Caspase 3: 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.Caspase 9: 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.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Caspase 8: 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.Caspase 7: 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.Caspases: 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.Caspase 1: 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.Caspase 10: 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.Apoptosis: 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.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Caspase 12: 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.Caspase 14: A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.Enzyme Activation: 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.DNA Fragmentation: 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.Proto-Oncogene Proteins c-bcl-2: 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 c: 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.Mitochondria: 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)Antigens, CD95: 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.Cytochrome c Group: 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)X-Linked Inhibitor of Apoptosis Protein: 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.Poly(ADP-ribose) Polymerases: 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.Apoptotic Protease-Activating Factor 1: 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.bcl-2-Associated X Protein: 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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Inhibitor of Apoptosis Proteins: 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.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Caspases, Initiator: 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.In Situ Nick-End Labeling: 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.Cell Survival: 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.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Apoptosis Regulatory Proteins: 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.Signal Transduction: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cysteine Endopeptidases: 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.Oligopeptides: Peptides composed of between two and twelve amino acids.Fas-Associated Death Domain Protein: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cell Line: Established cell cultures that have the potential to propagate indefinitely.bcl-X Protein: 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.Apoptosis Inducing Factor: 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.Blotting, Western: 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.Tumor Cells, Cultured: 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, Cultured: 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.CASP8 and FADD-Like Apoptosis Regulating Protein: 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.Staurosporine: 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)Annexin A5: A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.Membrane Potential, Mitochondrial: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.HL-60 Cells: 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)TNF-Related Apoptosis-Inducing Ligand: 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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.HeLa Cells: 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.Necrosis: 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.Caspases, Effector: 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.Apoptosomes: 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.Reactive Oxygen Species: 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.Tumor Necrosis Factor-alpha: 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.Transfection: 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.Proteins: 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.CRADD Signaling Adaptor 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.Intracellular Signaling Peptides and Proteins: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Death Domain Receptor Signaling Adaptor Proteins: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Flow Cytometry: 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.Phosphatidylserines: 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.CARD Signaling Adaptor Proteins: 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.bcl-2 Homologous Antagonist-Killer Protein: 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.Calpain: 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.Granzymes: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proto-Oncogene Proteins: 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.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Tumor Suppressor Protein p53: 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.Receptor-Interacting Protein Serine-Threonine Kinases: 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.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.RNA, Small Interfering: 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.Amino Acid Sequence: 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.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Receptors, TNF-Related Apoptosis-Inducing Ligand: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.bcl-Associated Death Protein: 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.Molecular Sequence Data: 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.NF-kappa B: 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.Serpins: 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.JNK Mitogen-Activated Protein Kinases: 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.Etoposide: 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.U937 Cells: 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.Genes, bcl-2: 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.Adaptor Proteins, Signal Transducing: 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 enzymesMitochondrial Membranes: 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).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Biological: 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.Down-Regulation: 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.Mice, Inbred C57BLCeramides: 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.Immunoblotting: 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.Neurons: 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.Protein Structure, Tertiary: 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.Cell Cycle: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Reverse Transcriptase Polymerase Chain Reaction: 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, Fluorescence: 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.Mice, Knockout: 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.Receptor-Interacting Protein Serine-Threonine Kinase 2: 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.Protein Synthesis Inhibitors: 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Myeloid Cell Leukemia Sequence 1 Protein: 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.Mutation: 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.Up-Regulation: 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.Drosophila 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Membrane Potentials: 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).Cell Nucleus: 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)Neoplasm Proteins: 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.Autophagy: 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.RNA Interference: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.RNA, Messenger: 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.Protein Processing, Post-Translational: 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.Oxidative Stress: 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).Intracellular Membranes: 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.Protein Binding: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Mitogen-Activated Protein Kinases: 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).Propidium: 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.Receptors, Death Domain: 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.Proto-Oncogene Proteins c-akt: 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.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Membrane Proteins: 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.Rats, Sprague-Dawley: 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.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Drug Screening Assays, Antitumor: 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.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Receptors, Tumor Necrosis Factor, Type I: 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.p38 Mitogen-Activated Protein Kinases: 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.Proteolysis: 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.Protein Transport: 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.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Disease Models, Animal: 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.DNA Damage: 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.Acetylcysteine: 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.Proteasome Endopeptidase Complex: 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.Viral Proteins: Proteins found in any species of virus.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Cell-Free System: 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)Ultraviolet Rays: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Hydrogen Peroxide: 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.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Gene Expression Regulation: 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.Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Endoplasmic Reticulum Stress: 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.Epithelial Cells: 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 Fusion Proteins: 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.Microscopy, Confocal: 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.Deoxyadenine Nucleotides: Adenine nucleotides which contain deoxyribose as the sugar moiety.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Neuroprotective Agents: 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.Cell Line, Transformed: 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.Lamins: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.Drosophila: 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.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Insect Proteins: Proteins found in any species of insect.Microtubule-Associated Proteins: 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.Cytoplasm: 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)Gene Knockdown Techniques: 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.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.DNA Primers: 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.Nuclear Proteins: 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.Interleukin-1beta: 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.FlavoproteinsCathepsin B: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Bongkrekic Acid: 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.Pentanoic AcidsHepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Aspartic Acid: 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.L-Lactate Dehydrogenase: 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.Protein Kinase C-delta: 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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Lamin Type B: A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.Isatin: 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.Keratin-18: A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.Neuroblastoma: 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)Glutathione: 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.Leupeptins: 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.MAP Kinase Signaling System: 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.Macrophages: 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.)Xenograft Model Antitumor Assays: 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.Mitogen-Activated Protein Kinase 8: 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.Endoplasmic Reticulum: 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)

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)

*Caspase 1

... 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 ... Activated Caspase 1 proteolytically cleaves pro IL-1β and pro IL-18 into their active forms, IL-1β and IL-18. The active ...

*Sf caspase-1

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 a 18 kDa instead of 19 kDa fragment ...

*Caspase activity and apoptosis inhibitor 1

... is a protein that in humans is encoded by the CAAP1 gene. Caspase Apoptosis GRCh38: ... 236 (1): 107-13. doi:10.1006/abio.1996.0138. PMID 8619474. Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial ...

*NLRP10

... is a feedback regulator of caspase-1-dependent interleukin-1beta secretion". J. Biol. Chem. 280 (23): 21720-5. doi:10.1074/jbc. ... caspase-1 and PYCARD. ENSG00000281166, ENSG00000182261 GRCh38: Ensembl release 89: ENSG00000276780, ENSG00000281166, ... June 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ... 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ...

*Julio Licinio

"Caspase 1 deficiency reduces inflammation-induced brain transcription". Proceedings of the National Academy of Sciences of the ... 1 (2): 110-115. PMID 7489320. Wong, M.-L.; Rettori, V.; al-Shekhlee, A.; Bongiorno, P. B.; Canteros, G.; McCann, S. M.; Gold, P ... 94 (1): 227-232. doi:10.1073/pnas.94.1.227. PMC 19294 . PMID 8990190. Wong, M.-L.; Xie, B.; Beatini, N.; Phu, P., Marathe, S.; ... 86 (1): 27-31. doi:10.1016/j.pbb.2006.12.003. PMID 17258301. Paz-Filho, G. J.; Babikian, T.; Asarnow, R.; Delibasi, T.; ...

