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 ...
Check out our best-in-class prices for Caspase Inhibitor Ac-DEVD-CHO 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.
Click to launch & play an online audio visual presentation by Prof. Guy Salvesen on Natural caspase inhibitors, part of a collection of online lectures.
Gentaur molecular products has all kinds of products like :search , Biovis \ Caspase-3 Inhibitor Z-DEVD-FMK ; Appearance Liquid \ 1009-20C for more molecular products just contact us
To protect your privacy, your account will be locked after 6 failed attempts. After that, you will need to contact Customer Service to unlock your account.. You have 4 remaining attempts.. You have 3 remaining attempts.. You have 2 remaining attempts.. You have 1 remaining attempt.. Contact Customer Service ...
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. ...
Buy Z-VAD-FMK, an irreversible general caspase inhibitor. Join researchers using high quality Z-VAD-FMK from Abcam and achieve your mission, faster.
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 ...
Buy Z-DEVD-FMK - an affordable, high quality Caspase 3 inhibitor from Hello Bio, a trusted supplier for life science researchers worldwide
Caspase detection antibodies and assays are used to help detect and study caspase activation in Apoptotic cells via immunoprecipitation and immunoblotting techniques.
Gentaur molecular products has all kinds of products like :search , Biovis \ Z-IETD-FMK; Appearance Lyophilized solid \ 1148-5 for more molecular products just contact us
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
Thank you for your interest in spreading the word about Science Signaling.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
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.
多种适用的Caspase 10ELISA试剂盒,如小鸡, Cow, 犬等。在antibodies-online.cn对比Caspase 10ELISA试剂盒,以便找到您需要的产品。
Orally-Administered Caspase Inhibitor PF-03491390 Is Retained in the Liver for Prolonged Periods With Low Systemic Exposure, Exerting a Hepatoprotective Effect Against α-Fas-Induced Liver Injury in a Mouse Model (2007 ...
Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor, blocks all features of apoptosis in THP.1 and Jurkat T-cells.
购买Z-LE(OMe)VD(OMe)-FMK,具有细胞渗透性的Z-LEVD-FMK caspase-4抑制剂 derivative。使用Abcam高品质的Z-LE(OMe)VD(OMe)-FMK帮助您更快取得科研成果。
Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
Welcome! For price inquiries, please feel free to contact us through the form on the left side. We will get back to you as soon as possible.. ...
To protect your privacy, your account will be locked after 6 failed attempts. After that, you will need to contact Customer Service to unlock your account.. You have 4 remaining attempts.. You have 3 remaining attempts.. You have 2 remaining attempts.. You have 1 remaining attempt.. Contact Customer Service ...
高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab32499 交差種: Ms,Hu 適用: WB,IP,IHC-P,Flow Cyt,ICC/IF
弊社製品は、最寄りの販売代理店を通してご注文ください。ご不明な場合、弊社までご連絡ください。. ※用途に[*]がついているものは一定の条件下での使用が推奨されたものです。製品詳細ページよりデータシートにてご確認ください。. バイオ・ラッド ラボラトリーズ株式会 ...
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 6 - C14: Caspase. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
The IUPHAR/BPS Guide to Pharmacology. Caspase 1 - C14: Caspase. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Kumar, A.P., Chang, M.K.X., Clement, M.-V., Fliegel, L., Pervaiz, S. (2007). Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death and Differentiation 14 (10) : 1733-1746. [email protected] Repository. https://doi.org/10.1038/sj.cdd. ...
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
... is a protein that in humans is encoded by the CAAP1 gene. Caspase Apoptosis GRCh38: ...
The anti-inflammatory drug indoprofen is an inhibitor of the activity of the caspase-4 enzyme. The Proteolysis Map Caspase ... The function of caspase 4 is not fully known, but it is believed to be an inflammatory caspase, along with caspase 1, caspase 5 ... Smith C, Soti S, Jones Torey A, Nakagawa A, Xue D, and Yin H (2017). "NSAIDs are Caspase Inhibitors". Cell Chem Biol. 24 (3): ... Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue (LEVD-), and belongs to a family ...
Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 ( ... Caspase-8 has been shown to interact with: BCAP31, BID, Bcl-2, CFLAR, Caspase-10, Caspase-2, Caspase-3, Caspase-6, Caspase-7, ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been ... The MEROPS online database for peptidases and their inhibitors: C14.009 Apoptosis & Caspase 8-The Proteolysis Map (animation) ...
... coli Effector Protein NleF Is a Caspase Inhibitor". PLOS ONE. 8 (3): e58937. Bibcode:2013PLoSO...858937B. doi:10.1371/journal. ... "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". ...
... many COPs are known inhibitors of Caspase activation. For Caspase-1, genes for specific COPs-ICEBERG, COP1 (ICE/Pseudo-ICE), ... Inhibitors Belnacasan (VX-765) Pralnacasan (VX-740) Activated Caspase 1 proteolytically cleaves pro IL-1β and pro IL-18 into ... May 2010). "A highly potent and selective caspase 1 inhibitor that utilizes a key 3-cyanopropanoic acid moiety". ChemMedChem. 5 ... Instead, it is thought to inhibit Caspase-1 activation by interfering with the interaction of Caspase-1 with other important ...
... induced caspase-dependent cleavage of p23. The cleavage could be catalyzed by either caspase-7 or caspase-3 and occurred at ... The Hsp90 inhibitor GA was found to enhance caspase activation, p23 cleavage and apoptosis induced by anthracyclines. Finally ... The first HSP90 inhibitors were developed from geldanamycin and radicicol which are the natural product inhibitors and are ... Furthermore, a number of Hsp90 inhibitors are currently undergoing clinical trials for a variety of cancers. Hsp90 inhibitors ...
Stierle AA, Stierle DB, Girtsman T (2012). "Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia ... 2005). "Structural analysis of epolactaene derivatives as DNA polymerase inhibitors and anti-inflammatory compounds". Int J Mol ... Polyozellus multiplex synthesizes prolyl endopeptidase inhibitors polyozellin, thelephoric acid, and kynapcins. Boletus badius ... Clavaric acid is a reversible farnesyltransferase inhibitor. Inonotus obliquus creates betulinic acid precursor betulin. ...
