activate caspase-12 and may affect a variety of other apoptosis and tumor related proteins. ... caspase-12 Activators. Caspase family members function as key components of the apoptotic machinery and act to destroy specific ... Caspase-12 Activators offered by Santa Cruz activate caspase-12 and, in some cases, other apoptosis and tumor related proteins ... An HDAC inhibitor and caspase activator. 1716-12-7. sc-200652. sc-200652A. sc-200652B. sc-200652C. sc-200652D. 1 g. 10 g. 100 g ...https://www.scbt.com/browse/caspase-12-Activators/_/N-a7a7l9
anti-Caspase 12 antibody [14F7] | GeneTex
Anti-Caspase 12 mAb (GTX10455) is tested in Mouse, Rat samples. 100% Ab-Assurance. ... Caspase 12 antibody [14F7] (caspase 12) for ICC/IF, IHC, IP, WB. ... Caspase-12 is localized to the ER but not to cytoplasm or ... Casp12, Caspase12, CASP12P1, Q6UXS9, caspase-12, 12364, 608633, 120329, Caspase 12. Specificity. Recognizes full length and ... Caspase-12 is colocalized to the ER with several proteins that are involved in Alzheimer s disease including g-secretase ...http://www.genetex.com/Caspase-12-antibody-14F7-GTX10455.html
CASP12 / Caspase 12 - LSBio
CASP12 / Caspase 12. caspase 12. Caspases are cysteine proteases that cleave C-terminal aspartic acid residues on their ... This gene is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. In rodents, ... CASP12, Caspase 12 pseudogene 1, Caspase 12, CASP-12, Caspase 12 (gene/pseudogene), Inactive caspase-12, CASP12P1. ... Rat Monoclonal [clone G1/G1-4] (IgG2a) to Mouse CASP12 / Caspase 12 ...https://www.lsbio.com/targets/casp12-caspase-12/g190520
Caspase-12 Inhibitor Z-ATAD-FMK | PromoCell
Caspase-12 Inhibitor Z-ATAD-FMK. Recommend to use at 1:1000 dilutions for tissue and cell lysate ...https://www.promocell.com/product/caspase-12-inhibitor-z-atad-fmk/
E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated Aβ neurotoxicity | JCB
Wild-type MEFs, caspase-11 (−/−) MEFs, and caspase-12 (−/−) MEFs were provided by J. Yuan (Harvard Medical School, Boston, MA ... Western analysis showed that in contrast to caspase-3 and -8, there was substantial dose-dependant accumulation of caspase-12 ... but not caspase-3 (Fig. 4 D, middle and right) or IκBα (not depicted). The stability of caspase-12 protein thus appears to ... Among the 14 caspase isoforms known to be expressed in mammals, the ER-resident caspase-12 was initially identified as a ...http://jcb.rupress.org/content/182/4/675
ER stress-induced apoptosis and caspase-12 activation occurs downstream of mitochondrial apoptosis involving Apaf-1 | Journal...
... pro-caspase-9, dATP, and cytochrome c. Apoptosome formation results in the activation of executioner caspases including caspase ... Caspase-3 mixed with Cleaved caspase-3 or caspase-12 (Cell Signaling). Optimal antibody concentrations were determined in pilot ... C3, caspase-3. (B) MEFs were introduced with wild or mutated caspase-12 and analyzed for caspase-12 processing by western ... Furthermore, a caspase-3 specific inhibitor, Ac-DNLD-CHO, inhibited the activation of caspase-12 during ER stress. Taken ...http://jcs.biologists.org/content/119/19/3958.full
Calpain and Caspase-12 Activation Mediates Apoptosis in Transgenic Mouse Lens Expressing a Dominant-Negative Mutant of FGFR |...
