Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
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.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
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.
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.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A 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.
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.
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.
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.
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.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
A 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.
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.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A 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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Peptides composed of between two and twelve amino acids.
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 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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
An 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.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
A 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.
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.
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.
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.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A 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.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A 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.
Established cell cultures that have the potential to propagate indefinitely.
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.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A cell line derived from cultured tumor cells.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A 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.
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.
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)
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.
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.
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.
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.
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.
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.
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.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
A 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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A 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.
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.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
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.
Elements of limited time intervals, contributing to particular results or situations.
Glycoproteins found on the membrane or surface of cells.
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.
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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.
Compounds that inhibit cell production of DNA or RNA.
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.
Proteins found in any species of virus.
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.
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.
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).
Physiologically inactive substances that can be converted to active enzymes.
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.
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.
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)
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.
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.
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.
Proteins prepared by recombinant DNA technology.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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).
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.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
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).
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.
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.
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.
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.
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.
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)
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.
Peptides composed of two amino acid units.
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.
The action of a drug in promoting or enhancing the effectiveness of another drug.
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.
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.
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.
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 of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A 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.
The family Passeridae comprised of small, mainly brown and grey seed-eating birds with conical bills.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
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.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
Proteins found in any species of insect.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A 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.
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)
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
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.
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 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.
The process of cleaving a chemical compound by the addition of a molecule of water.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
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.
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.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A 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.
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)
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
The 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.
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.
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
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)
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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 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.
A condition of decreased oxygen content at the cellular level.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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)
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)
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
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.
Organic compounds with the general formula R-NCS.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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 whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
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.
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 ...
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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 ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
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
Fingerprint Dive into the research topics of Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo. Together they form a unique fingerprint. ...
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Z-VAD-FMK is a cell-permeable pan caspase inhibitor that irreversibly binds to the catalytic site of caspases and can inhibit induction of apoptosis.
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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Caspase detection antibodies and assays are used to help detect and study caspase activation in Apoptotic cells via immunoprecipitation and immunoblotting techniques.
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TY - JOUR. T1 - Ceramide generation by the reaper protein is not blocked by the caspase inhibitor, p35. AU - Bose, Ron. AU - Chen, Po. AU - Loconti, Andrea. AU - Grüllich, Carsten. AU - Abrams, John M.. AU - Kolesnick, Richard N.. PY - 1998/10/30. Y1 - 1998/10/30. N2 - The Reaper (Rpr) gene encodes a 65-amino acid protein that induces apoptosis in Drosophila by an unknown mechanism. A previous study reported that Rpr expression induced generation of the lipid second messenger ceramide and through use of the peptide caspase inhibitor N-benzyloxycarbonyl-VAD- fluoromethylketone (zVAD.fmk) ordered ceramide generation downstream of caspases in SL2 cells (Pronk, G. J., Ramer, K., Amiri, P., and Williams, L. T. (1996) Science 271, 808-810). The present study re-evaluates these events in SL2 cells transfected with cDNA for Rpr, with or without the baculovirus caspase inhibitor p35, under the control of the metallothionein promoter. Following copper addition, Rpr protein was detected at 1.5 h and ...
Prevention of lymphocyte apoptosis by caspase inhibition has been proposed as a novel treatment approach in sepsis. However, it has not been clearly demonstrated that caspase inhibitors improve survival in sepsis models when dosed post-insult. Also, there are concerns that caspase inhibitors might suppress the immune response. Here we characterize VX-166, a broad caspase inhibitor, as a novel potential treatment for sepsis. VX-166 was studied in a number of enzymatic and cellular assays. The compound was then tested in a murine model of endotoxic shock (lipopolysaccharide (LPS), 20 mg/kg IV) and a 10 d rat model of polymicrobial sepsis by caecal ligation and puncture (CLP). VX-166 showed potent anti-apoptotic activity in vitro and inhibited the release of interleukin (IL)-1beta and IL-18. In the LPS model, VX-166 administered 0, 4, 8 and 12 h post-LPS significantly improved survival in a dose-dependent fashion (P | 0.0028). In the CLP model, VX-166 continuously administered by mini-osmotic pump
benzyloxycarbonyl-valyl-aspartic acid fluoromethyl ketone: a dipeptide caspase inhibitor with potent in vivo antiapoptotic activity
TY - JOUR. T1 - Caspases determine the vulnerability of oligodendrocytes in the ischemic brain. AU - Shibata, Mamoru. AU - Hisahara, Shin. AU - Hara, Hideaki. AU - Yamawaki, Takemori. AU - Fukuuchi, Yasuo. AU - Yuan, Junying. AU - Okano, Hideyuki. AU - Miura, Masayuki. PY - 2000/9. Y1 - 2000/9. N2 - Although oligodendrocytes (OLGs) are thought to be vulnerable to hypoxia and ischemia, little is known about the detailed mechanism by which these insults induce OLG death. From the clinical viewpoint, it is imperative to protect OLGs as well as neurons against ischemic injury (stroke), because they are the only myelin-forming cells of the central nervous system. Using the Cre/loxP system, we have established a transgenic mouse line that selectively expresses p35, a broad-spectrum caspase inhibitor, in OLGs. After hypoxia, cultured OLGs derived from wild-type mice exhibited significant upregulation of caspase-11 and substantial activation of caspase-3, which led to cell loss. Expression of p35 or ...
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:. ...
Z-VAD-FMK is a cell-permeable pan caspase inhibitor that irreversibly binds to the catalytic site of caspases and can inhibit induction of apoptosis.
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.
Q-VD-OPH,Boc-D-OPH,Z-DEVD-OPH,Z-VAD(OMe)-FMK,Z-VAD-FMK( non methylated)Boc-D-FMK,Z-DEVD-FMK,Z-IETD-FMK,Z-LEHD-FMK, Z-VEID-FMK, Z-AEVD-FMK, Z-VDVAD-FMK,Z-LEVD-FMK,Z-ATAD-FMK, Biotin-VAD-FMK, Biotin-DEVD-FMK,Z-LLY-FMK,FITC-VAD-FMK, FAM-VAD-FMK,FAM-DEVD-FMK,SR-VAD-FMK,SR-DEVD-FMK,CASPASE/ APOPTOSIS INHIBITORS
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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
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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
The preparation of this thematic proceeding came from the point of view that digital space is accepted as a huge field of challenges with...
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
During the maturation process, spermatids must eliminate most of their cytoplasm to become small, highly motile sperm with their characteristic small DNA-packed head and tail for swimming. In fruit flies, caspases contribute to the elimination of the cytoplasm in a process called individualization, which begins in the head and ends with the elimination of the cytoplasmic contents into a waste bag from the tail end. Kaplan et al. identified Scotti (abbreviated soti), in a yeast two-hybrid screen for partners of the adaptor Klhl10, which is part of the E3 ligase complex required for individualization, and confirmed this interaction by coimmunoprecipitation from transfected S2 cells. Spermatids from soti-null mutant flies failed to mature, and immunostaining for active caspase showed that the abundance of activated caspase was abnormally high and that the developing spermatids failed to generate waste bags. In flies double homozygous for soti and cullin3 (cul3) or klhl10, caspase activation ...
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.
The IUPHAR/BPS Guide to Pharmacology. Caspase 6 - 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. ...
Check out our best-in-class prices for Caspase Substrate Ac-DEVD-pNA at AG Scientific, Inc. With more than 20 years of experience in the life science industry, we can supply the chemicals you need to accelerate your scientific discoveries.
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 ...
Anti Caspase 13 Antibody product information; Anti Caspase 13 Antibody is available 3 times from supplier MyBioSource at Gentaur.com shop
Apoptosis or programmed death is a physiological process responsible for normal development and homeostasis of multicellular organisms. This process involves a well-functioning machinery of death, which are the main component of cysteine ​​proteases - caspases family. These enzymes are present in cells in a latent form and become activated during apoptosis induced by various factors. This review summarizes the progress made on structure, mechanism of activation, catalytic properties, are substrates of caspases and regulation of their activity. Also shown in the involvement of caspases in the major pathways of apoptosis.. ...
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.