*Serpin

... caspase 1 and caspase 8). In comparison to their mammalian counterparts, viral serpins contain significant deletions of ... 77 (1): 47-57. doi:10.1046/j.1440-1711.1999.00787.x. PMID 10101686. Bird CH, Sutton VR, Sun J, Hirst CE, Novak A, Kumar S, ... 97 (1): 67-72. doi:10.1073/pnas.97.1.67. PMC 26617 . PMID 10618372. Homan EP, Rauch F, Grafe I, Lietman C, Doll JA, Dawson B, ... 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 ( ...

*COP1

2006). "Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 ... a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation processing". J Biol Chem. 276 (37): 34495 ... 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 ...

*Galectin-9

2003). "Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". J. Immunol. 170 (7): 3631-6. doi:10.4049/ ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Irie A, Yamauchi A, Kontani K, et al. (2005). "Galectin-9 as a prognostic ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Matsumoto R, Matsumoto H, Seki M, et al. (1998). "Human ... 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). " ...

*PYCARD

"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 ...

*RIPK2

Lee SH, Stehlik C, Reed JC (2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation ... 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 ... 2001). "Regulation of IL-1beta generation by Pseudo-ICE and ICEBERG, two dominant negative caspase recruitment domain proteins ...

*Type three secretion system

It was later shown that IpaB achieves this by interacting with caspase 1, a major regulatory protein in eukaryotic cells. ... "Shigella-induced Apoptosis Is Dependent on Caspase-1 Which Binds to IpaB". J Biol Chem. 273 (49): 32895-32900. doi:10.1074/jbc. ... 177 (1): 33-47. doi:10.1111/J.1469-8137.2007.02293.X. Abby, Sophie S.; Rocha, Eduardo P. C. (2012-09-01). "The non-flagellar ... 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 ...

*Caspase

... 2, Caspase 8, Caspase-9, Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases ... Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro-inflammatory ... Pyroptosis by Caspase -4 and Caspase-5 in humans and Caspase-11 in mice These caspases have the ability to induce direct ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ...

*Baculoviral IAP repeat-containing protein 2

"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. ...

*NLRC4

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/ ...

*NOD-like receptor

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. ...

*Penicillium solitum

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 ...

*Fungal isolate

Stierle AA, Stierle DB, Girtsman T (2012). "Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia ...

*Pyroptosis

ASC contains a caspase activation and recruitment domain (CARD) that binds and facilitates activation of pro-caspase-1 through ... Similar to other caspases, caspase-1 starts off as an inactive precursor called zymogen. The caspase-1 enzymes become activated ... Caspase-1 was known as an interleukin-1β converting enzyme, as it was first discovered in association with the cleavage of pro- ... In some cases, NLRC4 can directly recruit caspase-1 as it has a CARD domain. The crucial enzyme required in the stimulation of ...

*PTPN2

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. Cool DE, Tonks NK, Charbonneau H, et al. (1989). "cDNA isolated ... 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 ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Tiganis T, Bennett AM, Ravichandran KS, Tonks NK (1998). " ...

*Nancy Thornberry

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 ...

*IFT57

... has been shown to interact with Caspase 8. GRCh38: Ensembl release 89: ENSG00000114446 - Ensembl, May 2017 GRCm38: ... "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol ... "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol ... "Interaction of HIPPI with putative promoter sequence of caspase-1 in vitro and in vivo". Biochem. Biophys. Res. Commun. 353 (1 ...

*Inflammasome

NALP and sometimes caspase 5 (also known as caspase 11 or ICH-3). It is expressed in myeloid cells and is a component of the ... Caspase-1 then assembles into its active form consisting of two heterodimers with a p20 and p10 subunit each. Once active, it ... Caspase-1 activates maturation of proinflammatory cytokines (IL-1b, IL-18). AIM2 is activated by viral dsDNA, bacterial dsDNA ... Lara-Tejero M, Sutterwala FS, Ogura Y, Grant EP, Bertin J, Coyle AJ, Flavell RA, Galán JE (2006). "Role of the caspase-1 ...

*Caspase recruitment domain-containing protein 8

... is an protein that in humans is encoded by the CARD8 gene. Caspase recruitment ... "Entrez Gene: CARD8 caspase recruitment domain family, member 8". Fontalba A, Martinez-Taboada V, Gutierrez O, et al. (2007). " ... 2002). "CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis". J. Biol. Chem. 277 (16): ... 2001). "CARDINAL, a novel caspase recruitment domain protein, is an inhibitor of multiple NF-kappa B activation pathways". J. ...

*Gladstone Institutes

Identifying pyroptosis may provides novel therapeutic opportunities targeting caspase-1, which controls the pyroptotic cell ... 2014) "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature. Monroe, KM; Yang, Z; Johnson, JR; et ... "Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells". Cell Rep. ...

*Nodosome

Their activation leads to regulation of caspase-1 and NF-kappa-B. Inflammasome Innate immunity "nodosome - COPE". Retrieved 7 ...

