A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Peptides composed of between two and twelve amino acids.
A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate indefinitely.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
Transport proteins that carry specific substances in the blood or across cell membranes.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Physiologically inactive substances that can be converted to active enzymes.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.
Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Elements of limited time intervals, contributing to particular results or situations.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glycoproteins found on the membrane or surface of cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
Proteins prepared by recombinant DNA technology.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Compounds that inhibit cell production of DNA or RNA.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Proteins found in any species of virus.
The process of cleaving a chemical compound by the addition of a molecule of water.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins found in any species of insect.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The process by which chemical compounds provide protection to cells against harmful agents.
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

ASC is an adaptor protein which contains two protein-protein interaction domains; N-terminal - pyrin domain (PYC) and C-terminal - caspase recruitment domain (CARD).. ASC plays an important role in inflammation and apoptosis. It is a component of several inflammatory complexes, inflammasomes, which are important for caspase-1 activation, processing and secretion of pro-inflammatory cytokines (IL-1β, IL-18). It promotes pyropoptosis in macrophages and induces caspase-mediated apoptosis (involving caspase-8 and caspase-9).. Additionally, ASC is involved in transcriptional control of cytokine and chemokine expression independent of the inflammasome.. ...
Background: Inflammatory responses play a key role in the pathophysiology of myocardial ischemia-reperfusion (I/R) injury. ASC is an adaptor protein that forms inflammasome whose activation leads to caspase-1-dependent interleukin (IL)-1β generation and subsequent inflammatory responses; however, the role of ASC in myocardial I/R injury remains to be determined.. Methods and Results: ASC deficient (ASC−/−) and wild-type (WT) mice were subjected to 30 min LAD occlusion, followed by reperfusion. ASC−/− mice showed improved LV dysfunction (%FS: 34.0% vs. 25.7% at 14 days p,0.01), reduced infarct area/area at risk (IA/AAR: 18.7% vs. 28.6% at 48 h, p,0.01), and scar formation (scar/LV area: 9.7% vs. 14.6% at 14 days, p,0.01) after myocardial I/R. Immunostaining revealed decreased infiltration of macrophages (Mac3) and neutrophils (Gr-1), but not neovascularization (CD31), in the injured myocardium of the ASC−/− mice. Real-time RT-PCR and ELISA analyses demonstrated that the myocardial ...
Shop NLR family ELISA Kit, Recombinant Protein and NLR family Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
NALP1 antibody [Nalpy1-4] (NLR family, pyrin domain containing 1) for ICC/IF, IHC-P, IP, WB. Anti-NALP1 mAb (GTX16091) is tested in Human samples. 100% Ab-Assurance.
NLRP13 antibody (NLR family, pyrin domain containing 13) for ELISA, ICC/IF, WB. Anti-NLRP13 pAb (GTX31990) is tested in Human samples. 100% Ab-Assurance.
cdna:known chromosome:VEGA66:16:3945610:3976632:-1 gene:OTTMUSG00000042324 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Nlrc3 description:NLR family, CARD domain containing 3 ...
NALP1兔多克隆抗体(ab36852)可与人样本反应并经WB, IHC, ICC/IF实验严格验证,被4篇文献引用。所有产品均提供质保服务,中国75%以上现货。
ASC2兔多克隆抗体(ab47092)可与小鼠, 大鼠, 人, 沙鼠样本反应并经WB, IP, IHC实验严格验证。所有产品均提供质保服务,中国75%以上现货。
I need some help. I have a ASC case where the MD did a cystourethroscopy w/ bilaterial retrograde ureterograms. He also did Litholapaxy with the extra
Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We developed transgenic mice that ectopically express the fluorescent adaptor protein, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and characterized the formation of assembled inflammasome complexes (specks) in primary cells and tissues. In addition to hematopoietic cells, we found that a stromal population in the lung tissues forms specks during the early phase of influenza infection whereas myeloid cells showed speck formation after two days. In a peritonitis and Group B streptococcus infection models, a higher percentage of neutrophils formed specks at early phases of infection, while dendritic cells formed specks at later time points. Furthermore, speck-forming cells underwent pyroptosis, and extensive release of specks to the extracellular milieu in vivo. These data underscore the ...
The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound conditioned medium activates caspase-1 and induces release of IL-1β and IL-18 in cultured Mp via a reactive oxygen species-mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from pro-inflammatory to healing-associated Mp phenotypes and increased levels of pro-healing growth factors. Furthermore, data ...
NLRP3 inflammasome assembly. CARD, caspase recruitment domain; LRR, leucine-rich repeat; NACHT/NBD, nucleotide binding domain; PYD, pyrin domain; CAP1, caspase-
PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome . NMR structure of full-length ASC: PDB ID 2KN6 [1] This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ...
Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22-82) in association with age. Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas
To the Editor. We read the article of Osuka et al. (1) entitled A Protective Role for Inflammasome Activation Following Injury with great interest. However, we are concerned that the authors have not sufficiently ruled out the possibility that the major effects attributed to inflammasome inhibition were merely due to the solvent used.. The authors describe inflammasome activation in burned mice 1 day after injury as revealed by caspase 1 activation and increased interleukin 1β (IL-1β) production. Interestingly, the data suggest that inhibiting caspase 1 activity-and thereby inhibiting inflammasome activation-with the Ac-YVAD-cmk peptide did not reduce inflammation as expected. On the contrary, it caused a significantly higher mortality and increased expression of the proinflammatory cytokines IL-6 and IL-33 as compared with untreated burned mice. The authors therefore conclude that inflammasome activation might have a protective role following severe injury. Inhibition of (pro)caspase 1 ...
The cytosolic pattern recognition receptor NLRP3 senses host-derived danger signals and certain microbe-derived products in both humans and rodents. NLRP3 activation assembles an inflammasome complex that contains the adapter proteins ASC and caspase-1, whose activation triggers the maturation and release of the proinflammatory cytokines IL-1β and IL-18. S5 phosphorylation of NLRP3 prevents its oligomerization and activation, whereas dephosphorylation of this residue by the phosphatase PP2A allows NLRP3 activation. However, the protein kinase that mediates NLRP3 S5 phosphorylation is unknown. In this study, we show that AKT associates with NLRP3 and phosphorylates it on S5, limiting NLRP3 oligomerization. This phosphorylation event also stabilizes NLRP3 by reducing its ubiquitination on lysine 496, which inhibits its proteasome-mediated degradation by the E3 ligase Trim31. Pharmacologic manipulation of AKT kinase activity reciprocally modulates NLRP3 inflammasome-mediated IL-1β production. ...
Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. The NLRP3 inflammasome requires two stages to contribute: priming and activation. The priming stage involves upregulation of inflammasome components while the activation stage results in the assembly and activation of the inflammasome complex. The priming step can be rate limiting and can connect insult to chronic inflammation, but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammation is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure (IOP) increased mRNA for inflammasome components IL-1β, NLRP3, ASC and CASP1 in rat and mouse retinas. The elevation was greater one day after
Chronic inflammation and inflammasome activation play roles in the pathogenesis of type 2 diabetes (2,29,30). NLRP3 is a member of the NLR family, which is responsible for cytosolic inflammasome activation. The NLRP3 inflammasome has been the focus of particular attention with regard to its roles in inflammatory responses, antimicrobial responses, and a variety of human diseases, including hereditary autoinflammatory syndromes, atherosclerosis, and diabetes (7,22,30,31). Recently, obesity-induced danger signals have been reported to activate the NLRP3 inflammasome and induce the production of IL-1β in adipose tissue in type 2 diabetic patients and mice fed a high-fat diet (9). Circulating levels of C-X-C motif chemokine 10 and CCL2, as well as interferon-γ mRNA and protein levels in adipose tissue, were significantly reduced in NLRP3-deficient mice, suggesting that the NLRP3 inflammasome plays a role in the macrophage-T-cell interactions that are associated with sustained levels of chronic ...
The ASC (apoptosis speck-like protein) is a key component of multimeric protein complexes that mediate inflammation and host defence. Comprising a PYD (Pyrin) domain and a CARD (caspase activation and recruitment domain), ASC functions downstream of NLRs (nucleotide-binding domain, leucine-rich repeat-containing receptors) and AIM2 (absent in melanoma 2) through the formation of supramolecular structures termed inflammasomes. However, the mechanism underlying ASC signalling and its dependency on oligomeric arrangements in inflammasome formation remain poorly understood. When expressed in cells, ASC forms discrete foci (called specks) typically with one speck per cell. We employed a BiFC (bimolecular fluorescence complementation) system to investigate and visualize ASC foci formation in living cells. We demonstrated that the CARD of ASC plays a central role in ASC inflammasome assembly, representing the minimal unit capable of forming foci in conjunction with the caspase 1 CARD. Mutational ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
On September 21, 2017, Posted by Birgit Rogell , In Press Releases, With Kommentare deaktiviert für EMBL: Visualization of inflammasome formation in real life ...
Exaggerated inflammasome activation in venous thrombosis in CD39-deficient mice. Extracellular release of ATP and ADP through cell death, injury, or activation is a potent stress response, altering the local microenvironment to activate paracrine and autocrine signaling pathways (18, 19). Binding of extracellular ATP to the plasma membrane receptor ionophore P2X7 activates a potent stress-response-signaling pathway characterized by potassium efflux, which triggers assembly and activity of the inflammasome, a multiprotein oligomer that activates highly proinflammatory cytokines including IL-1β (20). Gupta et al. recently reported increased NLRP3 inflammasome assembly in patients at high altitude at risk for DVT (21). Canonical inflammasome activation requires a priming step marked by NF-κB activation and inflammasome component transcription (20). A second signal initiates NLRP3-mediated assembly and oligomerization of inflammasome component fibers, proteolytic cleavage of pro-caspase-1 to ...
TroLucaM. Lemarchand E, Barrington J, Chenery A, Haley M, Coutts G, Allen JE, et al. Extent of Ischemic Brain Injury After Thrombotic Stroke Is Independent of the NLRP3 (NACHT, LRR and PYD Domains-Containing Protein 3) Inflammasome. Stroke. 2019;50:1232-1239.. Inflammation plays a key role in the fight against infection. However, following ischaemic brain injury, inflammation can play a very different role, exacerbating the severity of damage. Inflammation results in long lasting, ongoing damage from the onset of vessel blockage through to and during reperfusion of the ischaemic brain area. One possible player within the inflammation related post-stroke damage is the NLR family pyrin domain containing 3 (NLRP3) inflammasome. During ischaemic brain injury, NLRP3 senses multiple stroke-induced stimuli leading to the recruitment of the adaptor protein ASC (the apoptosis-associated speck-like pro-caspase-1) resulting in caspase 1 production leading to downstream IL-1β and IL-18 production and ...
There is a clear need for interdisciplinary research and publications that bring together scientists who work on the inflammasome. This protein complex, termed the inflammasome and many of its components are implicated in disease disorders, autoimmune and infectious diseases. The structure, activation and regulation of the inflammasome complex have been and are still studied in increasing number of laboratories around the world. Our goal is to provide an issue summarizing every fascinating aspect of inflammasome activation and modulation of the innate immune response to microbial and to danger signals. This issue will bring the experts in inflammasome research up to speed with the most recent findings. However, several reviews are geared towards introducing the new scientists to the inflammasome complex and to the fundamental and essential information that will help them understand and even pursue their studies in this direction. By looking at the two sides of the coin, notably, some authors focused on
AIM2 is a cytosolic DNA sensor of the inflammasome, which induces critical innate immune responses against various invading pathogens. Earlier biochemical studies showed that the binding of AIM2 to DNA triggered the self-oligomerization of AIM2, which is essential for AIM2 inflammasome activation. We recently reported that VP22, a virion tegument protein of herpes simplex virus 1 (HSV-1), inhibited activation of the AIM2 inflammasome in HSV-1-infected cells by preventing AIM2 oligomerization. VP22 binds nonspecifically to DNA; however, its role in HSV-1 replication is unclear. We investigated the role of VP22 DNA binding activity in the VP22-mediated inhibition of AIM2 inflammasome activation. We identified a VP22 domain comprising amino acids 227 to 258 as the minimal domain required for its binding to DNA in vitro. Consecutive alanine substitutions in this domain substantially impaired the DNA binding activity of VP22 in vitro and attenuated the inhibitory effect of VP22 on AIM2 inflammasome ...
THE Fas/APO-1 receptor is one of the major regulators of apoptosis(1-7). We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE)(8-10) which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.. ...
Active Caspase-1, rat recombinant protein , Interleukin-1 beta convertase, Interleukin-1 beta-converting enzyme, IL-1BC, p45. validated in (PBV11136r-25), Abgent
Cellulose nanocrystal cationic derivative induces NLRP3 inflammasome-dependent IL-1β secretion associated with mitochondrial ROS production
Buy NLRP1 elisa kit, Mouse NLR Family, Pyrin Domain Containing 1 (NLRP1) ELISA Kit (MBS109213) product datasheet at MyBioSource, ELISA Kits
Inflammasomes are large protein complexes formed in response to cellular stresses that are platforms for recruitment and activation of caspase 1
Supervisor: Dr Xuan Li. Title: Identification and characterisation of NLRP3 interactome. Abstract: Aberrant activation of the NLRP3 inflammasome is involved in sterile inflammation in multiple chronic diseases such as atherosclerosis, type 2 diabetes or Alzheimers disease. Identification of novel players regulating the NLRP3 inflammasome could therefore lead to the development of new therapeutic strategies.. Here, we propose to further characterize the NLRP3 interactome during inflammasome activation. We will then select and investigate the identified interaction partners in the NLRP3 inflammasome pathway. These experiments will not only shed light into the NLRP3 regulatory mechanism during inflammasome activation, but also reveal new role players in the NLRP3 inflammasome pathway.. ...
TY - CHAP. T1 - Pyroptosis. AU - Lawlor, Kathryn. AU - Conos, Stephanie A.. AU - Vince, James E. PY - 2018/12/9. Y1 - 2018/12/9. N2 - Pyroptosis is considered an inflammatory cell death pathway that can be triggered by caspase‐1 or caspase‐11, or the human caspase‐11 orthologs, caspase‐4 and caspase‐5. The activation of caspase‐1 is mediated by supramolecular cytosolic protein complexes, termed inflammasomes, which sense specific pathogen, host or environmental danger molecules. Prior to causing pyroptotic death, caspase‐1 can also cleave and thereby activate the potent pro‐inflammatory cytokines, interleukin‐1 (IL‐1 ) and IL‐18. In contrast, the activation of caspase‐11 is caused by its direct binding to cytosolic lipopolysaccharide (LPS) derived from gram‐negative bacteria. While caspase‐11 can promote caspase‐1 activity, caspase‐1 is not required for caspase‐11 killing, and caspase‐11 itself does not efficiently activate IL‐1 or IL‐18. Unlike apoptotic ...
