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.
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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
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 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.
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.
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.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
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 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.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
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.
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.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Cytochromes 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.
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 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.
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)
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.
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.
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 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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
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.
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.
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 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 cell line derived from cultured tumor cells.
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.
Peptides composed of between two and twelve amino acids.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate 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.
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.
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.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Cells 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.
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.
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)
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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 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.
Physiologically inactive substances that can be converted to active enzymes.
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.
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 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.
Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.
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.
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.
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.
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.
A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
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.
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
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Elements of limited time intervals, contributing to particular results or situations.
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.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
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.
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glycoproteins found on the membrane or surface of cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
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.
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 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.
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.
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.
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.
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
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).
Proteins prepared by recombinant DNA technology.
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 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.
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.
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.
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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Microscopy 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.
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.
A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
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.
The action of a drug in promoting or enhancing the effectiveness of another drug.
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.
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 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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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).
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)
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.
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 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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
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.
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.
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).
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.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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).
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.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
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.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
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 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.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Compounds that inhibit cell production of DNA or RNA.
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.
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.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
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.
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.
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.
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.
Proteins found in any species of virus.
The process of cleaving a chemical compound by the addition of a molecule of water.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
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.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Recombinant 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 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.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins found in any species of insect.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
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)
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The process by which chemical compounds provide protection to cells against harmful agents.
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.
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.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.
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)
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.
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.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

Bcl-2 regulates amplification of caspase activation by cytochrome c. (1/8107)

Caspases, a family of specific proteases, have central roles in apoptosis [1]. Caspase activation in response to diverse apoptotic stimuli involves the relocalisation of cytochrome c from mitochondria to the cytoplasm where it stimulates the proteolytic processing of caspase precursors. Cytochrome c release is controlled by members of the Bcl-2 family of apoptosis regulators [2] [3]. The anti-apoptotic members Bcl-2 and Bcl-xL may also control caspase activation independently of cytochrome c relocalisation or may inhibit a positive feedback mechanism [4] [5] [6] [7]. Here, we investigate the role of Bcl-2 family proteins in the regulation of caspase activation using a model cell-free system. We found that Bcl-2 and Bcl-xL set a threshold in the amount of cytochrome c required to activate caspases, even in soluble extracts lacking mitochondria. Addition of dATP (which stimulates the procaspase-processing factor Apaf-1 [8] [9]) overcame inhibition of caspase activation by Bcl-2, but did not prevent the control of cytochrome c release from mitochondria by Bcl-2. Cytochrome c release was accelerated by active caspase-3 and this positive feedback was negatively regulated by Bcl-2. These results provide evidence for a mechanism to amplify caspase activation that is suppressed at several distinct steps by Bcl-2, even after cytochrome c is released from mitochondria.  (+info)

Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. (2/8107)

The cyclin-dependent kinase inhibitor p21waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells.  (+info)

Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. (3/8107)

The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery. Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site. Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.  (+info)

Activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 kinase in calphostin C-induced apoptosis requires caspase-3-like proteases but is dispensable for cell death. (4/8107)

Apoptosis was induced in human glioma cell lines by exposure to 100 nM calphostin C, a specific inhibitor of protein kinase C. Calphostin C-induced apoptosis was associated with synchronous down-regulation of Bcl-2 and Bcl-xL as well as activation of caspase-3 but not caspase-1. The exposure to calphostin C led to activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 kinase and concurrent inhibition of extracellular signal-regulated kinase (ERK). Upstream of ERK, Shc was shown to be activated, but its downstream Raf1 and ERK were inhibited. The pretreatment with acetyl-Tyr-Val-Ala-Asp-aldehyde, a relatively selective inhibitor of caspase-3, or benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk), a broad spectrum caspase inhibitor, similarly inhibited calphostin C-induced activation of SAPK/JNK and p38 kinase as well as apoptotic nuclear damages (chromatin condensation and DNA fragmentation) and cell shrinkage, suggesting that caspase-3 functions upstream of SAPK/JNK and p38 kinase, but did not block calphostin C-induced surface blebbing and cell death. On the other hand, the inhibition of SAPK/JNK by transfection of dominant negative SAPK/JNK and that of p38 kinase by SB203580 induced similar effects on the calphostin C-induced apoptotic phenotypes and cell death as did z-VAD.fmk and acetyl-Tyr-Val-Ala-Asp-aldehyde, but the calphostin C-induced PARP cleavage was not changed, suggesting that SAPK/JNK and p38 kinase are involved in the DNA fragmentation pathway downstream of caspase-3. The present findings suggest, therefore, that the activation of SAPK/JNK and p38 kinase is dispensable for calphostin C-mediated and z-VAD.fmk-resistant cell death.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (5/8107)

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. (6/8107)

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)

p27Kip1 induces drug resistance by preventing apoptosis upstream of cytochrome c release and procaspase-3 activation in leukemic cells. (7/8107)

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

MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (8/8107)

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.  (+info)

