Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.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.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.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.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.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 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.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.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.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.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.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.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.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.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)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.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.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)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.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.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.Oligopeptides: Peptides composed of between two and twelve amino acids.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.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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.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.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.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.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.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.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.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.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.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Caspase 2: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.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.Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.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.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Caspase 6: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.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.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)Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.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.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)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.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.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.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.Pentanoic AcidsGenes, 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.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Receptor-Interacting Protein Serine-Threonine Kinases: A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.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.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.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.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.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.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.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.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.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).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.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Ceramides: 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.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.Viral Proteins: Proteins found in any species of virus.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.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.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).Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Cell 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)FlavoproteinsNeurons: 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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Mitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).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.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.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.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).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.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.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.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.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.Dactinomycin: A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)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.Dipeptides: Peptides composed of two amino acid units.Mice, Inbred C57BLMyeloid 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.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.Cathepsin 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.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.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.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.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.Sparrows: The family Passeridae comprised of small, mainly brown and grey seed-eating birds with conical bills.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Baculoviridae: Family of INSECT VIRUSES containing two subfamilies: Eubaculovirinae (occluded baculoviruses) and Nudibaculovirinae (nonoccluded baculoviruses). The Eubaculovirinae, which contain polyhedron-shaped inclusion bodies, have two genera: NUCLEOPOLYHEDROVIRUS and GRANULOVIRUS. Baculovirus vectors are used for expression of foreign genes in insects.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.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.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.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).Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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 enzymesLeupeptins: 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.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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.SesquiterpenesProtein 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.Insect Proteins: Proteins found in any species of insect.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.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.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)Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.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.Mice, Inbred BALB CProto-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.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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.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.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.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.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.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.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)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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.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.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.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.QuinolinesRNA 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.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Reperfusion Injury: Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.Tetrazolium Salts: Quaternary salts derived from tetrazoles. They are used in tests to distinguish between reducing sugars and simple aldehydes, for detection of dehydrogenase in tissues, cells, and bacteria, for determination of corticosteroids, and in color photography. (From Mall's Dictionary of Chemistry, 5th ed, p455)Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.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.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Glioma: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.Isothiocyanates: Organic compounds with the general formula R-NCS.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.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.Animals, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.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.Oligonucleotides, Antisense: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.

Activation of c-Abl tyrosine kinase requires caspase activation and is not involved in JNK/SAPK activation during apoptosis of human monocytic leukemia U937 cells. (1/2230)

Genotoxic stress triggers the activation of several sensor molecules, such as p53, JNK1/SAPK and c-Abl, and occasionally promotes the cells to apoptosis. We previously reported that JNK1/SAPK regulates genotoxic stress-induced apoptosis in p53-negative U937 cells by activating caspases. c-Abl is expected to act upstream of JNK1/SAPK activation upon treatment with genotoxic stressors, but its involvement in apoptosis development is still unclear. We herein investigated the kinase activities of c-Abl and JNK1/SAPK during apoptosis elicited by genotoxic anticancer drugs and tumor necrosis factor (TNF) in U937 cells and their apoptosis-resistant variant UK711 cells. We found that the activation of JNK1/SAPK and c-Abl correlated well with apoptosis development in these cell lines. Unexpectedly, however, the JNK1/SAPK activation preceded the c-Abl activation. Moreover, the caspase inhibitor Z-Asp suppressed c-Abl activation and the onset of apoptosis but not the JNK1/SAPK activation. Interestingly, c-Abl tyrosine kinase inhibition by CGP 57148 reduced apoptosis without interfering with JNK1/SAPK activation. These results indicate that c-Abl acts not upstream of JNK1/ SAPK but downstream of caspases during the development of p53-independent apoptosis and is possibly involved in accelerating execution of the cell death pathway.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (2/2230)

We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability.  (+info)

Phosphatidylinositol 3-kinase and protein kinase C are required for the inhibition of caspase activity by epidermal growth factor. (3/2230)

The mechanism by which growth factors exert an anti-apoptotic function on many cell types is not well understood. This issue is addressed in relation to epidermal growth factor (EGF) which inhibits apoptosis induced by staurosporine or wortmannin in an epithelial tumour cell line (CNE-2). The presence of EGF substantially reduced the in vitro Ac-DEVD-AMC hydrolytic activity and almost completely suppressed the intracellular cleavage of poly(ADP-ribose) polymerase in staurosporine- or wortmannin-treated cells. Staurosporine but not wortmannin caused the intracellular proteolytic processing of pro-caspase-3 and this event was transiently inhibited by EGF. Staurosporine-induced apoptosis was not inhibited by EGF in the presence of wortmannin or LY294002. Similarly, EGF failed to inhibit wortmannin-induced apoptosis in the presence of staurosporine, chelerythrine chloride or Go6850. These results suggest that phosphatidylinositol 3-kinase and protein kinase C play a role in the survival function of EGF but the reduction of cellular caspase activity cannot be satisfactorily explained by a lack of pro-caspase-3 activation.  (+info)

Altered cytochrome c display precedes apoptotic cell death in Drosophila. (4/2230)

Drosophila affords a genetically well-defined system to study apoptosis in vivo. It offers a powerful extension to in vitro models that have implicated a requirement for cytochrome c in caspase activation and apoptosis. We found that an overt alteration in cytochrome c anticipates programmed cell death (PCD) in Drosophila tissues, occurring at a time that considerably precedes other known indicators of apoptosis. The altered configuration is manifested by display of an otherwise hidden epitope and occurs without release of the protein into the cytosol. Conditional expression of the Drosophila death activators, reaper or grim, provoked apoptogenic cytochrome c display and, surprisingly, caspase activity was necessary and sufficient to induce this alteration. In cell-free studies, cytosolic caspase activation was triggered by mitochondria from apoptotic cells but identical preparations from healthy cells were inactive. Our observations provide compelling validation of an early role for altered cytochrome c in PCD and suggest propagation of apoptotic physiology through reciprocal, feed-forward amplification involving cytochrome c and caspases.  (+info)

Rubella virus-induced apoptosis varies among cell lines and is modulated by Bcl-XL and caspase inhibitors. (5/2230)

Rubella virus (RV) causes multisystem birth defects in the fetuses of infected women. To investigate the cellular basis of this pathology, we examined the cytopathic effect of RV in three permissive cell lines: Vero 76, RK13, and BHK21. Electron microscopy and the TUNEL assay showed that the cytopathic effect resulted from RV-induced programmed cell death (apoptosis) in all three cell lines, but the extent of apoptosis varied among these cells. At 48 h postinfection, the RK13 cell line showed the greatest number of apoptotic cells, the Vero 76 cell line was approximately 3-fold less, and BHK21 had very few. An increased multiplicity of infection and longer time postinfection were required for the BHK21 cell line to reach the level of apoptotic cells in Vero 76 at 48 h. Purified RV induced apoptosis in a dose-dependent fashion, but not UV-inactivated RV or virus-depleted culture supernatant. Specific inhibitors of the apoptosis-specific proteases caspases reduced RV-induced apoptosis and led to higher levels of RV components in infected cells. To address the role of regulatory proteins in RV-induced apoptosis, the antiapoptotic gene Bcl-2 or Bcl-XL was transfected into RK13 cells. Although a high level of Bcl-2 family proteins was expressed, no protection was observed from apoptosis induced by RV, Sindbis virus, or staurosporine in RK13 cells. In BHK21 cells, however, increased expression of Bcl-XL protected cells from apoptosis. The observed variability in apoptotic response to RV of these cell lines demonstrates that programmed cell death is dependent on the unique properties of each cell and may be indicative of how selective organ damage occurs in a congenital rubella syndrome fetus.  (+info)

Merbarone, a catalytic inhibitor of DNA topoisomerase II, induces apoptosis in CEM cells through activation of ICE/CED-3-like protease. (6/2230)

Merbarone (5-[N-phenyl carboxamido]-2-thiobarbituric acid) is an anticancer drug that inhibits the catalytic activity of DNA topoisomerase II (topo II) without damaging DNA or stabilizing DNA-topo II cleavable complexes. Although the cytotoxicity of the complex-stabilizing DNA-topo II inhibitors such as VP-16 (etoposide) has been partially elucidated, the cytotoxicity of merbarone is poorly understood. Here, we report that merbarone induces programmed cell death or apoptosis in human leukemic CEM cells, characterized by internucleosomal DNA cleavage and nuclear condensation. Treatment of CEM cells with apoptosis-inducing concentrations of merbarone caused activation of c-Jun NH2-terminal kinase/stress-activated protein kinase, c-jun gene induction, activation of caspase-3/CPP32-like protease but not caspase-1, and the proteolytic cleavage of poly(ADP-ribose) polymerase. Treatment of CEM cells with a potent inhibitor of caspases, Z-Asp-2. 6-dichlorobenzoyloxymethyl-ketone, inhibited merbarone-induced caspase-3/CPP32-like activity and apoptosis in a dose-dependent manner. These results indicate that the catalytic inhibition of topo II by merbarone leads to apoptotic cell death through a caspase-3-like protease-dependent mechanism. These results further suggest that c-Jun and c-Jun NH2-terminal kinase/stress-activated protein kinase signaling may be involved in the cytotoxicity of merbarone.  (+info)

Inhibitory sites in enzymes: zinc removal and reactivation by thionein. (7/2230)

Thionein (T) has not been isolated previously from biological material. However, it is generated transiently in situ by removal of zinc from metallothionein under oxidoreductive conditions, particularly in the presence of selenium compounds. T very rapidly activates a group of enzymes in which zinc is bound at an inhibitory site. The reaction is selective, as is apparent from the fact that T does not remove zinc from the catalytic sites of zinc metalloenzymes. T instantaneously reverses the zinc inhibition with a stoichiometry commensurate with its known capacity to bind seven zinc atoms in the form of clusters in metallothionein. The zinc inhibition is much more pronounced than was previously reported, with dissociation constants in the low nanomolar range. Thus, T is an effective, endogenous chelating agent, suggesting the existence of a hitherto unknown and unrecognized biological regulatory system. T removes the metal from an inhibitory zinc-specific enzymatic site with a resultant marked increase of activity. The potential significance of this system is supported by the demonstration of its operations in enzymes involved in glycolysis and signal transduction.  (+info)