Stierle AA, Stierle DB, Girtsman T (2012). "Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia ...
... is initiated by caspase-activated deoxyribonuclease following caspase-3 mediated cleavage of the enzyme's inhibitor, ICAD. In ... Additionally, apoptosis and the degradation of intracellular organelles is mediated by caspase activation, particularly caspase ... The anti-apoptotic gene product Bcl-2 is not an active inhibitor of UCP-2 initiated cell death, further distinguishing oncosis ... Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., & Nagata, S. (1998). A caspase-activated DNase that degrades ...
... S doesn't have central catalytic domain, therefore it functions as an inhibitor of caspase-9α by attaching to the ... Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other ... Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating ... Different protein isoforms of caspase-9 are produced due to alternative splicing. Similar to other caspases, caspase-9 has ...
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 ...
... 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 ...
October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... "Specific chaperone-like activity of inhibitor of caspase-activated DNase for caspase-activated DNase". The Journal of ... Sakahira H, Enari M, Nagata S (May 1999). "Functional differences of two forms of the inhibitor of caspase-activated DNase, ... CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ...
"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 ... The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and ... Caspase 7 has been shown to interact with: Caspase 8, Survivin and XIAP. The Proteolysis Map Caspase GRCh38: Ensembl release 89 ... Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved ...
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 ...
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 Portal: Biology v t e (Articles with short description ... 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 ...
... is a member of the inhibitor of apoptosis (IAP) family. The survivin protein functions to inhibit caspase activation, ... The inactive proforms of caspase-3 and -7 did not bind survivin. Survivin also does not bind to active caspase-8. Caspase-3 and ... which recruits activator caspases like caspase-8 upon binding TNF at the cell surface. The activation of the initiator caspases ... The human IAPs, XIAP, c-IAPl, C-IAP2 have been shown to bind to caspase-3 and -7, which are the effector caspases in the ...
... the 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 ...
Watson RW, Fitzpatrick JM (December 2005). "Targeting apoptosis in prostate cancer: focus on caspases and inhibitors of ... Caspase 3. Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1, MAP3K2, TAB1, and XAF1. GRCm38: Ensembl ... 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 activation of apoptosis is inhibited by the DNA fragmentation factor DFF45 but not by caspase inhibitors. Mice that lack ...
As a consequence RIP1 forms a cytosolic complex with the adaptor molecule FADD and caspase 8, which leads to cell death. When ... cIAP1 is an inhibitor of apoptosis protein. It directly ubiquitinates RIP1 and induces constitutive RIP1 ubiquitination in ... cIAP1 (also named BIRC2) is the abbreviation for a human protein, cellular inhibitor of apoptosis protein-1. It belongs to the ... Doiron K, Labbé K, Korneluk RG, Barker PA, Saleh M, Bertrand MJ (2009). "Cellular inhibitors of apoptosis cIAP1 and cIAP2 are ...
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/ ...
Guy Salvesen on Natural caspase inhibitors, part of a collection of multimedia 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 ...
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.
These inhibit caspase-3 and may affect a variety of other apoptosis and tumor related proteins. ... Caspase-3 Inhibitor Caspase-3 Inhibitor is an inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10 210344-95-9 sc-3075 ... Caspase-3/7 Inhibitor I Caspase-3/7 Inhibitor I is an inhibitor of caspase-3, caspase-7 and Caspase-9 220509-74-0 sc-293986 1 ... Caspase Inhibitor X Caspase Inhibitor X is a competitive inhibitor of caspase-3, caspase-7 and caspase-8 848782-29-6 sc-300322 ...
GA blocked caspase activation and apoptosis and delayed cell death caused by DOX. Inhibitors of translation and transcription ... We next compared cytoprotection by GA-induced Hsp70, caspase inhibitors (Z-VAD-fmk) and cell-cycle arrest. Whereas cell-cycle ... In these cells, doxorubicin (DOX) caused rapid apoptsis, whereas GA-induced heat-shock protein-70 (Hsp70) (a potent inhibitor ... Also GA failed to protect HL60 cells from cytotoxicity of actinomycin D and flavopiridol (FL), inhibitors of transcription. ...
CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A NICOTINIC ACID ALDEHYDE INHIBITOR ... Reducing the Peptidyl Features of Caspase-3 Inhibitors: A Structural Analysis.. Becker, J.W., Rotonda, J., Soisson, S.M., ... Many caspase structures are known, but most involve either peptide or protein inhibitors, unattractive candidates for drug ... Many caspase structures are known, but most involve either peptide or protein inhibitors, unattractive candidates for drug ...
Caspase-3 Inhibitor II controls the biological activity of Caspase-3. This small molecule/inhibitor is primarily used for ... The InSolution™ Caspase-3 Inhibitor II controls the biological activity of Caspase-3. This small molecule/inhibitor is ... More,, The InSolution™ Caspase-3 Inhibitor II controls the biological activity of Caspase-3. This small molecule/inhibitor is ... Life Science Research > Inhibitors and Biochemicals > Small Molecules & Inhibitors > Apoptosis/Necrosis Inhibitors > Caspase ...
Calbiochem The Caspase-3/7 Inhibitor II, also referenced under CAS 775289-20-8, controls the biological activity of Caspase-3/7 ... This small molecule/inhibitor is primarily used for Cancer applications. - Find MSDS or SDS, a COA, data sheets and more ... Caspase-3/7 Inhibitor II - CAS 775289-20-8 - Calbiochem. 218832 Sigma-AldrichCaspase-3/7 Inhibitor II - CAS 775289-20-8 - ... Life Science Research > Inhibitors and Biochemicals > Small Molecules & Inhibitors > Apoptosis/Necrosis Inhibitors > Caspase ...
Calbiochem Caspase-8 Inhibitor II, CAS 210344-98-2, is a potent, cell-permeable, irreversible inhibitor of caspase-8 and ... Caspase-8 Inhibitor II, CAS 210344-98-2, is a potent, cell-permeable, irreversible inhibitor of caspase-8 and granzyme B.. More ... Caspase-8 Inhibitor II, CAS 210344-98-2, is a potent, cell-permeable, irreversible inhibitor of caspase-8 and granzyme B.. ... irreversible inhibitor of caspase-8 and granzyme B. Less,, Caspase-8 Inhibitor II - Calbiochem MSDS (material safety data sheet ...