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.
Flow cytometry is used to detect the fragmented DNA. Conofocal microscopy to assesses the morphological features of apoptosis such as apoptotic blebs. DNA marker to detect the DNA fragmentation. The fragmented DNA, from the apoptic cell, will present a DNA ladder in comparison to the unfragmented live cell. Hoecht staining of apoptotic nuclei (with Hoescht 33342 as a blue stain) to determine the condensation and fragmentation of the nuclei. Hoechst 33342 binds preferentially to adenine-thymine (A-T) regions of DNA. This stain binds into the minor groove of DNA and exhibits distinct fluorescence emission spectra that are dependent on dye:base pair ratios. FLICA (flourochrome inhibitor of caspase) is a simple yet accurate method to measure apoptosis via caspase activity in whole cells. It applies the green fluorescent inhibitor probe FAM-VAD-FMK to label active caspase enzymes in the cell samples. FLICA probes are comprised of an inhibitor peptide sequence that binds to active caspase enzymes, a ...
Active Caspase 2 FITC Staining Kit (ab65612). Active caspase 2 detection in living cells by flow, microscopy or fluorescent plate reader.
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。
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.
Caspase detection antibodies and assays are used to help detect and study caspase activation in Apoptotic cells via immunoprecipitation and immunoblotting techniques.
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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 ...
The importance of the presented study lies in several key findings. First, our mechanistic knowledge of how the alternative splicing of caspase 9 is regulated has been expanded by our identification of a novel RNA cis-element via which SRSF1 (ASF/SF2) enhances the inclusion of the exon 3,4,5,6 cassette. Furthermore, SRSF1 was shown to specifically interact with this RNA cis-element, and regulate the alternative splicing of caspase 9 via this novel RNA cis-element. Second, we showed that the alternative splicing of caspase 9 is a relevant therapeutic target as shown by direct manipulation of this splicing cascade having significant effect on the sensitivity NSCLC cells to clinically relevant chemotherapeutics. Finally, one of the major findings of the report is our data showing that the synergism of erlotinib combination therapy is in part via modulation of the alternative splicing of caspase 9.. In regard to the RNA cis-element that specifically interacts with SRSF1, a purine-rich RNA ...
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Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
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Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner protein of apoptosis. Sequential activation
Effects of ponicidin on the activity of caspase-3 in MKN28 cells. After treatment, the activity of caspase-3 in MKN28 cells was analyzed by the caspase-3 assay
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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
Silibinin, a natural flavonolignan, induces apoptosis in human bladder transitional-cell papilloma RT4 cells both in vitro and in vivo; however, mechanisms of such efficacy are not completely identified. Here, we studied the mechanisms involved in silibinin-induced apoptosis of RT4 cells having intact p53. Silibinin increased p53 protein level together with its increased phosphorylation at serine 15, activated caspase cascade and caused Bid cleavage for apoptosis. Silibinin-caused p53 activation was mediated via ATM-Chk2 pathway, which in turn induced caspase 2-mediated apoptosis. Pifithrin-α, a p53 inhibitor, reversed silibinin-induced caspase activation including caspase 2; however, caspase 2 inhibitor also reversed p53 phosphorylation suggesting a bidirectional regulation between them. Further, silibinin caused a rapid translocation of p53 and Bid into mitochondria leading to increased permeabilization of mitochondrial membrane and cytochrome c release into the cytosol. JNK1/2 activation was ...
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 ...
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 ...
Purpose: To model the time evolution of active caspase-3 protein expression in a healthy lens, and in a lens exposed to UVR-300 nm (UVR-B). To develop an automated method to classify the fluorescent signal of biomarkers in the lens epithelial cells.. Methods: Six-week old Sprague-Dawley rats were used. Firstly, expression of active caspase-3 was studied in the lens epithelium of healthy rats. Secondly, rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-B for 15 minutes. At 0.5, 8, 16, and 24 hours after the UVR-B exposure, the exposed and the contralateral non-exposed lenses were removed. Immunohistochemistry was done on three mid-sagittal sections from each lens. The florescent labelling for active caspase-3 in each lens section was counted three times. The time evolution of active caspase-3 expression in response to UVR-B exposure was modelled as a function of cell position in the lens epithelium. An automated objective method was developed to quantify the lens epithelial cells and to ...
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 ...
[50 Pages Report] Check for Discount on Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC - Pipeline Review, H2 2016 report by Global Markets Direct. Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC...
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 ...
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Caspase Substrate Assay Kit (Colorimetric) is used for assaying activities of members of caspase 1/2/3/5/6/8/9. (KA3698) - Products - Abnova
Caspase 3 antibody LS-C88630 is a biotin-conjugated rabbit polyclonal that binds human, mouse, rat, bovine, dog, hamster, pig, rabbit, and sheep caspase 3 (also known as CASP3). Caspase 3 antibody is validated for use in IHC-paraffin, immunoprecipitation, and western blot.
Caspase-2, one of the most conserved of the caspase family members evolutionarily, provides been suggested as a factor in maintenance of chromosomal tumour and balance reductions. can either arise from different structural lesions, such simply because mutations, chromosomal translocations or deletions, or can result from statistical changes where cells lose or gain copies of entire chromosomes (aneuploidy).3 NVP-BEP800 As the most common chromosome abnormality in individuals, aneuploidy is the most common chromosome abnormality in individuals, is the trigger of many congenital delivery flaws and is found in the majority of good tumours.4 It is also regarded a key underlying factor to tumor onset and treatment. Aneuploidy occurs from extravagant mitotic occasions, including problems in centrosome quantity, kinetochore-microtubule accessories, spindle-assembly gate (SAC), chromosome telomeres or cohesion. 4 Aberrant mitotic police arrest systems normally result in cell loss of life by apoptosis, ...
Consistent with the reported role for the NLRP3 inflammasome in LPS plus Dox-induced IL-1β production by bone marrow-derived macrophages (14), we observed reduced IL-1β release at the early (≤8-h) stages of LPS plus Dox stimulation in BMDC lacking caspase-1 (Fig. 2A, 2B), ASC (Fig. 2C), or NLRP3 (Fig. 2C). However, when Dox stimulation was sustained, the relative contribution of this NLRP3/caspase-1 cascade to IL-1β accumulation was superseded by an alternative pathway that was attenuated in the absence of caspase-8 or TRIF (Figs. 2, 4, 5). Robust proteolytic maturation of caspase-1 per se was invariably observed in WT BMDC treated with LPS plus Dox (Figs. 1, 2, 4) or LPS plus STS (Fig. 6), despite the fact that caspase-1 was dispensable for maximal IL-1β processing. We initially expected that the activation of caspase-1 and caspase-8 in response to Dox or STS comprised independent IL-1β-processing pathways operating in parallel. However, our observations and recent studies by others ...
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.
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 ...
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. ...
Click to launch & play an online audio visual presentation by Prof. Guy Salvesen on Natural caspase inhibitors, part of a collection of online lectures.
We observed previously that cisplatin-resistant HeLa cells were cross-resistant to UV light due to accumulation of DDB2, a protein implicated in DNA repair. More recently, we found that cFLIP, which represents an anti-apoptotic protein whose level is induced by DDB2, was implicated in preventing apoptosis induced by deathreceptor signaling. In the present study, we investigated whether DDB2 has a protective role against UV irradiation and whether cFLIP is also involved in this process. Methods: We explored the role of DDB2 in mediating UV resistance in both human cells and Drosophila. ...
This video will show you how to perform an apoptosis assay using adherent cells on the Celigo image cytometer using caspase 3/7 and Hoechst reagents.
This gene encodes 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 which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013 ...
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.. ...
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Fig: Stem cell treatment after MCAO procedure reduces caspase-dependent apoptosis and brain damage. a Green fluorescence indicates cleaved caspase 3 protein expression. Representative cleaved caspase3 images were merged with respective DAPI images. Scale bar 100 lm. b Quantification of cleaved caspase-3 protein expression in the ipsilateral hemisphere of untreated [15] and hUCBSCs-treated animals. n C 3. Values are expressed as mean ± SEM; *p\0.05 compared to untreated MCAO subjected animals. c Representative hematoxylin and eosin stained paraffinembedded tissue sections from rat brains. Higher magnification images from the ischemic cortex and striatal regions of MCAOsubjected and untreated animals show interstitial edema and damaged neurons that have a condensed, irregular shaped and darkly stained nuclei which are absent or less frequent in control/hUCBSCs-treated brain sections. Each group consisted of a minimum of three animals. Scale bar value for the magnified images = 100 lm ...
|strong|Rabbit anti caspase-9 p10 antibody|/strong| recognizes caspase-9, a member of the cysteine-aspartic acid protease family. The active form of caspase-9 is generated by cleavage of the pro-caspa…
Caspase-1 Inhibitor I - CAS 143313-51-3 - Calbiochem The Caspase-1 Inhibitor I, also referenced under CAS 143313-51-3, controls the biological activity of Caspase-1. This small molecule/inhibitor is primarily used for Cancer applications. - Find MSDS or SDS, a COA, data sheets and more information.
Rabbit polyclonal active Caspase-3 antibody validated for WB, ICC/IF and tested in Human, Mouse and Rat. Referenced in 2 publications and 3 independent…
Research tested and proven Caspase-10/b-Flice 2 antibody. Antibody is guaranteed to work in western blot applications and is reactive in human and mouse.
The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
... which resembles that of the animal caspases. Similarly to the animal caspases, the phytaspase is a cell death promoting ... In contrast with the animal caspases, that exist in the cytoplasm in a form of pre-synthesized precursors, the activation of ... Porter, A. G.; Jänicke, R. U. (1999-02-01). "Emerging roles of caspase-3 in apoptosis". Cell Death and Differentiation. 6 (2): ... The phytaspase displays a strict substrate specificity, which resembles that of the animal caspase-3. It recognizes a ...
2003 nomenclature IA - Fas IB - Fas ligand IIA - Caspase 10 IIB - Caspase 8 III - unknown IV - Neuroblastoma RAS viral oncogene ... Caspase 10. Germline CASP10 mutation. 2% of patients ALPS-U: Undefined. 20% of patients CEDS: Caspase 8 deficiency state. No ... Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... 9 (3): 233-5. PMID 21475130. Archived from the original on 2012-04-26.[unreliable medical source?] Van Der Werff Ten Bosch, ...
Caspase proteins are crucial mediators of apoptosis, with caspase-3 and caspase-8 being death proteases. Considering ... RU, Porter AG and Jänicke (1999). "Emerging roles of caspase-3 in apoptosis. - PubMed - NCBI". Cell Death and Differentiation. ... This is due to an increased expression of caspase3 and caspase‐8. ... 77 (3): 182-185. doi:10.1016/j.jdermsci.2015.01.006. ISSN 0923-1811. Lee, Chang Seok; Joo, Yung Hyup; Baek, Heung Soo; Park, ...
Lo SS, Lo SH, Lo SH (2005). "Cleavage of cten by caspase-3 during apoptosis". Oncogene. 24 (26): 4311-4. doi:10.1038/sj.onc. ... 2007). "A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration". Nat. Cell Biol. 9 (8): 961-9. doi: ... 2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Mol. Cell. Proteomics. 4 (6 ... 13 (3): 317-9. doi:10.1016/j.devcel.2007.08.010. PMID 17765673. v t e. ...
In caspase-3 the 'hook' and 'sinker' attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. ... This is done through the binding to caspases directly. Similar to the functionality of NAIP, the BIR3 domain of XIAP binds to ... This is unexpected because, in nerve growth factor withdrawal, caspase-3 and -9 are activated, causing cell death, which are ... When overexpressed, XIAP is able to block caspases extremely well and prevents cell death of sympathetic neurons when nerve ...
Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs[5] have been ... Apoptosis & Caspase 8-The Proteolysis Map (animation). *Caspase 8 at the US National Library of Medicine Medical Subject ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1f9e: CASPASE-8 SPECIFICITY PROBED AT SUBSITE S4: CRYSTAL STRUCTURE OF THE CASPASE-8-Z-DEVD-CHO ...
Rho inactivation can activate caspase-3 and caspase-9; two key components of the apoptotic pathway. TcdA has been linked to ... 56 (3): 582-8. doi:10.1128/IAI.56.3.582-588.1988. PMC 259330. PMID 3343050. Lyras D, O'Connor JR, Howarth PM, Sambol SP, Carter ... 93 (3): 1257-65. doi:10.1172/JCI117080. PMC 294078. PMID 7907603. Flegel WA, Müller F, Däubener W, Fischer HG, Hadding U, ... 35 (3): 1032-40. doi:10.1128/IAI.35.3.1032-1040.1982. PMC 351151. PMID 7068210. von Eichel-Streiber C, Laufenberg-Feldmann R, ...
Chen, Y R; Kori R; John B; Tan T H (Nov 2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins ... Chen YR, Kori R, John B, Tan TH (2001). "Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins ... HCLS1 has been shown to interact with Caspase 3. GRCh38: Ensembl release 89: ENSG00000180353 - Ensembl, May 2017 GRCm38: ... induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells". ...
In residue 321, the change of aspartic acid (D) to Asparagine (N) reveals as loss of proteolytic cleavage by caspases. Those ... STK24 operates on serine and threonine residues and, as a response to oxidative stress and caspase activity, develops cell ... "Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis". The Journal ... "Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis". The Journal ...
"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 ... Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (January 1998). "A caspase-activated DNase that degrades DNA ... Liu X, Zou H, Widlak P, Garrard W, Wang X (May 1999). "Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase ...
Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... This allows normal caspase activity to proceed. The binding process of Smac/DIABLO to XIAP and caspase release requires a ... 2 region that is thought to contain the only element that comes into contact with the caspase molecule to form the XIAP/Caspase ... Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1, MAP3K2, TAB1, and XAF1. GRCm38: Ensembl release 89: ...
... induces apoptosis by increasing caspase-3 and PARP cleavage. These proteins induce programmed cell death when ... A shorter version that is also pointed out as the IUPAC name is (3b-5b)-3-[(6-deoxy-a-L-mannopyranosyl)oxy]-5,14-dihydroxy-19- ... This can be done via the Koenigs-Knorr method, in which strophanthidin is glycosylated with 2,3,4-tri-O-acetyl-a-L- ... However, it has been demonstrated that convallatoxin induces apoptosis and autophagy at a dose of 10 nM per 3 days. It was also ...