Read independent reviews on Caspase Fluorometric Substrate Set II Plus from AMS Biotechnology (Archived Products) on SelectScience
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
... coli Effector Protein NleF Is a Caspase Inhibitor". PLoS ONE. 8 (3). doi:10.1371/journal.pone.0058937. PMC 3597564. PMID ... "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". ...
Lee SH, Stehlik C, Reed JC (Sep 2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 ... "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 ...
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 ...
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. 391 ( ... 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 ...
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): 20-26. 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 ...
... 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 ...
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- ... The MEROPS online database for peptidases and their inhibitors: LI27.001 Biology portal v t e. ... 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 ...
... 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; Nagata, S (January 1998). "Cleavage of CAD inhibitor in CAD ... 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 ...
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 XIAP 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 ...
"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, ...
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 ...
May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute ... The substance acts as a pan-caspase inhibitor and has antiapoptotic and antiinflammatory effects. It was developed for the ... November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal ... a liver-targeted caspase inhibitor". The Journal of Pharmacology and Experimental Therapeutics. 309 (2): 634-40. doi:10.1124/ ...
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- ...
DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in ... "Frequent nuclear localization of ICAD and cytoplasmic co-expression of caspase-8 and caspase-3 in human lymphomas". The Journal ... Liu X, Zou H, Slaughter C, Wang X (April 1997). "DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger ... McCarty JS, Toh SY, Li P (October 1999). "Study of DFF45 in its role of chaperone and inhibitor: two independent inhibitory ...
... 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 ...
This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to activate apoptosis. Due to its proapoptotic ... to inhibit their caspase-binding activity and allow for caspase activation of apoptosis. SMAC is ubiquitously expressed in many ... "A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis". Nature. 410 (6824): ... Du C, Fang M, Li Y, Li L, Wang X (2000). "Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation ...
Lee SH, Stehlik C, Reed JC (2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation ... Inohara N, del Peso L, Koseki T, Chen S, Nunez G (Jun 1998). "RICK, a novel protein kinase containing a caspase recruitment ... 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/ ...
P35 has been shown to be a caspase inhibitor with a very wide spectrum of activity both in regard to inhibited caspase types ... irreversible inhibitor of caspases. P35 first serves as a caspase substrate and is cleaved between the amino acids D87 and G88 ... Doloff JC, Su T, Waxman DJ (September 2010). "Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by ... However, unlike other caspase substrate proteins, the fragments of P35 do not dissociate from the caspase after cleavage. ...
"The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640-8. doi: ... Due to the importance of both Ras and B-Raf mutations in tumorigenesis, several Raf inhibitors were developed to combat cancer ... Unfortunately, ATP-competitive B-Raf inhibitors may have an undesired effect in K-Ras-dependent cancers: They are simply too ... McKay MM, Freeman AK, Morrison DK (2011). "Complexity in KSR function revealed by Raf inhibitor and KSR structure studies". ...
"The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640-8. doi: ... "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. 16 (23): 6914-25. doi:10.1093/emboj/16.23 ... Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751- ... ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the ...
"The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Current Biology. 10 (11): 640-8. doi ... FLIP then binds to caspase-8, forming a caspase-8 FLIP heterodimer in the cytosol that disrupts the activity of caspase-8 and ... This new complex contains the caspase-8 FLIP heterodimer as well as RIPK1 and RIPK3. Caspase inhibition within this complex ... The activation of caspase 3 and 9 by the apoptosome starts a proteolitic cascade that eventually leads to the degradation of ...
"The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640-8. doi: ... "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. 16 (23): 6914-25. doi:10.1093/emboj/16.23 ... Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751- ... Shu HB, Halpin DR, Goeddel DV (1997). "Casper is an FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751-63. ...
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 ...
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 ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... CIAPIN1: Anamorsin (originally, Cytokine induced apoptosis inhibitor 1). *CKLF: Chemokine-like factor ...
Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions ... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[30 ... BDNF is a short-term promoter,[96] but a long-term inhibitor of pain sensitivity, as a result of its effect as inducer of ... an effect that was abolished in either the presence of a specific NR2B antagonist or a trk receptor tyrosine kinase inhibitor.[ ...
HER2 kinase inhibitors, such as lapatinib, have also demonstrated clinical efficacy in HER2 overexpressing breast cancers by ... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... EGFR-specific tyrosine kinase inhibitors such as gefitinib have shown limited therapeutic success. This resistance is proposed ... "Neuregulin-1-Mediated Autocrine Signaling Underlies Sensitivity to HER2 Kinase Inhibitors in a Subset of Human Cancers". Cancer ...
... inhibitors have effective anti-tumor activity in cell culture, inducing apoptosis by disrupting the regulated ... The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... Fluorescent inhibitors have also been developed to specifically label the active sites of the assembled proteasome.[115] ... Schenkein D (June 2002). "Proteasome inhibitors in the treatment of B-cell malignancies". Clinical Lymphoma. 3 (1): 49-55. doi: ...
Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... These disorders are sometimes treated by using a TNF inhibitor. This inhibition can be achieved with a monoclonal antibody such ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... On the other hand some patients treated with TNF inhibitors develop an aggravation of their disease or new onset of ...
HDAC inhibitor (small molecule) benzamide M344 MC 19 fatty acid Sodium butyrate M (y) 5, 6, 7 ; H (ny) D (y) 11 M (y) 14; R (y ... "Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... DNA methyltransferase inhibitors, and histone demethylase inhibitors.[6][7] The majority of epigenetic drugs tested for use ... DNA-methylation inhibitor chemical analogue of cytidine Azathioprine M (ny) M (ny) ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... As well, the amino-thalidomide and amino-EM-12 were potent inhibitors of TNF-α. These two analogs later got the name ... This effect is not related to TNF-α inhibition since potent TNF-α inhibitors such as rolipram and pentoxifylline did not ... Inhibition of TNF-α is not the mechanism of thalidomide's inhibition of angiogenesis since numerous other TNF-α inhibitors do ...
Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. ... "Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis". Proceedings of the ... Caspase 3. Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl- ... Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation. *UMich Orientation of Proteins in Membranes families/superfamily-78 ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ...
... Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ... This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... protein kinase inhibitor activity. • protein kinase binding. • macromolecular complex binding. Cellular component. • cytoplasm ... "Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1)".. *^ Gartel AL, Radhakrishnan SK (May 2005). "Lost in ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... "Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury". Nature Chemical Biology. 1 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ...
a b Nikolaev A. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19. februar 2009;457(7232): ... a b Birks J. Cholinesterase inhibitors for Alzheimer's disease. The Cochrane Database of Systematic Reviews. 2006;(1):CD005593 ... The new cholinesterase inhibitors for Alzheimer's disease, part 2: illustrating their mechanisms of action. The Journal of ... Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Medicine. 2007;4(11): ...
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 ...
The MEROPS online database for peptidases and their inhibitors: C01.037. *v. *t ... Caspase. *Caspase 1. *Caspase 2. *Caspase 3. *Caspase 4. *Caspase 5. *Caspase 6 ...
Reiss AB, Wirkowski E (2007). "Role of HMG-CoA reductase inhibitors in neurological disorders: progress to date". Drugs 67 (15 ... "N-APP binds DR6 to cause axon pruning and neuron death via distinct caspases". Nature 457 (7232): 981-989. doi:10.1038/ ... Raina P, Santaguida P, Ismaila A, et al. (2008). "Effectiveness of cholinesterase inhibitors and memantine for treating ... Birks J; Birks, Jacqueline (2006). "Cholinesterase inhibitors for Alzheimer's disease". Cochrane Database Syst Rev (1): ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ...
Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see "Controlling the Caspases", by Stephen W. Fesik ... and caspases 8 and 10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... The binding of TNF to TNF-R1 has been shown to fire-off the pathway that léads to activating the caspases (see "TNF-R1 ... This results in the reléase of caspase activators, including cytochrome c (see "Bcl-2 inhibits Bax translocation from cytosol ...
"U.S. FDA Approved Immune-Checkpoint Inhibitors and Immunotherapies". Medical Writer Agency , 香港醫學作家 , MediPR , MediPaper Hong ... The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds ...
Among the inflammatory products of NALP1 are caspase 1 and caspase 7, which activate the inflammatory cytokine interleukin-1β. ... and calcineurin inhibitors (such as tacrolimus or pimecrolimus) are considered to be first-line vitiligo treatments.[1] ...