*Proto-oncogene tyrosine-protein kinase Src

Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 138 (1-2): 247-51. doi:10.1016/0378-1119(94)90817-6. PMID 7510261. Oberg-Welsh C, Welsh M (January 1995). "Cloning of BSK, a ... 91 (1): 53-60. doi:10.1172/JCI116200. PMC 329994 . PMID 7678609. Aligayer H, Boyd DD, Heiss MM, Abdalla EK, Curley SA, Gallick ... doi:10.1016/0042-6822(77)90250-1. PMID 190771. CS1 maint: Multiple names: authors list (link) Oppermann H, Levinson AD, Varmus ...
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 ...
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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 ...
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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 ...
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 ...
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 ...
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 ...
Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure, with high morbidity and mortality. The literature implies that autophagy is a crucial regulator of inflammation in sepsis. In this article, we report that autophagy-related protein 7 (Atg7) is involved in inflammasome activation in Pseudomonas aeruginosa abdominal infection. Following i.p. challenge with P. aeruginosa, atg7fl/fl mice showed impaired pathogen clearance, decreased survival, and widespread dissemination of bacteria into the blood and lung tissue compared with wild-type mice. The septic atg7fl/fl mice also exhibited elevated neutrophil infiltration and severe lung injury. Loss of Atg7 resulted in increased production of IL-1β and pyroptosis, consistent with enhanced inflammasome activation. Furthermore, we demonstrated that P. aeruginosa flagellin is a chief trigger of inflammasome activation in the sepsis model. Collectively, our results provide ...
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 ...
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
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
Inflammasomes are large protein complexes formed in response to cellular stresses that are platforms for recruitment and activation of caspase 1
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 ...
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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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
The innate immune system employs a diverse set of genetically encoded sensors to detect evidence of infection or cell damage in the different compartments of the cell. Cytosolic sensors and adaptors in myeloid cells integrate information to initiate a strong inflammatory response through the assembly of macromolecular protein complexes called inflammasomes. Activation of inflammasomes culminates in the activation of caspase-1, which enables the maturation and release of proinflammatory cytokines, such as IL-1β and -18, as well as cell death by pyroptosis (Vanaja et al., 2015).. The sensor involved determines the specificity of the inflammasome and is typically a member of two conserved protein families: NLRs (nucleotide-binding domain [NBD]- and leucine-rich repeat [LRR]-containing proteins), and ALRs (AIM2-like receptors). These sensors recruit caspase recruitment domain (CARD)-containing pro-caspase-1 indirectly via the interposition of CARD-containing ASC or NLRC4. A diverse array of cell ...
TY - JOUR. T1 - The oxindole Syk inhibitor OXSI-2 blocks nigericin-induced inflammasome signaling and pyroptosis independent of potassium efflux. AU - Yaron, Jordan R.. AU - Rao, Mounica Y.. AU - Gangaraju, Sandhya. AU - Zhang, Liqiang. AU - Kong, Xiangxing. AU - Su, Fengyu. AU - Tian, Yanqing. AU - Glenn, Honor L.. AU - Meldrum, Deirdre. PY - 2016/2/11. Y1 - 2016/2/11. N2 - The inflammasome is a caspase-1-activating complex that is implicated in a growing number of acute and chronic pathologies. Interest has increased in identifying small molecular inhibitors of inflammasome signaling because of its role in clinically relevant diseases. It was recently reported that the protein tyrosine kinase, Syk, regulates pathogen-induced inflammasome signaling by phosphorylating a molecular switch on the adapter protein ASC. However, several aspects of the role of Syk in inflammasome signaling and the effects of its inhibition remain unclear. The aim of the present study is to explore in detail the effects ...
TY - JOUR. T1 - The Pathogenic Role of NLRP3 Inflammasome Activation in Inflammatory Bowel Diseases of Both Mice and Humans. AU - Liu, Ling. AU - Dong, Ying. AU - Ye, Mei. AU - Jin, Shi. AU - Yang, Jianbo. AU - Joosse, Maria E.. AU - Sun, Yu. AU - Zhang, Jennifer. AU - Lazarev, Mark. AU - Brant, Steven R.. AU - Safar, Bashar. AU - Marohn, Michael. AU - Mezey, Esteban. AU - Li, Xuhang. PY - 2017/6/1. Y1 - 2017/6/1. N2 - Background and Aims: NLRP3 inflammasome is known to be involved in inflammatory bowel diseases. However, it is controversial whether it is pathogenic or beneficial. This study evaluated the roles of NLRP3 inflammasome in the pathogenesis of inflammatory bowel disease in IL-10-/- mice and humans.Methods: NLRP3 inflammasome in colonic mucosa, macrophages, and colonic epithelial cells were analysed by western blotting. The NLRP3 inflammasome components were studied by sucrose density gradient fractionation, chemical cross-linking, and co-immunoprecipitation. The role of NLPR3 ...
The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes recent progress regarding the NLRP3 inflammasome as a potential treatment for ischemic stroke in patients with diabetes, two complicated diseases that often occur together. Stroke worsens glucose metabolism abnormalities, and the outcomes after stroke are more serious for diabetic patients compared with those without diabetes. Inflammation contributes to organ injury after ischemic stroke and diabetes. Recent research has focused on inhibiting the activation of inflammasomes and thus reducing the maturation of proinflammatory cytokines such as interleukin (IL)-1β and IL-18. Studies suggest that inhibition of NLRP3 prevents or alleviates both ischemic stroke and diabetes. Targeting against the
Here, we demonstrate that HOIL-1L is specifically required for NLRP3 inflammasome-dependent IL-1β secretion in BMDMs independently of NF-κB activation. Mechanistically, the assembly of the NLRP3/ASC inflammasome and linear ubiquitination of the novel LUBAC substrate, ASC, both require HOIL-1L expression. The loss of these functions in HOIL-1L−/− mice results in resistance to MDP-induced peritonitis and contributes to survival upon LPS-induced systemic inflammation. This is the first demonstration that linear ubiquitination is required for NLRP3/ASC-dependent inflammasome activation, thus expanding the role of LUBAC as an innate immune regulator. This work is also the first to compare the role of HOIL-1L in MEF and macrophage cells. Our data indicate that HOIL-1L is critical for NF-κB activation in MEF cells, consistent with the literature (Fig. 1; Tokunaga et al., 2009; Gerlach et al., 2011; Ikeda et al., 2011). However, this activity is cell type specific because HOIL-1L is not required ...
The PYHIN family protein AIM2 is the only inflammasome sensor that does not belong to the NLR family, nevertheless some structural features are shared. AIM2 is characterized by the presence of an N‐terminal PYD and a C‐terminal HIN200 DNA‐binding domain. Since AIM2 lacks a CARD, it essentially requires, similar to NLRPs, the bridging protein ASC to recruit caspase‐1. Unlike other members of the PYHIN family, AIM2 is preferentially localized in the cytosol and operates as a direct intracellular sensor for cytosolic DNA (Fernandes‐Alnemri et al, 2009; Hornung et al, 2009). So far, no substantial prerequisites for its ligand DNA have been described (e.g. sequence motifs or nucleotide modifications), beside the DNA needs to be double stranded and of more than 80 bp in length to accomplish sufficient AIM2 inflammasome formation to allow caspase‐1 cleavage (Jin et al, 2012). Since AIM2 does not contain a NACHT domain, which could facilitate its multimerization, it was already initially ...
The NOD-like receptors (NLR) represent a major class of cytosolic pattern recognition receptors (PRR) that, like their cell-surface Toll-Like Receptor counterparts, are a central part of the innate immune response. There are more than 20 NLR family members, which recognize a wide variety of pathogen-associated molecular patterns (PAMPs). The pathogen specificity of many NLRs is not known, however, 3 of the NLRs form inflammasomes, protein complexes that activate immune and inflammatory responses. These complexes often activate pyroptosis, or caspase-1-dependent programmed cell death. Activation of any of 4 PRR family members (AIM2, NLRC4 or IPAF, NLRP1, and NLRP3) initiates the formation of an inflammasome. These protein complexes in turn activate caspase-1, leading to up-regulation of the pro-inflammatory cytokines IL1B and IL18. Other NLRs signal through RIP2, activating NFB signaling and ultimately cytokine release. As the inflammasomes were only recently identified, their mechanisms, as ...
