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 3.4.22.4.
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.

Inhibition of NF-kappa B activity in human T lymphocytes induces caspase-dependent apoptosis without detectable activation of caspase-1 and -3. (1/222)

NF-kappa B is involved in the transcriptional control of various genes that act as extrinsic and intrinsic survival factors for T cells. Our findings show that suppression of NF-kappa B activity with cell-permeable SN50 peptide, which masks the nuclear localization sequence of NF-kappa B1 dimers and prevents their nuclear localization, induces apoptosis in resting normal human PBL. Inhibition of NF-kappa B resulted in the externalization of phosphatidylserine, induction of DNA breaks, and morphological changes consistent with apoptosis. DNA fragmentation was efficiently blocked by the caspase inhibitor Z-VAD-fmk and partially blocked by Ac-DEVD-fmk, suggesting that SN50-mediated apoptosis is caspase-dependent. Interestingly, apoptosis induced by NF-kappa B suppression, in contrast to that induced by TPEN (N,N,N',N'-tetrakis [2-pyridylmethyl]ethylenediamine) or soluble Fas ligand (CD95), was observed in the absence of active death effector proteases caspase-1-like (IL-1 converting enzyme), caspase-3-like (CPP32/Yama/apopain), and caspase-6-like and without cleavage of caspase-3 substrates poly(ADP-ribose) polymerase and DNA fragmentation factor-45. These findings suggest either low level of activation is required or that different caspases are involved. Preactivation of T cells resulting in NF-kappa B nuclear translocation protected cells from SN50-induced apoptosis. Our findings demonstrate an essential role of NF-kappa B in survival of naive PBL.  (+info)

Alternative, non-secretase processing of Alzheimer's beta-amyloid precursor protein during apoptosis by caspase-6 and -8. (2/222)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Although the pathogenesis of AD is unknown, it is widely accepted that AD is caused by extracellular accumulation of a neurotoxic peptide, known as Abeta. Mutations in the beta-amyloid precursor protein (APP), from which Abeta arises by proteolysis, are associated with some forms of familial AD (FAD) and result in increased Abeta production. Two other FAD genes, presenilin-1 and -2, have also been shown to regulate Abeta production; however, studies examining the biological role of these FAD genes suggest an alternative theory for the pathogenesis of AD. In fact, all three genes have been shown to regulate programmed cell death, hinting at the possibility that dysregulation of apoptosis plays a primary role in causing neuronal loss in AD. In an attempt to reconcile these two hypotheses, we investigated APP processing during apoptosis and found that APP is processed by the cell death proteases caspase-6 and -8. APP is cleaved by caspases in the intracellular portion of the protein, in a site distinct from those processed by secretases. Moreover, it represents a general effect of apoptosis, because it occurs during cell death induced by several stimuli both in T cells and in neuronal cells.  (+info)

Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. (3/222)

Neuronal cell death, neurofibrillary tangles, and amyloid beta peptide (Abeta) deposition depict Alzheimer's disease (AD) pathology, but neuronal loss correlates best with dementia. We have shown that increased production of Abeta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing. Here, we investigate key effectors of cell death, caspases, in human neuronal apoptosis and APP processing. We find that caspase-6 is activated and responsible for neuronal apoptosis by serum deprivation. Caspase-6 activity precedes the time of commitment to neuronal apoptosis by 10 h, indicating possible activity without subsequent apoptosis. Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Abeta. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Abeta-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons. A pulse-chase experiment reveals a precursor-product relationship between Capp6.5, intracellular Abeta, and secreted Abeta, indicating a potential alternate amyloidogenic pathway. Caspase-6 proenzyme is present in adult human brain tissue, and the p10 active caspase-6 fragment is detected in AD brain tissue. These results indicate a possible alternate pathway for APP amyloidogenic processing in human neurons and a potential implication for this pathway in the neuronal demise of AD.  (+info)

Cleavage and inactivation of ATM during apoptosis. (4/222)

The activation of the cysteine proteases with aspartate specificity, termed caspases, is of fundamental importance for the execution of programmed cell death. These proteases are highly specific in their action and activate or inhibit a variety of key protein molecules in the cell. Here, we study the effect of apoptosis on the integrity of two proteins that have critical roles in DNA damage signalling, cell cycle checkpoint controls, and genome maintenance-the product of the gene defective in ataxia telangiectasia, ATM, and the related protein ATR. We find that ATM but not ATR is specifically cleaved in cells induced to undergo apoptosis by a variety of stimuli. We establish that ATM cleavage in vivo is dependent on caspases, reveal that ATM is an efficient substrate for caspase 3 but not caspase 6 in vitro, and show that the in vitro caspase 3 cleavage pattern mirrors that in cells undergoing apoptosis. Strikingly, apoptotic cleavage of ATM in vivo abrogates its protein kinase activity against p53 but has no apparent effect on the DNA binding properties of ATM. These data suggest that the cleavage of ATM during apoptosis generates a kinase-inactive protein that acts, through its DNA binding ability, in a trans-dominant-negative fashion to prevent DNA repair and DNA damage signalling.  (+info)

Proteolytic cleavage of beta-catenin by caspases: an in vitro analysis. (5/222)

Cleavage of structural proteins by caspases has been associated with the severe morphological changes occurring during the apoptotic process. One of the proteins regulating the connection of the actin filament with cadherins in a cell-cell adhesion complex is beta-catenin. During apoptosis, both an N-terminal and a small C-terminal part are removed from beta-catenin. Removal of the N-terminal part may result in a disconnection of the actin filament from a cadherin cell-cell adhesion complex. We demonstrate that caspase-8, -3 and -6 directly proteolyse beta-catenin in vitro. However, the beta-catenin cleavage products generated by caspase-8 were different from those generated by caspase-3 or caspase-6. Caspase-1, -2, -4/11 and -7 did not or only very inefficiently cleave beta-catenin. These data suggest that activation of procaspase-3, -6 or -8 by different stimuli in the cell might result in a differential proteolysis of beta-catenin.  (+info)

Caspase-induced proteolysis of the cyclin-dependent kinase inhibitor p27Kip1 mediates its anti-apoptotic activity. (6/222)

The caspase-mediated cleavage of a limited number of cellular proteins is a common feature of apoptotic cell death. This cleavage usually inhibits the function of the target protein or generates peptides that actively contribute to the death process. In the present study, we demonstrate that the cyclin-dependent kinase inhibitor p27Kip1 is cleaved by caspases in human leukemic cells exposed to apoptotic stimuli. We have shown recently that p27Kip1 overexpression delayed leukemic cell death in response to cytotoxic drugs. In transient transfection experiments, the p23 and the p15 N-terminal peptides generated by p27Kip1 proteolysis demonstrate an anti-apoptotic effect similar to that induced by the wild-type protein, whereas cleavage-resistant mutants have lost their protective effect. Moreover, stable transfection of a cleavage-resistant mutant of p27Kip1 sensitizes leukemic cells to drug-induced cell death. Altogether, these results indicate that proteolysis of p27Kip1 triggered by caspases mediates the anti-apoptotic activity of the protein.  (+info)

Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. (7/222)

Caspase-3 initiates apoptotic DNA fragmentation by proteolytically inactivating DFF45 (DNA fragmentation factor-45)/ICAD (inhibitor of caspase-activated DNase), which releases active DFF40/CAD (caspase-activated DNase), the inhibitor's associated endonuclease. Here, we examined whether other apoptotic proteinases initiated DNA fragmentation via DFF45/ICAD inactivation. In a cell-free assay, caspases-3, -6, -7, -8, and granzyme B initiated benzoyloxycarbonyl-Asp-Glu-Val-Asp (DEVD) cleaving caspase activity, DFF45/ICAD inactivation, and DNA fragmentation, but calpain and cathepsin D failed to initiate these events. Strikingly, only the DEVD cleaving caspases, caspase-3 and caspase-7, inactivated DFF45/ICAD and promoted DNA fragmentation in an in vitro DFF40/CAD assay, suggesting that granzyme B, caspase-6, and caspase-8 promote DFF45/ICAD inactivation and DNA fragmentation indirectly by activating caspase-3 and/or caspase-7. In vitro, however, caspase-3 inactivated DFF45/ICAD and promoted DNA fragmentation more effectively than caspase-7 and endogenous levels of caspase-7 failed to inactivate DFF45/ICAD in caspase-3 null MCF7 cells and extracts. Together, these data suggest that caspase-3 is the primary inactivator of DFF45/ICAD and therefore the primary activator of apoptotic DNA fragmentation.  (+info)

Caspase-3 and caspase-7 but not caspase-6 cleave Gas2 in vitro: implications for microfilament reorganization during apoptosis. (8/222)

Apoptosis is characterized by proteolysis of specific cellular proteins by a family of cystein proteases known as caspases. Gas2, a component of the microfilament system, is cleaved during apoptosis and the cleaved form specifically regulates microfilaments and cell shape changes. We now demonstrate that Gas2 is a substrate of caspase-3 but not of caspase-6. Proteolytic processing both in vitro and in vivo is dependent on aspartic residue 279. Gas2 cleavage was only partially impaired in apoptotic MCF-7 cells which lack caspase-3, thus indicating that different caspases can process Gas2 in vivo. In vitro Gas2 was processed, albeit with low affinity, by caspase-7 thus suggesting that this caspase could be responsible for the incomplete Gas2 processing observed in UV treated MCF-7 cells. In vivo proteolysis of Gas2 was detected at an early stage of the apoptotic process when the cells are still adherent on the substrate and it was coupled to the specific rearrangement of the microfilament characterizing cell death. Finally we also demonstrated that Gas2 in vitro binds to F-actin, but this interaction was unaffected by the caspase-3 dependent proteolytic processing.  (+info)