Caspase 3/7 Activity Assay for Apoptosis Detection. To investigate Caspase 3/7 activity upon compound treatment, a Caspase-Glo® ... Both MV4-11 and MOLM13 showed a dose-dependent increase of Caspase 3/7 activity upon treatment with all used inhibitors. ... Inhibitors that target FLT3 in FLT3-ITD+ AML are often divided into first-generation and next-generation inhibitors [11]. First ... After adding Caspase-Glo® 3/7 reagent (Promega) to the cells (1:1 ratio) and 2 h of incubation, Caspase activity was measured ...
Caspase 3. ↑. EECL. [54]. Romidepsin. Caspase 9. ↑. EECL. [54]. Romidepsin. PARP-1 ↑. EECL. [54]. ... Table 2. Summary of the activities of histone deacetylase inhibitors in endometriotic lesions and other cell/tissues. Name of ... Many in vitro, in vivoand clinical studies have shown that histone deacetylase inhibitors (HDACIs) are promising in treating ... The desirable properties of histone deacetylase inhibitors as therapeutics for treating endometriosis are enumerated, and the ...
Furthermore, the pan-caspase inhibitor caspase inhibitor III (N-tert-butoxycarbonyl-aspartyl(OMe)-fluoromethylketone, Boc-D-FMK ... Furthermore, the pan-caspase inhibitor caspase inhibitor III (N-tert-butoxycarbonyl-aspartyl(OMe)-fluoromethylketone, Boc-D-FMK ... Furthermore, the pan-caspase inhibitor caspase inhibitor III (N-tert-butoxycarbonyl-aspartyl(OMe)-fluoromethylketone, Boc-D-FMK ... Furthermore, the pan-caspase inhibitor caspase inhibitor III (N-tert-butoxycarbonyl-aspartyl(OMe)-fluoromethylketone, Boc-D-FMK ...
Exploring the S4 and S1 prime subsite specificities in caspase-3 with aza-peptide epoxide inhibitors. ... Exploring the S4 and S1 prime subsite specificities in caspase-3 with aza-peptide epoxide inhibitors. Ganesan R, Jelakovic S, ... Caspase-3 subunit p12. > Peptidase C14 family * Occurring in:. *Caspase-3 subunit p17. *Caspase-3 subunit p12. > Caspase-like ... Caspase-3 subunit p12. > Peptidase C14A, caspase catalytic domain * Occurring in:. *Caspase-3 subunit p17. * ...
Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P, Caspase inhibitors improve survival in sepsis: a critical ... Methot N, Huang J, Coulombe N, Vaillancourt JP, Rasper D, Tam J, Differential efficacy of caspase inhibitors on apoptosis ... Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Pleiotropic defects in lymphocyte activation caused by caspase-8 ... In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice.Blood. 2005;106:2295-301. DOIPubMedGoogle ...
Although general structural features are shared between the initiator and the effector caspases, their activation, inhibition ... Caspases, which are the executioners of apoptosis, comprise two distinct classes, the initiators and the effectors. ... Molecular mechanisms of caspase regulation during apoptosis Nat Rev Mol Cell Biol. 2004 Nov;5(11):897-907. doi: 10.1038/nrm1496 ... Caspases / metabolism* * Enzyme Activation * Enzyme Inhibitors / pharmacology * Humans * Models, Biological * Models, Molecular ...
Interest in caspase-3 as a therapeutic target has led many to pursue the development of inhibitors. To date, only a few series ... Here, we report the screening of 70 novel small molecules against the caspase-3 enzyme which belongs to four different series ( ... and reasonable selectivity against other proteases including caspase-1, cathepsin B and D, and thrombin. On the basis of in ... of non-peptide inhibitors have been described, and these have limitations on their drug-like properties. ...
Angiotensin I Converting Enzyme 2, ACE-2/Caspase-1 Substrate. Home/Catalog peptide/Angiotensin I Converting Enzyme 2, ACE-2/ ... Angiotensin I Converting Enzyme 2, ACE-2/Caspase-1 SubstrateAdmin2021-01-04T11:12:17+00:00 ... Inhibitor and Agonist. Contact Info. No. 199 Huayuan Dong Road, Wuzhong Qu,Suzhou Shi, Jiangsu Sheng, China ...
cAMP, ROS, ATP, and caspase 3/7 assays. Confluent 10 cm plates were treated as indicated in the text. Following treatment, 2 × ... An Effective Epigenetic-PARP Inhibitor Combination Therapy for Breast and Ovarian Cancers Independent of BRCA Mutations ... C, PEO4 cells were treated with 20 nmol/L guadecitabine (Guad) with or without 5 μmol/L PKA inhibitor H89 for 72 hours. Twenty- ... C, PEO4 cells were treated with 20 nmol/L guadecitabine (Guad) with or without 5 μmol/L PKA inhibitor H89 for 72 hours. Twenty- ...
Caspase-3 inhibitor study. To examine the effects of a caspase-3 inhibitor,N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone ... Caspase-3 inhibitor reduced the hippocampal CA1 neuronal injury only in Wt animals but not in Tg animals. In the caspase-3 ... Active caspase-3 immunohistochemistry (A), Western blot studies of caspase-3 and PARP (B), and caspase-3 activity assay (C). A ... Western blot analysis of caspase-3 showed an increase in cleaved caspase-3 (p20) and caspase-3 proform (p32) at 3 d only in the ...
... inhibitor MGCD0103 induces apoptosis in B-cell chronic lymphocytic leukemia cells through a mitochondria-mediated caspase ... Dive into the research topics of The histone deacetylase inhibitor MGCD0103 induces apoptosis in B-cell chronic lymphocytic ... leukemia cells through a mitochondria-mediated caspase activation cascade. Together they form a unique fingerprint. ...
