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.

Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. (1/1249)

Shp-2 is an SH2 domain-containing protein tyrosine phosphatase. Although the mechanism remains to be defined, substantial experimental data suggest that Shp-2 is primarily a positive regulator in cell growth and development. We present evidence here that Shp-2, while acting to promote mitogenic signals, also functions as a negative effector in interferon (IFN)-induced growth-inhibitory and apoptotic pathways. Treatment of mouse fibroblast cells lacking a functional Shp-2 with IFN-alpha or IFN-gamma resulted in an augmented suppression of cell viability compared to that of wild-type cells. To dissect the molecular mechanism, we examined IFN-induced activation of signal transducers and activators of transcription (STATs) by electrophoretic mobility shift assay, using a specific DNA probe (hSIE). The amounts of STAT proteins bound to hSIE upon IFN-alpha or IFN-gamma stimulation were significantly increased in Shp-2(-/-) cells. Consistently, tyrosine phosphorylation levels of Stat1 upon IFN-gamma treatment and, to a lesser extent, upon IFN-alpha stimulation were markedly elevated in mutant cells. Furthermore, IFN-gamma induced a higher level of caspase 1 expression in Shp-2(-/-) cells than in wild-type cells. Reintroduction of wild-type Shp-2 protein reversed the hypersensitivity of Shp-2(-/-) fibroblasts to the cytotoxic effect of IFN-alpha and IFN-gamma. Excessive activation of STATs by IFNs was also diminished in mutant cells in which Shp-2 had been reintroduced. Together, these results establish that Shp-2 functions as a negative regulator of the Jak/STAT pathway. We propose that Shp-2 acts to promote cell growth and survival through two mechanisms, i.e., the stimulation of growth factor-initiated mitogenic pathways and the suppression of cytotoxic effect elicited by cytokines, such as IFNs.  (+info)

The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. (2/1249)

Recently, Salmonella spp. were shown to induce apoptosis in infected macrophages. The mechanism responsible for this process is unknown. In this report, we establish that the Inv-Spa type III secretion apparatus target invasin SipB is necessary and sufficient for the induction of apoptosis. Purified SipB microinjected into macrophages led to cell death. Binding studies show that SipB associates with the proapoptotic protease caspase-1. This interaction results in the activation of caspase-1, as seen in its proteolytic maturation and the processing of its substrate interleukin-1beta. Caspase-1 activity is essential for the cytotoxicity. Functional inhibition of caspase-1 activity by acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone blocks macrophage cytotoxicity, and macrophages lacking caspase-1 are not susceptible to Salmonella-induced apoptosis. Taken together, the data demonstrate that SipB functions as an analog of the Shigella invasin IpaB.  (+info)

Caspase-1 is not involved in experimental hepatitis in mouse. (3/1249)

Experimental hepatitis induced by tumor necrosis factor in D-(+)-galactosamine-sensitized mice or by an agonistic anti-Fas antibody in normal mice is accompanied by dramatic apoptosis of hepatocytes. Apoptosis is the final result of activation of a cascade of caspases. We used caspase-1-/- mice, generated by gene targeting, to study the role of this protease in TNF- and anti-Fas-induced lethal hepatitis. We found that mutant mice exhibited the typical caspase-1-/- phenotype, since they resisted to a lethal injection of LPS and released no interleukin-1beta in the circulation, in contrast to wild-type littermates. When caspase-1-/- mice were challenged with different doses of tumor necrosis factor/D-(+)-galactosamine or with anti-Fas, no increased survival was observed compared with control mice. Furthermore, apoptosis in the livers of these mice and serum levels of alanine aminotransferase were not reduced. These data indicate that caspase-1 deficiency does not lead to reduced apoptosis in these models, either because caspase-1 is irrelevant in this model or because of functional redundancy.  (+info)

Alkaline conditions accelerate polymorphonuclear leukocyte apoptosis in vitro. (4/1249)

Apoptosis was monitored in polymorphonuclear leukocytes (PMNs) cultured under mildly acidic, neutral, and alkaline conditions. Within 3 h, 9.0% of the PMNs underwent apoptosis at pH 6.7, as did 12% at pH 7.2, 38% at pH 7.7, and 60% at pH 8.2. Inhibitors of serine proteases, caspase-1, or caspase-3 significantly inhibited PMN apoptosis at pH 8.2, suggesting an involvement by these enzymes.  (+info)

Restoration of transforming growth factor beta signaling pathway in human prostate cancer cells suppresses tumorigenicity via induction of caspase-1-mediated apoptosis. (5/1249)

Previous studies (Y. Guo and N. Kyprianou, Cell Growth Diff., 9: 185-193, 1998) have demonstrated that overexpression of transforming growth factor (TGF) beta type II receptor (TbetaRII) gene in human prostate cancer cells LNCaP, which are refractory to TGF-beta1 and lack TbetaRII receptor expression, can restore TGF-beta1 sensitivity and suppress in vitro tumorigenic growth by inhibiting cell proliferation. In the present study, we investigated the effect of TbetaRII receptor overexpression in LNCaP cells on apoptosis induction and tumorigenicity. The ability of LNCaP cells that overexpress TbetaRII to undergo apoptosis in response to TGF-beta1 was examined by DNA fragmentation and terminal transferase-mediated dUTP-biotin end labeling analysis. To explore the potential apoptotic nature of TGF-beta1-mediated antitumor effect against human prostate cancer cells, the expression of apoptotic proteins bcl-2 and bax was examined by Western blot analyses. The significance of caspase 1 in TGF-beta1-mediated apoptosis was also determined by examining the expression and activation of caspase 1 by reverse transcription-PCR and Western blot analyses, respectively. Comparative analysis of tumorigenicity of the parental LNCaP and TbetaRII-overexpressing clones in severely combined immunodeficient mice revealed a significant suppression of tumor growth in TbetaRII transfectant clones compared with parental LNCaP cells and neomycin-control clones (P < 0.05). A significantly higher incidence of endogenous apoptosis was observed in TbetaRII clone-61-derived tumor compared with the parental LNCaP tumors. This induction of apoptosis in the LNCaP tumors with restored TGF-beta1 signaling was associated with decreased bcl-2 expression, increased bax, and caspase-1 immunoreactivty. Moreover, an increased expression of the cyclin-dependent kinase inhibitor p27Kip1 was detected in TbetaRII-overexpressing tumors compared with the parental tumors. LNCaP TbetaRII transfectant cells exhibited a marked induction of apoptosis, paralleled with a decreased bcl-2 expression in response to TGF-beta1 treatment in vitro. This TGF-beta1-mediated apoptosis induction in TbetaRII transfectant cells was significantly protected by the caspase-1 inhibitor (zVAD-fmk) in a dose-dependent manner. Furthermore, a significant temporal induction of caspase-1 mRNA and protein expression was detected in TbetaRII cells in response to TGF-beta1 treatment. Our findings suggest that restoration of TGF-beta1 signaling suppresses tumorigenicity of human prostate cancer cells by inducing apoptosis, potentially via a caspase-1-mediated pathway.  (+info)

The p42 variant of ETS1 protein rescues defective Fas-induced apoptosis in colon carcinoma cells. (6/1249)

ETS1 is a cellular homologue of the product of the viral ets oncogene of the E26 virus, and it functions as a tissue-specific transcription factor. It plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. ETS1 controls the expression of critical genes involved in these processes by binding to ets binding sites present in the transcriptional regulatory regions. The ETS1 gene generates two proteins, p51 and a spliced variant, p42, lacking exon VII. In this paper we show that p42-ETS1 expression bypasses the damaged Fas-induced apoptotic pathway in DLD1 colon carcinoma cells by up-regulating interleukin 1beta-converting enzyme (ICE)/caspase-1 and causes these cancer cells to become susceptible to the effects of the normal apoptosis activation system. ICE/caspase-1 is a redundant system in many cells and tissues, and here we demonstrate that it is important in activating apoptosis in cells where the normal apoptosis pathway is blocked. Blocking ICE/caspase-1 activity by using specific inhibitors of this protease prevents the p42-ETS1-induced apoptosis from occurring, indicating that the induced ICE/caspase-1 enzyme is responsible for killing the cancer cells. p42-ETS1 activates a critical alternative apoptosis pathway in cancer cells that are resistant to normal immune attack, and thus it may be useful as an anticancer therapeutic.  (+info)

Inhibition of caspases inhibits the release of apoptotic bodies: Bcl-2 inhibits the initiation of formation of apoptotic bodies in chemotherapeutic agent-induced apoptosis. (7/1249)

During apoptosis, the cell actively dismantles itself and reduces cell size by the formation and pinching off of portions of cytoplasm and nucleus as "apoptotic bodies." We have combined our previously established quantitative assay relating the amount of release of [3H]-membrane lipid to the degree of apoptosis with electron microscopy (EM) at a series of timepoints to study apoptosis of lymphoid cells exposed to vincristine or etoposide. We find that the [3H]-membrane lipid release assay correlates well with EM studies showing the formation and release of apoptotic bodies and cell death, and both processes are regulated in parallel by inducers or inhibitors of apoptosis. Overexpression of Bcl-2 or inhibition of caspases by DEVD inhibited equally well the activation of caspases as indicated by PARP cleavage. They also inhibited [3H]-membrane lipid release and release of apoptotic bodies. EM showed that cells overexpressing Bcl-2 displayed near-normal morphology and viability in response to vincristine or etoposide. In contrast, DEVD did not prevent cell death. Although DEVD inhibited the chromatin condensation, PARP cleavage, release of apoptotic bodies, and release of labeled lipid, DEVD-treated cells showed accumulation of heterogeneous vesicles trapped in the condensed cytoplasm. These results suggest that inhibition of caspases arrested the maturation and release of apoptotic bodies. Our results also imply that Bcl-2 regulates processes in addition to caspase activation.  (+info)

High and low molecular weight DNA cleavage in ovarian granulosa cells: characterization and protease modulation in intact cells and in cell-free nuclear autodigestion assays. (8/1249)

To continue elucidation of the biochemical and molecular pathways involved in the induction of apoptosis in granulosa cells (GC) of ovarian follicles destined for atresia, we characterized the occurrence and protease modulation of high and low molecular weight (MW) DNA fragmentation during rat GC death. Atresia of ovarian follicles, occurring either spontaneously in vivo or induced in vitro, was associated with both high MW and internucleosomal (low MW) DNA cleavage. Incubation of follicles in the presence of a putative irreversible and non-competitive inhibitor of caspase-1 (interleukin-1beta-converting enzyme or ICE), sodium aurothiomalate (SAM), completely prevented internucleosomal, but not high MW, DNA cleavage. As reported previously, morphological features of apoptosis (pyknosis, cellular condensation) and atresia (granulosa cell disorganization, oocyte pseudomaturation) remained detectable in SAM-treated follicles. The potential involvement of proteases in endonuclease activation was further analyzed in cell-free assays using nuclei from both GC (which autodigest their DNA) and HeLa cells (HC, which do not autodigest their DNA unless incubated with extracts prepared from other cell types). Crude cytoplasmic extracts prepared from GC induced both high MW and internucleosomal DNA cleavage in HC nuclei. The induction of low, but not high, MW DNA cleavage in HC nuclei by GC extracts was suppressed by pretreatment of the extracts with SAM or with any one of the serine protease inhibitors, dichloroisocoumarin (DCI), N-tosyl-L-leucylchloromethylketone (TLCK) or N-tosyl-L-phenylchloromethylketone (TPCK). Interestingly, SAM and DCI also prevented cation-induced low MW DNA fragmentation in GC nuclei; however, TLCK and TPCK were without effect. Our results support a role for cytoplasmic and nuclear serine proteases in the activation of the endonuclease(s) responsible for internucleosomal DNA cleavage during apoptosis.  (+info)