Neurodegenerative diseases pose one of the most pressing unmet medical needs today. It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently no disease-modifying therapies. Thus it is a potential target for neurodegenerative drug development. In the present study we report on the biochemistry and structure of caspase-6. As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free structure shows caspase-6 in a partially mature but latent conformation. The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase ...
Bandai Namco has released a new trailer for Code Vein that showcases the Invading Executioner boss. The Invading Executioner utilizes her scythe for swift attacks with rhythmic precision. She is…
ISIS butcher Jihadi John had a fearless and hate-filled nothing to lose mentality that catapulted him into his role as the bloodthirsty executioner in the...
Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of ...
Pain is a perceptive, unpleasant, multidimensional, sensory, emotional phenomenon that signals the possibility of physical harm. (Executioner) ...
48. Zavolan, M., Gerber, A.P. (2018) Mirroring the multifaceted role of RNA and its partners in gene expression. FEBS Lett. 592(17):2825-2827. doi: 10.1002/1873-3468.13230. 47. Albihlal, W.A., Gerber, A.P. (2018) Unconventional RNA-binding proteins: an uncharted zone in RNA biology. FEBS Lett. 592(17), 2917-2931. doi: 10.1002/1873-3468.13161. 46. Iadevaia, V. Matia-González, A.M, Gerber, A.P. (2018) An oligonucleotide-based tandem RNA isolation procedure to recover eukaryotic mRNA-protein complexes. J. Vis. Exp. 138. doi: 10.3791/58223. 45. King, H.A., El-Sharif, H.F., Matia-González, A.M., Iadevaia, V., Fowotade, A., Reddy, S.M., Gerber, A.P. (2017) Generation of ribosome imprinted polymers for sensitive detection of translational responses. Sci. Rep. 7(1), 6542. doi: 10.1038/s41598-017-06970-x. 44. Matia-González, A.M., Iadevaia, V., Gerber, A.P. (2017) A versatile tandem RNA isolation procedure to capture in vivo formed mRNA-protein complexes. Methods, 118-119, 93-100. (epub Oct 13, 2016. ...
India is preparing for its first executions in seven years, but the government could be forced to delay the hangings because of a lack of executioners.
TY - JOUR. T1 - Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury. AU - Singh, Amar B.. AU - Kaushal, Varsha. AU - Megyesi, Judit K.. AU - Shah, Sudhir V.. AU - Kaushal, Gur P.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Background. Caspase-6 is an important member of the executioner caspases in the caspase family of cell death proteases. The executioner caspases are the major active caspases detected in apoptotic cells and are generally considered to mediate the execution of apoptosis by cleaving and inactivating intracellular proteins. However, the complete characterization of mRNA and protein of caspase-6 in rat and its expression in normal kidney and in disease state has not been previously elucidated. Methods. A rat kidney cortex λgt10 cDNA library was screened to isolate the full-length caspase-6 cDNA. The recombinant caspase-6 protein was characterized by expression in bacteria and by transient transfection in mammalian cells. The expression in ...
Last month, federal Judge Beth Phillips said in a ruling in a death penalty case that it weighed heavily on her that condemned inmate Herbert Smulls had no legal means to learn more about how Missouris execution drug is made.. Under a Missouri law enacted in 2007, information that could be used to identify Missouri executioners is exempt from the states open records law. Under one of the laws provisions, executioners can sue anyone who knowingly releases their identities. When Missouri hired a compounding pharmacy last fall to produce drugs for its lethal injections, the Department of Corrections said it considered the pharmacy, as part of the execution team, to be secret under the law.. By the time Smulls case got to Phillips, the 8th Circuit U.S. Court of Appeals had already ruled that he was not entitled to learn more about the pharmacists making Missouris drugs for executions. The issue was moot, the court said, because Smulls had not proposed a more humane way to die. Phillips denied ...
Medieval style executioner. Full over-the-head latex mask. Individually hand painted for the most realistic look possible. (MC-TB26363)
ISTANBUL (AP) - Turkey's official news agency says three men suspected of carrying out murders on behalf of the Islamic State group were arrested.Anadolu...
On the morning of Jan. 8, 1908, the murderer John Boyd managed six hours of broken sleep in his Don Jail cell and, at around 7, newspaper readers lear...
4199-4207. The potential for best kratom strain to buy the use of cell proliferation and oncogene expression as intermediate markers during liver carcinogenesis. The p53-Mdm2 module and the ubiquitin system.. The fluorometric readings with SH-SY5Y cells which were treated with high doses Arena Ethnobotanicals Kratom Tincture ,iframe width=560″ height=315″ src=http://www.youtube.com/embed/to9joKDLAfM frameborder=0″ allowfullscreen,. of MSE as early as 4 hr failed to show any significant caspase 8 and 9 activities. A second incubation time point at 18 hr also showed negative results. The next step was investigating the possibility of involvement of executioner caspases such as caspase 3 and 7.. These effects kratom vendors reviews are noticeable after 5 to 10 minutes and can last for several hours. Kratom contains a number of active components so-called alkaloids of which mitragynine is believed to be responsible for most of its effects. Mitragynine is an opioid agonist meaning that it ...
Studying brain disorders in people and developing drugs to treat them has been slowed by the inability to investigate single living cells from adult patients. In a first-of-its-kind study published in Cell Reports this week, a team from the Perelman School of Medicine at the University of Pennsylvania led by James Eberwine, PhD, a professor of Pharmacology, Sean Grady, MD, chair of Neurosurgery, and Junhyong Kim, PhD, a professor of Biology in Penns School of Arts & Sciences, was able to grow adult human neurons donated from patients ...
Supplementary MaterialsDataSheet_1. the additional four baseline strategies. Furthermore, we validated the predictions from the MDADTI in six drug-target connections reference databases, as well as the outcomes demonstrated that MDADTI can identify unknown DTIs effectively. = 1,……,? and a couple of goals T?= = 1,……,, where represents the real variety of medications and represents the amount of goals. We also described the connections between D and T being a binary matrix Y whose component beliefs are 0 or 1, where = 1 represents the medication and similarity matrices of goals in = to get the topology framework feature of medication nodes. The RWR strategy can be developed as the next recurrence relationship: is normally a row vector of medication and its techniques starting from 99011-02-6 medication may be the preliminary one-hot vector, is the probability of restart, and is the one-step probability transition matrix acquired by applying row-wise normalization of the similarity matrix ...
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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 ...
The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis.: Acco
Chavoret Jaruboons memoirs in English and Thai Up until 1934, the official method of execution in Thailand was by decapitating (see The Last Public Be...
Police investigating the murder of newlywed Catherine Mullany are probing possible links between her killing and a recent execution-style shooting in Antigua.
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zVAD-fmk does not totally abrogate FasL-triggered apoptosis in HeLa cells expressing caspase-10 at low level.A, B, Casp10+ and Casp10- HeLa cells were incubated
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Outrageous indeed. I couldnt agree more with IPA director-general Hamish Pringles take on Thomas Cookes contribution to an increasingly acrimonious global media-buying debate. The travel operator is reported to be demanding a £1m signing-on fee at the conclusion of its £30m media review - in addition to a reduction in agency fees currently paid and…
TY - JOUR. T1 - Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis. AU - Mazroui, Rachid. AU - Di Marco, Sergio. AU - Clair, Eveline. AU - Von Roretz, Christopher. AU - Tenenbaum, Scott A.. AU - Keene, Jack D.. AU - Saleh, Maya. AU - Gallouzi, Imed Eddine. PY - 2008/1/14. Y1 - 2008/1/14. N2 - The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induced cell death. Upon lethal stress, HuR translocates into the cytoplasm by a mechanism involving its association with the apoptosome activator pp32/PHAP-I. Depleting the expression of pp32/PHAP-I by RNA interference reduces both HuR cytoplasmic accumulation and the efficiency of caspase activation. In the cytoplasm, HuR undergoes caspase-mediated cleavage at aspartate 226. This cleavage activity is ...
Apoptosis is a process of fundamental importance to multicellular organisms that enables control of cell populations and the removal of damaged or potentially harmful cells (Arends and Wyllie 1991). Apoptosis occurs in two phases: an initial commitment phase followed by an execution phase involving cytoskeletal disruption, membrane blebbing, condensation and fragmentation of chromatin, and the formation of apoptotic bodies (Earnshaw 1995). Caspases, a family of aspartate-specific cysteine proteases, play a critical role in the execution phase of apoptosis and are the key effectors responsible for many of the dramatic morphological and biochemical changes of apoptosis (for reviews see Cohen 1997; Thornberry and Lazebnik 1998). Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. Caspases can be divided into two classes: (1) initiator caspases, with long prodomains, such as caspases-8 and -9, which either ...
Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid β (Aβ) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (ΔTau) by executioner caspases. Following caspase-cleavage, ΔTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. ΔTau can be phosphorylated by glycogen synthase kinase-3β and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, ΔTau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, ΔTau colocalizes with Aβ1-42 and is induced by Aβ1-42 in vitro. Collectively, our data ...
The response of psoriasis to antibodies targeting the interleukin (IL)-23/IL-17A pathway suggests a prominent role of T-helper type-17 (Th17) cells in this disease. had not been detectable in neutrophils isolated from VX-950 dynamic plaques. Significant medical reactions to secukinumab had been noticed 2?weeks following a solitary infusion, connected with extensive clearance of cutaneous neutrophils parallel towards the normalization of keratinocyte abnormalities and reduced amount of IL-17-inducible neutrophil chemoattractants (e.g. (TNF-(monoclonal antibody selective for IL-17A, or placebo inside a 3:3:3:1 percentage (information regarding test size computation, randomization and blinding are given within the Assisting Information). There have been low- and middle- single-dose cohorts who received secukinumab 3 and 10?mg/kg, respectively, infused on Day time 1 (with placebo administered on Day time 15 and Day time 29) along with a high-dose cohort who have received 3 infusions of secukinumab ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Only days after U.S. President Donald J. Trump spoke about the situation in Sweden, a live hand grenade was found in a park in the city. Police say they were looking for a weapon in connection with a shooting in the same area but dont believe the grenade had anything to do with the shooting leading to speculation from many of what the object was doing there ...
First, the up to date Ensembl IDs have been retrieved for the many genes with SD three between rapamycin and Ly294002 therapies. The Amuvatinib 溶解度 GO lessons
As one of the Imperiums many staging grounds for the forces serving in the Great Crusade, the verdant world of Tallarn has long served as a transfer point for vast numbers of military personnel and their war machines. Now, destroyed by a deadly virus-bomb attack launched by the battered Iron Warriors fleet, the entire world is reduced to a toxic wasteland where the survivors must fight to defend what little remains of their home. The remnants of the once-mighty Jurnian 701st armoured regiment emerge from their underground shelters, and the opening movements of the Battle of Tallarn begin...[1] ...
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
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Summary of CASP8 (Casp-8, FLICE, MACH, MCH5) expression in human tissue. Cytoplasmic expression of varying intensity in most tissues.
Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...
We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...
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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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Epidemiological studies indicate that components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. In the present study, we investigated the effect of newly isolated phenylamine derivative N-benzyl-N-methyldecan-1-amine (NBNMA) from garlic cloves on the inhibition of the growth and apoptosis of human leukemia U937 cells and its potential anticancer mechanism. NBNMA exhibited an antiproliferative effect in U937 cells by inducing cell cycle arrest at the G2/M phase and apoptotic cell death. Western blot analyses revealed that NBNMA decreased the expression of the regulator genes of G2/M phase progression, cyclin dependent kinase (Cdk) 2 and Cdc2 and elevated the expression of the Cdk inhibitor p21WAF1/CIP1 in a p53-independent manner. In addition, NBNMA activated caspase-8 and caspase-9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis, respectively, which led to activation of executioner caspase-3 along with degradation of ...
INTRODUCTION Scientists are building detailed maps of the cellular composition in the human brain to learn about its development. In the human cortex, the largest area of the mammalian brain, neural circuits are formed through anatomical refinement, including axon and synaptic pruning, and the emergence of complex patterns of network activity during early fetal development. Cellular analyses in the human brain are restricted to postmortem material, which cannot reveal the process of development. Model organisms are, therefore, commonly used for studies of brain physiology, development, and pathogenesis, but the results from model organisms do not always translate to humans. RATIONALE Systems to model human neuron dynamics and their dysfunction in vivo are needed. While biopsy specimens and the generation of neurons from induced pluripotent stem cells (iPSCs) could provide the necessary human genetic background, two- and three-dimensional cultures lack factors that normally support neuronal ...
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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…
Complete information for CASP5 gene (Protein Coding), Caspase 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Caspase 6 in turn activates HIPK2. Conversely, p53 down regulates HIPK2 by activating the ubiquitin ligase mdm2. An interaction ... The activity of HIPK2 is increased through the action of caspase 6. Caspase 6 cleaves HIPK2 at residue D916 and D977. As a ... MacLachlan TK, El-Deiry WS (July 2002). "Apoptotic threshold is lowered by p53 transactivation of caspase-6". Proceedings of ... p53 binds to the third intron of the caspase 6 gene, and promotes the activation of the gene. ...