... spectrum neuroprotection profile of phosphodiesterase inhibitors as related to modulation of cell-cycle elements and caspase-3 ... Rolipram je PDE4-inhibitor. Poput većine PDE4-inhibitora, on je antiinflamatorni lek.[5] Rolipram je studiran kao mogući ... 2004). "Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications". Neuroscience 129 ( ... 2006). "Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity". Neuroscience 144 (1): 239-46 ...
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 ...
Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in assays for early apoptotic activity.[15] ... within the nucleus and degrade once there is a decrease in activity or if cells are treated with proteasome inhibitors.[29][51] ... The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin ... Cells that express mutant caspase-resistant lamins are deficient in nuclear changes related to apoptosis, suggesting that ...
Caspase-1 (Rattus norvegicus) and separase (Saccharomyces cerevisiae) CE. C5, C48, C55, C57, C63, C79. Adenain (human ... Protease inhibitors are usually proteins with domains that enter or block a protease active site to prevent substrate access. ... In non-competitive inhibition, the inhibitor binds to an allosteric site, which alters the active site and makes it ... Crystal structure of the cysteine peptidase papain in complex with its covalent inhibitor E-64. Rendered from PDB 1PE6 ...
Reiss AB, Wirkowski E (2007). "Role of HMG-CoA reductase inhibitors in neurological disorders : progress to date". Drugs. 67 ( ... "APP binds DR6 to trigger axon pruning and neuron death via distinct caspases". Nature. 457 (7232): 981-89. Bibcode:2009Natur. ... Birks J (January 2006). Birks J (ed.). "Cholinesterase inhibitors for Alzheimer's disease". The Cochrane Database of Systematic ... Five medications are currently used to treat the cognitive problems of AD: four are acetylcholinesterase inhibitors (tacrine, ...
Cholinesterase inhibitors for Alzheimer's disease». The Cochrane Database of Systematic Reviews (1): CD005593. PMID 16437532. ... APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases». Nature. 457 (7232): 981-989. ISSN 0028-0836. PMC ... Reiss AB, Wirkowski E (2007). «Role of HMG-CoA Reductase Inhibitors in Neurological Disorders: Progress to Date». Drugs. 67 (15 ... Birks J (2006). «Cholinesterase inhibitors for Alzheimer's disease». The Cochrane Database of Systematic Reviews (1): CD005593 ...
... the most notable ones being caspases 2, 3, and 9.[7] Cell death is not prevented by caspase inhibitors, or by BCL-2 or p53 ... Cells also showed decreased levels of mTOR, a known inhibitor of macroautophagy. HAMLET cells and cells under conditions of ... However, proteasome inhibition alone does not seem to be responsible for HAMLET-induced cell death, as proteasome inhibitors ... "Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET". Cancer Res. 67 (23): 11327-34. doi:10.1158/0008-5472. ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ...
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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, ...
Inhibition of both caspase-3 and caspase-8 by Z-VAD-fmk and of caspase-3 by the peptidomimetic inhibitors proceeds via two ... We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of ... We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of ... The crystal structures of inhibitor complexes of caspases-3 and -8 validate the design of the inhibitors by illustrating in ...
... 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.. ...
Caspase-7 in complex with DICA allosteric inhibitor. *DOI: 10.2210/pdb1SHJ/pdb ... The x-ray crystal structures of caspase-7 bound by either compound demonstrates that they inhibit caspase-7 by trapping a ... Caspase-7. A, B. 262. Homo sapiens. Mutation(s): 1 Gene Names: CASP7, MCH3. EC: 3.4.22 (PDB Primary Data), 3.4.22.60 (UniProt) ... Discovery of an allosteric site in the caspases. Hardy, J.A., Lam, J., Nguyen, J.T., OBrien, T., Wells, J.A.. (2004) Proc Natl ...
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 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 ...
This cysteine is also present in caspase-7, and the two inhibitors bound and inhibited the catalytic activity of both caspase-3 ... The cavity where the two inhibitors bound is also seen in other caspases, like initiator and inflammatory caspases. Thus, the ... structures of caspase-7 with the inhibitors showed that the two inhibitors bound in different orientations to the caspase but ... to identify an allosteric site inhibitor on the executioner caspases, caspase-3. Tethering, a commercial method, uses ...
... pancaspase inhibitor. Inhibits TNFα-mediated apoptosis in vitro (IC50 = 0.7 μM). Immunosuppressive, inhibits T cell ... Agonists, activators, antagonists and inhibitors. Cell lines and Lysates. Multiplex miRNA assays. Multiplex Assays. By research ... Irreversible, pancaspase inhibitor. Inhibits TNFα-mediated apoptosis in vitro (IC50 = 0.7 μM). Immunosuppressive, inhibits T ...
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 ...
We have solved the crystal structure of the caspase-9/NleF complex which shows that NleF uses a novel mode of caspase ... obtained for synthetic peptide-type inhibitors and as such deviates substantially from previously reported caspase-9 inhibitors ... Here we show that one of them, NleF, binds to caspase-4, -8, and -9 in yeast two-hybrid, LUMIER, and direct interaction assays ... NleF inhibits the catalytic activity of the caspases in vitro and in cell lysate and prevents apoptosis in HeLa and Caco-2 ...
... (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 ...
Tom OBrien on Caspase inhibitors in drug discovery, part of a collection of multimedia lectures. ... OBrien, T. (2007, October 1). Caspase inhibitors in drug discovery [Video file]. In The Biomedical & Life Sciences Collection ...
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Q-VD-Oph is a potent pan-caspase inhibitor with IC50 ranged from 25 to 400 nM for caspases 1,3,8, and 9. Q-VD-OPh can inhibits ... Caspase-3 Inhibitor) is a specific, irreversible Caspase-3 inhibitor, and also shows potent inhibition on caspase-6, caspase-7 ... caspase inhibitor with IC50 ranged from 25 to 400 nM for caspases 1,3,8, and 9. Q-VD-OPh can inhibits HIV infection.. ... caspase inhibitor with IC50 ranged from 25 to 400 nM for caspases 1,3,8, and 9. Q-VD-OPh can inhibits HIV infection. ...
... a potent and selective inhibitor of Caspase-8. Functionally validated in TNF-α-induced necroptosis cellular assays. Each lot is ... Caspase-8 inhibitor. Activation of apoptosis using Z-IETD-FMK Z-IETD-FMK is a potent small-molecule inhibitor of Caspase-8 ( ... Caspase-8 inhibitor - Z-IETD-FMK. Z-IETD-FMK. Unit size. Cat. code. Docs. Qty. Price. ... caspase-8 inhibitor). After overnight incubation, the level of HMGB1::Lucia released in the supernatant was assessed by ...
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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- ...