Nitric oxide inhibits caspase-3 by S-nitrosation in vivo. (8/2230)

In cultured human endothelial cells, physiological levels of NO prevent apoptosis and interfere with the activation of the caspase cascade. In vitro data have demonstrated that NO inhibits the activity of caspase-3 by S-nitrosation of the enzyme. Here we present evidence for the in vivo occurrence and functional relevance of this novel antiapoptotic mechanism. To demonstrate that the cysteine residue Cys-163 of caspase-3 is S-nitrosated, cells were transfected with the Myc-tagged p17 subunit of caspase-3. After incubation of the transfected cells with different NO donors, Myc-tagged p17 was immunoprecipitated with anti-Myc antibody. S-Nitrosothiol was detected in the immunoprecipitate by electron spin resonance spectroscopy after liberation and spin trapping of NO by N-methyl-D-glucamine-dithiocarbamate-iron complex. Transfection of cells with a p17 mutant, where the essential Cys-163 was mutated into alanine, completely prevented S-nitrosation of the enzyme. As a functional correlate, in human umbilical vein endothelial cells the NO donors sodium nitroprusside or PAPA NONOate (50 microM) significantly reduced the increase in caspase-3-like activity induced by overexpressing caspase-3 by 75 and 70%, respectively. When human umbilical vein endothelial cells were cotransfected with beta-galactosidase, morphological analysis of stained cells revealed that cell death induction by overexpression of caspase-3 was completely suppressed in the presence of sodium nitroprusside, PAPA NONOate, or S-nitroso-L-cysteine (50 microM). Thus, NO supplied by exogenous NO donors serves in vivo as an antiapoptotic regulator of caspase activity via S-nitrosation of the Cys-163 residue of caspase-3.  (+info)