ASC is an adaptor protein which contains two protein-protein interaction domains; N-terminal - pyrin domain (PYC) and C-terminal - caspase recruitment domain (CARD).. ASC plays an important role in inflammation and apoptosis. It is a component of several inflammatory complexes, inflammasomes, which are important for caspase-1 activation, processing and secretion of pro-inflammatory cytokines (IL-1β, IL-18). It promotes pyropoptosis in macrophages and induces caspase-mediated apoptosis (involving caspase-8 and caspase-9).. Additionally, ASC is involved in transcriptional control of cytokine and chemokine expression independent of the inflammasome.. ...
Background: Inflammatory responses play a key role in the pathophysiology of myocardial ischemia-reperfusion (I/R) injury. ASC is an adaptor protein that forms inflammasome whose activation leads to caspase-1-dependent interleukin (IL)-1β generation and subsequent inflammatory responses; however, the role of ASC in myocardial I/R injury remains to be determined.. Methods and Results: ASC deficient (ASC−/−) and wild-type (WT) mice were subjected to 30 min LAD occlusion, followed by reperfusion. ASC−/− mice showed improved LV dysfunction (%FS: 34.0% vs. 25.7% at 14 days p,0.01), reduced infarct area/area at risk (IA/AAR: 18.7% vs. 28.6% at 48 h, p,0.01), and scar formation (scar/LV area: 9.7% vs. 14.6% at 14 days, p,0.01) after myocardial I/R. Immunostaining revealed decreased infiltration of macrophages (Mac3) and neutrophils (Gr-1), but not neovascularization (CD31), in the injured myocardium of the ASC−/− mice. Real-time RT-PCR and ELISA analyses demonstrated that the myocardial ...
Shop NLR family ELISA Kit, Recombinant Protein and NLR family Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
NALP1 antibody [Nalpy1-4] (NLR family, pyrin domain containing 1) for ICC/IF, IHC-P, IP, WB. Anti-NALP1 mAb (GTX16091) is tested in Human samples. 100% Ab-Assurance.
NLRP13 antibody (NLR family, pyrin domain containing 13) for ELISA, ICC/IF, WB. Anti-NLRP13 pAb (GTX31990) is tested in Human samples. 100% Ab-Assurance.
cdna:known chromosome:VEGA66:16:3945610:3976632:-1 gene:OTTMUSG00000042324 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Nlrc3 description:NLR family, CARD domain containing 3 ...
NALP1兔多克隆抗体(ab36852)可与人样本反应并经WB, IHC, ICC/IF实验严格验证,被4篇文献引用。所有产品均提供质保服务,中国75%以上现货。
ASC2兔多克隆抗体(ab47092)可与小鼠, 大鼠, 人, 沙鼠样本反应并经WB, IP, IHC实验严格验证。所有产品均提供质保服务,中国75%以上现货。
I need some help. I have a ASC case where the MD did a cystourethroscopy w/ bilaterial retrograde ureterograms. He also did Litholapaxy with the extra
Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We developed transgenic mice that ectopically express the fluorescent adaptor protein, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and characterized the formation of assembled inflammasome complexes (specks) in primary cells and tissues. In addition to hematopoietic cells, we found that a stromal population in the lung tissues forms specks during the early phase of influenza infection whereas myeloid cells showed speck formation after two days. In a peritonitis and Group B streptococcus infection models, a higher percentage of neutrophils formed specks at early phases of infection, while dendritic cells formed specks at later time points. Furthermore, speck-forming cells underwent pyroptosis, and extensive release of specks to the extracellular milieu in vivo. These data underscore the ...
The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound conditioned medium activates caspase-1 and induces release of IL-1β and IL-18 in cultured Mp via a reactive oxygen species-mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from pro-inflammatory to healing-associated Mp phenotypes and increased levels of pro-healing growth factors. Furthermore, data ...
Ca2+ or other CaSR agonists activate the NLRP3 inflammasome in the absence of exogenous ATP, whereas knockdown of CaSR reduces inflammasome activation in response to known NLRP3 activators. The CaSR activates the NLRP3 inflammasome through phospholipase C (PLC), which catalyzes inositol trisphosphate (IP3) production and thereby induces release of Ca2+ from endoplasmic reticulum (ER) stores. The increased cytoplasmic Ca2+ promotes the assembly of inflammasome components, and intracellular Ca2+ is required for spontaneous inflammasome activity in cells from CAPS patients. CaSR stimulation also results in reduced intracellular cAMP, which independently activates the NLRP3 inflammasome. cAMP binds to NLRP3 directly to inhibit inflammasome assembly, and downregulation of cAMP relieves this inhibition. The binding affinity of cAMP for CAPS-associated mutant NLRP3 is substantially lower than for wild-type NLRP3, and the uncontrolled mature IL-1β production from CAPS patients peripheral blood ...
NLRP3 inflammasome assembly. CARD, caspase recruitment domain; LRR, leucine-rich repeat; NACHT/NBD, nucleotide binding domain; PYD, pyrin domain; CAP1, caspase-
PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome . NMR structure of full-length ASC: PDB ID 2KN6 [1] This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ...
Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22-82) in association with age. Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas
To the Editor. We read the article of Osuka et al. (1) entitled A Protective Role for Inflammasome Activation Following Injury with great interest. However, we are concerned that the authors have not sufficiently ruled out the possibility that the major effects attributed to inflammasome inhibition were merely due to the solvent used.. The authors describe inflammasome activation in burned mice 1 day after injury as revealed by caspase 1 activation and increased interleukin 1β (IL-1β) production. Interestingly, the data suggest that inhibiting caspase 1 activity-and thereby inhibiting inflammasome activation-with the Ac-YVAD-cmk peptide did not reduce inflammation as expected. On the contrary, it caused a significantly higher mortality and increased expression of the proinflammatory cytokines IL-6 and IL-33 as compared with untreated burned mice. The authors therefore conclude that inflammasome activation might have a protective role following severe injury. Inhibition of (pro)caspase 1 ...
The cytosolic pattern recognition receptor NLRP3 senses host-derived danger signals and certain microbe-derived products in both humans and rodents. NLRP3 activation assembles an inflammasome complex that contains the adapter proteins ASC and caspase-1, whose activation triggers the maturation and release of the proinflammatory cytokines IL-1β and IL-18. S5 phosphorylation of NLRP3 prevents its oligomerization and activation, whereas dephosphorylation of this residue by the phosphatase PP2A allows NLRP3 activation. However, the protein kinase that mediates NLRP3 S5 phosphorylation is unknown. In this study, we show that AKT associates with NLRP3 and phosphorylates it on S5, limiting NLRP3 oligomerization. This phosphorylation event also stabilizes NLRP3 by reducing its ubiquitination on lysine 496, which inhibits its proteasome-mediated degradation by the E3 ligase Trim31. Pharmacologic manipulation of AKT kinase activity reciprocally modulates NLRP3 inflammasome-mediated IL-1β production. ...
Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. The NLRP3 inflammasome requires two stages to contribute: priming and activation. The priming stage involves upregulation of inflammasome components while the activation stage results in the assembly and activation of the inflammasome complex. The priming step can be rate limiting and can connect insult to chronic inflammation, but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammation is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure (IOP) increased mRNA for inflammasome components IL-1β, NLRP3, ASC and CASP1 in rat and mouse retinas. The elevation was greater one day after
Chronic inflammation and inflammasome activation play roles in the pathogenesis of type 2 diabetes (2,29,30). NLRP3 is a member of the NLR family, which is responsible for cytosolic inflammasome activation. The NLRP3 inflammasome has been the focus of particular attention with regard to its roles in inflammatory responses, antimicrobial responses, and a variety of human diseases, including hereditary autoinflammatory syndromes, atherosclerosis, and diabetes (7,22,30,31). Recently, obesity-induced danger signals have been reported to activate the NLRP3 inflammasome and induce the production of IL-1β in adipose tissue in type 2 diabetic patients and mice fed a high-fat diet (9). Circulating levels of C-X-C motif chemokine 10 and CCL2, as well as interferon-γ mRNA and protein levels in adipose tissue, were significantly reduced in NLRP3-deficient mice, suggesting that the NLRP3 inflammasome plays a role in the macrophage-T-cell interactions that are associated with sustained levels of chronic ...
The ASC (apoptosis speck-like protein) is a key component of multimeric protein complexes that mediate inflammation and host defence. Comprising a PYD (Pyrin) domain and a CARD (caspase activation and recruitment domain), ASC functions downstream of NLRs (nucleotide-binding domain, leucine-rich repeat-containing receptors) and AIM2 (absent in melanoma 2) through the formation of supramolecular structures termed inflammasomes. However, the mechanism underlying ASC signalling and its dependency on oligomeric arrangements in inflammasome formation remain poorly understood. When expressed in cells, ASC forms discrete foci (called specks) typically with one speck per cell. We employed a BiFC (bimolecular fluorescence complementation) system to investigate and visualize ASC foci formation in living cells. We demonstrated that the CARD of ASC plays a central role in ASC inflammasome assembly, representing the minimal unit capable of forming foci in conjunction with the caspase 1 CARD. Mutational ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
On September 21, 2017, Posted by Birgit Rogell , In Press Releases, With Kommentare deaktiviert für EMBL: Visualization of inflammasome formation in real life ...
Exaggerated inflammasome activation in venous thrombosis in CD39-deficient mice. Extracellular release of ATP and ADP through cell death, injury, or activation is a potent stress response, altering the local microenvironment to activate paracrine and autocrine signaling pathways (18, 19). Binding of extracellular ATP to the plasma membrane receptor ionophore P2X7 activates a potent stress-response-signaling pathway characterized by potassium efflux, which triggers assembly and activity of the inflammasome, a multiprotein oligomer that activates highly proinflammatory cytokines including IL-1β (20). Gupta et al. recently reported increased NLRP3 inflammasome assembly in patients at high altitude at risk for DVT (21). Canonical inflammasome activation requires a priming step marked by NF-κB activation and inflammasome component transcription (20). A second signal initiates NLRP3-mediated assembly and oligomerization of inflammasome component fibers, proteolytic cleavage of pro-caspase-1 to ...
DrLinOng. Chan SJ, Esposito E, Hayakawa K, Mandaville E, Smith RAA, Guo S, Niu W, Wong PT-H, Cool SM, Lo EH, Nurcombe V. Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia. Stroke. 2020;51:2844-2853.. Angiogenesis and neurogenesis are crucial processes for brain recovery after stroke. While the brain has the capacity to form new cerebral blood vessels and to generate new neurons from neural stem cells after stroke, these self-repair mechanisms are limited. Therefore, strategies to promote brain restorative processes beyond the endogenous recovery are highly desirable. In this study, Chan and colleagues demonstrated that an exogenously applied heparan sulfate with increased affinity for vascular endothelial growth factor was able to enhance angiogenesis and neurogenesis within the peri-infarct regions, as well as to promote neurological recovery after experimental stroke.. The team first purified heparan sulfate variant 7, a ...
There is a clear need for interdisciplinary research and publications that bring together scientists who work on the inflammasome. This protein complex, termed the inflammasome and many of its components are implicated in disease disorders, autoimmune and infectious diseases. The structure, activation and regulation of the inflammasome complex have been and are still studied in increasing number of laboratories around the world. Our goal is to provide an issue summarizing every fascinating aspect of inflammasome activation and modulation of the innate immune response to microbial and to danger signals. This issue will bring the experts in inflammasome research up to speed with the most recent findings. However, several reviews are geared towards introducing the new scientists to the inflammasome complex and to the fundamental and essential information that will help them understand and even pursue their studies in this direction. By looking at the two sides of the coin, notably, some authors focused on
AIM2 is a cytosolic DNA sensor of the inflammasome, which induces critical innate immune responses against various invading pathogens. Earlier biochemical studies showed that the binding of AIM2 to DNA triggered the self-oligomerization of AIM2, which is essential for AIM2 inflammasome activation. We recently reported that VP22, a virion tegument protein of herpes simplex virus 1 (HSV-1), inhibited activation of the AIM2 inflammasome in HSV-1-infected cells by preventing AIM2 oligomerization. VP22 binds nonspecifically to DNA; however, its role in HSV-1 replication is unclear. We investigated the role of VP22 DNA binding activity in the VP22-mediated inhibition of AIM2 inflammasome activation. We identified a VP22 domain comprising amino acids 227 to 258 as the minimal domain required for its binding to DNA in vitro. Consecutive alanine substitutions in this domain substantially impaired the DNA binding activity of VP22 in vitro and attenuated the inhibitory effect of VP22 on AIM2 inflammasome ...
THE Fas/APO-1 receptor is one of the major regulators of apoptosis(1-7). We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE)(8-10) which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.. ...
Active Caspase-1, rat recombinant protein , Interleukin-1 beta convertase, Interleukin-1 beta-converting enzyme, IL-1BC, p45. validated in (PBV11136r-25), Abgent
Cellulose nanocrystal cationic derivative induces NLRP3 inflammasome-dependent IL-1β secretion associated with mitochondrial ROS production
Buy NLRP1 elisa kit, Mouse NLR Family, Pyrin Domain Containing 1 (NLRP1) ELISA Kit (MBS109213) product datasheet at MyBioSource, ELISA Kits
Inflammasomes are large protein complexes formed in response to cellular stresses that are platforms for recruitment and activation of caspase 1
Supervisor: Dr Xuan Li. Title: Identification and characterisation of NLRP3 interactome. Abstract: Aberrant activation of the NLRP3 inflammasome is involved in sterile inflammation in multiple chronic diseases such as atherosclerosis, type 2 diabetes or Alzheimers disease. Identification of novel players regulating the NLRP3 inflammasome could therefore lead to the development of new therapeutic strategies.. Here, we propose to further characterize the NLRP3 interactome during inflammasome activation. We will then select and investigate the identified interaction partners in the NLRP3 inflammasome pathway. These experiments will not only shed light into the NLRP3 regulatory mechanism during inflammasome activation, but also reveal new role players in the NLRP3 inflammasome pathway.. ...
Within the last decade numerous advances have already been manufactured in the part and regulation of inflammasomes during pathogenic and sterile insults. to a number of pathogenic and physiological stimuli. Inflammasome activation can be an essential element of the innate immune system response and is crucial for the clearance of pathogens or broken cells. Nevertheless overt inflammasome activation can be a major drivers of autoimmune and metabolic disorders root the need for understanding this technique in physiological and pathological contexts. The inflammasome detectors are grouped relating with their structural features into nucleotide-binding domain-like receptors (NLRs) absent in melanoma 2-like receptors (ALRs) as well as the lately identified pyrin. The power is got by These receptors to put together inflammasomes and activate the cysteine protease caspase-1. As well as the sensor (NLR ALR or pyrin) and enzymatic element (caspase-1) most inflammasomes also make use of an adaptor ...
TY - CHAP. T1 - Pyroptosis. AU - Lawlor, Kathryn. AU - Conos, Stephanie A.. AU - Vince, James E. PY - 2018/12/9. Y1 - 2018/12/9. N2 - Pyroptosis is considered an inflammatory cell death pathway that can be triggered by caspase‐1 or caspase‐11, or the human caspase‐11 orthologs, caspase‐4 and caspase‐5. The activation of caspase‐1 is mediated by supramolecular cytosolic protein complexes, termed inflammasomes, which sense specific pathogen, host or environmental danger molecules. Prior to causing pyroptotic death, caspase‐1 can also cleave and thereby activate the potent pro‐inflammatory cytokines, interleukin‐1 (IL‐1 ) and IL‐18. In contrast, the activation of caspase‐11 is caused by its direct binding to cytosolic lipopolysaccharide (LPS) derived from gram‐negative bacteria. While caspase‐11 can promote caspase‐1 activity, caspase‐1 is not required for caspase‐11 killing, and caspase‐11 itself does not efficiently activate IL‐1 or IL‐18. Unlike apoptotic ...
The nucleotide-binding site and leucine rich repeat containing family pyrin site containing 3 (NLRP3) inflammasome regulates capase-1-reliant maturation of interleukin-1β during infection with Gram-negative bacterial pathogens such as for example enterohemorrhagic mutant not capable of producing RNase H induced elevated degrees of NLRP3-reliant inflammasome activation. nucleotide-binding site and leucine wealthy repeat containing family members pyrin domain including 3 (NLRP3) inflammasome as an important mediator of EHEC-induced IL-1β. Whereas EHEC-specific virulence elements had been dispensable for NLRP3 activation bacterial nucleic acids such as for example RNA:DNA hybrids and RNA obtained cytosolic gain access to and mediated inflammasome-dependent reactions. Consistent with a primary part for RNA:DNA hybrids in inflammasome activation delivery of artificial EHEC RNA:DNA hybrids in to the cytosol activated NLRP3-reliant reactions and intro of RNase H Edoxaban tosylate which degrades such ...
Supplementary Material for: Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia
Recent study of the CAPS disease spectrum has led to significant advances in our understanding of the NLRP3 inflammasome and IL-1β-mediated inflammation. While translational studies have resulted in vital therapies for patients with CAPS, many questions about the inflammasome and other caspase-1-dependent pathways remain. Inflammasome-mediated IL-18 has largely been overlooked in the context of human disease. In addition, recent studies have demonstrated caspase-1 and inflammasome functions extending beyond cytokine maturation to cellular death pathways, but whether these processes have any bearing on CAPS remains to be seen. Here, we take advantage of mutant NLRP3 knockin mouse lines to investigate these questions.. Our studies demonstrate that dysregulated IL-18 secretion occurs from both patient and Nlrp3 mutant mouse cells in a manner similar to IL-1β. In vitro, a hallmark of CAPS is lack of reliance on the 2-signal paradigm generally required for secretion of active IL-1β. We used this ...