Her research focuses especially on caspases, apoptotic proteins involved in the regulation of cell death, and with impacts in ... "Chemist Jeanne A. Hardy to Give Talk at Brookhaven Lab on Caspases, Causative Factor in Neurodegenerative Diseases , 4/24 , BNL ... Hardy, Jeanne A.; Wells, James A. (2009-07-06). "Dissecting an allosteric switch in caspase-7 using chemical and mutational ... Velázquez-Delgado, Elih M.; Hardy, Jeanne A. (2012-10-19). "Zinc-mediated Allosteric Inhibition of Caspase-6". Journal of ...
Kanneganti's lab showed compensatory roles for NLRP3/caspase-1 and caspase-8 in the regulation of IL-1β production in ... Her lab identified caspase-8 and FADD as expression and activation regulators of both the canonical and non-canonical NLRP3 ... This finding went against the dogma that existed at that time that caspase-8 and FADD were involved only in the apoptotic ... This study demonstrated that the NLRP3 inflammasome/pyroptotic pathway is closely connected to the caspase-8-mediated ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... M (y) 5, 6, 7 ; H (ny) D (y) 11 M (y) 14; R (y) 15; D (y) 16, 18; H (ny) ... 106 (6): 2364-74. Bibcode:2006JNeur..26.9606G. doi:10.1111/j.1471-4159.2008.05578.x. PMID 18643871.. ... 14 (6): 488-92. Bibcode:1996CBio....6.1213A. doi:10.1016/j.cub.2004.03.003. PMID 15043813.. ...
2004). "Regulation of caspase-6 and FLIP by the AMPK family member ARK5". Oncogene. 23 (42): 7067-75. doi:10.1038/sj.onc. ... "ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but ...
Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition. „Blood ... Environ Health Perspect". 91, s. 165-6, Feb 1991. PMID: 2040245. *↑ a b c d B. Deschler, M. Lübbert. Acute myeloid leukemia: ... Blood". 98 (6), s. 1714-20, Sep 2001. PMID: 11535502. *↑ T. Mercher, GD. Raffel, SA. Moore, MG. Cornejo i inni. The OTT-MAL ... Blood". 98 (6), s. 1752-9, Sep 2001. PMID: 11535508. *↑ C. Thiede, C. Steudel, B. Mohr, M. Schaich i inni. Analysis of FLT3- ...
It is also involved in an apoptotic pathway characterized by activation of caspase-6. THOC7 is also part of the same subcomplex ... 6 (1): 19413. doi:10.1038/srep19413. ISSN 2045-2322. Xu, Xiu Qin; Soo, Set Yen; Sun, William; Zweigerdt, Robert (September 2009 ... The gene contains 12 distinct introns, 11 exons, produces 7 different mRNAs, and 6 alternatively spliced variants. The promoter ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
... the role of caspase 6 in HD, genetic variation in the human HD gene and the potential of allele-specific gene silencing using ... "Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus". Human Molecular ... CS1 maint: discouraged parameter (link) "CBC/DNTO: What Happened When You Found A Lost Cause?". Retrieved November 6, 2012. CS1 ... Archived from the original on November 6, 2011. Retrieved November 22, 2011. CS1 maint: discouraged parameter (link) "Carroll's ...
The best characterized IAP is XIAP, which binds caspase-9, caspase-3 and caspase-7, thereby inhibiting their activation and ... By inhibiting caspase 8, crmA prevents the other caspases from ever being activated. Inhibition of caspase 8 also prevents cell ... Caspase 8 initiates apoptosis by activating "executioner" caspases, numbered 3, 6, and 7. ... By inhibiting caspase 1, also known as interleukin 1β converting enzyme (ICE), crmA prevents cytokines interleukin 1β from ...
... including caspase-1/4/5 in humans and caspase-11 in mice. Pro-apoptotic caspases, including caspase-6/7/8/9, are not required ... Inflammasome activates a different set of caspases as compared to apoptosis, for example, caspase-1/4/5 in humans and caspase- ... of gram-negative bacteria directly onto caspase-4/5 in humans and caspase-11 in murines. Binding of LPS onto these caspases ... Caspase-3, an executioner caspase in apoptosis, can cleave gasdermin E (GSDME) to produce a N-terminal fragment and a C- ...
... 不同於一般細胞凋亡的機制需要激發caspase-3蛋白,神經軸突的退化需要激發caspase-6蛋白,而且是在神經軸突上呈現點狀散佈的激發,進而造成軸突的凋亡。此外,經由caspase-6路徑所啟動的細胞凋亡,也可能和另一種神經退化疾病-杭廷頓舞蹈症相關 ... Cleavage at the caspase-6 site is required for neuronal
2007). "Cells with defective p53-p21-pRb pathway are susceptible to apoptosis induced by p84N5 via caspase-6". Cancer Res. 67 ( ...
"Entrez Gene: CARD10 caspase recruitment domain family, member 10". Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S ... Caspase recruitment domain-containing protein 10 is a protein in the CARD-CC protein family that in humans is encoded by the ... The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates ... "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and ...
2010). Cleavage at the 586 Amino Acid Caspase-6 Site in Mutant huntingtin Influences Caspase-6 Activation In Vivo. The Journal ... 6. 10.1016/j.jalz.2010.05.923. Kudo, Lili & VI, Nancy & Lau, Kimbley & Parfenova, Liubov & Hui, Maria & Gray, Michelle & Yang, ...
Galande S, Dickinson LA, Mian IS, Sikorska M, Kohwi-Shigematsu T (August 2001). "SATB1 cleavage by caspase 6 disrupts PDZ ... 79 (6): 809-17. doi:10.1006/geno.2002.6772. PMID 12036295. Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T (October ... 79 (6): 809-17. doi:10.1006/geno.2002.6772. PMID 12036295. Dickinson LA, Joh T, Kohwi Y, Kohwi-Shigematsu T (August 1992). "A ... 280 (6): 5004-12. doi:10.1074/jbc.M411718200. PMID 15561718. Wen J, Huang S, Rogers H, Dickinson LA, Kohwi-Shigematsu T, ...
S30-S38 Graham, RK; Deng, Y; Slow, EJ; et al.Cleavage at the caspase-6 site is required for neuronal dysfunction and ... Surprisingly, both necrotic and apoptotic processes utilize a similar intracellular signaling cascade which uses caspase ... and Morphine-6-Glucuronide-induced Respiratory Depression in Healthy Volunteers: A Mechanism-based Pharmacokinetic- ...
2000). "Caspase-3 and caspase-7 but not caspase-6 cleave Gas2 in vitro: implications for microfilament reorganization during ... The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes ... 54 (6): 787-93. doi:10.1016/S0092-8674(88)91065-3. PMID 3409319. S2CID 37196421. Sgorbissa A, Benetti R, Marzinotto S, et al. ( ... 74 (6): 1255-61. doi:10.1086/421527. PMC 1182089. PMID 15124103. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status ...
2002). "The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during ... doi:10.1016/S0006-291X(02)02834-6. PMID 12504083. Krona C, Ejeskär K, Abel F, et al. (2003). "Screening for gene mutations in a ...
2002). "The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during ...
It also selectively inhibits effector caspases 2, 3, 6, and 7 but not caspases 8 and 10. This compound has been shown to block ... 177 (6): 3827-36. doi:10.4049/jimmunol.177.6.3827. PMID 16951345. S2CID 23419301. v t e. ...
Alcivar A, Hu S, Tang J, Yang X (Jan 2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2 ... Alcivar A, Hu S, Tang J, Yang X (2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2): ... Schickling O, Stegh AH, Byrd J, Peter ME (2002). "Nuclear localization of DEDD leads to caspase-6 activation through its death ... DEDD has been shown to interact with: CFLAR, Caspase 8, and FADD. GRCh38: Ensembl release 89: ENSG00000158796 - Ensembl, May ...
Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results ... "Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ...
"Transcription factor AP-2alpha is preferentially cleaved by caspase 6 and degraded by proteasome during tumor necrosis factor ... 21 (6): 665-76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373. Dixon MJ, Marazita ML, Beaty TH, Murray JC ... 272 (23): 14611-6. doi:10.1074/jbc.272.23.14611. PMID 9169421. Batsché E, Muchardt C, Behrens J, Hurst HC, Crémisi C (Jul 1998 ... 50 (6): 847-61. doi:10.1016/0092-8674(87)90512-5. PMID 3040262. S2CID 25657738. Williams T, Admon A, Lüscher B, Tjian R (Dec ...
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 ...
This trial will test the use of a synthetic siRNA that blocks caspase 2, an important enzyme in the apoptosis cycle. In ... "Ocular neuroprotection by siRNA targeting caspase-2". Cell Death & Disease. 2 (6): e173. doi:10.1038/cddis.2011.54. PMC 3168996 ... showed that visual acuity can improve up to 6 months and not after that. To minimize the risk of further visual loss in the ...
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". ...
"Beta-synuclein displays an antiapoptotic p53-dependent phenotype and protects neurons from 6-hydroxydopamine-induced caspase 3 ...
... of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase ... 460 (7255): 632-6. Bibcode:2009Natur.460..632Z. doi:10.1038/nature08177. PMC 2744588. PMID 19641596.. ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... TANGO6: encoding protein Transport and Golgi organization protein 6 homolog. *TAO2: encoding Serine/threonine-protein kinase ... ARL6IP1: encoding protein ADP-ribosylation factor-like protein 6-interacting protein 1 ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[30 ... 6 (1): 79-85. doi:10.3758/CABN.6.1.79. PMID 16869232.. *^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). " ... 57 (6): 884-95. doi:10.1007/pl00000731. PMID 10950304. S2CID 29317393.. *^ a b c Stevens RJ, Littleton JT (May 2011). "Synaptic ... Brain-derived neurotrophic factor (BDNF), or abrineurin,[5] is a protein[6] that, in humans, is encoded by the BDNF gene.[7][8] ...
... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... Interleukin 6 ACRONYM (IL-6) is a cytokine that is important for many aspects of cellular biology including immune responses, ... 116 (6): 1561-70. doi:10.1172/JCI24652. PMC 1469776 . PMID 16741576. Wilson, Timothy R.; Lee, Diana Y.; Berry, Leanne; Shames, ... 6 (5): 497-506. doi:10.1016/j.ccr.2004.09.032. PMID 15542433. Schlange, Thomas; Matsuda, Yutaka; Lienhard, Susanne; Huber, ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... doi:10.1016/s0166-2236(00)01998-6. PMID 11881748.. *^ a b Ikeda K, Akiyama H, Arai T, Ueno H, Tsuchiya K, Kosaka K (July 2002 ... 6 (4): 303-13. doi:10.1038/sj.cdd.4400505. PMID 10381632.. *^ Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G ( ... 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 ... 9 (6): 418-28. doi:10.1038/nri2566. PMC 4535331. PMID 19461672.. *^ a b c d Doan T (2008). Immunology. Lippincott Williams & ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ...
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 ... 6 (2): 97-105. doi:10.1038/ncb1086. PMID 14743216.. *^ Micheau O, Tschopp J (July 2003). "Induction of TNF receptor I-mediated ... Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer's disease,[6] cancer,[7] ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... 28 (6): 597-601. doi:10.1016/S0093-7754(01)90031-4. PMID 11740816. Lentzsch S, Rogers MS, LeBlanc R, et al. (April 2002). "S-3- ... The secretion of IL-6 by bone marrow stromal cells (BMSC) and the secretion of the adhesion molecules VCAM-1, ICAM-1 and LFA, ... In vitro proliferation of MM cell lines and inhibition of Fas-mediated apoptosis is promoted by IL-6. Thalidomide and its ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[27 ... 6 (1): 79-85. doi:10.3758/CABN.6.1.79. PMID 16869232.. *^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). " ... 57 (6): 884-95. doi:10.1007/pl00000731. PMID 10950304.. *^ a b c Stevens RJ, Littleton JT (May 2011). "Synaptic growth: dancing ... 5 (6): 311-22. doi:10.1038/nrneurol.2009.54. PMID 19498435.. *^ Zajac MS, Pang TY, Wong N, Weinrich B, Leang LS, Craig JM, ...
Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. ... 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 ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. ...
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 · ...
This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... 9 (6): 400-414. doi:10.1038/nrc2657. PMC 2722839. PMID 19440234.. *^ a b Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ ( ... and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does ... 76 (6): 1013-1023. doi:10.1016/0092-8674(94)90379-4.. *^ Brugarolas, James; Chandrasekaran, Chitra; Gordon, Jeffrey I.; Beach, ...
"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase ... 17 (6): 917-924. doi:10.1517/13543784.17.6.917. PMID 18491992.. *^ a b US patent 8,206,751, Gainer J, "New Class of ... 2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-Tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioic acid[2] ... 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+, ...
"A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site- ... 272 (2): 1110-6. doi:10.1074/jbc.272.2.1110. PMID 8995410.. *^ a b c d e f g Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie ... Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a protein that in humans is encoded by the EIF3A gene.[5][6][7] ... Morris-Desbois C, Réty S, Ferro M, Garin J, Jalinot P (December 2001). "The human protein HSPC021 interacts with Int-6 and is ...
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 ... 6 :(31.54 - 31.55 Mb) O factor de necrose tumoral alfa (TNFα), tamén chamado caquexina ou caquectina ou, simplemente, factor de ... Cell Biol. 6 (2): 97-105. PMID 14743216. doi:10.1038/ncb1086.. *↑ Micheau O, Tschopp J (July 2003). "Induction of TNF receptor ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ... 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 ... "DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration". 》PNAS》 111 (45): 16082 ... "Sequence organization of the human genome". Cell 6: 345-358, 1975 *↑ Hasler J, Strub K, (2006). "Alu elements as regulators of ... McClintock, Barbara,"The origin and behavior of mutable loci in maize". Proc Natl Acad Sci U S A. 36 (6): 344-55, 1950 ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... doi:10.1016/0005-2787(72)90509-6. PMID 5065779.. *^ Vilenchik, MM; Knudson, AG (2003). "Endogenous DNA double-strand breaks: ... This pattern of non-lethal injury is sometimes called hydropic change or vacuolar degeneration.[6] Hydropic degeneration is a ...
... -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 ... Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... "Nucleic Acids Res 33 (6): 1834-47. PMC 1072799. PMID 15800213. doi:10.1093/nar/gki324.. ... Putral L, Gu W, McMillan N (2006). "RNA interference for the treatment of cancer". Drug News Perspect 19 (6): 317-24. PMID ... "Plant J 6: 861-77. doi:10.1046/j.1365-313X.1994.6060861.x/abs/.. ... 633-6. PMID 15908945. doi:10.1038/ncb1265.. *↑ Lian S, Jakymiw ...
This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 ... When Hsp70 proteins are ADP bound, the lid is closed, and peptides are tightly bound to the substrate binding domain.[6] ... 151 (6): 1308-18. doi:10.1016/j.cell.2012.10.051. PMC 3778871. PMID 23217712.. ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... 117 (6): 1003-10. PMID 3298579.. *^ Heitmann P (January 1968). "A model for sulfhydryl groups in proteins. Hydrophobic ... Animal sources: meat (including pork and poultry), eggs, dairy;[6]. *Plant sources: red peppers, garlic, onions, broccoli, ... InChI=1S/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6) Y ... InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 ...