CASPASE-8 IN COMPLEX WITH AOMK INHIBITOR, AC-DW3-KE, FORMS TETRAHEDRAL ADDUCT - 6X8H , canSARS ... CASPASE-8 IN COMPLEX WITH AOMK INHIBITOR, AC-DW3-KE, FORMS TETRAHEDRAL ADDUCT ... CASPASE-8 IN COMPLEX WITH AOMK INHIBITOR, AC-DW3-KE, FORMS TETRAHEDRAL ADDUCT ...
Agonists, activators, antagonists and inhibitors. Cell lines and Lysates. Multiplex miRNA assays. Multiplex Assays. By research ... Caspase-2+Caspase-9+Caspase-8+Caspase-7+Caspase-1+Caspase-4+Caspase-6/CASP-6+Caspase-5+Caspase-10+Ca (1). ... Caspase-2+Caspase-9+Caspase-8+Caspase-7+Caspase-1+Caspase-6+Caspase-10+Caspase 3 (1). ... Caspase-3, Caspase-8 and Caspase-9 Multiplex Activity Assay Kit (Fluorometric) (ab219915) Specific References (16) ...
... cleaved caspase 3), and degradation of PARP, a direct substrate of active caspase 3 (Fig. 8). ... inhibitor of cyclin-dependent kinase 4A; part of cyclin-dependent kinase inhibitor 2A gene (. CDKN2A. ), also known as multiple ... Flaherty, K., et al., Phase I/II expansion cohort of BRAF inhibitor GSK2118436 + MEK inhibitor GSK1120212 in patients with BRAF ... 1, 61]. Cells were treated, alone or in combination, with MEK inhibitor PD98059 (22) and CDK4 inhibitor 219476 (23). As ...
Caspases are cysteine proteases involved in the signalling cascades of programmed cell death in which caspase-3 plays a central ... A low-barrier hydrogen bond is observed between the side-chains of the P4 inhibitor aspartic acid and Asp179 of the N-terminal ... Categories: Caspase-3 , Large Structures , Ganesan, R , Grutter, M G , Jelakovic, S , Mittl, P R.E , Apoptosis , Clan cd , ... Caspase 3D structures References *↑ Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin ...
Sodium glucose cotransporter 2 inhibitors (SGLT2i) are the first antidiabetic compounds that effectively reduce heart failure ... Sodium glucose cotransporter 2 inhibitors (SGLT2i) are the first antidiabetic compounds that effectively reduce heart failure ... Effects of Dapa on NLRP3, TNF-α and caspase-1 were similar to A769662, an AMPK activator, while co-administration of Dapa with ... NHE inhibitor; EXPEDITION 3.0% vs. 5.2% (p , 0.001); GUARDIAN-trial 1.0% vs. 1.5%; ESCAMI-trial 0.2 vs. 2.2% (not significant ...
These complexes form receptors that activate caspase-dependent cytokine pathways that cause pyroptosis. ... CRAC channel inhibitors could be useful in treating cases of severe COVID-19. A novel nanoemulsion formulation of CM4620, named ... Exploring the potential utility of calcium channel inhibitors in SARS-CoV-2 infection. *Download PDF Copy ... Several inhibitors of these channels, such as amlodipine, nifedipine, felodipine, verapamil and diltiazem are being tested for ...
Inflammasome activation was confirmed using inhibitors of cathepsin B and Caspase-1. Purification reduced the cell toxicity and ...
Normally CAD exists as an inactive complex with ICAD (inhibitor of CAD). During apoptosis, ICAD is cleaved by caspases, such as ... This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6. These caspases are ... as caspase 8 or caspase 10. These caspases can then activate other caspases in a cascade. ... Caspases and the apoptosome. The caspases are a family of proteins that are one of the main executors of the apoptotic process ...
The parallel EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) clinical trials are designed to provide clinically ... orally active pan-caspase inhibitor emricasan with Novartis. The deal terms call for Conatus to receive $50 million upfront and ...
Caspase inhibitors attenuate 1-methyl-4-phenylpyridinium toxicity in primary cultures of mesencephalic dopaminergic neurons. J ... Arrowheads indicate cleaved caspase-3-positive TH+ neurons. Arrows point to cleaved caspase-3-positive astrocytes. The death of ... Overexpression of transgenic α-synuclein triggered the accumulation of cleaved caspase-3, an active form of caspase-3, in TH- ... SIB1757-treated cells were stained with antibody against cleaved caspase-3 (Cell Signaling Technology, 1:100), TH (Abcam, 1: ...
1B,C). Second, other embryos were treated with the more narrow spectrum caspase inhibitor Z-VAD-fmk [less potent caspase-2 and ... For experiments with a more narrow spectrum caspase inhibitor (Fig. 1B,C), Q-VD-OPh was replaced by 200 µM Z-VAD-fmk ( ... h, H, hair cell; Haem, haematoxylin staining (Mayer); m, mantle cell; Q-VD-OPh, pan-caspase inhibitor; s, support cell; wec, ... h, H, hair cell; Haem, haematoxylin staining (Mayer); m, mantle cell; Q-VD-OPh, pan-caspase inhibitor; s, support cell; wec, ...
