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 3.4.22.4.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)

p27Kip1 induces drug resistance by preventing apoptosis upstream of cytochrome c release and procaspase-3 activation in leukemic cells. (1/311)

The cyclin-dependent kinase inhibitor p27Kip1 has been implicated as a drug resistance factor in tumor cells grown as spheroids or confluent monolayers. Here, we show that p27Kip1 overexpression also induces resistance to drug-induced apoptosis and cytotoxicity in human leukemic cells growing in suspension. The anti-apoptotic effect of p27Kip1 is not restricted to DNA-damaging agents but extends to the tubulin poison vinblastin, agonistic anti-Fas antibodies and macromolecule synthesis inhibitors. To further identify at which level this protein interferes with the cell death pathway, we investigated its influence on caspase activation and mitochondrial changes. Exposure of mock-transfected U937 cells to 50 microm etoposide activates procaspase-3 and the long isoform of procaspase-2 and induces mitochondrial potential decrease and cytochrome c release from mitochondria to the cytosol. All these events are prevented by p27Kip1 overexpression. p27Kip1 does not modulate Bcl-2, Bcl-X(L), Mcl-1 and Bax protein level in leukemic cells but suppresses Mcl-1 expression decrease observed in mock-transfected U937 cells undergoing etoposide-induced cell death. We conclude that p27Kip1 prevents cell death upstream of the final pathway common to many apoptotic stimuli that involves cytochrome c release from mitochondria and activation of downstream caspases.  (+info)

Bcl-2 regulates a caspase-3/caspase-2 apoptotic cascade in cytosolic extracts. (2/311)

Apoptosis is accompanied by the activation of a number of apoptotic proteases (caspases) which selectively cleave specific cellular substrates. Caspases themselves are zymogens which are activated by proteolysis. It is widely believed that 'initiator' caspases are recruited to and activated within apoptotic signalling complexes, and then cleave and activate downstream 'effector' caspases. While activation of the effector caspase, caspase-3, has indeed been observed as distal to activation of several different initiator caspases, evidence for a further downstream proteolytic cascade is limited. In particular, there is little evidence that cellular levels of caspase-3 that are activated via one pathway are sufficient to cleave and activate other initiator caspases. To address this issue, the ability of caspase-3, activated upon addition to cytosolic extracts of cytochrome c, to cause cleavage of caspase-2 was investigated. It was demonstrated that cleavage of caspase-2 follows, and is dependent upon, activation of caspase-3. Moreover, the activation of both caspases was inhibited by Bcl-2. Together, these data indicate that Bcl-2 can protect cells from apoptosis by acting at a point downstream from release of mitochondrial cytochrome c, thereby preventing a caspase-3 dependent proteolytic cascade.  (+info)

Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. (3/311)

Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems.  (+info)

CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. (4/311)

We have identified and characterized CIPER, a novel protein containing a caspase recruitment domain (CARD) in its N terminus and a C-terminal region rich in serine and threonine residues. The CARD of CIPER showed striking similarity to E10, a product of the equine herpesvirus-2. CIPER formed homodimers via its CARD and interacted with viral E10 but not with several apoptosis regulators containing CARDs including ARC, RAIDD, RICK, caspase-2, caspase-9, or Apaf-1. Expression of CIPER induced NF-kappaB activation, which was inhibited by dominant-negative NIK and a nonphosphorylable IkappaB-alpha mutant but not by dominant-negative RIP. Mutational analysis revealed that the N-terminal region of CIPER containing the CARD was sufficient and necessary for NF-kappaB-inducing activity. Point mutations in highly conserved residues in the CARD of CIPER disrupted the ability of CIPER to activate NF-kappaB and to form homodimers, indicating that the CARD is essential for NF-kappaB activation and dimerization. We propose that CIPER acts in a NIK-dependent pathway of NF-kappaB activation.  (+info)

DRONC, an ecdysone-inducible Drosophila caspase. (5/311)

Caspases play an essential role in the execution of programmed cell death in metazoans. Although 14 caspases are known in mammals, only a few have been described in other organisms. Here we describe the identification and characterization of a Drosophila caspase, DRONC, that contains an amino terminal caspase recruitment domain. Ectopic expression of DRONC in cultured cells resulted in apoptosis, which was inhibited by the caspase inhibitors p35 and MIHA. DRONC exhibited a substrate specificity similar to mammalian caspase-2. DRONC is ubiquitously expressed in Drosophila embryos during early stages of development. In late third instar larvae, dronc mRNA is dramatically up-regulated in salivary glands and midgut before histolysis of these tissues. Exposure of salivary glands and midgut isolated from second instar larvae to ecdysone resulted in a massive increase in dronc mRNA levels. These results suggest that DRONC is an effector of steroid-mediated apoptosis during insect metamorphosis.  (+info)

Analysis of apoptosis and expression of bcl-2 gene family members in the human and baboon ovary. (6/311)

Recent data support a role for apoptosis, under tight regulatory control by bcl-2, oxidative stress response, tumor suppressor, and CASP gene family members, in mediating granulosa cell demise during follicular atresia in the rodent and avian ovary. Herein we evaluated the occurrence of apoptosis in the human and baboon ovary relative to follicular health status, and analyzed expression of several cell death genes in these tissues. In situlocalization of DNA strand breaks in fixed human and baboon ovarian tissue sections indicated that apoptosis was essentially restricted to granulosa cells of atretic antral follicles. Biochemical analysis of DNA oligonucleosomes in individual follicles isolated from baboon ovaries during the ovulatory phase revealed the presence of apoptotic DNA fragments in subordinate but not dominant follicles, thus substantiating the in situ labeling studies. Messenger RNA transcripts encoded by the bax death susceptibility gene, the bcl-xlong survival gene, the bcl-xshort pro-apoptosis gene, the p53 tumor suppressor gene, and two members of the CASP gene family (CASP-2/Ich-1, CASP-3/CPP32), were detected by Northern blot analysis of total RNA prepared either from human ovaries or from Percoll-purified granulosa-lutein cells obtained from patients undergoing assisted reproductive technologies. Lastly, immunohistochemical localization of the BAX death-susceptibility protein in the human ovary revealed abundant expression in granulosa cells of early atretic follicles, whereas BAX protein was extremely low or non-detectable in healthy or grossly-atretic follicles. We conclude that apoptosis occurs during, and is probably responsible for, folicular atresia in the human and baboon ovary. Moreover, apoptosis in the human ovary is likely controlled by altered expression of the same cohort of cell death regulatory factors recently implicated as primary determinants of apoptosis induction or suppression in the rodent ovary.  (+info)