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on ... 12 (6): 605-24. doi:10.2174/156802612799436678. PMID 22242859.. *^ Fiorucci S, Mencarelli A, Distrutti E, Zampella A (May 2012 ... 277 (6): 4351-60. doi:10.1074/jbc.M108947200. PMID 11733517.. *. Cui J, Heard TS, Yu J, Lo JL, Huang L, Li Y, Schaeffer JM, ... negative regulation of interleukin-6 production. • triglyceride homeostasis. • negative regulation of interferon-gamma ...
Caspase. *Caspase 1. *Caspase 2. *Caspase 3. *Caspase 4. *Caspase 5. *Caspase 6 ... doi:10.1016/S1357-2725(99)00129-6. PMID 10716634.. *. Wex T, Levy B, Wex H, Brömme D (1999). "Human cathepsins F and W: A new ... Cathepsin W is a protein that in humans is encoded by the CTSW gene.[5][6][7] ...
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 ... 2003 Jun;159(6):759-67. PMID 12751958. *^ Darzynkiewicz Z, Juan G, Li X, Gorczyca W, Murakami, M. Traganos F. (1997) Cytometry ... The current record for a commercial instrument is ten lasers[6] and 30 fluorescence detectors.[7] Increasing the number of ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... 6][35] Reptile and bird brains do not show gyrification. Mammals with a high GI are generally larger than those with a low GI; ... 6] The only observed role that the cranium may play in gyrification is in flattening of gyri as the brain matures after the ... 6][19] In addition, the fibroblast growth factor (FGF)- and sonic hedgehog (SHH)-signaling pathways have recently been reported ...
"N-APP binds DR6 to cause axon pruning and neuron death via distinct caspases". Nature 457 (7232): 981-989. doi:10.1038/ ... ISBN 0-7817-6651-6. Retrieved on 2008-08-19.. *↑ Dennehy C (2006). "Analysis of patients' rights: dementia and PEG insertion". ... doi:10.1016/S1474-4422(04)00878-6. . PMID 15380154 . *Luchsinger JA, Noble JM, Scarmeas N (2007). "Diet and Alzheimer's disease ... Szekely CA, Breitner JC, Zandi PP (2007). "Prevention of Alzheimer's disease". Int Rev Psychiatry 19 (6): 693-706. doi:10.1080/ ...
"Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death". Journal of ... Retrieved 6 April 2019.. *^ "Virulent Newcastle Disease". California Department of Food and Agriculture. Retrieved 6 April 2019 ... 92 (6): 493-4. doi:10.1093/jnci/92.6.493. PMID 10716968.. *^ Csatary, LK (October 1971). "Viruses in the treatment of cancer". ... Retrieved 6 April 2019.. *^ "USDA confirms virulent Newcastle disease in Arizona". Feedstuffs. 5 April 2019. ...
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation ... Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene.CASP6 orthologs have been identified in numerous mammals for ... Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 ...
... Jun 17, 2006, 20:10, Reviewed by: Dr. Himanshu Tyagi. ... In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. By blocking the action ... In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. By blocking the action ...
Rabbit polyclonal active Caspase-6 antibody. Validated in WB and tested in Mouse, Rat, Human. Cited in 1 publication(s). ... The caspase family of cysteine proteases has been shown to play a key role in apoptosis. Similar to other caspases, caspase 6 ... The caspase family of cysteine proteases has been shown to play a key role in apoptosis. Similar to other caspases, caspase 6 ... Together with caspase 3, caspase 6 is one of the major caspases in apoptotic cells, and functions downstream of apoptosis ...
Rabbit polyclonal Caspase-6 / CASP-6 antibody validated for WB, IHC and tested in Human. Immunogen corresponding to recombinant ... Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits. ... Anti-Caspase-6 / CASP-6 antibody (ab155241) at 1/500 dilution + Jurkat whole cell lysate at 30 µg. Predicted band size: 33 kDa ... Anti-Caspase-6 / CASP-6 antibody. See all Caspase-6 / CASP-6 primary antibodies. ...
From: The prodomain of caspase-3 regulates its own removal and caspase activation ... b A caspase-3 activity assay was used to determine the ability to cleave a DEVD-chromphore substrate. c Cell death was ... d Cells were serum starved for 24 h and the cleavage pattern of caspase-3 was determined using western blot analysis. Actin was ... C3 D9E is inefficiently cleaved resulting in decreased caspase activation and cell death. , Cell Death Discovery ...
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.
Shop a large selection of products and learn more about Thermo Scientific Lab Vision Caspase 6 (Mch 2) Ab-3, Mouse Monoclonal ... Caspases play a major role in the transduction of the apoptotic signal and execution of apoptosis in mammalian cells. Caspase 3 ... Caspase-6 cleaves nuclear mitotic apparatus protein (NuMA) and mediates the shrinkage and fragmentation of nuclei. Host Species ... Ensure accurate, reproducible results in western blotting and immunoprecipitation procedures with Thermo Scientific Caspase 6 ( ...
Caspase-6 is detected in all cells of the blastocyst and is excluded from the nucleus. To assess the role of caspase-6 in the ... L. Hinck, J. P. Thissen, and R. De Hertogh "Identification of Caspase-6 in Rat Blastocysts and Its Implication in the Induction ... Identification of Caspase-6 in Rat Blastocysts and Its Implication in the Induction of Apoptosis by High Glucose. ... L. Hinck, J. P. Thissen, R. De Hertogh "Identification of Caspase-6 in Rat Blastocysts and Its Implication in the Induction of ...
Caspase-6 (Cysteine-Requiring Aspartate Proteases) is part of a family of intracellular cysteine proteases that cleave their ... Caspase-3, caspase-8 and caspase-10 can cleave procaspase-6. Active caspase-6 cleaves several other proteins such as lamins, ... Together with caspases-3 and -7, the isoform of caspase-6 is classified as an effector/execution caspase. ... Recombinant catalytically active caspase-6was western blotted with Active/Cleaved Caspase-6 antibody. Theantibody detected both ...
Caspases are a family of cysteine proteases which are the major executors of apoptosis and inflammation. Caspases can be ... Firstly, compared with those of initiator caspases, the pro-domains of effector caspases are short (23-28 residues in length) ... However, in contrast to the above scheme, CASP6 is often activated by CASP3 rather than initiator caspases (Slee et al., 1999. ... In addition, caspases prefer a small and uncharged residue after the P1 aspartate (also known as P1′; Timmer & Salvesen, 2007. ...
A caspase-6 and anti-human epidermal growth factor receptor-2 (HER2) antibody chimeric molecule suppresses the growth of HER2- ... and an active caspase-6, which can directly cleave lamin A leading to nucleus damage and inducing programmed cell death. We ... The immunocasp-6 gene was next transferred into BALB/c athymic mice bearing human breast SK-BR-3 tumors by i.m. injection of ... In this study, we extend the repertoire of chimeric proapoptotic proteins with immunocasp-6, a construct that comprises a HER2- ...
Caspase 6 antibody for Immunohistochemistry (Paraffin-embedded Sections) (IHC (p)). ... Apoptosis, Caspase Cascade in Apoptosis Application Details Product Details anti-Caspase 6 Antibody Target Details Caspase 6 ... Recommended Caspase 6 Antibody (supplied by: Log in to see ) Antigen Caspase 6, Apoptosis-Related Cysteine Peptidase (CASP6) ... This Caspase 6 antibody is un-conjugated Alternatives Biotin. (18), FITC. (17), HRP. (13), APC. (10), Alkaline Phosphatase (AP) ...
... as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60). These caspases are responsible for the proteolysis of the majo ... as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60). These caspases are responsible for the proteolysis of the ... Caspase-6 can cleave its prodomain to produce mature caspase-6, which directly activates caspase-8 (EC 3.4.22.61) and leads to ...
As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. The ligand-free ... The crystal structure of caspase-6, a selective effector of axonal degeneration. Renato Baumgartner, Gabriele Meder, Christophe ... It has long been recognized that caspase-6 may play a role in several neurodegenerative diseases for which there are currently ... The cleaved inter-domain linker remains partially inserted in the central groove of the dimer, as observed in other caspases. ...
Detect caspase-6 activation in vitro with the FAM FLICA Caspase 6 Assay Kit to investigate apoptosis and pyroptosis in whole ... FAM-FLICA® Caspase-6 Assay Kit. $195.00 - $561.00. Detect caspase-6 activity with the FLICA Caspase-6 Assay Kit. This in vitro ... FLICA Caspase-6 Reagent (FAM-VEID-FMK), 1 vial, #654. • 10X Apoptosis Wash Buffer, 15 mL, #635. • Fixative, 6 mL, #636. • ... FLICA Caspase-6 Reagent (FAM-VEID-FMK), 4 vials, #654. • 10X Apoptosis Wash Buffer, 60 mL, #634. • Fixative, 6 mL, #636. • ...
Induction of caspase-3 cleavage in human HuH7 cells at 2.5 to 5 uM incubated for 6 to 24 hrs by Western blot. ...
Caspase-mediated cleavage of Lamin A (Homo sapiens) * active caspase-6 [nucleoplasm] (Homo sapiens) ... Caspase-mediated cleavage of Lamin B1 (Homo sapiens) * active caspase-6 [nucleoplasm] (Homo sapiens) ... Caspase-6 translocates to the nucleus (Homo sapiens) * active caspase-6 [nucleoplasm] (Homo sapiens) ...
Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC... ... Check for Discount on Caspase 6 (Apoptotic Protease Mch 2 or ... Small Molecules to Inhibit Caspase 3 and Caspase 6 for Huntingtons Disease - Drug Profile 33. Product Description 33. ... Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) - Pipeline Review, H2 2016. Summary. Global Markets Directs, ... The report assesses Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) targeted therapeutics based on mechanism of ...
2012) Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules. Apoptosis. 2012 Mar 1; 17(3): ... Home , Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules ...
... and JNK may be an upstream effector of caspase activation. This article has been cited by other articles: Z. Chen, L. W. Forman ... The Recruitment of Fas-associated Death Domain/Caspase-8 in Ras-induced Apoptosis1 Chang-Yan Chen2, Peter Juo, James S. Liou, ... Suppression of JNK by dn-JNK1 blocked the interaction of FADD and caspase-8 and partially protected Jurkat/ras and Jurkat/Fasm/ ... During this Ras-induced apoptotic process, caspase-8 was activated, possibly through its binding to Fas-associated death domain ...
... which leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3; caspase-9 thus is the most ... Feedback cleavage of caspase-9 by caspase-3 again significantly increases the activity of the apoptosome . Caspase-9 plays a ... 7 are targets of caspase-9 activity . Caspase-9 forms dimers in the course of activation. Cytochrome c/Apaf-1/caspase-9 form a ... Apart from cleavage of caspase-3, the downstream enzymes caspase-6 and - ...
... irreversible inhibitor of caspase-1 (Ki = 760 pM), caspase-4, and caspase-5. - Find MSDS or SDS, a COA, data sheets and more ... Calbiochem Caspase-1 Inhibitor II, CAS 178603-78-6, is a cell-permeable, ... Caspase-1 inhibitor II is a cell-permeable, irreversible inhibitor of Caspase-1, Caspase-4, and Caspase-5. Inhibits CPP32/ ... irreversible inhibitor of caspase-1 (Ki = 760 pM), caspase-4, and caspase-5.. More,, Caspase-1 Inhibitor II, CAS 178603-78-6, ...
Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in ...
Increased caspase 3 immunopositivity, as compared to staining of normal breast ductal epithelium, was seen in 22% of benign ... In high-grade in situ lesions there were significantly more cases with strong caspase 3, 6 and 8 immunoreactivity than in low- ... In all cases strong caspase 3, 6 and 8 positivity was significantly associated with the extent of apoptosis (P , 0.001, P = ... The extent of apoptosis was assessed by the TUNEL method and caspase 3, 6 and 8 expression by immunohistochemistry with ...
Loegering, D. A. ; Ruchaud, S. ; Earnshaw, W. C. ; Kaufmann, Scott H. / Evaluation of the role of caspase-6 in anticancer drug- ... Loegering, D. A., Ruchaud, S., Earnshaw, W. C., & Kaufmann, S. H. (2006). Evaluation of the role of caspase-6 in anticancer ... Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis [1]. / Loegering, D. A.; Ruchaud, S.; Earnshaw, W. C. ... Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis [1]. Cell Death and Differentiation. 2006 Feb 1;13(2): ...
Caspase_6 Colorimetric Assay Kit \ K115-100 for more molecular products just contact us ... Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. The Caspase-6 Colorimetric Assay Kit ... Index / Biovis / Caspase_6 Colorimetric Assay Kit / Product Detail : K115-100 Caspase_6 Colorimetric Assay Kit. Related ... We have also other products like : Caspase_6 Colorimetric Assay Kit. Related products : Caspase_6 Colorimetric Assay Kit ...
Caspase-6 Inhibitor Z-VEID-FMK \ 1011-20C for more molecular products just contact us ... 11953316] Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation.. ... 24363090] A synergic role of caspase-6 and caspase-3 in Tau truncation at D421 induced by H2O 2.. [22259050] Honokiol traverses ... We recommend using 1000-5000X dilutions for inhibiting caspase-6 activity in Jurkat cell culture (e.g., Add 1 μl to 1-5 ml of ...
What is caspase recruitment domain-containing protein 6? Meaning of caspase recruitment domain-containing protein 6 medical ... What does caspase recruitment domain-containing protein 6 mean? ... Looking for online definition of caspase recruitment domain- ... containing protein 6 in the Medical Dictionary? caspase recruitment domain-containing protein 6 explanation free. ... redirected from caspase recruitment domain-containing protein 6) CARD6. A gene on chromosome 5p13.1 that encodes a ...
What is caspase 6, apoptosis-related cysteine protease? Meaning of caspase 6, apoptosis-related cysteine protease medical term ... What does caspase 6, apoptosis-related cysteine protease mean? ... Looking for online definition of caspase 6, apoptosis-related ... cysteine protease in the Medical Dictionary? caspase 6, apoptosis-related cysteine protease explanation free. ... A gene on chromosome 4q25 that encodes a so-called effector caspase belonging to the cysteine-aspartic acid protease (caspase) ...
Here, we demonstrate a gain-of-function role for cytoplasmic NPM in the inhibition of caspase signaling. The NPM mutant ... The cytoplasmic NPM mutant not only affords protection from death ligand-induced cell death but also suppresses caspase-6/-8- ... Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition. ... caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases. ...
  • To assess the role of caspase-6 in the glucose-induced apoptosis, rat blastocysts were incubated for 24 h in either 6 or 28 mM glucose in the presence or absence of a specific inhibitor of caspase-6 (VEID-CHO, 100 nM). (bioone.org)
  • This in vitro assay employs the fluorescent inhibitor probe FAM-VEID-FMK to label active caspase-6 enzyme in living cells. (immunochemistry.com)
  • Jurkat cells were treated with staurosporine, an apoptosis-inducing agent (bottom), or DMSO, a negative control (top), for 4 hours, then incubated with ICT's green caspase-6 inhibitor probe, FAM-VEID-FMK, for 1 hour. (immunochemistry.com)
  • Caspase-1 Inhibitor II, CAS 178603-78-6, is a cell-permeable, irreversible inhibitor of caspase-1 (Ki = 760 pM), caspase-4, and caspase-5. (merckmillipore.com)
  • A cell-permeable and irreversible inhibitor of caspase-1 (K i = 760 pM), caspase-4, and caspase-5. (merckmillipore.com)
  • The Caspase-6 Inhibitor XII, pep419 controls the biological activity of Caspase-6. (emdmillipore.com)
  • An 18-mer synthetic peptide that acts as a selective, non-competitive inhibitor of caspase-6 (IC 50 = 8.6 µM). (emdmillipore.com)
  • Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. (wikipedia.org)