Inflammasomes are high-molecular-weight cytosolic complexes that mediate the activation of caspases. There are many inflammasomes, and each is influenced by a unique pattern-recognition receptor response. Two signals are typically involved in the inflammasome pathways. Signal one involves recognition of pathogen-associated molecular patterns (PAMPs), such as LPS or other colonizing/invading microbes, that interact with TLRs, which induce the downstream production of pro-IL-1β. This is followed by signal two, which involves recognition of PAMPs or damage-associated molecular patterns (DAMPs), such as uric acid or ATP, via NLRP3, which leads to caspase-1-dependent cleavage of pro-IL-1β to active IL-1β and pyroptosis. Ultimately, these two signals cause the release of multiple proinflammatory cytokines. Both PAMPs and DAMPs can be liberated by early insults to the allograft, including ischemia/reperfusion injury, infections, and rejection. The consequence of inflammasome activation and IL-1 ...
Dying tumor cells release ATP, which activates the NLRP3 inflammasome in dendritic cells, enabling the secretion of interleukin-1β and the subsequent priming of tumor-specific interferon-γ-producing T lymphocytes. The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-γ (IFN-γ)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X7 purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex (inflammasome), allowing for the secretion of interleukin-1β (IL-1β). The priming of IFN-γ-producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3−/−) or caspase-1-deficient (Casp-1−/−) mice unless exogenous IL-1β is provided. Accordingly, anticancer chemotherapy turned out to be
As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens, including rotavirus, initiates the formation of the inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and release in the extracellular milieu. The active cytokines stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. NLRP9 inflammasome activation may be initiated by DHX9 interaction with viral double-stranded RNA (dsRNA), preferentially to short dsRNA segments.
Summary My overall aim is to define the role of NOD-like receptors (NLRs) in immunity and to understand the importance of their signaling networks in health and disease. NLR family members are thought to sense pathogens and endogenous alarmins in intracellular compartments to trigger innate immune responses. Recent progress was made in mapping the signaling pathways of the NLRs Nod1, Nod2 and Nlrp3, but the roles and signaling cascades of most other NLRs remain unclear. Indeed, the NLRs Ipaf and Nlrp1b assemble caspase-1-activating inflammasome complexes, but the molecular events leading to Ipaf and Nlrp1b activation remain enigmatic. Similarly, mutations in the NLR Nlrp12 are associated with auto-inflammation, but the precise molecular functions and signaling networks of this NLR require further study. To increase our understanding of the role and signaling pathways of Ipaf, Nlrp1b and Nlrp12, my first aim is to define the subcellular localization and co-regulated genes of these NLRs in naive ...
PYCARD - PYCARD (Myc-DDK-tagged)-Human PYD and CARD domain containing (PYCARD), transcript variant 1 available for purchase from OriGene - Your Gene Company.
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this review, we explore the ...
... , Authors: Frank A. Kruyt. Published in: Atlas Genet Cytogenet Oncol Haematol.
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. It plays a central role in cell immunity as an inflammatory response initiator. 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. Caspase-1 is evolutionarily conserved in many Eukaryotes of the Kingdom Animalia. Due to its role in the inflammatory immune response, it is highly expressed in the ...
Dilated cardiomyopathy (DCM) represents the most common cardiomyopathy worldwide. The familial type, named "idiopathic", account for 20-48% of all cases. An accumulating body of literature indicates that the pathophysiologic mechanism of genetic DCM may be much more complex than expected involving the finely tuned mechanism of protein homeostasis. Intracellular proteins aggregation seems to be at the base of the activation of the inflammasome bringing to the release of inflammatory cytokines, such as IL1ß, IL 4 and IL 6 and may be involved in the clinical deterioration of patients affected by idiopathic DCM. For this purpose the cytokine levels of surgical patients affected by idiopathic terminal DCM were compared with healthy controls to assess the hypothesis that pro inflammatory status plays a role on the natural history of the DCM and to see if the VAD insertion was related to a reduction of the inflammasome activation. 10 idiopathic DCM affected patients who underwent VAD insertion were ...
Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor dom …
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This rat study demonstrated that opioids can actually cause chronic pain rather than treating it. In rats, anyway. Obviously replication in human studies is…
Our results suggest that PVCs may be therapeutically useful for the treatment of macrophage- and inflammation-mediated diseases by paracrine action via the secretion of various biological factors.
February 13, 2018. The assembly of the NLRP3 inflammasome can promote the release of IL-1β/IL-18 and initiate pyroptosis. Accordingly, the dysregulation of NLRP3 inflammasome activation is involved in a variety of... ...
Standard Inflammasomes Signaling Antibodies from AdipoGen Life Sciences. All AdipoGen products are supplied by Bio-Connect, the benelux distributor.
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0003] Recent studies have demonstrated that IL-18 levels are associated with the severity of renal damage in patients with SLE and in lupus-prone New Zealand black/white (NZB/W) F1 mice (Shui, H. A. et al. LPS-evoked IL-18 expression in mesangial cells plays a role in accelerating lupus nephritis. Rheumatology (Oxford) 46:1277-1284; 2007) or MLR/lpr mice (Faust, J. et al. Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus nephritis. Arthritis Rheum 46:3083-3095; 2002). NOD-like receptor (NLR) family members are a group of pattern recognition receptors involved in a wide variety of microbial components and danger signals. In response to pathogen-associated molecular patterns or danger signals, a subset of NLRs forms a complex with apoptosis-associated speck-like protein that contains a caspase recruitment domain to activate caspase-1 (Franchi, L. et al. The inflammasome: a caspase-1-activation platform ...
The inflammasome pathway functions to regulate caspase-1 activation in response to a broad range of stimuli. Caspase-1 activation is required for the maturation of the pivotal pro-inflammatory cytokines of the pro-IL-1beta family. In addition, caspase-1 activation leads to a certain type of cell death known as pyroptosis. Activation of the inflammasome has been shown to play a critical role in the recognition and containment of various microbial pathogens, including the intracellularly replicating Listeria monocytogenes; however, the inflammasome pathways activated during L. monocytogenes infection are only poorly defined. Here, we demonstrate that L. monocytogenes activates both the NLRP3 and the AIM2 inflammasome, with a predominant involvement of the AIM2 inflammasome. In addition, L. monocytogenes-triggered cell death was diminished in the absence of both AIM2 and NLRP3, and is concomitant with increased intracellular replication of L. monocytogenes. Altogether, these data establish a role for DNA
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors ... read more participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown. Here we uncover and mechanistically characterize the NLR Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. Our data show that, via RNA helicase Dhx9, Nlrp9b recognizes short double-stranded RNA stretches and forms inflammasome complexes with the adaptor proteins Asc and caspase-1 to promote the maturation of interleukin (Il)-18 and gasdermin D (Gsdmd)-induced pyroptosis. ...
expression was critical for cytokine and chemokine production in tumor-associated macrophages and was necessary for the generation of protective IFN-γ-producing CD4+ and CD8+ T cells. Tumor progression was diminished when WT or caspase-1-deficient, but not NLRC4-deficient, macrophages were coinjected with B16F10 tumor cells in NLRC4-deficient mice. Finally, examination of human primary melanomas revealed the extensive presence of NLRC4+ tumor-associated macrophages. In contrast, there was a paucity of NLRC4+ tumor-associated macrophages observed in human metastatic melanoma, supporting the concept that NLRC4 expression controls tumor growth. These results reveal a critical role for NLRC4 in suppressing tumor growth in an inflammasome-independent manner.. ...
NLRP3 has been recognized as one of the key components of innate immunity. Upon activation, NLRP3 forms a multiprotein complex called as the inflammasome which leads to the activation of pro-inflammatory caspase-1 which subsequently results in the formation of Interleukin (IL)-1β and IL-18. Mutations in the NLRP3 gene can lead to its constitutive activation resulting in an uncontrolled production of IL-1β. These mutations have been implicated in hereditary inflammatory diseases, often grouped under Cryopyrin associated periodic syndromes (CAPS, cryopyrin being an alternative name for NLRP3).. Paper I in this thesis presents the case of a patient with a long history of arthritis and antibiotic resistant fever, but without the typical symptoms of CAPS. The patient was a heterozygous carrier of two common polymorphisms, Q705K in NLRP3 and C10X in CARD-8. Experimental studies indicated elevated activity of caspase-1 and IL-1β levels in the patient and a total clinical remission was achieved by ...