  • A potent, cell-permeable, and irreversible inhibitor of CPP-32/apopain, a member of the ICE/CED-3 family of cysteine proteases. (merckmillipore.com)
  • Note: aldehyde-based inhibitors are less cell-permeable than FMK-based inhibitors, so higher concentrations may be required for cell-based inhibition studies (e.g. 100 µM). (merckmillipore.com)
  • Caspase-8 Inhibitor II, CAS 210344-98-2, is a potent, cell-permeable, irreversible inhibitor of caspase-8 and granzyme B. (emdmillipore.com)
  • A potent, cell-permeable, and irreversible inhibitor of caspase-8 and granzyme B. Effectively inhibits influenza virus-induced apoptosis in HeLa cells. (emdmillipore.com)
  • SB 216763 is a potent and selective cell permeable ATP-competitive inhibitor of GSK3α with an IC50 value of 34 nM (similar potency for GSK3β). (dcchemicals.com)
  • Overall, these results demonstrate that inhibition of caspase-1 reduces renal ischemia-reperfusion injury to a greater extent than caspase-3 inhibition, supporting the notion that the mode of acute cell death in our model of renal ischemia-reperfusion is primarily via necrosis. (brighton.ac.uk)
  • Overall, these results demonstrate that inhibition of caspase-1 activity reduces renal ischemia-reperfusion injury and that this therapeutic strategy may be of benefit against ischemic acute renal failure. (brighton.ac.uk)
  • Although general structural features are shared between the initiator and the effector caspases, their activation, inhibition and release of inhibition are differentially regulated. (nih.gov)
  • Caspase-3 inhibition has been demonstrated to be therapeutically effective in moderating excessive programmed cell death. (springeropen.com)
  • The screening yielded series of hits with IC 50 values ranging from 0.11 to 10 μM with reasonable SAR, irreversible mode of inhibition, and reasonable selectivity against other proteases including caspase-1, cathepsin B and D, and thrombin. (springeropen.com)
  • Several reports demonstrated that inhibition of caspases protect the liver from apoptosis-associated liver injury in preclinical models. (springeropen.com)
  • A new plant-derived natural small molecule, called neferine, was also identified as a potential entry inhibitor of the virus, and showed 75% inhibition of infection in cell cultures in a pseudovirus assay, by inhibiting calcium channels in the cell membrane. (news-medical.net)
  • Using pharmacological inhibition of apoptosis-associated caspases, we find evidence that apoptosis eliminates hitherto undiscovered rudiments of the lateral line sensory system which, in fish and aquatic amphibia, serves to detect movements, pressure changes or electric fields in the surrounding water. (biologists.com)
  • Dorsomorphin (Compound C, BML-275) is a potent, reversible, selective AMPK inhibitor with K i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. (selleckchem.com)
  • The stimulation or inhibition of different Bcl-2 family receptors results in the leakage of cytochrome c from the mitochondria, and the formation of an apoptosome composed of cytochrome c, Apaf1 and caspase-9. (embl.de)
  • TLK117-mediated GSTP inhibition attenuates bleomycin-induced caspase activation and protein S-glutathionylation. (jci.org)
  • When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines. (biomedcentral.com)
  • Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. (rcsb.org)
  • Caspases are cysteine proteases involved in the signalling cascades of programmed cell death in which caspase-3 plays a central role, since it propagates death signals from intrinsic and extrinsic stimuli to downstream targets. (proteopedia.org)
  • Activated caspases act as cysteine proteases, using the sulphydryl group of a cysteine side chain for catalysing peptide bond cleavage at aspartyl residues in their substrates. (embl.de)
  • 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)
  • Caspase-3 Inhibitors offered by Santa Cruz inhibit caspase-3 and, in some cases, other apoptosis and tumor related proteins. (scbt.com)
  • A major biochemical pathway involved in the apoptosis includes a family of proteases, known as caspases, which act in a cascade to activate downstream caspases responsible for breakdown or cleavage of key cellular substrates required for normal cellular fashion, including structural proteins in the cytoskeleton and nuclear proteins such as DNA repair enzymes [ 2 , 3 ]. (springeropen.com)
  • The caspases are a family of proteins that are one of the main executors of the apoptotic process. (reading.ac.uk)
  • These caspases are responsible for the cleavage of the key cellular proteins, such as cytoskeletal proteins, that leads to the typical morphological changes observed in cells undergoing apoptosis. (reading.ac.uk)
  • The caspases play an important role in this process by activating DNases, inhibiting DNA repair enzymes and breaking down structural proteins in the nucleus. (reading.ac.uk)
  • The enzyme poly (ADP-ribose) polymerase, or PARP, was one of the first proteins identified as a substrate for caspases. (reading.ac.uk)
  • Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. (embl.de)
  • At the end of the cascade, caspases act on a variety of signal transduction proteins, cytoskeletal and nuclear proteins, chromatin-modifying proteins, DNA repair proteins and endonucleases that destroy the cell by disintegrating its contents, including its DNA. (embl.de)
  • Several families of proteins including the Bcl-2, tumor necrosis factor receptor 1, and caspase families play essential roles in the regulation, signaling, and execution of the genetic cell death program. (embl.de)
  • The disclosure provides proteasome inhibitors that can be used to halt cell division of rapidly dividing cells by preventing the degradation of cell cycle-regulating proteins, such as cyclins, cyclin-dependent kinase inhibitors, and p53. (justia.com)
  • Inhibitor of apoptosis proteins (IAP) are a class of regulatory proteins, with mainly anti-apoptotic properties, characterized by the presence of one to three domains known as baculoviral IAP repeat (BIR) domains [ 11 ]. (biomedcentral.com)
  • Among these IAP proteins, X-linked IAP (XIAP) is a direct inhibitor of caspase activity. (biomedcentral.com)
  • IAP proteins interact with and inhibit CASPASES , and they function as ANTI-APOPTOTIC PROTEINS. (bvsalud.org)