  • Conclusions: We provide evidence that FLIP is not simply an inhibitor of death-receptor-induced apoptosis but that it also mediates the activation of NF-κB and Erk by virtue of its capacity to recruit adaptor proteins involved in these signaling pathways. (mendeley.com)
  • This review focuses on mammalian target of rapamycin and apoptosis signaling pathways in polycystic kidney disease and the role of mammalian target of rapamycin inhibitors and apoptosis inhibitors as potential therapies to reduce cyst formation. (asnjournals.org)
  • For providing a better understanding of the mechanism of action of mTOR inhibitors and caspase/apoptosis inhibitors, the mTOR and caspase signaling pathways in normal and PKD kidneys are reviewed. (asnjournals.org)
  • Taken together, these results show that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, proapoptotic signaling pathways and induces apoptosis in U-251 cells. (aacrjournals.org)
  • Our data suggest that one should be cautious in treating apoptotic cell death just with caspase inhibitors as, despite their efficacy in preventing apoptosis, these inhibitors may trigger necrotic cell death," noted Wen-Xing Ding, PhD, Associate Professor, Department of Pharmacology, Toxicology and Therapeutics of The University of Kansas Medical Center (Kansas City). (medicalnewstoday.com)
  • Adding the caspase inhibitor ZVAD blocked early apoptotic cell death but revealed the presence of necrotic cell death at 48 hours. (medicalnewstoday.com)
  • Plant proteases with functional similarity to proteases involved in mammalian apoptotic cell death (caspases) are suggested as an integral part of the core mechanism of most PCD responses in plants, but participation of plant caspase-like proteases in TE PCD has not yet been documented. (ebscohost.com)
  • Exposure to both drug classes stimulated caspase activation consistent with apoptotic cell death. (springer.com)
  • Caspases are key enzymes responsible for mediating apoptotic cell death. (cam.ac.uk)
  • Consistently, loss of API5 sensitizes cells to caspase-2-dependent apoptotic cell death. (cam.ac.uk)
  • Caspases are proteases that initiate and execute apoptotic cell death. (staffs.ac.uk)
  • We screened a library of 10,000 thiol-containing compounds against accessible cysteines of two members of the caspase family of proteases, caspase-3 and -7. (rcsb.org)
  • Background -Z-Val-Ala-Asp(OMe)-CH 2 F (ZVAD-fmk), a tripeptide inhibitor of the caspase interleukin-1β-converting enzyme family of cysteine proteases, may reduce myocardial reperfusion injury in vivo by attenuating cardiomyocyte apoptosis within the ischemic area at risk. (ahajournals.org)
  • Apoptosis requires the action of various classes of proteases, including a family of cysteine proteases known collectively as the caspases. (ahajournals.org)
  • A cleavage-site-directed inhibitor of interleukin 1 β-converting enzyme-like proteases inhibits apoptosis in primary cultures of rat hepatocytes. (springer.com)
  • However, caspases are members of the clan of cysteine proteases designated CD, which also includes animal and plant legumains, and the bacterial proteases clostripain, gingipain-R and gingipain-K. Since these proteases have been proposed to have a common mechanism and evolutionary origin, we hypothesized that the caspase inhibitors may also regulate these other proteases. (biochemj.org)
  • Our data indicate that the virally encoded caspase inhibitors have adopted a mechanism that allows them to regulate disparate members of clan CD proteases. (biochemj.org)
  • Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type proteinase inhibitor that acts against a wide range of serine proteases through their nonproductive interaction with a P 1 residue in its first Kunitz-type domain ( 4 ). (aacrjournals.org)
  • P49 and P35 are two baculovirus-encoded apoptotic suppressors that function by inhibiting a broad range of the cell death proteases known as caspases ( 2 , 3 , 19 , 30 , 40 , 45 ). (pubmedcentralcanada.ca)
  • The caspases are a family of cysteinyl aspartate-specific proteases that are critical effectors of apoptosis in metazoans (reviewed in references 15 , 23 , 32 , and 33 ). (pubmedcentralcanada.ca)
  • The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. (nature.com)
  • Caspases, key mediators of apoptosis, are a structurally related family of cysteine proteases that cleave their substrates at aspartic acid residues either to cause cell death or to activate cytokines as part of an immune response. (edu.au)
  • We examined the temporal profile of apoptosis after fluid percussion-induced traumatic brain injury (TBI) in rats and investigated the potential pathophysiological role of caspase-3-like proteases in this process. (jneurosci.org)
  • Together, these results implicate caspase-3-like proteases in neuronal apoptosis induced by TBI and suggest that the blockade of such caspases can reduce post-traumatic apoptosis and associated neurological dysfunction. (jneurosci.org)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Caspases are the proteases responsible for dismantling the cell in an ordered and histologically distinct process termed apoptosis [ 1 ]. (mdpi.com)
  • Caspases are the most extensively studied proteases that are activated during STA-9090 nmr apoptosis. (egfr-inhibitor.com)
  • Caspases are cysteine proteases, expressed as inactive precursors, that mediate apoptosis by proteolysis of specific substrates. (abcam.cn)
  • Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue (LEVD-), and belongs to a family of cysteine proteases called caspases. (wikipedia.org)
  • Kinetic studies of caspase-3 and caspase-8 inhibition were carried out with these urazole ring-containing irreversible peptidomimetics and a known irreversible caspase inhibitor, Z-VAD-fmk. (rcsb.org)
  • Z-LEHD-FMK is a cell-permeable, competitive and irreversible inhibitor of enzyme caspase-9 , which helps in cell survival. (selleckchem.com)
  • Irreversible, pancaspase inhibitor. (abcam.com)
  • A potent, cell-permeable, and irreversible inhibitor of caspase-8 and granzyme B. Effectively inhibits influenza virus-induced apoptosis in HeLa cells. (alfa.com)
  • Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor. (adooq.com)
  • A potent, irreversible inhibitor of caspase-9. (merckmillipore.com)
  • FMK inhibitors are irreversible and non-toxic, and can be used in both in vivo and in vitro studies. (antibody-antibodies.com)
  • Irreversible, cell permeable, broad spectrum caspase inhibitor. (hellobio.com)
  • Irreversible and selective caspase 3 inhibitor (IC 50 = 0.13 µM). (hellobio.com)
  • Irreversible Caspase-9 inhibitor. (apexbt.com)
  • Z-LEHD-FMK Irreversible Caspase-9 inhibitor. (apexbt.com)
  • Z-LEHD-FMK is a specific and irreversible inhibitor of caspase-9 [1]. (apexbt.com)
  • Q-VD-OPh prevents caspase mediated cleavage of PARP and activation of the major initiator and effector caspases. (selleckchem.com)
  • 3) Z-VDVAD-FMK and Z-DEVD-FMK (100 μmol/L) attenuated OxyHb-induced cell detachment, reduced caspase-2 and -3 activities, abolished OxyHb-induced DNA ladders, and prevented OxyHb-induced cleavage of PARP. (ahajournals.org)
  • One of the compounds, RBC1023, was demonstrated to protect NIH3T3 cells from staurosporine-induced caspase-3 cleavage and activation. (dovepress.com)
  • In contrast, aldehyde inhibitor potency shows a distinct relationship to pNA substrate cleavage. (nih.gov)
  • This effect is associated with stimulation of apoptosis, through the proteolyetic cleavage death effects of caspase-8, 3 and PARP. (aacrjournals.org)
  • A high local concentration of caspase 8 zymogens is thought to facilitate self-processing and cleavage to the active enzyme ( 34 ). (asm.org)
  • Activated caspase 8 then initiates apoptosis by cleavage of the downstream effector caspases 3, 6, and 7 ( 10 ). (asm.org)
  • At this membrane-bound complex, called the death-inducing signaling complex, autolytic cleavage of pro-caspase-8 into active caspase-8 occurs ( 5 ). (aacrjournals.org)
  • 4E-BP1 undergoes caspase-dependent cleavage in cells undergoing apoptosis. (asm.org)
  • We report here that P49 and P35 use similar mechanisms for stoichiometric inhibition that require caspase cleavage of their reactive site loops (RSL) and chemical contributions of a conserved N-terminal cysteine to stabilize the resulting inhibitory complex. (pubmedcentralcanada.ca)
  • Caspase-mediated proteolysis promotes cellular disassembly that includes chromatin condensation, nuclear DNA cleavage, membrane blebbing, and cell fragmentation. (pubmedcentralcanada.ca)
  • Subsequently, the effector caspases are activated by initiator caspase-mediated cleavage of their inactive zymogen (procaspase) form. (pubmedcentralcanada.ca)
  • In muscle differentiation similar low level activation of caspase-3 signals differentiation by cleaving ICAD, releasing CAD, which executes a limited DNA cleavage and genetic reprograming of the cells. (arvojournals.org)