Caspase 3 is reported to be involved in the proteolytic processing of this protein. Two alternatively spliced transcript ... This cytokine is produced as a precursor peptide (pro-IL-16) that requires processing by an enzyme called caspase-3 to become ... 1998). "Processing and activation of pro-interleukin-16 by caspase-3". J. Biol. Chem. 273 (2): 1144-9. doi:10.1074/jbc.273.2. ... doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Zhang Y, Center DM, Wu DM, et al. ( ...
CARD: Caspase recruitment domain, retrieved 3 November 2016 Bouchier-Hayes, L; Martin, SJ (2002). "CARD games in apoptosis and ... DDs can also be found with other types of domains including Ankyrin repeats, caspase-like folds, kinase domains, leucine ... Protein modules containing the CARD domain are associated with apoptosis, through the regulation of caspases that they are ... There are four types of death domain subfamilies: death effector domain (DED), caspase recruitment domain (CARD), pyrin domain ...
Swanton E, Bishop N, Woodman P (Dec 1999). "Human rabaptin-5 is selectively cleaved by caspase-3 during apoptosis". The Journal ... 346 (3): 593-601. doi:10.1042/0264-6021:3460593. PMC 1220890. PMID 10698684. Hirst J, Lui WW, Bright NA, Totty N, Seaman MN, ... 83 (3): 423-32. doi:10.1016/0092-8674(95)90120-5. PMID 8521472. "Entrez Gene: RABEP1 rabaptin, RAB GTPase binding effector ... 508 (2): 201-9. doi:10.1016/s0014-5793(01)02993-3. PMID 11718716. S2CID 21545088. Xiao GH, Shoarinejad F, Jin F, Golemis EA, ...
Affar, E. B.; Germain, M.; Winstall, E.; Vodenicharov, M.; Shah, R. G.; Salvesen, G. S.; Poirier, G. G. (2000). "Caspase-3- ... 392 (3): 499-509. doi:10.1042/BJ20050792. PMC 1316289. PMID 16117724. This article incorporates text from the United States ...
"Characterization of beta-N-acetylglucosaminidase cleavage by caspase-3 during apoptosis". J. Biol. Chem. 283 (35): 23557-66. ...
... is able to suppress caspase-3 through MAPK and PKCalpha. Apoptosis as a result of anoxia/reoxygenation and H(2)O(2) ... "The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha". Biochimica et ... 284 (3): 1082-1094. PMID 9495870. Dong, J.; De Montigny, C.; Blier, P. (1998). "Full agonistic properties of BAY x 3702 on ... 3 (6): 924-7. PMID 12137415. Teal, P; Davis, S; Hacke, W; Kaste, M; Lyden, PD; Modified Randomized Exposure Controlled Trial ...
Mitchell DA, Marletta MA (August 2005). "Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine". Nat. ... Nitrosylated thioredoxin, via directed protein-protein interaction, trans-nitrosylates the active site cysteine of caspase-3 ... thus inactivating caspase-3 and preventing induction of apoptosis. As might be expected of an enzyme involved in regulating NO ... 129 (3): 511-22. doi:10.1016/j.cell.2007.02.046. PMID 17482545. S2CID 14171859. Que LG, Liu L, Yan Y, Whitehead GS, Gavett SH, ...
Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC, de Thé H (November 1998). "PML induces a novel caspase-independent death ... Retinoic acid induces a caspase-3 mediated degradation of the same chimera. In HHV, ICP0 disrupts nuclear dots in the early ... October 1998). "Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion ... doi:10.1007/978-3-662-08456-4_28. ISBN 978-3-540-07208-9. PMID 168720. Jones JM, Martinez AJ, Joshi VV, McWilliams N (March ...
However among the four WNK family members, only WNK3 has been shown to regulate and increase cell survival in a caspase-3- ... Veríssimo F, Silva E, Morris JD, Pepperkok R, Jordan P (Jul 2006). "Protein kinase WNK3 increases cell survival in a caspase-3- ... 7 (3): 221-8. doi:10.1038/nn1188. PMID 14966521. Llorens F, Gil V, Iraola S, Carim-Todd L, Martí E, Estivill X, Soriano E, del ... 7 (3): 221-8. doi:10.1038/nn1188. PMID 14966521. Shao Z, Browning JL, Lee X, Scott ML, Shulga-Morskaya S, Allaire N, Thill G, ...
In each case, caspase 9 activation leads to the activation of a full caspase cascade and subsequent cell death. It has been ... This functional apoptosome then can provide a platform activation of caspase 9. Caspase 9 exists as a zymogen in the cytosol ... Another targeted molecule for cancer therapy involves the caspase family and their regulators. The inhibition of caspase ... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ...
"Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the ... protein is cleaved by caspase-3 during apoptosis". The Journal of Biological Chemistry. 272 (46): 29238-42. doi:10.1074/jbc. ... 16 (3): 572-9. doi:10.1006/geno.1993.1232. PMID 8325628. Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, Malley T, ... 5 (3): 373-9. doi:10.1093/hmg/5.3.373. PMID 8852663. Margolis RL, Li SH, Young WS, Wagster MV, Stine OC, Kidwai AS, Ashworth RG ...
Takahashi M, Mukai H, Toshimori M, Miyamoto M, Ono Y (1998). "Proteolytic activation of PKN by caspase-3 or related protease ... The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal ... 234 (3): 621-5. doi:10.1006/bbrc.1997.6669. PMID 9175763. Goedert M, Hasegawa M, Jakes R, Lawler S, Cuenda A, Cohen P (1997). " ... 234 (3): 621-5. doi:10.1006/bbrc.1997.6669. PMID 9175763. Kato T, Gotoh Y, Hoffman A, Ono Y (May 2008). "Negative regulation of ...
Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y (Sep 1999). "Acinus is a caspase-3-activated protein required for ... 2001). "Caspase activation is required for terminal erythroid differentiation". J. Exp. Med. 193 (2): 247-54. doi:10.1084/jem. ... 2003). "Specific involvement of caspases in the differentiation of monocytes into macrophages". Blood. 100 (13): 4446-53. doi: ... 127 (3): 635-48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. Shu Y, Iijima T, Sun W, et al. (2007). "The ACIN1 gene is ...
"The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 ... "The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the caspase-8 ... "Proteolytic regulation of Forkhead transcription factor FOXO3a by caspase-3-like proteases". Oncogene. 22 (29): 4557-68. doi: ... 21 (3): 952-65. doi:10.1128/MCB.21.3.952-965.2001. PMC 86685. PMID 11154281. Schuur ER, Loktev AV, Sharma M, Sun Z, Roth RA, ...
2006). "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway". Oncogene. 25 (30): 4172-82. doi:10.1038/ ... and it plays a role in the increase of cell survival in a caspase 3 dependent pathway. GRCh38: Ensembl release 89: ... 33 (10): 2250-3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086. This article incorporates text from the United States ... "Entrez Gene: WNK lysine deficient protein kinase 3". Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the ...
Stierle, Donald B.; Stierle, Andrea A.; Girtsman, Teri; McIntyre, Kyle; Nichols, Jesse (2012). "Caspase-1 and -3 Inhibiting ... 104 (3): 604-12. doi:10.3852/11-119. PMID 22241612. Carl A. Batt (2014). Encyclopedia of Food Microbiology. Academic Press. ...
Smart AD, Pache RA, Thomsen ND, Kortemme T, Davis GW, Wells JA (September 2017). "Engineering a light-activated caspase-3 for ... 114 (3): 668a. Bibcode:2018BpJ...114..668A. doi:10.1016/j.bpj.2017.11.3607. Zhao S, Cunha C, Zhang F, Liu Q, Gloss B, ... 124 (3): 1114-29. doi:10.1172/JCI69050. PMC 3934189. PMID 24509078. Keppeler D, Merino RM, Lopez de la Morena D, Bali B, Huet ... 23 (3): 346-52. doi:10.1016/j.conb.2013.01.013. PMC 3672317. PMID 23402950. Karalis N, Dejean C, Chaudun F, Khoder S, Rozeske ...
A follow-up study researched to determine if the caspases were involved in the apoptosis seen in the previous study as well as ... The study confirmed that there was cleavage of caspase-3, -8, and -9. All three of these cysteine proteases play an important ... 8 (3): 343-52. PMID 9056677. Archived from the original on 2014-04-26. Thyrell L, Erickson S, Zhivotovsky B, et al. (February ... encoding interferon lambda 3, are associated with significant differences in response to the treatment. This finding, ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 18 (3): 914-22. PMC 2042137. PMID 9437013.. *^ Nielsen AL, Holm IE, Johansen M, Bonven B, Jørgensen P, Jørgensen AL (August ... 10 (3): 563-8. doi:10.1097/00001756-199902250-00022. PMID 10208590.. *^ Zhang W, Han SW, McKeel DW, Goate A, Wu JY (February ... doi:10.1016/S0896-6273(00)80291-3. PMID 8755489.. *^ Ratovitski T, Slunt HH, Thinakaran G, Price DL, Sisodia SS, Borchelt DR ( ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... ISBN 978-3-318-02253-7.. *^ Sethakulvichai, W.; Manitpornsut, S.; Wiboonrat, M.; Lilakiatsakun, W.; Assawamakin, A.; Tongsima, ... 3 (2): 243-54. PMID 10464676.. *. Martin J, et al. (2004). "The sequence and analysis of duplication-rich human chromosome 16 ... Chromosome 16 spans about 90 million base pairs (the building material of DNA) and represents just under 3% of the total DNA in ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[30 ... 1 (3): 191-98. doi:10.1038/35044558. PMID 11257907. S2CID 9750498.. *^ a b Zhong L, Yan CH, Lu CQ, Xu J, Huang H, Shen XM ( ... 3: 1. doi:10.3389/neuro.02.001.2010. PMC 2821174. PMID 20162032.. *^ Dincheva I, Lynch NB, Lee FS (October 2016). "The Role of ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ...
... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... 8 (3): 197-204. doi:10.1007/s10456-005-9010-0. PMID 16328160. Mercurio, Arthur M; Bachelder, Robin E; Bates, Richard C; Chung, ... STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase ... Their research showed that autocrine IL-6 signaling induced malignant features in Notch-3 expressing mammospheres. Another ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... 3 (4): 255-61. PMID 16978533.. *^ a b c Stadtmueller, BM; Hill, CP (7 January 2011). "Proteasome activators". Molecular Cell. ... 15 (3): 237-44. doi:10.1038/nsmb.1389. PMID 18278055.. *^ Zwickl P, Ng D, Woo KM, Klenk HP, Goldberg AL (September 1999). "An ... 3 (1): 20-6. doi:10.1038/ni0102-20. PMID 11753406.. *^ Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ... "Mucociliary escalator." Saunders Comprehensive Veterinary Dictionary, 3 ed.. 2007. Elsevier, Inc. 11 Jun. 2018 ...
Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... 1 (3): 264-75. PMID 12851985.. *^ Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T (2002). " ... 3. Analysis of mechanism". J. Exp. Med. 128 (6): 1267-79. doi:10.1084/jem.128.6.1267. PMC 2138574. PMID 5693925.. ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 117 (3): 659-71. doi:10.1172/JCI29562. PMC 1797603. PMID 17318264.. *^ a b Hahnen E, Eyüpoglu IY, Brichta L, Haastert K, ... M (y) 2; H (ni) 3 M (y) 9; H (ny) D (y) 11 R (y) 17; H (ny) MC 23, 24; M (y) 25; H (v) 26, 27, 28, 29 ... 19 (3): 895-907. doi:10.3233/JAD-2010-1284. PMID 20157245.. *^ Byun CJ, Seo J, Jo SA, Park YJ, Klug M, Rehli M, Park MH, Jo I ( ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... Pomalidomide (3-aminothalidomide) was the second thalidomide analog to enter the clinic being more potent than both of its ... April 2002). "S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice". Cancer Res. 62 ... 3 (4): 170-181. doi:10.1016/j.uct.2009.03.003. Zeldis, Jerome B.; Knight, Robert; Hussein, Mohamad; Chopra, Rajesh; Muller, ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[27 ... 1 (3): 191-98. doi:10.1038/35044558. PMID 11257907.. *^ a b Zhong L, Yan CH, Lu CQ, Xu J, Huang H, Shen XM (September 2009). " ... 22 (3): 123-31. doi:10.1080/08977190410001723308. PMC 2504526. PMID 15518235.. *^ a b Jones KR, Reichardt LF (October 1990). " ... 3: 1. doi:10.3389/neuro.02.001.2010. PMC 2821174. PMID 20162032.. *^ Dincheva I, Lynch NB, Lee FS (October 2016). "The Role of ...
This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 ... Caspase 3. Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl- ... Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation. *UMich Orientation of Proteins in Membranes families/superfamily-78 ... where it activates the caspase family of proteases is believed to be primary trigger leading to the onset of apoptosis.[27] ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ... 21 (FVII · FIX · FX · FXI · FXII · FD · PROC · Trombin) · .22 · .23 · .24 (.1 ALA · .7 MMP-1 · .17 MMP-3/MMP-6 · .19 BMP-1 · . ... 16 · .17 (.1 CPA · .2 CPB · .3 CPN · .4 CPS · .6 ACP · .9 CPS · .21 PSMA) · .18 ... 3 HSD · .4 · .5 · .6 · .7 · .8 · .9 · .10 · .11 · .12 · .13 · .14 · .15 · .16 · .17 · .18 · .19 · .20 · .21 · .22 · .23 · .24 · ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ... 21 (FVII · FIX · FX · FXI · FXII · FD · PROC · Trombin) · .22 · .23 · .24 (.1 ALA · .7 MMP-1 · .17 MMP-3/MMP-6 · .19 BMP-1 · . ... Kinase fosfatidil inositol-3 (bahasa Inggris: phosphatidyl inositol-3 kinase, Phosphoinositide 3-kinases, PI3K) merupakan enzim ... Fosfatidil inositol-3 kinase. Dari Wikipedia bahasa Indonesia, ensiklopedia bebas. (Dialihkan dari Kinase fosfatidil inositol-3 ...
This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does ... This page was last edited on 3 June 2019, at 12:47 (UTC). ... 8 (3): 400-5. doi:10.3748/wjg.v8.i3.400. PMC 4656409. PMID ... 18 Suppl 3 (90003): iii9-12. doi:10.1093/ndt/gfg1003. PMID 12771291.. ...
"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase ... Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower and Gardenia jasminoides[3] (fruits). ... InChI=1S/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+, ... InChI=1/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12 ...
"A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site- ... Eukaryotic initiation factor 3 (eIF3). References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000107581 - Ensembl, May ... 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.. *^ a b Morris-Desbois C, Réty S, Ferro M, Garin J, Jalinot P ( ... Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene.[5][6][7] ...
Non obstante, a TRADD únese a FADD, o cal despois recruta a cisteína protease caspase-8. Unha alta concentración de caspase-8 ... Por outra parte, as caspases activadas clivan varios compoñentes da vía NF-κB, incluíndo a RIP, IKK, e as propias subunidades ... 3. Analysis of mechanism". J. Exp. Med. 128 (6): 1267-79. PMC 2138574. PMID 5693925. doi:10.1084/jem.128.6.1267.. ... O xene humano que codifica o TNFα, denominado TNFA foi clonado en 1985.[17] Foi mapado no 6p21.3, e abrangue uns 3 kb e contén ...
Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ... Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine. 11 (7): 725-30. doi:10.1038/nm1263. PMID ...
Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases ... 2] IPM에 의하여 망막색소상피 전구체가 망막색소상피세포로 성숙된다.[3] 해부학적 위치[편집]. 망막색소상피세포는 육각형 모양의 세포들이 단일층을 구성하고 있다. [4] 이 세포들은 색소 과립 (pigmented ... "DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration". 》PNAS》 111 (45): 16082 ... 기형종(Teratoma, 테라토마) : 인체 내의 3배엽 중에서 한 가지 배엽 이상의 세포가 발견되는 암을 의미함.(출처 : [[2]]) 혹은, 3배엽(외배엽, 내배엽, 중배엽) 유래의 세포나 조직이 관찰되는 종양을 의미한다.[ ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... 77 (1): 3-10. doi:10.1093/bja/77.1.3. PMID 8703628.. *^ Klaassen, C.D., Ed.: Casarett and Doull's Toxicology: The Basic Science ... 3 Types of damage *3.1 Sub-lethal (reversible) *3.1.1 Cellular swelling ... 704 (1-3): 152-159. doi:10.1016/j.mrrev.2009.12.005. PMC 3074954. PMID 20060490.. ...
... -1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... Pyroptosis by Caspase-4 and Caspase-5 in humans and Caspase-11 in mice ... Activation of caspasesEdit. Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... 1,0 1,1 1,2 1,3 1,4 Daneholt, Bertil. "Advanced Information: RNA interference". The Nobel Prize in Physiology or Medicine 2006 ... doi:10.1007/3-540-27262-3_5.. *↑ Vanhecke D, Janitz M (2005). "Functional genomics using high-throughput RNA interference". ... "Proc Natl Acad Sci USA 99 (3): 1443-8. PMC 122210. PMID 11818553. doi:10.1073/pnas.032652399.. ...
This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 ... 978-3-319-11730-0. . PMID 25487014.. *^ Wegele H, Müller L, Buchner J (2004). Hsp70 and Hsp90 - a relay team for protein ... 978-3-540-22096-1. . PMID 14740253.. *^ Cvoro A, Dundjerski J, Trajković D, Matić G (1999-04-01). "The level and ... The Hsp70s are an important part of the cell's machinery for protein folding, and help to protect cells from stress.[2][3] ...