Extended therapeutic window for caspase inhibition and synergy with MK-801 in the treatment of cerebral histotoxic hypoxia. (7/311)

In rats, striatal histotoxic hypoxic lesions produced by the mitochondrial toxin malonate resemble those of focal cerebral ischemia. Intrastriatal injections of malonate induced cleavage of caspase-2 beginning at 6 h, and caspase-3-like activity as identified by DEVD biotin affinity-labeling within 12 h. DEVD affinity-labeling was prevented and lesion volume reduced in transgenic mice overexpressing BCL-2 in neuronal cells. Intrastriatal injection of the tripeptide, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a caspase inhibitor, at 3 h, 6 h, or 9 h after malonate injections reduced the lesion volume produced by malonate. A combination of pretreatment with the NMDA antagonist, dizocilpine (MK-801), and delayed treatment with zVAD-fmk provided synergistic protection compared with either treatment alone and extended the therapeutic window for caspase inhibition to 12 h. Treatment with cycloheximide and zVAD-fmk, but not with MK-801, blocked the malonate-induced cleavage of caspase-2. NMDA injections alone resulted in a weak caspase-2 cleavage. These results suggest that malonate toxicity induces neuronal death by more than one pathway. They strongly implicate early excitotoxicity and delayed caspase activation in neuronal loss after focal ischemic lesions and offer a new strategy for the treatment of stroke.  (+info)

Role of caspases and possible involvement of retinoblastoma protein during TGFbeta-mediated apoptosis of human B lymphocytes. (8/311)

In this study, we investigated the involvement of caspases in TGFbeta-induced apoptosis in human B cells. Our results show that TGFbeta-mediated nuclear fragmentation, observed in the Epstein-Barr virus-negative Burkitt's Lymphoma cell line BL41, was abolished in the presence of the tripeptide caspase inhibitor zVAD-fmk or the specific caspase-3 inhibitor DEVD-fmk. Other apoptotic manifestations such as cell shrinkage, surface phosphatidylserine expression and chromatin condensation were strongly inhibited by zVAD-fmk but only partially by DEVD-fmk. This suggests that other caspases in addition to caspase-3 control these apoptotis-associated features. Specific activation of caspase-3 during TGFbeta-induced apoptosis was demonstrated by the DEVD-fmk-sensitive expression of the active p17 subunit of caspase-3 and by in vivo cleavage of PARP. In addition, TGFbeta treatment of BL41 promoted the expression of both dephosphorylated and truncated forms of the retinoblastoma protein. Inhibition of caspase-3 activity abolished both nuclear fragmentation and expression of the truncated retinoblastoma protein, without modifying the G1 cell cycle arrest induced by TGFbeta. Our data thus demonstrate that TGFbeta-induced apoptosis of lymphoma B lymphocytes is dependent on caspase activation and involves caspase-dependent cleavage of the retinoblastoma protein.  (+info)

*RNA silencing

Caspase 2 Ocular and retinal disorders. AGN211745. Age-related macular degeneration, choroidal neovascularization. VEGFR1 ... 12 (2): 214-22. PMC 2861437. PMID 20373265.. *^ a b Meister G, Landthaler M, Dorsett Y, Tuschl T (Mar 2004). "Sequence-specific ... doi:10.1007/s00018-003-2245-2. PMID 12827277.. *^ a b c Tijsterman M, Ketting RF, Plasterk RH (2002). "The genetics of RNA ... 2 (2): 110-9. doi:10.1038/35052556. PMID 11253050.. *^ Bühler M (Apr 2009). "RNA turnover and chromatin-dependent gene ...

*Kaspaza-3 - Википедија, слободна енциклопедија

Nicholson, D. & Thornberry, N.A. (2004). „Caspase-3 and caspase-7". Ур.: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... Nicholson, D. & Thornberry, N.A. (2004). „Caspase-3 and caspase-7". Ур.: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. ... Chang, H.Y. & Yang, X. (2000). „Proteases for cell suicide: functions and regulation of caspases". Microbiol. Mol. Biol. Rev. ...

*Autoimmune lymphoproliferative syndrome

Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder ... T cells from patient and normal control supported in culture for ,10 days with mitogen stimulation and IL-2 expansion and then ... 148 (2): 205-16. doi:10.1111/j.1365-2141.2009.07991.x. PMC 2929682 . PMID 19930184.. ...

*Acetylation

But in contrast, the caspase-2, which is acetylated by NatA, can interact with the adaptor protein RIP associated Ich-1/Ced-3 ... This could activate caspase-2 and induce cell apoptosis. Ribosome proteins play an important role in the protein synthesis, ... 2 (6): 456-462. doi:10.1007/s13238-011-1063-9. PMC 3690542 . PMID 21748595. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W (2008). " ... Table 2. Overview of the expression of NatA subunits in various cancer tissues Proteins are typically acetylated on lysine ...

*CRADD

Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). "Activation of the NF-kappaB pathway by caspase 8 and its ... Through its CARD domain, this protein interacts with, and thus recruits, caspase 2/ICH1 to the cell death signal transduction ... Droin N, Beauchemin M, Solary E, Bertrand R (December 2000). "Identification of a caspase-2 isoform that behaves as an ... Droin N, Beauchemin M, Solary E, Bertrand R (2000). "Identification of a caspase-2 isoform that behaves as an endogenous ...

*FADD

... initiating the caspase cascade. The activated caspases can go on to cleave intracellular proteins such as inhibitor of caspase- ... Activated caspase 8 cleaves these kinases, inhibiting necroptosis. Since activation of caspase 8 requires FADD in order to ... "Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8". Journal of ... Caspase 8 then cleaves RIPK1, leading to inhibition of this signalling, inhibiting cell death. FADD knockout in mouse embryos ...

*Anterior ischemic optic neuropathy

This trial will test the use of a synthetic siRNA that blocks caspase 2, an important enzyme in the apoptosis cycle. In ... "Ocular neuroprotection by siRNA targeting caspase-2". Cell Death & Disease. 2 (6): e173. doi:10.1038/cddis.2011.54. PMC 3168996 ... 118 (2): 291-2. PMID 10676804. Pomeranz HD, Smith KH, Hart WM, Egan RA (March 2002). "Sildenafil-associated nonarteritic ... 18 (2): 191-221. doi:10.1016/S1350-9462(98)00016-0. PMID 9932283. IONDT(The Ischemic Optic Neuropathy Decompression Trial) ...