Caspase inhibition is effective in minimizing nucleosome accumulation in key cortical cultures stimulated by TNF and thrombin. In contrast, the exact same effect is simply not observed in differentiated PC12 cells. In PC12 cells TNF induced LDH release is decreased by caspase inhibition. For the reason that TNF remedy induces both LDH release and nucleosome accumulation in PC12 cells, caspase inhibition could possibly enrich cell survival below disorders that induce a mixed apoptotic necrotic response. Pytlowany and colleagues demonstrate that In PC12 cells NO released from SNP decreases cell viability inside a time and concentration dependent method, with a increased concentration of NO leading to immediate and sustained lower in cell survival with no evoking a corresponding immediate activation of caspase three . In the recent review we locate that NO created by 0.5 mM SNP activates caspase three inside a longer time frame ...
Click to launch & play an online audio visual presentation by Prof. Guy Salvesen on Natural caspase inhibitors, part of a collection of online lectures.
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In Figure 3, they added the DRACOs to these cells, either with, or without the inhibitor. They also included a product which makes cells which have just self destructed glow in the dark. The first four sections on the graph are simply controls, to pick up the background levels of cell death. Since the main function of caspases is to cause cell death to occur, you can guess what would happen if we were to add caspase inhibitors to a normal set of cells. The blue and red bars are both lower than the green bar , because they have the caspase inhibitors added. The next three sections show what happens when DRACOs are added to the mix, and they show that they kill off a lot of cells. And importantly, you can tell that its performed using caspases, because in the presence of inhibitor, the cells do not die as much. In fact, the levels of death seen is more or less the same as the other controls with inhibitors ...
During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market. ...
Z-VAD(OMe)-FMK is a cell permeable peptide which binds irreversibly to the catalytic site of intracellular enzymes known as caspases, which play an important role in the induction of apoptosis. The binding of Z-VAD(OMe)-FMK to caspases inhibits the acti
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CPAF expression causes nonapoptotic cell death. (A) CPAF reduces cell viability. CPAF K6 or T-REx-293 cells were treated with the indicated combinations of TET, CM, and the caspase inhibitor zVAD-fmk (zVAD). As a positive control, cells were treated with TNF-α (TNF) and cycloheximide (CHX). After indicated time points, cell viabilities were measured by MTT assay. Relative cell viability was calculated (untreated cells were set to 100%). Data are normalized means/SEM of three independent experiments. (B) Analysis of nuclear morphology after CPAF expression by Hoechst staining. CPAF K6 cells were treated with 10 ng/ml AHT, CM, or zVAD-fmk as indicated. As a positive control of apoptosis, cells were treated with TNF/CHX (as described in A). After 16 h, cells were stained with the Hoechst 33342 dye and analyzed by fluorescence microscopy. Bar, 15 μm. (C) Caspase-3 activation during CPAF-expression. CPAF K6 cells were treated as described in B and analyzed by flow cytometry using an antibody ...
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The Ac-YVAD-cmk and Ac-DEVD-CHO peptide inhibitors block TRAIL-induced DNA fragmentation in mouse and human cells. (A) Soluble DNA was extracted from mouse my
This is an Investigator Initiated, Phase I/II study, where Type 1 diabetic participants will receive a 14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following their first islet transplant. Two pilot studies are proposed to establish the optimal safety and efficacy dose of IDN-6556 (25 mg twice daily (Pilot 1) or a loading dose of 100 mg two hours prior to transplantation, then two 50 mg doses following transplant (Day 0) (Pilot 2). This will be followed by 50 mg three times daily). Participants of both pilot studies will receive islet cell transplants under the University of Albertas standard-of-care therapy.. Secondary objectives include:. ...
Materials.Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), z-Asp-Glu-Val-Asp-fmk (zDEVD-fmk), boc-aspartyl(OMe)-fluoromethylketone (BAF), and the fluorogenic caspase substrate zDEVD-AFC were purchased from Enzyme Systems Products (Livermore, CA). Staurosporine was obtained from ICN Pharmaceuticals (Costa Mesa, CA). A cell lysis buffer for fluorogenic caspase activity assays was obtained from Clontech (ApoAlert CPP32 Assay Kit; Palo Alto, CA).. Cell culture. p53-deficient mice were generated from a 129/Sv × C57BL/6 background as described (Donehower et al., 1992). The genotypes of the mating pairs and all offspring were determined by PCR, using DNA extracted from the tail (Timme and Thompson, 1994). p53−/− mice were generated routinely from (+/−) × (−/−) mating pairs, whereas p53 wild-type mice were obtained by crossing p53+/+ mice. The brains from individual animals were cultured separately and genotyped before treatment.. Neuronal cultures derived from embryonic day ...
In eukaryotic cells, there are 2 different forms of cell death: necrosis and apoptosis.19 Necrosis is considered to be a nonphysiological cell death. Necrosis is characterized as an uncoordinated collapse of cellular homeostasis, resulting in early damage of the plasma membrane and consequently the loss of the integrity of the cell. In contrast, apoptosis is a process of programmed cell death in which unnecessary cells are eliminated from multicellular organism. In apoptotic changes, condensation of the nucleus chromatin and fragmentation of the DNA are manifested. The cell shrinks as a result of cytoplasmic condensation, and organelles preserve their normal ultrastructure. The plasma membrane becomes ruffled and blebbed, which eventually separates the cell into a number of membrane-bound fragments of different sizes. The fragments are known as "apoptotic bodies."20 Besides its normal role in the development and maintenance of proliferating mature tissue, apoptosis is also involved in abnormal ...
BioAssay record AID 666968 submitted by ChEMBL: Inhibition of human recombinant caspase-3 catalytic domain using Ac-DEVD-pNA as substrate at 20 ug/ml preincubated for 30 mins before substrate addition measured after 3 mins.
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Active Caspase 3 FITC Staining Kit(Caspase 3FITC染色试剂盒)(ab65613)在活细胞中检测激活型caspase 3,基于流式、显微镜或荧光读板仪。
Active Caspase 2 FITC Staining Kit (ab65612). Active caspase 2 detection in living cells by flow, microscopy or fluorescent plate reader.
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Orally-Administered Caspase Inhibitor PF-03491390 Is Retained in the Liver for Prolonged Periods With Low Systemic Exposure, Exerting a Hepatoprotective Effect Against α-Fas-Induced Liver Injury in a Mouse Model (2007 ...
Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor, blocks all features of apoptosis in THP.1 and Jurkat T-cells.
购买Z-LE(OMe)VD(OMe)-FMK,具有细胞渗透性的Z-LEVD-FMK caspase-4抑制剂 derivative。使用Abcam高品质的Z-LE(OMe)VD(OMe)-FMK帮助您更快取得科研成果。
Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
Welcome! For price inquiries, please feel free to contact us through the form below through the form on the left side. We will get back to you as soon as possible.. ...
高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab32499 交差種: Ms,Hu 適用: WB,IP,IHC-P,Flow Cyt,ICC/IF
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First, the up to date Ensembl IDs have been retrieved for the many genes with SD three between rapamycin and Ly294002 therapies. The Amuvatinib 溶解度 GO lessons
Assay Kits , Caspase Assay Kits , SensoLyte AFC Caspase Profiling Kit *Fluorimetric*; Caspases play important roles in apoptosis and cell signaling. They are also identified as drug-screening targets. AFC-based substrates yield blue fluorescence upon protease cleavage. They are widely used to monitor caspase activity. The SensoLyte Caspase Profiling Kit contains a series of AFC-based peptide substrates (Ex/Em=380 nm/500 nm) as fluorogenic indicators for assaying caspase protease activities. The kit contains a well-designed plate in which a series of AFC-based caspase substrates are coated with both positive and negative controls. It provides the best solution for profiling caspases or caspase inhibitors. The kit contains: A 96-well plate coated with a series of AFC-based caspase substrates along with various controls* Cell lysis buffer Assay buffer AFC (fluorescence reference standard for calibration) A detailed protocol A detailed protocol
Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein (XIAP) against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by ...
This phenomenon was noted to be parallel to the cell cycle arrest and the right shifting of the DNA profile in the cell cycle analysis. How To Use Kratom Extract Powder Forman these events only occurred at high doses of MSE or MIT. SH-SY5Y cells which are known to have wild-type p53 have constitutive expression of p53 in the control and lower doses groups.. The inhibitors used were caspase kratom free overnight shipping 3 inhibitor caspase 8 inhibitor caspase 9 inhibitor general caspase inhibitor negative control and doxorubicin as a positive control ( as described in section 5. The positive control doxorubicin confirmed the assay works by showing a highly significant response for apoptosis. Thus this kratom buy online uk finding supported the notion that How To Use Kratom Extract Powder Forman there was no involvement of caspase executioner nor caspase initiator activation in cell death induced by high dose MSE. C o N ntr eg ol a (E what is kratom tea parma M tive tO C M SE co H) a C sp.. DNA ...
Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegenration in Huntingtons and Alzheimers disease. This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative ...
Background The fundamental oil (EO) of L. particular caspase inhibitors showed that activation of caspase-8 was following and reliant towards the activation of caspases-9 and -3. In addition, the fundamental essential oil triggered a disruption from the mitochondrial transmembrane potential (m), improved the discharge of cytochrome towards the cytosol, and modified the manifestation of certain people of Bcl-2 family members (Bcl-2, Bax and Bet), Apaf-1 and XIAP. Oddly enough, low dosages of AVO-b and AVO-1 induced apoptosis in a variety of malignancy cellular lines also, however, not in noncancerous cellular material. Conclusions The full total outcomes demonstrate how the EO-induced apoptosis in HL-60 cellular material is definitely mediated by caspase-dependent pathways, concerning caspases-3, -9, and -8, that are initiated by Bcl-2/Bax/Bid-dependent lack of 173039-10-6 manufacture m resulting in launch of cytochrome towards the cytoplasm to activate the caspase cascade. The discovering that ...
Background The fundamental oil (EO) of L. particular caspase inhibitors showed that activation of caspase-8 was following and reliant towards the activation of caspases-9 and -3. In addition, the fundamental essential oil triggered a disruption from the mitochondrial transmembrane potential (m), improved the discharge of cytochrome towards the cytosol, and modified the manifestation of certain people of Bcl-2 family members (Bcl-2, Bax and Bet), Apaf-1 and XIAP. Oddly enough, low dosages of AVO-b and AVO-1 induced apoptosis in a variety of malignancy cellular lines also, however, not in noncancerous cellular material. Conclusions The full total outcomes demonstrate how the EO-induced apoptosis in HL-60 cellular material is definitely mediated by caspase-dependent pathways, concerning caspases-3, -9, and -8, that are initiated by Bcl-2/Bax/Bid-dependent lack of 173039-10-6 manufacture m resulting in launch of cytochrome towards the cytoplasm to activate the caspase cascade. The discovering that ...