  • Cleavage of heterogeneous nuclear ribonucleoprotein A1 by caspase 3. (hellobio.com)
  • Ac-DEVD-CHO is a synthetic tetrapeptide competitive inhibitor for Caspase-3/7, and contains the amino acid sequence of the PARP cleavage site. (genetargetsolutions.com.au)
  • These caspase-dependent events are caused by cleavage of specific substrates that propagate the proapoptotic signal. (staffs.ac.uk)
  • Many of these techniques use molecules that are based on optimal peptide motifs for each caspase and on our understanding of caspase cleavage events that occur during apoptosis. (staffs.ac.uk)
  • Furthermore, caspase cleavage does not take into account the different caspase activation mechanisms. (staffs.ac.uk)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • vICA inhibits Fas-mediated apoptosis by binding to the pro-domain of caspase-8 and preventing its activation. (pnas.org)
  • The UL36 gene product inhibits a more proximal event in Fas-mediated apoptosis by complexing with pro-caspase-8 in a way that suppresses its proteolytic activation, prompting its designation as viral inhibitor of caspase-8-induced apoptosis (vICA). (pnas.org)
  • We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). (jci.org)
  • A synthetic peptide that irreversibly inhibits FLICE and related protease/caspase activity and blocks apoptosis. (creative-enzymes.com)
  • Inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM). (adooq.com)
  • A synthetic peptide inhibitor that inhibits caspase-13 and related caspase activity. (antibody-antibodies.com)
  • Interestingly, recombinant API5 directly inhibits full length but not processed caspase-2. (cam.ac.uk)
  • Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. (biochemj.org)
  • Radiation induces caspase activation fundamentally via the mitochondrial pathway. (sigmaaldrich.com)
  • These findings suggest that FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway rather than the death receptor pathway. (aacrjournals.org)
  • Apoptosis is mainly mediated by a family of caspases, with two pathways leading to caspase activation: the death receptor pathway and the mitochondrial pathway ( 7 ). (aacrjournals.org)
  • The death receptor pathway is initiated by ligations of transmembrane death receptors such as the Fas receptor, which activates caspase-8 and subsequently effector caspase-3. (aacrjournals.org)
  • Here, we showed that FR901228 induced caspase-dependent apoptosis through the mitochondrial pathway, accompanied by decreased BCL-2 and BCL-XL expression in SCLC cell lines. (aacrjournals.org)
  • The key constituent in the mitochondrial pathway is the efflux of cytochrome c from mitochondria to the cytosol, where it subsequently forms a complex (apoptosome) with Apaf-1 and caspase-9, activating other caspases including caspase-3 and -7 ( 17 ). (spandidos-publications.com)
  • Tissue factor pathway inhibitor-2 (TFPI-2) is a protease inhibitor that is abundant in the extracellular matrix and highly expressed in noninvasive cells but absent or undetectable in highly invasive human glioblastoma cells. (aacrjournals.org)
  • In this study, we determined whether TFPI-2 restoration could induce apoptosis through the caspase-mediated signaling pathway. (aacrjournals.org)
  • Expression of death receptor pathway inhibitor cellular FLICE inhibitory protein (cFLIP), initiator caspase-8, and granzyme B inhibitor protease inhibitor-9 (PI-9) have been reported to determine susceptibility to cell- and chemotherapy-mediated killing in several tumor types. (aacrjournals.org)
  • The expression patterns of cFLIP, caspase-8, and the absence of PI-9 provide a rationale to preferentially exploit the perforin/granzyme pathway in cytotoxic therapies against Ewing sarcoma. (aacrjournals.org)
  • Protein Kinase C Inhibitor and Irradiation-induced Apoptosis: Relevance of the Cytochrome c-mediated Caspase-9 Death Pathway -- Rocha et al. (aacrjournals.org)
  • Apoptosis of NG108-15 cells induced by buprenorphine hydrochloride occurs via the caspase-3 pathway. (hellobio.com)
  • We observed that Imatinib caused a rapid nuclear Caspase Pathway to cytosolic shift of b catenin, with decrease in Y phospho b catenin, thus indicating that Bcr Abl could control both b catenin nuclear import/export and its cytoplasmic degradation. (alk-inhibitors.com)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • Caspase-9 is an initiator caspase and plays an important role in the mitochondrial death pathway. (apexbt.com)
  • We demonstrate that the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) prevented hippocampal neuronal cell death and white blood cell influx into the cerebrospinal fluid compartment in experimental pneumococcal meningitis. (nih.gov)
  • Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties[J]. Apoptosis, 2003, 8(4): 345-352. (apexbt.com)
  • Q-VD-OPh (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone) is a broad spectrum caspase inhibitor, provides a cost effective, non toxic, and highly specific means of apoptotic inhibition and provides new insight into the design of new inhibitors. (apexbt.com)
  • The crystal structures of inhibitor complexes of caspases-3 and -8 validate the design of the inhibitors by illustrating in detail how they mimic peptide substrates. (rcsb.org)
  • Many designated substrates and inhibitors have been widely used to investigate the roles of caspases in apoptotic death during mammalian cell culture. (nih.gov)
  • However, the specificities of these substrates and inhibitors have not been systematically evaluated. (nih.gov)
  • In this study, the interaction between seven commercially available human caspases and their designated substrates and inhibitors was studied. (nih.gov)
  • All other substrates tested demonstrate cross-reactivity with several caspases. (nih.gov)
  • Caspase-3 and -7 cleave three substrates efficiently. (nih.gov)
  • They can be controlled upstream by the regulation of signals that lead to zymogen activation, or downstream by inhibitors that prevent them from reaching their substrates. (edu.au)
  • Emricasan has shown specificity in assays measuring caspase inhibition, and reduced apoptosis in a variety of cellular assays. (bio-medicine.org)
  • Fluoromethylketone (fmk) inhibitors exhibit no specificity towards different caspases even at low concentrations. (nih.gov)
  • The molecular basis of this novel caspase specificity is unknown. (pubmedcentralcanada.ca)
  • We tested the role of the P 4 -P 1 recognition motif for caspase specificity by monitoring virus-induced proteolytic processing of Sf-caspase-1, the principal effector caspase of the host insect Spodoptera frugiperda . (pubmedcentralcanada.ca)
  • In contrast, the effector caspase specificity of P35 was unaltered when P35's DQMD motif was replaced with TVTD. (pubmedcentralcanada.ca)
  • Our findings demonstrate a critical role for the P 4 -P 1 recognition site in caspase specificity by P49 and P35 and indicate that additional determinants are involved in target selection. (pubmedcentralcanada.ca)
  • Because selective inhibition of caspases may be advantageous in therapeutics for apoptosis-associated diseases, the molecular basis of target specificity by P49 and P35 is of considerable interest. (pubmedcentralcanada.ca)
  • The substrate specificity of initiator caspases differs from that of effector caspases, due in part to their unique functions during execution of apoptosis ( 37 ). (pubmedcentralcanada.ca)
  • Recently, probes having greater specificity for individual caspases have been developed and are being used successfully. (staffs.ac.uk)
  • This introduction provides background on the various caspases and introduces a set of complementary techniques to examine the activity, substrate specificity, and activation status of caspases from in vitro or cell culture experiments. (staffs.ac.uk)
  • Many acute and chronic liver diseases, including alcoholic hepatitis , result from apoptotic (programmed) cell death mediated by the enzyme caspase. (medicalnewstoday.com)
  • Caspase-1 is a protease, an enzyme that cleaves proteins. (sciencephoto.com)
  • Due to this activity caspase-1 is also known as ICE (interleukin-1-beta converting enzyme). (sciencephoto.com)
  • Our Enzyme Inhibitor portfolio includes inhibitors for caspases, calpain, kinases, granzyme as well as other useful molecules used in e.g. cancer, angiogenesis and stem cell research. (promocell.com)
  • Furthermore, an interaction was discovered between CARD and the catalytic core of caspase-9 in the presence of a properly formed substrate binding groove, a potential mechanism utilized by the apoptosome for activation of the enzyme. (umass.edu)
  • All in all, the regulation of caspase-9 occurs on a variety of levels that requires almost every surface of the enzyme. (umass.edu)
  • In relation to the enzyme, Caspase-2 is the most specific caspase, followed by caspase-9 and -6. (nih.gov)
  • Antón Barreiro-Iglesias and Michael I. Shifman, "Use of Fluorochrome-Labeled Inhibitors of Caspases to Detect Neuronal Apoptosis in the Whole-Mounted Lamprey Brain after Spinal Cord Injury," Enzyme Research , vol. 2012, Article ID 835731, 7 pages, 2012. (hindawi.com)