*AIFM1

In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. AIFM1 also ... "Mitochondrial release of caspase-2 and -9 during the apoptotic process". J. Exp. Med. 189 (2): 381-94. doi:10.1084/jem.189.2. ... a novel caspase-independent death effector released from mitochondria". Biochimie. 84 (2-3): 215-22. doi:10.1016/S0300-9084(02) ... "The C-terminal moiety of HIV-1 Vpr induces cell death via a caspase-independent mitochondrial pathway". Cell Death Differ. 9 ( ...

*MZB1

Bonfoco E, Li E, Kolbinger F, Cooper NR (August 2001). "Characterization of a novel proapoptotic caspase-2- and caspase-9- ... Proteomics-based identification of proapoptotic caspase adapter protein as a novel serum marker of non-small cell lung cancer ...

*BNIPL

Qin W, Hu J, Guo M, Xu J, Li J, Yao G, Zhou X, Jiang H, Zhang P, Shen L, Wan D, Gu J (Aug 2003). "BNIPL-2, a novel homologue of ... 308 (2): 379-85. doi:10.1016/S0006-291X(03)01387-1. PMID 12901880. Xie L, Qin WX, He XH, Shu HQ, Yao GF, Wan DF, Gu JR (May ... Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein is a protein that in humans is encoded by the BNIPL gene. BNIPL ... Zhou YT, Soh UJ, Shang X, Guy GR, Low BC (Mar 2002). "The BNIP-2 and Cdc42GAP homology/Sec14p-like domain of BNIP-Salpha is a ...

*PPP3CA

Mukerjee N, McGinnis KM, Gnegy ME, Wang KK (August 2001). "Caspase-mediated calcineurin activation contributes to IL-2 release ... 503 (2-3): 201-5. doi:10.1016/S0014-5793(01)02730-2. PMID 11513882. Esau C, Boes M, Youn HD, Tatterson L, Liu JO, Chen J ( ... November 2001). "Deletion of calcineurin and myocyte enhancer factor 2 (MEF2) binding domain of Cabin1 results in enhanced ...

*NLRP1

Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The ... The NLRP1 protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to ... NLRP1 has been shown to interact with caspase 9 and APAF1. GRCh38: Ensembl release 89: ENSG00000091592 - Ensembl, May 2017 ... Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases ...

*Inflammasome

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 ...

*Xenopus

Recently, oocytes were used recently to study the biochemical mechanisms of caspase-2 activation; importantly, this mechanism ... "Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2". Developmental Cell. 16 ... 408 (2): 180-187. doi:10.1016/j.ydbio.2015.02.003. Gurdon, J. B.; Lane, C. D.; Woodland, H. R.; Marbaix, G. (17 September 1971 ... 35 (2): 145-149. doi:10.1016/j.devcel.2015.09.017. ISSN 1878-1551. PMID 26506304. Rana AA, Collart C, Gilchrist MJ, Smith JC ( ...

*SFRS2IP

1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... 3.0.CO;2-5. PMID 10508479. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than ... 18 (2): 676-84. PMC 108778 . PMID 9447963. "Entrez Gene: SFRS2IP splicing factor, arginine/serine-rich 2, interacting protein ... the sensitivity of PS1 to caspases". FEBS Lett. 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. PMID 10069390. Scanlan MJ, ...

*Suzanne Cory

... prevents caspases from being activated. The caspases, a type of protease, remain inactive until signaled through a cascade to ... Bcl-2 is an important family of intracellular proteins that helps regulate apoptosis, or cell suicide. Bcl-2, paired with other ... Cory, Suzanne; Huang, David C. S.; Adams, Jerry M. (2003-01-01). "The Bcl-2 family: roles in cell survival and oncogenesis". ... In particular, the oncoprotein Myc and the Bcl-2 protein family are of interest to her current research lab. ...

*LRDD

2007). "Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway". EMBO J. 26 ( ... Tinel A, Tschopp J (2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic ... Vakifahmetoglu H, Olsson M, Orrenius S, Zhivotovsky B (2006). "Functional connection between p53 and caspase-2 is essential for ... and caspase 2. GRCh38: Ensembl release 89: ENSG00000177595 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000025507 ...

*GOLGA3

2000). "Caspase-2 Is Localized at the Golgi Complex and Cleaves Golgin-160 during Apoptosis". J. Cell Biol. 149 (3): 603-12. ... Maag RS, Mancini M, Rosen A, Machamer CE (Jun 2005). "Caspase-resistant Golgin-160 Disrupts Apoptosis Induced by Secretory ... Sbodio JI, Hicks SW, Simon D, Machamer CE (2006). "GCP60 preferentially interacts with a caspase-generated golgin-160 fragment ...

*Galectin

... novel inducer of T cell apoptosis with distinct profile of caspase activation". The Journal of Immunology. 173 (6): 3825-37. ... 52 (1-2): 100-110. doi:10.1007/s12026-012-8286-6. PMID 22418727. Reticker-Flynn NE, Malta DF, Winslow MM, Lamar JM, Xu MJ, ... Only galectin-1, -2, -3, -4, -7, -8, -9, -10, -12 and -13 have been identified in humans. Galectin-5 and -6 are found in ... Core 2 glycans terminate in galactose or sialic acid, whereas core 1 is branched and has potential for large carbohydrate ...

*David Kirsch

Conversion of Bcl-2 to a Bax-like death effector by caspases. 278:5345. Science. 1997 Andrea Ventura, David G Kirsch, Margaret ... His highest cited papers are "Conversion of Bcl-2 to a Bax-like death effector by caspases", at 1332 times, and "Restoration of ...

*HK2

"Hexokinase II detachment from the mitochondria potentiates cisplatin induced cytotoxicity through a caspase-2 dependent ... Hexokinase 2 also known as HK2 is an enzyme which in humans is encoded by the HK2 gene on chromosome 2. Hexokinases ... 31 (2): 197-212. doi:10.1016/s0047-6374(85)80030-0. PMID 4058069. Wyatt, E; Wu, R; Rabeh, W; Park, HW; Ghanefar, M; Ardehali, H ... 99 (2): 260-6. doi:10.1111/j.1349-7006.2007.00683.x. PMID 18271924. This article incorporates text from the United States ...