Supplementary Material for: Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia
Recent study of the CAPS disease spectrum has led to significant advances in our understanding of the NLRP3 inflammasome and IL-1β-mediated inflammation. While translational studies have resulted in vital therapies for patients with CAPS, many questions about the inflammasome and other caspase-1-dependent pathways remain. Inflammasome-mediated IL-18 has largely been overlooked in the context of human disease. In addition, recent studies have demonstrated caspase-1 and inflammasome functions extending beyond cytokine maturation to cellular death pathways, but whether these processes have any bearing on CAPS remains to be seen. Here, we take advantage of mutant NLRP3 knockin mouse lines to investigate these questions.. Our studies demonstrate that dysregulated IL-18 secretion occurs from both patient and Nlrp3 mutant mouse cells in a manner similar to IL-1β. In vitro, a hallmark of CAPS is lack of reliance on the 2-signal paradigm generally required for secretion of active IL-1β. We used this ...
Sigma-Aldrich offers abstracts and full-text articles by [Ying Yang, Dong-Mei Zhang, Jia-Hui Liu, Lin-Shui Hu, Qiao-Chu Xue, Xiao-Qin Ding, Ling-Dong Kong].
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Formation of the inflammasome results in the activation of multiple pathways responsible for co-ordinating our immune response, yet interestingly, there are multiple forms of inflammasomes made up and triggered by different sets of proteins. This initial step of activation has been covered very well before, here. The activated inflammsome goes on to trigger key downstream members of our innate immune system through the recruitment of an important regulatory protease (it cuts up other proteins) - caspase 1, which converts inactive molecules to active, pro-inflammatory ones, such as interleukin-1 beta and interleukin-18. This inflammatory cascade functions to initiate an effective local and systemic immune response through the control of the innate and adaptive immune system; for example, IL-beta is responsible for fever and the recruitment of immune cells to the site of infection, and IL-18 induces the development of key T cell responses ...
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NLRP7 - NLRP7 (untagged)-Human NLR family, pyrin domain containing 7 (NLRP7), transcript variant 1 available for purchase from OriGene - Your Gene Company.
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Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-a
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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
NALP3 is a component of the innate immune system that functions as a pattern recognition receptor (PRR) that recognizes pathogen-associated molecular patterns (PAMPs).[15] NALP3 belongs to the NOD-like receptor (NLR) subfamily of PRRs and NALP3 together with the adaptor ASC protein PYCARD forms a caspase-1 activating complex known as the NALP3 inflammasome. NALP3 in the absence of activating signal is kept in an inactive state complexed with HSP90 and SGT1 in the cytoplasm. NALP3 inflammasome detects danger signals such as crystalline uric acid and extracellular ATP released by damaged cells. These signals release HSP90 and SGT1 from and recruit ASC protein and caspase-1 to the inflammasome complex. Caspase-1 within the activated NALP3 inflammasome complex in turn activates the inflammatory cytokine, IL-1β.[15] The NALP3 inflammasome appears to be activated by changes in intracellular potassium caused by potassium efflux from mechanosensitive ion channels located in the cell membrane.[16] It ...
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 ...
Deubiquitination of NLRP3 has been suggested to contribute to inflammasome activation, but the roles and molecular mechanisms are still unclear. We here demonstrate that ABRO1, a subunit of the BRISC deubiquitinase complex, is necessary for optimal NLRP3‐ASC complex formation, ASC oligomerization, caspase‐1 activation, and IL‐1β and IL‐18 production upon treatment with NLRP3 ligands after the priming step, indicating that efficient NLRP3 activation requires ABRO1. Moreover, we report that ABRO1 deficiency results in a remarkable attenuation in the syndrome severity of NLRP3‐associated inflammatory diseases, including MSU‐ and Alum‐induced peritonitis and LPS‐induced sepsis in mice. Mechanistic studies reveal that LPS priming induces ABRO1 binding to NLRP3 in an S194 phosphorylation‐dependent manner, subsequently recruiting the BRISC to remove K63‐linked ubiquitin chains of NLRP3 upon stimulation with activators. Furthermore, deficiency of BRCC3, the catalytically active ...
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 ...
CARD8 (caspase recruitment domain family, member 8), Authors: Frank A. Kruyt. Published in: Atlas Genet Cytogenet Oncol Haematol.
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 ...
NLRP3 inflammasome-dependent inflammatory responses are triggered by a variety of signals of host danger, including infection, tissue damage and metabolic dysregulation. How these diverse activators cause inflammasome activation is poorly understood. Recent data suggest that the mitochondria integra …
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…
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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The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin ...
A hierarchical task manager with native XML support for custom reporting.; Author: .dan.g.; Updated: 20 Jan 2012; Section: Applications & Tools; Chapter: Web Development; Updated: 20 Jan 2012
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 ...
Her lab identified caspase-8 and FADD as expression and activation regulators of both the canonical and non-canonical NLRP3 ... This finding went against the dogma that existed at that time that caspase-8 and FADD were involved only in the apoptotic ... Kanneganti's lab showed compensatory roles for NLRP3/caspase-1 and caspase-8 in the regulation of IL-1β production in ... This study demonstrated that the NLRP3 inflammasome/pyroptotic pathway is closely connected to the caspase-8-mediated ...
Caspase-1 is important for the proteolytic processing of the pro-inflammatory cytokines IL-1β and IL-18. NLRP3 mutations are ... ASC contains PYD and CARD domain and links the NLRs to inactive form of caspase 1 through the CARD domain. All these protein- ... N-terminal domain is responsible for homotypic protein-protein interaction and it can consist of caspase recruitment domain ( ... The aggregation of the pro-caspase-1 causes the autocleavage and formation of an active enzyme. ...
Stierle, Donald B.; Stierle, Andrea A.; Girtsman, Teri; McIntyre, Kyle; Nichols, Jesse (2012). "Caspase-1 and -3 Inhibiting ... 329 (1): 9-17. doi:10.1111/j.1574-6968.2012.02497.x. PMID 22239643. Pitt, J. I. (1991). "Penicillium solitum Revived, and its ... doi:10.1016/S0031-9422(99)00015-1. Romanovskaya, I. I.; Bondarenko, G. I.; Davidenko, T. I. (2008). "Immobilization of ... doi:10.1016/S0031-9422(99)00015-1. Larsen, Thomas Ostenfeld; Lange, Lene; Schnorr, Kirk; Stender, Steen; Frisvad, Jens ...
July 2018). "mTORC2 Activity Disrupts Lysosome Acidification in Systemic Lupus Erythematosus by Impairing Caspase-1 Cleavage of ... Torin-1 can also be used to inhibit mTORC2. Similar to other PI3K regulated proteins, mTORC2 has a mSin1 subunit, which ... 28 (1): 61-70. doi:10.1128/MCB.01405-07. PMC 2223287. PMID 17967879. Kleinert M, Sylow L, Fazakerley DJ, Krycer JR, Thomas KC, ... 26 (1): 46-65. doi:10.1038/cr.2015.133. PMC 4816127. PMID 26584640. Zoncu R, Efeyan A, Sabatini DM (January 2011). "mTOR: from ...
It activates caspase-1 and assists in the maturation of the proinflammatory cytokines IL-1β and IL-18. As with other NOD-like ... creating a response under the concept of the inflammasome including K+ efflux and caspase 1 activation. NLRP is also known to ... "Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF". The Journal of Immunology ... Experiments have suggested that Muckle-Wells syndrome is closely tied to IL-1 signaling, as when IL-1 receptor antagonists are ...
Henderson G, Peng W, Jin L, Perng GC, Nesburn AB, Wechsler SL, Jones C (December 2002). "Regulation of caspase 8- and caspase 9 ... Other research showed that the products from the first 4,658 nucleotides of LAT inhibited caspase-8 and caspase-9 cellular ... Little is known about these two proteins (P17588 and P17589 in HHV-1; K4PBJ5 and Q77CA8 in BHV-1), although the loss of ORF2 in ... Jiang Y, Inman M, Zhang Y, Posadas NA, Jones C (March 2004). "A mutation in the latency-related gene of bovine herpesvirus 1 ...
... activate inflammatory caspases (e.g. caspase 1) causing cleavage and activation of important inflammatory cytokines such as IL- ... Other NLRs such as IPAF and NAIP5/Birc1e have also been shown to activate caspase-1 in response to Salmonella and Legionella. ... 91 (1): 36-47. doi:10.1016/j.ejcb.2011.01.011. PMID 21481967. Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, ... 6 (1): 9-20. doi:10.1038/nri1747. PMID 16493424. S2CID 33505741. Burberry A, Zeng MY, Ding L, Wicks I, Inohara N, Morrison SJ, ...
September 2013). "Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β ... Variant 1 mRNA is 1,243 base pairs long while Variant 2 mRNA is 1,241 base pairs long. Isoform 2 differs in the 5' UTR region ... Isoform 1 is18,882 Da and has a pI of 6.27. Using compositional analysis, the amino acid composition is similar to the average ... 289 (1): 253-61. doi:10.1016/j.ydbio.2005.10.041. PMID 16324689. "GDS5112 / 1448317_at". www.ncbi.nlm.nih.gov. Retrieved May 2 ...
"TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in ... 159 (1): 205-10. doi:10.1111/j.1365-2133.2008.08615.x. PMID 18476957. Wu JJ, Huang DB, Tyring SK (November 2004). "Resiquimod: ...
In each case, caspase 9 activation leads to the activation of a full caspase cascade and subsequent cell death. It has been ... This functional apoptosome then can provide a platform activation of caspase 9. Caspase 9 exists as a zymogen in the cytosol ... In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ... Another targeted molecule for cancer therapy involves the caspase family and their regulators. The inhibition of caspase ...
DRB1*04:06: caspase-8 autoantibodies silicosis-systemic sclerosis (SSc)-systemic lupus erythematosus (SLE). DRB1*04:09: T. ... Ueki A, Isozaki Y, Kusaka M (2005). "Anti-caspase-8 autoantibody response in silicosis patients is associated with HLA-DRB1, ... 46 (1): 143-9. doi:10.2337/diabetes.46.1.143. PMID 8971095. Gross D, Forsthuber T, Tary-Lehmann M, Etling C, Ito K, Nagy Z, ... 47 (1): 61-7. doi:10.1539/joh.47.61. PMID 15703453. García Borrás S, Diez C, Cotorruelo C, et al. (2006). "HLA class II DRB1 ...
36 (1-3): 119-26. doi:10.1385/ir:36:1:119. PMID 17337772. Carpenter D, Hsiang C, Brown DJ, Jin L, Osorio N, Benmohamed L, Jones ... 366 (1): 206-211. doi:10.1016/j.bbrc.2007.11.127. hdl:10069/22710. PMID 18054325. Hacein-Bey-Abina, S; Garrigue, A; Wang, GP; ... 369 (1): 12-8. doi:10.1016/j.virol.2007.07.023. PMC 2276668. PMID 17727910. Buzdin A (Nov 2007). "Human-specific endogenous ... 2006 Jan 16;3(1):7 Divito S, Cherpes TL, Hendricks RL (2006). "A triple entente: virus, neurons, and CD8+ T cells maintain HSV- ...
Activation of the NLRP3 inflammasome recruits the enzyme caspase 1, which converts pro-interleukin 1β into active interleukin 1 ... Gout affects about 1 to 2% of the Western population at some point in their lives. It has become more common in recent decades ... 78 (1): 35-40. doi:10.1016/j.jbspin.2010.02.027. PMID 20472486. Reginato AM, Mount DB, Yang I, Choi HK (2012). "The genetics of ... ISBN 978-1-4160-4842-8. Liu-Bryan, Ru; Terkeltaub, Robert (2006). "Evil humors take their Toll as innate immunity makes gouty ...
gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading ... 1] However, most antibodies that bind the CDbs region of gp120 do not neutralize HIV, and rare ones that do such as IgG1-b12 ... The diversity of env has been shown to increase by 1-2% per year in HIV-1 group M and the variable units are notable for rapid ... 383 (1): 47-59. doi:10.1016/j.virol.2008.09.017. PMC 2642736 . PMID 18973914. Wood N, Bhattacharya T, Keele BF, Giorgi E, Liu M ...
Caspase-1 within the activated NALP3 inflammasome complex in turn activates the inflammatory cytokine, IL-1β.[15] ... These signals release HSP90 and SGT1 from and recruit ASC protein and caspase-1 to the inflammasome complex. ... subfamily of PRRs and NALP3 together with the adaptor ASC protein PYCARD forms a caspase-1 activating complex known as the ... Proteins which contain the caspase recruitment domain, CARD, have been shown to be involved in inflammation and immune response ...
The function of caspase 4 is not fully known, but it is believed to be an inflammatory caspase, along with caspase 1, caspase 5 ... The Proteolysis Map Caspase Martinon F, Tschopp J (2007). "Inflammatory caspases and inflammasomes: master switches of ... Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue (LEVD-), and belongs to a family ... Smith C, Soti S, Jones Torey A, Nakagawa A, Xue D, and Yin H (2017). "NSAIDs are Caspase Inhibitors". Cell Chem Biol. 24 (3): ...
... is a protein that in humans is encoded by the CASP12 gene. The protein belongs to a family of enzymes called ... It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and ... It is found on chromosome 11 in humans in a locus with other inflammatory caspases.CASP12 orthologs have been identified in ... The trials were carried out on laboratory mice which had been implanted with the human caspase-12 gene. The inactive truncated ...
1] Massachusetts Department of Public Health - Rabies Control Plan - Chapter 1: General Information - "Definitions as Used in ... "Mechanisms of enveloped RNA virus budding." Trends in Cell Biology, Volume 12, Issue 12, 1 December 2002, pp. 569-79 Quemin ER ... "Human Immunodeficiency Virus Type 1 Vpr Induces Apoptosis through Caspase Activation." Journal of Virology, April 2000, pp. ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...
2 (1): 48-58. doi:10.1038/nrc706. PMID 11902585.. *^ Cho S, Lu M, He X, Ee PL, Bhat U, Schneider E, Miele L, Beck WT (December ... Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene.[5] Presenilin-1 is one of the four ... "Entrez Gene: PSEN1 presenilin 1 (Alzheimer disease 3)".. *^ Chan YM, Jan YN (August 1998). "Roles for proteolysis and ... In the prenilin 1 null mutant drosophila, Notch signaling is abolished and it displays a notch-like lethal phenotype.[18] ...