Fluorescent Dyes , Enzyme Detection Reagents , Caspase 3 (Apopain) Substrate 1r-z, fluorogenic; Rh110 (rhodamine 110)-derived caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase activities. Cleavage of Rh110 peptides by caspases generates strongly fluorescent Rh110 that is monitored fluorimetrically at 510-530 nm with excitation of 488 nm, the most common excitation light source used in fluorescence instruments.; Caspase-3 substrate and caspase-7 substrate; (Z-DEVD)2-Rh110; z-(Asp-Glu-Val-Asp)2-Rh110
Caspase Substrate Assay Kit (Colorimetric) is used for assaying activities of members of caspase 1/2/3/5/6/8/9. (KA3698) - Products - Abnova
BioAssay record AID 364025 submitted by ChEMBL: Induction of apoptosis in mouse TLT cells assessed as effect on caspase 3 activity at 100 ug/ml after 24 hrs by fluorometric assay in presence of 2 mM vitamin C.
Ac-YVAD-CMK | Ac-Tyr-Val-Ala-Asp-CH2Cl Ac-YVAD-Chloromethylketone3180-v 5 mg | 165.00 EUR Acetyl- L-tyrosyl- L-valyl- L-alanyl- ...
The IUPHAR/BPS Guide to Pharmacology. Caspase 1 - C14: Caspase. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Kumar, A.P., Chang, M.K.X., Clement, M.-V., Fliegel, L., Pervaiz, S. (2007). Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death and Differentiation 14 (10) : 1733-1746. [email protected] Repository. https://doi.org/10.1038/sj.cdd. ...
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 ...
Emricasan is the first caspase inhibitor tested in human which has received orphan drug status by FDA. It is developed by Pfizer and made in such a way that it protects liver cells from excessive apoptosis.
The intracellular redox position is intently connected to the levels of professional-inflammatory cytokines, IL-1β, IL-23 and TNF-α which are the major factors of inflammatory responses. IFN-γ has also been shown to be linked with swelling although TNF-α has been researched thoroughly for its function in the inflammatory method and generation of ROS.Maintaining the earlier mentioned information into thought, we evaluated the level of IL-1β and IL-seventeen employing ELISA even though IFN-γ, IL-23 and TNF-α mRNA expression fold transform was identified utilizing qRT-PCR. We located that IL-1β ranges had been considerably larger in the two diabetic teams as in MEDChem Express 415903-37-6 contrast to the wholesome handle topics. The IL-1β is typically expressed by in-filtering macrophages, once activated they synthesize larger volume of nitric oxide as well. Curiously, there have been outstanding discrepancies in both NO and cytokine levels in the patients of higher age teams with glucose ...
Detail záznamu - Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells - Detail záznamu - Knihovna Akademie věd České republiky
Apoptosis is a process of fundamental importance to multicellular organisms that enables control of cell populations and the removal of damaged or potentially harmful cells (Arends and Wyllie 1991). Apoptosis occurs in two phases: an initial commitment phase followed by an execution phase involving cytoskeletal disruption, membrane blebbing, condensation and fragmentation of chromatin, and the formation of apoptotic bodies (Earnshaw 1995). Caspases, a family of aspartate-specific cysteine proteases, play a critical role in the execution phase of apoptosis and are the key effectors responsible for many of the dramatic morphological and biochemical changes of apoptosis (for reviews see Cohen 1997; Thornberry and Lazebnik 1998). Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. Caspases can be divided into two classes: (1) initiator caspases, with long prodomains, such as caspases-8 and -9, which either ...
TY - JOUR. T1 - Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts. AU - Ulakcsai, Zsófia. AU - Bagaméry, Fruzsina. AU - Vincze, István. AU - Szöko, Éva. AU - Tábi, Tamás. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Aim: To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results: Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 μM. It also reduced ...
Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18. It is found on chromosome 11 in humans in a locus with other inflammatory caspases. CASP12 orthologs have been identified in numerous mammals for which complete genome data are available. The CASP12 gene is subject to polymorphism, which can generate a full length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS). A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block ...
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 ...
Caspase 3/7 Glo assay from Promega - posted in Apoptosis, Necrosis and Autophagy: Hello all, I recently purchased a Caspase 3/7 Glo assay kit from Promega for apoptosis detection.My assay was done with HEK293 cells which were stimulated with Etoposide.I performed the assay exactly described in the protocol,and detected the luminescence with our Luminoskan Ascent luminometer. Unfortunately, in my assay I observed no induction of caspase activity and that the highest reading was equal to the...
Caspase 3 antibody LS-C88630 is a biotin-conjugated rabbit polyclonal that binds human, mouse, rat, bovine, dog, hamster, pig, rabbit, and sheep caspase 3 (also known as CASP3). Caspase 3 antibody is validated for use in IHC-paraffin, immunoprecipitation, and western blot.
This video will show you how to perform an apoptosis assay using adherent cells on the Celigo image cytometer using caspase 3/7 and Hoechst reagents.
Poster (2015, June 14). Study question: In a model reproducing early ischemia after ovarian tissue transplantation, does the pan-caspase inhibitor Z-VAD-FMK could prevent granulosa cell apoptosis? Summary answer: Results ... [more ▼]. Study question: In a model reproducing early ischemia after ovarian tissue transplantation, does the pan-caspase inhibitor Z-VAD-FMK could prevent granulosa cell apoptosis? Summary answer: Results obtained with HGL5 granulosa cell line suggest that Z-VAD-FMK is efficient to protect granulosa cells from etoposide or CoCl2 induced apoptosis. What is known already: Removal, cryopreservation and subsequent graft of ovarian strips after cancer treatment have been successfully used to re-establish female fertility. However, the pregnancy rate after autografting of cryopreserved tissue is about 30%. Indeed, the major problem after transplantation is follicular loss due to ischemic reperfusion injury. Study design, size, duration: Three human granulosa cell lines (GC1a, ...
TY - JOUR. T1 - Activation of caspase-8 and Erk-1/2 in domes regulates cell death induced by confluence in MDCK cells. AU - Chang, Yung Heng. AU - Lin, Hsi Hui. AU - Wang, Yang Kao. AU - Chiu, Wen Tai. AU - Su, Hsiao Wen. AU - Tang, Ming Jer. PY - 2007/4/1. Y1 - 2007/4/1. N2 - Under normal culture conditions, cells adhere to culture dish, spread out, proliferate, and finally cover all areas and reach confluence. During the confluent stage, cell proliferation ceases and differentiation is enhanced. Meanwhile, cell death also appears as the monolayer confluence proceeds. To delineate the mechanism of cell death induced by the confluent process, we employed Madin-Darby canine kidney (MDCK) cells. When approaching confluence, MDCK cells exhibited increase the levels of caspase-2 and enhanced the activity of caspase-8. Using various caspase inhibitors to block apoptosis, we found that only z-VAD-fmk and z-IETD-fmk can inhibit confluent cell death, indicating that confluent cell death is mediated by ...
Caspase inhibitor. Acts as a regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. Also induces NF-kappa-B activation during the pro-inflammatory cytokine response. Also able to inhibit CASP1-mediated neuronal cell death, TNF-alpha, hypoxia-, UV-, and staurosporine-mediated cell death but not ER stress-mediated cell death. Acts by preventing activation of caspases CASP1 and CASP4, possibly by preventing the interaction between CASP1 and RIPK2 ...
Caspases, aspartate-specific cysteine proteases, have fate-determining roles in many cellular processes including apoptosis, differentiation, neuronal remodeling, and inflammation (for review, see Yuan & Kroemer, 2010). There are a dozen caspases in humans alone, yet their individual contributions toward these phenotypes are not well understood. Thus, there has been considerable interest in activating individual caspases or using their activity to drive these processes in cells and animals. We envision that such experimental control of caspase activity can not only afford novel insights into fundamental biological problems but may also enable new models for disease and suggest possible routes to therapeutic intervention. In particular, localized, genetic, and small-molecule-controlled caspase activation has the potential to target the desired cell type in a tissue. Suppression of caspase activation is one of the hallmarks of cancer and thus there has been significant enthusiasm for generating ...
A Suzuki coupling of an aryl boronic acid with an iodosancycline compound is shown. الواحة التى حباها الله بالجمال وقلاع العلم الشامخة. The court sentenced the husband to twenty years in prison and the wife to nine years in prison, azulfidine hund to be followed by her deportation back to Nigeria! At mortally xenical uk the time penicillin was in such short supply that after a patient had taken it, the drug was retrieved from his urine and recycled? Once deadly maxalt cost you have a massive amount of facts integrated as knowledge, then your mind will be superhuman in the same sense that mankind with writing is superhuman compared to mankind before writing! Alberto Aguirre Contreras Cédula Profesional 3005834 Gineco-Obstetra 4255236 Consejería: Psic? Pancaspase inhibitor Z-VAD-FMK improved survival of TCNAs-treated cells and decreased TCNAs-induced apoptosis! äramisel reglan cost largo lähtuti uuringutes määratud esinemissagedustest? Oral ...
Flow cytometry is used to detect the fragmented DNA. Conofocal microscopy to assesses the morphological features of apoptosis such as apoptotic blebs. DNA marker to detect the DNA fragmentation. The fragmented DNA, from the apoptic cell, will present a DNA ladder in comparison to the unfragmented live cell. Hoecht staining of apoptotic nuclei (with Hoescht 33342 as a blue stain) to determine the condensation and fragmentation of the nuclei. Hoechst 33342 binds preferentially to adenine-thymine (A-T) regions of DNA. This stain binds into the minor groove of DNA and exhibits distinct fluorescence emission spectra that are dependent on dye:base pair ratios. FLICA (flourochrome inhibitor of caspase) is a simple yet accurate method to measure apoptosis via caspase activity in whole cells. It applies the green fluorescent inhibitor probe FAM-VAD-FMK to label active caspase enzymes in the cell samples. FLICA probes are comprised of an inhibitor peptide sequence that binds to active caspase enzymes, a ...
We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...
Using a genome-wide technical knockout, we isolated a newly identified set of GRIM (genes associated with retinoid-interferon-induced mortality) genes; GRIM genes mediate IFN- and retinoic-acid (RA)-induced cell death. Here, we describe the isolation and characterization of one such gene, GRIM-1. Three proteins, with identical C-termini, were produced from the GRIM-1 open reading frame when this gene was transcribed and translated in vitro. These protein isoforms, designated GRIM-1α, GRIM-1β and GRIM-1γ, differentially suppressed growth via apoptosis in various cell lines. We also show that a caspase-dependent mechanism generates the proapoptotic GRIM-1 isoforms. Lastly, GRIM-1 isoforms differentially blocked maturation of 18S ribosomal RNA, consistent with their respective growth-suppressive ability. Together, these studies identified a novel protein involved in growth suppression and cell death. ...
PAC-1 is a procaspase-activating compound; activates procaspase-3 to produce caspase-3 (EC50 = 0.22 μM). Buy Caspase inhibitor PAC-1 from AbMole BioScience.