*PKN2

227 (1-2): 344-351. doi:10.1111/j.1432-1033.1995.tb20395.x. PMID 7851406. "Entrez Gene: PKN2 protein kinase N2". Koh H, Lee KH ... 41 (2): 561-9. doi:10.1021/bi010719z. PMID 11781095. Balendran A, Biondi RM, Cheung PC, Casamayor A, Deak M, Alessi DR (July ... 4 (2): 306-315. doi:10.1021/pr0498436. PMID 15822905. Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, ... 496 (2-3): 101-104. doi:10.1016/S0014-5793(01)02401-2. PMID 11356191. Hodgkinson CP, Sale GJ (2002). "Regulation of both PDK1 ...

*TFPI2

19 (2-3): 217-23. doi:10.1016/S0143-4004(98)90011-X. PMID 9548189. Shinoda E, Yui Y, Hattori R, et al. (1999). "Tissue factor ... 22 (2): 218-24. doi:10.1161/hq0102.101842. PMID 11834519. Konduri SD, Osman FA, Rao CN, et al. (2002). "Minimal and inducible ... 23 (2-3): 145-53. doi:10.1053/plac.2001.0774. PMID 11945080. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation ... 2003). "Methylation of TFPI-2 gene is not the sole cause of its silencing". Int. J. Oncol. 22 (4): 843-8. doi:10.3892/ijo.22.4. ...

*Major facilitator superfamily

... induces a caspase-independent autophagic cell death". Cell Death and Differentiation. 10 (7): 798-807. doi:10.1038/sj.cdd. ... 3.0.CO;2-P. PMID 10980529. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ... 46 (2): 215-9. doi:10.1093/rheumatology/kel205. PMID 16837472. Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, ... 478 (1-2): 11-8. doi:10.1016/j.gene.2010.10.011. PMID 21044875. Perland E, Hellsten SV, Lekholm E, Eriksson MM, Arapi V, ...

*Apoptosis

... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... along the caspase-9, caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...

*PSEN1

... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 2 (8). doi:10.1101/cshperspect.a006239. PMC 3405821. PMID 22908189.. *^ Su DM, Zhang Q, Wang X, He P, Zhu YJ, Zhao J, Rennert ... 2 (1): 48-58. doi:10.1038/nrc706. PMID 11902585.. *^ Cho S, Lu M, He X, Ee PL, Bhat U, Schneider E, Miele L, Beck WT (December ... doi:10.1016/S0969-9961(03)00123-2. PMID 14572442.. *^ Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, ...
Book Apollon Hotel, Rust on TripAdvisor: See 49 traveler reviews, 273 candid photos, and great deals for Apollon Hotel, ranked #1 of 21 hotels in Rust and rated 4.5 of 5 at TripAdvisor.
Looking for online definition of NEDD-3 in the Medical Dictionary? NEDD-3 explanation free. What is NEDD-3? Meaning of NEDD-3 medical term. What does NEDD-3 mean?
Clothos brain Apollon copies the purpose of Medulla in the human brain and the human hearts Sinoatrial Node and combines the features with the ability for interaction, programming, and functionality. The Apollon brain receives real-time signals from pressure, temperature, and displacement/Laser sensors. Apollon regulate by positive feedback control a set of proportional valves for the BpM, and the driving force and movement of the elastic Myocardium wall inside the Clio or Thalia SUPs.. The Apollon brain is a super compact PLC, which houses a 900 MHz quad-core ARM Cortex-A7 CPU and 16 GB Ram. A range of 15-bit high speed in/out analogue and digital channels corresponds with various sensors and actuators in real-time.. ...
Just as the Sun itself was perceived in the ancient world as the giver of light, Apollo as the representative of the Sun was perceived as the giver of inner light. Know thyself was the dictum carved in stone at his shrine at Delphi, and this emphasises the importance of Apollo as a symbol of consciousness.
Just as the Sun itself was perceived in the ancient world as the giver of light, Apollo as the representative of the Sun was perceived as the giver of inner light. Know thyself was the dictum carved in stone at his shrine at Delphi, and this emphasises the importance of Apollo as a symbol of consciousness.
09:39, 30 April 2015 Homo sapiens:Apoptosis Modulation and Signaling‎ (Corrected ID for AIFM1,CASP4,CASP2,CASP1,HSPA1A,PIDD,TP53,PRKD1,NAIP,XIAP,AIFM2,RIPK1 and PEA15 genes) ...
Use and dose of Nolvadex. To treat breast cancer, patients are recommended to take a tablet of Nolvadex 20 mg 1-2 times per day. If the side effects are absent, a one-time dose of Nolvadex may be increased up to 40 mg.. To treat cancer of kidneys or endometrium, patients are also prescribed a tablet of Nolvadex 20-30 mg 1-2 times per day.. A therapeutic effect is kept only during the prolonged treatment. The action of a tablet of Nolvadex 20 mg lasts for 12 to 20 hours, and therefore if you forgot to take a dose, there is an expectancy of the restored activity of the estrogenic receptors and a reduction of the treatment efficiency.. The treatment of tumors may take 1 to 5 years depending on the sensitivity to Nolvadex. In case of the prolonged treatment, a tolerance of Nolvadex may be developed. If a growth of the cancerous cells is restored during the medical study because of the use of Nolvadex, the treatment is terminated.. Recommendations for the use. ...
Obesity is associated with low-grade chronic inflammation without bacterial or viral infection, but the triggers and molecular mechanisms that lead to obesity-associated metabolic inflammation remain to be further explored. Although recent studies demonstrated palmitate triggered thioglycollate-elicited macrophage death under the stimulation of Gram-negative bacteria-derived LPS (39, 40), it did not explain the sterile inflammation associated with obesity, and it also raised concerns regarding physiology and activated status of these thioglycollate-activated macrophages (41). In this article, we report that when various dietary FAs were uptaken by stable macrophage cell lines or primary BMMs, only sFAs (e.g., PA, SA) were metabolized to produce Cers to induce macrophage cell death. Most importantly, we identified A-FABP as a new molecular sensor in mediating excess sFA-induced Cer production and in promoting macrophage cell death, thus contributing to the sterile chronic inflammation in ...
Apollon, also called Baculoviral IAP Repeat-Containing Protein 6 (BIRC6) or Baculoviral IAP Repeat-containing Ubiquitin Conjugating Enzyme (BRUCE), is an anti-apoptotic protein belonging to the IAP family, which consists of eight members. The genes of this family render cancer cells insensitive to apoptotic stimulation. The aim of the present study was to investigate and assess the role of small interference RNA (siRNA) in the regulation of Apollon gene expression in four different human cancerous cell lines; breast cancer (MCF-7), cervical cancer (HeLa), colon cancer (CaCo-2) and hepatocellular carcinoma (HepG-2). Lipofection was carried out to introduce the Apollon-specific siRNA into the cancerous cells and the Apollon expression levels were determined using RT-PCR. Trypan blue assay was conducted to assess the integrity of the cell membranes after being transfected. 3-(4, 5-dimethylthiazol-2-yl)-2-5- Diphenyl tetrazolium bromide (MTT) assay was also implemented to assess the cell viability ...
Caspase-3 plays a key role in initiation of cellular events during the apoptotic process. PromoKines Caspase-3 and Caspase-7 Immunoassay Kits allow quantification of the specific activity of caspase-3 and -7, respectively. Since caspase-3 and -7 share the same target substrate sequence (DEVD), it is difficult to differentiate the cleavage activity attributed by these two caspases in vitro. Thus, the assays utilize caspase-3 or -7 specific antibodies to capture the activated caspase-3 or -7 in cell lysate. Specific activity of caspase-3 or -7 can then be analyzed using the common caspase-3/7 substrate DEVD-AFC. The assay system ensures absolute specific detection of only caspase-3 or caspase-7 activity in apoptotic samples. Other caspases and non-specific proteases are not detected.. ...
... , Authors: Frank A. Kruyt. Published in: Atlas Genet Cytogenet Oncol Haematol.
Effects of ponicidin on the activity of caspase-3 in MKN28 cells. After treatment, the activity of caspase-3 in MKN28 cells was analyzed by the caspase-3 assay
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Caspase-12兔多克隆抗体(ab87348)可与小鼠, 大鼠样本反应并经WB实验严格验证并得到2个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
Caspase-8兔多克隆抗体(ab61755)可与人样本反应并经WB, ELISA, IHC实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
Neurodegenerative diseases pose one of the most pressing unmet medical needs today. It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently no disease-modifying therapies. Thus it is a potential target for neurodegenerative drug development. In the present study we report on the biochemistry and structure of caspase-6. As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free structure shows caspase-6 in a partially mature but latent conformation. The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase ...
The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Salmonella induces programmed cell death in macrophages by complex mechanisms that involve distinct pathways and require the bacterial TTSS encoded in the pathogenicity island 1 (SPI-1 TTSS). One death pathway, which results in rapid macrophage death with features of necrosis, is dependent on caspase-1 and the SPI-1 TTSS-secreted protein SipB (Hersh et al., 1999; Brennan and Cookson, 2000; Jesenberger et al., 2000). However, macrophages from caspase-1−/− mice also undergo programmed cell death, although with delayed kinetics and different morphological features. Here, we have described another death pathway induced by Salmonella that is independent of caspase-1. A systematic bacterial genetic analysis led us to conclude that this cell death pathway is also dependent on SipB, a protein with membrane fusion activity that is delivered into host cells by the SPI-1 TTSS. This analysis was complicated by the known dual function of SipB, which acts both as an effector of virulence within cells and ...
Progression of the cell cycle and control of apoptosis are crucial and intimately linked processes that occur in all multicellular organisms during development, normal cellular differentiation and tissue homeostasis. Survivin (TIAP, BIRC5), a 16 kDa protein, is a member of the inhibitors of apoptosis (IAP)/BIRP gene family, which includes XIAP, c-IAP-1, c-IAP-2, ILP-2, NAIP, Livin and Apollon.
Hertz LD, Owzar K, Lessans S, Wing C, Jiang C, Kelly WK, Patel JN, Halabi S, Furukawa Y, Wheeler HE, Sibley A, Lassiter C, Weisman LS, Watson D, Krens SD, Mulkey F, Renn CN, Small EJ, Febbo PG, Shterev I, Kroetz D, Friedman PN, Mahoney JF, Carducci MA, Kelley MJ, Nakamura Y, Kubo M, Dorsey SG, Dolan ME, Morris MJ, Ratain MJ and McLeod HL. Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy. Clin Cancer Res. 2016 Oct 1. PMID: 27143689 ...
In order to implement search with assistance from the Android system (to deliver search queries to an activity and provide search suggestions), your application must provide a search configuration in the form of an XML file. This page describes the search…