  • Here, using Yersinia pseudotuberculosis in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME) in murine macrophages, resulting in pyroptosis. (pnas.org)
  • Intracerebroventricular administration of z-DEVD-fmk-a specific tetrapeptide inhibitor of caspase-3-before and after injury markedly reduced post-traumatic apoptosis, as demonstrated by DNA electrophoresis and TUNEL staining, and significantly improved neurological recovery. (jneurosci.org)
  • Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). (elsevier.com)
  • View detailed caspase-10 Inhibitor specifications, including caspase-10 Inhibitor CAS number, molecular weight, molecular formula and chemical structure, by clicking on the product name. (scbt.com)
  • Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor. (adooq.com)
  • Thus, ARC represents an inhibitor of apoptosis expressed in muscle that appears to selectively target caspases. (pnas.org)
  • Mixture therapy with either HDAC inhibitor and lithium (lanes 4 and 6) impacts both pathways concurrently. (rmrfotoarts.com)
  • 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. (rupress.org)
  • Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. (springer.com)
  • This did not require protease activity, as it was not inhibited by the addition of a pan-caspase inhibitor. (sciencemag.org)
  • However, although treatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone inhibited caspase activity per se in SNP-treated 661W cells, it did not prevent apoptosis. (csic.es)
  • Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound. (nih.gov)
  • The ability of Dox to stimulate release of mature (17-kDa) IL-1β was nearly equivalent in wild-type (WT) BMDC, Casp1 −/− Casp11 −/− BMDC, WT BMDC treated with the caspase-1 inhibitor YVAD, and BMDC lacking the inflammasome regulators ASC, NLRP3, or NLRC4. (jimmunol.org)
  • Notably, Dox-induced production of mature IL-1β was temporally correlated with caspase-8 activation in WT cells and greatly suppressed in Casp8 −/− Rip3 −/− or Trif −/− BMDC, as well as in WT BMDC treated with the caspase-8 inhibitor, IETD. (jimmunol.org)
  • The responses were temporally correlated with downregulation of cellular inhibitor of apoptosis protein 1, suggesting suppressive roles for this and likely other inhibitor of apoptosis proteins on the stability and/or proteolytic activity of the caspase-8 platforms. (jimmunol.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)
  • The caspase 8 inhibitor c-FLIP L can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). (asm.org)
  • 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. (wikipedia.org)
  • Caspase 6 (CASP6) is a neuron degeneration-related protease and is widely considered to be a potential drug-design target against neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. (iucr.org)
  • Global Markets Direct's, 'Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) - Pipeline Review, H2 2016', provides in depth analysis on Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) targeted pipeline therapeutics. (reportsnreports.com)
  • The report provides comprehensive information on the Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59), targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
  • Additionally, the report provides an overview of key players involved in Caspase 6 (Apoptotic Protease Mch 2 or CASP6 or EC 3.4.22.59) targeted therapeutics development and features dormant and discontinued projects. (reportsnreports.com)
  • Rabbit IgG polyclonal antibody for Caspase-6(CASP6) detection. (bosterbio.com)
  • Human caspase 6 ELISA kit is designed for detecting in vitro quantitative concentrations of caspase-6 (CASP6) in human tissue homogenates, serum, cell lysates, other biological fluids, cell culture supernatant and plasma. (elisakits.co.uk)
  • Caspase 6 (CASP6 or Mch2) is one of the main executioner caspases that is important for the cellular apoptotic process. (elisakits.co.uk)
  • Minimum detection limits of a caspase-6 (CASP6) using current human caspase 6 ELISA kit was 0.069 ng/ml. (elisakits.co.uk)
  • The Sheep CASPASE-6 casp6 (Catalog # MBS033072 ) is an ELISA Kit and is intended for research purposes only. (mybiosource.com)
  • The CASPASE-6 casp6 product has the following accession number(s) (GI #157951736) (NCBI Accession #NP_033941.3) (Uniprot Accession #O08738). (mybiosource.com)
  • Caspase-6 belongs to caspase family of cysteinyl-aspartate specific proteases.Precursor of CASP6 produces two subunits, large (18kDa) and small (16kDa) that dimerize. (ptgcn.com)
  • Neutrophils Activate Alveolar Macrophages by Producing Caspase-6-Mediated Cleavage of IL-1 Receptor-Associated Kinase-M". The Journal of Immunology. (wikipedia.org)
  • In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. (rxpgnews.com)
  • d Cells were serum starved for 24 h and the cleavage pattern of caspase-3 was determined using western blot analysis. (nature.com)
  • Procaspase-6 (Mch2), a member of the ICE/ced-3 subfamily, is an inactive proenzyme that is activated to form caspase-6 by proteolytic cleavage at certain aspartic acid residues. (acris-antibodies.com)
  • A possible cleavage of caspases-8 and -10 in cytochrome-C dependent apoptosis was reported recently. (acris-antibodies.com)
  • Activation of caspases during apoptosis results in the cleavage of critical cellular substrates so precipitating the dramatic morphological changes of apoptosis. (biovendor.com)
  • Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. (wikipedia.org)
  • Caspase-6 and related caspase activity can be quantified by fluorescent detection of free AFC after cleavage from the peptide substrate VEID-AFC at Ex/Em = 400/505, using a fluorometer or multi-well fluorescence plate reader. (antibody-antibodies.com)
  • 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)
  • Essentially caspase 6 can interact with caspase 8, one of its main target includes the membrane associated protein lamin A and also the cleavage of this protein is found to result in cell membrane bleebing, malfunction and leading to eventual cell death. (elisakits.co.uk)
  • Here we demonstrate that Yersinia YopJ-induced murine macrophage death involves caspase-8-induced cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME). (pnas.org)
  • Our work extends these studies and shows that activation of caspase-8 in the context of TAK1 inhibition results in cleavage of both GSDMD and GSDME, leading to pyroptotic-like cell death. (pnas.org)
  • Activation of apical caspases, such as caspase-8, through cell death receptors or other apoptotic stimuli leads to activation of downstream caspases, precipitous cleavage of target proteins and execution of the apoptotic program ( 7 , 8 ). (pnas.org)
  • Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. (rupress.org)
  • Caspase-3 cleavage also occurs in vivo during negative selection of thymocytes through TCR signaling, where only the p17 is detected ( 4 )( 5 ). (rupress.org)
  • The current model suggests that after apoptotic stimulation, activation of "upstream" caspases containing a large prodomain such as caspase-8, -2, or -9 leads to the proteolytic cleavage of "downstream" caspases (caspase-3, -6, and -7), which mediate the apoptotic response ( 1 )( 6 ). (rupress.org)
  • Caspase activity results in the cleavage of several cellular proteins, which leads to the apoptotic response (for a review, see reference 7). (rupress.org)
  • The retention of Spi-2 proteins' caspase-8 specificity during chordopoxvirus evolution, despite this function being readily lost through cleavage site mutagenesis, suggests that caspase-8 inhibition is crucial for poxviral pathogenesis and spread. (portlandpress.com)
  • 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)
  • Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 3.4.22.56) pipeline Target constitutes close to 16 molecules. (researchmoz.us)
  • 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 3.4.22.56) targeted therapeutics development with respective active and dormant or discontinued projects. (researchmoz.us)
  • Cleavage of caspase-8 and its preferred substrate, Bid, preceded processing of caspases-7 and -9, indicating that caspase-8 is the apical initiator caspase in TRAIL-induced apoptosis. (rupress.org)
  • These inclusions, which were also induced in untransfected cells, contained cytokeratins 8, 18, and 19, together with both a phosphorylated form and a caspase-cleavage fragment of cytokeratin 18. (rupress.org)
  • We propose that effector caspase-mediated cleavage of cytokeratins, resulting in disassembly of the cytoskeleton and formation of cytoplasmic inclusions, may be a characteristic feature of epithelial cell apoptosis. (rupress.org)
  • The system of action of the enzymes, which are crucial in managing bacterial DNA topology, requires DNA cleavage as well as the passage of ZM-447439 distributor another DNA dual strand through the break, accompanied by re-ligation from the cleaved DNA [6, 7]. (ac-devd-cho.com)
  • To clarify the relationship between the cleaved form of Lyn by caspases and psoriasis, the investigators intend to develop a clinical study to analyze the expression, cleavage and activity of Lyn and the activation of caspases from skin biopsies of patients with this disease. (clinicaltrials.gov)
  • Thus, the investigators will verify that the cleavage by caspases of Lyn is associated specifically with psoriasis, as the investigators believe, or more generally to the skin inflammation. (clinicaltrials.gov)
  • The investigators work would then define the cleavage by caspases of Lyn as a new potential marker of human psoriasis. (clinicaltrials.gov)
  • The cleavage of Lyn will be determined in the different extracts of skin of patients with western blotting using an antibody specific for Lyn recognizing the native form but also the form cleaved by caspases. (clinicaltrials.gov)
  • The canonical cleavage and processing of proIL-1β into mature IL-1β cytokine (17 kDa) are catalyzed by caspase-1, a pathway regulated by multiprotein inflammasome signaling complexes. (jimmunol.org)
  • Cleavage of the procaspase at the specific Asp-X bonds leads to the formation of the mature caspase, which comprises the heterotetramer p20 2 -p10 2 , and the release of the prodomain. (jci.org)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • A high local concentration of caspase 8 zymogens is thought to facilitate self-processing and cleavage to the active enzyme ( 34 ). (asm.org)
  • Activated caspase 8 then initiates apoptosis by cleavage of the downstream effector caspases 3, 6, and 7 ( 10 ). (asm.org)
  • Caspases belong to a class of specific Cys proteases that show a high degree of specificity with an absolute requirement for cleavage adjacent an Asp residue and a recognition sequence of at least four amino acids N-terminal to this cleavage site. (plantphysiol.org)
  • Cleavage of a caspase molecule yields a large (α) subunit and a small (β) subunit that form the enzymatically active heterodimer. (plantphysiol.org)
  • The caspase family of cysteine proteases has been shown to play a key role in apoptosis. (abcam.com)
  • Caspase-6 (Cysteine-Requiring Aspartate Proteases) is part of a family of intracellular cysteine proteases that cleave their substrates after aspartic acid residues. (acris-antibodies.com)
  • Caspases are a family of cysteine proteases which are the major executors of apoptosis and inflammation. (iucr.org)
  • The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. (nature.com)
  • Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. (antibody-antibodies.com)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Caspases are the proteases responsible for dismantling the cell in an ordered and histologically distinct process termed apoptosis [ 1 ]. (mdpi.com)
  • Apoptosis involves a signaling cascade that, ultimately, activates a family of proteases known as caspases. (mdpi.com)
  • We examined the temporal profile of apoptosis after fluid percussion-induced traumatic brain injury (TBI) in rats and investigated the potential pathophysiological role of caspase-3-like proteases in this process. (jneurosci.org)
  • Together, these results implicate caspase-3-like proteases in neuronal apoptosis induced by TBI and suggest that the blockade of such caspases can reduce post-traumatic apoptosis and associated neurological dysfunction. (jneurosci.org)
  • In mammals, a family of cysteine proteases (designated caspases) related to the Caenorhabditis elegans CED-3 protein appears to represent a major effector arm of the apoptotic program ( 5 ). (pnas.org)
  • The mammalian cell death proteases have been divided into proximal and distal caspases based on the their sites of action in the proteolytic caspase cascade ( 6 ). (pnas.org)
  • Mammalian IAP-1, -2, and XIAP directly bind and inhibit enzymatically active death proteases, caspase-3, and -7, but not the upstream protease caspase-8 ( 18 , 19 ). (pnas.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. (rupress.org)
  • Cysteine proteases of the IL-1β-converting enzyme (ICE) family (caspases) are critical executioners of apoptosis in several mammalian cell death pathways ( 1 ). (rupress.org)
  • Caspases are synthesized as inactive precursors that require proteolytic conversion to become active proteases. (rupress.org)
  • Caspase-6 is an important member of the executioner caspases in the caspase family of cell death proteases. (elsevier.com)
  • In this disease, the inflammatory caspases, cysteine proteases involved in the processing of many proteins, are activated. (clinicaltrials.gov)
  • Proteases, also known as peptidases, proteinases or proteolytic enzymes, are enzymes that hydrolyze amino acids bonds not only in proteins, but also in peptides [1] - [6] . (plos.org)
  • Prior to its subclassification within the caspase family of proteases, caspase-1 was originally described as the IL-converting enzyme. (jimmunol.org)
  • Caspases, a family of cysteine proteases, play a central role in apoptosis. (jci.org)
  • In animal systems PCD is synonymous with apoptosis, a cell death process characterized by a distinct set of morphological and biochemical features, mediated by a class of specific Cys proteases called cysteinyl aspartate-specific proteinases (caspases). (plantphysiol.org)
  • Caspase 3 (CPP32) and Caspase 6 (Mch2) are the major active caspases in apoptotic cells, and are activated in response to distinct apoptosis-inducing stimuli in all cell lines analyzed. (fishersci.com)
  • VEID is the specific recognition sequence for caspase-6/Mch2. (antibody-antibodies.com)
  • This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
  • This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. (wikipedia.org)
  • Caspase-6 cleaves nuclear mitotic apparatus protein (NuMA) and mediates the shrinkage and fragmentation of nuclei. (fishersci.com)
  • 2007) NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1 . (merckmillipore.com)
  • They are named caspases due to their specific cysteine protease activity - a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. (wikipedia.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)
  • Also, caspase 6 has the ability to cleave nuclear mitotic apparatus protein and mediate the fragmentation or shrinkage of the nuclei. (elisakits.co.uk)
  • After 10 hours, cells were lysed and Caspase-6 knockdown at the protein level was measured via Western Blot. (enquirebio.com)