... ,Apoptosis is an evolutionarily conserved form of cell suicide, which follows a specialized cellular process. The central component of this process is a cascade of proteolytic enzymes called caspases. These enzymes participate in a series of reactions that are triggered in response to pro-apoptoti,biological,biology supply,biology supplies,biology product
IAP (Inhibitors of Apoptosis) is a family of functionally and structurally related proteins, which serve as endogenous inhibitors of programmed cell death (apoptosis). A common feature of all IAPs is the presence of a BIR in one to three copies. The human IAP family consists of 8 members, and IAP homologs have been identified in numerous organisms. The members of the IAPs included IAPs, Cp-IAP, Op-IAP, XIAP, c-IAPl, C-IAP2, NAIP, Livin and Survivin. The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase 7, thereby inhibiting their activation and preventing apoptosis. Also cIAP1 and cIAP2 have been shown to bind caspases, although how the IAPs inhibit apoptosis mechanistically at the molecular level is not completely understood.. ...
72 products from 18 suppliers. Compare and order Caspase 8 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended products for the most popular species. Our scientists will help you find the right ELISA kit for your needs.
Induction of apoptosis and NF-kB activation by Apaf-1/Nod1 family members and DD proteins (Inohara et al., 2000). The more recent study suggested that IKKgamma binds to the site in C-terminal regulatory region of IKKbeta which is located after the HLH motif. Images ...
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Silibinin, a natural flavonolignan, induces apoptosis in human bladder transitional-cell papilloma RT4 cells both in vitro and in vivo; however, mechanisms of such efficacy are not completely identified. Here, we studied the mechanisms involved in silibinin-induced apoptosis of RT4 cells having intact p53. Silibinin increased p53 protein level together with its increased phosphorylation at serine 15, activated caspase cascade and caused Bid cleavage for apoptosis. Silibinin-caused p53 activation was mediated via ATM-Chk2 pathway, which in turn induced caspase 2-mediated apoptosis. Pifithrin-α, a p53 inhibitor, reversed silibinin-induced caspase activation including caspase 2; however, caspase 2 inhibitor also reversed p53 phosphorylation suggesting a bidirectional regulation between them. Further, silibinin caused a rapid translocation of p53 and Bid into mitochondria leading to increased permeabilization of mitochondrial membrane and cytochrome c release into the cytosol. JNK1/2 activation was ...
Khat is the Celastraceus edulis plant, a flowering evergreen tree or large shrub, which grows in the Horn of Africa and southwestern Arabia. Khat use has been associated with development of oral cancer, but its molecular effects remain controversial. This study describes a novel cytotoxic effect of whole khat extract on three leukemia cell lines. Cells were exposed to khat extract and harvested for analysis by fluorescent and electron microscopy, trypan blue exclusion, as well as immunoblotting to characterize the mode of cell death. In a separate series, cells were pretreated with a panel of caspase inhibitors for possible inhibitory effects. Khat induced a rapid cell death effect in HL-60, Jurkat, and NB4 cells that occurred within 2 h of exposure. The treated cells retained their ability to exclude trypan blue dye, a key feature in the apoptotic process. Exposed cells consistently developed morphological features of manifest apoptosis. Z-VAD, a pan-caspase inhibitor, completely inhibited ...
Severn Biotech, Limited SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde - SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde MW: 492.5 Ac-Tyr-Val-Ala-Asp-CHO A specific reversible inhibitor of caspase 1 (ICE, Interleukin 1ß Converting Enzyme) Thornberry N.A. et al. (1992) Nature 356, 768; Molineaux S.M. et al. (1993) Proc. Natl. Acad. Sci. USA 90, 1809; Walker N.P.C. et al. (1994) Cell 78, 343; Wilson K.P. et al. (1994) Nature 370, 270;
Human caspase 2 ELISA kit can be used for detecting in vitro quantitative levels of caspase-2 (CASP2) in human serum, cell culture supernatant, plasma, tissue
F CD8+ T lymphocytes before operation, but this difference was not statistically BI 78D3 Significant (P.0.05). The percentages of CD8+ T lymphocytes in the
The ApoTox-Glo™ Triplex Assay combines three Promega assay chemistries to assess viability, cytotoxicity and apoptosis within a single assay well. The first part of the assay simultaneously measures two protease activities: GF-AFC is used to measure cell viability, and bis-AAF-R110 to cytotoxicity. The second part of the assay uses the Caspase-GloR to measure caspase activity. - ApoTox-Glo™ Triplex Assay - AbVideo™ - Support - Abnova
Plasmid pcDNA-Caspase 12 from Dr. Junying Yuans lab contains the insert Caspase 12 and is published in Nature. 2000 Jan 6. 403(6765):98-103. This plasmid is available through Addgene.
Aggregatibacter actinomycetemcomitans (Aa) expresses a 64-kDa GroEL protein belonging to the heat shock family of proteins. This protein has been shown to influence human host cells, but the apoptotic capacity of the GroEL protein regarding T cells is not yet known. The purpose of this study was to investigate the ability of A. actinomycetemcomitans GroEL (AaGroEL) protein to induce human peripheral blood T-cell apoptosis. Endogenous, purified AaGroEL protein was used as an antigen. In AaGroEL-treated T cells, the data indicated that phosphatidylserine exposure, an early apoptotic event, was dose- and time-dependent. The AaGroEL-treated T cells were also positive for active caspase-3 in a dose-dependent manner. The rate of AaGroEL-induced apoptosis was suppressed by the addition of the general caspase inhibitor Z-VAD-FMK. Furthermore, cleaved caspase-8 bands (40/36 kDa and 23 kDa) were identified in cells responding to AaGroEL. DNA fragmentation was also detected in the AaGroEL-treated T cells. ...
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.. ...
Human X-linked inhibitor of apoptosis (XIAP) protein belongs to a family of apoptotic suppressor proteins that share a conserved motif, the baculovirus IAP repeat (BIR). The BIR motif is necessary for antiapoptotic function. XIAP plays a variety of other functional roles, such as also modulation of inflammatory signaling and immunity, mitogenic kinase signaling, cell proliferation, and copper homeostasis. XIAP acts as a caspase inhibitor by binding to the active site of caspase 3 and 7; it also inactivates caspase 9 by preventing it from forming active homodimers. Mutations in the XIAP gene are associated with X-linked lymphoproliferative syndrome. XIAP is also known as baculoviral IAP repeat-containing 4 (BIRC4), inhibitor of apoptosis protein 3 (IAP3), hIAP3, IAP-like protein, API3, ILP1, MIHA, and XLP2.. ...
Human X-linked inhibitor of apoptosis (XIAP) protein belongs to a family of apoptotic suppressor proteins that share a conserved motif, the baculovirus IAP repeat (BIR). The BIR motif is necessary for antiapoptotic function. XIAP plays a variety of other functional roles, such as also modulation of inflammatory signaling and immunity, mitogenic kinase signaling, cell proliferation, and copper homeostasis. XIAP acts as a caspase inhibitor by binding to the active site of caspase 3 and 7; it also inactivates caspase 9 by preventing it from forming active homodimers. Mutations in the XIAP gene are associated with X-linked lymphoproliferative syndrome. XIAP is also known as baculoviral IAP repeat-containing 4 (BIRC4), inhibitor of apoptosis protein 3 (IAP3), hIAP3, IAP-like protein, API3, ILP1, MIHA, and XLP2.. ...
This group of sequences represent the core of p45 (45 kDa) precursor of caspases, which can be processed to produce the active p20 (20 kDa) and p10 (10 kDa) subunits. Caspases (Cysteine-dependent ASPartyl-specific proteASE) are cysteine peptidases that belong to the MEROPS peptidase family C14 (caspase family, clan CD) based on the architecture of their catalytic dyad or triad [(PUBMED:11517925)]. Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. Activated caspases act as cysteine proteases, using the sulphydryl group of a cysteine side chain for catalysing peptide bond cleavage at aspartyl residues in their substrates. The catalytic cysteine and histidine residues are on the p20 subunit after cleavage of the p45 precursor.. Caspases are mainly involved in mediating cell death (apoptosis) [(PUBMED:10578171), (PUBMED:10872455), (PUBMED:15077141)]. They have two main roles within the apoptosis cascade: ...
Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 (Golgi reassembly and stacking protein of 65 kD) as a novel caspase substrate. GRASP65 is cleaved specifically by caspase-3 at conserved sites in its membrane distal COOH terminus at an early stage of the execution phase. Expression of a caspase-resistant form of GRASP65 partially preserved cisternal stacking and inhibited breakdown of the Golgi ribbon in apoptotic cells. Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity.
Apoptotic cells release the nucleotides ATP and UTP to attract phagocytic cells, which in turn clear the apoptotic cells. Chekeni et al. found that carbenoxolone (CBX), which inhibits connexins (which form gap junctions) and pannexins (which form plasma membrane channels), and probenicid, which is thought to be more specific for pannexins, reduced ATP release from apoptotic Jurkat cells to a similar extent as the caspase inhibitor zVAD (which blocks the release of ATP from apoptotic cells). Small interfering RNAs (siRNAs) directed against pannexin 1 (PANX1) decreased the release of ATP and UTP from apoptotic Jurkat cells but did not prevent apoptosis. Supernatant from PANX1 siRNA-transfected apoptotic cells recruited fewer monocytes in an in vitro assay of cell migration and when placed in a subcutaneous air pouch in mice. In contrast, Jurkat cells stably overexpressing PANX1 released more ATP and UTP, and supernatants from these cells (after apoptosis had been induced) recruited more monocytes ...
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Looking for the meaning of x-linked inhibitor of apoptosis protein? Find out what is the meaning of x-linked inhibitor of apoptosis protein on Phrases.net! The Webs largest and most authoritative phrases and idioms resource.
Whistlings post on the neat article published by researchers at Sunesis Pharma on tethering as a strategy to discover caspase inhibitors reminded me of Jim Wells, who had come to give a talk at Emory a couple of months ago. Wells moved from being president of Sunesis to UCSF. At UCSF, he commands a formidable repertoire of resources, including NMR, X-Ray and High Res Mass, as well as synthesis and molecular biology facilities. Who in academia can compete with such an immense wall of capability? I am sure Wells must have been offered great incentives including these facilities at UCSF to facilitate his transition from industry to academia. His move is symbolic of the power that academia has now started to command. Part of this power no doubt comes from it being allowed to have patents on drugs, from which they can get considerable finances through royalties. My own advisor, Prof. Dennis Liotta, got Emory 500 million $ in royalties, as one of the co-discoverers of the anti-HIV drug Emtricitabine ...
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LB-18 compound: synthetic drug closely related to lembehyne-A (derived from a marine sponge) induces caspase-independent cell death to human neuroblastoma cells; structure in first source
Caspase 12 antibody [14F7] (caspase 12) for ICC/IF, IHC, IP, WB. Anti-Caspase 12 mAb (GTX10455) is tested in Mouse, Rat samples. 100% Ab-Assurance.