A low level of cleaved caspase-12 was present in the WT lens. In comparison, the level was significantly increased in the DN- ... In contrast to the WT lens, caspase-12 immunofluorescence in the DN-FGFR lens did not co-localize with the cell nuclear ... Calpain and Caspase-12 Activation Mediates Apoptosis in Transgenic Mouse Lens Expressing a Dominant-Negative Mutant of FGFR ... Calpain and Caspase-12 Activation Mediates Apoptosis in Transgenic Mouse Lens Expressing a Dominant-Negative Mutant of FGFR ...https://iovs.arvojournals.org/article.aspx?articleid=2371274
Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells - Semantic Scholar
However, when DNA damage is involved, and in the absence of caspase-2 and -3, caspase-12 becomes upregulated and mediates ... Those data also revealed dispensability of caspase-3, although we found this caspase critical for ovarian granulosa cell death ... require caspase-2 and caspase-3 as obligatory executioners of the ensuing cell death cascade. ... Because of the mutual interdependence of germ cells and granulosa cells, herein we generated caspase-2 and -3 double-mutant ( ...https://www.semanticscholar.org/paper/Caspase-12-compensates-for-lack-of-caspase-2-and-in-Takai-Matikainen/1d5afa67d87eb60e5b9acfa8ecda2a25960ff7c1
Gentaur Molecular :Biovis \ Caspase-12 Substrate ATAD-AFC; Appearance Liquid \ 1117-1000
Caspase-12 Substrate ATAD-AFC; Appearance Liquid \ 1117-1000 for more molecular products just contact us ... The ready-to-use caspase substrate provides an economic alternative for researchers who perform large amount of caspase assays ... 20640600] Calpain and caspase processing of caspase-12 contribute to the ER stress-induced cell death pathway in differentiated ... Ready-to-use fluorometric substrate for caspases that recognize the amino acid sequence ATAD. Caspase activity can be ...http://antibody-antibodies.com/product1988531-search-Caspase_12%20%20Substrate%20ATAD_AFC
Caspase 12 Antibody 55238-1-AP | Proteintech
Caspase 12 Antibody 55238-1-AP has been identified with IF, IHC, IP, WB, ELISA. 55238-1-AP detected 36-42 kDa, 50 kDa band in ... It is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. Caspase-12 is ... Caspase 12 is an enzyme known as a cysteine protease. It belongs to a family of enzymes called caspases that cleave their ... Caspase 12 Antibody 22 Publications. Rabbit Polyclonal, Catalog number: 55238-1-AP ...http://ptgcn.com/products/CASP12-Antibody-55238-1-AP.htm
Gentaur Molecular :Biovis \ Caspase-12 Substrate ATAD-AFC; Appearance Liquid \ 1117-200
Caspase-12 Substrate ATAD-AFC; Appearance Liquid \ 1117-200 for more molecular products just contact us ... Dronc Nc CG8091] Caspase Dronc (EC 3.4.22.-) (NEDD2-like caspase) [Cleaved into: Caspase Nc subunit 1; Caspase Nc subunit 2]. [ ... CASP3] Caspase-3 (CASP-3) (EC 220.127.116.11) [Cleaved into: Caspase-3 subunit p17; Caspase-3 subunit p12]. [CASP14] Caspase-14 ( ... Drice ICE CG7788] Caspase (EC 3.4.22.-) (drICE) [Cleaved into: Caspase subunit p21; Caspase subunit p12]. [CASP3] Caspase-3 ( ...http://www.antibody-antibodies.com/product_det.php?id=1988532&supplier=search&name=Caspase_12%20%20Substrate%20ATAD_AFC%3B%20Appearance%20Liquid
Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats. - Semantic Scholar
Caspase-3 protein content and caspase-3 activity were significantly increased after day four of doxorubicin treatment in both ... Caspase-12, localized in the SR, is considered a central caspase, and its activation by cleavage via calpain indicates ... Cleaved caspase-12 content and calpain activity significantly increased after day four of doxorubicin treatment in both sexes. ... The receptor-mediated pathway (caspase-8 and c-FLIP) showed no evidence of being significantly activated by doxorubicin ...https://www.semanticscholar.org/paper/Doxorubicin-treatment-in-vivo-activates-caspase-12-Jang-Kendaiah/87725c5273070ac208532d8a5fde31add91cd2c8
Gentaur Molecular :Biovis \ Caspase-12 Inhibitor Z-ATAD-FMK \ 1079-100
Caspase-12 Inhibitor Z-ATAD-FMK \ 1079-100 for more molecular products just contact us ... Caspase-2 subunit p18; Caspase-2 subunit p13; Caspase-2 subunit p12]. [Decay CAS3 Cas3 cas3 Casp3 caspase 3 Caspase-3 caspase-3 ... Caspase-14 subunit p17, mature form; Caspase-14 subunit p10, mature form; Caspase-14 subunit p20, intermediate form; Caspase-14 ... Drice ICE CG7788] Caspase (EC 3.4.22.-) (drICE) [Cleaved into: Caspase subunit p21; Caspase subunit p12]. Bibliography :. No ...http://www.antibody-antibodies.com/product_det.php?id=1772496&supplier=search&name=Caspase_12%20Inhibitor%20Z_ATAD_FMK
The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event - pdf descargar