One novel protein (ProAgio) has been designed to bind at an unusual site, and then induces apoptosis by recruiting caspase 8. ... 9 (1): 7. doi:10.1186/1479-5876-9-7. PMC 3027097. PMID 21232121. Turaga, Ravi Chakra; Yin, Lu; Yang, Jenny J.; Lee, Hsiauwei; ... 7 (1): 11675. doi:10.1038/ncomms11675. PMC 4895024. PMID 27241473. Van Agthoven JF, Xiong JP, Alonso JL, Rui X, Adair BD, ... It is designed by mutating domain 1 of CD2 (D1-CD2), which naturally binds weakly to the receptor. Fibronectin domain 10 ...
12 (1): 8-16. doi:10.2310/7750.2008.07050. ISSN 1203-4754. PMID 18258152. S2CID 34516905. Hoffman, Hal M.; Rosengren, Sanna; ... Seitz, M.; Kamgang, R. K.; Simon, H. U.; Villiger, P. M. (2005-12-01). "Therapeutic interleukin (IL) 1 blockade normalises ... The mutation in NLRP3 leads to aberrant formation of this inflammasome and subsequent unregulated production of interleukin 1β ... doi:10.1016/S0140-6736(04)17401-1. ISSN 1474-547X. PMC 4321997. PMID 15541451. Goldbach-Mansky, Raphaela; Dailey, Natalie J.; ...
... caspase-3 activation and PARP cleavage. Intense upregulation of NAG-1 and ATF3 and downregulation of Mcl-1 and Egr-1 were also ...
Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity". Cell Death and Differentiation. 9 (1): 20-6. ... reducing the cell's inhibition to caspase activation. In summary, HTRA2/Omi contributes to apoptosis through both caspase- ... Suzuki Y, Takahashi-Niki K, Akagi T, Hashikawa T, Takahashi R (Feb 2004). "Mitochondrial protease Omi/HtrA2 enhances caspase ... caspase-independent, necrosis-like programmed cell death mediated by serine protease activity". Blood. 103 (6): 2299-307. doi: ...
"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase ... InChI=1/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12 ... InChI=1S/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+, ... semi-preparative scale preparation of crocin-1 and trans-crocetin". Fitoterapia. 92: 290-5. doi:10.1016/j.fitote.2013.11.014. ...
varian caspase recruitment domain (CARD15) dan reseptor interleukin-23 (IL23R) atau polimorfisme autophagy-related 16-like 1 ( ... 1072 (1): 135-54. doi:10.1196/annals.1326.039. PMID 17057196.. *^ Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al- ... Perempuan sedikit lebih terpengaruh dibandingkan pria dengan rasio kisaran 1: 1 sampai 1.8: 1.[2] Penyebab penyakit Crohn tidak ... Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 ...
"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. (ENGLAND ... functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7". J. Biol. Chem. 275 (35 ... Bakulovirusni protein 3 koji sadrži IAP ponavljanje (cIAP2) je protein koji je kod ljudi kodiran BIRC3 genom.[1][2] ...
"Relationship between Caspase Activity and Apoptotic Markers in Human Sperm in Response to Hydrogen Peroxide and Progesterone". ... 207 (1): 202-205. doi:10.1006/excr.1993.1182. PMID 8391465. Lozano GM, Bejarano I, Espino J, González D, Ortiz A, García JF, ... 3 (1): 1-7. Lozano GM, Bejarano I, Espino J, González D, Ortiz A, García JF, Rodríguez AB, Pariente JA (2009). " ... 1 (6): 639-648. doi:10.3892/ijo.1.6.639. PMID 21584593. Gavrieli Y, Sherman Y, Ben-Sasson SA (1992). "Identification of ...
Wang KK (Jan 2000). "Calpain and caspase: can you tell the difference?". Trends in Neurosciences. 23 (1): 20-26. doi:10.1016/ ... Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B (Mar 1998). "Calpain inhibitors, but not caspase inhibitors, ... doi:10.1016/0022-2836(83)90117-1. PMID 6842590.. *^ a b c d Biología celular (in Spanish). Elsevier España. 2002. p. 132. ISBN ... 5 (1): 1-13. doi:10.1007/s12195-011-0181-z.. *^ Plopper G, Lewin B, Cassimeris L (2007). Cells. Boston: Jones and Bartlett ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ... ISBN 978-1-136-84407-2.. *^ a b Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). ... PMFBP1: encoding protein Polyamine-modulated factor 1-binding protein 1. *POLR3K: encoding enzyme DNA-directed RNA polymerase ... SHCBP1: encoding protein SHC SH2 domain-binding protein 1. *SLZ1: encoding protein SLX1 structure-specific endonuclease subunit ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[30 ... 6 (1): 79-85. doi:10.3758/CABN.6.1.79. PMID 16869232.. *^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). " ... doi:10.1016/S0896-6273(00)80540-1. PMID 9728912. S2CID 13983709.. *^ a b c d e Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, ... 1 (3): 191-98. doi:10.1038/35044558. PMID 11257907. S2CID 9750498.. *^ a b Zhong L, Yan CH, Lu CQ, Xu J, Huang H, Shen XM ( ...
... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... When interleukin-1 is produced in response to external stimuli, it can bind to cell-surface receptors on the same cell that ... 75 (1): 196-207. doi:10.1124/mol.108.049544. PMC 2669785 . PMID 18849352. Yi, Eun Hee; Lee, Chang Seok; Lee, Jin-Ku; Lee, Young ... 13 (1): 7-9. doi:10.1016/j.ccr.2007.12.020. PMID 18167335. Gao, Sizhi Paul; Mark, Kevin G.; Leslie, Kenneth; Pao, William; ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... 278 (1): 311-8. doi:10.1074/jbc.M206279200. PMID 12401807.. *^ a b c Gille C, Goede A, Schlöetelburg C, Preissner R, Kloetzel ... 31 (1): 137-55. doi:10.1007/BF02705243. PMID 16595883.. *^ a b Heinemeyer W, Fischer M, Krimmer T, Stachon U, Wolf DH (October ... 3 (1): 20-6. doi:10.1038/ni0102-20. PMID 11753406.. *^ Egerer K, Kuckelkorn U, Rudolph PE, Rückert JC, Dörner T, Burmester GR, ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ... Lotze MT, Tracey KJ (April 2005). "High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal". Nature ...
Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... 10 (1): 45-65. doi:10.1038/sj.cdd.4401189. PMID 12655295.. *^ Chen G, Goeddel DV (2002). "TNF-R1 signaling: a beautiful pathway ... 1 (3): 264-75. PMID 12851985.. *^ Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T (2002). " ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 18 (1): 131-9. doi:10.3233/JAD-2009-1134. PMID 19625751.. *^ a b c d e Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, ... 12 (1): 59-65. doi:10.1038/sj.ejhg.5201102. PMID 14560316.. *^ a b c Mercuri E, Bertini E, Messina S, Solari A, D'Amico A, ... 26 (1): 187-97. doi:10.3233/JAD-2011-110080. PMID 21593570.. *^ a b Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, ...
... to upregulate the activity of caspase-8. This causes cross talking of apoptotic signaling between caspase-8 and caspase-9 ... 2012: 1-11. doi:10.1155/2012/842945. Huang, Yen-Ta; Hsu, Chih W.; Chiu, Ted H. (1 September 2008). "Thalidomide and Its Analogs ... 2 (1): 36. doi:10.1186/1756-8722-2-36. PMC 2736171 . PMID 19674465. Vacca A, Ribatti D, Roncali L, et al. (July 1994). "Bone ... The secretion of IL-6 by bone marrow stromal cells (BMSC) and the secretion of the adhesion molecules VCAM-1, ICAM-1 and LFA, ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[27 ... 6 (1): 79-85. doi:10.3758/CABN.6.1.79. PMID 16869232.. *^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). " ... doi:10.1016/S0896-6273(00)80540-1. PMID 9728912.. *^ a b c d e Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, Miller FD ( ... 41 (1): 22-28. doi:10.1002/eat.20474. PMID 17922530.. *^ a b Vargas-Perez H, Ting-A Kee R, Walton CH, Hansen DM, Razavi R, ...
Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. ... Caspase 3. Pro-apoptotic:. BAX. BAK1/Bcl-2 homologous antagonist killer. Bcl-2-associated death promoter. Anti-apoptotic:. Bcl- ... Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation. *UMich Orientation of Proteins in Membranes families/superfamily-78 ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ... 21 (FVII · FIX · FX · FXI · FXII · FD · PROC · Trombin) · .22 · .23 · .24 (.1 ALA · .7 MMP-1 · .17 MMP-3/MMP-6 · .19 BMP-1 · . ... Helikase · Girase · Konvertase (C3/C5) · Permease (ATPase · EEAT · FATP · GLUT · MCT · OATP · SGLT · UCP-1) · Aldolase · ... 1 ADH · .2 ALR · .54 LAD · .90 RAD · .91 RAD · .144 PAD · .194 CAD · .195 CAD ...
This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2 ... and may be instrumental in the execution of apoptosis following caspase activation. However p21 may inhibit apoptosis and does ... 258 (1): 92-100. doi:10.1006/excr.2000.4906. PMID 10912791.. *^ Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ...
"A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site- ... 83 (1-2): 74-5. doi:10.1159/000015130. PMID 9925932.. *. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D ( ... The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res ... Morris JA, Kandpal G, Ma L, Austin CP (July 2003). "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein ...
Non obstante, a TRADD únese a FADD, o cal despois recruta a cisteína protease caspase-8. Unha alta concentración de caspase-8 ... Por outra parte, as caspases activadas clivan varios compoñentes da vía NF-κB, incluíndo a RIP, IKK, e as propias subunidades ... 1] doi 10.1113/jphysiol.2009.179515 *↑ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, ... A desregulación da produción do TNFα foi implicada en diversas doenzas humanas, como a enfermidade de Alzheimer,[1] cancro,[2] ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ... Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine. 11 (7): 725-30. doi:10.1038/nm1263. PMID ...
Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases ... "DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration". 》PNAS》 111 (45): 16082 ... 123(1):9-18, 2016 *↑ Berninger TA, Polkinghorne PJ, Capon MR, et al. Color vision defect. A early sign of Sorsby retinal ... insulin-like growth factor-1 (IGF-1)[23], ciliary neurotrophic factor (CNTF)[24], pigment epithelium-derived factor (PEDF)[25] ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... 77 (1): 3-10. doi:10.1093/bja/77.1.3. PMID 8703628.. *^ Klaassen, C.D., Ed.: Casarett and Doull's Toxicology: The Basic Science ... 978-0-07-135469-1. .. *^ Chien, S; Toledo-Pereyra, L, eds. (2008). 'Metabolic Management - Organ Procurement and Preservation ... doi:10.1016/s1383-5742(02)00009-1. PMID 12052432.. *^ Narayanan, L; Fritzell, JA; Baker, SM; Liskay, RM; Glazer, PM (1997). " ...
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7]. *Caspase-1 is key in activating pro-inflammatory cytokines ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ... Pyroptosis by Caspase-4 and Caspase-5 in humans and Caspase-11 in mice ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... 1,0 1,1 1,2 1,3 1,4 Daneholt, Bertil. "Advanced Information: RNA interference". The Nobel Prize in Physiology or Medicine 2006 ... doi:10.1016/S0092-8674(02)71133-1.. *↑ Luciano D, Mirsky H, Vendetti N, Maas S (2004). "RNA editing of a miRNA precursor". RNA ... doi:10.1016/S1046-2023(03)00050-1.. *↑ Boutros M, Kiger A, Armknecht S, Kerr K, Hild M, Koch B, Haas S, Paro R, Perrimon N ( ...
This complex then cleaves procaspase-9, activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 ... 27 (1): 88-93. doi:10.1053/ejso.1999.1018. PMID 11237497.. *^ Ramp U, Mahotka C, Heikaus S, Shibata T, Grimm MO, Willers R, ... 978-3-540-22096-1. . PMID 14740253.. *^ Cvoro A, Dundjerski J, Trajković D, Matić G (1999-04-01). "The level and ... 1113 (1): 1-14. Bibcode:2007NYASA1113....1M. doi:10.1196/annals.1391.018. PMID 17513460.. ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 ... InChI=1S/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6) Y ... InChI=1/C3H7NO2S/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6) ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases. Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ...
Stegh AH, Barnhart BC, Volkland J, Algeciras-Schimnich A, Ke N, Reed JC, Peter ME (Feb 2002). "Inactivation of caspase-8 on ... "Entrez Gene: NR1H4 nuclear receptor subfamily 1, group H, member 4".. *^ a b Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, ... 9 (1): 72-85. doi:10.1210/mend.9.1.7760852. PMID 7760852.. *^ Fiorucci S, Zampella A, Distrutti E (2012). "Development of FXR, ... The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member ...
... is a protein that in humans is encoded by the CTSW gene.[5][6][7]. The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2.[7]. ...
Also, it is extensively used in research for the detection of DNA damage,[34][35] caspase cleavage and apoptosis.[36] In ... Apoptosis (quantification, measurement of DNA degradation, mitochondrial membrane potential, permeability changes, caspase ... 18: 1-13. doi:10.1163/156853897x00260.. *^ Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z. (2006) Constitutive ... 78 Suppl 1: S69. doi:10.1002/cyto.b.20554. PMC 3084630 . PMID 20839340.. ...
Is í an aidhm atá leis an liosta seo ná bithmhóiliní a thuairisciú.[1] ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... 5 (1): 56-63. doi:10.1093/cercor/5.1.56. PMID 7719130.. *^ a b c Budday, Silvia; Raybaud, Charles; Kuhl, Ellen (2014-07-10). "A ... 145 (1): 61-83. doi:10.1002/cne.901450105. PMID 4624784.. *^ LaMonica, BE; Lui, JH; Wang, X; Kriegstein, AR (October 2012). " ... Gyrification is the process of forming the characteristic folds of the cerebral cortex.[1] The peak of such a fold is called a ...
"N-APP binds DR6 to cause axon pruning and neuron death via distinct caspases". Nature 457 (7232): 981-989. doi:10.1038/ ... Neurol. 63 (1): 112-8. doi:10.1002/ana.21212. . PMID 18023012 . *Ikonomovic MD, Klunk WE, Abrahamson EE, et al. (Juni 2008). " ... doi:10.1007/1-4020-5688-5_11 . PMID 17612054 . *↑ Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL (Aprili 2005). " ... ISBN 1-4325-0833-4.. *↑ Katzman Robert, Terry Robert D, Bick Katherine L (editors) (1978). Alzheimer's disease: senile dementia ...
Further, improved myocardial I/R injury was also observed in the caspase-1−/− mice, compared with WT mice (IA/AAR: 20.2% vs. ... ASC is an adaptor protein that forms inflammasome whose activation leads to caspase-1-dependent interleukin (IL)-1β generation ... Abstract 5053: Deficiency of ASC (Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain) in Bone ... Abstract 5053: Deficiency of ASC (Apoptosis-associated Speck-like Protein Containing a Caspase Recruitment Domain) in Bone ...