  • The agents being tested in these clinical trials include the vasopressin V-2 receptor antagonist tolvaptan, octreotide (somatostatin), mammalian target of rapamycin (mTOR) inhibitors (sirolimus, everolimus), renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers), statins, and high- and low-salt diets (see http://www.clinicaltrials.gov and http://www.pkdcure.org ). (asnjournals.org)
  • The anti-inflammatory drug indoprofen is an inhibitor of the activity of the caspase-4 enzyme. (wikipedia.org)
  • Z-VAD-fmk and the peptidomimetic inhibitors inhibit caspase-3 and caspase-8 via a three-step kinetic mechanism. (rcsb.org)
  • The x-ray crystal structures of caspase-7 bound by either compound demonstrates that they inhibit caspase-7 by trapping a zymogen-like conformation. (rcsb.org)
  • Caspase-5 Inhibitors offered by Santa Cruz inhibit caspase-5 and, in some cases, other apoptosis and tumor related proteins. (scbt.com)
  • Although related, P49 and P35 inhibit initiator and effector caspases, respectively, during infection of permissive insect cells. (pubmedcentralcanada.ca)
  • Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation. (ucdenver.edu)
  • Q-VD-OPh is equally effective at inhibiting the three major apoptotic pathways, it can inhibit recombinant caspases 1, 3, 8, and 9 with IC50 values ranging from 25 to 400 nM2. (apexbt.com)
  • Ac-DEVD-CHO can be used to inhibit Caspase-3/7 activity in apoptotic cells, and to study events downstream of Caspase-3/7 activation. (genetargetsolutions.com.au)
  • The result showed that Z-LEHD-FMK could significantly inhibit the activation of Caspase-3 induced by Drug A, which indicated that activation of Caspase-3 induced by Drug A is Caspase-9 dependent. (apexbt.com)
  • Caspase-9 and caspase-3 activity assays showed increased activity, indicating enhanced apoptosis. (aacrjournals.org)
  • These results suggest that combination treatment of radiation with selective COX-2 inhibitor improve the therapeutic efficacy of irradiation in NSCLC by down-regulation of anti-apoptotic signal and up-regulation of apoptotic signal including caspase activation. (aacrjournals.org)
  • Results: Under conditions in which proliferation of CD3-activated human T lymphocytes is increased by recombinant FasL, there was activation of the transcription factors NF-κB and AP-1 and recruitment of the caspase-8 inhibitor and FADD-interacting protein FLIP (FLICE-like inhibitory protein). (mendeley.com)
  • 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. (biochemj.org)
  • Based on known mechanisms, such as the unique inhibitory complex of caspase-9 and XIAP-BIR3, development of synthetic regulators can be envisioned, while other mechanisms such as zinc-mediated inhibition and CARD activation of caspse-9 remain undefined. (umass.edu)
  • 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 site in p35, required for inhibition of gingipain-K, was mapped to Lys 94 , seven residues C-terminal to the caspase inhibitory site. (biochemj.org)
  • When P49's TVTD recognition motif was replaced with P35's DQMD motif, P49 was impaired for inhibition of the initiator caspase that cleaves and activates pro-Sf-caspase-1 and instead formed a stable inhibitory complex with active Sf-caspase-1. (pubmedcentralcanada.ca)
  • By interfering with caspase-8 activation, vICA functions in a manner similar to the viral and cellular FLIPs ( 8 ), but lack of any sequence homology suggests that this CMV death suppressor may represent a new class of viral and potentially cellular antiapoptotic proteins. (pnas.org)
  • Richter and Duckett review the recently discovered and characterized inhibitors of apoptosis proteins (IAPs). (sciencemag.org)
  • Caspase family members function as key components of the apoptotic machinery and act to destroy specific target proteins which are critical to cellular longevity. (scbt.com)
  • 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. (biochemj.org)
  • Subsequently, the intracellular death domains of these death receptors attract adaptor proteins that, in turn, recruit the proform of caspase-8. (aacrjournals.org)
  • Upon apoptotic signaling, initiator caspases are autoactivated through interactions of their N-terminal prodomain with specific adaptor proteins ( 1 , 31 , 35 , 42 ). (pubmedcentralcanada.ca)
  • By cleaving critical proteins, caspases lead to the changes that characterize apoptosis both morphologically and biochemically, such as chromatin condensation, loss of cell adhesion, cell shrinkage, membrane blebbing, DNA fragmentation, and finally formation of apoptotic bodies, which stimulate their own engulfment by phagocytes. (mdpi.com)
  • As apoptosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors might provide a new therapeutic option directed specifically at reducing brain damage. (nih.gov)
  • Caspase inhibitors have therapeutic potential to treat and prevent apoptosis-mediated liver injury, and some are currently in clinical trials. (medicalnewstoday.com)
  • Therefore it remains important to gain a detailed understanding of the mechanisms behind native caspase-9 regulatory pathways and harness these mechanisms for therapeutic purposes. (umass.edu)
  • We tested the therapeutic effect of caspase inhibitors on endothelial apoptosis and on cerebral vasospasm in an established dog double-hemorrhage model. (omicsonline.org)
  • Not surprisingly, because of their central role in cell death, both types of caspases are important therapeutic targets for the treatment of apoptosis-associated diseases ( 11 , 23 ). (pubmedcentralcanada.ca)
  • Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. (nature.com)
  • Collectively, RBC1023 protects NIH3T3 cells against staurosporine-induced apoptosis via inhibiting caspase activity, restoring mitochondrial membrane potential, and possibly upregulating some cell survival-related gene expressions and pathways. (dovepress.com)
  • Anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop. (nih.gov)
  • Cytochrome c functions with Apaf-1 to activate caspase-9, thereby promoting the activation of effector caspase-3. (aacrjournals.org)
  • Upon activation of Fas by its ligand, the DD undergoes homotypic interaction with a DD in the adaptor protein FADD, which then recruits the initiator caspase 8 via their mutual N-terminal death effector domains (DED) ( 3 ). (asm.org)
  • Activated initiator caspases then process effector caspases, such as Caspase 3 and Caspase 7, which in turn cause cell collapse. (abcam.cn)
  • TIMP3-induced apoptosis was associated with activation of caspases, up-regulation of bax/Bcl2 ratio and inhibition of tyrosine phosphorylation of FAK, association with paxillin and focal adhesion formation on matrix. (arvojournals.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)
  • 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)
  • Controlling apoptosis by inhibition of caspases. (invivogen.com)
  • At first, we postulated to suppress neuronal death by inhibition of caspases. (nii.ac.jp)
  • Inhibition of caspases can delay apoptosis, implicating a potential role in drug screening efforts. (creativebiomart.net)
  • Inhibition of caspases protected cells from bortezomib-induced acute (but not clonogenic) death and mutagenesis, implying caspases were required for the mutagenic action of bortezomib. (springer.com)
  • Although vICA is dispensable for viral replication in vitro , the common targeting of caspase-8 activation by diverse herpesviruses argues for an important role for this antiapoptotic mechanism in the pathogenesis of viral infection in the host, most likely in avoiding immune clearance by cytotoxic lymphocytes and natural killer cells. (pnas.org)
  • ZVAD-fmk (fluoro-methylketone), a tripeptide inhibitor of the caspase, is reported to attenuate cardiomyocyte apoptosis in vitro. (ahajournals.org)
  • These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro , yet fails to block caspase-9-mediated cell death. (biochemj.org)
  • Both in vitro and in vivo studies suggest that caspase or apoptosis inhibition attenuates cyst formation. (asnjournals.org)
  • The caspase 8 inhibitor c-FLIP L can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). (asm.org)
  • Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. (nature.com)
  • A number of techniques have been developed to follow caspase activity in vitro and from apoptotic cellular extracts. (staffs.ac.uk)
  • A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. (invivogen.com)
  • 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)
  • However, caspase-8 inhibition by the peptidomimetics goes through a rapid equilibrium step, a slow-binding reversible step, and an extremely slow inactivation step. (rcsb.org)
  • The C-terminal DEVD-CHO sequence of this peptide is a highly specific, potent, and reversible inhibitor of caspase-3 (K i 50 = 200 pM). (merckmillipore.com)