When hypertonicity is imposed with sufficient intensity and acuteness, cells die. Here we investigated the cellular pathways involved in death using a cell line derived from renal epithelium. We found that hypertonicity rapidly induced activation of an intrinsic cell death pathway- release of cytochrome c and activation of caspase-3 and caspase-9-and an extrinsic pathway-activation of caspase-8. Likewise, a lysosomal pathway of cell death characterized by partial lysosomal rupture and release of cathepsin B from lysosomes to the cytosol was also activated. Relationships among the pathways were examined using specific inhibitors. Caspase inhibitors did not affect cathepsin B release into the cytosol by hypertonicity. In addition, cathepsin B inhibitors and caspase inhibitors did not affect hyper-tonicity-induced cytochrome c release, suggesting that the three pathways were independently activated. Combined inhibition of caspases and cathepsin B conferred significantly more protection from ...
The P4 position of caspase cleavage sites confers protease specificity (10). Consistent with the preference for Asp at the P4 position of caspase-3 cleavage sites, mutation of Asp31 (D31A) also abolished cleavage of Bcl-2 by caspase-3 in vitro (11). However, Asp31 itself apparently does not serve as a cleavage site because this site is preserved in the loop deletion mutant Δloop, which is not cleaved. (Deletion of the loop region reconstitutes Ala32.) The Asp residues at P1 and P4 in human Bcl-2 are also conserved in the rat and murine Bcl-2 proteins.. To determine whether Bcl-2 is cleaved inside cells, we cotransfected COS cells with plasmids expressing Bcl-2 and caspase-3. Approximately 50% of the Bcl-2 protein was cleaved in the presence of caspase-3 (Fig. 1B). Similar to results obtained in vitro, mutation of Asp31 or Asp34 abolished proteolysis in transfected cells, whereas mutation of Asp64 had no effect. Cotransfection of the baculovirus caspase inhibitor P35 abolished proteolysis of ...
Caspase-1, originally called ICE, was the first mammalian analogue of the Caenorhabditis elegans death genes to be identified.11 Like all caspases, it is expressed as a proform, which is activated through proteolytic cleavage of an amino-terminal 11-kDa prodomain to release p20 and p10 subunits. Active caspase-1/ICE consists of a (p20/p10)2 tetramer, which is sufficient to process precursor IL-1β9,12-14 and, in at least some cell types, to induce apoptosis.16 Additionally, the prodomain has been postulated to have independent proapoptotic activity by enhancing death receptor-mediated caspase-8 activation.39 Although caspase-1 has conventionally been regarded as a proinflammatory, not a proapoptotic, caspase,10-12 it has been observed to induce or amplify apoptosis in tissue culture models.15,16. Regulated expression of caspase-1 in cardiac hypertrophy,17 the dilated cardiomyopathy of TNF-α overexpression,19 ischemia/infarction,21 and endotoxin-induced myocardial dysfunction18 prompted our ...
SY26-01 The inhibitor of apoptosis (IAP) proteins are major regulators of apoptosis that bind to and inhibit caspases 3, 7, and/or 9. Overexpression of IAP proteins has been demonstrated to confer protection against a variety of pro apoptotic stimuli, including chemotherapies, and is a marker for poor prognosis in a variety of solid tumors and hematologic malignancies. All IAP proteins contain one to three copies of the baculoviral IAP repeat (BIR) domain, zinc-binding domains of about 80 amino acids, that are necessary for their interactions with a number of cytosolic target proteins, including activated caspases 3, 7, and/or 9. Antagonism of the IAP protein mediated inhibition of these caspases is required for caspase dependent cell death, and can be achieved by the mitochondrial protein second mitochondria derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO), which is released into the cytoplasm in response to pro apoptotic stimuli. The pro apoptotic function of ...
Ironically, the term programmed cell death was coined during the observation of intersegmental muscle cells of Manduca sexta, a type of cell that manifests massive autophagic vacuolization-the digestion of part of a cell, which can either rescue the cell or lead to its death-before the cells show signs of apoptosis (Beaulaton & Lockshin, 1977). This raises questions about the relationship between autophagy and apoptosis, as pointed out by R. Lockshin (Jamaica, NY, USA). In addition, when the salivary gland of a developing fruit fly (Drosophila melanogaster) undergoes involution, its cells undergo massive autophagic vacuolization. E. Baehrecke (College Park, MD, USA) reported that transgenic expression of the caspase inhibitor p35 in the salivary gland prevents nuclear pyknosis-a sign of apoptosis-but does not affect vacuolization-a sign of autophagy-placing autophagy either upstream from or parallel to apoptosis. Transgenic expression of inhibitors of autophagy enhances the growth of salivary ...
Retinas were isolated from Brown Norwegian male rats 9-12 weeks of age and cultured on 0.4 µm Millicell culture plate inserts in Neurobasal-A medium at 37ºC in 5% CO2. A Helios gene gun system was used for particle-mediated transfer of a YFP-expressing plasmid to RGCs. Retinal explants were treated with a broad-spectrum, irreversible caspase inhibitor (Boc-D-FMK) to prevent apoptosis. The morphology of RGCs was observed by confocal microscopy. ...
Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family.
The importance of the presented study lies in several key findings. First, our mechanistic knowledge of how the alternative splicing of caspase 9 is regulated has been expanded by our identification of a novel RNA cis-element via which SRSF1 (ASF/SF2) enhances the inclusion of the exon 3,4,5,6 cassette. Furthermore, SRSF1 was shown to specifically interact with this RNA cis-element, and regulate the alternative splicing of caspase 9 via this novel RNA cis-element. Second, we showed that the alternative splicing of caspase 9 is a relevant therapeutic target as shown by direct manipulation of this splicing cascade having significant effect on the sensitivity NSCLC cells to clinically relevant chemotherapeutics. Finally, one of the major findings of the report is our data showing that the synergism of erlotinib combination therapy is in part via modulation of the alternative splicing of caspase 9.. In regard to the RNA cis-element that specifically interacts with SRSF1, a purine-rich RNA ...
Apoptosis is a programmed form of cell death with well-defined morphological traits that are often associated with activation of caspases. More recently evide
In this study, we define a critical role for Grx in TNF-α-mediated caspase-3 activation through regulation of caspase-3 cleavage and glutathiolation. Data to support this notion include (1) caspase-3 cleavage by TNF-α inversely correlated with glutathiolation; (2) TNF-α activated Grx. In Grx knock-down cells, TNF-α-induced apoptosis was attenuated and caspase-3 cleavage was significantly reduced, concomitant with increased caspase-3 glutathiolation; (3) enhanced caspase-3 cleavage by Grx overexpression was reversed by a thioltransferase inactive Grx (C22S); (4) in vitro glutathiolation experiments showed that caspase-3 cleavage by caspase-8 was inversely correlated with caspase-3 glutathiolation; (5) mutations of cysteines (C184 and C220) in caspase-3 show significant increase in cleavage; and (6) Grx binds caspase-3. Our data suggest a model in which TNF-α activates Grx, Grx deglutathiolates caspase-3, and then Grx dissociates from caspase-3, leading to caspase-3 activation. The present ...
Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity". Cell Death and Differentiation. 9 (1): 20-6. ... caspase inhibitors such as XIAP and CIAP1/2. Once bound, the serine protease cleaves the IAP, reducing the cell's inhibition to ... "Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase ... mitochondria during apoptosis and uses its four most N-terminal amino acids to mimic a caspase and be recruited by inhibitor of ...
"The E. Coli Effector Protein NleF is a Caspase Inhibitor". PLoS ONE. 8 (3): e58937. doi:10.1371/journal.pone.0058937. PMC ... "The Interplay between the Escherichia coli Rho Guanine Nucleotide Exchange Factor Effectors and the Mammalian RhoGEF Inhibitor ... "NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection". ...
... a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation processing". J Biol Chem. 276 (37): 34495 ... "Entrez Gene: COP1 caspase-1 dominant-negative inhibitor pseudo-ICE". Human CARD16 genome location and CARD16 gene details page ... 2006). "Protective role of Cop in Rip2/caspase-1/caspase-4-mediated HeLa cell death". Biochim. Biophys. Acta. 1762 (8): 742-54 ... 2006). "Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 ...
TPCK is an irreversible inhibitor of chymotrypsin. Also inhibits some cysteine proteases such as caspase, papain, bromelain or ... TPCK is observed covalently bound in the active site of Caspase 3 in the crystal structure of the complex solved in 2010. The ... Tosyl phenylalanyl chloromethyl ketone (TPCK) is a protease inhibitor. Its structural formula is 1-chloro-3-tosylamido-4-phenyl ...
... the Inhibitor of Caspase Activated DNase (ICAD). During apoptosis, the apoptotic effector caspase, caspase 3, cleaves ICAD and ... "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD". Article. Nature Publishing Group. ... The enzyme responsible for apoptotic DNA fragmentation is the Caspase-activated DNase. CAD is normally inhibited by another ...
Stierle AA, Stierle DB, Girtsman T (2012). "Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia ... 2005). "Structural analysis of epolactaene derivatives as DNA polymerase inhibitors and anti-inflammatory compounds". Int J Mol ... Polyozellus multiplex synthesizes prolyl endopeptidase inhibitors polyozellin, thelephoric acid, and kynapcins. Boletus badius ... Clavaric acid is a reversible farnesyltransferase inhibitor. Inonotus obliquus creates betulinic acid precursor betulin. ...
Stierle AA, Stierle DB, Girtsman T (2012). "Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia ...
... is initiated by caspase-activated deoxyribonuclease following caspase-3 mediated cleavage of the enzyme's inhibitor, ICAD. In ... Additionally, apoptosis and the degradation of intracellular organelles is mediated by caspase activation, particularly caspase ... The anti-apoptotic gene product Bcl-2 is not an active inhibitor of UCP-2 initiated cell death, further distinguishing oncosis ... Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., & Nagata, S. (1998). A caspase-activated DNase that degrades ...
... s are therefore the largest and most diverse superfamily of protease inhibitors. Most serpins are protease inhibitors, ... caspase 1 and caspase 8). In comparison to their mammalian counterparts, viral serpins contain significant deletions of ... Some serpins are both protease inhibitors and perform additional roles. For example, the nuclear cysteine protease inhibitor ... Serpins are classed as irreversible inhibitors and as suicide inhibitors since each serpin protein permanently inactivates a ...
Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B (Mar 1998). "Calpain inhibitors, but not caspase inhibitors, ... Wang KK (Jan 2000). "Calpain and caspase: can you tell the difference?". Trends in Neurosciences. 23 (1): 20-6. doi:10.1016/ ... Machesky LM, Tang HR (Jul 2009). "Actin-based protrusions: promoters or inhibitors of cancer invasion?". Cancer Cell. 16 (1): 5 ... just as the use of calpain inhibitors has been shown to decrease actin proteolysis and the degradation of DNA (another of the ...
1998). "Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis". Arch. Biochem. Biophys. 356 ... The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N- ... "Entrez Gene: CAST calpastatin". The MEROPS online database for peptidases and their inhibitors: LI27.001 Murachi T (1989). " ... 1995). "Autoantibodies to calpastatin (an endogenous inhibitor for calcium-dependent neutral protease, calpain) in systemic ...
These include: Caspase inhibitors: These are primarily used and studied for their anti apoptotic effects. Trophic factors: The ... property of human alpha-synuclein in neuronal cell lines is associated with the inhibition of caspase-3 but not caspase-9 ...