It promotes pyropoptosis in macrophages and induces caspase-mediated apoptosis (involving caspase-8 and caspase-9). ... 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). ...
Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs.. Niu Z, Shi Q, Zhang W, Shu Y, Yang N, Chen B, Wang Q, ... Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. [J Leukoc Biol. 2016] Caspase-1 as a ... LSBio CASP1 / Caspase 1 Elisa Kits [LifeSpan BioSciences, Inc.] LSBio CASP1 / Caspase 1 Elisa Kits. LifeSpan BioSciences, Inc. ... Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs. [Nat Commun. 2017] ...
Caspase-1: the inflammasome and beyond.. Sollberger G1, Strittmatter GE, Garstkiewicz M, Sand J, Beer HD. ... Caspase-1 plays a fundamental role in innate immunity and in several important inflammatory diseases as the protease activates ... Caspase-1 itself is activated in different inflammasome complexes, which assemble in response to a variety of exogenous and ... More recently, pyroptosis, a caspase-1-dependent type of programmed cell death, has been identified that is able to support ...
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Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. Genomics. 2004 Sep;84(3):587-91 ... Lamkanfi M, Denecker G, Kalai M, Dhondt K, Meeus A, Declercq W, Saelens X, Vandenabeele P: INCA, a novel human caspase ... Romanowski MJ, Scheer JM, OBrien T, McDowell RS: Crystal structures of a ligand-free and malonate-bound human caspase-1: ... interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9982-7. Epub ...
Rabbit polyclonal Caspase-1 antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, Human. Cited in 32 publication(s ... Anti-Caspase-1 antibody (ab1872). Rabbit polyclonal Caspase-1 antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, ... Immunofluorescence analysis of caspase-1 in H9c2 cardiomyocytes treated with control, medium and high glucose using ab1872 (1: ... Immunocytochemistry/ Immunofluorescence - Anti-Caspase-1 antibody (ab1872)This image is courtesy of an Abreview submitted by ...
Hsp70 Inhibits Apaf-1-Mediated Caspase Activation Message Subject. (Your Name) has forwarded a page to you from Science ...
Buy our Recombinant Human Caspase-1 protein. Ab158029 is a full length protein produced in Wheat germ and has been validated in ... Recombinant Human Caspase-1 protein. See all Caspase-1 proteins and peptides. ... Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety ...
... derived caspase substrates are widely used for the colorimetric detection of various caspase activities. Cleavage of pNA ... pNA has maximum absorption around 408 nm.; Caspase-9 substrate; Ac-LEHD-pNA; Ac-Leu-Glu-His-Asp-pNA ... peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. ... pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. ...
... derived caspase substrates are widely used for the colorimetric detection of various caspase activities. Cleavage of pNA ... pNA has maximum absorption around 408 nm.; Caspase-8 substrate with Km = 66 uM; Substrate for granzyme B; Ac-IETD-pNA; Ac - Ile ... peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. ... pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. ...
Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response. Mary K. Stewart ... Salmonella mutants lacking YdiV are unable to fully repress flagellin at systemic sites, rendering them vulnerable to caspase-1 ... Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response ... Regulation of phenotypic heterogeneity permits Salmonella evasion of the host caspase-1 inflammatory response ...
... including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. The interaction with caspase-9 was mediated ... The human caspase-3, caspase-4, wild type, and mutant (C287S) caspase-9 cDNAs were cloned into the BamHI and XhoI sites of a ... 6A). In contrast to caspase-9, we did not observe any enhancement of caspase-4 or caspase-8 processing using this in vitro ... Lower) The expression of caspase-3 and -4 (B), caspase-9 (C), and CED-3 and Apaf-1 proteins (D). Reduced level of pro-caspase-9 ...
Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1-/- mice from ARF. In wild-type animals, we ... This conversion is not observed in caspase-1-/- ARF mice or sham-operated controls. We then injected wild-type mice with IL-18- ... We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1β and IL-18, ... Finally, we confirmed histologically that caspase-1-/- mice show decreased neutrophil infiltration, indicating that the ...
Caspase-3 should NOT be activated, which is the issue. Caspase-1 is the only think Im looking to be activated and that doesnt ... Caspase-3 activation is almost the last step of cell death. All different pathways end up with activation of caspase-3. So Im ... is a unique form of cell death that does not depend on the activation of caspase-3. There is detectable activation of caspase-7 ... Protocol to activate caspase-1 - Please help! - (Jul/02/2013 ). Ive followed a LOT of protocols from the literature and ...
Caspase-1 is a protease, an enzyme that cleaves proteins. It is found predominantly in the cell cytoplasm, where it activates ... Due to this activity caspase-1 is also known as ICE (interleukin-1-beta converting enzyme). Like other caspases it also plays a ... Molecular model of caspase-1 complexed with an inhibitor. ... interleukin-1-beta, a molecule that mediates immune and ... Caspase-1 is a protease, an enzyme that cleaves proteins. It is found predominantly in the cell cytoplasm, where it activates ...
Proteintech Anti-Caspase 8 Polyclonal, Catalog # 13423-1-AP. Tested in Western Blot (WB), Immunofluorescence (IF), ... caspase 8, apoptosis-related cysteine protease; Caspase-8; Caspase-8 precursor; Caspase-8 subunit p10; Caspase-8 subunit p18; ... Caspase 8 (CASP8) is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases play a ... Activated Caspase 8 then activates other downstream caspases including Caspase 9, thereby committing the cell to undergo ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
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 ...
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. ...
Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ... Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ... Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ... Regulation of an ATG7-beclin 1 Program of Autophagic Cell Death by Caspase-8 ...
Caspases play an instrumental role in neurodegeneration in transgenic mSOD1G93A mice, which suggests that caspase inhibition ... a broad caspase inhibitor, delays disease onset and mortality. Moreover, zVAD-fmk inhibits caspase-1 activity as well as ... To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant ... Functional Role of Caspase-1 and Caspase-3 in an ALS Transgenic Mouse Model ...
The induction of PSP/reg was glucose dependent and mediated by caspase activation during apoptosis. Interestingly, the ... 1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland; ... INS-1 Cells Undergoing Caspase-Dependent Apoptosis Enhance the Regenerative Capacity of Neighboring Cells. ... Inactivating mutations in transcription factor 1 (tcf-1)/hepatocyte nuclear factor1a (hnf1a) result in decreased β-cell mass ...
Cardioprotection Caspase-1 Ischemia/reperfusion injury Myocardial infarction P2Y12 receptor antagonist VX-765 ... Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term ... Syed FM, Hahn HS, Odley A, Guo Y, Vallejo JG, Lynch RA, Mann DL, Bolli R, Dorn GW (2005) Proapoptotic effects of caspase-1/ ... Holly TA, Drincic A, Byun Y, Nakamura S, Harris K, Klocke FJ, Cryns VL (1999) Caspase inhibition reduces myocyte cell death ...
In addition, caspase cleavage and p53 activation were found to be significantly enhanced in F3-treated THP-1 cells. We ... Jia-Wei Hsu,1 Hsuan-Cheng Huang,2 Shui-Tein Chen,1,3 Chi-Huey Wong,1,3,4 and Hsueh-Fen Juan1 ... 1Institute of Molecular and Cellular Biology, Department of Life Science, Graduate Institute of Biomedical Electronics and ... unraveled the role of caspases and p53 in F3-induced THP-1 cells differentiation into macrophages. Our results provide a ...
SUMMARY Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls ... mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. Here, we ... Caspase-11 Controls Interleukin-1β Release through Degradation of TRPC1. dc.contributor.author. Py, Bénédicte F.. en_US. ... "Caspase-11 Controls Interleukin-1β Release through Degradation of TRPC1." Cell reports 6 (6): 1122-1128. doi:10.1016/j.celrep. ...
... 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 ...
Objective We set out to investigate whether the nebulized and inhaled specific caspase-1 inhibitor Ac-YVAD-CHO has the ... Targeting caspase-1 by inhalation-therapy: effects of Ac-YVAD-CHO on IL-1β, IL-18 and downstream proinflammatory parameters as ... Mathiak G, Grass G, Herzmann T, Luebke T, Zetina CC, Boehm SA, Bohlen H, Neville LF, Hoelscher AH (2000) Caspase-1-inhibitor ac ... We set out to investigate whether the nebulized and inhaled specific caspase-1 inhibitor Ac-YVAD-CHO has the potential to ...
... β and Interleukin-18 Secretion by Increasing Caspase-1 Expression in Murine Macrophages. Ken Shirato,1 Kazuhiko Imaizumi,2 ... β and Interleukin-18 Secretion by Increasing Caspase-1 Expression in Murine Macrophages," Mediators of Inflammation, vol. 2017 ... 1Department of Molecular Predictive Medicine and Sport Science, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, ... 3Social Medical Corporation, The Yamatokai Foundation, 1-13-12 Nangai, Higashiyamato, Tokyo 207-0014, Japan. ...
Caspase-1 Substrate YVAD-AFC. Provided in the ready-to-use form ...
... 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. ...
Caspase-8 interacts with ASC and active caspase-8 specifically colocalizes with the AIM2/ASC speck thus identifying the AIM2/ ... Francisella tularensis, the agent of tularaemia, triggers AIM2/ASC-dependent caspase-3-mediated apoptosis in caspase-1- ... ASC complex as a novel caspase-8 activation platform. Furthermore, we demonstrate that caspase-1-independent apoptosis requires ... Caspase-1 causes pyroptosis, a necrotic-like cell death. AIM2 is an inflammasome sensor for cytosolic DNA. The adaptor molecule ...
  • Cleavage of pNA peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. (anaspec.com)
  • Activation of downstream caspases through several stimuli leads to cleavage of target proteins and execution of the apoptotic program ( 13 ). (pnas.org)
  • I have tried western blotting for IL-1beta maturation and caspase-1 cleavage. (protocol-online.org)
  • Further, DNA degradation in caspase-1-dependent cell death is independent of ICAD cleavage, which is the substrate of caspase-3 and further supports the lack of caspase-3 involvement. (protocol-online.org)
  • In addition, caspase cleavage and p53 activation were found to be significantly enhanced in F3-treated THP-1 cells. (hindawi.com)
  • TRPC1 deficiency increases the secretion of IL-1β without modulating caspase-1 cleavage or cell death in cultured macrophages. (harvard.edu)
  • The Caspase-1 substrate sequence (NEAYVHDAPVRSLN) corresponds to the native cleavage site C-terminal to Asp-116 of the precursor IL-1β. (scbt.com)
  • The canonical cleavage and processing of proIL-1β into mature IL-1β cytokine (17 kDa) are catalyzed by caspase-1, a pathway regulated by multiprotein inflammasome signaling complexes. (jimmunol.org)
  • The retention of Spi-2 proteins' caspase-8 specificity during chordopoxvirus evolution, despite this function being readily lost through cleavage site mutagenesis, suggests that caspase-8 inhibition is crucial for poxviral pathogenesis and spread. (portlandpress.com)
  • On the other hand, Caspase-1 cleavage induced by DICER1 knockdown in human RPE cells was inhibited by simultaneous antisense-mediated knockdown of Alu RNA. (arvojournals.org)
  • Several mechanisms have been proposed for the cytotoxic activity of proteasome inhibition, including stabilization of p53 ( 23 ) and the BH3-only proteins ( 37 ), cleavage of Mcl-1 ( 42 ), downregulation of XIAP and survivin ( 51 ), inhibition of NF-κB activity ( 3 ), and downregulation of the PI3K/Akt survival pathway ( 13 ). (asm.org)
  • 4E-BP1 undergoes caspase-dependent cleavage in cells undergoing apoptosis. (asm.org)
  • Finally, (v) whereas cleavage of BAD at ASP56 and ASP61 has been reported and results in the generation of a more effective proapoptotic protein with an M r of 15,000, in this report we also show the existence of a second caspase-dependent cleavage site most likely at the ASP156 that is predicted to inactivate the proapoptotic activity of BAD. (asm.org)
  • The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. (usgs.gov)
  • Treating the HMEC-1 cells with oxLDL did not result in detectable activation of procaspase 3 or cleavage of PARP [poly(ADP-ribose) polymerase], but it did cause polyubiquitination of caspase 3, indicating inactivation and possible degradation of this protease. (biochemj.org)
  • Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 3.4.22.56) pipeline Target constitutes close to 16 molecules. (researchmoz.us)
  • It also reviews key players involved in Caspase 3 (Apopain or Cysteine Protease CPP32 or Protein Yama or SREBP Cleavage Activity 1 or CASP3 or EC 3.4.22.56) targeted therapeutics development with respective active and dormant or discontinued projects. (researchmoz.us)
  • Caspase 1 expression was determined both at the mRNA level using in situ hybridisation and reverse transcription polymerase chain reaction, and at the protein level by immunoblotting experiments using antibodies specific for the proform of caspase 1 and for its cleavage forms. (bmj.com)
  • Sequence analysis of processed proIL-18 demonstrated that cleavage sites of MMP-2 and MMP-8 differ from that of Caspase-1. (uni-koeln.de)
  • The Alzheimer's disease-associated presenilin (PS) 1 is intimately involved in gamma-secretase cleavage of beta-amyloid precursor protein and other proteins. (semanticscholar.org)
  • These enzymes participate in a series of reactions that are triggered in response to pro-apoptotic signals and result in cleavage of protein substrates, causing the disassembly of the cell (1). (celltechnology.com)
  • Caspases can be detected via immunoprecipitation, immuno-blotting techniques using caspase specific antibodies, or by employing fluorogenic substrates which become fluorescent upon cleavage by the caspase. (celltechnology.com)
  • Caspase mediated cleavage of desmoglein 1 leads to decreased expression at the cell surface and re-localization of its C terminus diffusely throughout the cytoplasm. (reactome.org)
  • Caspase-1 and related caspase activity can be quantified by spectrophotometric detection of free pNA (= 400 nm) after cleavage from the peptide substrate YVAD-pNA, using a spectrophotometer or multi-well plate reader. (antibody-antibodies.com)
  • Finally, we identify the AIM2/ASC-dependent caspase-1-independent pathway as an innate immune mechanism able to restrict bacterial replication in vitro and control IFN-γ levels in vivo in Casp1(KO) mice. (archives-ouvertes.fr)
  • The current study determined endometrial expression of caspase 1 (CASP1) and interleukin-18 (IL18) during the estrous cycle and early pregnancy, and following early estrogen administration, which induces conceptus loss during early development in pigs. (sigmaaldrich.com)
  • Similarly, STS stimulated robust IL-1β processing and release in Casp1 −/− Casp11 −/− BMDC that was IETD sensitive. (jimmunol.org)
  • Caspase 1 antibody LS-C353917 is an unconjugated rabbit polyclonal antibody to human Caspase 1 (CASP1). (lsbio.com)