The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event. . Biblioteca virtual para leer y descargar libros, ... Caspase-12 CASP12 modulates the susceptibility to sepsis. In humans, the -C- allele at CASP12 rs497116 has been associated with ... The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event - Descarga este documento en PDF. Documentación en PDF ... We demonstrate that the loss of caspase-12 in Europe predates animal domestication and that consequently CASP12 loss is ...http://libros.duhnnae.com/2017/jun7/149813458327-The-Loss-of-Functional-Caspase-12-in-Europe-Is-a-Pre-Neolithic-Event.php
Targeting Caspase-12 to Preserve Vision in Mice With Inherited Retinal Degeneration | IOVS | ARVO Journals
... and cleaved caspase-3 9664 from Cell Signaling [Danvers, MA, USA] and caspase-12 ab18766 from Abcam [Cambridge, MA, USA]) ... Results: Caspase-12 ablation significantly prevented a decline in the a- and b-wave ERG amplitudes in T17M mice during three ... Methods: One, two-, and three-month-old C57BL6/J, caspase-12−/−, T17M, and T17M caspase-12−/− mice were analyzed by scotopic ... However, the level of active caspases was still 50% higher as compared to that in wt retinas. (C) Reduction of Csp-3 was ...http://iovs.arvojournals.org/article.aspx?articleid=2411354
CACHE . Inhibition of ER-Stress Associated Caspase-12 Rescues Cultured Cells from Ethanol Toxicity . Kalamazoo College
Chinese hamster ovary cells (CHO695) were treated with a pan-caspase inhibitor, a caspase-9 inhibitor or a caspase-12 inhibitor ... Caspase-9 and caspase-12 are thought to be downstream of mitochondria and the endoplasmic reticulum respectively, however it is ... Ethanol induces apoptosis in cells via a caspase-dependent mechanism. Control of caspase activity, and thus apoptosis, is ... while caspase-9 inhibition did not provide significant rescue. Caspase-12 and pan-caspase inhibition were not statistically ...https://cache.kzoo.edu/handle/10920/12013?show=full
Minocycline blocks c-terminal fragments of amyloid precursor protein-induced neurotoxicity by inhibition of cytochrome c...
... reduces neurotoxicity induced by various C-terminal fragments of APP through inhibition of cytochrome c release and caspase-12 ... reduces neurotoxicity induced by various C-terminal fragments of APP through inhibition of cytochrome c release and caspase-12 ... c-terminal fragments of amyloid precursor protein-induced neurotoxicity by inhibition of cytochrome c release and caspase-12 ... c-terminal fragments of amyloid precursor protein-induced neurotoxicity by inhibition of cytochrome c release and caspase-12 ...http://ijpr.sbmu.ac.ir/article_214.html
ER stress-induced apoptosis and caspase-12 activation occurs downstream of mitochondrial apoptosis involving Apaf-1<...
Shiraishi H, Okamoto H, Yoshimura A, Yoshida H. ER stress-induced apoptosis and caspase-12 activation occurs downstream of ... Shiraishi, H., Okamoto, H., Yoshimura, A., & Yoshida, H. (2006). ER stress-induced apoptosis and caspase-12 activation occurs ... Despite comparable induction of ER stress in both wild type and Apaf-1-deficient cells, activation of caspase-3 was only ... Shiraishi, H, Okamoto, H, Yoshimura, A & Yoshida, H 2006, ER stress-induced apoptosis and caspase-12 activation occurs ...https://keio.pure.elsevier.com/en/publications/er-stress-induced-apoptosis-and-caspase-12-activation-occurs-down
ApoptosisAntibodyEndoplasmic reticulumCASP12ProteasesRole of caspase-12Mouse caspase 12Activates caspase-12PeptideCell differentiationTissue and cell lysateDetected by western blotInhibitionSusceptibilityInhibitorExecutionerMitochondriaPathwayMolecularModulatesMediatesAlleleSubstrateKnockdownActivateTissues
- Caspase-12 is activated by ER stress, including disruption of ER calcium homeostasis, and mediates ER stress-induced apoptosis. (thermofisher.com)
- Caspase-12 Activators offered by Santa Cruz activate caspase-12 and, in some cases, other apoptosis and tumor related proteins. (scbt.com)
- We have identified a new calpain activated caspase-12 mediated apoptosis pathway in the lens fiber cells. (arvojournals.org)
- We propose that accumulation of folding-incompetent DN-FGFR proteins in the lens fiber cells can induce ER stress, disrupt calcium homeostasis, and result in the activation of calpain and caspase-12 which contributes to the mechanism of apoptosis. (arvojournals.org)
- Previously, we analyzed mice lacking either caspase-2 or caspase-3 and documented a role for caspase-2 in developmental and chemotherapy-induced apoptosis of oocytes. (semanticscholar.org)
- Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. (semanticscholar.org)
- Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs. (semanticscholar.org)
- Inhibition of Autophagy Promotes Caspase-Mediated Apoptosis by Tunicamycin in HepG2 cells. (ptgcn.com)
- Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats. (semanticscholar.org)
- Therefore, we wanted to explore the role of caspase-12 in the mechanism of retinopathy in T17M mice and determine if inhibiting apoptosis in this way is a viable approach for halting retinal degeneration. (arvojournals.org)
- Ethanol induces apoptosis in cells via a caspase-dependent mechanism. (kzoo.edu)