a b Nikolaev A. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19. februar 2009;457(7232): ... 1987;1(1):3-8. PMID 3331112.. *. Maurer Ulrike; Maurer Konrad (2003). Alzheimer: The Life of a Physician and the Career of a ... 3: CD007726. PMID 23543555. doi:10.1002/14651858.CD007726.pub2.. *^ Huperzine A for Alzheimer's disease. The Cochrane Database ... 2006;21(3):175-81. doi:10.1159/000090733. PMID 16401889. *^ a b Informal Costs of Dementia Care: Estimates from the National ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... Cysteine (symbol Cys or C;[3] /ˈsɪstiiːn/)[4] is a semiessential[5] proteinogenic amino acid with the formula HO2CCH(NH2)CH2SH ... 3 (11): 836-47. doi:10.1038/nrm954. PMID 12415301.. *^ Huang, Tzou-Chi; Ho, Chi-Tang. Hui, Y. H.; Nip, Wai-Kit; Rogers, Robert ... ISBN 3-527-30673-0.. *^ Hell R (1997). "Molecular physiology of plant sulfur metabolism". Planta. 202 (2): 138-48. doi:10.1007/ ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases. Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on ... 18 (3): 289-97. doi:10.1097/MOL.0b013e3281338d08. PMID 17495603.. *. Seol W, Choi HS, Moore DD (Jan 1995). "Isolation of ... doi:10.1016/S0016-5085(03)00388-3. PMID 12806625.. *. Holt JA, Luo G, Billin AN, Bisi J, McNeill YY, Kozarsky KF, Donahee M, ... Polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene, benzo[a]pyrene, benzanthracenes, benzoflavones (e.g., beta- ...
doi:10.1007/0-306-46826-3_29. PMID 10849754.. *. Brinkworth RI, Tort JF, Brindley PJ, Dalton JP (2000). "Phylogenetic ... Caspase. *Caspase 1. *Caspase 2. *Caspase 3. *Caspase 4. *Caspase 5. *Caspase 6 ...
Also, it is extensively used in research for the detection of DNA damage,[34][35] caspase cleavage and apoptosis.[36] In ... Apoptosis (quantification, measurement of DNA degradation, mitochondrial membrane potential, permeability changes, caspase ... 45 (3): 194-205. doi:10.1002/1097-0320(20011101)45:3,194::aid-cyto1163,3.0.co;2-c. ISSN 0196-4763. PMID 11746088.. ... 27 (3): 653-70, viii. doi:10.1016/j.cll.2007.05.008. PMC 2034394 . PMID 17658411.. ...
Aigéad éarúcach Erucic acid] - CH3(CH2)7CH=CH(CH2)11COOH ... Caspase. *Ceallaláis Cellulase. *Ceallalós Cellulose. * ... Aigéad úrach Uric acid - C5H4N4O3 ... Cytosine - C4H5N3O. D[cuir in eagar , athraigh foinse]. *Aigéad ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Molecular Docking Analysis of Caspase-3 Activators as Potential Anticancer Agents.. Kashaw SK, Agarwal S, Mishra M, Sau S, Iyer ... Pharmacophore Modeling, Docking and Molecular Dynamics Studies on Caspase-3 Activators Binding at β-Tubulin Site. Bhunia SS et ... Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinsons Disease. Yuan J et al. PLoS ... Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. Sharma S et al. Biomed Res Int. (2013 ...
Caspases are crucial mediators of programmed cell death (apoptosis). Among them, caspase-3 is a frequently activated death ... Caspase-3 is essential for normal brain development and is important or essential in other apoptotic scenarios in a remarkable ... Thus, caspase-3 is essential for certain processes associated with the dismantling of the cell and the formation of apoptotic ... Pathways to caspase-3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c ...
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Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ... caspase activity would kill cells indiscriminately. As an executioner caspase, the caspase-3 zymogen has virtually no activity ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10 ...
Caspase-3. A. 175. Homo sapiens. Mutation(s): 2 Gene Names: CASP3, CPP32. EC: ... Caspase-3. B. 102. Homo sapiens. Mutation(s): 1 Gene Names: CASP3, CPP32. EC: ... Ser 150 evolved with the apoptotic caspases, whereas Thr 152 is a more recent evolutionary event in mammalian caspase-3. ... Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is ...
Caspase-3 subunit p17. A. 175. Homo sapiens. Mutation(s): 1 Gene Names: CASP3, CPP32. EC: ... Caspase-3 subunit p12. B. 102. Homo sapiens. Mutation(s): 0 Gene Names: CASP3, CPP32. EC: ... Ser 150 evolved with the apoptotic caspases, whereas Thr 152 is a more recent evolutionary event in mammalian caspase-3. ... Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is ...
MCF-7 human breast cancer cells do not express caspase 3, thought by some to be a critical component of the apoptosis cascade. ... Apoptosis in the absence of caspase 3 Oncogene. 2001 Oct 4;20(45):6570-8. doi: 10.1038/sj.onc.1204815. ... MCF-7 human breast cancer cells do not express caspase 3, thought by some to be a critical component of the apoptosis cascade. ... Using a series of caspase inhibitors with overlapping specificities, enzyme-specific chromogenic substrates, and an antibody ...
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Rabbit polyclonal Caspase-3 antibody. Validated in WB, IP, IHC, ICC/IF and tested in Mouse, Rat, Rabbit, Human, Monkey. Cited ... Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the ... Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice ... associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the ...
Caspase-7 Activation , Caspase-9 Activation, Chemopreventive. Additional Keywords : Beet, Benzo(a)pyrene, Betaine, lung cancer ... Caspase-8 activation, Caspase-9 Activation, Tumor Suppressor Protein p53 Upregulation ... Caspase-8 activation, Caspase-9 Activation, Cell cycle arrest, Chemotherapeutic ... Baicalein could increase caspase-3 and Bax expression and decrease survivin and Bcl-2 to induce apoptosis.Aug 31, 2017. ...
Cleaved caspase-3 product listings, product citations, comparison tables and educational resources for apoptosis signaling from ... Caspases, a family of cysteine proteases, are the central regulators of apoptosis. Initiator caspases (including caspase-2, -8 ... Once activated, initiation caspases cleave and activate downstream effector caspases (including caspase-3, -6, and -7), which ... Caspase-3 Western Blotting Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664. Western blot analysis of extracts from C6 (rat ...
Rabbit polyclonal Caspase-3 antibody validated for WB, IHC and tested in Human, Mouse, Rat and Rabbit. Referenced in 16 ... Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the ... Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice ... associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the ...
Effector caspases-3, -6 and -7 are responsible for producing the morphological features associated with apoptosis, such as DNA ... Inhibition of caspase-7 activity reduced the extent of apoptosis induced, indicating that activation of caspase-7 is involved ... Apoptosis was accompanied by DNA fragmentation and the activation of caspase-7, but not caspases-3 and -6. ... Caspase-3 is not essential for DNA fragmentation in MCF-7 cells during apoptosis induced by the pyrrolo-1,5-benzoxazepine, PBOX ...
Both caspase-3- and caspase-9-deficient mice exhibit a variably severe neurodevelopmental phenotype that may include marked ... Targeted gene disruptions have revealed significant roles for caspase family members in the regulation of neuronal programmed ... strain-dependent compensatory caspase activation and/or its inhibition may influence the severity of the caspase-3-deficient ... Strain-dependent neurodevelopmental abnormalities in caspase-3-deficient mice J Neuropathol Exp Neurol. 2002 Aug;61(8):673-7. ...
Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage (By similarity). ... Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it ... PS01122 CASPASE_CYS, 1 hit. PS01121 CASPASE_HIS, 1 hit. PS50207 CASPASE_P10, 1 hit. PS50208 CASPASE_P20, 1 hit. ... PS01122 CASPASE_CYS, 1 hit. PS01121 CASPASE_HIS, 1 hit. PS50207 CASPASE_P10, 1 hit. PS50208 CASPASE_P20, 1 hit. ...
MilliporeSigma Calbiochem Caspase-3 Substrate IV, Fluorogenic 5mg Life Sciences:Protein Biology:Protein Extraction and ...
Characterization of a novel proapoptotic caspase-2- and caspase-9-binding protein. Bonfoco, E., Li, E., Kolbinger, F., Cooper, ... A DEVD-inhibited caspase other than CPP32 is involved in the commitment of cerebellar granule neurons to apoptosis induced by ... Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. ... Rapid upregulation of caspase-3 in rat spinal cord after injury: mRNA, protein, and cellular localization correlates with ...
Cleavage of Rh110 peptides by caspases generates strongly fluorescent Rh110 that is monitored fluorimetrically at 510-530 nm ... caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase ... Caspase-3 substrate and caspase-7 substrate; (Z-DEVD)2-Rh110; z-(Asp-Glu-Val-Asp)2-Rh110 ... Caspase 3 (Apopain) Substrate 1r-z, fluorogenic; Rh110 (rhodamine 110)-derived ...
caspase-3-like Symbol and Name status set to provisional. 70820. PROVISIONAL. ... 3. 0.0001. tibia size trait (VT:0100001). tibia midshaft cross-sectional area (CMO:0001717). 8. 33558660. 89058369. Rat. ... Hepatocarcinoma resistance QTL 3. 2.9. 0.0005. liver integrity trait (VT:0010547). volume of individual liver tumorous lesion ( ... 3. blood glucose amount (VT:0000188). blood glucose level (CMO:0000046). 8. 30144800. 75144800. Rat. ...
It has been widely accepted that the activation of effector caspases, such as caspase-3, will eventually lead to apoptosis of a ... The cleavage of PARP by caspases (such as caspase-3) facilitates cellular disassembly and serves as a marker of cells ... I: Quantitation of caspase-3 labeled neurons. *P ≤ 0.05. Bar = 50 μm in A-C, F, and G; 100 μm in D and E; and 7.4 μm in H. ... with Apaf-1 and caspase-9, forms the apoptosome, which then generates a downstream cascade of caspase activation. Other ...
Invitrogen Anti-Caspase 3 Polyclonal, Catalog # PA5-96077. Tested in Western Blot (WB), Immunofluorescence (IF), ... Cite Caspase 3 Polyclonal Antibody. The following antibody was used in this experiment: Caspase 3 Polyclonal Antibody from ... Caspase-3; Caspase-3 subunit p12; Caspase-3 subunit p17; CPP-32; CPP32beta; Cysteine protease CPP32; IRP; LICE; PARP cleavage ... Caspase 3 apoptosis related cysteine protease (ICE-like cysteine protease); caspase 3, apoptosis related cysteine protease; ...
Invitrogen Anti-Caspase 3 Monoclonal (3CSP03), Catalog # MA1-26415. Tested in Immunohistochemistry (Paraffin) (IHC (P)) ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. It is the ... Cite Caspase 3 Monoclonal Antibody (3CSP03). The following product was used in this experiment: Caspase 3 Monoclonal Antibody ( ...
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by ... Caspase Colorimetric Assay Kits & Caspase Fluorescent Assay Kits. The Caspase-3 Colorimetric Assays measure the proteolytic ... Caspase Colorimetric and Fluorescent Assay Kits. The ApoAlert Caspase Assay Kits provide a simple and convenient way to detect ... Simultaneously profile multiple caspases *Perform the assay directly on cell lysates *Fast and easy: caspase colorimetric ...
The Caspase-3 and -8 Colorimetric Assays kits measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by ... The ApoAlert Caspase Profiling Plate measures the activation of four different caspases (caspase-2, -3, -8, and -9) using a ... Caspase Colorimetric Assay Kits & Caspase Fluorescent Assay Kits. The Caspase-3 Colorimetric Assays measure the proteolytic ... We offer caspase detection assays in two formats: assay kits and 96-well plates. The assay kits detect caspase activation by ...
Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular ... Caspase-3 enzyme is a member of the family of endoproteases which regulate inflammation and apoptosis signaling networks. ... caspase-9, and granzyme B to generate the active heterodimer of caspase-3 subunits (1). ... Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular ...
... products and learn more about Caspase-3/CPP32 Mouse anti-Mouse, Unlabeled, Clone: 46, BD 150µg; 150µg; Unlabeled. ... Caspase-3 (CPP32, Yama, apopain) is a member of the family of cysteine proteases which includes interleukin-1beta-converting ... This antibody recognizes the mouse 32kDa pro-Caspase-3 and the p17 cleaved form of Caspase 3 in T cell lymphocytes treated with ... The active form of Caspase-3 cleaves several other apoptotic proteins including proteins such as DNA fragmentation factor (DFF ...
Protein target information for Caspase-3 (pig). Find diseases associated with this biological target and compounds tested ...
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.
  • Among them, caspase-3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins. (nih.gov)
  • It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. (wikipedia.org)
  • In vitro, caspase-3 has been found to prefer the peptide sequence DEVDG (Asp-Glu-Val-Asp-Gly) with cleavage occurring on the carboxy side of the second aspartic acid residue (between D and G). Caspase-3 is active over a broad pH range that is slightly higher (more basic) than many of the other executioner caspases. (wikipedia.org)
  • Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. (abcam.com)
  • Activation of caspase-3 requires cleavage at Asp175 into the activated p17/p19 and p12 protein fragments. (cellsignal.com)
  • CST Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664 recognizes the activated large fragment after cleavage (seen as a 17 kDa and 19 kDa doublet on western blot). (cellsignal.com)
  • CST Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664 recognizes the activated large fragment after cleavage (seen as a 17 kDa and 19 kDa doublet). (cellsignal.com)
  • A lower molecular weight band refers to a proteolytic cleavage product of caspase-3. (abcam.com)
  • Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol. (abcam.com)
  • 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. (anaspec.com)
  • The assay kits detect caspase activation by assaying for the cleavage of a fluorescent or a colorimetric substrate. (clontech.com)
  • The Caspase-3 Colorimetric Assays measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by caspase-3. (clontech.com)
  • Cleavage and activation of pro caspase-3 is catalyzed by caspase-8 , caspase-9 , and granzyme B to generate the active heterodimer of caspase-3 subunits (1). (novusbio.com)
  • used caspase-3 antibodies to monitor the induction of apoptosis and caspase-3 cleavage and activation through western blotting (2). (novusbio.com)
  • This study used cleavage of caspase-3 as measured through western blotting with the caspase-3 antibody to show veliparib potentiates sensitivity to chemotherapeutic agents (3). (novusbio.com)
  • An apoptotic signal such as granzyme B of cytotoxic T-cells (CTLs) or ICE-like proteases induces the intracellular cleavage of Caspase-3 from the inactive proform (32kDa) to the active form which consists of the p20, p17, and p12 subunits. (fishersci.com)
  • Caspase-3 is either partially or totally responsible for the proteolytic cleavage of many key proteins, such as the nuclear enzyme poly (ADP-ribose) polymerase (PARP). (fluidigm.com)
  • They are cell membrane-permeable, and non-fluorescent until cleavage by active caspases. (biotium.com)
  • Investigators at Burnham Institute for Medical Research have identified novel cleavage sites for the enzyme caspase-3 (an enzyme that proteolytically cleaves target proteins). (phys.org)
  • Using an advanced proteomic technique called N-terminomics, Guy Salvesen, Ph.D., professor and director of the Apoptosis and Cell Death Research program of Burnham's NCI-designated Cancer Center, and colleagues determined the cleavage sites on target proteins and found, contrary to previous understanding, that caspase-3 targets α-helices as well as unstructured loops. (phys.org)
  • However, when hybrid human/ E. coli proteins were constructed, cleavage was greatly improved, leading researchers to conclude that caspase-3 co-evolved with its human substrates. (phys.org)
  • We have used it in-house with Jurkat cells at 6 hrs and had good results, but other publications show caspase cleavage after 24 hours but not at 16 in HEK293. (protocol-online.org)
  • 13 14 Caspase 2 is activated by cleavage into three fragments that are then further processed into 18- and 12-kD active subunits. (bloodjournal.org)
  • The results showed that ATP treatment induced lytic cell death morphologically resembling canonical pyroptosis in both MCC950-treated BMDMs and RAW264.7 cells, but did not cause the activation of caspase-1 (by detecting caspase-1p10 and mature interleukin-1β) and cleavage of GSDMD. (springer.com)