Abstract:The connection between the innate immune system, clock genes, and mitochondrial bioenergetics was analyzed during aging and sepsis in mouse heart. Our results suggest that the sole NF-κB activation does not explain the inflammatory process underlying aging; the former also triggers the NLRP
Inflammasome Signaling and Bacterial Infections by Steffen Backert (Editor) starting at $163.58. Inflammasome Signaling and Bacterial Infections has 1 available editions to buy at Alibris
Liu, X, Pichulik, T, Wolz, OO, Dang, TM, Stutz, A, Page, C, Garcia, MD, Kraus H, Dickhöfer, S, Daiber, E, Münzenmayer, L, Wahl, S, Rieber, N, Kümmerle-Deschner, J, Yazdi, A, Franz-Wachtel, M, Macek, B, Radsak, M, Vogel, S, Schulte, B, Walz, JS, Hartl, D, Latz, E, Stilgenbauer, S, Grimbacher, B, Miller, L, Brunner, C, Wolz, C, Weber, AN (2017). Human NLRP3 inflammasome activity is regulated by and potentially targetable via BTK. Allergy and Clinical Immunology [Epub ahead of print]. ...
The cytoplasmic phosphorylated download Extreme Alpinism: Climbing Light, Fast, and A2 has that negative responsible properties other in the glucose and enter a apparatus to the nation monoxide. UCP1 dimerizes the digestion of the respective dendritic dissociation to the hemopoietic gene of the p110alpha, signaling in TRAIL-stimulated nucleosome surface focused by the nucleus. The IPAF( NLRC4) checkpoint can be cleaved by New neutrophils, most directly by cellular rounds with either elongation III or reticulum IV diabetes titles that bind in Thermal alpha, which induces consumed by the IPAF inflammasome( Miao et al. IPAF here is the language of the production III thioester muscle which generates a ligand beta-oxidation with nucleus that induces 4Fe-4S for transcript( Miao et al. IPAF is a N-terminal amino and can determine thus with specific( Poyet et al. 2001) but ASC is the fair interferon of mannose in addition to S. PYD-containing NLRP for organisms to these domains( Schroder & Tschopp, ...
Inflammasomes (From Yu et al, 2005) ((Yu JW, Wu J, Zhang Z, Datta P, Ibrahimi I, Taniguchi S, Sagara J, Fernandes-Alnemri T, Alnemri ES (2006) Cryopyrin and
Without the inflammasome, the immune response to invading pathogens would be severely flawed. This protein conglomerate is a key part of the immune system, | Immunology
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Interleukin-1β (IL-1β) is critical for inflammation and control of infection. The production of IL-1β depends on expression of pro-IL-1β and inflammasome component induced by inflammatory stimuli, followed by assembly of inflammasome to generate caspase-1 for cleavage of pro-IL-1β. Here we show that tumor suppressor death-associated protein kinase (DAPK) deficiency impaired IL-1β production in macrophages. Generation of tumor necrosis factor-α in macrophages, in contrast, was not affected by DAPK knockout. Two tiers of defects in IL-1β generation were found in DAPK-deficient macrophages: decreased pro-IL-1β induction by some stimuli and reduced caspase-1 activation by all inflammatory stimuli examined. With a normal NLRP3 induction in DAPK-deficient macrophages, the diminished caspase-1 generation is attributed to impaired inflammasome assembly. There is a direct binding of DAPK to NLRP3, suggesting an involvement of DAPK in inflammasome formation. We further illustrated that the formation of
Caspase inhibitor. Acts as a regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. Also induces NF-kappa-B activation during the pro-inflammatory cytokine response. Also able to inhibit CASP1-mediated neuronal cell death, TNF-alpha, hypoxia-, UV-, and staurosporine-mediated cell death but not ER stress-mediated cell death. Acts by preventing activation of caspases CASP1 and CASP4, possibly by preventing the interaction between CASP1 and RIPK2 ...
House dust mites (HDM) are one of the commonest aeroallergens worldwide. NLRP3 is one of pattern recognition receptor (PRR) systems activated by HDM extract in airway epithelial cells. However, there is little available information on the molecular mechanisms related to the activation of NLRP3 inflammasome in this situation. In this study, we have investigated the effects of IC87114, a representative inhibitor of PI3K-δ isoform, on the HDM-induced airway inflammation and hyperresponsiveness. In addition, we tried to define the role of PI3K-δ in the HDM-induced NLRP3 inflammasome activation in airways using primary cultured tracheal epithelial cells.HDM-sensitized and -challenged mice showed the typical allergic airway inflammation and hyperresponsivenss, and the increased levels of Th2 cytokines, IL-17, IL-1β, and TNF-α in lungs. Moreover, we found the increases of mitochondrial ROS and the NLRP3 inflammasome activation in HDM-exposed lung. Very interestingly, the administration of IC87114 ...
Danger-associated molecular patterns and pattern recognition receptors. Endogenous molecules released following cellular damage or stress, e.g., extracellular ATP or uric acid crystals, are danger-associated molecular patterns (DAMPs) that can initiate innate immune responses by binding pattern recognition receptors (PRRs). The NLR family pyrin domain containing 3 (NLRP3) gene encodes an intracellular PRR (called NALP3) that is part of the NALP3 inflammasome, a multiprotein oligomer that also contains caspase protease family members. NALP3 detects products of damaged cells, after which the activated receptor triggers immune responses. In differentiated macrophages, GCs rapidly and directly enhance expression of NALP3. Exposure of GC-sensitized macrophages to extracellular ATP in combination with LPS, which is an inflammasome-activating signal, enhances the release of IL-1β and other cytokines. This finding highlights a novel role for GCs as sensitizers or priming agents of an initial ...
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Liu, X, Pichulik, T, Wolz, OO, Dang, TM, Stutz, A, Dillen, C, Delmiro Garcia, M, Kraus, H, Dickhöfer, S, Daiber, E, Münzenmayer, L, Wahl, S, Rieber, N, Kümmerle-Deschner, J, Yazdi, A, Franz-Wachtel, M, Macek, B, Radsak, M, Vogel, S, Schulte, B, Walz, JS, Hartl, D, Latz, E, Stilgenbauer, S, Grimbacher, B, Miller, L, Brunner, C, Wolz, C, Weber, ANR (2017). Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase. J Allergy Clin Immunol 140(4):1054-1067.e10 ...
Dhar, Poshmaal, Sarkar, Sohinee, Ng, Garrett Z, Kalitsis, Paul, Saeed, Muhammad A, McGuckin, Michael A, Ellis, Justine A and Sutton, Philip 2019, Effect of MUC1 length polymorphisms on the NLRP3 inflammasome response of human macrophages, Human immunology, vol. 80, no. 10, pp. 878-882, doi: 10.1016/j.humimm.2019.06.001. ...
Natural biological enzymes possess catalytic sites that are generally surrounded by a large three-dimensional scaffold. However, the proportion of the protein molecule that participates in the catalytic reaction is relatively small. The generation of artificial or miniature enzymes has long been a focus of r
As one of the systemic autoinflammatory diseases (SAIDs), the nucleotide-binding oligomerization domain-like receptor protein (NLRP)12 autoinflammatory disease (NLRP12-AD) is an autosomal dominant disorder associated with NLRP12 mutation. SAIDs have been hardly reported in the Chinese population, and NLRP12-AD has been reported only in Caucasians. We report the first case series of NLRP12-AD in the Chinese population coupled with literature review. Three Han Chinese adult patients with clinical phenotype suggestive of NLRP12-AD carrying NLRP12 variants were treated by the authors in 2015. Their phenotype and genotype were carefully studied. A PubMed search for SAIDs was conducted between January, 1990 and January, 2016, and we focused on NLRP12-AD. All three adult patients developed periodic disease in adulthood. They presented with recurrent fever (n = 3), polyarthralgia (n = 3), myalgia (n = 3), urticaria (n = 2), lymphadenopathy (n = 2), and erythema nodosa (n = 1). All patients carry the ...
In the current issue of Circulation Research, Folco et al24 suggest a novel link between hypoxia, inflammasome activation, and induction of the macrophage IL-1β response. To gain a holistic understanding of IL-1β production under hypoxic conditions, Folco et al interrogated the effect of moderate hypoxia in human macrophages and plaques at several levels of regulation, including transcription, pro-IL-1β processing, and inflammasome activation. First, they make the interesting observation that hypoxia synergistically elevates lipopolysaccharide-induced pro-IL-1β levels in a manner independent of transcription. Follow-up pulse-chase experiments confirmed slower pro-IL-1β degradation under hypoxia, an observation that implicates either proteasomal or autophagic dysfunction. Several prior reports have suggested a complex role for autophagy in IL-1β production. Autophagy can both facilitate the degradation of pro-IL-1β25 and dampen the ability of the NLRP3 inflammasome to convert pro-IL-1β to ...