  • The robust proapoptotic activity was found to be the consequence of a positive feedback mechanism-governed amplification of caspase activation and cleavage of both Mcl-1 and Akt proteins, and exhibited a relative selectivity in MPM cells than in non-tumorigenic Met-5A mesothelial cells. (cdc.gov)
  • Cystatin A (Cys A), a cysteine protease inhibitor, is a precursor of proteins involves in keratinocyte keratinization, and is expressed during the late phase of differentiation of these cells. (bvsalud.org)
  • In these cells, doxorubicin (DOX) caused rapid apoptsis, whereas GA-induced heat-shock protein-70 (Hsp70) (a potent inhibitor of apoptosis) and G1 arrest without significant apoptosis. (nature.com)
  • 2007) NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1 . (emdmillipore.com)
  • The inhibitor of cyclin-dependent kinase 4A ( INK4A ) gene encode the p16 protein, a critical cell cycle regulator that interacts with cyclin dependent kinase (CDK) 4, inhibiting its ability to phosphorylate and inactivate RB [ 12 , 13 ]. (intechopen.com)
  • This effect is mediated through the formation of an apoptosome, a multi-protein complex consisting of cytochrome C, Apaf-1, pro-caspase 9 and ATP. (reading.ac.uk)
  • Oropharyngeal administration of the GSTP inhibitor, TLK117, at a time when fibrosis was already apparent, attenuated bleomycin- and AdTGFβ-induced remodeling, α-SMA, caspase activation, FAS S-glutathionylation, and total protein S-glutathionylation. (jci.org)
  • RIC-3 was originally identified in the nematode Caenorhabditis elegans as the protein encoded by the gene ric-3 (resistance to inhibitors of cholinesterase) and has subsequently been cloned and characterized from mammalian and insect species. (wormbase.org)
  • Second mitochondria-derived activator of caspase (Smac) is an endogenous antagonist of IAP protein [ 17 ]. (biomedcentral.com)
  • We further validate 2 downstream candidates (oxidative stress-induced growth inhibitor 1) and (X-ray repair cross-complementing protein 5) and evaluate their functional relationship with PEL cell survival/proliferation and chemoresistance respectively. (biotech2012.org)
  • TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages. (cdc.gov)
  • Caspase 3, Apoptosis-Related Cysteine Peptidase (aa 176-277) Protein, tagged with His tag. (creative-biolabs.com)
  • CHIR-99021 is a GSK-3α/β inhibitor with an IC50 of 10 and 6.7 nM,showing 500-fold selectivity over its closest homologs CDC2 and ERK2, as well as other protein kinases. (dcchemicals.com)
  • A couple months ago we highlighted how fragment-based approaches were used to discover inhibitors of a methyltransferase, one of many classes of protein-modifying enzymes that underlie epigenetics. (blogspot.com)
  • A highly fluorescent substrate for caspase 1. (bestbiochem.com)
  • The atomic resolution (1.06 Angstroms) crystal structure of the caspase-3 DEVD-cmk complex reveals the structural basis for substrate selectivity in the S4 pocket. (proteopedia.org)
  • Ganesan R, Mittl PR, Jelakovic S, Grutter MG. Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis. (proteopedia.org)
  • Cytosolic expression of cytochrome c and Smac and activation of caspases were evaluated by immunohistochemistry, Western blot, and caspase activity assay. (jneurosci.org)
  • Everolimus (RAD001, SDZ-RAD, Afinitor) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM in a cell-free assay. (selleckchem.com)
  • Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. (selleckchem.com)
  • Involvement of intrinsic or extrinsic pathways in the CACF-induced A375 cell death mechanism was examined using a caspase luminescence assay. (biomedcentral.com)
  • Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. (greenmedinfo.com)
  • Caspase 3/7 activity assay Cells had been plated as referred to for cell viability and treated with raising concentrations of TM5275 or TM5441 for 48 hours. (exposed-skin-care.net)
  • This is a "connection" page, showing publications Teresita Bellido has written about Enzyme Inhibitors. (uams.edu)
  • Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. (kamiyabio.com)
  • This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6. (reading.ac.uk)
  • Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES . (nih.gov)
  • A short pro-domain caspase that plays an effector role in APOPTOSIS . (nih.gov)
  • Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. (proteopedia.org)
  • The ability of PARP to repair DNA damage is prevented following cleavage of PARP by caspase-3. (reading.ac.uk)
  • 2008). Importantly, cell death of apoptotic morphology can be shifted to a necrotic phenotype when caspase 8 activity is compromised, otherwise active caspase 8 blocks necroptosis by the proteolytic cleavage of RIPK1 and RIPK3 (Kalai M et al. (wikipathways.org)
  • Notably, calcium-dependent alterations are reversible and targetable by small molecule inhibitors. (open.ac.uk)
  • We show here that the specific mTOR kinase inhibitor AZD8055 blocked mTORC1 and mTORC2 signaling in AML. (crick.ac.uk)
  • CHIR-99021 is a glycogen synthase kinase 3 beta inhibitor that has antiproliferative activity in vitro and in vivo. (dcchemicals.com)
  • mTOR kinase inhibitor AZD2014 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. (biochempartner.com)
  • Activation of caspases can be mediated by other caspase homologues. (embl.de)
  • Hsp70 blocks several steps of the apoptotic cascade: upstream from mitochondria, release of cytochrome C and apoptosis-inducing factor (AIF), nuclear import of AIF, activation of procaspases-9 and -3, and even downstream of active caspase-3. (nature.com)
  • Mitochondria are known to be involved in the early stage of apoptosis by releasing cytochrome c , caspase-9, and the second mitochondria-derived activator of caspases (Smac). (jneurosci.org)
  • In the Wt animals, early superoxide production, mitochondrial release of cytochrome c , Smac, and cleaved caspase-9 were observed after ischemia. (jneurosci.org)
  • These results suggest that overexpression of SOD1 reduced oxidative stress, thereby attenuating the mitochondrial release of cytochrome c and Smac, resulting in less caspase activation and apoptotic cell death. (jneurosci.org)
  • Release of cytochrome C from mitochondria can lead to the activation of caspase 9, and then of caspase 3. (reading.ac.uk)
  • Disruption of the MMP facilitated the release of mitochondrial cytochrome c, which activates caspase-9 and downstream caspase-3/7, resulting in DNA fragmentation and up-regulation of p53 in melanoma cells. (biomedcentral.com)