  • Apoptosis, or programmed cell death, is mediated by the activation of caspases (Casp), a family of cysteine proteases present as proenzymes in all cells and activated by cleavage and reorganization of their subunits after an intracellular or extracellular apoptotic signal ( Nicholson, 1999 ). (jneurosci.org)
  • In the native form, LS498 fluorescence is quenched until caspase-3 cleavage of the peptide substrate. (spiedigitallibrary.org)
  • Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells. (nih.gov)
  • Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. (nih.gov)
  • A and B) Caspase cleavage is detected in CD4+, CD8+, CD45RO+, or CD45RA+ lymphocytes. (nih.gov)
  • In apoptotic cells, caspase-8 undergoes two sequential autoproteolytic cleavage reactions that separate the large and small catalytic subunits as well as deleting a small linker peptide sequence (amino acids 374-384) and the prodomain (amino acids 1-216), releasing the mature tetramer form into the cytoplasm ( 10 ). (aacrjournals.org)
  • Caspase-3 cleavage and activation are known to play central roles in apoptosis. (ahajournals.org)
  • However, the mechanisms that regulate caspase-3 cleavage remain elusive. (ahajournals.org)
  • Here we show the essential role of Grx in caspase-3 cleavage via regulation of caspase-3 glutathiolation. (ahajournals.org)
  • Small interference RNA knock down of Grx significantly inhibited tumor necrosis factor-α-induced endothelial cell death because of attenuated caspase-3 cleavage concomitant with increased caspase-3 glutathiolation. (ahajournals.org)
  • Enhanced caspase-3 cleavage by wild-type Grx overexpression was reversed by catalytically inactive Grx (C22S), demonstrating a requirement for thioltransferase activity. (ahajournals.org)
  • Cysteine-to-serine mutations (C163S, C184S, and C220S) of caspase-3 that were predicted to prevent glutathiolation showed increased cleavage compared with wild-type caspase-3. (ahajournals.org)
  • This inverse correlation between caspase-3 glutathiolation and cleavage was further confirmed by the observation that in vitro glutathiolation of caspase-3 inhibited its cleavage with recombinant caspase-8. (ahajournals.org)
  • Specifically, we show that Grx plays a key role in caspase-3 cleavage by regulating caspase-3 glutathiolation in response to TNF-α, thereby modulating TNF-α-induced death signaling. (ahajournals.org)
  • The cellular processes leading to apoptosis induction are not completely understood, but an important event is the activation of a cascade of cysteine proteases named caspases (2), leading to cleavage of specific substrates involved in cell death. (scielo.br)
  • Further downstream, caspase-8 triggers the proteolytic activation of other caspases and cleavage of cellular substrates. (rupress.org)
  • In addition to the processing site identified in NC (DESD 358 /F) being similar to the optimal recognition sequence of group II caspases, DExD, cleavage site mutations confirmed the involvement of caspase(s) in NC processing. (springer.com)
  • Immunogen: Synthetic peptide around the cleavage site of human caspase-3. (agscientific.com)
  • Collectively, the data suggest that CO extract has the potential to induce apoptosis of HepG2 cells and may act by suppressing the cell cycle, which leads to caspase‑3 cleavage and p53 signaling. (spandidos-publications.com)
  • The cell death was associated with activation of caspase 3, nuclear translocation of activated caspase 3, and cleavage of DNA repair enzyme poly(ADP-ribose) polymerase, which is known to be an important substrate for activated caspase 3. (asm.org)
  • Apoptosis is a complex multi-step process driven by caspase-dependent proteolytic cleavage cascades. (sciencemag.org)
  • Originally identified among other family members of Caenorhabditis elegans death proteins ( 4 ), it is now known that caspases are key proteases that activate and mediate apoptotic cell death through a cascade of protein cleavage. (sciencemag.org)
  • Caspase-3 activity can be assessed using synthetic substrates with a consensus cleavage site (DEVD) attached to reporter molecules (colorimetric or fluorescent). (arvojournals.org)
  • Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC pipeline Target constitutes close to 13 molecules. (researchandmarkets.com)
  • It also reviews key players involved in Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC targeted therapeutics development with respective active and dormant or discontinued projects. (researchandmarkets.com)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • Using a series of caspase inhibitors with overlapping specificities, enzyme-specific chromogenic substrates, and an antibody specific for activated caspase 7, we have determined that apoptosis in MCF-7 cells proceeds via sequential activation of caspases 9, 7 and 6. (nih.gov)
  • Immunohistochemical analysis of frozen H1650 xenograft section, using Cleaved Caspase-3 (Asp175) Antibody #9661 . (cellsignal.com)
  • Company 1 cleaved caspase-3 rabbit polyclonal antibody shows high background and does not detect distinct bands in the expected 19/17 kDa range. (cellsignal.com)
  • Company 2 active caspase-3 rabbit polyclonal antibody detects multiple non-specific bands at various molecular weights but weakly detects the bands of interest in the 19/17 kDa and 12 kDa range. (cellsignal.com)
  • Company 1 active caspase-3 rabbit monoclonal antibody detects multiple non specific bands at various molecular weights. (cellsignal.com)
  • The antibody recognizes only the 17 kDa band corresponding to one form of the large fragment of cleaved caspase-3. (cellsignal.com)
  • The following antibody was used in this experiment: Caspase 3 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-96077. (thermofisher.com)
  • The following product was used in this experiment: Caspase 3 Monoclonal Antibody (3CSP03) from Thermo Fisher Scientific, catalog # MA1-26415, RRID AB_779525. (thermofisher.com)
  • This antibody recognizes the mouse 32kDa pro-Caspase-3 and the p17 cleaved form of Caspase 3 in T cell lymphocytes treated with camptothecin. (fishersci.com)
  • We are unable to >get good results using an rabbit anti-mouse anti-caspase-3 antibody. (histosearch.com)
  • The 5A1E antibody reacts with the active cleaved form of caspase-3. (fluidigm.com)
  • There are currently no images for Caspase-3 Antibody (NB100-56709R). (novusbio.com)
  • A recombinant full-length human Caspase-3 protein was used as the immunogen for this antibody. (novusbio.com)
  • Caspase-3 antibody was raised against a 17 amino acid synthetic peptide near the center of human Caspase-3.The immunogen is located within amino acids 70 - 120 of Caspase-3. (genetex.com)
  • IHC-P analysis of human tonsil tissue using GTX31698 Caspase 3 antibody. (genetex.com)
  • Western blotting using polyclonal anti-caspase-3 antibody and mouse anti-human poly(ADP-ribose) polymerase (PARP) monoclonal antibody was performed to investigate caspase-3 and PARP activity. (fluoridealert.org)
  • Non-transfected (-) and transfected (+) HeLa whole cell extracts (30 μg) were separated by 12% SDS-PAGE, and the membrane was blotted with Caspase 3 antibody (GTX110543) diluted at 1:4000. (genetex.com)
  • Wild-type (WT) and Caspase 3 knockout (KO) HeLa cell extracts (30 μg) were separated by 12% SDS-PAGE, and the membrane was blotted with Caspase 3 antibody (GTX110543) diluted at 1:4000. (genetex.com)
  • Caspase 3 antibody detects Caspase 3 protein by western blot analysis. (genetex.com)
  • Caspase 3 antibody detects CASP3 protein at Cytoplasm by immunofluorescent analysis. (genetex.com)
  • Green: CASP3 protein stained by Caspase 3 antibody (GTX110543) diluted at 1:500. (genetex.com)
  • Immunohistochemistry-Paraffin: Caspase-3 Antibody [ABIN269423] - Human tonsil. (antikoerper-online.de)
  • Fresh PBMCs (To) were cultured with medium alone (NS), anti-CD3 and IL-2 (CD3), or SAC for 4 d, and whole PBMCs (lane 1-3) or sorted CD19+ B lymphocytes (lane 4) were lysed in Laemmli buffer and subjected to Western blot analysis using the anti-caspase-3 antibody. (nih.gov)
  • Caspase 3 antibody LS-C172091 is a Magnetic beads-conjugated rabbit polyclonal antibody to Caspase 3 (CASP3) (C-Terminus) from human. (lsbio.com)
  • Caspase 3 Substrate antibody LS-C779475 is an unconjugated rabbit polyclonal antibody to Caspase 3 Substrate from human. (lsbio.com)
  • Caspase 3 and caspase 7 share similar substrate specificity by recognizing tetra-peptide motif Asp-x-x-Asp. (wikipedia.org)
  • Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. (wikipedia.org)
  • Fluorogenic caspase-3 substrate. (fishersci.com)
  • These kits provides two apoptosis markers, our novel NucView® 488 Caspase-3 Substrate and Annexin V conjugated with your choice of red or far-red dye. (biotium.com)
  • NucView® 405 Caspase-3 Substrate, 1 mM in DMSO, provides a convenient tool for detecting apoptosis in intact cells based on caspase-3/7 activity using either confocal microscopy or flow cytometry. (biotium.com)
  • In the family, Caspase-3 in its inactive zymogens, pro-caspase-3 is a remarkable protein as the enzyme shows a large substrate diversity, as a variety of proteins have been cleaved in cell maintenance. (thefreelibrary.com)
  • Activity of caspase-3 was measured by using fluorogenic substrate peptide, Ac-DEVD-AMC. (arvojournals.org)
  • The two dyes are separated by a cleavable peptide substrate for caspase-3, a diagnostic enzyme that is upregulated in dying cells. (spiedigitallibrary.org)
  • Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. (nih.gov)
  • Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. (nih.gov)
  • Caspase and substrate processing occur in nonapoptotic lymphocytes. (nih.gov)
  • The EarlyTox™ Caspase-3/7 NucView 488 Assay Kits enable detection of apoptosis within intact cell populations through use of the NucView 488 Caspase-3 substrate. (moleculardevices.com)
  • This substrate consists of a fluorogenic DNA dye coupled to the caspase-3/7 DEVD recognition sequence. (moleculardevices.com)
  • If the cell is apoptotic the substrate is cleaved by caspase-3/7, releasing a dye that enters the nucleus and binds to DNA, resulting in bright green fluorescence. (moleculardevices.com)
  • 3. Using the fluorescent substrate (Ac-DESD-AMC), the characteristic proteolytic activities, which cleaved it more effectively than caspase-3 and whose pH dependences were different from those of caspase-3, were endogenously identified in the muscle extract. (springer.com)
  • Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2. (springer.com)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
  • The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
  • This assay has high sensitivity and excellent specificity for detection of Caspase 3 (CASP3). (antibodies-online.com)
  • No significant cross-reactivity or interference between Caspase 3 (CASP3) and analogues was observed. (antibodies-online.com)
  • We biochemically isolated caspase-7 from B6-caspase-3-null ( Casp3 -/- ) tissues as being the enzyme with caspase-3-like properties and capability of performing a caspase-3 surrogate function, apoptotic DNA fragmentation. (jneurosci.org)
  • Low levels of caspase-7 expression and activation correlate with lack of DNA fragmentation in 129- Casp3 -/- apoptotic precursor neurons, whereas B6- Casp3 -/- cells, which can fragment their DNA, show higher levels of caspase-7 expression and activation. (jneurosci.org)
  • Together, our findings demonstrate for the first time a strong correlation between caspase-7 activity, normal brain development, and apoptotic DNA fragmentation in Casp3 -/- mice. (jneurosci.org)
  • This extrinsic activation then triggers the hallmark caspase cascade characteristic of the apoptotic pathway, in which caspase-3 plays a dominant role. (wikipedia.org)
  • This pathway bypasses the need for activated caspase 3 in these cells. (nih.gov)
  • S-nitrosylated on its catalytic site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. (abcam.com)
  • Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. (sciencemag.org)
  • This caspase-8 initiates other downstream proteins including procaspase-3 in two ways: the first is a complex pathway, wherein caspase8 cleaves Bcl-2 interacting protein named Bid and also releases cytochrome-c. (thefreelibrary.com)
  • In the second simple pathway, caspase-8 cleaves procaspase-3 directly and activates it. (thefreelibrary.com)
  • These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. (sigmaaldrich.com)
  • Collectively, our results indicate that ATP induces pyroptosis in macrophages through the caspase-3/GSDME axis when the canonical NLRP3 pathway is blocked, suggestive of an alternative mechanism for combating against pathogen evasion. (springer.com)
  • In conclusion, microwave radiation induced neural cell apoptosis via the classical mitochondria-dependent caspase-3 pathway. (medsci.org)
  • Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway. (sigmaaldrich.com)
  • Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating COL2 in rat NPCs in vitro via Bax/Bcl-2/caspase-3 pathway. (sigmaaldrich.com)
  • Caspase-3, caspase-7, and caspase-8 are important caspases in the apoptosis pathway and play an important role in the development and progression of cancer. (aacrjournals.org)
  • we aimed to demonstrate the protective effect of TXL on cerebral ischemia/reperfusion (I/R) injury and provide the evidence for the involvement of Connexin 43/Calpain II/ Bax/Caspase-3 pathway in TXL-mediated neuroprotection. (unboundmedicine.com)
  • TXL could effectively protect against I/R injury and reduced cell death via Cx43/Calpain II/Bax/Caspase-3 pathway, which contribute to I/R injury prevention and therapy. (unboundmedicine.com)
  • In the type I pathway, initiator caspases cleave and activate executor caspases directly. (jimmunol.org)
  • The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. (nih.gov)
  • Pretreatment with the pan-caspase inhibitor z-VAD-fmk partially, but significantly, blocked the berberine-induced apoptosis, as also confirmed by the comet assay analysis of DNA fragmentation, suggesting that berberine-induced apoptosis of human prostate cancer cells is mediated primarily through the caspase-dependent pathway. (aacrjournals.org)
  • These results suggest that chemotherapeutic drug-induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function. (rupress.org)
  • Taken together, our present results suggest that HCV infection induces apoptosis of the host cell through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway(s). (asm.org)
  • On the other hand, the extrinsic cell death pathway involves the activation of caspase 8 through binding to the adaptor protein Fas-associated protein with death domain (FADD), which in turn activates caspase 3 to facilitate cell death. (asm.org)
  • Caspase-3 activity is associated with the apoptosis pathway. (arvojournals.org)
  • In summary, this study showed that inhibition of EPAC2 activation by ESI-05 suppressed SBI induced by ICH via the p38/BIM/caspase-3 signaling pathway. (springer.com)
  • For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase heterotetramer whereas for the activation pathway, the zymogen appears to remain intact perhaps to limit its proteolytic function but enhance its capability as an adapter protein. (wikipedia.org)
  • Under normal circumstances, caspases recognize tetra-peptide sequences on their substrates and hydrolyze peptide bonds after aspartic acid residues. (wikipedia.org)
  • Rh110 (rhodamine 110)-derived caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase activities. (anaspec.com)
  • NucView® Caspase-3 Substrates are novel, fluorogenic peptide caspase 3 & 7 substrates invented by Biotium. (biotium.com)
  • The NucView® substrates come in 3 color options: blue (405), green (488) and orange (530). (biotium.com)
  • Fluorescent caspase-3/7 substrates for detecting apoptosis in intact cells by confocal microscopy, flow cytometry, or live cell imaging. (biotium.com)
  • In addition, researchers found that caspase-3 and the substrates it binds to co-evolved. (phys.org)
  • The activated caspases abrogate the effect of substrates that protect cellular integrity, such as the DNA-repair enzyme poly(ADP-ribose) polymerase (PARP), and thereby induce apoptotic cell death. (bloodjournal.org)