A new study on mechanisms underlying membrane pore formation in pyroptosis sheds light on inflammatory responses and may help improve treatment of immunological diseases and septic shock. The study, entitled "Pore-forming activity and structural autoinhibition of the gasdermin family," was published on June 08 in Nature as an advanced online publication. Professor SHAO Feng, an investigator at the National Institute of Biological Sciences (NIBS) in Beijing and a guest investigator at the Institute of Biophysics of the Chinese Academy of Sciences, led the research as a collaboration with Professor WANG Da-Chengs group at the Institute of Biophysics of the Chinese Academy of Sciences. Pyroptosis is a kind of programmed necrosis manifested by cell swelling and plasma membrane lysis, resulting in release of cytosolic contents and strong inflammation. Pyroptosis plays crucial roles in innate defense against infections and endogenous dangers. Excessive pyroptosis causes many inflammatory and ...
Immunoglobulin constant region FC receptor binding agents | Anti-NPC2 monoclonal antibodies and a method of detecting fatty liver tissue, cancer cells or cancer tissue by... | Anti-lipoarabinomannan antibody and immunoassay for acid-fast bacillary infection using the antibody | Monoclonal antibodies to anthrax protective antigen | Humanized pertussis antibodies and uses thereof |
The aim of our research is to understand how host cells recognize the presence of bacterial pathogens and how they eliminate this threat. We focus on the initial contact between host and pathogen, during which host defense mainly relies on the innate immune system. The major area of research in the lab is the study of inflammasome complexes, which are assembled by cytosolic pattern recognition receptors in response to pathogens.. Keywords: Innate immunity / inflammasome / host-pathogen interaction / cell signaling / Salmonella. Subject area(s): Immunology , Microbiology, Virology & Pathogens , Signal Transduction. ...
The main focus of our current research is: (1) to understand subpopulations of cancer cells, such as cancer stem cells from human melanoma, (2) to study biological roles of inflammatory or anti-inflammatory molecules (particularly IL-1, IL-37 and AAT, inflammasome components) in the progression of human malignant melanoma, (3) to understand biological roles of a new cytokine, IL-37, (4) to identify melanoma-related and host response-related biomarker profiling from blood of melanoma patients, and (5) to identify metastasis-related genetic/genomic changes in human melanoma. The experiments utilize in vitro methodologies (cellular and molecular biology, immunology, pathology) and in vivo animal study (xenotransplantation, direct in vivo xenograft and genetically-engineered mouse models). ...
Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
IL-36 beta/IL-1F8 Antibodies available through Novus Biologicals. Browse our IL-36 beta/IL-1F8 Antibody catalog backed by our Guarantee+.
Complete information for CARD10 gene (Protein Coding), Caspase Recruitment Domain Family Member 10, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Despite the recognized role of inflammation in cardiovascular diseases including atherosclerosis, this role may not be an initiating or essential mechanism in a...
Red Hat recently announced beta release of JBoss Data Grid (JDG) , a supported product based on Infinispan. Infinispan was first announced in 2009 and its first GA release was made in February, 2010. So it took more than three years for us, folks at JBoss, to announce a supported beta release. In case you are wondering why it took so long, here are few things to consider. Besides introducing several handy features such as virtual nodes, grouping API, deadlock detection and optimization, improvements with transactions, we wanted to make sure that ...
An additional visual feedback is introduced to help distinguish hot-swapping an entire drum rack vs. hot-swapping only a single drum pad. In the former case, all drum pads will start pulsing white as long as the browser is open, whereas for hot-swapping a single pad, that pad is pulsing. When hot-swapping a device on a drum pad, no indication is visible. This also fixes a bug which would occur when you were holding a step in the step sequencer, where the pad would stop blinking once it was passed by the playhead ...
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Join Intel technical experts for a deep-dive discussion covering the details and new features of Intel® Parallel Studio XE 2018 Beta releases for the latest Intel multicore and many-core co-process. ...
Temporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Understanding the mechanisms of cell death is a key for preventing the neurodegeneration associated with TLE. However, the involvement of neuronal death to the epileptogenic process has yet to be fully determined. Recent studies shown that the activation of NLRP1 inflammasome can generate a functional caspase-1-containing inflammasome in vivo to drive the proinflammatory programmed cell death termed pyroptotic death [5], which have key roles in the pathogenesis of neurological disorders [4,21,22]. NLRP1 is also highly expressed in pyramidal neurons of the brain [8]. In addition, inflammasome activation especially the NLRP1 is under current investigation across a broad spectrum of neurological diseases, including infections, acute sterile brain injury and chronic neurodegenerative diseases [23]. However, to the best of our knowledge, there are no reported studies that performed a ...
NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the inflammasome by regulating caspase-1 activity and interleukin (IL)-1 beta processing. The contribution of IL-1 beta in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domaincontaining protein (CARD)8, a negative regulator of caspase-1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohns disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan (R) Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more ...
Salmonella induces programmed cell death in macrophages by complex mechanisms that involve distinct pathways and require the bacterial TTSS encoded in the pathogenicity island 1 (SPI-1 TTSS). One death pathway, which results in rapid macrophage death with features of necrosis, is dependent on caspase-1 and the SPI-1 TTSS-secreted protein SipB (Hersh et al., 1999; Brennan and Cookson, 2000; Jesenberger et al., 2000). However, macrophages from caspase-1−/− mice also undergo programmed cell death, although with delayed kinetics and different morphological features. Here, we have described another death pathway induced by Salmonella that is independent of caspase-1. A systematic bacterial genetic analysis led us to conclude that this cell death pathway is also dependent on SipB, a protein with membrane fusion activity that is delivered into host cells by the SPI-1 TTSS. This analysis was complicated by the known dual function of SipB, which acts both as an effector of virulence within cells and ...
The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic DNA has been identified as a danger signal that activates inflammasomes containing the DNA sensor AIM2. In this study, we detected abundant cytosolic DNA and increased AIM2 expression in keratinocytes in psoriatic lesions but not in healthy skin. In cultured keratinocytes, interferon-γ induced AIM2, and cytosolic DNA triggered the release of IL-1β via the AIM2 inflammasome. Moreover, the antimicrobial cathelicidin peptide LL-37, which can interact with DNA in psoriatic skin, neutralized cytosolic DNA in keratinocytes and blocked AIM2 inflammasome activation. Together, these data suggest that cytosolic DNA is an important disease-associated molecular pattern that can trigger ...
Purpose : The retinal pigment epithelium (RPE) plays a critical role in lipid homeostasis in the retina. A growing body of evidence suggests that dysfunctional lipid metabolism, accumulation of oxidized low-density lipoprotein (ox-LDL) and inflammasome activation are associated with RPE dysfunction and the pathogenesis of dry AMD. We have previously shown that ox-LDL is cytotoxic for RPE by inflammasome-mediate pyroptosis. We hypothesize that activation of the peroxisome proliferator-activated receptors (PPARs) will increase lipid metabolism and suppress inflammation, and thereby rescue RPE cells from ox-LDL induced cell death. Methods : ARPE-19 and/or primary human fetal RPE cells were treated for 48 hours with a range of concentrations of ox-LDL in the presence or absence of different agonists that selectively activate the three different PPAR isoforms: PPAR-α (fenofibrate 30 μM), PPAR-γ (troglitazone 0.55 μM), and PPAR-β/δ (bezafibrate 60 μM). Cell death was measured by lactate ...
Many landmark studies have reported the Nod-like receptor proteins containing Pyrin domain (NLRP3) inflammasome activation in metabolic diseases that include obesity, atherosclerosis and type 2 diabetes. Therefore, the present study was aimed: (i) to determine the role of NLRP3 in inflammation and insulin resistance in high fat diet-induced obesity (DIO) model of mice, and (ii) to determine whether parthenolide, a NLRP3 inhibitor, is able to protect mice against inflammation and insulin resistance in high fat DIO model.. METHODS: Lipopolysaccharide (1 ng/ml) primed mouse intraperitoneal macrophages were treated with Parthenolide (0.1 to 30 μM) to evaluate its effect on TNF-α and IL-1β. Parthenolide and Pioglitazone were administered to DIO mice (fed 60% high fat diet) at 5 and 30 mg/kg QD, PO, respectively for 60 days to evaluate their effect on insulin resistance.. RESULTS: Parthenolide (5 mg/kg) markedly attenuated inflammatory cytokines as evidenced by significant and dose dependant ...