The NFκB pathway is complex and regulates many downstream effects depending on the type of stimulating ligand and cell context. [13] TLR9 can be activated by mycobaterial DNA. Further, intracellular viral ssRNA and dsRNA activate the inflammation that induces cleavage of the pro-form of IL-1β into its mature active form.95 In fact, mice lacking the TLR3, which recognizes dsRNA and activates cytokine synthesis, if infected with mouse-adapted influenzavirus have attenuated increases in NREM sleep, hypothermia, and body weight loss compared to the prototypical responses of normal mice infected with influenza.96 Further, intracellular dsRNA that is produced during viral replication is also recognized by cytoplasmic PAMPs.97 Thus, PAMPs play a crucial role in the recognition of pathogens that lead to the production of sleep regulatory cytokines and the acute phase response to infections. Potentially, mitochondria simply act as a physical scaffold that promotes inflammasome assembly. By continuing ...
Sigma-Aldrich offers abstracts and full-text articles by [Ying Yang, Dong-Mei Zhang, Jia-Hui Liu, Lin-Shui Hu, Qiao-Chu Xue, Xiao-Qin Ding, Ling-Dong Kong].
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Formation of the inflammasome results in the activation of multiple pathways responsible for co-ordinating our immune response, yet interestingly, there are multiple forms of inflammasomes made up and triggered by different sets of proteins. This initial step of activation has been covered very well before, here. The activated inflammsome goes on to trigger key downstream members of our innate immune system through the recruitment of an important regulatory protease (it cuts up other proteins) - caspase 1, which converts inactive molecules to active, pro-inflammatory ones, such as interleukin-1 beta and interleukin-18. This inflammatory cascade functions to initiate an effective local and systemic immune response through the control of the innate and adaptive immune system; for example, IL-beta is responsible for fever and the recruitment of immune cells to the site of infection, and IL-18 induces the development of key T cell responses ...
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NLRP7 - NLRP7 (untagged)-Human NLR family, pyrin domain containing 7 (NLRP7), transcript variant 1 available for purchase from OriGene - Your Gene Company.
Complete information for NLRP12 gene (Protein Coding), NLR Family Pyrin Domain Containing 12, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-a
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... caspase 1 and caspase 8). In comparison to their mammalian counterparts, viral serpins contain significant deletions of ... 183 (1): 49-59. doi:10.1016/j.ajpath.2013.03.009. PMID 23669344. Scarff KL, Ung KS, Nandurkar H, Crack PJ, Bird CH, Bird PI ( ... Dai E, Guan H, Liu L, Little S, McFadden G, Vaziri S, Cao H, Ivanova IA, Bocksch L, Lucas A (May 2003). "Serp-1, a viral anti- ... 77 (1): 47-57. doi:10.1046/j.1440-1711.1999.00787.x. PMID 10101686. S2CID 44268106. Bird CH, Sutton VR, Sun J, Hirst CE, Novak ...
Lee SH, Stehlik C, Reed JC (Sep 2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 ... 2006). "Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 ... Fagol Caspase recruitment domain-containing protein 16 is an enzyme that in humans is encoded by the CARD16 gene. GRCh38: ... "Entrez Gene: COP1 caspase-1 dominant-negative inhibitor pseudo-ICE". Human CARD16 genome location and CARD16 gene details page ...
In 1992, her work on proteases led to the identification of the first caspase, caspase-1/Interleukin-1 converting enzyme (ICE ... In 1992, Thornberry identified the first caspase, Caspase-1/Interleukin-1 converting enzyme (ICE). In 1999, Thornberry ... "The caspase family of cysteine proteases". British Medical Bulletin. 53 (3): 478-490. doi:10.1093/oxfordjournals.bmb.a011625. ... "A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B". Journal of Biological ...
gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading ... 1] However, most antibodies that bind the CDbs region of gp120 do not neutralize HIV, and rare ones that do such as IgG1-b12 ... The diversity of env has been shown to increase by 1-2% per year in HIV-1 group M and the variable units are notable for rapid ... 383 (1): 47-59. doi:10.1016/j.virol.2008.09.017. PMC 2642736 . PMID 18973914. Wood N, Bhattacharya T, Keele BF, Giorgi E, Liu M ...
"Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". Journal of Immunology. 170 (7): 3631-6. doi: ... 70 (1): 120-135.e8. doi:10.1016/j.molcel.2018.03.009. PMC 5911935. PMID 29625033. Jia J, Bissa B, Brecht L, Allers L, Choi SW, ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Matsumoto R, Matsumoto H, Seki M, Hata M, Asano Y, ... 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano ...
Pan G, O'Rourke K, Dixit VM (1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841-5. ... The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which ... 505 (1): 23-6. doi:10.1016/S0014-5793(01)02768-5. PMID 11557035. Aouacheria A, Arnaud E, Venet S, et al. (2001). "Nrh, a human ... 359 (1): 76-82. doi:10.1016/j.bbrc.2007.05.090. PMID 17532299. Guillemin Y, Lalle P, Gillet G, et al. (2009). "Oocytes and ...
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Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results ... hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner". The Journal of Cell Biology. ... Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ... Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ...
"Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain ... Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to ... Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM (2000). "TMS1, a novel proapoptotic caspase recruitment ... Moriai R, Tsuji N, Kobayashi D, Yagihashi A, Namiki Y, Takahashi H, Watanabe N (2003). "A proapoptotic caspase recruitment ...
Lee SH, Stehlik C, Reed JC (2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation ... Inohara N, del Peso L, Koseki T, Chen S, Nunez G (Jun 1998). "RICK, a novel protein kinase containing a caspase recruitment ... The encoded protein contains a C-terminal caspase recruitment domain (CARD), and is a component of signaling complexes in both ... Chen YR, Clark AC (2003). "Equilibrium and kinetic folding of an alpha-helical Greek key protein domain: caspase recruitment ...
It was later shown that IpaB achieves this by interacting with caspase 1, a major regulatory protein in eukaryotic cells. ... December 1998). "Shigella-induced apoptosis is dependent on caspase-1 which binds to IpaB". The Journal of Biological Chemistry ... 156 (Pt 1): 116-127. doi:10.1099/mic.0.032318-0. PMC 2889428. PMID 19762438. Blocker A, Jouihri N, Larquet E, Gounon P, Ebel F ... 18 (1): 7-12. doi:10.1016/0968-0004(93)90080-7. PMID 8438237. Gophna U, Ron EZ, Graur D (July 2003). "Bacterial type III ...
"The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1". Proceedings of the National Academy of ... Scientists calculate that between 1% and 6% of individuals infected with Salmonella typhi become chronic, asymptomatic carriers ...
"IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. 17 (8): ... "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. 17 (8): ... cIAP1 is a member of the Inhibitor of Apoptosis family that inhibit apoptosis by interfering with the activation of caspases. ... a RIP-like kinase that associates with caspase-1". Curr. Biol. 8 (15): 885-8. doi:10.1016/S0960-9822(07)00352-1. PMID 9705938. ...
Sadasivam S, Gupta S, Radha V, Batta K, Kundu TK, Swarup G (Jan 2005). "Caspase-1 activator Ipaf is a p53-inducible gene ... Thalappilly S, Sadasivam S, Radha V, Swarup G (Jun 2006). "Involvement of caspase 1 and its activator Ipaf upstream of ... Damiano JS, Newman RM, Reed JC (Nov 2004). "Multiple roles of CLAN (caspase-associated recruitment domain, leucine-rich repeat ... a human caspase-1-activating protein related to Apaf-1". The Journal of Biological Chemistry. 276 (30): 28309-13. doi:10.1074/ ...
Beclin-1 is a protein that in humans is encoded by the BECN1 gene. Beclin-1 is a mammalian ortholog of the yeast autophagy- ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, et ... 59 (1): 59-65. doi:10.1006/geno.1999.5851. PMID 10395800. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, ... Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ (February 2004). "Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b ...
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 ... Kanneganti's lab showed compensatory roles for NLRP3/caspase-1 and caspase-8 in the regulation of IL-1β production in ... This study demonstrated that the NLRP3 inflammasome/pyroptotic pathway is closely connected to the caspase-8-mediated ...
Caspase-1 is important for the proteolytic processing of the pro-inflammatory cytokines IL-1β and IL-18. NLRP3 mutations are ... ASC contains PYD and CARD domain and links the NLRs to inactive form of caspase 1 through the CARD domain. All these protein- ... N-terminal domain is responsible for homotypic protein-protein interaction and it can consist of caspase recruitment domain ( ... The aggregation of the pro-caspase-1 causes the autocleavage and formation of an active enzyme. ...
Stierle, Donald B.; Stierle, Andrea A.; Girtsman, Teri; McIntyre, Kyle; Nichols, Jesse (2012). "Caspase-1 and -3 Inhibiting ... 329 (1): 9-17. doi:10.1111/j.1574-6968.2012.02497.x. PMID 22239643. Pitt, J. I. (1991). "Penicillium solitum Revived, and its ... doi:10.1016/S0031-9422(99)00015-1. Romanovskaya, I. I.; Bondarenko, G. I.; Davidenko, T. I. (2008). "Immobilization of ... doi:10.1016/S0031-9422(99)00015-1. Larsen, Thomas Ostenfeld; Lange, Lene; Schnorr, Kirk; Stender, Steen; Frisvad, Jens ...
Stierle AA, Stierle DB, Girtsman T (2012). "Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia ...
It recognizes bacterial molecules and stimulates an immune reaction . NOD1 protein contains a caspase recruitment domain (CARD ... "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". The Journal of ... enhances pro-interleukin-1beta processing through the interaction with pro-caspase-1". Biochemical and Biophysical Research ... Inohara N, Koseki T, del Peso L, Hu Y, Yee C, Chen S, Carrio R, Merino J, Liu D, Ni J, Núñez G (May 1999). "Nod1, an Apaf-1- ...
Gupta S, Radha V, Sudhakar Ch, Swarup G (2003). "A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1- ... 280 (1): 65-9. doi:10.1016/0014-5793(91)80205-H. PMID 1849097. S2CID 10568838. Cool DE, Tonks NK, Charbonneau H, et al. (1989 ... 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Johnson CV, Cool DE, Glaccum MB, et al. (1993). "Isolation ... 532 (1-2): 61-6. doi:10.1016/S0014-5793(02)03628-1. PMID 12459463. S2CID 33468275. Strausberg RL, Feingold EA, Grouse LH, et al ...
... caspase-11 or caspase-5 in humans, which is responsible for some of the effects that had been attributed to caspase-1, ... Dixit was among the first scientists to demonstrate that other immune caspases besides death caspases are incorporated into the ... In particular, caspase-1 activates cytokines of the interleukin-1 family, which are immune effectors that initiate an immune ... He is best known for leading one of the first teams that elucidated the role of caspases in apoptosis and inflammasome pathways ...
Yang XM, Downey JM, Cohen MV, Housley NA, Alvarez DF, Audia JP (November 2017). "The Highly Selective Caspase-1 Inhibitor VX- ... Flores J, Noël A, Foveau B, Lynham J, Lecrux C, LeBlanc AC (September 2018). "Caspase-1 inhibition alleviates cognitive ... Cornelis S, Kersse K, Festjens N, Lamkanfi M, Vandenabeele P. "Inflammatory caspases: targets for novel therapies". Current ... converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and ...
January 22, 1999). "Bax-induced Caspase Activation and Apoptosis via Cytochromec Release from Mitochondria Is Inhibitable by ... which leads to caspase activation and ultimately, programmed cell death. It is a well-established concept in the field of ... cytochrome c is released leading to initiation of caspase cascade and apoptotic events. While the exact signaling pathway of ... B-cell lymphoma-extra large (Bcl-xL), encoded by the BCL2-like 1 gene, is a transmembrane molecule in the mitochondria. It is a ...
39 (1): 86-92. doi:10.1038/ng1940. PMID 17187068. S2CID 22757727. Yin, H; Morioka H; Towle C A; Vidal M; Watanabe T; Weissbach ... HCLS1-associated protein X-1 is a protein that in humans is encoded by the HAX1 gene. The protein encoded by this gene is known ... 34 (1): 43-54. doi:10.1089/dna.2014.2657. PMC 4281894. PMID 25289648. Klein C, Grudzien M, Appaswamy G, et al. (January 2007 ... 214 (1): 14-19. doi:10.1002/jcp.21305. PMID 17929250. S2CID 36596625. Klein C, Grudzien M, Appaswamy G, et al. (2007). "HAX1 ...
Nakagawa, Akihisa; Sullivan, Kelly D.; Xue, Ding (NaN). "Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis ... 72: 1-7. doi:10.1016/j.exger.2015.09.006. PMID 26363351. Lee, RY (2001). "Regulation of C. elegans DAF-16 and its human ... In nutrient rich conditions, DAF-2 and AKT-1/AKT-2 in the insulin pathway inhibits entry of DAF-16 to the nucleus as it is ... DAF-16 is known to interact with: RLE-1 PRMT-1 UNC-43 TAX-6 JNK-1 FTT-2 In 1963 Sydney Brenner realised the success of biology ...
1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/238040151162165141. PMID 10069390. S2CID 31218178. Scanlan MJ, ... the sensitivity of PS1 to caspases". FEBS Lett. ...
2 (1): 48-58. doi:10.1038/nrc706. PMID 11902585.. *^ Cho S, Lu M, He X, Ee PL, Bhat U, Schneider E, Miele L, Beck WT (December ... Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene.[5] Presenilin-1 is one of the four ... "Entrez Gene: PSEN1 presenilin 1 (Alzheimer disease 3)".. *^ Chan YM, Jan YN (August 1998). "Roles for proteolysis and ... In the prenilin 1 null mutant drosophila, Notch signaling is abolished and it displays a notch-like lethal phenotype.[18] ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... ISBN 978-1-136-84407-2.. *^ a b Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). ... PMFBP1: encoding protein Polyamine-modulated factor 1-binding protein 1. *POLR3K: encoding enzyme DNA-directed RNA polymerase ... SHCBP1: encoding protein SHC SH2 domain-binding protein 1. *SLZ1: encoding protein SLX1 structure-specific endonuclease subunit ...
... 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). " ... doi:10.1016/S0896-6273(00)80540-1. PMID 9728912. S2CID 13983709.. *^ a b c d e Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, ... 1 (3): 191-98. doi:10.1038/35044558. PMID 11257907. S2CID 9750498.. *^ a b Zhong L, Yan CH, Lu CQ, Xu J, Huang H, Shen XM ( ...
... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... When interleukin-1 is produced in response to external stimuli, it can bind to cell-surface receptors on the same cell that ... 75 (1): 196-207. doi:10.1124/mol.108.049544. PMC 2669785 . PMID 18849352. Yi, Eun Hee; Lee, Chang Seok; Lee, Jin-Ku; Lee, Young ... 13 (1): 7-9. doi:10.1016/j.ccr.2007.12.020. PMID 18167335. Gao, Sizhi Paul; Mark, Kevin G.; Leslie, Kenneth; Pao, William; ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... 278 (1): 311-8. doi:10.1074/jbc.M206279200. PMID 12401807.. *^ a b c Gille C, Goede A, Schlöetelburg C, Preissner R, Kloetzel ... 31 (1): 137-55. doi:10.1007/BF02705243. PMID 16595883.. *^ a b Heinemeyer W, Fischer M, Krimmer T, Stachon U, Wolf DH (October ... 3 (1): 20-6. doi:10.1038/ni0102-20. PMID 11753406.. *^ Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ... Lotze MT, Tracey KJ (April 2005). "High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal". Nature ...
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 ... 10 (1): 45-65. doi:10.1038/sj.cdd.4401189. PMID 12655295.. *^ Chen G, Goeddel DV (2002). "TNF-R1 signaling: a beautiful pathway ... 1 (3): 264-75. PMID 12851985.. *^ Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T (2002). " ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 18 (1): 131-9. doi:10.3233/JAD-2009-1134. PMID 19625751.. *^ a b c d e Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, ... 12 (1): 59-65. doi:10.1038/sj.ejhg.5201102. PMID 14560316.. *^ a b c Mercuri E, Bertini E, Messina S, Solari A, D'Amico A, ... 26 (1): 187-97. doi:10.3233/JAD-2011-110080. PMID 21593570.. *^ a b Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... 2012: 1-11. doi:10.1155/2012/842945. Huang, Yen-Ta; Hsu, Chih W.; Chiu, Ted H. (1 September 2008). "Thalidomide and Its Analogs ... 2 (1): 36. doi:10.1186/1756-8722-2-36. PMC 2736171 . PMID 19674465. Vacca A, Ribatti D, Roncali L, et al. (July 1994). "Bone ... The secretion of IL-6 by bone marrow stromal cells (BMSC) and the secretion of the adhesion molecules VCAM-1, ICAM-1 and LFA, ...
... 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). " ... doi:10.1016/S0896-6273(00)80540-1. PMID 9728912.. *^ a b c d e Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, Miller FD ( ... 41 (1): 22-28. doi:10.1002/eat.20474. PMID 17922530.. *^ a b Vargas-Perez H, Ting-A Kee R, Walton CH, Hansen DM, Razavi R, ...
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 · . ... Helikase · Girase · Konvertase (C3/C5) · Permease (ATPase · EEAT · FATP · GLUT · MCT · OATP · SGLT · UCP-1) · Aldolase · ... 1 ADH · .2 ALR · .54 LAD · .90 RAD · .91 RAD · .144 PAD · .194 CAD · .195 CAD ...
This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does ... 258 (1): 92-100. doi:10.1006/excr.2000.4906. PMID 10912791.. *^ Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ...
"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase ... InChI=1/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12 ... 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+, ... semi-preparative scale preparation of crocin-1 and trans-crocetin". Fitoterapia. 92: 290-5. doi:10.1016/j.fitote.2013.11.014. ...
"A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site- ... 83 (1-2): 74-5. doi:10.1159/000015130. PMID 9925932.. *. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D ( ... The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res ... Morris JA, Kandpal G, Ma L, Austin CP (July 2003). "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein ...
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 ... 1] doi 10.1113/jphysiol.2009.179515 *↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, ... A desregulación da produción do TNFα foi implicada en diversas doenzas humanas, como a enfermidade de Alzheimer,[1] cancro,[2] ...
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 ... 123(1):9-18, 2016 *↑ Berninger TA, Polkinghorne PJ, Capon MR, et al. Color vision defect. A early sign of Sorsby retinal ... insulin-like growth factor-1 (IGF-1)[23], ciliary neurotrophic factor (CNTF)[24], pigment epithelium-derived factor (PEDF)[25] ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... 77 (1): 3-10. doi:10.1093/bja/77.1.3. PMID 8703628.. *^ Klaassen, C.D., Ed.: Casarett and Doull's Toxicology: The Basic Science ... 978-0-07-135469-1. .. *^ Chien, S; Toledo-Pereyra, L, eds. (2008). 'Metabolic Management - Organ Procurement and Preservation ... doi:10.1016/s1383-5742(02)00009-1. PMID 12052432.. *^ Narayanan, L; Fritzell, JA; Baker, SM; Liskay, RM; Glazer, PM (1997). " ...