  • Caspases orchestrate the organized death of the cell by cleaving a small but specific complement of protein substrates. (jneurosci.org)
  • Caspase-8 is a cysteine protease, which cleaves downstream substrates such as effector caspases, to initiate the apoptotic cascade and transmit apoptotic signals downstream of death receptors ( 16 ). (aacrjournals.org)
  • In that scenario, pro-caspase-8 could potentially cleave key substrates for motility-remaining to be identified-or could function noncatalytically as an interaction partner for a motility factor. (aacrjournals.org)
  • Caspases lead to the proteolysis of a number of cellular substrates, a process which finally results in the apoptotic collapse of the cell. (rupress.org)
  • A large number of substrates for caspases have been identified and include structural proteins such as nuclear lamins, but also proteins involved in DNA repair, DNA damage signalling and genomic stability, such as polyADP‐ribose polymerase (PARP). (embopress.org)
  • The identification of substrates for caspases is of fundamental importance to understand the downstream events that occur during apoptosis. (embopress.org)
  • Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. (wikipedia.org)
  • and the protein itself is processed and activated by caspases 8, 9, and 10. (wikipedia.org)
  • Phosphorylation of caspase-3 at a conserved allosteric site by p38-MAPK (mitogen-activated protein kinase) promotes survival in human neutrophils, and the modification of the loop is thought to be a key regulator in many developmental processes. (rcsb.org)
  • Recombinant full length protein corresponding to Human Caspase-3. (abcam.com)
  • Caspase-3 (CPP32, Yama, apopain) is a member of the family of cysteine proteases which includes interleukin-1beta-converting enzyme (ICE) and C. elegans protein, Ced-3. (fishersci.com)
  • We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. (hindawi.com)
  • The human caspase-3 gene encodes a cytoplasmic protein that is highly expressed in lung, spleen, heart, liver, kidney and cells of the immune system. (scbt.com)
  • Recombinant protein encompassing a sequence within the center region of human Caspase 3. (genetex.com)
  • The discovery that caspase-3 also cleaves α-helices contradicts a current dogma and offers new insights into protein signaling pathways. (phys.org)
  • Taken together, caspase 2 and caspase 3 protein levels obtained at diagnosis may constitute a reliable prognostic factor in AML. (bloodjournal.org)
  • In this study, we used cellular models to mimic such blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression. (springer.com)
  • In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels. (frontiersin.org)
  • Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. (frontiersin.org)
  • For instance, FLIP blocks activation of initiator caspases, Bcl-2 prevents mitochondrial disruption, and X-linked inhibitor of apoptosis protein (XIAP) 3 inhibits downstream caspases (i.e., caspase-9 and caspase-3). (jimmunol.org)
  • Furthermore, the present study explored whether various signaling molecules associated with HepG2 cell death were affected by CO treatment, including caspase‑3, B‑cell lymphoma 2 (Bcl-2), tumor protein p53 (p53), cyclin‑dependent kinase 4 (CDK4) and cyclin D. The expression levels of these genes were examined by reverse‑transcription polymerase chain reaction and western blotting. (spandidos-publications.com)
  • Inhibition of EPAC2 decreased the apoptosis rate of nerve cells in the cortex accompanied by a corresponding decrease in the protein expression of phosphorylated p38, Bcl-2-like protein 11 (BIM), and caspase-3. (springer.com)
  • Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoptosis in human neutrophils in vitro. (nel.edu)
  • Caspase-8 is a caspase protein, encoded by the CASP8 gene. (wikipedia.org)
  • Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (wikipedia.org)
  • Caspase 3 is responsible for cellular differentiation, although it is unclear how this kind of protein can promote the cell apoptosis. (wikipedia.org)
  • Caspases, a family of cysteine proteases, are the central regulators of apoptosis. (cellsignal.com)
  • Apoptosis can be inhibited by coexpression of Bcl-2 as well as inhibitors of Caspase-3 or other members of the family of cysteine proteases. (fishersci.com)
  • Caspase is a family of cysteine proteases, with specific cysteine residue that cleaves proteins after the aspartic acid residue, a specificity which is not normal among proteases to produce the active mature caspases [5]. (thefreelibrary.com)
  • The caspases are a family of cysteine proteases that are key regulators of apoptosis and their activity may thus serve as a good marker to monitor cell death. (rsc.org)
  • For both pathways, caspases, a family of cysteine proteases, are crucial for both the initiation and execution of apoptosis. (jimmunol.org)
  • A central component of the apoptotic machinery is a family of cysteine proteases (caspases), which cleave a select set of proteins at aspartic acid (Asp, D) residues, generally at only one or a few specific sites. (embopress.org)
  • Caspase-3, in particular, (also known as CPP32/Yama/apopain) is formed from a 32 kDa zymogen that is cleaved into 17 kDa and 12 kDa subunits. (wikipedia.org)
  • Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. (hindawi.com)
  • Caspase-3 (CPP32/Yama/apopain ) is a 32 kDa cysteine protease that is activated during the early stages of apoptosis. (fluidigm.com)
  • Adenovirus-mediated delivery of p53 to cerebellar granule neurons resulted in caspase-3 (CPP32) activation followed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining and loss of viability as determined by an MTT survival assay. (jneurosci.org)
  • Caspase-3, also known as apopain, SCA-1, Yama and CPP32, is an aspartate-specific cysteine protease that belongs to the ICE subfamily of caspases. (scbt.com)
  • 2-4 Consistent with this scheme, caspase 3 (CPP32, prICE, or Yama) 6-8 has been found to be involved in leukemia-cell apoptosis induced by cytotoxic agents such as ara-C, 9 10 etoposide, mitoxantrone, 10 and CPT-11. (bloodjournal.org)
  • Apoptosis involves a signaling cascade that, ultimately, activates a family of proteases known as caspases. (mdpi.com)
  • Because they alter the functions of other proteins, proteases like caspase-3 are critical to cell signaling. (phys.org)
  • Most signals that lead to apoptosis do so by activating interleukin-1β converting enzyme (ICE)-like proteases termed caspases. (bloodjournal.org)
  • Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. (nih.gov)
  • FN, COL and LPA decreased caspase-3 activity 0.2 to 0.5 fold, whereas, Y27632 increased caspase-3 activity 1.4 fold in the presence of COL and 2 fold without COL. Increasing doses of Y27632 also caused increasing amounts of FITC-PhiPhiLux, indicating that the tissues were positive for caspase-3. (arvojournals.org)
  • These molecules are sufficient to activate caspase-3 in vitro, but other regulatory proteins are necessary in vivo. (wikipedia.org)
  • Once activated, initiation caspases cleave and activate downstream effector caspases (including caspase-3, -6, and -7), which in turn execute apoptosis by cleaving targeted cellular proteins. (cellsignal.com)
  • Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular structures such as DNA fragmentation or degradation of cytoskeletal proteins (1). (novusbio.com)
  • The active form of Caspase-3 cleaves several other apoptotic proteins including proteins such as DNA fragmentation factor (DFF). (fishersci.com)
  • Upon activation, these "executioner" caspases cleave various structural and repair proteins at the aspartate-glutamate-valine-aspartate (DEVD) amino acid sequence, resulting in apoptotic cell death [ 2 ]. (mdpi.com)
  • Several factors are contributed in apoptosis, but the key elements are categorized in two main families of proteins including caspase enzymes and Bcl-2 family [ 18 ]. (hindawi.com)
  • Notably, caspase-3 did not cleave E. coli proteins as effectively as it did human proteins. (phys.org)
  • Additionally, Bcl‑2, Bax and caspase‑3 proteins may exert a significant effect on neuron injury. (spandidos-publications.com)
  • In the context of cellular apoptosis, it has been shown previously that caspase-3 activation, a hallmark of mitochondrial dysregulation, promotes hydrolysis of several key cellular proteins. (biomedsearch.com)
  • In principle, it could also facilitate the interactions of caspase-8 promigratory proteins containing phosphotyrosine binding domains. (aacrjournals.org)
  • 2,3 It is well established that, as an antioxidant enzyme, Grx protects cells from oxidative stress, whereas S -glutathiolation (glutathiolation), a posttranslational modification, protects proteins from irreversible oxidation. (ahajournals.org)
  • TNF induces apoptosis through the recruitment of the death domain-containing adaptor proteins FADD and TRADD to its receptor, which in turn leads to the activation of the initiator caspase, caspase-8. (ahajournals.org)
  • The berberine-induced inhibition of proliferation of DU145, PC-3, and LNCaP cells was associated with G 1 -phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk. (aacrjournals.org)
  • 0.05-0.001) enhanced apoptosis of DU145 and LNCaP cells with induction of a higher ratio of Bax/Bcl-2 proteins, disruption of mitochondrial membrane potential, and activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase. (aacrjournals.org)
  • Apoptosis can be induced by either extrinsic stimulus through death receptors [such as the tumor necrosis factor-α (TNFα) or FAS receptors] that specifically activate caspase-8 or intrinsic stimulus (such as expression of BCL2 family BH3-only proteins BIM or puma) that leads to mitochondrial depolarization and activation of caspase-9 ( 6 , 7 ). (sciencemag.org)
  • Cleaves and activates caspase-6, -7 and -9. (abcam.com)
  • Caspase-3 cleaves and activates SREBPs between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. (scbt.com)
  • This procaspase-9 comes and activates caspase-9 and simultaneously this activates procaspase-3 and then activates caspase-3. (thefreelibrary.com)
  • 14 The activated caspase-8 cleaves and activates caspase-3. (ahajournals.org)
  • This, in turn, activates downstream death programs, such as caspase 3 and poly(ADP-ribose) polymerase (PARP). (asm.org)
  • 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. (wikipedia.org)
  • Caspase-3 is expressed in cells as an inactive precursor from which the p17 and p11 subunits of the mature caspase-3 are proteolytically generated during apoptosis. (scbt.com)
  • The active caspase-3 enzyme is a heterodimer composed of two p17 and two p11 subunits. (scbt.com)
  • The cleaved form of caspase 3 consists of biologically active subunits p17 and p12. (bloodjournal.org)
  • The complex pattern of caspase-3 subunits suggested that they could originate from several proenzyme species observed in nonstimulated cells (Fig. 2 B), or from different cell subsets. (nih.gov)
  • Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. (wikipedia.org)
  • The presence of Thr 152 in the conserved loop introduces a "kill switch" in mammalian caspase-3, whereas the more ancient Ser 150 reduces without abolishing enzyme activity. (rcsb.org)
  • In contrast, diabetic sensory neurons had elevated expression of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) in their nuclei, cytoplasm, and proximal axonal segments not overlapping with caspase-3 localization. (diabetesjournals.org)
  • Caspase-3 enzyme is a member of the family of endoproteases which regulate inflammation and apoptosis signaling networks. (novusbio.com)
  • We applied this technique to image real-time activation of a reporter for the proteolytic enzyme, caspase-3, in response to apoptotic cell death. (mdpi.com)
  • Activation of caspase-3 requires proteolytic processing of its inactive zymogen into activated p17 and p12 fragments, which associate to form the active enzyme. (fluidigm.com)
  • The proapoptotic enzyme caspase-3 is activated at a point of convergence for the intrinsic and extrinsic apoptosis induction pathways ( 20 ), so its activity should give a reliable measure of ongoing levels of apoptosis in tumor samples. (aacrjournals.org)
  • Materials and Method: The roles of GM3 synthase (α2,3-sialyltransferase, ST3Gal V), in attenuating Taxol-induced apoptosis and triggering drug resistance were determined by cloning and overexpressing this enzyme in SKOV3 human ovarian cancer cell line, treating SKOV3 and the transfectants (SKOV3/GS) with Taxol and determining apoptosis, cell survival, clonogenic ability, and caspase-3 activation. (scirp.org)
  • These cleavages remove an -N[H.sub.2] peptide terminal and separate the small and large domains of the pro-enzyme so that it produces the mature hetero tetrameric caspases containing two large and two small domains. (thefreelibrary.com)
  • Conversely, a high level of cleaved caspase 3 denoted improved survival and correlated with the inactivation of the DNA-repair enzyme poly(ADP-ribose) polymerase. (bloodjournal.org)
  • Caspase-3 activity was measured using an enzyme-linked immunosorbent assay. (medsci.org)
  • Enzyme kinetics assay shows that LS498 is readily cleaved by caspase-3, with excellent enzyme kinetic parameters k cat and K M of 0.55±0.01 s -1 and 1.12±0.06 μM, respectively. (spiedigitallibrary.org)
  • Herein, we investigated the transcriptional profile of renoprotection induced by CHBP and its potential synergistic effects with caspase-3 (an executing enzyme of apoptosis and inflammation) siRNA (CASP3siRNA) on ischemia/reperfusion (IR)-induced AKI. (aspetjournals.org)
  • Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly. (nel.edu)
  • Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme activity. (nel.edu)
  • Pathways to caspase-3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c release and caspase-9 function. (nih.gov)
  • Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
  • We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis. (sciencemag.org)
  • Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of DeltaPsim and the activation of caspase-3. (sigmaaldrich.com)
  • Based on these findings, we conclude that etoposide induces loss in cell viability by inducing mitochondrial dysfunction, caspase-3 activation and degradation of FTase/GGTase α-subunit. (biomedsearch.com)
  • Furthermore, deletion of caspase-3 and -7 decreased mitochondrial depolarization and cytochrome c release upon apoptosis activation. (sciencemag.org)
  • Brouillet E, Jacquard C, Bizat N, Blum D (2005) 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease. (springer.com)
  • Caspase-3 antibodies serve as excellent biomarkers to monitor induction of apoptosis by detecting the levels of pro caspase-3 and its active form. (novusbio.com)
  • Caspase-3 antibodies have proven to be valuable tools in mechanistic investigations of new cancer drugs. (novusbio.com)
  • investigated the experimental drug moscatilin and used caspase-3 antibodies to examine the ability of moscatilin to inhibit proliferation of colorectal cancer cells and induce apoptosis (4). (novusbio.com)
  • alternatively, strain-dependent compensatory caspase activation and/or its inhibition may influence the severity of the caspase-3-deficient neuronal phenotype. (nih.gov)
  • To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1 G93A ). (sciencemag.org)
  • Caspases play an instrumental role in neurodegeneration in transgenic mSOD1 G93A mice, which suggests that caspase inhibition may have a protective role in ALS. (sciencemag.org)
  • We measured caspase-3 activity to clarify the mechanism of the inhibition of apoptosis under the existence of DTT or not Because the caspase-3 activity could be reactivated by the existence of DTT. (arvojournals.org)
  • The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP), spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. (frontiersin.org)
  • In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. (rupress.org)
  • Caspase-3/7 double knockout cells exhibited almost complete inhibition of caspase-8 or -9 activation. (sciencemag.org)