  • CASP1 / Caspase 1 is a protein which is a member of the cysteine-aspartic acid protease (caspase) family. (lsbio.com)
  • In patients suffering from unexplained recurrent febrile episodes we detected several genetic variants of CASP1 leading to reduced enzymatic activity due to destabilization of the caspase-1 dimer interface. (biomedcentral.com)
  • We analyzed ER stress markers in THP-1 cells and lymphoblastoid cells lines (LCL, EBV transformed B cells) from healthy donors and individuals with CASP1 variants. (biomedcentral.com)
  • Furthermore, spliced XBP1 and Bip expression were significantly increased in unstimulated CASP1 knock-down THP-1 cells and in native patients' LCLs expressing variant caspase-1 with reduced enzymatic activity. (biomedcentral.com)
  • Besides, Interleukin 1 Alpha (IL1a) has been identified as an interactor of CASP1, thus a binding ELISA assay was conducted to detect the interaction of recombinant rat CASP1 and recombinant rat IL1a. (uscnk.com)
  • The binding activity of of CASP1 and IL1a was shown in Figure 1, and this effect was in a dose dependent manner. (uscnk.com)
  • The N-terminal FADD-like death effector domain of Caspase 8 suggests that it may interact with Fas-interacting protein FADD. (thermofisher.com)
  • Caspase 8 binds to the death effector domain (DED) of FADD through an analogous DED domain present in tandem in the pro-form of the Caspase 8 protein. (thermofisher.com)
  • A gene on chromosome 11q23 that encodes a protein belonging to the cysteine-aspartic acid protease (caspase) family which, once activated by proteolytic processing, plays a central role in the execution-phase of cell apoptosis, as well as various stages of embryological development. (thefreedictionary.com)
  • A feature of the inflammasomes is the use of the adaptor ASC (apoptosis-related speck-like protein) to link NLRs to pro-caspase-1, a critical step in the activation of caspase-1. (frontiersin.org)
  • We will test the hypothesis that caspase-1 inhibition will down- regulate α-synuclein (α-SYN) at mRNA and/or protein levels within the SN and restore impaired function of the dopamine system in two pre-clinical models of Parkinson's disease (PD). (michaeljfox.org)
  • In our first experiment, we expect that caspase-1 inhibition will 1) reduce the expression of α-SYN mRNA and aggregated protein within SN, 2) block nigrostriatal dopaminergic degeneration (pretreatment experiment), 3) prevent or delay the onset of motor disability (pretreatment experiment), 4) reverse dopamine degeneration (post-treatment experiment) 5) reverse motor disability (post-treatment experiment) in transgenic α-SYN over expressing pre-clinical models. (michaeljfox.org)
  • In experiment 2, we expect that caspase-1 inhibition will 1) reduce α-SYN mRNA and protein levels within SN, 2) protect against nigrostriatal dopaminergic degeneration, and 3) reverse or retard motor disability in this AAV6-SYN induced pre-clinical PD model. (michaeljfox.org)
  • The human caspase-3 gene encodes a cytoplasmic protein that is highly expressed in lung, spleen, heart, liver, kidney and cells of the immune system. (scbt.com)
  • We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. (nih.gov)
  • Our study revealed that apoptosis-associated specklike protein containing a caspase recruitment domain (ASC), an adaptor protein for inflammasome receptors such as nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2), is essentially required for the induction of caspase-1 activation by S. pneumoniae . (jimmunol.org)
  • Pneumolysin (PLY), a 53-kDa multifunctional protein toxin that is produced by virtually all clinical isolates of pneumococcus, is one of the key virulence factors of S. pneumoniae ( 1 - 4 ). (jimmunol.org)
  • Activation of TLRs or receptors for proinflammatory cytokines (including IL-1β per se) induces the NF-κB-dependent expression of proIL-1β (33 kDa) as a cytosolic, biologically inactive precursor protein. (jimmunol.org)
  • We discovered that six cell death genes- death caspase-1 ( Dcp-1 ), hid , Bruce , Buffy , debcl , and p53 -as well as Ras-Raf-mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. (rupress.org)
  • Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous antiapoptotic protein. (aacrjournals.org)
  • Here, we report that ARC contributes to chemotherapy resistance by abolishing mitochondrial fission mediated by dynamin-related protein-1 (Drp1). (aacrjournals.org)
  • ARC is originally identified to be a caspase-inhibiting protein and can specifically inhibit the activation of caspase-2 and caspase-8, thereby blocking apoptosis induced by a variety of stimuli requiring the engagement of these caspases ( 1 ). (aacrjournals.org)
  • To clarify the molecular mechanism of TRAIL-induced apoptosis, we focused on transforming growth factor-β-activated kinase 1 (TAK1) mitogen-activated protein kinase (MAPK) kinase kinase, a key regulator of the TNF-α-induced activation of p65/RelA and c-Jun NH 2 -terminal kinase/p38 MAPKs. (aacrjournals.org)
  • This complex consists of trimerized receptors, the death domain-containing adaptor protein Fas-associated death domain, and caspase-8 ( 12 - 14 ). (aacrjournals.org)
  • Transforming growth factor-β-activated kinase 1 (TAK1) was originally identified as a MAPK kinase kinase (MAP3K), which can be activated by transforming growth factor-β, bone morphologic protein ( 20 ). (aacrjournals.org)
  • Recognizes endogenous levels of Caspase 1 protein. (lsbio.com)
  • Additionally, TT‑1 stimulated caspase‑3, caspase‑9 and Bax, and inhibited B‑cell lymphoma 2 mRNA and protein expression. (spandidos-publications.com)
  • This enhanced caspase-8 oligomerization and activation are promoted through its interaction with the ubiquitin-binding protein SQSTM1/p62 and the microtubule-associated protein light chain 3 (LC3), which are enriched at intracellular membranes in response to proteotoxic stress. (asm.org)
  • Our results unveiled a previously unknown mechanism through which disruption of protein homeostasis induces caspase-8 oligomerization, activation, and apoptosis. (asm.org)
  • Mucin 1 (MUC1) is a highly glycosylated transmembrane protein expressed on the apical surface of epithelial cells and is aberrantly overexpressed in the majority of malignant epithelial tumors, including breast, lung, ovarian, prostate and pancreatic cancer and several types of malignant hematological tumor ( 1 ). (spandidos-publications.com)
  • The occurrence of HCC is associated directly or indirectly with the abnormal expression of multiple genes, including B lymphoma Moloney murine leukemia virus insertion region 1 homolog (BMI1) ( 16 ), glypican-3 ( 17 ), heat shock protein 70 ( 18 ) and Sal-like protein 4 ( 19 ). (spandidos-publications.com)
  • An earlier report showed that the U S 3 protein kinase blocked the apoptosis induced by the herpes simplex virus 1 (HSV-1) d 120 mutant at a premitochondrial stage. (asm.org)
  • ii) In cells cotransduced with the U S 3 protein kinase, the BAD protein was not cleaved and the caspase 3 activity was not elevated. (asm.org)
  • We conclude that the primary effect of U S 3 was to block the caspases that cleave BAD at either residue 56 or 61 predicted to render the protein more proapoptotic or at residue 156, which would inactivate the protein. (asm.org)
  • The focus of the present study is on the U S 3 protein kinase shown in earlier studies to block apoptosis induced by d 120, an HSV-1 mutant lacking the gene encoding the infected cell protein no. 4, the major regulatory protein of the virus ( 19 , 21 ). (asm.org)
  • Studies from this laboratory showed that ectopically expressed HSV-1 U S 3 protein kinase blocks apoptosis induced by the d 120 mutant ( 19 , 21 ). (asm.org)
  • The Bcl-2 protein Bid was also cleaved during oxLDL-elicited cell death, and this was prevented by calpain inhibitors, but not by inhibitors of cathepsin B and caspases. (biochemj.org)
  • We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. (chinaphar.com)
  • The normal colonic epithelium strongly expressed caspase 1, both at the mRNA level and at the protein level in its latent form. (bmj.com)
  • Our results show that caspase 1 is present in 74% of epithelial preparations, both at the RNA and protein levels. (bmj.com)
  • LF cleaves members of the mitogen-activated protein kinase kinase family (MEKs) [1] - [2] . (prolekare.cz)
  • 2007) NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1 . (merckmillipore.com)
  • Fas-AssociatedDeathDomain (FADD) and receptor interacting protein 1 (RIP1) are death domain containing molecules that interact with the C-terminal portion of IPS-1 and induce NF-kB through interaction and activation of initiator caspases (caspase-8 and -10). (reactome.org)
  • Following up on her original discovery that NLRP3 senses viral RNAs, her lab has discovered Z-DNA binding protein 1 (ZBP1)/DAI as an innate sensor of influenza virus upstream of the NLRP3 inflammasome/pyroptosis and also showed ZBP1 is a key regulator of apoptosis and necroptosis, establishing it as a master regulator of these cell death pathways. (wikipedia.org)
  • The preclinical data demonstrate that DPP 8 and DPP 9 inhibition may cause the activation of caspase-1 which leads to an increase in a key cytokine, interleukin-1beta (IL-1beta). (thefreedictionary.com)
  • To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1 G93A ). (sciencemag.org)
  • Caspases play an instrumental role in neurodegeneration in transgenic mSOD1 G93A mice, which suggests that caspase inhibition may have a protective role in ALS. (sciencemag.org)
  • We further show that AIM2 engagement leads to ASC-dependent, caspase-1-independent activation of caspase-8 and caspase-9 and that caspase-1-independent death is reverted upon caspase-8 inhibition. (archives-ouvertes.fr)
  • Co-P.I. Dr. Petsko demonstrated previously that inhibition of caspase 3 protect nigral neurons in culture. (michaeljfox.org)
  • Mice deficient in AIF also exhibit quantitatively normal PCD of postmitotic neurons after caspase inhibition. (jneurosci.org)
  • Emricasan has shown specificity in assays measuring caspase inhibition, and reduced apoptosis in a variety of cellular assays. (bio-medicine.org)
  • In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. (nih.gov)
  • Whereas one study of pharmacological caspase-3 inhibition reported decreased myocardial apoptosis and diminished infarct size, 7 the antithetic experiment of forced myocardial caspase-3 expression increased myocardial infarct size without clearly stimulating cardiomyocyte apoptosis. (ahajournals.org)
  • All potently blocked caspases-1, -4, -5 and -8 activity but exhibited negligible inhibition of caspases-2, -3 and -6. (portlandpress.com)
  • We show here that inhibition of proteasomal degradation results in an increased oligomerization and activation of caspase-8 on the cytosolic side of intracellular membranes. (asm.org)
  • Indeed, inhibition of the proteasomal and autophagolysosomal degradation pathways is clinically used or under investigation for treating cancer ( 1 , 4 , 12 , 18 , 38 , 54 , 55 ). (asm.org)
  • We went on to study the molecular mechanism and significance of caspase-8 activation in response to proteasome inhibition. (asm.org)
  • The above results indicate that MUC1 gene silencing induces growth inhibition in SMMC‑7721 cells through Bax‑mediated mitochondrial and caspase-8-mediated death receptor apoptotic pathways. (spandidos-publications.com)
  • Inhibition of caspase-1 activity can be determined by comparison of the fluorescence intensity in samples with and without the testing inhibitors. (antibody-antibodies.com)
  • Inhibition of caspases can delay apoptosis, implicating a potential role in drug screening efforts. (antibody-antibodies.com)
  • Compounds to be screened can directly be added to the reaction and the level of inhibition of caspase-1 activity can be determined by comparison of the fluorescence intensity in samples with and without the testing inhibitors. (antibody-antibodies.com)
  • Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. (sciencemag.org)
  • Altogether, our data suggest that caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1. (harvard.edu)
  • Furthermore, we demonstrate that caspase-1-independent apoptosis requires the activation of caspase-9 and of the intrinsic pathway in a typical type II cell manner. (archives-ouvertes.fr)
  • These results show for the first time that DHA can inhibit proliferation and induce apoptosis via caspase-3-dependent mitochondrial death pathway in ASTC-a-1 cells. (sigmaaldrich.com)
  • We next characterized the morphological mode of PCD in these mice and show that the neurons degenerate by a caspase-independent, nonapoptotic pathway that involves autophagy. (jneurosci.org)
  • Together, these data indicate that, when key components of the type 1 apoptotic pathway (i.e., caspases and Apaf-1) are perturbed in vivo , developing postmitotic neurons nonetheless undergo quantitatively normal PCD by a caspase-independent pathway involving autophagy and not requiring AIF. (jneurosci.org)
  • In HeLa cells stably transfected with caspase-1, sensitisation to cisplatin was due to an amplification of the cisplatin-induced mitochondrial apoptotic pathway activation. (csic.es)
  • We found a heretofore unappreciated role for caspase-8 as a major pathway for IL-1β processing and release in murine bone marrow-derived dendritic cells (BMDC) costimulated with TLR4 agonists and proapoptotic chemotherapeutic agents such as doxorubicin (Dox) or staurosporine (STS). (jimmunol.org)
  • 1-5 Antiapoptotic therapeutic strategies have been designed that target the evolutionarily conserved caspase (calcium-activated aspartate protease) apoptosis effector pathway. (ahajournals.org)
  • Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo . (biologists.org)
  • We investigated the involvement of the apoptosome in ER stress-induced cell death pathway using mouse embryonic fibroblasts (MEFs) and mice deficient for Apaf-1. (biologists.org)
  • These data collectively demonstrated that Apaf-1 and the mitochondrial pathway of apoptosis play significant roles in ER stress-induced apoptosis. (biologists.org)
  • One is the extrinsic pathway, in which ligation of death receptors by death ligands is followed by recruitment of adaptor molecules and activation of caspase-8 or caspase-10. (biologists.org)
  • The other is the intrinsic pathway, in which the release of cytochrome c from mitochondria triggers the formation of the apoptosome composed of Apaf-1, pro-caspase-9, dATP, and cytochrome c . (biologists.org)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • This study demonstrated that the NLRP3 inflammasome/pyroptotic pathway is closely connected to the caspase-8-mediated programmed cell death pathway. (wikipedia.org)
  • This finding went against the dogma that existed at that time that caspase-8 and FADD were involved only in the apoptotic pathway. (wikipedia.org)
  • Caspase-1 plays a fundamental role in innate immunity and in several important inflammatory diseases as the protease activates the pro-inflammatory cytokines proIL-1β and proIL-18. (nih.gov)
  • Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. (drugbank.ca)
  • A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. (drugbank.ca)
  • In the presence of dATP and cytochrome c , a molecule that is released from mitochondria during apoptosis, Apaf-1 binds to caspase-9 and induces the activation of caspase-3, a downstream death protease ( 20 ). (pnas.org)
  • Caspase 8 (CASP8) is a member of the cysteine-aspartic acid protease (caspase) family. (thermofisher.com)