Caspase-2 - WikipediaCaspase-2 - Wikipedia

... as are caspase-8 (EC 3.4.22.61), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63). Kumar, S.; Kinoshita, M.; Noda, M.; ... caspase-2L, caspase-2S, neural precursor cell expressed developmentally down-regulated protein 2, CASP-2, NEDD2 protein) is an ... Caspase-2 at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and Cellular Biology portal. ... Mancini, M.; Machamer, C.E.; Roy, S.; Nicholson, D.W.; Thornberry, N.A.; Casciola-Rosen, L.A.; Rosen, A. (2000). "Caspase-2 is ...
more infohttps://en.wikipedia.org/wiki/Caspase-2

Caspase 2 - WikipediaCaspase 2 - Wikipedia

... including caspase 1, caspase 4, caspase 5, and caspase 9. It is produced as a zymogen, which contains a long pro-domain that is ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... It is one of the most conserved caspases in different species of animal. Caspase 2 has a similar amino acid sequence to ... and Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000106144 - Ensembl, May 2017 GRCm38: Ensembl ...
more infohttps://en.wikipedia.org/wiki/Caspase_2

Caspase 2 Assay Kit (ab39794) | AbcamCaspase 2 Assay Kit (ab39794) | Abcam

Assay Caspase 2 activity in 2 hr in cell/tissue extracts with Caspase 2 Assay Kit (Fluorometric) ab39794. For microplate ... Abcams Caspase 2 Assay Kit (Fluorometric) provides a simple and convenient means for assaying the activity of caspases that ... Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some ... The mature protease can process its own propeptide, but not that of other caspases. ...
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Recombinant Human Caspase-2 protein (ab158031) | AbcamRecombinant Human Caspase-2 protein (ab158031) | Abcam

Buy our Recombinant Human Caspase-2 protein. Ab158031 is a full length protein produced in Wheat germ and has been validated in ... Recombinant Human Caspase-2 protein. See all Caspase-2 proteins and peptides. ... Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some ... The mature protease can process its own propeptide, but not that of other caspases. ...
more infohttps://www.abcam.com/recombinant-human-caspase-2-protein-ab158031.html

Caspase-2 Mediates Neuronal Cell Death Induced by β-Amyloid | Journal of NeuroscienceCaspase-2 Mediates Neuronal Cell Death Induced by β-Amyloid | Journal of Neuroscience