  • The current model of apoptosis holds that upstream signals lead to activation of downstream effector caspases. (sciencemag.org)
  • The formation of active caspases forms a cascade in which initiator caspases (8, 9) interact with the downstream effector molecules (3, 7) to facilitate their own activation. (thefreelibrary.com)
  • During apoptosis in humans, initiator caspases integrate molecular signals into proteolytic activity ( 11 ) and subsequently activate the downstream effector caspases, thus transmitting and amplifying the apoptotic signal ( 12 ). (aacrjournals.org)
  • FADD, in addition, contains an NH 2 -terminal so-called death effector domain (DED), which binds to one of the DEDs of caspase-8. (rupress.org)
  • Thus, activation of effector caspase-3 or -7 sets off explosive feedback amplification of upstream apoptotic events, which is a key feature of apoptotic signaling essential for efficient apoptotic cell death. (sciencemag.org)
  • Apoptotic caspases are hierarchically organized into apical caspases (caspase-2, -8, -9, and -10) and effector caspases (caspase-3, -7, and -6) ( 5 ). (sciencemag.org)
  • Fourteen mammalian caspases have been identified so far, three of which, caspases 3, 6 and 7, act as the effector caspases that are largely responsible for the morphological and biochemical changes that occur during apoptosis. (embopress.org)
  • Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa. (abcam.com)
  • The ApoAlert Caspase Assay Kits provide a simple and convenient way to detect caspase protease activity using fluorometric or colorimetric methods. (clontech.com)
  • The team tested the human caspase-3 and the Staphylococcal protease glutamyl endopeptidase (GluC) against the Escherichia coli ( E. coli ) proteosome. (phys.org)
  • 15 16 Caspase 3 is a cysteine protease homologous with ICE. (bloodjournal.org)
  • A new independent 54 page research with title 'Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC - Pipeline Review, H2 2017'guarantees you will remain better informed than your competition. (medgadget.com)
  • Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC pipeline Target constitutes close to 6 molecules. (medgadget.com)
  • The latest report Caspase 7 - Pipeline Review, H2 2017, outlays comprehensive information on the Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (medgadget.com)
  • Furthermore, this report also reviews key players involved in Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC targeted therapeutics development with respective active and dormant or discontinued projects. (medgadget.com)
  • A synthetic peptide inhibitor that irreversibly inhibits caspase-3 and related protease/caspase activity and blocks apoptosis. (creative-enzymes.com)
  • In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. (rupress.org)
  • Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. (wikipedia.org)
  • The clinical phenotype of CEDS patients represented a paradox since caspase-8 was considered to be chiefly a proapoptotic protease, that was mainly involved in signal transduction from Tumor necrosis factor receptor family death receptors such as Fas. (wikipedia.org)
  • Hello all, I recently purchased a Caspase 3/7 Glo assay kit from Promega for apoptosis detection.My assay was done with HEK293 cells which were stimulated with Etoposide.I performed the assay exactly described in the protocol,and detected the luminescence with our Luminoskan Ascent luminometer. (protocol-online.org)
  • I used etoposide to treat my cells for different time,and i also use different concentration.I also use the caspase 3/7 glo assay kit from promega. (protocol-online.org)
  • Caspase-3 Assay Kit (Colorimetric) is used for detecting the activity of caspases that recognize the sequence DEVD using colorimetric method. (abnova.com)
  • The EarlyTox ™ Caspase-3/7 R110 Assay Kit provides a single-step, homogenous assay that is specifically designed for microplate readers. (moleculardevices.com)
  • In this application note we report the use of the EarlyTox Caspase-3/7 R110 Assay Kit in combination with SpectraMax ® fluorescence microplate readers . (moleculardevices.com)
  • EarlyTox Caspase-3/7-D NucView 488 Assay Kit (Explorer Kit Cat. (moleculardevices.com)
  • Both pathways finally end up in the level of activation of caspases for cell death. (thefreelibrary.com)
  • These data show that a low concentration of caffeine can induce p53-dependent apoptosis in JB6 cells through the Bax and caspase 3 pathways. (aacrjournals.org)
  • The model integrates current information concerning the signaling network downstream of Fas activation, through both type I and type II pathways, until activation of caspase-3. (jimmunol.org)
  • The pathways diverge after activation of initiator caspases (e.g., caspase-8 and caspase-10) and converge at the end by activating executor caspases (e.g., caspase-3). (jimmunol.org)
  • While loss of apical initiator caspase-8 or -9 partially blocked extrinsic or intrinsic apoptosis, respectively, only combined loss of caspase-3 and -7 fully inhibited both apoptotic pathways, with no discernible effect of caspase-6 deficiency alone or in combination. (sciencemag.org)
  • Moreover, the biochemical form of caspase-8 differed in the two pathways. (wikipedia.org)
  • In response to various stimuli, apoptosis begins with the activation of "initiator" caspases, which cleave and activate "executioner" caspases (caspase-3, -6, and/or -7) [ 1 , 2 , 3 ]. (mdpi.com)
  • Fluoride led to the activation of caspase-3 which was evident by the loss of the 32 kDa precursor and appearance of the 17 kDa subunit. (fluoridealert.org)
  • The caspase-3 precursor is first cleaved at Asp175-Ser176 to produce the p11 subunit and the p20 peptide. (scbt.com)
  • We report herein that exposure of insulin-secreting INS 832/13 cells or normal rat islets to etoposide leads to significant activation of caspase-3 and subsequent degradation of the common α-subunit of farnesyl/geranylgeranyl transferases (FTase/GGTase). (biomedsearch.com)
  • In addition, treatment of cell lysates with recombinant caspase-3 also caused FTase/GGTase α-subunit degradation. (biomedsearch.com)
  • Moreover, nifedipine, a calcium channel blocker, markedly attenuated etoposide-induced caspase-3 activation, FTase/GGTase α-subunit degradation in INS 832/13 cells and normal rat islets. (biomedsearch.com)
  • Stimulation of motility with epidermal growth factor induced the phosphorylation of caspase-8 on tyrosine-380 and the interaction of caspase-8 with the p85α subunit of phosphatidylinositol 3-kinase. (aacrjournals.org)
  • In this report, we show that Y380-phosphorylated pro-caspase-8 interacts with the p85 subunit of PI3K, promoting cell adhesion and motility. (aacrjournals.org)
  • and recombinant caspase-8 was from Biomol. (ahajournals.org)
  • 2. However, both the recombinant NC and the synthetic octapeptide (YL DESDFG) were scarcely cleaved in vitro by caspase-3 or -7. (springer.com)
  • Membrane associated changes determining the life span of neutrophils and human recombinant caspase-3 assay were examined. (nel.edu)
  • One such signaling event is the introduction of granzyme B, which can activate initiator caspases, into cells targeted for apoptosis by killer T cells. (wikipedia.org)
  • As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after apoptotic signaling events have occurred. (wikipedia.org)
  • Instead, both apoptotic initiator (caspase-8 and -9) and executioner (caspase-3 and -7) caspases were evidently activated and gasdermin E (GSDME) was cleaved to generate its N-terminal fragment (GSDME-NT) which executes pyroptosis. (springer.com)
  • C2C12 cells were treated with Staurosporine, a PKC inhibitor that induces apoptosis (1 μM for 3 hours). (cellsignal.com)
  • Fluoride induces apoptosis by caspase-3 activation in human leukemia HL-60 cells. (fluoridealert.org)
  • The mechanisms by which butyrate induces apoptosis in different cell types are not known, but there is evidence that butyrate cell death induced in some cancer cells is triggered via activation of the caspase cascade (14). (scielo.br)
  • The results clearly suggest that fluoride causes cell death in HL-60 cells by causing the activation of caspase-3 which in turn cleaves PARP leading to DNA damage and ultimately cell death. (fluoridealert.org)
  • At the onset of apoptosis, caspase-3 proteolytically cleaves PARP at an Asp216-Gly217 bond. (scbt.com)
  • The expressions of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and PARP were examined by immunoblotting or immunocytochemistry. (medsci.org)
  • Furthermore, the ratio of Bax/Bcl-2, expression of cytochrome c, cleaved caspase-3 and PARP all increased. (medsci.org)
  • The zymogen feature of caspase-3 is necessary because if unregulated, caspase activity would kill cells indiscriminately. (wikipedia.org)
  • Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is also required for developmental processes such as lymphoid proliferation and erythroid differentiation. (rcsb.org)
  • 1997). Fluorometric and colorimetric detection of caspase activity associated with apoptosis. (anaspec.com)
  • The activity of caspase-3 is tightly regulated and it is produced as zymogen in an inactive pro-form (1). (novusbio.com)
  • This caspase-3 reporter activity provides valuable insight into cancer cell responsiveness to therapy and overall viability at a single-cell scale. (mdpi.com)
  • The present study evaluated the use of biochemical detection of enzymatic caspase-3 activity as preoperative marker for apoptosis to preselect patients that are unlikely to develop a local recurrence to spare these patients from overtreatment and the negative side effects of radiotherapy. (aacrjournals.org)
  • Level of apoptosis was determined by measuring the enzymatic activity of caspase-3 in a biochemical assay. (aacrjournals.org)
  • Detection of tumor apoptosis levels by measuring caspase-3 activity, for which a preoperative biopsy can be used, accurately predicted local recurrence in rectal cancer patients. (aacrjournals.org)
  • These findings indicate that caspase-3 activity is an important denominator of local recurrence and should be evaluated prospectively to be added to the criteria to select rectal cancer patients in which radiotherapy is redundant. (aacrjournals.org)
  • The present study evaluated the use of biochemical detection of caspase-3 activity as a simple and quantitative technique to measure apoptosis in tissue samples and preoperative biopsies of rectal cancer to predict local recurrences in rectal cancer. (aacrjournals.org)
  • Unfortunately, in my assay I observed no induction of caspase activity and that the highest reading was equal to the 'vehicle control'.To rule out the problems with the system I also tested the same kit with purified caspase 3 in different amounts and observed the same outcome.I use Corning Costar 3610 96 well plates and seal the bottom of my wells with white opaque vinyl sealing tapes. (protocol-online.org)
  • Meanwhile I was in contact with the tech support and I was suggested to let the Glo buffer be at room temp for half an hour before using it.I did so and used the buffer for measuring purified Caspase 3 activity and it looks much better than my previous experiment (see attached). (protocol-online.org)
  • Out of the complex DFF40 and DFF45 (DNA fragmentation factor 45), the caspase-3 cleaves DFF45 and as a result of that, DFF45 dissociates from DFF40, causing oligomerization of DFF40 which has DNase activity. (thefreelibrary.com)
  • Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. (sigmaaldrich.com)
  • Here, we show that apigenin reduced lipopolysaccharide (LPS)-induced apoptosis by decreasing ROS production and the activity of caspase-3 in endothelial cells. (mdpi.com)
  • We have developed a quenched fluorescent activity-based probe (qABP) that is selective for caspase-3 activity and emits a fluorescent signal after covalently modifying its target. (rsc.org)
  • The probe has a wide range of potential applications, e.g. in real-time imaging, FACS analysis or biochemical quantification of caspase activity in intact cells. (rsc.org)
  • Furthermore, we showed that neuronal apoptosis is increased in the diabetic retina, as measured by caspase-3 activity. (diabetesjournals.org)
  • Minocycline represses diabetes-induced inflammatory cytokine production, reduces the release of cytotoxins from activated microglia, and significantly reduces measurable caspase-3 activity within the retina. (diabetesjournals.org)
  • The caspase-3 activity was increased by the addition of DTT. (arvojournals.org)
  • Inverted phase-contrast microscopy, flow cytometry and caspase-3 activity assays were used and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. (sigmaaldrich.com)
  • The catalytic activity of caspase-8 was not required for cell motility. (aacrjournals.org)
  • Caspase-Glo 3/7 Assay System - Apoptosis Assays and Systems, Promega - Model PAG8090 - Each : Apo-ONE Homogeneous Caspase-3/7 Assay: Use for fast, sensitive, fluorescent measurement of caspase-3 and -7 activity in a homogenous format. (egeneralmedical.com)
  • The activity of caspase-3 was enhanced during macrophage apoptosis induced by butyrate and the caspase inhibitor z-VAD-FMK (100 µM) inhibited the butyrate effect, indicating the major role of the caspase cascade in the process. (scielo.br)
  • The cellular caspase-3 activity and DNA ladder were examined in SW620 cells or HCT-8 cells.The cellular caspase-3 activity was determined in SW620 cells (I) and HCT-8 cells (II) treated with different doses of γ-tocotrienol as well as DNA ladder in SW620 cells treated with PBS (A), 1.0 and 1.5 µmol/L of PTX or γ-tocotrienol (D) for 24 h. (nih.gov)
  • As shown in Fig. 6 II, the caspase-3 activity also determined in HCT-8 cells after treated with different doses of γ-tocotrienol (10, 20, 30 and 40 µmol/L). The results showed that γ-tocotrienol-induced cell death in HCT-8 cells was also caspase-independent. (nih.gov)
  • To visualize caspase-3 activity, PhiPhiLux was added to the media of the live tissues for 1hr. (arvojournals.org)
  • Control tissues incubated without ECM had moderate levels of caspase-3 activity that was decreased to background with the ZVAD caspase-3 inhibitor. (arvojournals.org)
  • Corneal epithelial cells increase the apoptosis marker, caspase-3 activity in the absence of extracellular matrix. (arvojournals.org)
  • In addition, blocking the reorganization of the actin cortical mat by inhibiting Rho kinase increased the level of caspase-3 activity. (arvojournals.org)
  • Mangosteen (Garcinia mangostana) extract has been shown to inhibit the activation of caspase 3 in B-amyloid treated human neuronal cells. (wikipedia.org)
  • MCF-7 human breast cancer cells do not express caspase 3, thought by some to be a critical component of the apoptosis cascade. (nih.gov)
  • Western blot analysis of extracts from C6 (rat), NIH/3T3 (mouse), and Jurkat (human) cells, untreated or treated with staurosporine #9953 (1uM, 3 hrs) or etoposide #2200 (25uM, 5hrs) as indicated, using Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664 . (cellsignal.com)
  • In a study of small cell lung cancer, the experimental drug veliparib and its effect on cells in conjunction with chemotherapy (3). (novusbio.com)
  • Cells of lymphoid origin express high levels, and active caspase-3 is a marker for cells undergoing apoptosis. (fluidigm.com)
  • To determine whether Bax is essential for caspase-3 activation, p53 was expressed in Bax-deficient cells. (jneurosci.org)
  • Our results indicate that caspase-3-deficient neurons exhibit a remarkable delay in apoptosis and a dramatic decrease in TUNEL-positive cells. (jneurosci.org)
  • In the present study, the toxicity of fluoride on human leukemia (HL-60) cells was investigated and the involvement of caspase-3 was also studied. (fluoridealert.org)
  • The Annexin-V and Caspase 3 assays were performed by flow cytometric analysis to determine the extent of phosphatidylserine externalization and Caspase 3 activation in mercury-treated HepG 2 cells. (mdpi.com)
  • Cells were exposed to mercury for 10 and 48 hours respectively at doses of 0, 1, 2, and 3 μg/mL based on previous cytotoxicity results in our laboratory indicating an LD 50 of 3.5 ± 0.6 μg/mL for mercury in HepG 2 cells. (mdpi.com)