- Control of caspase activity, and thus apoptosis, is directly modulated by the Bcl-2 family of proteins, which includes both pro- and anti-apoptotic members. (kzoo.edu)
- Anti-apoptotic Bcl-2 protects cells from apoptosis by inhibiting caspase activation. (kzoo.edu)
- Caspase-9 and caspase-12 are thought to be downstream of mitochondria and the endoplasmic reticulum respectively, however it is unknown which of these caspases is activated in ethanol-induced apoptosis. (kzoo.edu)
- This work suggests that ethanol-induced apoptosis does not occur via a mitochondrial stress pathway and caspase-9 activation, but rather through an ER-stress pathway and subsequent caspase-12 activation. (kzoo.edu)
- Myocardial apoptosis rate was measured by TUNEL staining, and expression of glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, total- and phospho-(Ser473)-Akt were assessed by Western blot analyses. (medsci.org)
- GRP78, caspase-12 and CHOP were highly expressed in ischemic myocardium, while NGF significantly inhibited the overexpression of these proteins which were involved in ER stress-induced myocardial apoptosis. (medsci.org)
- Caspases ( c ysteine- asp artic prote ases , c ysteine asp art ases or c ysteine-dependent asp artate-directed prote ases ) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis , pyroptosis and necroptosis ) and inflammation . (wikipedia.org)
- Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis . (wikipedia.org)
- DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (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)
- The following antibody was used in this experiment: Caspase 12 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-19963, RRID AB_11153731. (thermofisher.com)
- Western blot analysis of Caspase-12 in mouse brain tissue lysate in the absence (A) or presence (B) of blocking peptide with Caspase-12 antibody (GTX28117)at 1μg/ml. (genetex.com)
- Caspase-12 Antibody detects endogenous levels of full-length caspase-12 protein (50 kDa) and its cleaved product (40-44 kDa). (ptgcn.com)
- This antibody does not cross-react with other caspases. (ptgcn.com)
- The endoplasmic reticulum (ER) stress is the third apoptotic pathway and caspase-12 is involved. (thermofisher.com)
- Levels of endoplasmic reticulum (ER)-resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. (rupress.org)
- Caspase-12 is located in the endoplasmic reticulum (ER). (ptgcn.com)
- Recently it has been demonstrated that the endoplasmic reticulum stress-associated caspase-12 is activated during progression of retinal degeneration in different animal models. (arvojournals.org)
- For example, we found that full knockout of the UPR proapoptotic CHOP protein in degenerating retinas dramatically accelerated the rate of retinal degeneration 4 , 5 while full ablation of the UPR downstream marker, the endoplasmic reticulum (ER) stress-associated caspase (Csp)-7, significantly slowed the rate of retinal degeneration. (arvojournals.org)
- A peptide corresponding to amino acids 100 to 116 of murine caspase-12. (thermofisher.com)
- Caspase activity can be quantified by fluorescent detection of free AFC after cleaved from the peptide substrate ATAD-AFC at Ex/Em = 400/505 nm using a fluorometer or a fluorescence plate reader. (antibody-antibodies.com)
- A synthetic peptide that irreversibly inhibits caspase-12 and related caspase activity. (antibody-antibodies.com)
- During fiber cell differentiation, caspase-12 was localized to the nuclei of the fiber cells. (arvojournals.org)
- There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing. (wikipedia.org)
- Caspase signals resulting from the activation of nuclease CAD indicate that the cell differentiation is due to a CAD modification in chromatin structure. (wikipedia.org)
- The factor that seems to induce more cell differentiation is caspase-3 protease. (wikipedia.org)
- Caspase-12 inhibition conferred significant protection from ethanol toxicity to cells, while caspase-9 inhibition did not provide significant rescue. (kzoo.edu)
- Caspase-12 and pan-caspase inhibition were not statistically different. (kzoo.edu)
- In this study, it was found out that minocycline reduces neurotoxicity induced by various C-terminal fragments of APP through inhibition of cytochrome c release and caspase-12 activation. (ac.ir)
- CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
- We also demonstrated that caspase-12 was processed downstream of Apaf-1 and caspase-3, and neither overexpression nor knockdown of caspase-12 affected susceptibility of the cells to ER stress-induced cell death. (biologists.org)
- Active full-length caspase-12 (CASP12L), confined to the people of African descent, has been associated with increased susceptibility to and mortality from severe sepsis. (cdc.gov)
- Insufficient activation of these caspases can increase an organism's susceptibility to infection, as an appropriate immune response may not be activated. (wikipedia.org)