  • A potent, specific, and reversible inhibitor of caspase-1 (K i = 200 pM for human recombinant caspase-1), caspase-4, and caspase-5. (emdmillipore.com)
  • The objective of this study was to discover small-molecule caspase inhibitors with which to achieve cytoprotective effect. (dovepress.com)
  • Caspases are enzymes responsible for executing apoptotic pathways, or programmed cell death and are also involved in processing cytokines involved in inflammation. (bio-medicine.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)
  • We now demonstrate that culture of Ras-transformed cells in the presence of the farnesyltransferase inhibitor (FTI) LB42722 leads to up-regulation of Fas expression, both under basal growth conditions and in the presence of the inflammatory cytokines IFN-γ and tumor necrosis factor α. (aacrjournals.org)
  • There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. (mdpi.com)
  • These data seem to question a general tumor-suppressive role of caspases. (mdpi.com)
  • 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)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. (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)
  • 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)
  • These results establish API5/AAC-11 as a direct inhibitor of caspase-2 and shed further light onto mechanisms driving the activation of this poorly understood caspase. (cam.ac.uk)
  • 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)
  • THP1-HMGB1-Lucia™ cells were incubated with recombinant human TNF-α (100 ng/ml), BV6 (cIAP inhibitor, 5 µM), and increasing concentrations of Z-IETD-FMK (caspase-8 inhibitor). (invivogen.com)
  • Active caspase-3 cleaves the synthetic substrate to release free AFC which can then be quantified by fluorometry. (creativebiomart.net)
  • Caspase-9 is activated during programmed cell death and cleaves procaspase-7 and procaspase-3. (apexbt.com)
  • Caspase 9 is involved in the caspase activation cascade responsible for apoptosis execution and cleaves/activates Caspase 3 and Caspase 6. (abcam.cn)
  • Because of their central role in programmed cell death, the caspases are attractive targets for developing new therapeutics against cancer and autoimmunity, myocardial infarction and ischemic damage, and neurodegenerative diseases. (rcsb.org)
  • Like other caspases it also plays a role in apoptosis (programmed cell death), but only when over-expressed. (sciencephoto.com)
  • 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)
  • The cell plugs were then irradiated, incubated to allow them to repair, and evaluated by PFGE, caspase-3, and histone H2AX activation (γH2AX). (biomedcentral.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)
  • SAN DIEGO and EDMONTON, Alberta, July 19, 2012 /PRNewswire/ -- Conatus Pharmaceuticals Inc. and the University of Alberta announced today the treatment of the first patient in an investigator-initiated islet cell transplant Phase I/II trial of emricasan (IDN-6556), a pan-caspase inhibitor. (bio-medicine.org)
  • Emricasan is a novel small molecule inhibitor of activated caspases. (bio-medicine.org)
  • Here, we tested the hypothesis that emricasan, a pan-caspase inhibitor, ameliorates PHT and reduction in release of MPs. (springer.com)
  • Although effective in preventing apoptosis, caspase inhibitors may lead to necrotic cell death, according to a report in The American Journal of Pathology . (medicalnewstoday.com)
  • 1] It is significantly more effective in preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk. (apexbt.com)
  • Q-VD-OPh is also equally effective in preventing apoptosis mediated by the three major apoptotic pathways, caspase 9/3, caspase 8/10, and caspase 12. (apexbt.com)
  • 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)
  • The caspase inhibitors, that is, ICE-like protease inhibitors, 11 interfere with apoptosis at a point subsequent to the initiation of the proapoptotic process in cells that have already received apoptosis-promoting signals. (ahajournals.org)
  • As opposed to reducing the exposure of cardiomyocytes to injurious stimuli, apoptosis of these cells is attenuated through modulation of the caspase-related proapoptotic process, and this may allow ischemic myocardium to survive even after receiving significant injury. (ahajournals.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)
  • Conclusions -OxyHb activates caspase-2 and -3 in cultured 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)
  • Control cells received 1.0% DMSO in the cell density study and DNA ladder and 0.5% DMSO in the caspase activity study and Western blot study. (ahajournals.org)
  • As a result, conclusions on the roles of specific caspases in apoptotic cells have been published inaccurately. (nih.gov)
  • 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)
  • In the present study, the effects of exogenous H2O2 on cell growth and death in HeLa cervical cancer cells were investigated, and the anti-apoptotic effects of various caspase (pan-caspase, caspase-3, -8 or -9) inhibitors on H2O2-treated HeLa cells were also evaluated with regard to reactive oxygen species (ROS) and glutathione (GSH) levels. (spandidos-publications.com)
  • H2O2 decreased the GSH level in HeLa cells at 1 h, and several caspase inhibitors attenuated the decreased level of GSH at this time. (spandidos-publications.com)
  • Caspase inhibitors are suggested to suppress H2O2-induced oxidative stress to rescue HeLa cells at the early time point of 1 h. (spandidos-publications.com)
  • In contrast, activation-induced cell death of T cells in c-FLIP L Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. (asm.org)
  • When we investigated the relationship between nuclear morphology and activities of caspases (caspase 1,2,3,6,9) in cultured cells, SHSY5Y, we found a clear discrepancy. (nii.ac.jp)
  • 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)
  • DNA damage and mutations were also detected in cells treated with the proteasome inhibitor bortezomib. (springer.com)
  • Cells deficient in caspase-activated DNase (CAD) also failed to acquire DNA damage or mutations following treatment with bortezomib. (springer.com)
  • Wedelolactone induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt. (medchemexpress.com)
  • Caspase-2 requires dimerization for its activation which is primarily accomplished by recruitment to high molecular weight protein complexes in cells. (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)
  • 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)
  • 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)
  • Manasanch EE, Orlowski RZ (2017) Proteasome inhibitors in cancer therapy. (springer.com)
  • Tight regulation of caspase-9, a key initiator of apoptosis, is required to uphold cellular homeostasis. (umass.edu)
  • Caspase 3 is responsible for cellular differentiation, although it is unclear how this kind of protein can promote the cell apoptosis. (wikipedia.org)
  • The Caspase-3 Inhibitor I, Cell-Permeable controls the biological activity of Caspase-3. (merckmillipore.com)
  • The Caspase-9 Inhibitor III, also referenced under CAS 403848-57-7, controls the biological activity of Caspase-9. (merckmillipore.com)
  • The Caspase-1 Inhibitor I, also referenced under CAS 143313-51-3, controls the biological activity of Caspase-1. (emdmillipore.com)
  • To advance strategies for selective inhibition of the cell death caspases, we investigated biochemical differences between these baculovirus substrate inhibitors. (pubmedcentralcanada.ca)
  • An exclusive from Hello Bio, Cmpd101 is a novel, potent, selective G-protein coupled receptor kinase 2 and 3 inhibitor. (hellobio.com)
  • Z-IETD-FMK is a potent small-molecule inhibitor of Caspase-8 (CASP-8) [1,2]. (invivogen.com)
  • In a rat model for myocardial reperfusion injury, infarct size and the appearance of presumed apoptotic cardiomyocytes were assessed in two groups that were or were not administered this protease inhibitor. (ahajournals.org)
  • Caspase activity is regulated in vivo by members of three distinct protease inhibitor families, two of which, baculovirus p35 and members of the inhibitor of apoptosis (IAP) family, are thought to be caspase specific. (biochemj.org)
  • Background: Activation of Fas (CD95) by its ligand (FasL) rapidly induces cell death through recruitment and activation of caspase-8 via the adaptor protein Fas-associated death domain protein (FADD). (mendeley.com)
  • However, a new study published in The American Journal of Pathology raises serious safety concerns regarding the clinical use of caspase inhibitors by demonstrating the occurrence of delayed-onset necrotic, non-caspase-dependent liver cell injury. (medicalnewstoday.com)
  • A liver cell can die in many different ways, but caspase-dependent apoptosis and caspase-independent necrosis are the predominant cell death pathways that contribute to liver injury," explained Dr. Ding. (medicalnewstoday.com)