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7]. *Caspase-1 is key in activating pro-inflammatory cytokines ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ... Pyroptosis by Caspase-4 and Caspase-5 in humans and Caspase-11 in mice ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... 1,0 1,1 1,2 1,3 1,4 Daneholt, Bertil. "Advanced Information: RNA interference". The Nobel Prize in Physiology or Medicine 2006 ... doi:10.1016/S0092-8674(02)71133-1.. *↑ Luciano D, Mirsky H, Vendetti N, Maas S (2004). "RNA editing of a miRNA precursor". RNA ... doi:10.1016/S1046-2023(03)00050-1.. *↑ Boutros M, Kiger A, Armknecht S, Kerr K, Hild M, Koch B, Haas S, Paro R, Perrimon N ( ...
This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 ... 27 (1): 88-93. doi:10.1053/ejso.1999.1018. PMID 11237497.. *^ Ramp U, Mahotka C, Heikaus S, Shibata T, Grimm MO, Willers R, ... 978-3-540-22096-1. . PMID 14740253.. *^ Cvoro A, Dundjerski J, Trajković D, Matić G (1999-04-01). "The level and ... 1113 (1): 1-14. Bibcode:2007NYASA1113....1M. doi:10.1196/annals.1391.018. PMID 17513460.. ...
a b Nikolaev A. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19. februar 2009;457(7232): ... 61 (1): 59-66. PMID 14732621. doi:10.1001/archneur.61.1.59.. *^ a b c d e f g h i j k l m n o p q r s Clinical Features of ... 2009;21(1):25-32. doi:10.1017/S1041610208008053. PMID 19026089. *^ a b c d e Nutrition and the Risk of Alzheimer's Disease. ... 1987;1(1):3-8. PMID 3331112.. *. Maurer Ulrike; Maurer Konrad (2003). Alzheimer: The Life of a Physician and the Career of a ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 ... 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) ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases. Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on ... "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4".. *^ a b Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, ... 9 (1): 72-85. doi:10.1210/mend.9.1.7760852. PMID 7760852.. *^ Fiorucci S, Zampella A, Distrutti E (2012). "Development of FXR, ... The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member ...
... is a protein that in humans is encoded by the CTSW gene.[5][6][7]. The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2.[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 ... 18: 1-13. doi:10.1163/156853897x00260.. *^ Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z. (2006) Constitutive ... 78 Suppl 1: S69. doi:10.1002/cyto.b.20554. PMC 3084630 . PMID 20839340.. ...
Is í an aidhm atá leis an liosta seo ná bithmhóiliní a thuairisciú.[1] ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... 5 (1): 56-63. doi:10.1093/cercor/5.1.56. PMID 7719130.. *^ a b c Budday, Silvia; Raybaud, Charles; Kuhl, Ellen (2014-07-10). "A ... 145 (1): 61-83. doi:10.1002/cne.901450105. PMID 4624784.. *^ LaMonica, BE; Lui, JH; Wang, X; Kriegstein, AR (October 2012). " ... Gyrification is the process of forming the characteristic folds of the cerebral cortex.[1] The peak of such a fold is called a ...
Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs.. Niu Z, Shi Q, Zhang W, Shu Y, Yang N, Chen B, Wang Q, ... Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. [J Leukoc Biol. 2016] Caspase-1 as a ... LSBio CASP1 / Caspase 1 Elisa Kits [LifeSpan BioSciences, Inc.] LSBio CASP1 / Caspase 1 Elisa Kits. LifeSpan BioSciences, Inc. ... Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs. [Nat Commun. 2017] ...
Caspase-1: the inflammasome and beyond.. Sollberger G1, Strittmatter GE, Garstkiewicz M, Sand J, Beer HD. ... Caspase-1 plays a fundamental role in innate immunity and in several important inflammatory diseases as the protease activates ... Caspase-1 itself is activated in different inflammasome complexes, which assemble in response to a variety of exogenous and ... More recently, pyroptosis, a caspase-1-dependent type of programmed cell death, has been identified that is able to support ...
... and a caspase, in this case Caspase-1. In some cases, where the signaling proteins contain their own CARDs, like in NLRP1 and ... Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the ... Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both ... For Caspase-1, genes for specific COPs-ICEBERG, COP1 (ICE/Pseudo-ICE), and INCA (Inhibitory Card)-are all found near its locus ...
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Like other caspases, Sf caspase-1 is an aspartate-specific cysteine protease that is produced as an inactive proenzyme and ... The Sf caspase-1 proenzyme is cleaved after the amino acid residues Asp-28 and Asp-195, resulting in a smaller 12 kDa fragment ... The protein Sf caspase-1 is the insect ortholog of the human effector caspases CASP3 (CPP32) and CASP7 (MCH3) in the species ... Some experiments also showed cleavage of Sf caspase-1 at the residue Asp-184, resulting in an 18 kDa instead of 19 kDa fragment ...
Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. Genomics. 2004 Sep;84(3):587-91 ... Lamkanfi M, Denecker G, Kalai M, Dhondt K, Meeus A, Declercq W, Saelens X, Vandenabeele P: INCA, a novel human caspase ... Romanowski MJ, Scheer JM, OBrien T, McDowell RS: Crystal structures of a ligand-free and malonate-bound human caspase-1: ... interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9982-7. Epub ...
Rabbit polyclonal Caspase-1 antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, Human. Cited in 32 publication(s ... Anti-Caspase-1 antibody (ab1872). Rabbit polyclonal Caspase-1 antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, ... Immunofluorescence analysis of caspase-1 in H9c2 cardiomyocytes treated with control, medium and high glucose using ab1872 (1: ... Immunocytochemistry/ Immunofluorescence - Anti-Caspase-1 antibody (ab1872)This image is courtesy of an Abreview submitted by ...
... J Clin Invest. 2015 Apr;125(4):1471-84. ... Furthermore, caspase-1 specifically facilitated cell surface actin exposure, which was required for the final release of highly ... inflammasome-induced activation of an intracellular caspase-1/calpain cysteine protease cascade degraded filamin, thereby ...
Hsp70 Inhibits Apaf-1-Mediated Caspase Activation Message Subject. (Your Name) has forwarded a page to you from Science ...
... bioluminescent method to selectively measure the activity of caspase-1, a member of the cysteine aspartic acid-specific ... protease (caspase) family and an essential component of the inflammasome. ... The Caspase-Glo 1 Inflammasome Assay is a homogeneous, ... Caspase-Glo® 8 Assay Systems. Measure caspase-8 activity with ... Caspase-Glo® 3/7 Assay System. An easy-to-use, plate-based luminescent assay for detecting caspase-3/7 activity. ...
Buy our Recombinant Human Caspase-1 protein. Ab158029 is a full length protein produced in Wheat germ and has been validated in ... Recombinant Human Caspase-1 protein. See all Caspase-1 proteins and peptides. ... Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety ...
... derived caspase substrates are widely used for the colorimetric detection of various caspase activities. Cleavage of pNA ... pNA has maximum absorption around 408 nm.; Caspase-9 substrate; Ac-LEHD-pNA; Ac-Leu-Glu-His-Asp-pNA ... peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. ... pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. ...
... derived caspase substrates are widely used for the colorimetric detection of various caspase activities. Cleavage of pNA ... pNA has maximum absorption around 408 nm.; Caspase-8 substrate with Km = 66 uM; Substrate for granzyme B; Ac-IETD-pNA; Ac - Ile ... peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. ... pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. ...
Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response. Mary K. Stewart ... Salmonella mutants lacking YdiV are unable to fully repress flagellin at systemic sites, rendering them vulnerable to caspase-1 ... Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response ... Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response ...
... including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. The interaction with caspase-9 was mediated ... The human caspase-3, caspase-4, wild type, and mutant (C287S) caspase-9 cDNAs were cloned into the BamHI and XhoI sites of a ... 6A). In contrast to caspase-9, we did not observe any enhancement of caspase-4 or caspase-8 processing using this in vitro ... Lower) The expression of caspase-3 and -4 (B), caspase-9 (C), and CED-3 and Apaf-1 proteins (D). Reduced level of pro-caspase-9 ...
... caspase 1 include Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages ... Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction, Visualization of Bacterial ... Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation, A Simple Fluorescence Assay ... Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells, ...
Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1-/- mice from ARF. In wild-type animals, we ... This conversion is not observed in caspase-1-/- ARF mice or sham-operated controls. We then injected wild-type mice with IL-18- ... We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1β and IL-18, ... Finally, we confirmed histologically that caspase-1-/- mice show decreased neutrophil infiltration, indicating that the ...
Caspase-3 should NOT be activated, which is the issue. Caspase-1 is the only think Im looking to be activated and that doesnt ... Caspase-3 activation is almost the last step of cell death. All different pathways end up with activation of caspase-3. So Im ... is a unique form of cell death that does not depend on the activation of caspase-3. There is detectable activation of caspase-7 ... Protocol to activate caspase-1 - Please help! - (Jul/02/2013 ). Ive followed a LOT of protocols from the literature and ...
Caspase-1 is a protease, an enzyme that cleaves proteins. It is found predominantly in the cell cytoplasm, where it activates ... Due to this activity caspase-1 is also known as ICE (interleukin-1-beta converting enzyme). Like other caspases it also plays a ... Molecular model of caspase-1 complexed with an inhibitor. ... interleukin-1-beta, a molecule that mediates immune and ... Caspase-1 is a protease, an enzyme that cleaves proteins. It is found predominantly in the cell cytoplasm, where it activates ...
Proteintech Anti-Caspase 8 Polyclonal, Catalog # 13423-1-AP. Tested in Western Blot (WB), Immunofluorescence (IF), ... caspase 8, apoptosis-related cysteine protease; Caspase-8; Caspase-8 precursor; Caspase-8 subunit p10; Caspase-8 subunit p18; ... Caspase 8 (CASP8) is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases play a ... Activated Caspase 8 then activates other downstream caspases including Caspase 9, thereby committing the cell to undergo ...
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What is Caspase-1? Meaning of Caspase-1 medical term. What does Caspase-1 mean? ... Looking for online definition of Caspase-1 in the Medical Dictionary? Caspase-1 explanation free. ... Caspases -2, -3, -6, and -9, but not caspase-1, are activated in sepsis-induced thymocyte apoptosis.. Is suppression of ... The initiator caspases including caspase-1, -8, -9, typically caspase-8 and caspase-9, are activated by two alternative ...
... a NACHT-leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1beta. However, the specific ... Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf Nat Immunol. 2006 Jun;7(6):569-75. doi: ... We show here that cytosolic bacterial flagellin activated caspase-1 through Ipaf but was independent of Toll-like receptor 5, a ... Edward A Miao 1 , Celia M Alpuche-Aranda, Monica Dors, April E Clark, Martin W Bader, Samuel I Miller, Alan Aderem ...
Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. ... Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. ...
Caspase-3. A, B, C, D. 249. Homo sapiens. Mutation(s): 0 Gene Names: CASP3, CPP32. EC: 3.4.22.56. ... Crystal Structures of Caspase-3 with Bound Isoquinoline-1,3,4-trione Derivative Inhibitors. *DOI: 10.2210/pdb3DEH/pdb ... Crystal structures of caspase-3 in complexes with isoquinoline-1,3,4-trione derivatives show that the catalytic cysteine is ... Caspase-3 is an attractive therapeutic target for treatment of diseases involving disregulated apoptosis. We report here the ...
Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ... Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ... Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ... Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ...
Caspases play an instrumental role in neurodegeneration in transgenic mSOD1G93A mice, which suggests that caspase inhibition ... a broad caspase inhibitor, delays disease onset and mortality. Moreover, zVAD-fmk inhibits caspase-1 activity as well as ... To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant ... Functional Role of Caspase-1 and Caspase-3 in an ALS Transgenic Mouse Model ...
The induction of PSP/reg was glucose dependent and mediated by caspase activation during apoptosis. Interestingly, the ... 1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; ... INS-1 Cells Undergoing Caspase-Dependent Apoptosis Enhance the Regenerative Capacity of Neighboring Cells. ... Inactivating mutations in transcription factor 1 (tcf-1)/hepatocyte nuclear factor1a (hnf1a) result in decreased β-cell mass ...
Cardioprotection Caspase-1 Ischemia/reperfusion injury Myocardial infarction P2Y12 receptor antagonist VX-765 ... Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term ... Syed FM, Hahn HS, Odley A, Guo Y, Vallejo JG, Lynch RA, Mann DL, Bolli R, Dorn GW (2005) Proapoptotic effects of caspase-1/ ... Holly TA, Drincic A, Byun Y, Nakamura S, Harris K, Klocke FJ, Cryns VL (1999) Caspase inhibition reduces myocyte cell death ...
In addition, caspase cleavage and p53 activation were found to be significantly enhanced in F3-treated THP-1 cells. We ... Jia-Wei Hsu,1 Hsuan-Cheng Huang,2 Shui-Tein Chen,1,3 Chi-Huey Wong,1,3,4 and Hsueh-Fen Juan1 ... 1Institute of Molecular and Cellular Biology, Department of Life Science, Graduate Institute of Biomedical Electronics and ... unraveled the role of caspases and p53 in F3-induced THP-1 cells differentiation into macrophages. Our results provide a ...
  • It was identified as the target of the baculoviral caspase inhibitor protein P35, which it cleaves and by which it is inhibited. (wikipedia.org)
  • Molecular model of caspase-1 complexed with an inhibitor. (sciencephoto.com)
  • Intracerebroventricular administration of zVAD-fmk, a broad caspase inhibitor, delays disease onset and mortality. (sciencemag.org)
  • We tested whether the caspase-1 inhibitor VX-765 given at reperfusion (a requirement for clinical use) can provide sustained reduction of infarction and long-term preservation of ventricular function in a pre-clinical model of ischemia/reperfusion that had been treated with a P2Y 12 receptor antagonist. (springer.com)
  • We set out to investigate whether the nebulized and inhaled specific caspase-1 inhibitor Ac-YVAD-CHO has the potential to attenuate the pulmonary and systemic release of the caspase-1-dependent cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) as well as their downstream enzymes iNOS and COX-2 in rat experimental endotoxaemia. (springer.com)
  • 0.05) in BALF were found in animals pretreated with inhaled caspase-1 inhibitor compared with animals without therapy. (springer.com)
  • Our data demonstrate that administration of the caspase-1 inhibitor Ac-YVAD-CHO by inhalation is able to reduce the pulmonary and systemic release of proinflammatory mediators in rat endotoxaemia. (springer.com)
  • Presence of the caspase 1 inhibitor Ac-YVAD-CMK significantly blocked the leukotoxin-induced lysis of monocytes only. (diva-portal.org)
  • We will test the hypothesis the caspase-1 inhibitor VX-765 will prevent or delay (pre-treatment) or reverse (post-treatment) α-SYN accumulation and aggregation and prevent (pre-treatment) or reverse (post-treatment) motor disability in α-SYN over-expressing pre-clinical models. (michaeljfox.org)
  • For one week, pre-clinical models will receive daily injections of the caspase-1 inhibitor VX-765 or vehicle. (michaeljfox.org)
  • Caspase-3 activities measured with or without Z-VAD-fmk (a broad spectrum caspase inhibitor) pretreatment by FRET techniques, caspase-3 activity measurement, and western blotting analysis. (sigmaaldrich.com)
  • In addition, THC treatment of splenocytes resulted in a decrease of Bcl-2 mRNA and protein as measured by Northern and Western blotting, respectively, and the drug induced apoptosis was blocked by the caspase inhibitor, Ac-Tyr-Val-Ala-L-aspartic acid aldehyde. (biomedsearch.com)
  • Caspase Inhibitor Enters Clinical Trial In Islet Transplantation As Treatment Fo. (bio-medicine.org)
  • SAN DIEGO and EDMONTON Alberta July 19 2012 /- Co... Preclinical studies support the use of a pan-caspase inhibitor therap. (bio-medicine.org)
  • SAN DIEGO and EDMONTON, Alberta, July 19, 2012 /PRNewswire/ -- Conatus Pharmaceuticals Inc. and the University of Alberta announced today the treatment of the first patient in an investigator-initiated islet cell transplant Phase I/II trial of emricasan (IDN-6556), a pan-caspase inhibitor. (bio-medicine.org)
  • Preclinical studies support the use of a pan-caspase inhibitor therapy to broaden the availability of clinical islet transplantation. (bio-medicine.org)
  • Emricasan is a novel small molecule inhibitor of activated caspases. (bio-medicine.org)
  • Also functions as a competitive inhibitor of caspase-1. (scbt.com)
  • ICT's caspase-1 inhibitor reagent, FAM-YVAD-FMK (kit catalog #9146) was used to monitor the caspase-1 induction response in Jurkat cells treated with Nigericin for various periods of time. (immunochemistry.com)
  • Our inhibitor studies further implicated CaMKII g in the activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) culminating in caspase-8/caspase-3 mediated apoptosis of HKM cells. (fluoridealert.org)
  • 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)
  • This in vitro assay employs the fluorescent inhibitor probe FAM-YVAD-FMK to label active caspase-1 enzyme in living cells. (immunochemistry.com)
  • Suspension cells were treated with an apoptosis-inducing agent or DMSO, a negative control, for 4 hours, washed twice, then incubated with ICT's green caspase-1 inhibitor probe, FAM-YVAD-FMK, for 1 hour and examined under a fluorescence microscope. (immunochemistry.com)
  • At these two stages, the effector caspase Dcp-1 and the inhibitor of apoptosis protein Bruce function to regulate both autophagy and starvation-induced cell death. (rupress.org)
  • This conclusion is supported by the observation that in HL-60/Apaf-1 cells, ectopic expression of dominant negative caspase-9, its inhibitory short isoform caspase-9b, or XIAP or treatment with the caspase inhibitor zVAD (50μ m ) inhibited Apaf-1-induced caspase-8 and Bid cleavage, mitochondrial ΔΨm, release of cyt c , and apoptosis. (aacrjournals.org)
  • In contrast, a transient transfection of dominant negative caspase-8 or CrmA or exposure to caspase-8 inhibitor zIETD-fmk inhibited the processing of procaspase-8 and Bid but did not inhibit the cytosolic accumulation of cyt c in either the untreated HL-60/Apaf-1 cells or the etoposide-treated HL-60/Apaf-1 and HL-60/neo cells. (aacrjournals.org)