  • The percentages of cells undergoing early apoptosis were 0.03 ± 0.03%, 5.19 ± 0.04%, 6.36 ± 0.04%, and 8.84 ± 0.02% for 0, 1, 2, and 3 μg/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. (mdpi.com)
  • The percentages of Caspase 3 positive cells undergoing late apoptosis were 3.58 ± 0.03%, 17.06 ± 0.05%, 23.32 ± 0.03%, and 34.51 ± 0.01% for 0, 1, 2, and 3 μg/mL of mercury respectively, also indicating a gradual increase in Caspase positive cells with increasing doses of mercury. (mdpi.com)
  • S. Huang, K. Bijangi-Vishehsaraei, M. Saadatzadeh and A. Safa, "Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells," Journal of Cancer Therapy , Vol. 3 No. 5, 2012, pp. 504-510. (scirp.org)
  • Apoptosis or programmed cell death is a physiological process in which cells respond to a variety of stimuli and undergo a controlled and regulated manner of cell death [1, 2, 3]. (thefreelibrary.com)
  • Using quantitative Western blot analysis, we studied the levels of nonactivated (uncleaved) caspase 2 and 3 in peripheral blood low-density cells from 185 patients with newly diagnosed AML. (bloodjournal.org)
  • 11 In addition, activation of caspase 3 and, to some extent, caspase 2 (ICH-1) 12-16 appears to be necessary to induce apoptosis in HL-60 myeloid leukemia cells. (bloodjournal.org)
  • Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. (sigmaaldrich.com)
  • Application of the probe allowed us to monitor caspase-3 activation after chemotherapy-treatment and to distinguish between apoptosis sensitive and resistant cells. (rsc.org)
  • This led to the surprising finding that in cancerous cells active caspase-3 is not only found at the familiar cellular locations but also in mitochondria and the endoplasmic reticulum. (rsc.org)
  • Caspase-3 and caspase-7 have been identified as key executors of apoptosis in mammalian cells and play a central role in the execution phase of apoptosis ( 14 , 15 ). (aacrjournals.org)
  • Total population (Tot) or sorted cells were then lysed as in the legend to Fig. 3, and subjected to Western blot analysis for caspase-3 processing. (nih.gov)
  • Processing of caspase-3 was similar in both CD4 and CD8 T cell subsets and occurred not only in CD45RO+, but also in the remaining CD45RA+/CD25+ cells (Fig. 3a and Fig. b), further confirming that caspase activation was an early event after TCR triggering. (nih.gov)
  • Nifedipine prevents etoposide-induced caspase-3 activation, prenyl transferase degradation and loss in cell viability in pancreatic β-cells. (biomedsearch.com)
  • Herein, we report that pro-caspase-8 is capable of restoring cell migration/adhesion to caspase-8-null cells, establishing the first biological function of a pro-caspase. (aacrjournals.org)
  • Tyrosine-380 was required for the restoration of cell motility and cell adhesion in caspase-8-null cells, demonstrating the importance of the caspase-8-p85 interaction for these nonapoptotic functions. (aacrjournals.org)
  • Caspase-8 has also been implicated in the proinvasive effects of FASL in tumor cells ( 3 ). (aacrjournals.org)
  • However, the pro-caspase-8 form predominates in nonapoptotic cells. (aacrjournals.org)
  • Cells at passages 3 to 5 were used for experiments. (ahajournals.org)
  • Here, we report that in vitro treatment of androgen-insensitive (DU145 and PC-3) and androgen-sensitive (LNCaP) prostate cancer cells with berberine inhibited cell proliferation and induced cell death in a dose-dependent (10-100 μmol/L) and time-dependent (24-72 hours) manner. (aacrjournals.org)
  • The major cause of the mortality associated with this disease is the metastasis of cancer cells that fail to respond to hormone ablation therapy ( 3 , 4 ). (aacrjournals.org)
  • We further examined the cell growth state distribution and activation of caspase-3 in SW620 cells treated with γ-tocotrienol for 24 h. (nih.gov)
  • In order to determine caspase-3 activation, SW620 cells were pre-treated with z.VAD.fmk, a pan-specific caspase inhibitor and then treated with different concentrations of γ-tocotrienol for 24 h. (nih.gov)
  • Furthermore, transiently expressed NC was cleaved even in the caspase-3-deficient cell line, MCF-7 cells, and this efficiency was not altered by the transfectional expression of caspase-3. (springer.com)
  • To assess the complex interactions among caspases during apoptosis, we disrupted caspase-8, -9, -3, -7, or -6 and combinations thereof, using CRISPR-based genome editing in living human leukemia cells. (sciencemag.org)
  • Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 μM) in the presence or absence of propofol (40 μM, 80 mM and 160 μM). (eurekaselect.com)
  • Rosaria Acquaviva, Agata Campisi, Giuseppina Raciti, Roberto Avola, Maria Luisa Barcellona, Luca Vanella and Giovanni Li Volti, " Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1", Current Neurovascular Research (2005) 2: 141. (eurekaselect.com)
  • Further work revealed that caspase-8 was essential for the induction of the transcription factor "nuclear factor κB" (NF-κB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. (wikipedia.org)
  • Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
  • Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. (nih.gov)
  • The Caspase-9/6 Fluorescent Assay detects the shift in fluorescence of 7- amino-4-methoxy coumarin (AMC). (clontech.com)
  • The Caspase-3 Fluorescent Assays detect the shift in fluorescence emission of 7-amino-4-trifluoromethyl coumarin (AFC). (clontech.com)
  • Targeted gene disruptions have revealed significant roles for caspase family members in the regulation of neuronal programmed cell death. (nih.gov)
  • Caspase 2 was isolated from a human fetal cDNA library by screening with a probe of the mouse ICE-homolog Need-2 gene, 12 13 and the caspase 2 gene has been assigned to chromosome 7q35. (bloodjournal.org)
  • Of 35 selected single-nucleotide polymorphisms, four in the caspase-7 gene were in high linkage disequilibrium (rs11593766, rs3124740, rs11196445, and rs11196418) and associated with the risk for endometrial cancer. (aacrjournals.org)
  • No association was observed between polymorphisms of the caspase-8 gene and risk for endometrial cancer. (aacrjournals.org)
  • Caspase-3 is also required for some typical hallmarks of apoptosis, and is indispensable for apoptotic chromatin condensation and DNA fragmentation in all cell types examined. (nih.gov)
  • Moreover, we show that, in contrast to the human enzymes, mouse caspase-7 is as efficient as caspase-3 at cleaving and thus inactivating ICAD (inhibitor of caspase-activated DNase), the inhibitor of apoptotic DNA fragmentation. (jneurosci.org)
  • This is the first report supporting a role for caspase-7 in brain development and DNA fragmentation in the absence of caspase-3. (jneurosci.org)
  • Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. (springer.com)
  • It is also known as caspase activated nuclease (CPAN), dna fragmentation factor 40 (DFF-40), DFF2 and DFFB. (wikipedia.org)
  • Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
  • Those studies also demonstrated that the expressed Bax activated caspase-3, indirectly inhibited Bcl-2 expression, formed Bax-Bcl-2 heterodimers and initiated cell apoptosis following cerebral ischemia/reperfusion injury. (spandidos-publications.com)
  • Furthermore, after the intracerebroventricular injection of carbenoxolone (CBX, the inhibitor of Cx43) at 30min before MCAO surgery, Calpain II, Bax and cleaved Caspased-3 immunoreactivity in ischemic penumbra region was detected by immunofluorescent staining, and cell apoptosis was detected by TUNEL staining. (unboundmedicine.com)
  • They are non-toxic and do not inhibit caspases during the experiments. (biotium.com)
  • Results: In this report, we demonstrated that Taxol treatment resulted in apoptosis which was associated with caspase-3 activation. (scirp.org)
  • Increased tumor [ 18 F]ICMT-11 uptake was associated with caspase-3 activation measured ex vivo , and early radiotracer uptake predicted apoptosis, distinct from the glucose metabolism with [ 18 F]fluorodeoxyglucose-PET, which depicted continuous loss of cell viability. (aacrjournals.org)
  • This specificity allows caspases to be incredibly selective, with a 20,000-fold preference for aspartic acid over glutamic acid. (wikipedia.org)
  • Fluorescence detection is highly sensitive and can be used to measure even very small amounts of active caspase. (clontech.com)
  • Using radiolabeled 64 Cu-LS498 in a controlled and localized in-vivo model of caspase-3 activation, a time-dependent five-fold NIR fluorescence enhancement is observed, but radioactivity remains identical in caspase-3 positive and negative controls. (spiedigitallibrary.org)
  • The amount of caspase-7 activation in apoptotic precursor neurons is independent of the presence of caspase-3. (jneurosci.org)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (abcam.com)
  • Caspase enzymes are working as a cascade and caspase 3 is the most important member of this family which plays an effective role in apoptosis of neurons of central nervous system [ 19 ]. (hindawi.com)
  • During the execution of the apoptotic cascade, activated caspase-3 releases SREBP from the membrane of the ER in a proteolytic reaction that is distinct from their normal sterol-dependent activation. (scbt.com)
  • Thus, cleaved caspase 3 could stimulate the apoptotic cascade further, and lack of its activation likely caused an accumulation of the uncleaved caspase. (bloodjournal.org)
  • Within this article, we describe methods for measuring caspase-3 activation at single-cell resolution in various complex environments using FLIM. (mdpi.com)
  • The effects of a single dose of the alkylating agent cyclophosphamide (CPA or 4-hydroperoxycyclophosphamide), or the mechanism-based small molecule SMAC mimetic birinapant on caspase-3 activation was assessed in vitro and by [ 18 F]ICMT-11-PET in mice bearing 38C13 B-cell lymphoma, HCT116 colon carcinoma, or MDA-MB-231 breast adenocarcinoma tumors. (aacrjournals.org)
  • Despite this confirmation that sensory neurons survive, neurons had elevated expression of activated caspase-3 in unique patterns that included their nuclei, cytoplasm, and proximal axonal segments. (diabetesjournals.org)
  • Caspase-3 expression is widely distributed. (fluidigm.com)
  • Although caspase-7 is expressed in both strains during brain development, its expression level is lower in 129 compared with B6 brains. (jneurosci.org)
  • The expression of caspase‑3, Bax and Bcl‑2 genes was detected by the reverse transcriptase polymerase chain reaction (RT‑PCR). (spandidos-publications.com)
  • The present study investigated the expression of caspase-3, Bcl-2 and Bax and neuron apoptosis, as well as the ethological alterations following cerebral ischemia-reperfusion injury in a rat model. (spandidos-publications.com)
  • The expression levels of caspases in tumors are found to be distinct from levels in normal tissue in a series of cancers. (aacrjournals.org)
  • For example, expression of caspase-3 was observed to be down-regulated in pediatric neuroblastoma ( 17 ), breast cancer ( 18 ), and gastric carcinoma ( 19 ), whereas caspase-7 was found to be down-regulated in colonic carcinoma ( 20 ), breast cancer ( 21 ), and gastric cancer ( 22 ). (aacrjournals.org)
  • Decreased expression of caspase-8 was also reported in neuroblastoma ( 23 ) and pediatric tumors ( 24 ). (aacrjournals.org)
  • Genetic polymorphisms in the caspase genes may affect cancer risk through altering expression levels and functions of these genes. (aacrjournals.org)
  • The abnormalities in the fetal thyroid gland seemed to depend on the activation of caspase-3, Bcl-2, BAX, Cox2, and NF-κB mRNA expression. (rsc.org)
  • Moreover, although Bcl-2 overexpression strongly reduces caspase-3 activation, Bcl-2 knockdown has a negligible effect, demonstrating a general model finding that varying the expression levels of signal molecules frequently has asymmetric effects on the outcome. (jimmunol.org)
  • We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. (nih.gov)
  • Although the genesis of certain tumor types such as neuroblastoma and small-cell lung cancer involves the loss of caspase-8 expression, which suppresses anoikis in neuroblastomas ( 4 ), expression is maintained or increased in most tumor types (Supplementary Fig. S1). (aacrjournals.org)
  • Utilizing a mouse model with renal bilateral 30-min ischemia and 48-h reperfusion, the renoprotective effects of a single dose of CHBP (24 nmol/kg) or CASP3siRNA (0.03 mg/kg) were demonstrated on renal function and structure, active 17 kDa caspase-3 and HMGB1 expression in IR kidneys. (aspetjournals.org)
  • The expression levels of caspase‑3 and p53 were upregulated with CO extract treatment, whereas those of Bcl‑2, CDK4 and cyclin D were significantly downregulated. (spandidos-publications.com)
  • Cleaved caspase‑3 expression was upregulated following treatment with CO extract in a dose‑dependent manner. (spandidos-publications.com)
  • Appropriate propofol concentrations (ranging from 40 μM to 160 μM) significantly increased HO- 1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. (eurekaselect.com)
  • Expression of caspase‐uncleavable mutant HuCdc6 attenuates apoptosis, delaying cell death. (embopress.org)
  • A key feature of caspases in the cell is that they are present as zymogens, termed procaspases, which are inactive until a biochemical change causes their activation. (wikipedia.org)
  • Using a biochemical approach to investigate the molecular mechanism responsible for the resistance of the B6 strain to the loss of caspase-3, we identified caspase-7 as having similar properties to caspase-3 in the mouse. (jneurosci.org)
  • There are 14 caspases found in human [6]. (thefreelibrary.com)
  • Description Human and some mouse caspases are active in apoptosis and cell death and even in necrosis and inflammation. (gentaur.com)
  • Our previous studies ( 2 , 3 ) indicated that the loci of brain tissue damage and pathological characteristics in a rat ischemia model coincided with human cerebral infarction loci and clinical symptoms with regard to injury as the same target tissue is involved in both rats and humans. (spandidos-publications.com)
  • Human rabaptin-5 is selectively cleaved by caspase-3 during apoptosis. (springer.com)
  • Synthetic peptide corresponding to a sequence at the C-Terminus of human Caspase-3 (P10), identical to the related rat and mouse sequence. (lsbio.com)
  • Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts. (harvard.edu)
  • The neurons expressing caspase‑3, Bax and Bcl‑2 in the cortical area, CA3, CA1, stratum lucidum (Slu) and molecular layer of the dentate gyrus (MoDG) of the hippocampus were detected using immunohistochemistry or the TUNEL method. (spandidos-publications.com)
  • When the procaspase is cleaved at a particular residue, the active heterotetramer can then be formed by hydrophobic interactions, causing four anti-parallel beta-sheets from p17 and two from p12 to come together to make a heterodimer, which in turn interacts with another heterodimer to form the full 12-stranded beta-sheet structure surrounded by alpha-helices that is unique to caspases. (wikipedia.org)
  • This broad range indicates that caspase-3 will be fully active under normal and apoptotic cell conditions. (wikipedia.org)
  • Oligomerization of procaspase-8 in the DISC leads to self activation with release of active caspase-8 in to the cytosol. (thefreelibrary.com)
  • Moreover, it enabled real-time high-resolution visualization of active caspase-3 during apoptosis. (rsc.org)
  • At last, western blot was used to find that levofloxacin increased the ratio of Bax/Bcl-2 and active caspase-3 in a dose-dependent manner. (sigmaaldrich.com)
  • Combined treatment of CHBP and CASP3siRNA further preserved kidney structure, and reduced active caspase-3 and HMGB1. (aspetjournals.org)
  • Epithelia (25/group) were homogenized, and assayed for active caspase-3 with the caspACE TM (Promega) system. (arvojournals.org)
  • The caspase-3 His-237 stabilizes the target Aspartate causing the break of the association of ICAD and CAD leaving the endonuclease CAD active allowing it to degrade chromosomal DNA. (wikipedia.org)