  • Likewise, Apaf-1, a human protein that resembles C. elegans CED-4, interacts with caspase-9, a step that is required for the activation of the downstream protease caspase-3 ( 11 ). (pnas.org)
  • The prodomains of several apical caspases contain a protein module termed caspase recruitment domain (CARD) that is conserved in several apoptosis regulatory molecules, including Apaf-1, RAIDD, and cellular inhibitors of apoptosis proteins (IAPs) ( 12 ). (pnas.org)
  • Analysis by real-time PCR and Western blot revealed that ATRA treatment strongly increased the mRNA and protein expression of p53 and caspase-3, -6, -7, and -9, which are key regulators of apoptosis. (aacrjournals.org)
  • However, the complete characterization of mRNA and protein of caspase-6 in rat and its expression in normal kidney and in disease state has not been previously elucidated. (elsevier.com)
  • The recombinant caspase-6 protein was characterized by expression in bacteria and by transient transfection in mammalian cells. (elsevier.com)
  • Chen YC, Shen SC, Lee WR, Lin HY, Ko CH, Shih CM, Yang LL (2002) Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1. (springer.com)
  • Caspase activation, dependent on Caspase-3, Caspase-9, and p38 mitogen-activated protein kinase (MAPK), rapidly increased at branch points corresponding with branch tip addition. (rupress.org)
  • Using transient transfection of COOH-terminal-tagged green fluorescent protein fusion constructs, caspases-3, -7, and -8 were localized throughout the cytoplasm of MCF-7 cells. (rupress.org)
  • The protein levels of caspase-12 were examined by Western blot analysis. (bvsalud.org)
  • Analysis of caspase 3 protein expression by Western blot analysis revealed that 4-HPR resulted in a significant increase in the appearance of the active p17 subunit without effecting a concomitant change in p32 procaspase 3 levels. (aacrjournals.org)
  • Caspase 3 Activity and Protein Expression. (aacrjournals.org)
  • Affinity purification experiments identified actin interacting protein 1 (AIP1) as a binding partner for caspase 11. (sciencemag.org)
  • m-IgG Fc BP-HRP (mouse IgG Fc binding protein-HRP) is the preferred secondary detection reagent for caspase-3 Antibody (E-8) for WB and IHC(P) applications. (scbt.com)
  • caspase-3 Antibody (E-8) is a high quality monoclonal caspase-3 antibody (also designated CASP3 antibody or CPP32 antibody) suitable for the detection of the caspase-3 protein of human origin. (scbt.com)
  • 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)
  • Upon activation of Fas by its ligand, the DD undergoes homotypic interaction with a DD in the adaptor protein FADD, which then recruits the initiator caspase 8 via their mutual N-terminal death effector domains (DED) ( 3 ). (asm.org)
  • and protein carbonyl, IL-1B, and caspase-1 determination. (cdc.gov)
  • Recent work demonstrates anticarcinogenic action both in vitro and in vivo, and that work is coupled with a proof-of-principle mechanism of action data showing induction of the pro-apoptotic protein, caspase-6. (naturalmedicinejournal.com)
  • This antibody recognizes the large subunit (18 kDa) of the active caspase-6. (abcam.com)
  • The antibody does not recognize any other caspase. (abcam.com)
  • Ensure accurate, reproducible results in western blotting and immunoprecipitation procedures with Thermo Scientific Caspase 6 (Mch 2) Ab-3, Mouse Monoclonal Antibody. (fishersci.com)
  • Western blot analysis using caspase-6 antibody (AM05283PU-N) on MCF-7 cells negative (-) and positive (+) for caspase-3 after treatment for 48 hours with thapsigargin. (acris-antibodies.com)
  • Formalin-fixed and paraffin embedded human kidney labeled with Anti-Caspase-6 (NT) Polyclonal Antibody, Unconjugated at 1:500 followed by conjugation to the secondary antibody and DAB staining. (antibodies-online.com)
  • Caspase 6 ELISA kit applies the competitive enzyme immunoassay technique utilizing a monoclonal anti-Caspase 6 antibody and an Caspase 6-HRP conjugate. (biobool.com)
  • The intensity of the color is inversely proportional to the Caspase 6 concentration since Caspase 6 from samples and Caspase 6-HRP conjugate compete for the anti-Caspase 6 antibody binding site. (biobool.com)
  • This reagent is now offered in a bundle with caspase-3 Antibody (E-8) ( see ordering information below ). (scbt.com)
  • caspase-3 Antibody (E-8) is available as both the non-conjugated anti-caspase-3 antibody form, as well as multiple conjugated forms of anti-caspase-3 antibody, including agarose, HRP, PE, FITC and multiple Alexa Fluor ® conjugates. (scbt.com)
  • Development of a monoclonal antibody specific for the form cleaved by caspases of Lyn. (clinicaltrials.gov)
  • Together with caspase 3, caspase 6 is one of the major caspases in apoptotic cells, and functions downstream of apoptosis inhibitors Bcl-2 and Bcl-xL. (abcam.com)
  • Effector (also called executioner) caspases CASP3, -6 and -7 are responsible for cleaving downstream substrates. (thefreedictionary.com)
  • Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. (elsevier.com)
  • 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. (rupress.org)
  • It is well established that caspase-1 exerts its biological activities through its downstream targets such as IL-1β, IL-18, and Sirt-1. (springer.com)
  • We used these statistical methods to integrate different microarray datasets conducted on different caspase-1 knockout tissues and datasets where caspase-1 downstream targets were manipulated. (springer.com)
  • Genetic analysis showed that Caspase-3, Caspase-9, and p38 MAPK interacted with Slit1a-Robo2 signaling, suggesting that localized activation of caspases lie downstream of a ligand receptor system, acting as key promoters of axonal branch tip and synaptic dynamics to restrict arbor growth in vivo in the central nervous system. (rupress.org)
  • We also demonstrated that caspase-12 was processed downstream of Apaf-1 and caspase-3, and neither overexpression nor knockdown of caspase-12 affected susceptibility of the cells to ER stress-induced cell death. (biologists.org)
  • In general, apoptotic cell death involves a sequence of caspase activation events in which initiator caspases activate downstream executioner caspases that process a variety of target proteins eventually leading to the apoptotic phenotype. (plantphysiol.org)
  • Active caspase-6 cleaves several other proteins such as lamins, NuMa and Keratin 18. (acris-antibodies.com)
  • In this study, we extend the repertoire of chimeric proapoptotic proteins with immunocasp-6, a construct that comprises a HER2-specific single-chain Ab, a single-chain Pseudomonas exotoxin A, and an active caspase-6, which can directly cleave lamin A leading to nucleus damage and inducing programmed cell death. (nih.gov)
  • Tumour growth can occur by a combination of factors, including a mutation in a cell cycle gene which removes the restraints on cell growth, combined with mutations in apoptopic proteins such as Caspases that would respond by inducing cell death in abnormally growing cells. (wikipedia.org)
  • By cleaving critical proteins, caspases lead to the changes that characterize apoptosis both morphologically and biochemically, such as chromatin condensation, loss of cell adhesion, cell shrinkage, membrane blebbing, DNA fragmentation, and finally formation of apoptotic bodies, which stimulate their own engulfment by phagocytes. (mdpi.com)
  • These molecules are sufficient to activate caspase-3 in vitro, but other regulatory proteins are necessary in vivo. (wikipedia.org)
  • 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)
  • Caspase family members function as key components of the apoptotic machinery and act to destroy specific target proteins which are critical to cellular longevity. (scbt.com)
  • Caspase-10 Inhibitors offered by Santa Cruz inhibit caspase-10 and, in some cases, other apoptosis and tumor related proteins. (scbt.com)
  • The CARD has been proposed to play a regulatory role in apoptosis by allowing proteins such as Apaf-1 to associate with caspase-9 ( 13 ). (pnas.org)
  • Two viral proteins, baculovirus p35 and cowpox virus CrmA, inhibit apoptosis by directly targeting caspases ( 14 , 15 ). (pnas.org)
  • In both cell lines, treatment for 2 times using the HDAC inhibitors VPA (street 3) 418788-90-6 or SBHA (street 5) escalates the quantity of cleaved Notch1 proteins (NICD). (rmrfotoarts.com)
  • Spi-2 proteins like CrmA potently inhibit caspases-1, -4 and -5, which produce proinflammatory cytokines, and caspase-8, which facilitates cytotoxic lymphocyte-mediated target cell death. (portlandpress.com)
  • The executioner caspases are the major active caspases detected in apoptotic cells and are generally considered to mediate the execution of apoptosis by cleaving and inactivating intracellular proteins. (elsevier.com)
  • Since caspase-6 is involved in the degradation of nuclear matrix proteins and in activation of caspase-3, it may play an important role during renal ischemic injury. (elsevier.com)
  • Our findings suggest that caspase-1 regulates many new signaling pathways potentially via its known substrates and also via transcription factors and other proteins that are yet to be identified. (springer.com)
  • Also, other proteins which involved in the same pathway with Caspase were listed below. (creativebiomart.net)
  • Some of the functions are cooperated with other proteins, some of the functions could acted by Caspase itself. (creativebiomart.net)
  • We selected most functions Caspase had, and list some proteins which have the same functions with Caspase. (creativebiomart.net)
  • Caspase has direct interactions with proteins and molecules. (creativebiomart.net)
  • We selected proteins and molecules interacted with Caspase here. (creativebiomart.net)
  • 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)
  • Similar to other caspases, caspase 6 is also synthesized as an inactive pro-enzyme that is processed in cells undergoing apoptosis. (abcam.com)
  • As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. (biochemj.org)
  • The remaining green fluorescent signal is a direct measure of the active caspase-6 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)
  • Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified. (wikipedia.org)
  • The active enzyme often exists as a heterotetramer in the biological environment, where a pro-caspase dimer is cleaved together to form a heterotetramer. (wikipedia.org)
  • 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)
  • Sheep Caspase 6 ELISA Kit or ELISA (enzyme-linked immunosorbant assays) Kits in general, are a valuable research tool for a myriad of applications in a range of scientific settings. (mybiosource.com)
  • Researchers identified the mechanisms underlying the innate immune function of the enzyme caspase-6, offering ways to combat viral infection, inflammatory diseases and cancer. (covid-19-news.net)
  • Bacterial expression of recombinant rat caspase-6 resulted in production of both of the proform and active form of the enzyme suggesting autoactivation. (elsevier.com)
  • Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. (rupress.org)
  • The active caspase-3 enzyme is a heterodimer composed of two p17 and two p11 subunits. (scbt.com)
  • We demonstrate that the secreted immunocasp-6 molecule selectively recognizes and induces apoptosis in HER2-overexpressing tumor cells in vitro, but not in cells with undetectable HER2. (nih.gov)
  • Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. (nature.com)
  • In vitro , we show that genetic deletion of Caspase-3 is fully protective against sensory axon degeneration initiated by trophic factor withdrawal, but not injury-induced Wallerian degeneration, and we define a biochemical cascade from prosurvival Bcl2 family regulators to Caspase-9, then Caspase-3, and then Caspase-6. (jneurosci.org)
  • Intended Use Human Caspase 6 ELISA Kit allows for the in vitro quantitative determination of Caspase 6 , concentrations in serum, Plasma , tissue homogenates and Cell culture supernates and Other biological fluids. (biobool.com)
  • Inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM). (adooq.com)
  • Analogous to the observed ATRA effects in monolayer cultures, in vitro -generated organotypic skin cultures reacted with up-regulation of p53 and proapoptotic caspases and displayed increased sensitivity to UVB-induced apoptosis. (aacrjournals.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)
  • In vitro actin polymerization assays showed that caspase 11 synergized with AIP1 to stimulate cofilin-mediated actin depolymerization, whereas caspase 11 in the absence of AIP1 did not affect cofilin-mediated actin depolymerization. (sciencemag.org)
  • Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. (mdpi.com)
  • There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. (mdpi.com)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • 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)
  • 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)
  • 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)
  • Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. (elsevier.com)
  • Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) -induced apoptosis, in transformed human breast epithelial MCF-7 cells, resulted in a time-dependent activation of the initiator caspases-8 and -9 and the effector caspase-7. (rupress.org)
  • it is a prime candidate for an initiator caspase in many other forms of receptor-mediated apoptosis. (rupress.org)
  • Depending on the structure of the prodomain and their function, caspases are typically divided into 3 major groups (Figure 1 A). The caspases with large prodomains are referred to as inflammatory caspases (group I) and initiator of apoptosis caspases (group II), while caspases with a short prodomain of 20-30 amino acids are named effector caspases (group III). (jci.org)
  • Initiator caspases may be activated by autoprocessing when clustering occurs e.g. at the cytosolic part of (activated) cell death receptors. (plantphysiol.org)
  • Caspase-6 can cleave its prodomain to produce mature caspase-6, which directly activates caspase-8 (EC 3.4.22.61) and leads to the release of cytochrome c from the mitochondria. (creative-enzymes.com)
  • Cleaves and activates caspase-6, -7 and -9. (uniprot.org)
  • A critical substrate for caspase-3 during apoptosis is the 45-kD subunit of DNA fragmentation factor (DFF45) that once cleaved by caspase-3 activates DNA fragmentation by releasing the caspase-activated DNase ( 14 )( 15 )( 16 ). (rupress.org)
  • [ 133 , 206 ] Caspase-1 cleaves and activates interleukin-1β and interleukin-18 and acts as a key component of inflammasome, which contributes to the pathogenesis of chronic pain. (medscape.com)
  • Binding of caspase-9 to Apaf-1 leads to activation of the protease which cleaves and activates caspase-3. (grandresearchstore.com)
  • Activated m-calpain cleaves Bcl-X L and proteolytically activates caspase-12 ( Nakagawa and Yuan, 2000 ). (biologists.org)
  • b A caspase-3 activity assay was used to determine the ability to cleave a DEVD-chromphore substrate. (nature.com)
  • However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. (biochemj.org)
  • Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase structures are part of an elongation of the central α-helix. (biochemj.org)
  • Blocks the activity of processed caspase-6 as evidenced by its reduced ability to process VEID-AMC substrate. (emdmillipore.com)