  • but, the levels of IL-1β in the supernatant or lysate did not change in the presence of caspase-1 inhibitor. (bmj.com)
  • In addition, pretreatment of cells with 5Z-7-oxozeaenol, a selective TAK1 kinase inhibitor, enhanced the TRAIL-induced cleavage of caspases and binding of Annexin V. The TAK1-mediated antiapoptotic effects were also observed in human lung adenocarcinoma A549 cells. (aacrjournals.org)
  • The addition of a specific synthetic inhibitor of NF-κB abolished propofol-mediated HO-1 induction, suggesting a possible role for this nuclear transcriptional factor in our experimental conditions. (eurekaselect.com)
  • In the present study, we first treated a number of breast cancer cell lines with the proteasome inhibitor MG132 and observed that caspase-8 activation plays an important role in MG132-induced apoptosis. (asm.org)
  • Specifically, (i) in uninfected cells, BAD was processed by at least two proteolytic cleavages that were blocked by a general caspase inhibitor. (asm.org)
  • 2007) (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. (guidetopharmacology.org)
  • The μ-calpain inhibitor PD 151746 decreased oxLDL-induced cytotoxicity, whereas the general caspase inhibitor BAF (t-butoxycarbonyl-Asp-methoxyfluoromethylketone) had no effect. (biochemj.org)
  • 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)
  • Once inside the cell, the inhibitor binds covalently to the active caspase (10). (celltechnology.com)
  • Instead, their methodology is based on a unique cell-permeable and non-cytotoxic reagent called the Fluorochrome Inhibitor of Caspases (FLICA). (bio-rad-antibodies.com)
  • The FLICA reagent contains a caspase inhibitor sequence linked to a far-red fluorescent 660 dye. (bio-rad-antibodies.com)
  • As expected, expression levels of spliced Xbp1, Bip, EDEM, and Chop were increased after induction of ER stress by Tunicamycin (inhibitor of protein glycosylation) in THP-1 cells and LCLs. (biomedcentral.com)
  • The Caspase-1 Inhibitor I, also referenced under CAS 143313-51-3, controls the biological activity of Caspase-1. (emdmillipore.com)
  • A potent, specific, and reversible inhibitor of caspase-1 (K i = 200 pM for human recombinant caspase-1), caspase-4, and caspase-5. (emdmillipore.com)
  • 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)
  • Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells. (wikipedia.org)
  • Like other caspases, Sf caspase-1 is an aspartate-specific cysteine protease that is produced as an inactive proenzyme and becomes activated by autocatalytic cleavage. (wikipedia.org)
  • Just like with human caspases CASP3 or CASP7, the two cleavage fragments form heterodimers, which again form biologically active dimers-of-heterodimers consisting of two smaller and two larger fragments. (wikipedia.org)
  • Some experiments also showed cleavage of Sf caspase-1 at the residue Asp-184, resulting in an 18 kDa instead of 19 kDa fragment, however this result is likely an in vitro artefact. (wikipedia.org)
  • Cleavage of pNA peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. (anaspec.com)
  • Activation of downstream caspases through several stimuli leads to cleavage of target proteins and execution of the apoptotic program ( 13 ). (pnas.org)
  • I have tried western blotting for IL-1beta maturation and caspase-1 cleavage. (protocol-online.org)
  • Further, DNA degradation in caspase-1-dependent cell death is independent of ICAD cleavage, which is the substrate of caspase-3 and further supports the lack of caspase-3 involvement. (protocol-online.org)
  • In addition, caspase cleavage and p53 activation were found to be significantly enhanced in F3-treated THP-1 cells. (hindawi.com)
  • TRPC1 deficiency increases the secretion of IL-1β without modulating caspase-1 cleavage or cell death in cultured macrophages. (harvard.edu)
  • The Caspase-1 substrate sequence (NEAYVHDAPVRSLN) corresponds to the native cleavage site C-terminal to Asp-116 of the precursor IL-1β. (scbt.com)
  • 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)
  • Apaf-1+/− MEFs) or Apaf-1−/− MEFs also induced the processing of procaspase-9 and procaspase-8, Bid cleavage, and apoptosis. (aacrjournals.org)
  • This triggers the mitochondrial ΔΨm and cyt c release into the cytosol through a predominant mechanism other than cleavage of caspase-8 and/or Bid. (aacrjournals.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)
  • On the other hand, Caspase-1 cleavage induced by DICER1 knockdown in human RPE cells was inhibited by simultaneous antisense-mediated knockdown of Alu RNA. (arvojournals.org)
  • Several mechanisms have been proposed for the cytotoxic activity of proteasome inhibition, including stabilization of p53 ( 23 ) and the BH3-only proteins ( 37 ), cleavage of Mcl-1 ( 42 ), downregulation of XIAP and survivin ( 51 ), inhibition of NF-κB activity ( 3 ), and downregulation of the PI3K/Akt survival pathway ( 13 ). (asm.org)
  • 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 13 molecules. (researchandmarkets.com)
  • It also reviews key players involved in Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 3.4.22.56) targeted therapeutics development with respective active and dormant or discontinued projects. (researchandmarkets.com)
  • 4E-BP1 undergoes caspase-dependent cleavage in cells undergoing apoptosis. (asm.org)
  • Finally, (v) whereas cleavage of BAD at ASP56 and ASP61 has been reported and results in the generation of a more effective proapoptotic protein with an M r of 15,000, in this report we also show the existence of a second caspase-dependent cleavage site most likely at the ASP156 that is predicted to inactivate the proapoptotic activity of BAD. (asm.org)
  • The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. (usgs.gov)
  • Treating the HMEC-1 cells with oxLDL did not result in detectable activation of procaspase 3 or cleavage of PARP [poly(ADP-ribose) polymerase], but it did cause polyubiquitination of caspase 3, indicating inactivation and possible degradation of this protease. (biochemj.org)
  • Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reverse transcription polymerase chain reaction, and at the protein level by immunoblotting experiments using antibodies specific for the proform of caspase 1 and for its cleavage forms. (bmj.com)
  • Sequence analysis of processed proIL-18 demonstrated that cleavage sites of MMP-2 and MMP-8 differ from that of Caspase-1. (uni-koeln.de)
  • The Alzheimer's disease-associated presenilin (PS) 1 is intimately involved in gamma-secretase cleavage of beta-amyloid precursor protein and other proteins. (semanticscholar.org)
  • These enzymes participate in a series of reactions that are triggered in response to pro-apoptotic signals and result in cleavage of protein substrates, causing the disassembly of the cell (1). (celltechnology.com)
  • Caspases can be detected via immunoprecipitation, immuno-blotting techniques using caspase specific antibodies, or by employing fluorogenic substrates which become fluorescent upon cleavage by the caspase. (celltechnology.com)
  • Caspase mediated cleavage of desmoglein 1 leads to decreased expression at the cell surface and re-localization of its C terminus diffusely throughout the cytoplasm. (reactome.org)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. (wikipedia.org)
  • Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the active enzyme. (wikipedia.org)
  • Molecular cloning of the interleukin-1 beta converting enzyme. (drugbank.ca)
  • Alnemri ES, Fernandes-Alnemri T, Litwack G: Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. (drugbank.ca)
  • Kronheim SR, Mumma A, Greenstreet T, Glackin PJ, Van Ness K, March CJ, Black RA: Purification of interleukin-1 beta converting enzyme, the protease that cleaves the interleukin-1 beta precursor. (drugbank.ca)
  • 1998). Enzymatic activity of two caspases related to interleukin-1beta-converting enzyme. (anaspec.com)
  • 2000). Caspase 8: an efficient method for large-scale autoactivation of recombinant procaspase 8 by matrix adsorption and characterization of the active enzyme. (anaspec.com)
  • The ced-3 product is homologous to the mammalian interleukin 1β-converting enzyme ( 4 ). (pnas.org)
  • Caspase-1 is a protease, an enzyme that cleaves proteins. (sciencephoto.com)
  • Due to this activity caspase-1 is also known as ICE (interleukin-1-beta converting enzyme). (sciencephoto.com)
  • Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. (thermofisher.com)
  • This triggers the activation of the human enzyme caspase-1 and leads to pyroptosis, a fiery and highly inflammatory form of cell death. (thefreedictionary.com)
  • The extracellular adenosine activates the enzyme caspase-1 , which triggers production of the cytokine IL-1 beta, a critical player in inflammation, he said. (thefreedictionary.com)
  • These cleavages remove an -N[H.sub.2] peptide terminal and separate the small and large domains of the pro-enzyme so that it produces the mature hetero tetrameric caspases containing two large and two small domains. (thefreelibrary.com)
  • In the family, Caspase-3 in its inactive zymogens, pro-caspase-3 is a remarkable protein as the enzyme shows a large substrate diversity, as a variety of proteins have been cleaved in cell maintenance. (thefreelibrary.com)
  • The active caspase-3 enzyme is a heterodimer composed of two p17 and two p11 subunits. (scbt.com)
  • Plasma levels of IL-18 and its converting enzyme, caspase-1, were significantly elevated in CTCL. (aacrjournals.org)
  • IL-18, like IL-1β, is synthesized as an inactive precursor (pro-IL-18, 24 kDa) and then cleaved by the IL-1β-converting enzyme, caspase-1, into an active 18-kDa mature form and secreted. (aacrjournals.org)
  • Prior to its subclassification within the caspase family of proteases, caspase-1 was originally described as the IL-converting enzyme. (jimmunol.org)
  • Caspase-1/interleukin-converting enzyme (ICE) is a cysteine protease traditionally considered to have importance as an inflammatory mediator, but not as an apoptotic effector. (ahajournals.org)
  • The remaining green fluorescent signal is a direct measure of the active caspase-1 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)
  • Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce 2 subunits, large and small, that dimerize to form the active enzyme. (lsbio.com)
  • A synthetic peptide that irreversibly inhibits ICE (interleukin-1β converting enzyme, Ki = 0.76 nM) activity. (creative-enzymes.com)
  • Interleukin 1 and interleukin 1β converting enzyme (caspase 1) expression in the human colonic epithelial barrier. (bmj.com)
  • BACKGROUND Interleukin (IL) 1β converting enzyme (now known as caspase 1) is able to process pro-IL-1β into its active form and is involved in proapoptotic signalling. (bmj.com)
  • Interleukin (IL) 1β converting enzyme (formerly known as ICE and now as caspase 1) is a cysteine protease synthesised as a latent 45 kDa proenzyme that is proteolytically activated by unknown mechanisms into an active form composed of two subunits, one of 20 kDa and one of 10 kDa. (bmj.com)
  • The objective of this study was to examine the expression of IL-1β and its processing enzyme caspase 1 in the human colonic epithelium by using several complementary methodological approaches. (bmj.com)
  • Caspase-1 is a proinflammatory enzyme that is activated by the NLRP3 inflammasome in response to endoplasmic reticulum (ER) stress independent of the classical unfolded protein response. (biomedcentral.com)
  • Finally, we identify the AIM2/ASC-dependent caspase-1-independent pathway as an innate immune mechanism able to restrict bacterial replication in vitro and control IFN-γ levels in vivo in Casp1(KO) mice. (archives-ouvertes.fr)
  • The current study determined endometrial expression of caspase 1 (CASP1) and interleukin-18 (IL18) during the estrous cycle and early pregnancy, and following early estrogen administration, which induces conceptus loss during early development in pigs. (sigmaaldrich.com)
  • Similarly, STS stimulated robust IL-1β processing and release in Casp1 −/− Casp11 −/− BMDC that was IETD sensitive. (jimmunol.org)
  • Caspase 1 antibody LS-C353917 is an unconjugated rabbit polyclonal antibody to human Caspase 1 (CASP1). (lsbio.com)
  • CASP1 / Caspase 1 is a protein which is a member of the cysteine-aspartic acid protease (caspase) family. (lsbio.com)
  • In patients suffering from unexplained recurrent febrile episodes we detected several genetic variants of CASP1 leading to reduced enzymatic activity due to destabilization of the caspase-1 dimer interface. (biomedcentral.com)
  • We analyzed ER stress markers in THP-1 cells and lymphoblastoid cells lines (LCL, EBV transformed B cells) from healthy donors and individuals with CASP1 variants. (biomedcentral.com)
  • Furthermore, spliced XBP1 and Bip expression were significantly increased in unstimulated CASP1 knock-down THP-1 cells and in native patients' LCLs expressing variant caspase-1 with reduced enzymatic activity. (biomedcentral.com)
  • Besides, Interleukin 1 Alpha (IL1a) has been identified as an interactor of CASP1, thus a binding ELISA assay was conducted to detect the interaction of recombinant rat CASP1 and recombinant rat IL1a. (uscnk.com)
  • The binding activity of of CASP1 and IL1a was shown in Figure 1, and this effect was in a dose dependent manner. (uscnk.com)
  • The inflammasome complex is a ring complex composed of trimers of a signal specific sensor protein such as those of the NLR family and the AIM-1 (Absent in Melanoma) like receptors, an adaptor protein such as ASC, and a caspase, in this case Caspase-1. (wikipedia.org)
  • The protein Sf caspase-1 is the insect ortholog of the human effector caspases CASP3 (CPP32) and CASP7 (MCH3) in the species Spodoptera frugiperda (Fall armyworm). (wikipedia.org)
  • The N-terminal FADD-like death effector domain of Caspase 8 suggests that it may interact with Fas-interacting protein FADD. (thermofisher.com)
  • Caspase 8 binds to the death effector domain (DED) of FADD through an analogous DED domain present in tandem in the pro-form of the Caspase 8 protein. (thermofisher.com)
  • A gene on chromosome 11q23 that encodes a protein belonging to the cysteine-aspartic acid protease (caspase) family which, once activated by proteolytic processing, plays a central role in the execution-phase of cell apoptosis, as well as various stages of embryological development. (thefreedictionary.com)
  • A feature of the inflammasomes is the use of the adaptor ASC (apoptosis-related speck-like protein) to link NLRs to pro-caspase-1, a critical step in the activation of caspase-1. (frontiersin.org)
  • This caspase-8 initiates other downstream proteins including procaspase-3 in two ways: the first is a complex pathway, wherein caspase8 cleaves Bcl-2 interacting protein named Bid and also releases cytochrome-c. (thefreelibrary.com)
  • We will test the hypothesis that caspase-1 inhibition will down- regulate α-synuclein (α-SYN) at mRNA and/or protein levels within the SN and restore impaired function of the dopamine system in two pre-clinical models of Parkinson's disease (PD). (michaeljfox.org)
  • In our first experiment, we expect that caspase-1 inhibition will 1) reduce the expression of α-SYN mRNA and aggregated protein within SN, 2) block nigrostriatal dopaminergic degeneration (pretreatment experiment), 3) prevent or delay the onset of motor disability (pretreatment experiment), 4) reverse dopamine degeneration (post-treatment experiment) 5) reverse motor disability (post-treatment experiment) in transgenic α-SYN over expressing pre-clinical models. (michaeljfox.org)
  • In experiment 2, we expect that caspase-1 inhibition will 1) reduce α-SYN mRNA and protein levels within SN, 2) protect against nigrostriatal dopaminergic degeneration, and 3) reverse or retard motor disability in this AAV6-SYN induced pre-clinical PD model. (michaeljfox.org)
  • The human caspase-3 gene encodes a cytoplasmic protein that is highly expressed in lung, spleen, heart, liver, kidney and cells of the immune system. (scbt.com)
  • Our study revealed that apoptosis-associated specklike protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae . (jimmunol.org)
  • Pneumolysin (PLY), a 53-kDa multifunctional protein toxin that is produced by virtually all clinical isolates of pneumococcus, is one of the key virulence factors of S. pneumoniae ( 1 - 4 ). (jimmunol.org)
  • Activation of TLRs or receptors for proinflammatory cytokines (including IL-1β per se) induces the NF-κB-dependent expression of proIL-1β (33 kDa) as a cytosolic, biologically inactive precursor protein. (jimmunol.org)
  • We discovered that six cell death genes- death caspase-1 ( Dcp-1 ), hid , Bruce , Buffy , debcl , and p53 -as well as Ras-Raf-mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. (rupress.org)
  • Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous antiapoptotic protein. (aacrjournals.org)
  • Here, we report that ARC contributes to chemotherapy resistance by abolishing mitochondrial fission mediated by dynamin-related protein-1 (Drp1). (aacrjournals.org)
  • ARC is originally identified to be a caspase-inhibiting protein and can specifically inhibit the activation of caspase-2 and caspase-8, thereby blocking apoptosis induced by a variety of stimuli requiring the engagement of these caspases ( 1 ). (aacrjournals.org)
  • To clarify the molecular mechanism of TRAIL-induced apoptosis, we focused on transforming growth factor-β-activated kinase 1 (TAK1) mitogen-activated protein kinase (MAPK) kinase kinase, a key regulator of the TNF-α-induced activation of p65/RelA and c-Jun NH 2 -terminal kinase/p38 MAPKs. (aacrjournals.org)
  • This complex consists of trimerized receptors, the death domain-containing adaptor protein Fas-associated death domain, and caspase-8 ( 12 - 14 ). (aacrjournals.org)
  • Transforming growth factor-β-activated kinase 1 (TAK1) was originally identified as a MAPK kinase kinase (MAP3K), which can be activated by transforming growth factor-β, bone morphologic protein ( 20 ). (aacrjournals.org)
  • Recognizes endogenous levels of Caspase 1 protein. (lsbio.com)
  • Additionally, TT‑1 stimulated caspase‑3, caspase‑9 and Bax, and inhibited B‑cell lymphoma 2 mRNA and protein expression. (spandidos-publications.com)
  • This enhanced caspase-8 oligomerization and activation are promoted through its interaction with the ubiquitin-binding protein SQSTM1/p62 and the microtubule-associated protein light chain 3 (LC3), which are enriched at intracellular membranes in response to proteotoxic stress. (asm.org)
  • Our results unveiled a previously unknown mechanism through which disruption of protein homeostasis induces caspase-8 oligomerization, activation, and apoptosis. (asm.org)
  • Mucin 1 (MUC1) is a highly glycosylated transmembrane protein expressed on the apical surface of epithelial cells and is aberrantly overexpressed in the majority of malignant epithelial tumors, including breast, lung, ovarian, prostate and pancreatic cancer and several types of malignant hematological tumor ( 1 ). (spandidos-publications.com)