  • The proteasome inhibitor compounds can be used to inhibit the proliferation of cancer cells. (justia.com)
  • GDC-0349 (RG-7603) is a potent and selective ATP-competitive inhibitor of mTOR with K i of 3.8 nM, 790-fold inhibitory effect against PI3Kα and other 266 kinases. (selleckchem.com)
  • Rapamycin (AY-22989, Rapamune, Sirolimus, NSC-2260804,AY-22989) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells. (selleckchem.com)
  • AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. (selleckchem.com)
  • There are also agents directed at the HSP90 and mTOR/HIF pathways including the inhibitor geldanamycin. (cdc.gov)
  • Vistusertib, also known as AZD2014, is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. (biochempartner.com)
  • Induction of apoptosis via death receptors typically results in the activation of an initiator caspase such as caspase 8 or caspase 10. (reading.ac.uk)
  • 2013. SfDronc, an initiator caspase involved innapoptosis in the fall armyworm Spodoptera frugiperda . (k-state.edu)
  • CASP3_HUMAN ] Involved in the activation cascade of caspases responsible for apoptosis execution. (proteopedia.org)
  • These caspases can then activate other caspases in a cascade. (reading.ac.uk)
  • There are a number of other mechanisms, aside from activation of the death receptors, through which the caspase cascade can be activated. (reading.ac.uk)
  • The mitochondria are also key regulators of the caspase cascade and apoptosis. (reading.ac.uk)
  • The subsequent activation of caspase-8 initiates the apoptosis cascade involving caspases 3, 4, 6, 7, 9 and 10. (embl.de)
  • Caspase activation has been implicated in the development of ischemia-reperfusion injury. (brighton.ac.uk)
  • Both caspase-1 and -3 inhibitors markedly reduced the evidence of oxidative and nitrosative stress in rat kidneys subjected to ischemia-reperfusion. (brighton.ac.uk)
  • Furthermore, our finding that a pan-caspase inhibitor did not reduce the renal dysfunction and injury suggests that activation of some caspases during ischemia-reperfusion could provide protection against acute ischemic renal injury. (brighton.ac.uk)
  • Active caspase-3 was subsequently increased, and 85% of the hippocampal CA1 neurons showed apoptotic DNA damage 3 d after ischemia. (jneurosci.org)
  • Subsequent active caspase-3 expression was not evident, and only 45% of the neurons showed apoptotic DNA damage. (jneurosci.org)
  • Degradation of lamins by caspase 6 results in the chromatin condensation and nuclear fragmentation commonly observed in apoptotic cells. (reading.ac.uk)
  • Remarkably, CHIKV hiding into apoptotic blebs was able to infect neighboring cells and these events were inhibited specifically by inhibitors of caspases, blebbing and engulfment. (archives-ouvertes.fr)
  • Our data show the apoptotic aftereffect of these inhibitors against many tumor cell lines but indicate their present limited activity when utilized alone tests. (exposed-skin-care.net)
  • Methods: Proteasome inhibitors (PIs) and TNFá-Related Apoptosis Inducing Ligand (TRAIL), have emerged as promising new anti-MPM agents. (cdc.gov)
  • To investigate the effects of Banxia Houpo decoction on the renal NLRP3/Caspase-1/IL-1β signaling pathway in chronic intermittent hypoxia mice. (magtech.com.cn)
  • TNF-α binds specific receptors on the cell surface that transduce death signals via the extrinsic pathway of apoptosis, in other words by activating caspase 8. (mimetech.eu)
  • The relative levels of Dickkopf-relatedprotein 1 (an inhibitor of the canonical Wnt pathway) decreased remarkably. (who.int)
  • For example, the proteasome inhibitor, bortezimab, targets the NF-kB pathway, which is in part regulated by HSP70 and HSP90. (cdc.gov)
  • PKR Inhibitor inhibits RNA-induced PKR autophosphorylation, as well as caspase-3 and caspase-8, and prevents increases in pT(451)-PKR and pS(194)-FADD levels in SH-SY5Y nuclei. (scbt.com)
  • Deguelin, an Akt inhibitor, down-regulates NF-κB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice. (greenmedinfo.com)
  • We present seven crystal structures of inhibited caspase-3 that illustrate several approaches to reducing the peptidyl characteristics of the inhibitors while maintaining their potency and selectivity. (rcsb.org)
  • A tetrapeptidyl aldehyde that acts as a potent, reversible and active site binding inhibitor of caspases-3 and -7 (IC 50 = 3.2 nM and 22.6 nM, respectively) and displays ~100-fold greater selectivity over caspases-8 and -9 (IC 50 = 577.6 nM and 364.7 nM, respectively). (merckmillipore.com)
  • BIO (6-bromoindirubin-3'-oxime) is a specific inhibitor of GSK-3 with IC50 of 5 nM for GSK-3α/β, shows >16-fold selectivity over CDK5, also a pan-JAKinhibitor. (dcchemicals.com)
  • The InSolution™ Caspase-3 Inhibitor II controls the biological activity of Caspase-3. (merckmillipore.com)
  • The Caspase-3/7 Inhibitor II, also referenced under CAS 775289-20-8, controls the biological activity of Caspase-3/7. (merckmillipore.com)
  • A caspase-like decoy molecule enhances the activity of a paralogous caspase in the yellow fever mosquito, Aedes aegypti. (ebi.ac.uk)
  • A and B ) Measurement of caspase-3 and -8 activity in mouse lungs homogenates. (jci.org)
  • Most programmed cell deaths in the nematode C. elegans require ced-3 caspase activity. (wormbase.org)
  • Although non-nucleoside reverse transcriptase inhibitors (NNRTIs) exhibit potent anti-HIV-1 activity and play an important role in the active antiretroviral therapy of AIDS, the emergence of drug-resistant strains has seriously reduced their clinical efficacy. (bvsalud.org)
  • Bellido T, Huening M, Raval-Pandya M, Manolagas SC, Christakos S. Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase-3 activity. (uams.edu)
  • in ovarian cancers cells shows that these inhibitors could also come with an anti-cancer activity [19]. (exposed-skin-care.net)
  • the BMP-2 inhibitor Noggin represses Sox9 expression in limb bud chondrogenic precursors while inducing the ligament/tendon-specific transcription factor Scx" "the histone acetyltransferase (HAT) activity of p300 has the potential to facilitate transcriptional activity by modulating the chromatin structure. (heightquest.com)
  • ABL-N administration induced apoptosis of PC3 cells in a dose-dependent manner, along with the enhanced activity of caspases and increased Bax/Bcl-2 ratio. (cusabio.com)
  • The desirable properties of histone deacetylase inhibitors as therapeutics for treating endometriosis are enumerated, and the obstacles in evaluating histone deacetylases in clinical trials are listed. (medscape.com)