  • Caspases exist as inactive proenzymes composed of a pro-domain, a large protease subunit, and a small protease subunit. (thermofisher.com)
  • Caspase-3, also known as apopain, SCA-1, Yama and CPP32, is an aspartate-specific cysteine protease that belongs to the ICE subfamily of caspases. (scbt.com)
  • Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (nih.gov)
  • A new independent 54 page research with title 'Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) - Pipeline Review, H2 2017'guarantees you will remain better informed than your competition. (medgadget.com)
  • Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) pipeline Target constitutes close to 6 molecules. (medgadget.com)
  • The latest report Caspase 7 - Pipeline Review, H2 2017, outlays comprehensive information on the Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (medgadget.com)
  • Furthermore, this report also reviews key players involved in Caspase 7 (Apoptotic Protease Mch 3 or ICE Like Apoptotic Protease 3 or CMH 1 or CASP7 or EC 3.4.22.60) targeted therapeutics development with respective active and dormant or discontinued projects. (medgadget.com)
  • The present work aims to evaluate the in vivo role of this cytokine and its activating protease Caspase-1 in atherosclerosis. (uni-koeln.de)
  • Auf diesen Ergebnissen aufbauend besteht das Ziel der vorliegenden Arbeit darin, die in vivo Rolle von IL-18 und seiner aktivierenden Protease Caspase-1 in der Arteriosklerose am Mausmodell zu evaluieren. (uni-koeln.de)
  • Caspase-1 is the inflammasome effector protease that cleaves the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18. (gallusimmunotech.com)
  • She determined that ICE was the cysteine protease responsible for IL-1β processing in monocytes. (wikipedia.org)
  • Several studies have shown that these apoptosis inhibitors regulate the activation of caspases ( 16 , 17 ). (pnas.org)
  • Overexpression of Caspase 8 induces apoptosis, which can be blocked by inhibitors specific for the ICE family. (thermofisher.com)
  • Research Design: A total of 105 pre-clinical models (α-SYN over expressors, α-SYN knockouts, and wild-type) will comprise Experiment Groups (1-2) of one month old transgenic over-expressing pre-clinical models who will receive caspase-1 inhibitors (10 (low dose) or 50 (high dose) mg/kg, based on similarities to the Vertex compound) for 8 weeks. (michaeljfox.org)
  • Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. (biologists.org)
  • Caspase-1 and MyD88 activation in vivo were suppressed by intravitreous injection of known inhibitors. (arvojournals.org)
  • Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. (usgs.gov)
  • 2005) Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. (guidetopharmacology.org)
  • 2005) Caspase inhibitors: a pharmaceutical industry perspective. (guidetopharmacology.org)
  • The methodology is based on carboxyfluorescein (FAM) labeled fluoromethyl ketone (FMK)-peptide inhibitors of caspases. (celltechnology.com)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • Applications- Effective means for screening caspase inhibitors using fluorometric methods. (antibody-antibodies.com)
  • Caspase-1: the inflammasome and beyond. (nih.gov)
  • Caspase-1 itself is activated in different inflammasome complexes, which assemble in response to a variety of exogenous and endogenous stressors. (nih.gov)
  • Caspase-11 controls interleukin 1β (IL-1β) secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide (LPS) and Gram-negative bacteria. (harvard.edu)
  • In mouse macrophages cytosolic flagellin promote the assembly of the NLRC4 inflammasome inducing the activation of caspase-1 and secretion of IL-1β and IL-18. (frontiersin.org)
  • evaluated the inflammasome and found that unlike in non-permissive mouse macrophages, Legionella did not induce caspase-1 activation in human monocytes. (frontiersin.org)
  • The inflammasome is a signalling platform leading to caspase-1 activation. (archives-ouvertes.fr)
  • This is critical for the oligomerization of the NLRP3 inflammasome and activation of caspase-1 in pyroptosis. (immunochemistry.com)
  • It acts as a potassium ionophore, inducing a net decrease in intracellular levels of potassium, which is crucial for oligomerization of the NLRP3 inflammasome and activation of caspase-1. (immunochemistry.com)
  • 3. Use Nigericin at 1-20 µM to induce NLRP3 inflammasome activation in cells. (immunochemistry.com)
  • 4. NLRP3 inflammasome activation can be detected by ELISA or Western blot measuring secreted pro-inflammatory cytokines IL-1β or IL-18, or through the use of caspase-1 activation assays, such as ICT's Caspase-1 Assay Kits or Pyroptosis/Caspase-1 Assay Kit. (immunochemistry.com)
  • The most intensively studied inflammasome comprises an oligomeric complex of procaspase-1 with the NLRP3 and ASC adapter proteins that rapidly assembles in response to diverse stress stimuli such as increased reactive oxygen species (ROS) ( 3 ), mitochondrial dysfunction ( 4 ), perturbation of intracellular ion homeostasis ( 5 - 7 ), disruption of lysosomal membrane integrity ( 8 ), and activation of deubiquitinases ( 9 - 11 ). (jimmunol.org)
  • Pro-Caspase-1, once activated by an inflammasome complex is processed into p20 and p10 subunits that assembles to form a p20-p20 /p10-p10 active complex that is secreted by a nonconventional (non-ER-dependent) mechanism. (biovendor.com)
  • ATP activates the P2X7 receptor, resulting in rapid assembly of the inflammasome, an IL-1β-activation and -processing platform. (biologists.org)
  • Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. (clinsci.org)
  • This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. (clinsci.org)
  • Monocytes from ACS patients are 'primed' to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β. (clinsci.org)
  • Here, we reveal that DICER1 is an essential endogenous negative regulator of NLRP3 inflammasome activation, and that DICER1 deficiency leads to Alu RNA and Caspase-1-mediated, MyD88-dependent, microRNA-independent RPE degeneration. (arvojournals.org)
  • Taken together, MHV68 impairs the inflammasome response by inhibiting IL-1β production during the initial stages of infection. (gallusimmunotech.com)
  • Unexpectedly, we found that murine gammaherpesvirus pathogenesis was not enhanced in mice lacking caspase-1, a critical inflammasome component. (gallusimmunotech.com)
  • Infection also prevented the host cell inflammasome response to other pathogen-associated molecular patterns, indicated by reduced production of the proinflammatory cytokine IL-1β upon bacterial coinfection. (gallusimmunotech.com)
  • An inflammasome represents a high molecular weight complex that activates inflammatory caspases and activates cytokines of the IL-1 family. (adipogen.com)
  • Even though mechanisms that regulate inflammasome activity remain elusive, various proteins were identified that may interfere with inflammasome activation and inflammasome dependent inflammatory caspase processing. (adipogen.com)
  • Such proteins encompass not only host derived inflammasome regulators, but also various bacterial virulence factors inhibiting caspase-1 activation and viral PYD proteins. (adipogen.com)
  • As MSU is a potent NLRP3 inflammasome agonist, it is believed inflammasome-regulated IL-1β exerts a pathogenic role in gout. (adipogen.com)
  • Furthermore, IL-1β secretion by the NLRP3 inflammasome is triggered by high extracellular glucose in b-cells. (adipogen.com)
  • Her studies along with those from other groups published in 2006 provided the first genetic evidence for the role of NLRP3 in the formation of the inflammasome, caspase-1 activation, and IL-1β/IL-18 maturation. (wikipedia.org)
  • Her lab identified caspase-8 and FADD as expression and activation regulators of both the canonical and non-canonical NLRP3 inflammasome/pyroptosis. (wikipedia.org)
  • Her lab also established that transforming growth factor beta-activated kinase 1 (TAK1) can act as a master regulator that maintains cellular homeostasis by negatively regulating the NLRP3 inflammasome and pyroptosis, apoptosis, and necroptosis. (wikipedia.org)
  • Kanneganti's research group recently further elucidated the molecular mechanism of PANoptosis and showed that the enigmatic caspase-6 is critical for ZBP1-mediated NLRP3 inflammasome activation, PANoptosis, innate immune responses, and host defense against IAV. (wikipedia.org)
  • The initiator caspases including caspase-1 , -8, -9, typically caspase-8 and caspase-9, are activated by two alternative pathways (Salvesen and Dixit, 1997). (thefreedictionary.com)
  • In apoptosis, caspases are responsible for proteolytic cleavages that lead to cell disassembly (effector caspases), and are involved in upstream regulatory events (initiator caspases). (celltechnology.com)
  • Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. (mdpi.com)
  • There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. (mdpi.com)
  • Since caspase-1 activates IL-18, lack of mature IL-18 might protect these caspase-1-/- mice from ARF. (jci.org)
  • It is found predominantly in the cell cytoplasm, where it activates interleukin-1-beta, a molecule that mediates immune and inflammatory responses. (sciencephoto.com)
  • Activated Caspase 8 then activates other downstream caspases including Caspase 9, thereby committing the cell to undergo apoptosis. (thermofisher.com)
  • Caspase-3 cleaves and activates SREBPs between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. (scbt.com)
  • Caspase-3 also cleaves and activates caspase-6, -7 and -9. (scbt.com)
  • Activated caspase-9 in turn cleaves and activates caspase-3. (nih.gov)
  • Activated m-calpain cleaves Bcl-X L and proteolytically activates caspase-12 ( Nakagawa and Yuan, 2000 ). (biologists.org)
  • I'm using THP-1 cells which I differentiate to macrophages using PMA. (protocol-online.org)
  • We unraveled the role of caspases and p53 in F3-induced THP-1 cells differentiation into macrophages. (hindawi.com)
  • AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. (archives-ouvertes.fr)
  • Francisella tularensis, the agent of tularaemia, triggers AIM2/ASC-dependent caspase-3-mediated apoptosis in caspase-1-deficient macrophages. (archives-ouvertes.fr)
  • Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. (biomedsearch.com)
  • We showed that this anti-inflammatory effect of chrysophanol is through suppression of the activation of NF-kB and caspase-1 in LPS-stimulated macrophages. (mdpi.com)
  • We have previously reported that PLY is an essential factor for activation of caspase-1 and consequent secretion of IL-1β and IL-18 in macrophages infected with S. pneumoniae . (jimmunol.org)
  • To further elucidate the mechanism of caspase-1 activation in macrophages infected with S. pneumoniae , we examined the involvement of inflammasomes in inducing this cellular response. (jimmunol.org)
  • Caspase-1 activation was partially impaired in NLRP3 −/− macrophages, whereas knockdown and knockout of AIM2 resulted in a clear decrease in caspase-1 activation in response to S. pneumoniae . (jimmunol.org)
  • We determined that infection of macrophages with MHV68 led to a robust interferon response but failed to activate caspase-1 or induce the secretion of IL-1β. (gallusimmunotech.com)
  • Taken together, murine gammaherpesvirus impairment of the inflammatory cytokine IL-1β in macrophages identifies one mechanism by which the virus may inhibit caspase-1-dependent immune responses in the infected animal. (gallusimmunotech.com)
  • Whereas these 'canonical' activities are well appreciated, this review also highlights less-known pathways and molecules activated by caspase-1. (nih.gov)
  • However, there is increasing evidence that caspase-1 contributes to innate and adaptive immunologic defense mechanisms, repair and pathologic conditions by the regulation of several different and partially opposing pathways. (nih.gov)
  • you can check caspase-3 activation or other proteins to make sure cell death pathways are activated. (protocol-online.org)
  • All different pathways end up with activation of caspase-3. (protocol-online.org)
  • Although this normal programmed cell death (PCD) can occur by distinct morphological pathways ( Clarke, 1990 , 1998 ), the biochemical and molecular pathways involved have been generally considered to require a relatively conserved core of so-called "proapoptotic" genes comprised of Bcl-2 family members, the apoptosome (cytochrome c , Apaf-1, caspase 9) and downstream caspases (e.g., caspase-3). (jneurosci.org)
  • Caspases are enzymes responsible for executing apoptotic pathways, or programmed cell death and are also involved in processing cytokines involved in inflammation. (bio-medicine.org)
  • The identification of noncanonical (caspase-1-independent) pathways for IL-1β production has unveiled an intricate interplay between inflammatory and death-inducing signaling platforms. (jimmunol.org)
  • Poxviruses employ numerous strategies to achieve this goal [ 1 ], including the expression of multiple proteins that inhibit various components of host cell death pathways [ 2 , 3 ]. (portlandpress.com)
  • Rather, TAK1 was recently found to be a crucial regulator of the JNK, p38, and p65 pathways in response to TNF-α, interleukin-1, and ligands of Toll-like receptor, such as lipopolysaccharide ( 21 - 26 ). (aacrjournals.org)
  • However, the role of TAK1 in the TRAIL-induced p65/JNK/p38 pathways and caspase-mediated apoptotic cell death remains to be investigated. (aacrjournals.org)
  • In addition, the finding that caspase 1 was downregulated in colonic adenocarcinomas supports the concept that disrupted apoptosis pathways may be involved in tumour formation and/or may confer resistance to treatment. (bmj.com)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • More recently, pyroptosis, a caspase-1-dependent type of programmed cell death, has been identified that is able to support secreted IL-1 and IL-18 in triggering an inflammatory response. (nih.gov)
  • Caspase-1-dependent programmed cell death (known as pyroptosis) is a unique form of cell death that does not depend on the activation of caspase-3. (protocol-online.org)
  • Moreover, VX-765 decreased circulating IL-1β, prevented loss of cardiac glycolytic enzymes, preserved mitochondrial complex I activity, and decreased release of lactate dehydrogenase, a marker of pyroptosis. (springer.com)
  • Caspase-1 causes pyroptosis, a necrotic-like cell death. (archives-ouvertes.fr)
  • Inflammatory caspases, such as caspase-1, play a critical role in the mechanism to trigger the lytic programmed cell death known as pyroptosis. (immunochemistry.com)
  • There is evidence that caspase-1 supports cell survival by activation of NF-κB, induction of membrane repair and regulation of unconventional secretion of certain proteins. (nih.gov)
  • The physiologic effects of processing of other downstream targets, such as proteins involved in glycolysis or activation of caspase-7, are less well understood. (nih.gov)
  • Spi-2 proteins like CrmA potently inhibit caspases-1, -4 and -5, which produce proinflammatory cytokines, and caspase-8, which facilitates cytotoxic lymphocyte-mediated target cell death. (portlandpress.com)
  • Despite its key role in initiating inflammation, many aspects of IL-1β activity remain poorly understood, in part due to its unconventional secretion mechanism but also due to the complex array of proteins involved in its activation ( Schroder and Tschopp, 2010 ). (biologists.org)