  • The occurrence of HCC is associated directly or indirectly with the abnormal expression of multiple genes, including B lymphoma Moloney murine leukemia virus insertion region 1 homolog (BMI1) ( 16 ), glypican-3 ( 17 ), heat shock protein 70 ( 18 ) and Sal-like protein 4 ( 19 ). (spandidos-publications.com)
  • An earlier report showed that the U S 3 protein kinase blocked the apoptosis induced by the herpes simplex virus 1 (HSV-1) d 120 mutant at a premitochondrial stage. (asm.org)
  • ii) In cells cotransduced with the U S 3 protein kinase, the BAD protein was not cleaved and the caspase 3 activity was not elevated. (asm.org)
  • We conclude that the primary effect of U S 3 was to block the caspases that cleave BAD at either residue 56 or 61 predicted to render the protein more proapoptotic or at residue 156, which would inactivate the protein. (asm.org)
  • The focus of the present study is on the U S 3 protein kinase shown in earlier studies to block apoptosis induced by d 120, an HSV-1 mutant lacking the gene encoding the infected cell protein no. 4, the major regulatory protein of the virus ( 19 , 21 ). (asm.org)
  • Studies from this laboratory showed that ectopically expressed HSV-1 U S 3 protein kinase blocks apoptosis induced by the d 120 mutant ( 19 , 21 ). (asm.org)
  • The Bcl-2 protein Bid was also cleaved during oxLDL-elicited cell death, and this was prevented by calpain inhibitors, but not by inhibitors of cathepsin B and caspases. (biochemj.org)
  • We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. (chinaphar.com)
  • The normal colonic epithelium strongly expressed caspase 1, both at the mRNA level and at the protein level in its latent form. (bmj.com)
  • Our results show that caspase 1 is present in 74% of epithelial preparations, both at the RNA and protein levels. (bmj.com)
  • LF cleaves members of the mitogen-activated protein kinase kinase family (MEKs) [1] - [2] . (prolekare.cz)
  • 2007) NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1 . (merckmillipore.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)
  • These observations raise the possibility that the salmonella pathogenicity island 1 type III secretion system cannot completely exclude 'promiscuous' secretion of flagellin and that the host capitalizes on this 'error' by activating a potent host-defense pathway. (nih.gov)
  • Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. (sciencemag.org)
  • Altogether, our data suggest that caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1. (harvard.edu)
  • Furthermore, we demonstrate that caspase-1-independent apoptosis requires the activation of caspase-9 and of the intrinsic pathway in a typical type II cell manner. (archives-ouvertes.fr)
  • In this paper, we describe the extrinsic pathway which are activated by death receptors like the tumour necrosis factor receptor (Fas receptor -APO-1 or CD95) that belongs to TNF receptor super family [8]. (thefreelibrary.com)
  • In the second simple pathway, caspase-8 cleaves procaspase-3 directly and activates it. (thefreelibrary.com)
  • These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. (sigmaaldrich.com)
  • We next characterized the morphological mode of PCD in these mice and show that the neurons degenerate by a caspase-independent, nonapoptotic pathway that involves autophagy. (jneurosci.org)
  • Together, these data indicate that, when key components of the type 1 apoptotic pathway (i.e., caspases and Apaf-1) are perturbed in vivo , developing postmitotic neurons nonetheless undergo quantitatively normal PCD by a caspase-independent pathway involving autophagy and not requiring AIF. (jneurosci.org)
  • In HeLa cells stably transfected with caspase-1, sensitisation to cisplatin was due to an amplification of the cisplatin-induced mitochondrial apoptotic pathway activation. (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)
  • 1-5 Antiapoptotic therapeutic strategies have been designed that target the evolutionarily conserved caspase (calcium-activated aspartate protease) apoptosis effector pathway. (ahajournals.org)
  • Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo . (biologists.org)
  • We investigated the involvement of the apoptosome in ER stress-induced cell death pathway using mouse embryonic fibroblasts (MEFs) and mice deficient for Apaf-1. (biologists.org)
  • These data collectively demonstrated that Apaf-1 and the mitochondrial pathway of apoptosis play significant roles in ER stress-induced apoptosis. (biologists.org)
  • 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)
  • Similarly, some POPs (Pyrin only proteins) are also known to regulate Caspase-1 activation through inhibition of inflammasome activation by binding to and blocking PYD interactions, which also play a role in the formation of the inflammasomes, though the exact mechanisms are not yet well established. (wikipedia.org)
  • The preclinical data demonstrate that DPP 8 and DPP 9 inhibition may cause the activation of caspase-1 which leads to an increase in a key cytokine, interleukin-1beta (IL-1beta). (thefreedictionary.com)
  • To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1 G93A ). (sciencemag.org)
  • Caspases play an instrumental role in neurodegeneration in transgenic mSOD1 G93A mice, which suggests that caspase inhibition may have a protective role in ALS. (sciencemag.org)
  • We further show that AIM2 engagement leads to ASC-dependent, caspase-1-independent activation of caspase-8 and caspase-9 and that caspase-1-independent death is reverted upon caspase-8 inhibition. (archives-ouvertes.fr)
  • Co-P.I. Dr. Petsko demonstrated previously that inhibition of caspase 3 protect nigral neurons in culture. (michaeljfox.org)
  • Mice deficient in AIF also exhibit quantitatively normal PCD of postmitotic neurons after caspase inhibition. (jneurosci.org)
  • Emricasan has shown specificity in assays measuring caspase inhibition, and reduced apoptosis in a variety of cellular assays. (bio-medicine.org)
  • Whereas one study of pharmacological caspase-3 inhibition reported decreased myocardial apoptosis and diminished infarct size, 7 the antithetic experiment of forced myocardial caspase-3 expression increased myocardial infarct size without clearly stimulating cardiomyocyte apoptosis. (ahajournals.org)
  • All potently blocked caspases-1, -4, -5 and -8 activity but exhibited negligible inhibition of caspases-2, -3 and -6. (portlandpress.com)
  • We show here that inhibition of proteasomal degradation results in an increased oligomerization and activation of caspase-8 on the cytosolic side of intracellular membranes. (asm.org)
  • Indeed, inhibition of the proteasomal and autophagolysosomal degradation pathways is clinically used or under investigation for treating cancer ( 1 , 4 , 12 , 18 , 38 , 54 , 55 ). (asm.org)
  • We went on to study the molecular mechanism and significance of caspase-8 activation in response to proteasome inhibition. (asm.org)
  • The above results indicate that MUC1 gene silencing induces growth inhibition in SMMC‑7721 cells through Bax‑mediated mitochondrial and caspase-8-mediated death receptor apoptotic pathways. (spandidos-publications.com)
  • Rabbit polyclonal Caspase-1 antibody. (abcam.com)
  • The following product was used in this experiment: Caspase 8 Polyclonal Antibody from Thermo Fisher Scientific, catalog # 13423-1-AP. (thermofisher.com)
  • This antibody can recognize the pro- and cleaved-caspase 8. (thermofisher.com)
  • Untreated and Staurosporine treated Jurkat cells were subjected to SDS PAGE followed by western blot with 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:300 incubated at room temperature for 1.5 hours. (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human heart tissue slide using 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:50 (under 10x lens). (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human heart tissue slide using 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:50 (under 40x lens). (ptglab.com)
  • Immunofluorescent analysis of () fixed HepG2 cells using 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:25 and Rhodamine-Goat anti-Rabbit IgG. (ptglab.com)
  • 1X10^6 HepG2 cells were stained with 0.2ug Caspase 9/p35/p10 antibody (10380-1-AP, red) and control antibody (blue). (ptglab.com)
  • Owing to the importance of CARD-CARD interactions in inflammasome formation, many COPs are known inhibitors of Caspase activation. (wikipedia.org)
  • Inhibitors Belnacasan (VX-765) Pralnacasan (VX-740) Activated Caspase 1 proteolytically cleaves pro IL-1β and pro IL-18 into their active forms, IL-1β and IL-18. (wikipedia.org)
  • Several studies have shown that these apoptosis inhibitors regulate the activation of caspases ( 16 , 17 ). (pnas.org)
  • Overexpression of Caspase 8 induces apoptosis, which can be blocked by inhibitors specific for the ICE family. (thermofisher.com)
  • Oxygen-free radical scavenger catalase and superoxide dismutase eliciting the inactivation of caspase-3 by the inhibitors confirm that ROS mediates the inactivation process. (rcsb.org)
  • Further mutagenesis study shows that the binding of the inhibitors with caspase-3 appears to be nonspecific. (rcsb.org)
  • Isoquinoline-1,3,4-trione derivative-catalyzed caspase-3 inactivation could also be observed when DTT is substituted with dihydrolipoic acid, which exists widely in cells and might play an important role in the in vivo inactivation process in which the inhibitors inactivate caspase-3 in cells and then prevent the cells from apoptosis. (rcsb.org)
  • These results provide valuable information for further development of small molecular inhibitors against caspase-3 or other oxidation-sensitive proteins. (rcsb.org)
  • Research Design: A total of 105 pre-clinical models (α-SYN over expressors, α-SYN knockouts, and wild-type) will comprise Experiment Groups (1-2) of one month old transgenic over-expressing pre-clinical models who will receive caspase-1 inhibitors (10 (low dose) or 50 (high dose) mg/kg, based on similarities to the Vertex compound) for 8 weeks. (michaeljfox.org)
  • Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. (biologists.org)
  • Caspase-1 and MyD88 activation in vivo were suppressed by intravitreous injection of known inhibitors. (arvojournals.org)
  • Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. (usgs.gov)
  • 2005) Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. (guidetopharmacology.org)
  • 2005) Caspase inhibitors: a pharmaceutical industry perspective. (guidetopharmacology.org)
  • The methodology is based on carboxyfluorescein (FAM) labeled fluoromethyl ketone (FMK)-peptide inhibitors of caspases. (celltechnology.com)
  • The insect immunophilin FKBP46 is a substrate of Sf caspase-1, which cleaves full length FKBP46 (~46 kDa) resulting in a ~25 kDa fragment. (wikipedia.org)
  • 1997). Substrate specificities of caspase family proteases. (anaspec.com)
  • Here, we identify the cationic channel subunit transient receptor potential channel 1 (TRPC1) as a substrate of caspase-11. (harvard.edu)
  • Caspase-1 substrate is an IL-1β convertase substrate. (scbt.com)
  • CONCLUSIONS The demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1β reinforces the concept that, under certain conditions, the epithelium could trigger an inflammatory reaction. (bmj.com)
  • Caspase enzymes specifically recognize a 4 amino acid sequence (on their substrate) which necessarily includes an aspartic acid residue. (celltechnology.com)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
  • Caspase-1 plays a fundamental role in innate immunity and in several important inflammatory diseases as the protease activates the pro-inflammatory cytokines proIL-1β and proIL-18. (nih.gov)
  • Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. (drugbank.ca)
  • A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. (drugbank.ca)
  • Additionally, inflammasome-induced activation of an intracellular caspase-1/calpain cysteine protease cascade degraded filamin, thereby severing bonds between the cytoskeleton and tissue factor (TF), the cell surface receptor responsible for coagulation activation. (nih.gov)
  • In the presence of dATP and cytochrome c , a molecule that is released from mitochondria during apoptosis, Apaf-1 binds to caspase-9 and induces the activation of caspase-3, a downstream death protease ( 20 ). (pnas.org)
  • Caspase 8 (CASP8) is a member of the cysteine-aspartic acid protease (caspase) family. (thermofisher.com)
  • Caspases exist as inactive proenzymes composed of a pro-domain, a large protease subunit, and a small protease subunit. (thermofisher.com)
  • 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)
  • A new independent 54 page research with title 'Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) - Pipeline Review, H2 2017'guarantees you will remain better informed than your competition. (medgadget.com)
  • Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) pipeline Target constitutes close to 6 molecules. (medgadget.com)
  • The latest report Caspase 7 - Pipeline Review, H2 2017, outlays comprehensive information on the Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (medgadget.com)
  • Furthermore, this report also reviews key players involved in Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) targeted therapeutics development with respective active and dormant or discontinued projects. (medgadget.com)
  • The present work aims to evaluate the in vivo role of this cytokine and its activating protease Caspase-1 in atherosclerosis. (uni-koeln.de)
  • Auf diesen Ergebnissen aufbauend besteht das Ziel der vorliegenden Arbeit darin, die in vivo Rolle von IL-18 und seiner aktivierenden Protease Caspase-1 in der Arteriosklerose am Mausmodell zu evaluieren. (uni-koeln.de)
  • Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. (nih.gov)
  • More recently, pyroptosis, a caspase-1-dependent type of programmed cell death, has been identified that is able to support secreted IL-1 and IL-18 in triggering an inflammatory response. (nih.gov)
  • Following infection, the inflammatory response increases expression of Caspase-1, by a positive feedback mechanism that amplifies the response. (wikipedia.org)
  • It is found predominantly in the cell cytoplasm, where it activates interleukin-1-beta, a molecule that mediates immune and inflammatory responses. (sciencephoto.com)
  • SUMMARY Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. (harvard.edu)
  • We showed that this anti-inflammatory effect of chrysophanol is through suppression of the activation of NF-kB and caspase-1 in LPS-stimulated macrophages. (mdpi.com)
  • Kim S-J, Kim M-C, Lee B-J, Park D-H, Hong S-H, Um J-Y. Anti-Inflammatory Activity of Chrysophanol through the Suppression of NF-kB/Caspase-1 Activation in Vitro and in Vivo . (mdpi.com)
  • Inflammatory caspases, such as caspase-1, play a critical role in the mechanism to trigger the lytic programmed cell death known as pyroptosis. (immunochemistry.com)
  • 4. NLRP3 inflammasome activation can be detected by ELISA or Western blot measuring secreted pro-inflammatory cytokines IL-1β or IL-18, or through the use of caspase-1 activation assays, such as ICT's Caspase-1 Assay Kits or Pyroptosis/Caspase-1 Assay Kit. (immunochemistry.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)
  • 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)
  • Caspase-1 is the best-described inflammatory caspase. (biovendor.com)
  • Endothelial cells (ECs) are critically involved in the pathogenesis of atherosclerosis by producing inflammatory mediators, including interleukin-1 beta (IL-1β). (bmj.com)
  • Dysregulated IL-1β function has been described in the pathology of a number of auto- or chronic inflammatory diseases, leading to this cytokine being described as the 'gatekeeper' of inflammation ( Dinarello, 2011c ). (biologists.org)
  • IL-1β secretion is proposed to occur via a number of different mechanisms, ranging from lysosomal and microvesicular to pyroptotic, dependent on the strength of the inflammatory stimulus and the cell type in question ( López-Castejón and Brough, 2011 ). (biologists.org)
  • Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. (clinsci.org)
  • This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. (clinsci.org)
  • Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. (usgs.gov)
  • Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. (usgs.gov)
  • We showed that isosibiricin (10−50 μM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-18 (IL-18). (chinaphar.com)
  • Finally, the presence of mature/processed IL-18 in atherosclerotic tissue of Caspase-1-deficient mice highlighted the potential in vivo relevance of such an alternative, MMP-mediated IL-18 activation mechanism for this pro-inflammatory disease. (uni-koeln.de)
  • Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs. (nih.gov)
  • We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1β and IL-18, were protected against ischemic acute renal failure (ARF). (jci.org)
  • Caspase is a family of cysteine proteases, with specific cysteine residue that cleaves proteins after the aspartic acid residue, a specificity which is not normal among proteases to produce the active mature caspases [5]. (thefreelibrary.com)
  • Out of the complex DFF40 and DFF45 (DNA fragmentation factor 45), the caspase-3 cleaves DFF45 and as a result of that, DFF45 dissociates from DFF40, causing oligomerization of DFF40 which has DNase activity. (thefreelibrary.com)
  • At the onset of apoptosis, caspase-3 proteolytically cleaves PARP at an Asp216-Gly217 bond. (scbt.com)
  • Caspase-3 cleaves and activates SREBPs between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. (scbt.com)
  • Caspase-3 also cleaves and activates caspase-6, -7 and -9. (scbt.com)
  • NE enters ECs, cleaves proIL-1β (31kDa) inside cells resulting in release of active isoforms of IL-1β in microparticles. (bmj.com)
  • Activated m-calpain cleaves Bcl-X L and proteolytically activates caspase-12 ( Nakagawa and Yuan, 2000 ). (biologists.org)
  • The initiator caspases including caspase-1 , -8, -9, typically caspase-8 and caspase-9, are activated by two alternative pathways (Salvesen and Dixit, 1997). (thefreedictionary.com)
  • The formation of active caspases forms a cascade in which initiator caspases (8, 9) interact with the downstream effector molecules (3, 7) to facilitate their own activation. (thefreelibrary.com)
  • In apoptosis, caspases are responsible for proteolytic cleavages that lead to cell disassembly (effector caspases), and are involved in upstream regulatory events (initiator caspases). (celltechnology.com)
  • Activated Caspase 8 then activates other downstream caspases including Caspase 9, thereby committing the cell to undergo apoptosis. (thermofisher.com)
  • Although this normal programmed cell death (PCD) can occur by distinct morphological pathways ( Clarke, 1990 , 1998 ), the biochemical and molecular pathways involved have been generally considered to require a relatively conserved core of so-called "proapoptotic" genes comprised of Bcl-2 family members, the apoptosome (cytochrome c , Apaf-1, caspase 9) and downstream caspases (e.g., caspase-3). (jneurosci.org)
  • These events were secondary to the activity of the downstream caspases induced by Apaf-1. (aacrjournals.org)
  • Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1-/- mice from ARF. (jci.org)
  • Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT-leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1beta. (nih.gov)
  • This procaspase-9 comes and activates caspase-9 and simultaneously this activates procaspase-3 and then activates caspase-3. (thefreelibrary.com)
  • ATP activates the P2X7 receptor, resulting in rapid assembly of the inflammasome, an IL-1β-activation and -processing platform. (biologists.org)
  • Whereas these 'canonical' activities are well appreciated, this review also highlights less-known pathways and molecules activated by caspase-1. (nih.gov)
  • However, there is increasing evidence that caspase-1 contributes to innate and adaptive immunologic defense mechanisms, repair and pathologic conditions by the regulation of several different and partially opposing pathways. (nih.gov)
  • you can check caspase-3 activation or other proteins to make sure cell death pathways are activated. (protocol-online.org)
  • All different pathways end up with activation of caspase-3. (protocol-online.org)
  • Both pathways finally end up in the level of activation of caspases for cell death. (thefreelibrary.com)
  • Caspases are enzymes responsible for executing apoptotic pathways, or programmed cell death and are also involved in processing cytokines involved in inflammation. (bio-medicine.org)
  • Poxviruses employ numerous strategies to achieve this goal [ 1 ], including the expression of multiple proteins that inhibit various components of host cell death pathways [ 2 , 3 ]. (portlandpress.com)
  • Rather, TAK1 was recently found to be a crucial regulator of the JNK, p38, and p65 pathways in response to TNF-α, interleukin-1, and ligands of Toll-like receptor, such as lipopolysaccharide ( 21 - 26 ). (aacrjournals.org)
  • However, the role of TAK1 in the TRAIL-induced p65/JNK/p38 pathways and caspase-mediated apoptotic cell death remains to be investigated. (aacrjournals.org)
  • In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathways may be involved in tumour formation and/or may confer resistance to treatment. (bmj.com)
  • Caspase-1: the inflammasome and beyond. (nih.gov)
  • Caspase-1 itself is activated in different inflammasome complexes, which assemble in response to a variety of exogenous and endogenous stressors. (nih.gov)
  • Caspase-1, normally in its physiologically inactive zymogen form, autoactivates when it is assembled into the filamentous inflammasome complex by autoproteolysis into the p10 and p20 subunits. (wikipedia.org)
  • INCA, on the other hand, directly blocks inflammasome assembly by capping Caspase-1 CARD oligomers, thus blocking further polymerization into the inflammasome filaments. (wikipedia.org)
  • Caspase-11 controls interleukin 1β (IL-1β) secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide (LPS) and Gram-negative bacteria. (harvard.edu)
  • In mouse macrophages cytosolic flagellin promote the assembly of the NLRC4 inflammasome inducing the activation of caspase-1 and secretion of IL-1β and IL-18. (frontiersin.org)
  • evaluated the inflammasome and found that unlike in non-permissive mouse macrophages, Legionella did not induce caspase-1 activation in human monocytes. (frontiersin.org)
  • The inflammasome is a signalling platform leading to caspase-1 activation. (archives-ouvertes.fr)
  • This is critical for the oligomerization of the NLRP3 inflammasome and activation of caspase-1 in pyroptosis. (immunochemistry.com)
  • It acts as a potassium ionophore, inducing a net decrease in intracellular levels of potassium, which is crucial for oligomerization of the NLRP3 inflammasome and activation of caspase-1. (immunochemistry.com)
  • 3. Use Nigericin at 1-20 µM to induce NLRP3 inflammasome activation in cells. (immunochemistry.com)
  • The most intensively studied inflammasome comprises an oligomeric complex of procaspase-1 with the NLRP3 and ASC adapter proteins that rapidly assembles in response to diverse stress stimuli such as increased reactive oxygen species (ROS) ( 3 ), mitochondrial dysfunction ( 4 ), perturbation of intracellular ion homeostasis ( 5 - 7 ), disruption of lysosomal membrane integrity ( 8 ), and activation of deubiquitinases ( 9 - 11 ). (jimmunol.org)
  • Pro-Caspase-1, once activated by an inflammasome complex is processed into p20 and p10 subunits that assembles to form a p20-p20 /p10-p10 active complex that is secreted by a nonconventional (non-ER-dependent) mechanism. (biovendor.com)
  • Monocytes from ACS patients are 'primed' to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β. (clinsci.org)
  • Here, we reveal that DICER1 is an essential endogenous negative regulator of NLRP3 inflammasome activation, and that DICER1 deficiency leads to Alu RNA and Caspase-1-mediated, MyD88-dependent, microRNA-independent RPE degeneration. (arvojournals.org)
  • I'm using THP-1 cells which I differentiate to macrophages using PMA. (protocol-online.org)
  • We unraveled the role of caspases and p53 in F3-induced THP-1 cells differentiation into macrophages. (hindawi.com)
  • AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. (archives-ouvertes.fr)
  • Francisella tularensis, the agent of tularaemia, triggers AIM2/ASC-dependent caspase-3-mediated apoptosis in caspase-1-deficient macrophages. (archives-ouvertes.fr)
  • Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. (biomedsearch.com)
  • We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1β and IL-18 in macrophages infected with S. pneumoniae . (jimmunol.org)
  • To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae , we examined the involvement of inflammasomes in inducing this cellular response. (jimmunol.org)
  • Caspase-1 activation was partially impaired in NLRP3 −/− macrophages, whereas knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae . (jimmunol.org)
  • Moreover, VX-765 decreased circulating IL-1β, prevented loss of cardiac glycolytic enzymes, preserved mitochondrial complex I activity, and decreased release of lactate dehydrogenase, a marker of pyroptosis. (springer.com)
  • Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of DeltaPsim and the activation of caspase-3. (sigmaaldrich.com)
  • In this report, we demonstrate that in HL-60/Apaf-1 cells, the activity of caspase-9 and -3 induced by Apaf-1 overexpression was associated with a significant increase (5-fold) in the cytosolic accumulation of cytochrome c (cyt c ), loss of mitochondrial membrane potential (ΔΨm), and an increase in the reactive oxygen species. (aacrjournals.org)
  • This mechanism may involve a cytosolic mitochondrial permeability transition factor, which may be processed and activated by the downstream effector caspases, thereby completing an amplifying feedback loop, which triggers the mitochondrial events during apoptosis. (aacrjournals.org)
  • MitoCasp A simultaneous dual parameter Assay For: Mitochondrial Membrane Potential Detection & Caspase (poly, 3/7, 8, 9, 1) Activity. (celltechnology.com)
  • Simultaneous detection of mitochondrial membrane potential and caspase activity. (celltechnology.com)
  • Utilizing these two reagents in combination Caspase activity and mitochondrial membrane potential can be analyzed simultaneously. (celltechnology.com)
  • There is evidence that caspase-1 supports cell survival by activation of NF-κB, induction of membrane repair and regulation of unconventional secretion of certain proteins. (nih.gov)
  • The physiologic effects of processing of other downstream targets, such as proteins involved in glycolysis or activation of caspase-7, are less well understood. (nih.gov)
  • Instead, it is thought to inhibit Caspase-1 activation by interfering with the interaction of Caspase-1 with other important CARD containing proteins. (wikipedia.org)
  • 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)
  • Despite its key role in initiating inflammation, many aspects of IL-1β activity remain poorly understood, in part due to its unconventional secretion mechanism but also due to the complex array of proteins involved in its activation ( Schroder and Tschopp, 2010 ). (biologists.org)
  • For Caspase-1, genes for specific COPs-ICEBERG, COP1 (ICE/Pseudo-ICE), and INCA (Inhibitory Card)-are all found near its locus, and are thus thought to have emerged from gene duplication events and subsequent deletions of the catalytic domains. (wikipedia.org)
  • Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. (drugbank.ca)
  • Interestingly, the supernatant from DN-HNF1A-expressing cells, but not DN-HNF1A-expressing cells treated with zVAD.fmk, was sufficient to induce PSP/reg gene expression and increase cell proliferation in naïve, untreated INS-1 cells. (diabetesjournals.org)
  • Dynamic gene expression profiles showed that cell differentiation was induced in F3-treated THP-1 cells. (hindawi.com)
  • Apoptosis is programed cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. (biomedsearch.com)
  • However, autophagy does not appear to be involved in the normal PCD of postmitotic neurons in which caspases and Apaf-1 are present and functional because quantitatively normal neuronal PCD occurred in the absence of a key gene required for autophagy (ATG7). (jneurosci.org)
  • 10-12 This conclusion is based largely on the phenotype obtained with caspase-1 gene ablation: caspase-1 −/− mice had no mature interleukin-1β (IL-1β) or IL-18 and were defective in producing IL-1α, IL-6, and tumor necrosis factor-α (TNF-α) in response to lipopolysaccharide. (ahajournals.org)
  • Further investigation using western blotting revealed that cytochrome c was released from the mitochondria into the cytoplasm, and caspase‑8 and caspase‑9 were activated in MUC1 gene‑silenced SMMC‑7721 cells. (spandidos-publications.com)
  • In addition, results from the co‑immunoprecipitation experiments demonstrated that the MUC1 cytoplasmic tail can bind directly to Bax or caspase‑8 and these interactions were reduced upon MUC1 gene silencing in SMMC‑7721 cells. (spandidos-publications.com)
  • 1 Furthermore, several lines of evidence suggest that caspase 1, a mammalian homologue of the Caeonorhabditis elegans cell death gene CED-3, is involved in apoptosis. (bmj.com)
  • Overexpression of the murine caspase 1 gene induces apoptosis in Rat-1 cells, which is abrogated by mutations in the catalytic Cys residue. (bmj.com)
  • Each caspase contains conserved residues important for specific proteolytic activity cleaving after aspartic acid residues ( 13 ). (pnas.org)
  • During the execution of the apoptotic cascade, activated caspase-3 releases SREBP from the membrane of the ER in a proteolytic reaction that is distinct from their normal sterol-dependent activation. (scbt.com)
  • 1 2 Caspase 1 is responsible for the proteolytic conversion of the 31 kDa inactive cytokine precursor pro-IL-1β into its 17 kDa active form. (bmj.com)
  • Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis. (semanticscholar.org)
  • The central component of this process is a cascade of proteolytic enzymes called caspases. (celltechnology.com)
  • As is common with other proteases, caspases are synthesized as precursors that undergo proteolytic maturation, either autocatalytically or in a cascade by enzymes with similar specificity (5). (celltechnology.com)
  • Caspase-1 also controls the secretion of IL-1E-, but the mechanism and route of secretion are unknown. (thefreedictionary.com)
  • In our previous study, we found that fucose-containing polysaccharide fraction F3 extracted from Ganoderma lucidum can bring about cytokine secretion and cell death in human leukemia THP-1 cells. (hindawi.com)
  • Consistently, trpc1−/− mice show higher IL-1β secretion in the sepsis model of intraperitoneal LPS injection. (harvard.edu)
  • Furthermore, ASC −/− mice were more susceptible than wild-type mice to S. pneumoniae , with impaired secretion of IL-1β and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae . (jimmunol.org)
  • This is the first description of the secretion of IL-1β by microvesicle shedding from ECs which is caspase-1 independent. (bmj.com)
  • Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. (biologists.org)
  • Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. (biologists.org)
  • However, it has not been possible to combine the key features of such models to determine, in an intact organism, the vesicular component of IL-1β secretion and how IL-1β is specifically targeted to effector cells. (biologists.org)
  • As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. (usgs.gov)
  • These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation. (usgs.gov)
  • Additionally rTgPrx treatment reduced caspase-1 activity and IL-1β secretion, while simultaneously increasing IL-10 release. (youscribe.com)
  • Quantification of IL-1β, IL-8, and TNF-α secretion was performed by cytometric bead arrays. (biomedcentral.com)
  • In THP-1 cells such induction of ER stress lead to secretion of IL-1β, IL-8, and TNF-α. (biomedcentral.com)
  • Caspase-1-dependent programmed cell death (known as pyroptosis) is a unique form of cell death that does not depend on the activation of caspase-3. (protocol-online.org)
  • Caspase-1 causes pyroptosis, a necrotic-like cell death. (archives-ouvertes.fr)
  • Sequential activation of caspases play a central role in the execution-phase of cell apoptosis. (thermofisher.com)
  • Fluoride-induced headkidney macrophage cell apoptosis involves activation of the CaMKIIg-ERK 1/2-caspase-8 axis: the role of superoxide in initiating the apoptotic cascade. (fluoridealert.org)
  • By contrast, MUC1 interacts directly with several signaling molecules, including p53 ( 11 , 12 ), HSP70/90 ( 13 , 14 ) and caspase-8 ( 15 ) to regulate cell apoptosis. (spandidos-publications.com)
  • Here we show that a mammalian homolog of CED-4, Apaf-1, can associate with several death proteases, including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. (pnas.org)
  • A family of cysteine proteases (designated caspases) related to the C. elegans CED-3 appears to represent the effector arm of the apoptotic program ( 13 ). (pnas.org)
  • The N-terminal region of Apaf-1 shares amino acid homology with CED-4 and the prodomains of CED-3 and several CED-3-like proteases with long prodomains. (pnas.org)
  • The region of homology shared between Apaf-1 and the prodomains of CED-3-like proteases has been termed caspase recruitment domain ( 19 ). (pnas.org)
  • Pugin J, Ricou B, Steinberg K, Suter P, Martin T (1996) Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS: a prominent role for interleukin-1. (springer.com)
  • IL-1β is a pleiotropic proinflammatory cytokine that is predominantly expressed in myeloid leukocytes. (jimmunol.org)
  • 11 It is generally felt that the most relevant actions of capsase-1 are proinflammatory, being related to cytokine processing. (ahajournals.org)
  • Both caspase-1 and caspase-3, ie, the prototypical proinflammatory and proapoptotic caspases, are upregulated in diseased hearts. (ahajournals.org)
  • 22 Assigning a meaningful role for upregulated caspase-1 in cardiomyocyte apoptosis is also controversial because its dominant function in the heart is assumed to be proinflammatory rather than proapoptotic. (ahajournals.org)
  • These data indicate that ER stress induced activation of wildtype caspase-1 might be involved in a negative feed back reduction of ER stress and that impaired caspase-1 activity might allow for a perpetuation of ER stress thus contributing to the proinflammatory phenotype of our patients. (biomedcentral.com)
  • These experiments demonstrate that Bcl-X L associates with caspase-9 and Apaf-1, and show that Bcl-X L inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans. (pnas.org)
  • The apoptotic mechanism is evolutionarily conserved and controlled by a genetic program ( 1 - 3 ). (pnas.org)
  • However, the precise mechanism by which Bcl-2 and Bcl-X L control caspase activation and apoptosis remains controversial. (pnas.org)
  • We report here the mechanism of caspase-3 inactivation by isoquinoline-1,3,4-trione derivatives. (rcsb.org)
  • CONCLUSIONS Our results suggest that apoptosing INS-1 cells shed microparticles that may stimulate PSP/reg induction in neighboring cells, a mechanism that may facilitate the recovery of β-cell mass in HNF1A-MODY. (diabetesjournals.org)
  • However, we still know very little about the downstream mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. (harvard.edu)
  • This study investigates the effect of neutrophil elastase (NE) on ECs in terms of IL-1β release and explores the underlying mechanism. (bmj.com)
  • NE is detected in the endothelium of murine atherosclerotic plaques and, therefore, this is a plausible mechanism to promote local IL-1β release in the vasculature. (bmj.com)
  • Although doxorubicin may initiate apoptotic program by using molecules such as p53, reactive oxygen species, and caspases ( 7 , 8 ), the detailed mechanism by which doxorubicin induces apoptosis has not been fully clarified. (aacrjournals.org)
  • Bcl-X L , an antiapoptotic member of the Bcl-2 family, was shown to physically interact with Apaf-1 and caspase-9 in mammalian cells. (pnas.org)
  • Expression of Bcl-X L inhibited the association of Apaf-1 with caspase-9 in mammalian cells. (pnas.org)
  • Recent studies have identified and partially characterized Apaf-1, a mammalian homolog of C. elegans CED-4 ( 18 ). (pnas.org)
  • Caspase-1/ICE was the first mammalian caspase to be described. (ahajournals.org)
  • The orthologs differed markedly in their propensity to inhibit non-mammalian caspases. (portlandpress.com)
  • The mammalian caspases play distinct roles in apoptosis and inflammation. (celltechnology.com)
  • The Caspase FLICA Kits are suitable for cells in suspension and adherent cells from many species including mammalian, insect and yeast. (bio-rad-antibodies.com)
  • pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. (anaspec.com)
  • Caspase substrates and cellular remodeling. (semanticscholar.org)
  • Significantly, recombinant Bcl-X L purified from Escherichia coli or insect cells inhibited Apaf-1-dependent processing of caspase-9. (pnas.org)
  • In addition, Caspase 8 also reacts with Jurkat cells and Tonsil. (thermofisher.com)
  • The expression of mast cells-derived caspase-1 was suppressed by NJJ in AD-like lesional skin. (thefreedictionary.com)
  • Caspase-1 expression in multiple sclerosis plaques and cultured glial cells. (thefreedictionary.com)
  • Here, we investigated the effect of a dominant-negative HNF1A mutant (DN-HNF1A) induced apoptosis on the regenerative capacity of INS-1 cells. (diabetesjournals.org)
  • RESEARCH DESIGN AND METHODS DN-HNF1A was expressed in INS-1 cells using a reverse tetracycline-dependent transactivator system. (diabetesjournals.org)
  • Further experiments demonstrated that annexin-V-positive microparticles originating from apoptosing INS-1 cells mediated the induction of PSP/reg . (diabetesjournals.org)
  • We integrated time-course microarray analysis and network modeling to study the F3-induced effects on THP-1 cells. (hindawi.com)
  • Furthermore, F3-treated THP-1 cells exhibited enhanced macrophage differentiation, as demonstrated by changes in cell adherence, cell cycle arrest, NBT reduction and expression of differentiation markers including CD11b, CD14, CD68, matrix metalloproteinase-9 and myeloperoxidase. (hindawi.com)