  • Ready-to-use fluorometric substrate for caspase-6 and related caspases that recognize the amino acid sequence VEID. (antibody-antibodies.com)
  • The ready-to-use caspase substrate provides an economic alternative for researchers who perform large amount of caspase-6 assays. (antibody-antibodies.com)
  • Caspase 3 and caspase 7 share similar substrate specificity by recognizing tetra-peptide motif Asp-x-x-Asp. (wikipedia.org)
  • 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. (rupress.org)
  • Caspase and substrate processing occur in nonapoptotic lymphocytes. (rupress.org)
  • 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)
  • The principle of this test is based on the use of a specific substrate of caspases coupled to a fluorochrome that fluoresces when it is released after the action of caspase-level target aspartate. (clinicaltrials.gov)
  • This Review gives an overview of caspases and their classification, structure, and substrate specificity. (jci.org)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
  • A gene on chromosome 4q25 that encodes a so-called effector caspase belonging to the cysteine-aspartic acid protease (caspase) family which, once activated by proteolytic processing, plays a central role in the execution phase of apoptosis. (thefreedictionary.com)
  • Each caspase contains conserved sequences important for proteolytic activity cleaving after specific aspartic acid residues ( 6 ). (pnas.org)
  • These findings indicate the presence of proteolytic activities that are distinguishable from caspase-3. (springer.com)
  • All these biological activities of caspase-1 occur at post-translational level (proteolytic processing). (springer.com)
  • Caspases are proteolytic enzymes that are closely involved in the induction and execution phases of apoptosis, but their role in the development of diabetic retinopathy has not been studied previously. (nih.gov)
  • It is tempting to speculate that comparable caspase-mediated proteolytic events cause the apoptotic phenotype observed in dying plant cells. (plantphysiol.org)
  • Caspases are synthesized as inactive pro-enzymes and are activated by directed proteolysis that removes the N-terminal peptide and cleaves the proteolytic domain at specific recognition sites (Fig. 1 ). (plantphysiol.org)
  • Under normal circumstances, caspases recognize tetra-peptide sequences on their substrates and hydrolyze peptide bonds after aspartic acid residues. (wikipedia.org)
  • Further study will be needed to determine whether caspase-8 cleaves GSDMD directly or via intermediate substrates. (pnas.org)
  • However, it is not known whether all the effects exerted by caspase-1 on transcriptome are mediated only by its well-known substrates. (springer.com)
  • However, it remains unclear whether caspase-1 regulates gene transcription independent of the three well-characterized caspase-1 substrates IL-1β, IL-18, and Sirt-1. (springer.com)
  • The cell-permeable caspase inhibitors DEVD-CHO and YVAD-CHO and the caspase colorimetric substrates Ac-DEVD-pNA and Ac-YVAD-pNA were purchased from Biomol and dissolved in DMSO as stock solutions. (aacrjournals.org)
  • Many caspase substrates are cleaved during apoptosis and pertaining to their functional significance have yet to merge. (agscientific.com)
  • AG Scientific provides various selection of caspase substrates and be able to ship FedEx directly to your lab, from small-scale to bulk orders. (agscientific.com)
  • Subsequently, active caspases specifically process various substrates that are implicated in apoptosis and inflammation. (jci.org)
  • Regardless of the method used, expression of immunocasp-6 suppressed tumor growth and prolonged animal survival significantly. (nih.gov)
  • Our data show that the chimeric immunocasp-6 molecule can recognize HER2-positive tumor cells, promptly attack their nucleus, and induce their apoptotic death, suggesting the potential of this strategy for the treatment of human cancers that overexpress HER2. (nih.gov)
  • These data seem to question a general tumor-suppressive role of caspases. (mdpi.com)
  • We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
  • First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. (mdpi.com)
  • We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
  • Consistent with the inhibition of caspase-8, ARC attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation of death receptors coupled to caspase-8, including CD95/Fas, tumor necrosis factor-R1, and TRAMP/DR3. (pnas.org)
  • [ 194 ] demonstrated a direct induction of central sensitization by the proinflammatory cytokines tumor necrosis factor, interleukin-1β, and interleukin-6. (medscape.com)
  • In support of this direct modulation, tumor necrosis factor, interleukin-1β, and interleukin-6 rapidly modulate the function of neurotransmitter receptors such as AMPA receptor, NMDA receptor, glycine receptor, and GABAR, which results in enhanced excitatory synaptic transmission and suppressed inhibitory synaptic transmission in the spinal pain circuit. (medscape.com)
  • [ 194 ] In agreement with this finding, intrathecal injection of tumor necrosis factor, interleukin-1β, or interleukin-6 elicits rapid pain hypersensitivity in naive animals. (medscape.com)
  • [ 204 ] Notably, caspase-6 triggers tumor necrosis factor release from microglia to elicit central sensitization via tumor necrosis factor receptor signaling. (medscape.com)
  • Thus, proapoptotic chemotherapeutic agents stimulate the caspase-8-mediated processing and release of IL-1β, implicating direct effects of such drugs on a noncanonical inflammatory cascade that may modulate immune responses in tumor microenvironments. (jimmunol.org)
  • On the one hand, NLRP3/caspase-1 inflammasomes play a central role in the regulation of IL-1β production within tumor loci or in response to chemotherapeutic drugs. (jimmunol.org)
  • Elevated levels of caspases 3/7 and 9 in B2-treated PC3 cells suggest the induction of apoptosis through nuclear and mitochondrial pathways. (hindawi.com)
  • Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
  • The knock-on effects of the action of caspases keep us alive, initiating many vital cellular pathways. (bioportfolio.com)
  • Some caspases are activated by fas in the pro-apoptosis cell pathway, and then go on to activate further caspases (caspase 3), which induce apoptosis, while others interact with Apaf-1 in other cell pathways. (bioportfolio.com)
  • and (5) The meta-analysis identified new cooperatively and non-cooperatively regulated genes in caspase-1, IL-1β, IL-18, and Sirt-1 pathways. (springer.com)
  • The identification of noncanonical (caspase-1-independent) pathways for IL-1β production has unveiled an intricate interplay between inflammatory and death-inducing signaling platforms. (jimmunol.org)
  • Caspase involved in several pathways and played different roles in them. (creativebiomart.net)
  • We selected most pathways Caspase participated on our site, such as , which may be useful for your reference. (creativebiomart.net)
  • Over-expression of the isoform of caspase-6 without its prodomain can induce apoptosis. (acris-antibodies.com)
  • Caspases, a family of c ysteinyl a spartate- s pecific p rote ases , are synthesized as zymogens with a prodomain of variable length followed by a large subunit (p20) and a small subunit (p10). (jci.org)
  • A, Caspases are synthesized as inactive pro-enzymes with an N-terminal prodomain and a large and small subunit of 17 to 21 and 10 to 13 kD, respectively. (plantphysiol.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)
  • O-Alkylated derivatives of quercetin induce apoptosis of MCF-7 cells via a caspase-independent mitochondrial pathway. (ptgcn.com)
  • 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. (rupress.org)
  • Caspases are a family of enzymes with very specific characteristics that can be used in almost every biological pathway in the body. (bioportfolio.com)
  • In addition to being critical for apoptosis, components of the apoptotic pathway, such as caspases, are involved in other physiological processes in many types of cells, including neurons. (rupress.org)
  • The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. (bvsalud.org)
  • These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12. (bvsalud.org)
  • In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. (hindawi.com)
  • One is the extrinsic pathway, in which ligation of death receptors by death ligands is followed by recruitment of adaptor molecules and activation of caspase-8 or caspase-10. (biologists.org)
  • The other is the intrinsic pathway, in which the release of cytochrome c from mitochondria triggers the formation of the apoptosome composed of Apaf-1, pro-caspase-9, dATP, and cytochrome c . (biologists.org)
  • On the other hand, CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran) acted as a scavenger of ROS and reduced 661W photoreceptor apoptosis induced by SNP by preventing the activation of a pathway in which calpains have a key role. (csic.es)
  • We found a heretofore unappreciated role for caspase-8 as a major pathway for IL-1β processing and release in murine bone marrow-derived dendritic cells (BMDC) costimulated with TLR4 agonists and proapoptotic chemotherapeutic agents such as doxorubicin (Dox) or staurosporine (STS). (jimmunol.org)
  • Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. (cdc.gov)
  • However, targeting the latent conformation in search for specific and bio-available caspase-6 inhibitors might offer an alternative to active-site-directed approaches. (biochemj.org)
  • Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. (nature.com)
  • Santa Cruz Biotechnology now offers a broad range of caspase-10 Inhibitors. (scbt.com)
  • Furthermore, when combined with HDAC inhibitors, lithium didn't affect the quantity of energetic Notch1 in either GI or pulmonary carcinoid cell lines (lanes 4 and 6). (rmrfotoarts.com)
  • Identification of Allosteric Inhibitors against Active Caspase-6. (iric.ca)
  • The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. (elsevier.com)
  • Cagnol S, Van Obberghen-Schilling E, Chambard JC (2006) Prolonged activation of ERK1, 2 induces FADD-independent caspase 8 activation and cell death. (springer.com)
  • These data suggest that TLR4 induces assembly of caspase-8-based signaling complexes that become licensed as IL-1β-converting enzymes in response to Dox and STS. (jimmunol.org)
  • Recombinant fragment corresponding to Human Caspase-6/ CASP-6 aa 1-182. (abcam.com)
  • The extent of apoptosis was assessed by the TUNEL method and caspase 3, 6 and 8 expression by immunohistochemistry with specific antibodies. (semanticscholar.org)
  • The immunocasp-6 gene was next transferred into BALB/c athymic mice bearing human breast SK-BR-3 tumors by i.m. injection of liposome-encapsulated vectors, by intratumor injection of adenoviral vectors, or by i.v. injection of PBMC modified by retroviral infection. (nih.gov)
  • In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. (mdpi.com)
  • To determine new global and tissue-specific gene regulatory effects of caspase-1, we took novel microarray data analysis approaches including Venn analysis, cooperation analysis, and meta-analysis methods. (springer.com)
  • This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. (cancerindex.org)
  • Surprisingly, caspase-3 processing and activity have been observed in the absence of apoptosis after polyclonal activation of PBMCs, and in the absence of DNA fragmentation ( 17 )( 18 ). (rupress.org)
  • Caspase-6 is an effector/executioner caspase, as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60). (creative-enzymes.com)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (abcam.com)
  • caspase-9 thus is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (biovendor.com)
  • Cytochrome c/Apaf-1/caspase-9 form a socalled apoptosome, amplifying the caspase cascade. (biovendor.com)
  • It cleaves poly(ADP-ribose) polymerase, as well as lamins and is involved in the activation cascade of caspases responsible for apoptosis execution. (ptgcn.com)
  • The caspases activity pattern changed with increasing duration of disease, suggesting a slowly developing caspases cascade. (nih.gov)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • The FAM FLICA Caspase-6 assay probe allows researchers to assess caspase-6 activation. (immunochemistry.com)
  • The Caspase-6 Colorimetric Assay Kit provides a simple and convenient means for assaying the activity of caspases that recognize the sequence VEID. (antibody-antibodies.com)
  • Specificity This assay has high sensitivity and excellent specificity for detection of Caspase 6. (biobool.com)
  • The assay sample and buffer are incubated together with Caspase 6-HRP conjugate in pre-coated plate for one hour. (biobool.com)
  • In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4′-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. (springer.com)
  • RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. (bvsalud.org)
  • In an actin pelleting assay, the addition of caspase 11 with cofilin and AIP1 increased the soluble actin, consistent with enhanced depolymerization. (sciencemag.org)
  • Synthetic peptide corresponding to Human active Caspase 6. (abcam.com)
  • Only low levels of active Caspase-3 appear to be required, helping explain why its critical role has been obscured in prior studies. (jneurosci.org)
  • Using an unbiased caspase-trapping technique in vivo, weisolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. (elsevier.com)
  • The fluorescence emission, which is proportional to the amount of active caspase in the sample is then measured with a fluorometer. (clinicaltrials.gov)
  • In contrast, activation-induced cell death of T cells in c-FLIP L Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. (asm.org)
  • Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis . (wikipedia.org)
  • Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke. (elsevier.com)
  • Inhibition of p53 and caspases with α-pifithrin and z-Val-Ala-Asp-fluoromethyl ketone, respectively, blocked UVB- and doxorubicin-induced apoptosis in ATRA-treated KCs. (aacrjournals.org)
  • All potently blocked caspases-1, -4, -5 and -8 activity but exhibited negligible inhibition of caspases-2, -3 and -6. (portlandpress.com)
  • Treatment with staurosporine induced caspase-6 activity in 95.2% of the experimental cells (P3, bottom right), whereas the negative control treatment exhibited caspase-6 activity in only 5.9% of the cell population (P3, top right). (immunochemistry.com)
  • Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide together with one large and one small subunit. (biovendor.com)
  • Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an appropriate stimulus. (wikipedia.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)
  • The caspases are synthesized as inactive precursors that are proteolytically processed to generate active subunits. (pnas.org)
  • Overexpression of a catalytically inactive caspase 11 restored migration to the AIP knockdown cells. (sciencemag.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)
  • Existing in inactive forms within the cell, caspases are cleaved to become active enzymes upon the start of apoptosis. (agscientific.com)
  • This specificity allows caspases to be incredibly selective, with a 20,000-fold preference for aspartic acid over glutamic acid. (wikipedia.org)
  • We compared the caspase specificity of CrmA to three orthologs from orthopoxviruses and four from more distant chordopoxviruses. (portlandpress.com)