  • By cleaving critical proteins, caspases lead to the changes that characterize apoptosis both morphologically and biochemically, such as chromatin condensation, loss of cell adhesion, cell shrinkage, membrane blebbing, DNA fragmentation, and finally formation of apoptotic bodies, which stimulate their own engulfment by phagocytes. (mdpi.com)
  • Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. (drugbank.ca)
  • Interestingly, the supernatant from DN-HNF1A-expressing cells, but not DN-HNF1A-expressing cells treated with zVAD.fmk, was sufficient to induce PSP/reg gene expression and increase cell proliferation in naïve, untreated INS-1 cells. (diabetesjournals.org)
  • Dynamic gene expression profiles showed that cell differentiation was induced in F3-treated THP-1 cells. (hindawi.com)
  • Apoptosis is programed cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. (biomedsearch.com)
  • However, autophagy does not appear to be involved in the normal PCD of postmitotic neurons in which caspases and Apaf-1 are present and functional because quantitatively normal neuronal PCD occurred in the absence of a key gene required for autophagy (ATG7). (jneurosci.org)
  • 10-12 This conclusion is based largely on the phenotype obtained with caspase-1 gene ablation: caspase-1 −/− mice had no mature interleukin-1β (IL-1β) or IL-18 and were defective in producing IL-1α, IL-6, and tumor necrosis factor-α (TNF-α) in response to lipopolysaccharide. (ahajournals.org)
  • Further investigation using western blotting revealed that cytochrome c was released from the mitochondria into the cytoplasm, and caspase‑8 and caspase‑9 were activated in MUC1 gene‑silenced SMMC‑7721 cells. (spandidos-publications.com)
  • In addition, results from the co‑immunoprecipitation experiments demonstrated that the MUC1 cytoplasmic tail can bind directly to Bax or caspase‑8 and these interactions were reduced upon MUC1 gene silencing in SMMC‑7721 cells. (spandidos-publications.com)
  • 1 Furthermore, several lines of evidence suggest that caspase 1, a mammalian homologue of the Caeonorhabditis elegans cell death gene CED-3, is involved in apoptosis. (bmj.com)
  • Overexpression of the murine caspase 1 gene induces apoptosis in Rat-1 cells, which is abrogated by mutations in the catalytic Cys residue. (bmj.com)
  • In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. (mdpi.com)
  • Our results provide a molecular explanation for the differentiation effect of F3 on human leukemia THP-1 cells and offer a prospect for a potential leukemia differentiation therapy. (hindawi.com)
  • However, the host molecular factors involved in caspase-1 activation are still unclear. (jimmunol.org)
  • 1. Avivi-Green C, Polak-Charcon S, Madar Z, Schwartz B. (2002) Different molecular events account for butyrate-induced apoptosis in two human colon cancer cell lines. (guidetopharmacology.org)
  • We sought to determine whether mice deficient in the proinflammatory caspase-1, which cleaves precursors of IL-1β and IL-18, were protected against ischemic acute renal failure (ARF). (jci.org)
  • Pugin J, Ricou B, Steinberg K, Suter P, Martin T (1996) Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS: a prominent role for interleukin-1. (springer.com)
  • IL-1β is a pleiotropic proinflammatory cytokine that is predominantly expressed in myeloid leukocytes. (jimmunol.org)
  • 11 It is generally felt that the most relevant actions of capsase-1 are proinflammatory, being related to cytokine processing. (ahajournals.org)
  • Both caspase-1 and caspase-3, ie, the prototypical proinflammatory and proapoptotic caspases, are upregulated in diseased hearts. (ahajournals.org)
  • 22 Assigning a meaningful role for upregulated caspase-1 in cardiomyocyte apoptosis is also controversial because its dominant function in the heart is assumed to be proinflammatory rather than proapoptotic. (ahajournals.org)
  • These data indicate that ER stress induced activation of wildtype caspase-1 might be involved in a negative feed back reduction of ER stress and that impaired caspase-1 activity might allow for a perpetuation of ER stress thus contributing to the proinflammatory phenotype of our patients. (biomedcentral.com)
  • pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. (anaspec.com)
  • However, we still know very little about the downstream mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. (harvard.edu)
  • Caspase substrates and cellular remodeling. (semanticscholar.org)
  • The inflammatory caspases all have a CARD domain followed by a domain containing the catalytic residue cysteine and are called inflammatory caspases because their main substrates are cytokines (such as pro-IL-1β, pro-IL-18 and eventually pro-IL-33) which are cleaved to their active and secreted form. (adipogen.com)
  • Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. (nih.gov)
  • These experiments demonstrate that Bcl-X L associates with caspase-9 and Apaf-1, and show that Bcl-X L inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans. (pnas.org)
  • Furthermore, Apaf-1 promoted the processing and activation of caspase-9 in vivo . (pnas.org)
  • Previous studies have shown that caspases and Apaf-1 are required for the normal programmed cell death (PCD) in vivo of immature postmitotic neurons and mitotically active neuronal precursor cells. (jneurosci.org)
  • Kim S-J, Kim M-C, Lee B-J, Park D-H, Hong S-H, Um J-Y. Anti-Inflammatory Activity of Chrysophanol through the Suppression of NF-kB/Caspase-1 Activation in Vitro and in Vivo . (mdpi.com)
  • Caspase-1 mediated sensitisation to cisplatin and γ-radiation was also observed in vivo. (csic.es)
  • Altogether, we conclude that caspase-1 can act as a radio- and chemo-sensitiser, in vitro and in vivo. (csic.es)
  • We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. (biologists.org)
  • The present study is aimed to elucidate the effects and relative mechanisms of TT‑1 on a human thyroid cancer cell line (TT) in vitro and in vivo. (spandidos-publications.com)
  • In summary, TT‑1 may inhibit the proliferation of TT cells by inducing apoptosis in vitro and in vivo, indicating that TT‑1 may be a potential candidate for the treatment of thyroid cancer. (spandidos-publications.com)
  • Furthermore, in the kidneys of Apaf-1-deficient mice, apoptosis induced by in vivo administration of tunicamycin was remarkably suppressed as compared with wild type mice. (biologists.org)
  • Finally, the presence of mature/processed IL-18 in atherosclerotic tissue of Caspase-1-deficient mice highlighted the potential in vivo relevance of such an alternative, MMP-mediated IL-18 activation mechanism for this pro-inflammatory disease. (uni-koeln.de)
  • Caspase-1-/- 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)
  • Consistently, trpc1−/− mice show higher IL-1β secretion in the sepsis model of intraperitoneal LPS injection. (harvard.edu)
  • We examined the survival of these more mature postmitotic neuronal populations in mice in which Apaf-1 has been genetically deleted and find that they exhibit quantitatively normal PCD of developing postmitotic neurons. (jneurosci.org)
  • Transgenic mice that overexpress IL-18 ( 18 ) or caspase-1 ( 19 ) in their keratinocytes showed high serum IL-18 and IgE levels. (aacrjournals.org)
  • Furthermore, ASC −/− mice were more susceptible than wild-type mice to S. pneumoniae , with impaired secretion of IL-1β and IL-18 into the bronchoalveolar lavage after intranasal infection, suggesting that ASC inflammasomes contribute to the protection of host from infection with PLY-producing S. pneumoniae . (jimmunol.org)
  • In tumor-bearing mice treated with oxaliplatin, NLRP3-dependent IL-1β release from dendritic cells (DCs) occurs via paracrine activation of P2X7 receptors (P2X7R) in response to ATP released from dying tumor cells ( 12 ). (jimmunol.org)
  • 13,14 Notably, apoptotic processes appeared normal in the caspase-1 −/− mice. (ahajournals.org)
  • Additional experiments employing chimeric mice, that lacked the IL-18R alpha on either the hematopoietic or the vascular cells, generated by bone-marrow transplantation, revealed that IL-18R alpha does not participate in the pro-atherogenic effects of IL-18 Surprisingly, deficiency of Caspase-1 did not diminish atherogenesis, thus suggesting alternative mechanisms of IL-18 activation during atherosclerosis. (uni-koeln.de)
  • Inbred and congenic mice harboring macrophage-sensitizing Nlrp1b S/S alleles (which allow activation of caspase-1 and IL-1β release in response to anthrax lethal toxin challenge) effectively controlled bacterial growth and dissemination when compared to mice having Nlrp1b R/R alleles (which cannot activate caspase-1 in response to toxin). (prolekare.cz)
  • Resistance to infection required the actions of both caspase-1 and IL-1β as Nlrp1b S/S mice deleted of caspase-1 or the IL-1 receptor, or treated with the Il-1 receptor antagonist anakinra, were sensitized to infection. (prolekare.cz)
  • Comparison of circulating neutrophil levels and IL-1β responses in Nlrp1b S/S ,Nlrp1b R/ R and IL-1 receptor knockout mice implicated Nlrp1b and IL-1 signaling in control of neutrophil responses to anthrax infection. (prolekare.cz)
  • Murine Gammaherpesvirus 68 Pathogenesis Is Independent of Caspase-1 and Caspase-11 in Mice and Impairs Interleukin-1β Production upon Extrinsic Stimulation in Culture. (gallusimmunotech.com)
  • We infected caspase-1-deficient mice with murine gammaherpesvirus 68 (MHV68) and observed no impact on acute replication in the lung or latency and reactivation from latency in the spleen. (gallusimmunotech.com)
  • These results suggest that ASC inflammasomes, including AIM2 and NLRP3, are critical for caspase-1 activation induced by S. pneumoniae . (jimmunol.org)
  • On the one hand, NLRP3/caspase-1 inflammasomes play a central role in the regulation of IL-1β production within tumor loci or in response to chemotherapeutic drugs. (jimmunol.org)
  • Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 μM) or sultopride (1 μM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1β. (chinaphar.com)
  • Contrary to NLRP1, NLRP3 and AIM2, IPAF does not recruit an adapter molecule but directly interacts with procaspase-1 via its CARD domain (see Figure below). (adipogen.com)
  • Caspase-1 also controls the secretion of IL-1E-, but the mechanism and route of secretion are unknown. (thefreedictionary.com)
  • In our previous study, we found that fucose-containing polysaccharide fraction F3 extracted from Ganoderma lucidum can bring about cytokine secretion and cell death in human leukemia THP-1 cells. (hindawi.com)
  • This is the first description of the secretion of IL-1β by microvesicle shedding from ECs which is caspase-1 independent. (bmj.com)
  • Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. (biologists.org)
  • Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. (biologists.org)
  • IL-1β secretion is proposed to occur via a number of different mechanisms, ranging from lysosomal and microvesicular to pyroptotic, dependent on the strength of the inflammatory stimulus and the cell type in question ( López-Castejón and Brough, 2011 ). (biologists.org)
  • However, it has not been possible to combine the key features of such models to determine, in an intact organism, the vesicular component of IL-1β secretion and how IL-1β is specifically targeted to effector cells. (biologists.org)
  • As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. (usgs.gov)
  • These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation. (usgs.gov)
  • Additionally rTgPrx treatment reduced caspase-1 activity and IL-1β secretion, while simultaneously increasing IL-10 release. (youscribe.com)
  • Quantification of IL-1β, IL-8, and TNF-α secretion was performed by cytometric bead arrays. (biomedcentral.com)
  • In THP-1 cells such induction of ER stress lead to secretion of IL-1β, IL-8, and TNF-α. (biomedcentral.com)
  • Our results indicated that DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of DeltaPsim and the activation of caspase-3. (sigmaaldrich.com)
  • MitoCasp A simultaneous dual parameter Assay For: Mitochondrial Membrane Potential Detection & Caspase (poly, 3/7, 8, 9, 1) Activity. (celltechnology.com)
  • Simultaneous detection of mitochondrial membrane potential and caspase activity. (celltechnology.com)
  • Utilizing these two reagents in combination Caspase activity and mitochondrial membrane potential can be analyzed simultaneously. (celltechnology.com)
  • I need to activate caspase-1 to trigger inflammation and pyroptotic cell death. (protocol-online.org)
  • Caspases play important roles in apoptosis and inflammation. (immunochemistry.com)
  • Interleukin-1 (IL-1), the 'gatekeeper' of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. (biologists.org)
  • Interleukin-1 (IL-1) is an important activator of inflammation. (biologists.org)
  • Dysregulated IL-1β function has been described in the pathology of a number of auto- or chronic inflammatory diseases, leading to this cytokine being described as the 'gatekeeper' of inflammation ( Dinarello, 2011c ). (biologists.org)
  • The mammalian caspases play distinct roles in apoptosis and inflammation. (celltechnology.com)
  • Caspases are usually involved in apoptosis and inflammation but they also exhibit nonapoptotic functions. (reactome.org)
  • 1997). Substrate specificities of caspase family proteases. (anaspec.com)
  • Here we show that a mammalian homolog of CED-4, Apaf-1, can associate with several death proteases, including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. (pnas.org)
  • A family of cysteine proteases (designated caspases) related to the C. elegans CED-3 appears to represent the effector arm of the apoptotic program ( 13 ). (pnas.org)
  • The N-terminal region of Apaf-1 shares amino acid homology with CED-4 and the prodomains of CED-3 and several CED-3-like proteases with long prodomains. (pnas.org)
  • The region of homology shared between Apaf-1 and the prodomains of CED-3-like proteases has been termed caspase recruitment domain ( 19 ). (pnas.org)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Caspases are the proteases responsible for dismantling the cell in an ordered and histologically distinct process termed apoptosis [ 1 ]. (mdpi.com)
  • The apoptotic mechanism is evolutionarily conserved and controlled by a genetic program ( 1 - 3 ). (pnas.org)
  • However, the precise mechanism by which Bcl-2 and Bcl-X L control caspase activation and apoptosis remains controversial. (pnas.org)
  • CONCLUSIONS Our results suggest that apoptosing INS-1 cells shed microparticles that may stimulate PSP/reg induction in neighboring cells, a mechanism that may facilitate the recovery of β-cell mass in HNF1A-MODY. (diabetesjournals.org)
  • This study investigates the effect of neutrophil elastase (NE) on ECs in terms of IL-1β release and explores the underlying mechanism. (bmj.com)
  • NE is detected in the endothelium of murine atherosclerotic plaques and, therefore, this is a plausible mechanism to promote local IL-1β release in the vasculature. (bmj.com)
  • Although doxorubicin may initiate apoptotic program by using molecules such as p53, reactive oxygen species, and caspases ( 7 , 8 ), the detailed mechanism by which doxorubicin induces apoptosis has not been fully clarified. (aacrjournals.org)
  • The exact mechanism by which caspases mediate NF-kB activation is unclear, but the prodomains of caspase-8/10 may act as a scaffolding and allow the recruitment of the IKK complex in association with other signaling molecules. (reactome.org)
  • Processed caspases (caspase-8/10) encoding the DED (death effector domain) strongly activate NF-kB. (reactome.org)