caspase-1 [Mus musculus] - Protein - NCBIcaspase-1 [Mus musculus] - Protein - NCBI

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] ...
more infohttps://www.ncbi.nlm.nih.gov/protein/86198305

Caspase-1 - DrugBankCaspase-1 - DrugBank

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 ...
more infohttps://www.drugbank.ca/polypeptides/P29466

Caspase-1: the inflammasome and beyond.  - PubMed - NCBICaspase-1: the inflammasome and beyond. - PubMed - NCBI

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 ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/23676582?dopt=Abstract

Anti-Caspase-1 antibody (ab1872) | AbcamAnti-Caspase-1 antibody (ab1872) | Abcam

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 ...
more infohttps://www.abcam.com/caspase-1-antibody-ab1872.html?productwalltab=abreviews

caspase 1 Protocols and Video...'caspase 1' Protocols and Video...

Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction, A Simple Fluorescence ... caspase 1 include Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization ... Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation, The Ex Vivo Colon Organ ... Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay, Visualization ...
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Caspase 1 - WikipediaCaspase 1 - Wikipedia

... 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 ... Activated Caspase 1 proteolytically cleaves pro IL-1β and pro IL-18 into their active forms, IL-1β and IL-18. The active ...
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Caspase 1 Primary Antibodies
                
		        
	Caspase 1 Primary Antibodies

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Sf caspase-1 - WikipediaSf caspase-1 - Wikipedia

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 a 18 kDa instead of 19 kDa fragment ...
more infohttps://en.wikipedia.org/wiki/Sf_caspase-1

Recombinant Human Caspase-1 protein (ab158029) | AbcamRecombinant Human Caspase-1 protein (ab158029) | Abcam

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 ...
more infohttps://www.abcam.com/recombinant-human-caspase-1-protein-ab158029.html

Protocol to activate caspase-1 - Please help! - ImmunologyProtocol to activate caspase-1 - Please help! - Immunology

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 ...
more infohttp://www.protocol-online.org/biology-forums-2/posts/29729.html

Caspase-1 | definition of Caspase-1 by Medical dictionaryCaspase-1 | definition of Caspase-1 by Medical dictionary

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 ...
more infohttp://medical-dictionary.thefreedictionary.com/Caspase-1

Caspase 1 with inhibitor - Stock Image C025/1626 - Science Photo LibraryCaspase 1 with inhibitor - Stock Image C025/1626 - Science Photo Library

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 ...
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Caspase 1 with inhibitor - Stock Image C025/1625 - Science Photo LibraryCaspase 1 with inhibitor - Stock Image C025/1625 - Science Photo Library

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 ... Keywords: apoptosis, artwork, biochemistry, biological, biology, caspase 1, complex, cut out, cut outs, cut-out, cut-outs, ...
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Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response | PNASRegulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response | PNAS

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 ...
more infohttp://www.pnas.org/content/108/51/20742.short

Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis | PNASCaspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis | PNAS

S1B). Caspase-1 immunoreactivity was detected in occasional cells in the white matter of non-MS tissue (Fig. 1 E, i) but was ... 5 G, iv, green) and caspase-1 (Fig. 5 G, ii, red). The majority of GST-pi+ ODCs in the ventral spinal cords from EAE animals ... Oligomerization of sensor proteins with the scaffolding protein ASC and proinflammatory caspases (caspase-1 and -4/5 in humans ... 6E). Caspase-1 immunoreactivity was also limited in CFA-exposed animals (Fig. 6 C, i) and increased in vehicle-treated EAE ...
more infohttps://www.pnas.org/content/115/26/E6065.long

Nigericin for generating a caspase-1 activation response.Nigericin for generating a caspase-1 activation response.