  • Specific inhibitors of caspase-independent necrosis, necrostatins, have recently been identified (Degterev A et al. (wikipathways.org)
  • The first evidence raised from the observation that Tumor Necrosis Factor-α (TNF-α) is able to induce both apoptosis and necrosis, especially in the presence of caspase-inhibitors. (mimetech.eu)
  • However, when caspase 8 is blocked by synthetic or viral inhibitors, or by drastic depletion of energy (ATP depletion), there is a shift from apoptosis toward necrosis, mediated by the RIP kinases , RIPK1 and RIPK3 . (mimetech.eu)
  • PARP inhibitors (PARPi) are primarily effective against BRCA1/2-mutated breast and ovarian cancers, but resistance due to reversion of mutated BRCA1/2 and other mechanisms is common. (aacrjournals.org)
  • CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl), B-cell lymphoma 2 (Bcl-2), cleaved caspase-9, and cleaved poly ADP ribose polymerase (PARP) levels but increased the expression level of Bcl-2-associated X (Bax). (dovepress.com)
  • AZD8055 induces caspase-dependent apoptosis and also induces autophagy . (selleckchem.com)
  • Laduviglusib (CHIR-99021, CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. (selleckchem.com)
  • Viability (indicated like a % of control to DMSO treated cells) was plotted on the logarithmic scale as well as the fifty percent maximal inhibitor focus (IC50) was PF-2341066 determined from the very best match line. (exposed-skin-care.net)
  • TWS119 is a GSK-3β inhibitor with IC50 of 30 nM. (dcchemicals.com)
  • The GSK3β Inhibitor XIX, IM-12 is a selective GSK-3β inhibitor with IC50 of 53 nM, and also enhances canonical Wnt signalling. (dcchemicals.com)
  • CHIR-98014 is a potent GSK-3α/β inhibitor with IC50 of 0.65 nM/0.58 nM, with the ability to distinguish GSK-3 from its closest homologs Cdc2 and ERK2. (dcchemicals.com)
  • This domain includes the core of p45 (45kDa) precursor of caspases, which can be processed to produce the active p20 (20kDa) and p10 (10kDa) subunits. (embl.de)
  • While the response to selective BRAF inhibitors (BRAFi) in BRAF -mutant melanoma is encouraging, virtually all patients rapidly develop secondary resistance [ 6 , 7 ]. (intechopen.com)
  • In order to identify highly selective and potent BuChE inhibitors, a 53-membered compound library was constructed via the oxime-based tethering approach based on microscale synthesis. (bvsalud.org)
  • CP21R7 is a potent and selective GSK-3β inhibitor. (dcchemicals.com)
  • Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers. (greenmedinfo.com)
  • Inflammasome activation was confirmed using inhibitors of cathepsin B and Caspase-1. (cdc.gov)
  • Crystal structures of caspase-3 in complex with aza-peptide epoxide inhibitors. (ebi.ac.uk)
  • To date, only a few series of non-peptide inhibitors have been described, and these have limitations on their drug-like properties. (springeropen.com)
  • Caspases are synthesised as zymogens and activated by proteolysis of the peptide backbone adjacent to an aspartate. (embl.de)
  • The activation of apoptosis can sometimes lead to caspase-1 activation, providing a link between apoptosis and inflammation, such as during the targeting of infected cells. (embl.de)
  • These complexes form receptors that activate caspase-dependent cytokine pathways that cause pyroptosis. (news-medical.net)
  • Caspase-mediated apoptosis follows two main pathways, one extrinsic and the other intrinsic or mitochondrial-mediated. (embl.de)
  • Granzyme B can be delivered into cells by cytotoxic T lymphocytes and is able to directly activate caspases 3, 7, 8 and 10. (reading.ac.uk)
  • Launch Plasminogen activator inhibitor-1 (PAI-1) is certainly a serine protease inhibitor that has an important function in lots of physiological and pathological circumstances, including wound curing, obesity, metabolic symptoms, coronary disease and cancers [1]. (exposed-skin-care.net)
  • Q-VD-OPH is a low toxicity broad-spectrum inhibitor of caspase-3, caspase-1, caspase-8 and caspase-9. (scbt.com)
  • Efficacy with the broad-spectrum caspase inhibitors in preclinical models suggests that they have potential for the treatment of liver diseases in humans. (springeropen.com)
  • Significantly, AZD8055 decreased AML blast cell proliferation and cell cycle progression, reduced the clonogenic growth of leukemic progenitors and induced caspase-dependent apoptosis in leukemic cells but not in normal immature CD34+ cells. (crick.ac.uk)
  • By impairing the develop- with specific inhibitors, markedly improves survival in ment of adaptive immune responses needed for recovery, murine sepsis models. (cdc.gov)
  • It helps protect these cells from self-destructing (undergoing apoptosis) by blocking (inhibiting) the action of certain enzymes called caspases, which are necessary for apoptosis. (medlineplus.gov)
  • Inhibitors of translation and transcription and siRNA Hsp70 abrogated cytoprotective effects of GA. Also GA failed to protect HL60 cells from cytotoxicity of actinomycin D and flavopiridol (FL), inhibitors of transcription. (nature.com)
  • We have reported that combination of BRAFi or MEKi with the expression of wild-type INK4A or a CDK4 inhibitor (CDK4i) significantly suppresses growth and enhances apoptosis in melanoma cells [ 1 - 3 ]. (intechopen.com)
  • Bystander apoptosis was also evidenced in neighboring cells in a caspase 8-dependent manner. (archives-ouvertes.fr)
  • similarly, microglia (resident immune cells in the central nervous system) undergoes necroptotic death mediated by JNK when caspase 8 is blocked. (mimetech.eu)
  • Our results indicated that all the 5 genes (and (Oxidative stress-induced growth inhibitor 1) one of the highly upregulated genes in SASP-treated KSHV+ PEL cells from microarray data to determine its role in SASP-induced cell apoptosis. (biotech2012.org)
  • Sodium glucose cotransporter 2 inhibitors (SGLT2i) are the first antidiabetic compounds that effectively reduce heart failure hospitalization and cardiovascular death in type 2 diabetics. (frontiersin.org)
  • The parallel EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) clinical trials are designed to provide clinically relevant efficacy, dosing, and safety data from chronic administration in patients with nonalcoholic steatohepatitis (NASH) cirrhosis and fibrosis to support the design of Phase 3 efficacy and safety trials in these indications. (drugdiscoverynews.com)