  • DFFA is encoded by an alternatively encrypted mRNAs originating two distinct forms: short (ICAD-S) and long (ICAD-L), which act like a specific chaperone ensuring the correct CAD's folding Besides, it contains two aspartic acid residues (Asp117 and Asp224) where CAD is identified and, consequently, it stays bounded until Caspase-3 splits this union. (wikipedia.org)
  • Caspases play a major role in the transduction of the apoptotic signal and execution of apoptosis in mammalian cells. (fishersci.com)
  • Caspase-6 is detected in all cells of the blastocyst and is excluded from the nucleus. (bioone.org)
  • Additionally, scientists have used caspases as cancer therapy to kill unwanted cells in tumours. (wikipedia.org)
  • The zymogen feature of caspase-3 is necessary because if unregulated, caspase activity would kill cells indiscriminately. (wikipedia.org)
  • Mangosteen (Garcinia mangostana) extract has been shown to inhibit the activation of caspase 3 in B-amyloid treated human neuronal cells. (wikipedia.org)
  • Caspase 3 and 6 are the main active caspases found in apoptotic cells and both of these are activated as a result of different apoptosis inducing stimuli. (elisakits.co.uk)
  • Starting with cultured cells in growth media seed plates with cells and incubated at 37°C. For the above data 6 well plates were seeded with 1x10 5 cells and incubated at 37°C overnight. (enquirebio.com)
  • For 6 well plates this will entail adding the solution to cells in approximately 2.5 ml serum-free medium. (enquirebio.com)
  • Further analysis showed that the enzymatic activity of caspase-8 was inhibited by ARC in 293T cells. (pnas.org)
  • Open up 418788-90-6 in another window Physique 2 Mixture therapy escalates the quantity of energetic Notch1-mediated CBF1 binding as assessed by comparative luciferase activity in gastrointestinal carcinoid cells. (rmrfotoarts.com)
  • 6,9] In GI carcinoid cells, our combination therapy contains 2 mM VPA or 15 M SBHA with 15 mM lithium. (rmrfotoarts.com)
  • In contrast, when the cells were treated with 1 μmol/L ATRA for 6 days and subsequently irradiated with different doses of UVB, they underwent massive apoptosis as assessed by morphology, expression of activated caspase-3, and DNA fragmentation. (aacrjournals.org)
  • On the other hand, activation of caspase-8, -9, and -3, phosphorylation of Bcl-2 and Bid, and increased release of cytochrome c from mitochondria into cytosolic fraction were detected in OODBL-treated HL-60 cells. (researchwithnj.com)
  • However, there is no evidence yet for a role of caspases during T cell activation, and a recent report suggested that the observed caspase processing was due to the production of granzyme B by CD8 + activated cells and artifactual release during cell lysis of PBMCs ( 19 ). (rupress.org)
  • 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)
  • For example, in drug-resistant forms of cancer, caspase-8 is in part responsible for making cells responsive to combination therapies such as eroltinib and cell-cycle inhibitiors. (bioportfolio.com)
  • Transient overexpression of rat caspase-6 in COS-1 cells induced DNA fragmentation, a hallmark of apoptosis. (elsevier.com)
  • Activities of executioner caspases (e.g., cas-6 and -3) became elevated after longer duration of diabetes, and the induction of cas-3 activity was associated with the duration of diabetes at which capillary cells begin to show evidence of undergoing apoptosis. (nih.gov)
  • Similarly, in untransfected breast HBL100 and lung A549 epithelial cells, TRAIL induced the formation of cytoplasmic inclusions that contained cleaved cytokeratin 18 and colocalized with active endogenous caspase-3. (rupress.org)
  • HOSE cells displayed prominent levels of lamin A/C and low level of caspase-6 expression in contrast to cancer cell lines A2780 and OVCAR5. (biomedcentral.com)
  • Briefly, the cell pellet was resuspended in hypotonic lysis buffer (50μ l/10 6 cells) containing 10 m m HEPES (pH 8.0), 1.5 m m MgCl 2 , 10 m m KCl, 1 m m DTT, 0.5 m m phenylmethylsulfonyl fluoride, and 10 μg/ml each of aprotinin, leupeptin, and pepstatin. (aacrjournals.org)
  • RNA interference experiments confirmed that AIP1 was important for cell migration with membrane ruffling defective in the absence of AIP1 (ruffling was also defective in the caspase 11-deficient cells). (sciencemag.org)
  • The authors propose that caspase 11 may serve early in the inflammatory response by aiding the delivery of cytokine-producing cells to the site of infection and then by terminating cytokine production through stimulation of apoptosis. (sciencemag.org)
  • Despite comparable induction of ER stress in both wild type and Apaf-1-deficient cells, activation of caspase-3 was only observed in wild type, but not Apaf-1-deficient, MEFs. (biologists.org)
  • Recently, Caspase-6 was implicated based on pharmacological and knockdown evidence, and we report here that genetic deletion of Caspase-6 indeed provides partial protection from degeneration. (jneurosci.org)
  • Time-lapse imaging revealed that knockdown of Caspase-3 and Caspase-9 led to more stable arbors and presynaptic sites. (rupress.org)
  • Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits. (abcam.com)
  • 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)
  • TRAIL-induced apoptosis resulted in activation of caspases-3 and -7, and the redistribution of most of their detectable catalytically active small subunits into large spheroidal cytoplasmic inclusions, which lacked a limiting membrane. (rupress.org)
  • Perform heat mediated antigen retrieval with citrate buffer pH 6 before commencing with IHC staining protocol. (abcam.com)
  • The orthologs differed markedly in their propensity to inhibit non-mammalian caspases. (portlandpress.com)
  • Schematic representation of structural features of mammalian caspases. (plantphysiol.org)
  • Caspase 9 (Apoptotic Protease Mch 6 or Apoptotic Protease Activating Factor 3 or ICE Like Apoptotic Protease 6 or CASP9 or EC 3.4.22.62) pipeline Target constitutes close to 7 molecules. (grandresearchstore.com)
  • The latest report Caspase 9 - Pipeline Review, H2 2018, outlays comprehensive information on the Caspase 9 (Apoptotic Protease Mch 6 or Apoptotic Protease Activating Factor 3 or ICE Like Apoptotic Protease 6 or CASP9 or EC 3.4.22.62) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (grandresearchstore.com)
  • It also reviews key players involved in Caspase 9 (Apoptotic Protease Mch 6 or Apoptotic Protease Activating Factor 3 or ICE Like Apoptotic Protease 6 or CASP9 or EC 3.4.22.62) targeted therapeutics development with respective active and dormant or discontinued projects. (grandresearchstore.com)
  • Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) pipeline Target constitutes close to 5 molecules. (researchandmarkets.com)
  • The following caspase 6 ELISA kit is ideal for measuring various diagnostic applications. (elisakits.co.uk)
  • The MBS033072 ELISA Kit recognizes Sheep (Ovine, General) CASPASE-6. (mybiosource.com)
  • Vasculogenic mimicry: Possible role of effector caspase-3, caspase-6 and caspase-7. (elisakits.co.uk)
  • Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
  • Fig. 6: C3 D9E is inefficiently cleaved resulting in decreased caspase activation and cell death. (nature.com)
  • The FLICA reagent FAM-VEID-FMK enters each cell and irreversibly binds to activated caspase-6. (immunochemistry.com)
  • Evaluation of caspase-3 and caspase-8 deregulation in tongue squamous cell carcinoma, based on immunohistochemistry and computerised image analysis. (semanticscholar.org)
  • Axon degeneration initiated by trophic factor withdrawal shares many features with programmed cell death, but many prior studies discounted a role for caspases in this process, particularly Caspase-3. (jneurosci.org)
  • We recommend using 1000-5000X dilutions for inhibiting caspase-6 activity in Jurkat cell culture (e.g. (antibody-antibodies.com)
  • Caspases ( c ysteine- asp artic prote ases , c ysteine asp art ases or c ysteine-dependent asp artate-directed prote ases ) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis , pyroptosis and necroptosis ) and inflammation . (wikipedia.org)
  • Activation of Caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues . (wikipedia.org)
  • Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis . (wikipedia.org)
  • There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing. (wikipedia.org)
  • [5] Conversely, over-activation of some caspases such as caspase -3 can lead to excessive programmed cell death. (wikipedia.org)
  • [5] The integral role caspases play in cell death and disease has led to research on using caspases as a drug target. (wikipedia.org)
  • Most caspases play a role in programmed cell death. (wikipedia.org)
  • Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation. (wikipedia.org)
  • Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. (mdpi.com)
  • This broad range indicates that caspase-3 will be fully active under normal and apoptotic cell conditions. (wikipedia.org)
  • This caspase-3 reporter activity provides valuable insight into cancer cell responsiveness to therapy and overall viability at a single-cell scale. (mdpi.com)
  • Within this article, we describe methods for measuring caspase-3 activation at single-cell resolution in various complex environments using FLIM. (mdpi.com)
  • Recently, both GSDMD and GSDME were reported to be critical effectors of caspase-1/11-driven pyroptosis and caspase-3-dependent secondary necrosis, which prompted the redefinition of pyroptosis as cell death-mediated by gasdermin activation. (pnas.org)
  • Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8-mediated cell death. (pnas.org)
  • The CARD domain of ARC exhibited significant homology to the prodomains of apical caspases and the CARDs present in the cell death regulators Apaf-1 and RAIDD. (pnas.org)
  • Open up in another window Shape 3 Treatment using the 418788-90-6 mix of lithium and either VPA 418788-90-6 or SBHA decreases CgA a lot more than treatment with complete doses from the medications by itself in GI and pulmonary carcinoid cell lines. (rmrfotoarts.com)
  • 1,6-O,O-diacetylbritannilactone (OODBL) isolated from Inula britannica, exhibits potent antitumor activity against several human cancer cell lines. (researchwithnj.com)
  • Identification of a New Caspase Homologue: Caspase-14," Cell Death and Differentiation 5: 838-846, 1998. (patentgenius.com)
  • Caspase-3 processing occurs in different T cell subsets (CD4 + , CD8 + , CD45RA + , and CD45RO + ), and in activated B lymphocytes. (rupress.org)
  • Interestingly, such a role for caspases in T cell activation is indirectly supported by several recent observations. (rupress.org)
  • In the same way caspases are activated, many anti-apoptotic molecules can also inhibit caspases to prevent cell death, by a similar mechanism of structural alteration. (bioportfolio.com)
  • Further neurological implications include the caspase-3 dependent cell death in cerebellar granule neurons, which highlights potential neuro-toxicity of any caspase inhibiting compound. (bioportfolio.com)
  • Caspase-1 has been shown to induce cell necrosis, pyroptosis, or pyrop-apoptosis [ 4 ] and exerts functions in various developmental stages. (springer.com)
  • We show that caspases were locally active in vivo at the branch points of young, dynamic retinal ganglion cell axonal arbors but not in the cell body or in stable mature arbors. (rupress.org)
  • Freeze thaw will destroy a percentage in every cycle and should be avoided.Human and some mouse caspases are active in apoptosis and cell death and even in necrosis and inflammation. (gentaur.com)
  • Caspases are well known for their roles in programmed cell death and for their roles in maturation of inflammatory cytokines. (sciencemag.org)
  • now show that caspase 11 also has a role in regulating actin dynamics that contributes to cell migration. (sciencemag.org)
  • Leukocytes deficient for caspase 11 were defective in cell migration in culture (transwell assays) and in vivo. (sciencemag.org)
  • Thus, caspase 11 now appears to influence multiple inflammatory cell processes: cytokine secretion, apoptosis, and cell migration. (sciencemag.org)
  • Caspase 11 promotes cell migration by participating in regulation of actin dynamics. (sciencemag.org)
  • Caspases are a type of cysteine protease closely linked to the process of apoptosis (cell self-destruction). (agscientific.com)
  • We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (jci.org)
  • Caspase-3 is activated in the apoptotic cell. (wikipedia.org)
  • Caspase-3 activation is a cell requirement during early stages of the skeletal myoblast differentiation. (wikipedia.org)
  • Caspase signals resulting from the activation of nuclease CAD indicate that the cell differentiation is due to a CAD modification in chromatin structure. (wikipedia.org)
  • Although to date no functional homologs of animal caspases have been identified in plants, a vast amount of indirect evidence suggesting the existence in plants of true caspase-like activity and its functional involvement in plant cell death has accumulated. (plantphysiol.org)
  • Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. (cdc.gov)
  • Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. (cdc.gov)
  • 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)
  • Caspase 6 has also been shown involving in the proteolysis of poly (ADP-ribose) polymerase (PARP) and nuclear lamin A. (abcam.com)
  • These caspases are responsible for the proteolysis of the majority of cellular polypeptides [e.g. poly(ADP-ribose) polymerase (PARP)], which leads to the apoptotic phenotype. (creative-enzymes.com)
  • Activation and regulation of caspase-6 and its role in neurodegenerative diseases. (elisakits.co.uk)
  • Little is known about the regulation of caspase activity during apoptosis. (pnas.org)
  • Due to the importance of caspase 3 in the execution phase of apoptosis and because the mechanism of caspase 3 modulation by 4-HPR remains ill-defined, we investigated regulation of caspase 3 by 4-HPR. (aacrjournals.org)
  • However, we find at a biochemical level that Caspase-6 is activated effectively only by Caspase-3 but not other "upstream" caspases, prompting us to revisit the role of Caspase-3. (jneurosci.org)
  • The value of the caspase market is hard to establish, since while central to many mechanisms of actions for many drugs, these drugs act slightly further upstream, modulating the relative activity of caspase molecules, but it is clear that they offer significant potential for R&D in pharma! (bioportfolio.com)
  • Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. (wikipedia.org)
  • [5] Caspases involved with processing inflammatory signals are also implicated in disease. (wikipedia.org)
  • Activated caspase-1 is required for cleaving/processing of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 into mature pro-inflammatory cytokines IL-1β and IL-18, respectively. (springer.com)
  • Transgenic mice expressing the cleaved form of caspases by Lyn, a tyrosine kinase Src family, develop an inflammatory syndrome with the characteristics of human psoriasis. (clinicaltrials.gov)
  • Thus, the investigators will evaluate the expression and activity of Lyn from skin lesion (L) and non-lesional (NL) from the same patient in parallel with the level of caspase activation and apoptotic inflammatory. (clinicaltrials.gov)