"An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7". Biochemistry. 40 (4): 1117-23. doi:10.1021 ... The inactive proforms of caspase-3 and -7 did not bind survivin. Survivin also does not bind to active caspase-8. Caspase-3 and ... which recruits activator caspases like caspase-8 upon binding TNF at the cell surface. The activation of the initiator caspases ... The human IAPs, XIAP, c-IAPl, C-IAP2 have been shown to bind to caspase-3 and -7, which are the effector caspases in the ...
The X-linked IAP (XIAP) is an extremely powerful inhibitor of apoptosis. This is done through the binding to caspases directly ... In caspase-3 the 'hook' and 'sinker' attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. ... Similar to the functionality of NAIP, the BIR3 domain of XAIP binds to the carboxyl-terminal subunit of caspase-9. Between S1 ... This is unexpected because in nerve growth factor withdrawal, caspase-3 and -9 are activated, causing cell death, which are the ...
Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ...
Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 ( ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs[5] have been ... The MEROPS online database for peptidases and their inhibitors: C14.009. *Apoptosis & Caspase 8-The Proteolysis Map (animation) ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...
"Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. 60 (24): ... "Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. 60 (24): ... "Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment". Cell. 94 (2 ... Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). "Activation of the NF-kappaB pathway by caspase 8 and its ...
June 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ... 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ... 2005). "PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta ... caspase-1 and PYCARD. ENSG00000281166, ENSG00000182261 GRCh38: Ensembl release 89: ENSG00000276780, ENSG00000281166, ...
Additionally, research found that caspase inhibitors (zVAD.fmk, p53, BAF), x-chromosome-linked inhibitor (xiap), and Bcl-xL( ... in conjugation with a paratotic stimulus can result in cell death that is unable to be inhibited by caspase inhibitors. Many ... PEBP, or Raf kinase inhibitor protein (RKIP) is diminished in paraptotic cells, thus resultant down regulation of PEBP and/or ... Cell death induced by IGFIR-IC in 293T cells demonstrated cell death without associated caspase activity. This is in comparison ...
2011). Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor. Cell Death & Disease ... it is suggested that a Caspase inhibitor, TRP601, is a candidate for neuroprotective strategy in prenatal brain injury ... Apoptosis involves the mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF), which activate caspase- ...
... the Inhibitor of Caspase Activated DNase (ICAD). During apoptosis, the apoptotic effector caspase, caspase-3, cleaves ICAD and ... Caspase-activated DNase DNA laddering Sakahira H, Enari M, NagataS. (1998) Cleavage of CAD inhibitor in CAD activation and DNA ... that cleaves chromosomal DNA in a caspase-dependent manner. CAD is synthesized with the help of ICAD (inhibitor of CAD), which ... When cells are induced to undergo apoptosis, caspase 3 cleaves ICAD to dissociate the CAD:ICAD complex, allowing CAD to cleave ...
Watson RW, Fitzpatrick JM (December 2005). "Targeting apoptosis in prostate cancer: focus on caspases and inhibitors of ... XIAP has been shown to interact with: ALS2CR2, Caspase 3. Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1 ... Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking ...
Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspases Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...
... called Inhibitor of caspase-activated DNase (ICAD). In order for apoptosis to begin, an enzyme called caspase 3 cleaves ICAD so ... "Caspase-activated DNase Is Required for Maintenance of Tolerance to Lupus Nuclear Autoantigens." Arthritis and Rheumatism 64.4 ... Apoptotic DNA fragmentation relies on an enzyme called Caspase-Activated DNase (CAD). CAD is usually inhibited by another ... "Identification of ICAD-derived Peptides Capable of Inhibiting Caspase-activated DNase." FEBS Journal 279.16 (2012): 2917-928. ...
This leads to the activation of caspases-3, -8, and -9. When these T lymphocytes were pretreated with caspase inhibitors, DNA ... This suggests that apoptosis that is triggered by zinc deficiency is dependent on caspase proteins. Similar results were shown ... the same study found that TPEN increased the expression of pro-apoptotic genes and led to the activation of caspase-11, a ...
This activation of apoptosis is inhibited by the DNA fragmentation factor DFF45 but not by caspase inhibitors. Mice that lack ...
The same step can be also blocked by several gamma-secretase inhibitors, shown in the same study.[19] These evidences ... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... "Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1". Nature. 405 (6787): 689- ... Based on evidence that a gamma-secretase inhibitor binds to the fragments,[11] the cleaved presenilin complex is considered to ...
Lee SH, Stehlik C, Reed JC (2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation ... The encoded protein contains a C-terminal caspase recruitment domain (CARD), and is a component of signaling complexes in both ... 1999). "Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB". J. Biol. Chem. 274 (21): 14560-7. doi:10.1074/ ... Chen YR, Clark AC (2003). "Equilibrium and kinetic folding of an alpha-helical Greek key protein domain: caspase recruitment ...
Another autophagy inhibitor that works in a similar way as chloroquine is bafilomycin A1. 3B) Autophagic vacuole accumulation ... In PC3 cells, inhibition of autophagy induction prevented p62 accumulation and hence caspase-8 activation 2 days ago · ... Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy currently FDA-approved for use in the treatment ... An advantage to monitoring p62 to measure autophagic flux is that lysosomal inhibitors are not necessary, because unlike LC3-II ...
Neuroprotection by a caspase inhibitor in acute bacterial meningitis.. Braun JS1, Novak R, Herzog KH, Bodner SM, Cleveland JL, ... We demonstrate that the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) ... As apoptosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors might provide a new therapeutic option ...
viral inhibitor of caspase-8-induced apoptosis;. vMIA,. viral mitochondria-localized inhibitor of apoptosis. ... prompting its designation as viral inhibitor of caspase-8-induced apoptosis (vICA). By interfering with caspase-8 activation, ... A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Anna Skaletskaya, Laura M. Bartle, ... A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Anna Skaletskaya, Laura M. Bartle, ...
... Raja S. Mahidhara, R. Hoffman, R.L. Simmons, and T ...
... rapidly induces cell death through recruitment and activation of caspase-8 via the adaptor protein Fas-associated death domain ... The caspase-8 inhibitor FLIP promotes activation of NF-κB and Erk signaling pathways. *Kataoka T ... there was activation of the transcription factors NF-κB and AP-1 and recruitment of the caspase-8 inhibitor and FADD- ... We provide evidence that FLIP is not simply an inhibitor of death-receptor-induced apoptosis but that it also mediates the ...
New Caspase Inhibitors & Activators. Cat.No.. Product Name. Information. S7313 Z-LEHD-FMK. Z-LEHD-FMK is a cell-permeable, ... competitive and irreversible inhibitor of enzyme caspase-9, which helps in cell survival.. ...
The IAP Proteins: Caspase Inhibitors and Beyond Message Subject. (Your Name) has forwarded a page to you from Science Signaling ... Richter and Duckett review the recently discovered and characterized inhibitors of apoptosis proteins (IAPs). Not surprisingly ...
Caspase Inhibitors Promote Alternative Cell Death Pathways Message Subject. (Your Name) has forwarded a page to you from ...
... caspase inhibitors may lead to necrotic cell death, according to a report in The American Journal of Pathology. ... cell death mediated by the enzyme caspase. Caspase inhibitors have therapeutic potential to treat and prevent apoptosis- ... Adding the caspase inhibitor ZVAD blocked early apoptotic cell death but revealed the presence of necrotic cell death at 48 ... "New study questions the safety of caspase inhibitors for the treatment of liver disease." Medical News Today. MediLexicon, Intl ...
Caspase activity and apoptosis inhibitor 1 is a protein that in humans is encoded by the CAAP1 gene. Caspase Apoptosis GRCh38: ...
More From BioPortfolio on "A Caspase Inhibitor in Chronic Hepatitis C (HCV) Patients". *Related Companies*Related Events* ... A Caspase Inhibitor in Chronic Hepatitis C (HCV) Patients. 2014-07-23 21:51:58 , BioPortfolio ... Home » Topics » Gastroenterology » Research » A Caspase Inhibitor in Chronic Hepatitis C (HCV) Patients ... Safety and Efficacy Study of a Caspase Inhibitor in Patients Undergoing Liver Transplantation ...
Guy Salvesen on Natural caspase inhibitors, part of a collection of online lectures. ... Natural caspase inhibitors. *Prof. Guy Salvesen - The Burnham Institute for Medical Research, USA ... Salvesen, G. (2007, October 1). Natural caspase inhibitors [Video file]. In The Biomedical & Life Sciences Collection, Henry ...
The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways.. Kataoka T1, Budd RC, Holler N, Thome ... there was activation of the transcription factors NF-kappaB and AP-1 and recruitment of the caspase-8 inhibitor and FADD- ... We provide evidence that FLIP is not simply an inhibitor of death-receptor-induced apoptosis but that it also mediates the ... Activation of Fas (CD95) by its ligand (FasL) rapidly induces cell death through recruitment and activation of caspase-8 via ...
The caspase inhibitors, that is, ICE-like protease inhibitors,11 interfere with apoptosis at a point subsequent to the ... Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor. Hiroyuki Yaoita, Kazuei Ogawa, Kazuhira Maehara, ... Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor. Hiroyuki Yaoita, Kazuei Ogawa, Kazuhira Maehara and ... Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor. Hiroyuki Yaoita, Kazuei Ogawa, Kazuhira Maehara and ...
... (34)*Caspase Inhibitors(33). *FMK Inhibitors(11). *Next Generation Caspase Inhibitors(8) ... Pan Caspases(27)*Caspase Family Enzyme Sets(7). *Caspase Family Inhibitors & Sets(9) ...
Due to this activity caspase-1 is also known as ICE (interleukin-1-beta converting enzyme). Like other caspases it also plays a ... Caspase-1 is a protease, an enzyme that cleaves proteins. It is found predominantly in the cell cytoplasm, where it activates ... Molecular model of caspase-1 complexed with an inhibitor. ... Caspase 1 with inhibitor. C025/1626 Rights Managed. Request low ... Caption: Molecular model of caspase-1 complexed with an inhibitor. Caspase-1 is a protease, an enzyme that cleaves proteins. It ...
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These inhibit caspase-5 and may affect a variety of other apoptosis and tumor related proteins. ... Caspase-1 inhibitor VI A cell-permeable, inhibitor of caspase-1, caspase-4, and caspase-5 activity sc-3071 500 µg. $179.00 20 ... Caspase-1 Inhibitor II An inhibitor of caspase-1, caspase-4, and caspase-5 178603-78-6. sc-300323 5 mg. $250.00 0 ... Caspase-1 Inhibitor IV An inhibitor of caspase-1, caspase-4 and caspase-5 154674-81-4. sc-300324 1 mg. $180.00 0 ...
These inhibit caspase-10 and may affect a variety of other apoptosis and tumor related proteins. ... Caspase-3 Inhibitor I, Cell Permeable An inhibitor of caspase-3, caspase-6, caspase-7, caspase-8, and caspase-10 sc-3074 1 mg. ... Caspase-3 Inhibitor An inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10 210344-95-9. sc-3075 0.5 mg. $100.00 30 ... An inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10 210344-95-9. sc-311558 sc-311558A 1 mg. 5 mg. $228.00 $970.00 ...