  • Our results provide a molecular explanation for the differentiation effect of F3 on human leukemia THP-1 cells and offer a prospect for a potential leukemia differentiation therapy. (hindawi.com)
  • Apoptosis or programmed cell death is a physiological process in which cells respond to a variety of stimuli and undergo a controlled and regulated manner of cell death [1, 2, 3]. (thefreelibrary.com)
  • Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. (sigmaaldrich.com)
  • In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. (sigmaaldrich.com)
  • These data suggest that THC treatment of cultured immune cells induces apoptosis through the regulation of Bcl-2 and caspase activity. (biomedsearch.com)
  • 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)
  • Previous studies have shown that caspases and Apaf-1 are required for the normal programmed cell death (PCD) in vivo of immature postmitotic neurons and mitotically active neuronal precursor cells. (jneurosci.org)
  • Although normally these cells use caspases for PCD, in the absence of caspase activity these neurons undergo a distinct nonapoptotic type of degeneration. (jneurosci.org)
  • These studies clearly demonstrate that the extensive PCD of immature postmitotic neurons and mitotically active progenitor cells in the nervous system require cytochrome c , Apaf-1, and caspases. (jneurosci.org)
  • It has been shown to generate a robust caspase-1 activation response in various cell lines, including Jurkat and THP-I cells. (immunochemistry.com)
  • the longer the cells were exposed to Nigericin, the larger the proportion of caspase-1 positive cells found in the sample. (immunochemistry.com)
  • Caspase-1 expression mediated by an adenoviral vector was able to kill directly cells and to sensitise the remaining cells to cisplatin or γ-radiation in vitro. (csic.es)
  • We conclude that fluoride -induced apoptosis is largely dependent on Ca 2+ induced superoxide generation leading to elevation in CaMKII g which in turn induces the phosphorylation of ERK 1/2 and downstream activation of extrinsic caspase cascade in HKM cells. (fluoridealert.org)
  • In tumor-bearing mice treated with oxaliplatin, NLRP3-dependent IL-1β release from dendritic cells (DCs) occurs via paracrine activation of P2X7 receptors (P2X7R) in response to ATP released from dying tumor cells ( 12 ). (jimmunol.org)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • 5. Add diluted FLICA to each sample at 1:30 (e.g., add 10 μL to 290 μL of cultured cells). (immunochemistry.com)
  • The top images reveal several experimental cells, all of which fluoresce green, therefore they have active caspase-1. (immunochemistry.com)
  • none of these cells have active caspase-1 (Dr. Brian W. Lee, ICT). (immunochemistry.com)
  • Human coronary artery endothelial cells (HCAEC) were treated with a combination of tumour necrosis factor-alpha and interleukin-1 alpha then incubated with NE for 2 or 6 h. (bmj.com)
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a typical member of the TNF-α ligand family that induces apoptosis in various types of tumor cells but not in most normal cells ( 1 - 3 ). (aacrjournals.org)
  • Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 μM) in the presence or absence of propofol (40 μM, 80 mM and 160 μM). (eurekaselect.com)
  • Rosaria Acquaviva, Agata Campisi, Giuseppina Raciti, Roberto Avola, Maria Luisa Barcellona, Luca Vanella and Giovanni Li Volti, " Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1", Current Neurovascular Research (2005) 2: 141. (eurekaselect.com)
  • Alu RNA-induced Caspase-1 activation in human RPE cells was inhibited by DICER1 overexpression. (arvojournals.org)
  • Furthermore, a tumor‑xenograft model was established to investigate the apoptotic mechanisms of TT‑1 on TT cells. (spandidos-publications.com)
  • The results obtained indicated that TT‑1 was able to suppress the proliferation of TT cells and exhibited low cytotoxicity to normal thyroid cells in vitro. (spandidos-publications.com)
  • The apoptotic rates of TT cells were also increased following TT‑1 treatment. (spandidos-publications.com)
  • In summary, TT‑1 may inhibit the proliferation of TT cells by inducing apoptosis in vitro and in vivo, indicating that TT‑1 may be a potential candidate for the treatment of thyroid cancer. (spandidos-publications.com)
  • Apaf-1-deficient MEFs showed more resistance to ER stress-inducing reagents as compared with wild type cells. (biologists.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)
  • 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)
  • The untreated transduced cells expressed elevated caspase 3 activity. (asm.org)
  • Two diametrically opposed events take place in cells infected with herpes simplex virus 1 (HSV-1) and also in cells infected with many other viruses. (asm.org)
  • In the human SK-N-SH cells, the events leading to the proapoptotic death of the cells are caspase independent. (asm.org)
  • Results: The TF signaling complexes were shown to prevent apoptosis induced by serum starvation and TRAIL in cancer cells by reduced activation of caspase-8 in a PI3k/AKT-dependent manner. (diva-portal.org)
  • Detection:10380-1-AP 1:200) with HeLa cells lysate 2500 ug. (ptglab.com)
  • In the present study we made the novel observation that oxLDL-induced death of HMEC-1 cells is accompanied by activation of calpain. (biochemj.org)
  • Also, oxLDL provoked calpain-dependent proteolysis of cytoskeletal α-fodrin in the HMEC-1 cells. (biochemj.org)
  • AIMS To characterise IL-1 and caspase 1 expression in human colonic epithelial cells. (bmj.com)
  • First isolated from monocytic cells, caspase 1 has been recently found in other cell types-for example, keratinocytes, where its main function is to convert pro-IL-1β into mature IL-1β under irritant stress. (bmj.com)
  • Additional experiments employing chimeric mice, that lacked the IL-18R alpha on either the hematopoietic or the vascular cells, generated by bone-marrow transplantation, revealed that IL-18R alpha does not participate in the pro-atherogenic effects of IL-18 Surprisingly, deficiency of Caspase-1 did not diminish atherogenesis, thus suggesting alternative mechanisms of IL-18 activation during atherosclerosis. (uni-koeln.de)
  • The FLICA 660 caspase-1 kit uses a target sequence (YVAD) sandwiched between a far-red fluorescent 660 dye and a fluoromethylketone (FMK) to make a quick and flexible method to analyze active caspase-1 in apoptotic cells. (bio-rad-antibodies.com)
  • Additionally, we knocked down endogenous caspase-1 in THP-1 cells to analyze caspase-1 involvement in ER stress responses. (biomedcentral.com)
  • Strongly inhibits anti-APO-1 induced apoptosis in L929-APO-1 cells. (emdmillipore.com)
  • Caspase-1 is evolutionarily conserved in many eukaryotes of the Kingdom Animalia. (wikipedia.org)
  • The Sf caspase-1 proenzyme is cleaved after the amino acid residues Asp-28 and Asp-195, resulting in a smaller 12 kDa fragment and a larger 19 kDa fragment. (wikipedia.org)
  • 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)
  • Expression of Apaf-1 enhanced the killing activity of caspase-9 that required the CED-4-like domain of Apaf-1. (pnas.org)
  • The lack of caspase-1 activation could be explained by the ability of Legionella to inhibit the expression of NLRC4 and, to a lesser extent, ASC. (frontiersin.org)
  • Though lysis requires expression of the receptor lymphocyte function-associated molecule 1 (LFA-1) on the cell surface, not all LFA-1-expressing leukocyte populations are equally susceptible to the toxin. (diva-portal.org)
  • In this study, the susceptibility of human leukocytes to leukotoxin-induced lysis is compared to their expression of LFA-1 and the activity of caspase 1. (diva-portal.org)
  • Similar LFA-1 expression was found in all susceptible cell populations irrespective of their degree of sensitivity to the toxin. (diva-portal.org)
  • Ectopic expression of caspase-1 has been shown to trigger apoptosis. (csic.es)
  • In patients, high levels of caspase-1 expression may be associated with spontaneous regression in neuroblastomas and with a good clinical response to chemotherapy in acute myeloid leukemia and osteosarcoma. (csic.es)
  • Endometrial caspase 1 and interleukin-18 expression during the estrous cycle and peri-implantation period of porcine pregnancy and response to early exogenous estrogen administration. (sigmaaldrich.com)
  • Here, the consequences of increased myocardial expression of procaspase-1 were examined on the normal and ischemically injured heart. (ahajournals.org)
  • 17-21 However, data supporting a pathophysiological effect of increased myocardial caspase expression have been inconsistent. (ahajournals.org)
  • In this study, we used forced myocardial expression of inactive procaspase-1 in normal and ischemic hearts to address the following questions: (1) Can caspase-1 be activated in cardiac myocytes? (ahajournals.org)
  • No remarkable effects were seen on NALP3 or caspase-1 expression in EC lysates. (bmj.com)
  • Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. (biologists.org)
  • Appropriate propofol concentrations (ranging from 40 μM to 160 μM) significantly increased HO- 1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. (eurekaselect.com)
  • Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 μM) or sultopride (1 μM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1β. (chinaphar.com)
  • Here our experiments show that rTgPrx promotes AAM as indicated by high arginase-1 (arg-1), YM1 and FIZZ expression via both signal transducer and activator of transcription (STAT)6-dependent and -independent mechanisms. (youscribe.com)
  • Local expression of mIgf-1 modulates ubiquitin, caspase and CDK5 expression in skeletal muscle of an ALS mouse model. (semanticscholar.org)
  • article{Dobrowolny2008LocalEO, title={Local expression of mIgf-1 modulates ubiquitin, caspase and CDK5 expression in skeletal muscle of an ALS mouse model. (semanticscholar.org)
  • I need to activate caspase-1 to trigger inflammation and pyroptotic cell death. (protocol-online.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 play important roles in apoptosis and inflammation. (immunochemistry.com)
  • Interleukin-1 (IL-1), the 'gatekeeper' of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. (biologists.org)
  • We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. (biologists.org)
  • Interleukin-1 (IL-1) is an important activator of inflammation. (biologists.org)
  • Altogether, we conclude that caspase-1 can act as a radio- and chemo-sensitiser, in vitro and in vivo. (csic.es)
  • The present study is aimed to elucidate the effects and relative mechanisms of TT‑1 on a human thyroid cancer cell line (TT) in vitro and in vivo. (spandidos-publications.com)
  • In post-ischemic hearts, procaspase-1 overexpression was associated with strikingly increased cardiac myocyte apoptosis in the peri- and noninfarct regions and with 50% larger myocardial infarctions. (ahajournals.org)
  • These results indicate that Apaf-1 overexpression lowers the apoptotic threshold by activating caspase-9 and caspase-3. (aacrjournals.org)
  • These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae . (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)
  • At sublytic concentrations, leukotoxin induced no apoptotic activity in monocytes, as revealed by the lack of caspase 3 activation and DNA fragmentation. (diva-portal.org)
  • Despite the lack of caspase 3 activation, oxLDL treatment led to the formation of nucleosomal DNA fragments characteristic of apoptosis. (biochemj.org)
  • Caspase-1 mediated sensitisation to cisplatin and γ-radiation was also observed in vivo. (csic.es)
  • The caspase-3 precursor is first cleaved at Asp175-Ser176 to produce the p11 subunit and the p20 peptide. (scbt.com)
  • The adaptor ASC regulates not only caspase-1 activation, but also cell death and the transcription factor NF-κB by mechanisms that remain poorly understood. (frontiersin.org)
  • The adaptor molecule ASC mediates AIM2-dependent caspase-1 activation. (archives-ouvertes.fr)
  • However, the host molecular factors involved in caspase-1 activation are still unclear. (jimmunol.org)
  • 1. Avivi-Green C, Polak-Charcon S, Madar Z, Schwartz B. (2002) Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines. (guidetopharmacology.org)
  • Caspase-1-/- mice developed less ischemic ARF as judged by renal function and renal histology. (jci.org)
  • This conversion is not observed in caspase-1-/- ARF mice or sham-operated controls. (jci.org)
  • We then injected wild-type mice with IL-18-neutralizing antiserum before the ischemic insult and found a similar degree of protection from ARF as seen in caspase-1-/- mice. (jci.org)
  • In addition, we observed a fivefold increase in myeloperoxidase activity in control mice with ARF, but no such increase in caspase-1-/- or IL-18 antiserum-treated mice. (jci.org)
  • Finally, we confirmed histologically that caspase-1-/- mice show decreased neutrophil infiltration, indicating that the deleterious role of IL-18 in ischemic ARF may be due to increased neutrophil infiltration. (jci.org)
  • We examined the survival of these more mature postmitotic neuronal populations in mice in which Apaf-1 has been genetically deleted and find that they exhibit quantitatively normal PCD of developing postmitotic neurons. (jneurosci.org)
  • Transgenic mice that overexpress IL-18 ( 18 ) or caspase-1 ( 19 ) in their keratinocytes showed high serum IL-18 and IgE levels. (aacrjournals.org)
  • 13,14 Notably, apoptotic processes appeared normal in the caspase-1 −/− mice. (ahajournals.org)
  • Inbred and congenic mice harboring macrophage-sensitizing Nlrp1b S/S alleles (which allow activation of caspase-1 and IL-1β release in response to anthrax lethal toxin challenge) effectively controlled bacterial growth and dissemination when compared to mice having Nlrp1b R/R alleles (which cannot activate caspase-1 in response to toxin). (prolekare.cz)
  • Resistance to infection required the actions of both caspase-1 and IL-1β as Nlrp1b S/S mice deleted of caspase-1 or the IL-1 receptor, or treated with the Il-1 receptor antagonist anakinra, were sensitized to infection. (prolekare.cz)
  • Comparison of circulating neutrophil levels and IL-1β responses in Nlrp1b S/S ,Nlrp1b R/ R and IL-1 receptor knockout mice implicated Nlrp1b and IL-1 signaling in control of neutrophil responses to anthrax infection. (prolekare.cz)
  • Because cannabinoids have also been reported to induce apoptosis and because the release of IL-1 and suppression of lymphoproliferation are related to apoptosis, we tested for the induction of apoptosis by THC in murine immune cell cultures. (biomedsearch.com)
  • It requires signaling through pannexin-1 to induce caspase-1 activation and IL-1ß processing and release. (immunochemistry.com)
  • Silencing LC3 by shRNA, or the LC3 mutants defective in membrane localization or p62 interaction fail to induce caspase-8 activation and apoptosis. (asm.org)
  • Several caspases including caspase-4, -8, and -9 structurally resemble CED-3 in that they contain long prodomains and appear to act upstream in the caspase cascade ( 13 , 14 ). (pnas.org)
  • It is involved in the activation cascade of caspases responsible for apoptosis execution. (medgadget.com)
  • In contrast, TAK1-deficient mouse embryonic fibroblasts are resistant to TRAIL-induced apoptosis, and treatment of control mouse embryonic fibroblasts with 5Z-7-oxozeaenol did not drastically promote the TRAIL-induced activation of a caspase cascade. (aacrjournals.org)
  • In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. (usgs.gov)
  • For example, ICEBERG nucleates the formation of Caspase-1 filaments and is thus incorporated into the filaments, but lacks the ability to inhibit the activation of inflammasomes. (wikipedia.org)
  • Almost all variants retained the ability to inhibit caspase-1, but many lacked caspase-8 inhibitory activity. (portlandpress.com)
  • We examined plasma of 95 CTCL patients and skin of 20 CTCL patients for IL-18, caspase-1, IL-12, and other cytokines. (aacrjournals.org)
  • It processes the cytokines interleukin- 1β (IL-1β) and interleukin-18 (IL-18) and induces pyroptotic cell death. (biovendor.com)
  • The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. (usgs.gov)
  • Apoptosome formation results in the activation of executioner caspases including caspase-3, -6, and -7. (biologists.org)
  • METHODS Intracellular IL-1 content (IL-1α and IL-1β) was measured by ELISA in freshly isolated human normal colonocytes. (bmj.com)
  • Cytolysis was determined by the activity of lactate dehydrogenase released from peripheral human leukocytes after 1-h exposure to leukotoxin. (diva-portal.org)
  • Exposure of monocytes to leukotoxin increased their caspase 1 activity about fivefold within 10 to 20 min. (diva-portal.org)
  • In contrast, caspase activity is not necessary for the normal PCD of more mature postmitotic neurons that are establishing synaptic connections. (jneurosci.org)
  • In experimental therapeutics for cancer, caspase-1 has been related to some anticancer activity. (csic.es)
  • Detect caspase-1 activity with the FAM FLICA Caspase-1 Assay Kit. (immunochemistry.com)
  • Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis , primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. (usgs.gov)
  • We investigated a possible association of reduced enzymatic activity of variant caspase-1 with impaired ER-stress responses. (biomedcentral.com)
  • The released cyt c binds to Apaf-1 together with dATP and procaspase-9. (thefreelibrary.com)
  • The FLICA reagent FAM-YVAD-FMK enters each cell and irreversibly binds to activated caspase-1. (immunochemistry.com)
  • Caspase-1 is synthesized as inactive pro-Caspase-1, wich is activated and processed by multiprotein complexes called inflammasomes in response to numerous stimuli that are detected through distinct inflammasomes. (biovendor.com)
  • Intracellularly, caspases exist as inactive zymogens (procaspases) that have NH 2 -terminal prodomains plus large and small catalytically active subunits. (aacrjournals.org)
  • Polo-like kinase 1 (Plk1) plays several roles in mitosis, and it has been suggested to have a role in tumorigenesis. (harvard.edu)
  • Innate and adaptive immune responses play important roles in cancer progression and therapy ( 1 , 2 ). (jimmunol.org)
  • These data confirm an inverse relationship between murine macrophage sensitivity to lethal toxin and mouse susceptibility to spore infection, and establish roles for Nlrp1b S , caspase-1, and IL-1β in countering anthrax infection. (prolekare.cz)
  • Caspases: key players in programmed cell death. (anaspec.com)
  • Programmed cell death or apoptosis, a morphologically distinguished form of cell death, is critical for development and tissue homeostasis in multicellular organisms ( 1 , 2 ). (pnas.org)
  • Like other caspases it also plays a role in apoptosis (programmed cell death), but only when over-expressed. (sciencephoto.com)
  • Caspase 8 is involved in the programmed cell death induced by Fas and various apoptotic stimuli. (thermofisher.com)
  • Numerous publications have shown that HSV-1 blocks programmed cell death induced by heat shock ( 18 ), tumor necrosis factor alpha ( 10 , 35 ), Fas ligand ( 10 , 16 , 30 ), osmotic shock ( 11 , 17 ), and virtually every proapoptotic substance tested to date. (asm.org)