In contrast, downregulation of caspase-1 or caspase-3 did not block Aβ1-42-induced death. Neurons from caspase-2 null mice were ... a substrate for caspases related to caspase-3. This peptide is not cleaved by caspase-2 and minimally cleaved by caspase-1 ... There is no cross regulation of the other caspases; that is, V-ACasp2 does not affect caspase-1 or caspase-3 levels, etc. (Troy ... The activation of caspase-3 may be occurring in parallel with that of caspase-2, or caspase-2 may be activating caspase-3. ...
more infohttp://www.jneurosci.org/content/20/4/1386

Caspase 2 Primary Antibodies
                
		        
	Caspase 2 Primary Antibodies

15 Caspase 2 Primary Antibodies: Thermo Fisher antibodies are validated for applications including western blotting, ...
more infohttps://www.thermofisher.com/antibody/primary/query/Caspase+2

Casp8ap2 MGI Mouse Gene Detail - MGI:1349399 - caspase 8 associated protein 2Casp8ap2 MGI Mouse Gene Detail - MGI:1349399 - caspase 8 associated protein 2

J:55798 Imai Y, et al., The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis ... Casp8ap2 interacts with 232 markers (Mir1b, Mir9-1, Mir9-2, ...) View All ...
more infohttp://www.informatics.jax.org/marker/MGI:1349399

Cadmium induces caspase-mediated cell death: suppression by Bcl-2.Cadmium induces caspase-mediated cell death: suppression by Bcl-2.

Apoptosis is a process of active cell death and is characterized by activation of caspases, DNA fragmentation, and biochemical ... as a substrate as well as intracellular caspase assays using a fluorigenic caspase-3 substrate confirmed that caspase-3 is ... selective inhibitors of caspase-3 and caspase-1, respectively, suppressed significantly cadmium-induced cell death. However, ... Caspases / physiology*. Cells, Cultured. DNA Fragmentation / drug effects. Dose-Response Relationship, Drug. Enzyme Activation ...
more infohttp://www.biomedsearch.com/nih/Cadmium-induces-caspase-mediated-cell/10771129.html

anti-Caspase 2 Primary Antibodiesanti-Caspase 2 Primary Antibodies

Ausgesuchte Qualitäts-Hersteller für Caspase 2 Antikörper. Hier bestellen. ... Monoklonale und polyklonale Caspase 2 Antikörper für viele Methoden. ... anti-Caspase Recruitment Domain Family, Member 9 Antikörper * anti-Caspase Recruitment Domain-Containing Protein 18 (ICEBERG) ... anti-Caspase 3, Apoptosis-Related Cysteine Peptidase Antikörper * anti-Caspase 4, Apoptosis-Related Cysteine Peptidase ...
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Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer : Table 2Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer : Table 2

Table 2: EC50 and maximum proapoptotic activity, expressed in percentage of apoptotic cells. Results were observed after 24 h ( ...
more infohttps://www.hindawi.com/journals/omcl/2015/154164/tab2/

Neuronal caspase 2 activity and function requires RAIDD, but not PIDD. | Sigma-AldrichNeuronal caspase 2 activity and function requires RAIDD, but not PIDD. | Sigma-Aldrich

Caspase 2 activity can be induced in neurons from PIDD-null mice, and NGF deprivation or Aβ use caspase 2 and RAIDD to execute ... Neuronal caspase 2 activity and function requires RAIDD, but not PIDD.. [Elena M Ribe, Ying Y Jean, Rebecca L Goldstein, ... We show that treatment of wild-type or PIDD-null neurons with Aβ or NGF deprivation induces formation of a complex of caspase 2 ... Caspase 2 was initially identified as a neuronally expressed developmentally down-regulated gene (HUGO gene nomenclature CASP2 ...
more infohttps://www.sigmaaldrich.com/catalog/papers/22515271

Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells...Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells...

TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and ... Caspase-independent cell death. Nat Med. 2005;11:725-30.CrossRefPubMedGoogle Scholar ... Timosaponin AIII mediates caspase activation and induces apoptosis through JNK1/2 pathway in human promyelocytic leukemia cells ... Essential role of STAT1 in caspase-independent cell death of activated macrophages through the p38 mitogen-activated protein ...
more infohttps://link.springer.com/article/10.1007/s13277-014-2985-7

Caspase-2 EnzymesCaspase-2 Enzymes

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.
more infohttps://www.biovision.com/products/cancer-research/apoptosis-related-products/caspases/caspase-2/caspase-2-enzymes.html

Evaluation of Bcl-2 Family Gene Expression and Caspase-3 Activity in Hippocampus STZ-Induced Diabetic RatsEvaluation of Bcl-2 Family Gene Expression and Caspase-3 Activity in Hippocampus STZ-Induced Diabetic Rats

... and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, ... 4. Detection of Caspase-3 Activity. Caspase-3 activity was determined using the Caspase-3/CPP32 Fluorometric Assay Kit (K105) ... Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. The result showed that mRNA and protein ... Evaluation of Caspase-3 Activity in Tissue Extracts. Caspase-3 activity was significantly higher in STZ-induced diabetic group ...
more infohttps://www.hindawi.com/journals/jdr/2008/638467/

Caspase 2 and Caspase 3 Protein Levels as Predictors of Survival in Acute Myelogenous Leukemia | Blood JournalCaspase 2 and Caspase 3 Protein Levels as Predictors of Survival in Acute Myelogenous Leukemia | Blood Journal

Cleaved caspase 3 was detected in several AML samples, and in two of 16 cases a high level of cleaved caspase 3 was associated ... When the effect of each uncleaved caspase was considered individually, a high level of uncleaved caspase 3 (P = .04), but not ... Patients with high levels of cleaved caspase 3 had a better survival rate than patients with low levels of cleaved caspase 3 ( ... Effect of uncleaved and cleaved caspase 3 levels on survival.. Patients with uncleaved caspase 3 levels in the highest third ( ...
more infohttp://www.bloodjournal.org/content/92/9/3090?sso-checked=true

Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1.Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1.

... cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. The ... Caspase 1. Cysteine Endopeptidases / physiology*. DNA / biosynthesis, isolation & purification. DNA Fragmentation. ... and the drug induced apoptosis was blocked by the caspase inhibitor, Ac-Tyr-Val-Ala-L-aspartic acid aldehyde. These data ... 25152024 - Mig-2 attenuates cisplatin-induced apoptosis of human glioma cells in vitro through akt.... 9772874 - Zonal ...
more infohttp://www.biomedsearch.com/nih/Delta9-tetrahydrocannabinol-induces-apoptosis-in/9694974.html

Anti-Dog (Canine) Caspase 2 antibody for Flow Cytometry (FACS)Anti-Dog (Canine) Caspase 2 antibody for Flow Cytometry (FACS)

Apoptosis, Caspase Cascade in Apoptosis, Neurotrophin Signaling Pathway Application Details Product Details anti-Caspase 2 ... Recommended Caspase 2 Antibody (supplied by: Log in to see ) Antigen Caspase 2, Apoptosis-Related Cysteine Peptidase (CASP2) ... This Caspase 2 antibody is un-conjugated Alternatives Biotin. (6), FITC. (6), HRP. (3), Alexa Fluor 488. (2), Alexa Fluor 647. ... Target Details Caspase 2 Application Details Handling Images Specificity Recognizes an epitope in the p19 subunit of human, ...
more infohttp://www.antibodies-online.com/apoptosis-pathway-9/caspase-2-antibody-2843/dog-facs-13535/

RCSB PDB - 2H4W: Crystal structure of human caspase-1 (Glu390->Asp) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl...RCSB PDB - 2H4W: Crystal structure of human caspase-1 (Glu390->Asp) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl...

2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK) ... Crystal structure of human caspase-1 (Glu390-,Asp) in complex with 3-[ ... An allosteric circuit in caspase-1.. Datta, D., Scheer, J.M., Romanowski, M.J., Wells, J.A.. (2008) J.Mol.Biol. 381: 1157-1167 ... Structural studies of caspase-1 reveal that the dimeric thiol protease can exist in two states: in an on-state, when the active ...
more infohttps://www.rcsb.org/structure/2h4w

Delaying Caspase Activation by Bcl-2: A Clue to Disease Retardation in a Transgenic Mouse Model of Amyotrophic Lateral...Delaying Caspase Activation by Bcl-2: A Clue to Disease Retardation in a Transgenic Mouse Model of Amyotrophic Lateral...

Activation of caspase-1 and caspase-3 in transgenic mSOD1 mice. Caspase-1 and caspase-3 are synthesized, respectively, as 45 ... This study also shows pro-caspase-1 and pro-caspase-3 cleavage products and increased caspase-1-like and caspase-3-like ... Increased caspase-1- and caspase-3-like activities in the spinal cords of transgenic mSOD1 mice. Caspase-1-like activity (black ... Relevant to this is the demonstration that active caspase-1 can cleave pro-caspase-3, thus activating caspase-3 (Xue et al., ...
more infohttp://www.jneurosci.org/content/20/24/9119

IJERPH | Free Full-Text | The Association between Splenocyte Apoptosis and Alterations of Bax, Bcl-2 and Caspase-3 mRNA...IJERPH | Free Full-Text | The Association between Splenocyte Apoptosis and Alterations of Bax, Bcl-2 and Caspase-3 mRNA...

... in Bax and Caspase-3, and were significantly lower (p , 0.05 or p , 0.01) in Bcl-2 of the 300, 600 and 900 mg/kg groups. Also, ... In conclusion, dietary NiCl2 in excess of 300 mg/kg caused apoptosis, altered Bax, Bcl-2 and Caspase-3 mRNA expression levels ... Also, splenocyte apoptosis was closely related to the alternations of Bax, Bcl-2 and Caspase-3 mRNA expression, and oxidative ... in Bax and Caspase-3, and were significantly lower (p , 0.05 or p , 0.01) in Bcl-2 of the 300, 600 and 900 mg/kg groups. Also, ...
more infohttps://www.mdpi.com/1660-4601/10/12/7310

RCSB PDB - 2HBZ: Crystal structure of human caspase-1 (Arg286->Ala, Glu390->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino...RCSB PDB - 2HBZ: Crystal structure of human caspase-1 (Arg286->Ala, Glu390->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino...

2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK) ... Crystal structure of human caspase-1 (Arg286-,Ala, Glu390-,Ala) in complex with 3-[ ... A Common Allosteric Site and Mechanism in Caspases. Scheer, J.M., Romanowski, M.J., Wells, J.A.. (2006) Proc.Natl.Acad.Sci.USA ... Highly specific thiol-containing inhibitors of the human inflammatory caspase-1 were identified by using disulfide trapping, a ...
more infohttps://www.rcsb.org/structure/2HBZ

Conversion of Bcl-2 to a Bax-like Death Effector by Caspases | ScienceConversion of Bcl-2 to a Bax-like Death Effector by Caspases | Science

1B), which indicates that the transfected caspase-3, or potentially other cellular proteases activated by caspase-3, are ... which suggested that the caspase cleavage site is localized within the loop. Two potential caspase cleavage sites occur within ... caspases cleave the proenzyme precursors to produce the active subunits of caspases themselves (8). Here, we investigated the ... Mutation of the caspase cleavage site in Bcl-2 enhances antiapoptotic activity. (A) Ba/F3 cell lines were established by ...
more infohttps://science.sciencemag.org/content/278/5345/1966?ijkey=29aced4995b2bcc865a09a9410a81cc582846429&keytype2=tf_ipsecsha

Caspase-10/b-Flice 2Caspase-10/b-Flice 2

Research tested and proven Caspase-10/b-Flice 2 antibody. Antibody is guaranteed to work in western blot applications and is ... frequently other caspases). Human caspases can be subdivided into three functional groups: cytokine activation (caspase-1, -4 ... Caspases are regulated by a variety of stimili, including APAF1, CFLAR/FLIP, NOL3/ARC, and members of the inhibitor of ... Caspase 10/b Immunoblotting of SDS-extracts from 2 x 105 human Jurkat cells. Extracts were electrophoresed on 20% gels and ...
more infohttps://www.neuromics.com/RA15047

Abstract 3494: Combined MEK1/2 and PI3K inhibition induces synergistic caspase-dependent apoptosis in neuroblastoma | Cancer...Abstract 3494: Combined MEK1/2 and PI3K inhibition induces synergistic caspase-dependent apoptosis in neuroblastoma | Cancer...