Caspase Inhibitors Promote Vestibular Hair Cell Survival and Function after Aminoglycoside Treatment In Vivo. Jonathan I. ... Direct infusion of caspase inhibitors promotes vestibular hair cell survival. Our results demonstrate that direct infusion of ... Liu W, Staecker H, Stupak H, Malgrange B, Lefebvre P, Van De Water TR ( 1998) Caspase inhibitors prevent cisplatin-induced ... Sympathetic neurons deprived of nerve growth factor (NGF) in vitro are rescued by application of the general caspase inhibitor ...
The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques. ... The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques. ... We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV- ...
Caspase Inhibitors. Cysteine Proteinase Inhibitors. Protease Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of ... Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis (ENCORE-LF). The safety and ... A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Emricasan, an Oral Caspase Inhibitor, in Subjects With ... Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 ...
Z-VDVAD-FMK (caspase-2 inhibitor I) and Z-DEVD-FMK (caspase-3 inhibitor II) were purchased from Calbiochem. Caspase inhibitor ... The irreversible caspase inhibitors Z-VDVAD-FMK (caspse-2 inhibitor) and Z-DEVD-FMK (caspase-3 inhibitor) significantly reduced ... caspase-7, caspase-8, and caspase-10; and the ICE and CED-3 homologue (ICH)-like family, which includes caspase-2 and caspase-9 ... First, caspase inhibitors have cross actions: Z-VDVAD-FMK reduced caspase-3 activity, and Z-DEVD-FMK reduced caspase-2 activity ...
Inhibition of apoptosis and promotion of normal cell survival by caspase inhibitors would be a tremendous benefit for reducing ... The objective of this study was to discover small-molecule caspase inhibitors with which to achieve cytoprotective effect. We ... One of the compounds, RBC1023, was demonstrated to protect NIH3T3 cells from staurosporine-induced caspase-3 cleavage and ... Collectively, RBC1023 protects NIH3T3 cells against staurosporine-induced apoptosis via inhibiting caspase activity, restoring ...
Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis. Overview. *. Study type. ... Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 ...
  • We report the first stabilized α-helical peptides that harness the native regulatory mechanism of caspase-9 and the BIR3 domain which lead to the understanding of the importance of exosites in inhibitory complexes. (umass.edu)
  • The functional significance of diabetes-induced apoptosis was studied by treating diabetic mice with a pancaspase inhibitor, z-VAD-fmk ( N -benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone). (diabetesjournals.org)
  • The functional role of apoptosis in the repair process was established using a pancaspase inhibitor. (diabetesjournals.org)
  • To test for caspase dependent TH-ir cell loss, the pancaspase inhibitor ZVAD ( N -benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone) was used to rescue TH-ir cells from estradiol-mediated reduction in number. (jneurosci.org)
  • Through exploring these underlying molecular details behind the various mechanisms, not only has the field of caspase-9 regulation mechanisms been extended, essential information was gained for further pursuit in an advancement towards the design of caspase-9 activators and inhibitors. (umass.edu)
  • To investigate mechanisms by which this might occur, RNA profiling and caspase activity was measured after inoculation of Porphyromonas gingivalis . (diabetesjournals.org)
  • To better understand mechanisms by which diabetes may modulate the apoptotic process, mRNA profiling of genes that directly or indirectly affect apoptosis was undertaken, as were measurements of diabetes-enhanced caspase activity. (diabetesjournals.org)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Thus, a fuller understanding of the mechanisms involved in regulating ER stress, caspase-12 activity, and their roles in Aβ neurotoxicity would be highly desirable. (rupress.org)
  • Conclusions -OxyHb activates caspase-2 and -3 in cultured brain microvessel endothelial cells. (ahajournals.org)
  • DNA breakdown and appearance of TUNEL-positive nuclei was observed in xylogenic cultures and this was suppressed in the presence of caspase inhibitors. (ebscohost.com)
  • 5. Significant degradation was only observed when the flower draw out was buffered below pH 5, but this proteolysis could be abrogated by addition of protease inhibitors. (rmrfotoarts.com)
  • Most commonly, protease inhibitors are added to extraction buffers but these are expensive and therefore not economically viable for extraction at large level. (rmrfotoarts.com)
  • We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo , making the potency of inhibitors highly context-dependent. (biochemj.org)
  • However, lots of them are complete inhibitors that are either toxic in vivo or not tested in glioblastoma. (aacrjournals.org)
  • We recently identified a viral mitochondria-localized inhibitor of apoptosis (vMIA) encoded by the CMV immediate-early UL37 gene that protects cells from apoptosis induced by a variety of stimuli ( 2 ). (pnas.org)
  • This study was undertaken to investigate the effect of 2 caspase inhibitors, Z-VDVAD-FMK and Z-DEVD-FMK, in the protection of endothelial cells from OxyHb-induced apoptosis. (ahajournals.org)
  • Methods -Cultured bovine brain microvascular endothelial cells (passages 5 to 9) were exposed to OxyHb (10 μmol/L) for 24 to 72 hours with and without caspase inhibitors. (ahajournals.org)
  • 2) OxyHb increased caspase-2 and -3 activities, produced DNA ladders, and cleaved PARP in endothelial cells. (ahajournals.org)
  • In this study we investigated the effect of OxyHb on the activities of caspase-2 and -3 and the prophylaxis effect of caspase inhibitors on OxyHb-induced apoptosis in bovine brain microvessel endothelial cells. (ahajournals.org)
  • During treatments with caspase inhibitors and OxyHb, the cells were incubated in CS-C Medium (Cell Systems Corporation) without growth factor and with 1% (vol/vol) fetal bovine serum. (ahajournals.org)
  • Caspases play an important role in the ability of animal cells to kill themselves by apoptosis. (biochemj.org)
  • Positive staining of TUNEL, poly(ADP)-ribose polymerase (PARP), caspase-3, and caspase-8 was observed in the endothelial cells of the spastic arteries. (omicsonline.org)
  • The mechanism of apoptosis in endothelial cells involves TNFR1 and the caspase-8 and caspase-3 pathways. (omicsonline.org)
  • Our results provide a proof-of-concept that VCP inhibitors can be used as a single agent and can be synergized with compounds that enhance CHOP expression to induce cell death in ovarian cancer cells. (selleckchem.com)
  • The HDAC inhibitors vorinostat/SAHA and romidepsin/FK288 were found to induce DNA damage, and mis-repair of this damage manifested into mutations in clonogenically viable surviving cells. (springer.com)
  • Cells deficient in caspase-activated DNase (CAD) also failed to acquire DNA damage or mutations following treatment with bortezomib. (springer.com)
  • Consistently, loss of API5 sensitizes cells to caspase-2-dependent apoptotic cell death. (cam.ac.uk)
  • To analyze the effects of broad spectrum caspase inhibitors on actinomycin D-induced apoptosis in WEHI 231 cells, DNA fragmentation was analyzed after 4 h, when substantial apoptosis, in the absence of caspase inhibitors, had occurred. (apexbt.com)
  • Furthermore, DN10764 induced caspase 3/7-mediated apoptosis in breasts cancer tumor cells and inhibited pipe formation of individual umbilical vein endothelial cells. (conferencedequebec.org)
  • The caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. (apexbt.com)
  • In HeLa cells, caspase 2 bosom was readily apparent at 2-4 hpIR within the pres-ence of Go 6976. (inhibitorkits.com)
  • This effect was synergistic since neither IR nor Go 6976 alone caused substantial increases in cleaved caspase 2 levels compared to basal levels observed in get a handle on cells. (inhibitorkits.com)
  • By comparison, the levels of Doxorubicin ic50 cleaved caspase 3 in Go 6976 treated cells at 2-4 hpIR were negligible and did not differ from those observed in irradiated cells not confronted with the chemical. (inhibitorkits.com)
  • Induction of apoptosis by protease inhibitor also was detected in U937 and TF-1 leukemia cell lines and cells obtained from acute myelogenous leukemia patients but not in normal human blood monocytes. (aacrjournals.org)
  • We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
  • First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
  • We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
  • Interestingly, thapsigargin treatment enhanced caspase-4 and -9 activities in I143T-mutant PS1-transfected cells, while hydrogen peroxide treatment enhanced caspase-4, -8 and -9 activities in G384A-mutant PS1-transfected cells, indicating diverse apoptosis-promoting effects of PS1 gene mutations. (elsevier.com)
  • Further work revealed that caspase-8 was essential for the induction of the transcription factor "nuclear factor κB" ( NF-κB ) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells . (wikipedia.org)
  • 6 rodents per glioma linked cancer-initiating cells series) had been being injected in the best frontal lobes of 5C8-week-old naked rodents, the rodents created tumors that had been extremely infiltrative along white matter tracts-a quality Caspase-3/7 Inhibitor I manufacture of individual GBM (Fig. 1C). (world-of-links.com)
  • Amount 1 Portrayal of individual glioma linked cancer-initiating cells from GBM individuals Immunological phenotype of glioma linked cancer-initiating cells To define their immunological phenotype, the glioma linked cancer-initiating cells (d=5) had been evaluated for their reflection of MHC I, MHC II, Compact disc40, Compact disc80, Compact Caspase-3/7 Inhibitor I manufacture disc86, and C7-L1 by stream cytometry. (world-of-links.com)
  • It remains inactive in growing cells while it is associated with its inhibitor (ICAD, DNA fragmentation factor 45 kDa subunit, DFFA or DFF45) resulting into a complex ICAD-CAD. (wikipedia.org)
  • Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
  • Western blot analysis showed increased transcriptional activities of Fas ligand, tumor necrosis factor-α, Bax, Fas-associated death domain, and tumor necrosis factor receptor 1-associated death domain as well as elevated levels of cleaved caspases and poly(ADP-ribose) polymerase. (aacrjournals.org)
  • Histone deacetylase inhibitors modulate the transcription of target genes and represent a new class of anticancer agents. (aacrjournals.org)
  • Eckschlager T, Plch J, Stiborova M, Hrabeta J (2017) Histone deacetylase inhibitors as anticancer drugs. (springer.com)
  • Suberoylanilide hydroxamic acidity (SAHA) is one of the histone deacetylases (HDAC) inhibitors (HDACi) which represent a fresh course of anti-cancer therapeutics. (angiogenesis-blog.com)
  • BGB324 (previously referred to as R428) MLN2238 is normally a first-in-class, extremely selective small-molecule AXL inhibitor that's currently in Stage I clinical studies to assess its scientific responses in sufferers with severe myeloid lymphoma and non-small cell lung cancers (NSCLC) [3, (conferencedequebec.org)
  • Kinase inhibitors Imatinib was synthesized by Dr Alfonso Zambon. (alk-inhibitors.com)
  • SU6656, an Src family kinase inhibitor, was from Calbiochem. (alk-inhibitors.com)
  • RESULTS Id of DN10764 being a potential inhibitor of TAM family members RTKs Prior data highlighted AXL being a focus on kinase of DN10764 . (conferencedequebec.org)
  • Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex which were crucial for the induction of nuclear translocation of NF-κB. (wikipedia.org)
  • Caspases have the ability to cleave after aspartic acid residues. (abcam.cn)
  • 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)