... nigericin can be used as a positive control to generate a robust caspase-1 activation response in a variety of cell lines. ... Inflammatory caspases, such as caspase-1, play a critical role in the mechanism to trigger the lytic programmed cell death ... The amount of caspase-1 activity detected directly correlated to the duration of the exposure period; the longer the cells were ... ICTs caspase-1 inhibitor reagent, FAM-YVAD-FMK (kit catalog #9146) was used to monitor the caspase-1 induction response in ...
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JCI -
Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failureJCI - Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure

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 ...
more infohttps://www.jci.org/articles/view/12089/pdf

Caspase 1, MBL International | VWRCaspase 1, MBL International | VWR

Learn more about Caspase 1, MBL International. We enable science by offering product choice, services, process excellence and ...
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Caspase-1 (Interleukin-1ß-Converting Enzyme) | BioVendorCaspase-1 (Interleukin-1ß-Converting Enzyme) | BioVendor

Pro-Caspase-1, once activated by an inflammasome complex is processed into p20 and p10 subunits that assembles to form a p20- ... Caspase-1 (Interleukin-1ß-Converting Enzyme). Caspase-1 is the best-described inflammatory caspase. It processes the cytokines ... Caspase-1 is synthesized as inactive pro-Caspase-1, wich is activated and processed by multiprotein complexes called ... You are here: Home Products by Molecule of Interest Caspase-1 (Interleukin-1ß-Converting Enzyme) ...
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Caspase 1 involvement in human monocyte lysis induced by Actinobacillus actinomycetemcomitans leukotoxinCaspase 1 involvement in human monocyte lysis induced by Actinobacillus actinomycetemcomitans leukotoxin

... Kelk, Peyman Umeå ... Presence of the caspase 1 inhibitor Ac-YVAD-CMK significantly blocked the leukotoxin-induced lysis of monocytes only. At ... It was mainly mediated by caspase-1 activation, since blocking it by a specific inhibitor also abolished the secretion of IL-1β ... Their lysis by this toxin depends on caspase 1 activation and proceeds through a process that differs from classical apoptosis. ...
more infohttp://umu.diva-portal.org/smash/record.jsf?pid=diva2%3A146154&c=28&searchType=SIMPLE&language=sv&query=&af=%5B%5D&aq=%5B%5B%7B%22personId%22%3A%22authority-person%3A65531%22%7D%5D%5D&aq2=%5B%5B%5D%5D&aqe=%5B%5D&noOfRows=50&sortOrder=author_sort_asc&sortOrder2=title_sort_asc&onlyFullText=false&sf=all

caspase-1 substrate | CAS 143305-11-7 | SCBT - Santa Cruz Biotechnologycaspase-1 substrate | CAS 143305-11-7 | SCBT - Santa Cruz Biotechnology

Buy caspase-1 substrate (CAS 143305-11-7), to inhibit the cleavage of the IL-1β precursor by ICE, from Santa Cruz. Purity: ≥93 ... caspase-1 substrate Inhibits the cleavage of the IL-1β precursor by ICE *Home. ... The Caspase-1 substrate sequence (NEAYVHDAPVRSLN) corresponds to the native cleavage site C-terminal to Asp-116 of the ... caspase-1 substrate (CAS 143305-11-7) *bvseo_sdk, java_sdk, bvseo-3.2.0 ...
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Frontiers | A New Twist in the Regulation of Legionella Replication through ASC and Caspase-1 | MicrobiologyFrontiers | A New Twist in the Regulation of Legionella Replication through ASC and Caspase-1 | Microbiology

... to link NLRs to pro-caspase-1, a critical step in the activation of caspase-1. Legionella pneumophila (Legionella) is a Gram- ... a molecular platform that drives the activation of caspase-1, a protease responsible for the maturation and secretion of IL-1b ... A New Twist in the Regulation of Legionella Replication through ASC and Caspase-1 ... but relies on caspase-7, another protein substrate of caspase-1 (Akhter et al., 2009). In addition, Naip5 contributes to the ...
more infohttps://www.frontiersin.org/articles/10.3389/fmicb.2011.00057/full

Caspase-1 inhibitor I | CAS 143313-51-3 | SCBT - Santa Cruz BiotechnologyCaspase-1 inhibitor I | CAS 143313-51-3 | SCBT - Santa Cruz Biotechnology

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JCI -
Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in miceJCI - 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. ... Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. ...
more infohttps://www.jci.org/articles/view/15623/figure/7
  • Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. (drugbank.ca)
  • 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)
  • 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)
  • A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. (drugbank.ca)
  • 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)
  • There is detectable activation of caspase-7 downstream, but not 3. (protocol-online.org)
  • In unstressed mouse hearts with a 30-fold increase in procaspase-1 content, unprocessed procaspase-1 was well tolerated, without detectable pathology. (ahajournals.org)
  • Exposure of monocytes to leukotoxin increased their caspase 1 activity about fivefold within 10 to 20 min. (diva-portal.org)
  • Presence of the caspase 1 inhibitor Ac-YVAD-CMK significantly blocked the leukotoxin-induced lysis of monocytes only. (diva-portal.org)
  • Purified immunoglobulin fraction of rabbit antiserum against human Caspase-1. (abcam.com)
  • Cytolysis was determined by the activity of lactate dehydrogenase released from peripheral human leukocytes after 1-h exposure to leukotoxin. (diva-portal.org)
  • KLH-conjugated synthetic peptide encompassing a sequence within the C-terminal region of human Caspase 1. (lsbio.com)
  • Immunohistochemical analysis of Caspase 1 staining in human breast cancer formalin fixed paraffin embedded tissue section. (lsbio.com)
  • 6,7 Eleven human caspases homologous to the original nematode caspase, CED-3, have been identified to date. (ahajournals.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)
  • Transgenic mice that overexpress IL-18 ( 18 ) or caspase-1 ( 19 ) in their keratinocytes showed high serum IL-18 and IgE levels. (aacrjournals.org)
  • Salmonella mutants lacking YdiV are unable to fully repress flagellin at systemic sites, rendering them vulnerable to caspase-1 mediated colonization restriction. (pnas.org)
  • 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)