Furthermore, the cell death response was rescued by treatment with the caspase inhibitory peptide, QVD-OPh. By immunoblot ... Abstract 3494: Combined MEK1/2 and PI3K inhibition induces synergistic caspase-dependent apoptosis in neuroblastoma. Lori S. ... Combined MEK1/2 and PI3K inhibition induces synergistic caspase-dependent apoptosis in neuroblastoma. [abstract]. In: ... Conclusions: Synergistic activity of combined MEK1/2 and PI3K inhibition in human neuroblastoma cell lines via the induction of ...
more infohttp://cancerres.aacrjournals.org/content/75/15_Supplement/3494

WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells | Cancer ResearchWP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells | Cancer Research

WP1066-induced apoptosis was caspase dependent because it was partially reversed by treatment with the pan-caspase inhibitor Z- ... We found that WP1066 induced dose-dependent caspase-3 cleavage. Also, previous studies found that activated caspase-3 abrogated ... we investigated the effect of treatment with WP1066 on the activation of caspase-3, a downstream executioner caspase in the ... WP1066 induces caspase-dependent apoptosis. A, OCIM2 cells (left) and K562 cells (right) were incubated alone or with 1, 2, or ...
more infohttps://cancerres.aacrjournals.org/content/67/23/11291?ijkey=27d0b298ca02fac9df2b69a043fda8bd779dae0e&keytype2=tf_ipsecsha
  • Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2 gene. (wikipedia.org)
  • Caspase 2 was initially identified as a neuronally expressed developmentally down-regulated gene (HUGO gene nomenclature CASP2) and has been shown to be required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and Aβ (β-amyloid). (sigmaaldrich.com)
  • Using quantitative Western blot analysis, we studied the levels of nonactivated (uncleaved) caspase 2 and 3 in peripheral blood low-density cells from 185 patients with newly diagnosed AML. (bloodjournal.org)
  • The loop domain of Bcl-2 is cleaved at Asp 34 by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. (sciencemag.org)
  • Bcl-2 is cleaved by caspases both in vitro and in intact cells. (sciencemag.org)
  • B ) COS-1 cells (5 × 10 5 ) were cotransfected using lipofectamine (Life Technologies) with equal amounts of DNA [2 μg of each of the indicated expression plasmids + control vector pSG5 control vector (Stratagene) as required] and cell lysates were immunoblotted 24 hours after transfection with antibody to Bcl-2 (from D. Mason). (sciencemag.org)
  • C ) Jurkat cells were treated with anti-Fas (1 μg/ml) for 2 hours with or without a 30-min pretreatment with 300 mM Ac-DEVD-CHO, then assessed for viability by trypan blue exclusion in three independent experiments, and the percentage of viable cells was calculated relative to untreated cells. (sciencemag.org)
  • D ) Jurkat cells treated as in (C) were immunoblotted with Bcl-2 antibody 100 (Santa Cruz). (sciencemag.org)
  • Caspase 10/b Immunoblotting of SDS-extracts from 2 x 105 human Jurkat cells. (neuromics.com)
  • Several cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). (aacrjournals.org)
  • Human coronary artery endothelial cells (HCAEC) were treated with a combination of tumour necrosis factor-alpha and interleukin-1 alpha then incubated with NE for 2 or 6 h. (bmj.com)
  • Neuronal caspase 2 activity and function requires RAIDD, but not PIDD. (sigmaaldrich.com)
  • To investigate the requirement for the PIDDosome in caspase-2-dependent neuronal death, we have examined the necessity for each component in induction of active caspase 2 and in execution of caspase-2-dependent neuronal death. (sigmaaldrich.com)
  • Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2-mediated cell death. (rupress.org)
  • 2000) que podem ser classificadas em iniciadoras (2, 8, 9 e 10) e executoras (3, 6 e 7) (Amarante-Mendes e Green, 1999). (scielo.br)
  • In vitro translated human Bcl-2 was digested with purified recombinant caspase-3 (CPP32). (sciencemag.org)
  • A ) 35 S-labeled in vitro translated Bcl-2 and the indicated Bcl-2 mutants were digested with purified recombinant caspase-3 and analyzed on 12% SDS-polyacrylamide gels ( 24 ). (sciencemag.org)
  • Alternatively, Jurkat cell lysates were digested for 4 hours with recombinant caspase-3. (sciencemag.org)
  • and (2) degradation, i.e., recognition of the Lys48 polyubiquitin chain by 26S proteasome and degradation of the target protein with generation of free ubiquitin by ubiquitin-recycling enzymes. (rupress.org)
  • The data demonstrate that cell death is prevented during mitosis through the inhibitory phosphorylation of caspase-2 and suggest that under conditions of mitotic arrest, cdk1-cyclin B1 activity must be overcome for apoptosis to occur. (antikoerper-online.de)
  • Furthermore, the cell death response was rescued by treatment with the caspase inhibitory peptide, QVD-OPh. (aacrjournals.org)
  • In the present study, we investigated a novel AG490 analogue, ( E )-3(6-bromopyridin-2-yl)-2-cyano- N -((S0-1-phenylethyl)acrylamide) (WP1066), whose solubility and protein kinase-inhibitory profile suggested that this compound might be a good candidate for clinical development. (aacrjournals.org)
  • Our study also suggests that modulation of caspase activity may provide protective benefit in the treatment of ALS, a view that is consistent with our recent demonstration of caspase inhibition extending the survival of transgenic mSOD1 mice. (jneurosci.org)
  • 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)
  • Moreover, Western blot analysis also showed that TAIII increased phosphorylation of JNK1/2 and p38 MAPK in a dose-dependent manner. (springer.com)
  • We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. (hindawi.com)
  • Our previous studies ( 2 , 3 ) indicated that the loci of brain tissue damage and pathological characteristics in a rat ischemia model coincided with human cerebral infarction loci and clinical symptoms with regard to injury as the same target tissue is involved in both rats and humans. (spandidos-publications.com)
  • Conversely, a high level of cleaved caspase 3 denoted improved survival and correlated with the inactivation of the DNA-repair enzyme poly(ADP-ribose) polymerase. (bloodjournal.org)
  • Bcl-2 is an integral intracellular membrane protein that inhibits programmed cell death induced by multiple insults in a wide variety of cell types ( 1 ). (sciencemag.org)
  • It is produced as a zymogen, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain. (wikipedia.org)
  • DFFA is encoded by an alternatively encrypted mRNAs originating two distinct forms: short (ICAD-S) and long (ICAD-L), which act like a specific chaperone ensuring the correct CAD's folding Besides, it contains two aspartic acid residues (Asp117 and Asp224) where CAD is identified and, consequently, it stays bounded until Caspase-3 splits this union. (wikipedia.org)