  • Although blocking caspase protected against endotoxin-induced liver injury at an early time point (six hours), this protection was lost after 24 hours due to the switch of liver cell apoptosis to necrosis. (medicalnewstoday.com)
  • CASP-8 plays a key role in regulated cell death, acting as an initiator of apoptosis but an inhibitor of necroptosis [2-4]. (invivogen.com)
  • Cell attachment, DNA ladder, Western blotting of poly(ADP-ribose) polymerase (PARP), and caspase activities were measured to confirm the cytotoxic effect of OxyHb and the protective effect of the caspase inhibitors. (ahajournals.org)
  • Inhibition of apoptosis and promotion of normal cell survival by caspase inhibitors would be a tremendous benefit for reducing the side effects of cancer therapy and for control of neurodegenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. (dovepress.com)
  • Specific inhibitors of these enzymes are newly available tools which can be used to test for their participation in particular physiological and experimental cell death systems (Henkart, 1996). (springer.com)
  • Fas-induced activation of the cell death-related protease CPP-32 is inhibited by Bcl-2 and by ICE family protease inhibitors. (springer.com)
  • To test this hypothesis, combinations of Z-DEVD (caspase-3 inhibitor), RAD001 (mTOR inhibitor) and irradiation were tested in cell and mouse models. (nih.gov)
  • Apoptosis-inducing factor (AIF) and leukocyte elastase inhibitor/L-DNase II (LEI/LDNaseII), can interact to conduct caspase-independent cell death. (sigmaaldrich.com)
  • Lot of work has been performed to characterize the caspase-dependent cell death. (sigmaaldrich.com)
  • Caspase-independent cell death, although important in many physiological situations, is less investigated. (sigmaaldrich.com)
  • In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and leukocyte elastase inhibitor derived DNase II interact and can cooperate to induce cell death. (sigmaaldrich.com)
  • Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8. (alfa.com)
  • Conclusions: To the best of our knowledge this is the first report showing that caspase inhibitors can modulate the process of trans-differentiation in Zinnia xylogenic cell cultures. (ebscohost.com)
  • As caspase inhibitors are closely associated with cell death inhibition in a variety of plant systems, this suggests that the altered TE formation results from suppression of PCD. (ebscohost.com)
  • The inhibitor is designed as a methyl ester to facilitate cell permeability. (creative-enzymes.com)
  • Caspase inhibitors significantly prevented H2O2-induced HeLa cell death. (spandidos-publications.com)
  • Ewing sarcoma cell lines ( n = 8) were tested for cFLIP, PI-9, and caspase-8 expression. (aacrjournals.org)
  • Although all tested Ewing sarcoma cell lines expressed cFLIP, resistance to CD95/Fas-mediated apoptosis was only observed in two cell lines lacking caspase-8 expression. (aacrjournals.org)
  • A cell-permeable inhibitor of caspase-3, as well as caspase-6, caspase-7, caspase-8, and caspase-10. (merckmillipore.com)
  • A 5 mM (1 mg/100 µl) solution of Caspase-3 Inhibitor I, Cell-permeable (Cat. (merckmillipore.com)
  • Although related to one another, P49 and P35 display different caspase specificities in the infected insect cell ( 21 , 22 , 45 ). (pubmedcentralcanada.ca)
  • We recommend using 1000-5000X dilutions for inhibiting caspase-6 activity in Jurkat cell culture (e.g. (antibody-antibodies.com)
  • Apart from cell death, caspase-2 also regulates autophagy, genomic stability and ageing. (cam.ac.uk)
  • The effectiveness of Q-VD-OPh as an apoptotic inhibitor is evidenced by the complete suppression of an apoptotic inducer capable of inducing substantial cell death in less than 4 hours. (apexbt.com)
  • Involvement of caspase-3-like protease in the mechanism of cell death following focally evoked limbic seizures. (hellobio.com)
  • Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. (mdpi.com)
  • caspase activation, DNA fragmentation and externalization of phosphatidylserine, a cell surface marker for phagocytosis [7]. (egfr-inhibitor.com)
  • Caspase-3 is activated in the apoptotic cell. (wikipedia.org)
  • Caspase-3 activation is a cell requirement during early stages of the skeletal myoblast differentiation. (wikipedia.org)
  • Caspase signals resulting from the activation of nuclease CAD indicate that the cell differentiation is due to a CAD modification in chromatin structure. (wikipedia.org)
  • The protease family of the caspases, the mammalian homologues of the Caenorhabditis elegans death gene, is required for mammalian apoptosis. (ahajournals.org)
  • IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. (alfa.com)
  • This Apaf-1/cytochrome c complex allows the interaction of pro-caspase-9 with Apaf-1, thus placing pro-caspase-9 molecules in close proximity with each other and promoting their activation [12]. (egfr-inhibitor.com)
  • We specialize in small molecule inhibitors, agonists, antagonists and screening libraries! (apexbt.com)
  • Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. (nature.com)
  • The optimal peptide motifs are not unique recognition sites for each caspase, so techniques that use them may yield information about more than one caspase. (staffs.ac.uk)
  • Z-VDVAD-FMK (caspase-2 inhibitor I) and Z-DEVD-FMK (caspase-3 inhibitor II) were purchased from Calbiochem. (ahajournals.org)
  • SU6656, an Src family kinase inhibitor, was from Calbiochem. (alk-inhibitors.com)
  • 15 Different death stimuli may activate different caspases. (ahajournals.org)
  • After 24 hours, we detected the protein levels of cleaved Caspase-3 by Western Blot. (apexbt.com)
  • One of the caspase-8 structures also shows binding at a secondary, allosteric site, providing a possible route to the development of noncovalent small molecule modulators of caspase activity. (rcsb.org)
  • Caspase activity and apoptosis inhibitor 1 is a protein that in humans is encoded by the CAAP1 gene. (wikipedia.org)
  • Intrigued by the multiple ways to control caspase-9's activity, we sought after designing synthetic caspase-9 inhibitors in addition to defining the mechanistic details metal regulation and CARD domain activation. (umass.edu)
  • In addition, the combination of bcl-2 antisense oligonucleotides with FR901228 enhanced FR901228-induced caspase-3 activity and cytotoxicity. (aacrjournals.org)
  • Compounds to be screened can directly be added to the reaction and the level of inhibition of caspase-3 activity can be determined by comparison of the fluorescence intensity in samples with and without the testing inhibitors. (creativebiomart.net)
  • Inhibition of caspase-3 activity can be determined by comparison of the fluorescence intensity in samples with and without the testing inhibitors. (creativebiomart.net)
  • Surprisingly, vorinostat and romidepsin maintained an equivalent level of killing and mutagenic ability regardless of caspase or CAD activity. (springer.com)
  • We recommend using 1000-5000X dilutions for inhibiting caspase-13 and related caspase activity (e.g. (antibody-antibodies.com)
  • Pan-caspase inhibitor with in vivo activity (Ki values 18.4 μM, 0.45 μM, and 17.1 μM for Caspase-3, -8, and -9 resp). (axonmedchem.com)
  • Diabetes caused a more than twofold induction of 71 genes that directly or indirectly regulate apoptosis and significantly enhanced caspase-8, -9, and -3 activity. (diabetesjournals.org)
  • Thus, diabetes-enhanced apoptosis represents an important mechanism through which healing is impaired, and this can be explained, in part, by diabetes-increased expression of proapoptotic genes and caspase activity. (diabetesjournals.org)
  • Increased caspase-3-like, but not caspase-1-like, enzymatic activity was found in cytosolic extracts from injured cortex. (jneurosci.org)
  • Caspase activity (RFU) in presence of 0µM - 40µM of z-VAD-FMK (generic caspase inhibitor), assessed using WEHDD-AFC as caspase substrate and following Caspase 5 Inhibitor Drug Detection Kit (ab102493) protocol. (abcam.cn)
  • The present study performed immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot analysis and identified no significant changes in the expression of the X-linked inhibitor of apoptosis protein (XIAP) following radiation (P>0.05). (sigmaaldrich.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)
  • The final DMSO concentrations of caspase inhibitor treatment groups (10 μmol/L, 100 μmol/L, and combined 100 μmol/L) were 0.05%, 0.5%, and 1.0% (vol/vol), respectively. (ahajournals.org)
  • The dual Src/Abl inhibitor SKI 606 was dissolved in DMSO. (alk-inhibitors.com)
  • The GSK3 inhibitor SB 216763 was from Sigma Chemicals Co, and was prepared in DMSO at 10mM and stored at 41C. (alk-inhibitors.com)
  • According to Dr. Ding, "We still don't know the mechanism underlying caspase inhibitor-induced necrosis of the liver. (medicalnewstoday.com)
  • A pan caspase inhibitor decreases caspase-1, IL-1a and IL-1ß, and protects against necrosis of cisplatin-treated freshly isolated proximal tubules. (ucdenver.edu)