  • Expression of Apaf-1 enhanced the killing activity of caspase-9 that required the CED-4-like domain of Apaf-1. (pnas.org)
  • Expression of Bcl-X L inhibited the association of Apaf-1 with caspase-9 in mammalian cells. (pnas.org)
  • The expression of mast cells-derived caspase-1 was suppressed by NJJ in AD-like lesional skin. (thefreedictionary.com)
  • Caspase-1 expression in multiple sclerosis plaques and cultured glial cells. (thefreedictionary.com)
  • Furthermore, F3-treated THP-1 cells exhibited enhanced macrophage differentiation, as demonstrated by changes in cell adherence, cell cycle arrest, NBT reduction and expression of differentiation markers including CD11b, CD14, CD68, matrix metalloproteinase-9 and myeloperoxidase. (hindawi.com)
  • The lack of caspase-1 activation could be explained by the ability of Legionella to inhibit the expression of NLRC4 and, to a lesser extent, ASC. (frontiersin.org)
  • Though lysis requires expression of the receptor lymphocyte function-associated molecule 1 (LFA-1) on the cell surface, not all LFA-1-expressing leukocyte populations are equally susceptible to the toxin. (diva-portal.org)
  • In this study, the susceptibility of human leukocytes to leukotoxin-induced lysis is compared to their expression of LFA-1 and the activity of caspase 1. (diva-portal.org)
  • Similar LFA-1 expression was found in all susceptible cell populations irrespective of their degree of sensitivity to the toxin. (diva-portal.org)
  • Ectopic expression of caspase-1 has been shown to trigger apoptosis. (csic.es)
  • In patients, high levels of caspase-1 expression may be associated with spontaneous regression in neuroblastomas and with a good clinical response to chemotherapy in acute myeloid leukemia and osteosarcoma. (csic.es)
  • Caspase-1 expression mediated by an adenoviral vector was able to kill directly cells and to sensitise the remaining cells to cisplatin or γ-radiation in vitro. (csic.es)
  • Endometrial caspase 1 and interleukin-18 expression during the estrous cycle and peri-implantation period of porcine pregnancy and response to early exogenous estrogen administration. (sigmaaldrich.com)
  • Here, the consequences of increased myocardial expression of procaspase-1 were examined on the normal and ischemically injured heart. (ahajournals.org)
  • 17-21 However, data supporting a pathophysiological effect of increased myocardial caspase expression have been inconsistent. (ahajournals.org)
  • In this study, we used forced myocardial expression of inactive procaspase-1 in normal and ischemic hearts to address the following questions: (1) Can caspase-1 be activated in cardiac myocytes? (ahajournals.org)
  • No remarkable effects were seen on NALP3 or caspase-1 expression in EC lysates. (bmj.com)
  • Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. (biologists.org)
  • Appropriate propofol concentrations (ranging from 40 μM to 160 μM) significantly increased HO- 1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. (eurekaselect.com)
  • We showed that isosibiricin (10−50 μM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-18 (IL-18). (chinaphar.com)
  • AIMS To characterise IL-1 and caspase 1 expression in human colonic epithelial cells. (bmj.com)
  • Here our experiments show that rTgPrx promotes AAM as indicated by high arginase-1 (arg-1), YM1 and FIZZ expression via both signal transducer and activator of transcription (STAT)6-dependent and -independent mechanisms. (youscribe.com)
  • Local expression of mIgf-1 modulates ubiquitin, caspase and CDK5 expression in skeletal muscle of an ALS mouse model. (semanticscholar.org)
  • article{Dobrowolny2008LocalEO, title={Local expression of mIgf-1 modulates ubiquitin, caspase and CDK5 expression in skeletal muscle of an ALS mouse model. (semanticscholar.org)
  • Caspase-8 interacts with ASC and active caspase-8 specifically colocalizes with the AIM2/ASC speck thus identifying the AIM2/ASC complex as a novel caspase-8 activation platform. (archives-ouvertes.fr)
  • The top images reveal several experimental cells, all of which fluoresce green, therefore they have active caspase-1. (immunochemistry.com)
  • none of these cells have active caspase-1 (Dr. Brian W. Lee, ICT). (immunochemistry.com)
  • An active caspase consists of two large (~20 kD) and two small (~10 kD) sub units to form two heterodimers, which associate in a tetramer (2-4). (celltechnology.com)
  • The FLICA 660 caspase-1 kit uses a target sequence (YVAD) sandwiched between a far-red fluorescent 660 dye and a fluoromethylketone (FMK) to make a quick and flexible method to analyze active caspase-1 in apoptotic cells. (bio-rad-antibodies.com)
  • Active caspase-1 cleaves the synthetic substrate to release free AFC which can then be quantified by fluorometry. (antibody-antibodies.com)
  • Thus inflammatory caspases are brought into close proximity what permits autoactivation and formation of the active caspase. (adipogen.com)
  • After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction. (nih.gov)
  • We report that minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA upregulation, and decreases inducible nitric oxide synthetase activity. (nih.gov)
  • Rosaria Acquaviva, Agata Campisi, Giuseppina Raciti, Roberto Avola, Maria Luisa Barcellona, Luca Vanella and Giovanni Li Volti, " Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1", Current Neurovascular Research (2005) 2: 141. (eurekaselect.com)
  • Strongly inhibits anti-APO-1 induced apoptosis in L929-APO-1 cells. (emdmillipore.com)
  • Caspase-1 is the best-described inflammatory caspase. (biovendor.com)
  • Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. (usgs.gov)
  • However, caspase-1 appears to be the most dominant inflammatory caspase associated with inflammasomes. (adipogen.com)
  • Bcl-X L , an antiapoptotic member of the Bcl-2 family, was shown to physically interact with Apaf-1 and caspase-9 in mammalian cells. (pnas.org)
  • Recent studies have identified and partially characterized Apaf-1, a mammalian homolog of C. elegans CED-4 ( 18 ). (pnas.org)
  • Caspase-1/ICE was the first mammalian caspase to be described. (ahajournals.org)
  • The orthologs differed markedly in their propensity to inhibit non-mammalian caspases. (portlandpress.com)
  • The Caspase FLICA Kits are suitable for cells in suspension and adherent cells from many species including mammalian, insect and yeast. (bio-rad-antibodies.com)
  • It requires signaling through pannexin-1 to induce caspase-1 activation and IL-1ß processing and release. (immunochemistry.com)
  • These data suggest that THC treatment of cultured immune cells induces apoptosis through the regulation of Bcl-2 and caspase activity. (biomedsearch.com)
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a typical member of the TNF-α ligand family that induces apoptosis in various types of tumor cells but not in most normal cells ( 1 - 3 ). (aacrjournals.org)
  • Significantly, recombinant Bcl-X L purified from Escherichia coli or insect cells inhibited Apaf-1-dependent processing of caspase-9. (pnas.org)
  • In addition, Caspase 8 also reacts with Jurkat cells and Tonsil. (thermofisher.com)
  • Here, we investigated the effect of a dominant-negative HNF1A mutant (DN-HNF1A) induced apoptosis on the regenerative capacity of INS-1 cells. (diabetesjournals.org)
  • RESEARCH DESIGN AND METHODS DN-HNF1A was expressed in INS-1 cells using a reverse tetracycline-dependent transactivator system. (diabetesjournals.org)
  • Further experiments demonstrated that annexin-V-positive microparticles originating from apoptosing INS-1 cells mediated the induction of PSP/reg . (diabetesjournals.org)
  • We integrated time-course microarray analysis and network modeling to study the F3-induced effects on THP-1 cells. (hindawi.com)
  • Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. (sigmaaldrich.com)
  • In this study, cell counting kit (CCK-8) assay was employed to evaluate the survival of DHA-treated ASTC-a-1 cells. (sigmaaldrich.com)
  • Caspase-3 is expressed in cells as an inactive precursor from which the p17 and p11 subunits of the mature caspase-3 are proteolytically generated during apoptosis. (scbt.com)
  • Although normally these cells use caspases for PCD, in the absence of caspase activity these neurons undergo a distinct nonapoptotic type of degeneration. (jneurosci.org)
  • These studies clearly demonstrate that the extensive PCD of immature postmitotic neurons and mitotically active progenitor cells in the nervous system require cytochrome c , Apaf-1, and caspases. (jneurosci.org)
  • It has been shown to generate a robust caspase-1 activation response in various cell lines, including Jurkat and THP-I cells. (immunochemistry.com)
  • the longer the cells were exposed to Nigericin, the larger the proportion of caspase-1 positive cells found in the sample. (immunochemistry.com)
  • We conclude that fluoride -induced apoptosis is largely dependent on Ca 2+ induced superoxide generation leading to elevation in CaMKII g which in turn induces the phosphorylation of ERK 1/2 and downstream activation of extrinsic caspase cascade in HKM cells. (fluoridealert.org)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • 5. Add diluted FLICA to each sample at 1:30 (e.g., add 10 μL to 290 μL of cultured cells). (immunochemistry.com)
  • Endothelial cells (ECs) are critically involved in the pathogenesis of atherosclerosis by producing inflammatory mediators, including interleukin-1 beta (IL-1β). (bmj.com)
  • Human coronary artery endothelial cells (HCAEC) were treated with a combination of tumour necrosis factor-alpha and interleukin-1 alpha then incubated with NE for 2 or 6 h. (bmj.com)
  • NE enters ECs, cleaves proIL-1β (31kDa) inside cells resulting in release of active isoforms of IL-1β in microparticles. (bmj.com)
  • Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 μM) in the presence or absence of propofol (40 μM, 80 mM and 160 μM). (eurekaselect.com)
  • Alu RNA-induced Caspase-1 activation in human RPE cells was inhibited by DICER1 overexpression. (arvojournals.org)
  • Furthermore, a tumor‑xenograft model was established to investigate the apoptotic mechanisms of TT‑1 on TT cells. (spandidos-publications.com)
  • The results obtained indicated that TT‑1 was able to suppress the proliferation of TT cells and exhibited low cytotoxicity to normal thyroid cells in vitro. (spandidos-publications.com)
  • The apoptotic rates of TT cells were also increased following TT‑1 treatment. (spandidos-publications.com)
  • Apaf-1-deficient MEFs showed more resistance to ER stress-inducing reagents as compared with wild type cells. (biologists.org)
  • Despite comparable induction of ER stress in both wild type and Apaf-1-deficient cells, activation of caspase-3 was only observed in wild type, but not Apaf-1-deficient, MEFs. (biologists.org)
  • We also demonstrated that caspase-12 was processed downstream of Apaf-1 and caspase-3, and neither overexpression nor knockdown of caspase-12 affected susceptibility of the cells to ER stress-induced cell death. (biologists.org)
  • The untreated transduced cells expressed elevated caspase 3 activity. (asm.org)
  • Two diametrically opposed events take place in cells infected with herpes simplex virus 1 (HSV-1) and also in cells infected with many other viruses. (asm.org)
  • In the human SK-N-SH cells, the events leading to the proapoptotic death of the cells are caspase independent. (asm.org)
  • Results: The TF signaling complexes were shown to prevent apoptosis induced by serum starvation and TRAIL in cancer cells by reduced activation of caspase-8 in a PI3k/AKT-dependent manner. (diva-portal.org)
  • Detection:10380-1-AP 1:200) with HeLa cells lysate 2500 ug. (ptglab.com)
  • In the present study we made the novel observation that oxLDL-induced death of HMEC-1 cells is accompanied by activation of calpain. (biochemj.org)
  • Also, oxLDL provoked calpain-dependent proteolysis of cytoskeletal α-fodrin in the HMEC-1 cells. (biochemj.org)
  • First isolated from monocytic cells, caspase 1 has been recently found in other cell types-for example, keratinocytes, where its main function is to convert pro-IL-1β into mature IL-1β under irritant stress. (bmj.com)
  • Caspase FLICA kits measure apoptosis by detecting active caspases in whole, living cells. (bio-rad-antibodies.com)
  • Additionally, we knocked down endogenous caspase-1 in THP-1 cells to analyze caspase-1 involvement in ER stress responses. (biomedcentral.com)
  • We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
  • First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
  • We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
  • 1. Induce apoptosis in cells by desired method. (antibody-antibodies.com)
  • 2. Count cells and pellet 1-5 x 106 cells. (antibody-antibodies.com)
  • Several caspases including caspase-4, -8, and -9 structurally resemble CED-3 in that they contain long prodomains and appear to act upstream in the caspase cascade ( 13 , 14 ). (pnas.org)
  • Tissue culture studies revealed that procaspase-1 processing/activation is stimulated by hypoxia, and that caspase-1 acts in synergy with hypoxia to stimulate caspase-3 mediated apoptosis without activating upstream caspases. (ahajournals.org)
  • Note: Active recombinant human caspase-1 is available to use as a positive control (BioVision, Cat. (antibody-antibodies.com)
  • In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. (usgs.gov)
  • Furthermore, Bcl-X L failed to inhibit caspase-9 processing mediated by a constitutively active Apaf-1 mutant, suggesting that Bcl-X L regulates caspase-9 through Apaf-1. (pnas.org)
  • Purified immunoglobulin fraction of rabbit antiserum against human Caspase-1. (abcam.com)
  • 6,7 Eleven human caspases homologous to the original nematode caspase, CED-3, have been identified to date. (ahajournals.org)
  • Structurally, zebrafish IL-1β shares a β-sheet-rich trefoil structure with its human counterpart. (biologists.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)
  • METHODS Intracellular IL-1 content (IL-1α and IL-1β) was measured by ELISA in freshly isolated human normal colonocytes. (bmj.com)
  • RESULTS Low amounts of IL-1β were found in nearly all preparations (92%), and IL-1α was detected in only 45% of human colonocyte preparations. (bmj.com)
  • CONCLUSIONS The demonstration that the human colonic epithelial barrier is able to express caspase 1 and its substrate IL-1β reinforces the concept that, under certain conditions, the epithelium could trigger an inflammatory reaction. (bmj.com)
  • Our demonstration that caspase 1 and IL-1β are both expressed in the intestinal epithelium supports the concept recently put forward that the human intestinal barrier has an immunoregulatory role. (bmj.com)
  • 6 We also show that caspase 1 is present only as a proform in human normal colonocytes. (bmj.com)
  • These include caspase-1, -4 and -5 in human and caspase-1, -11 and -12 in mouse. (adipogen.com)
  • Indeed, some human hereditary or acquired diseases have been linked to elevated IL-1β, some of which can be treated by antagonists against IL-1β or its receptor. (adipogen.com)
  • In post-ischemic hearts, procaspase-1 overexpression was associated with strikingly increased cardiac myocyte apoptosis in the peri- and noninfarct regions and with 50% larger myocardial infarctions. (ahajournals.org)
  • The adaptor ASC regulates not only caspase-1 activation, but also cell death and the transcription factor NF-κB by mechanisms that remain poorly understood. (frontiersin.org)
  • The adaptor molecule ASC mediates AIM2-dependent caspase-1 activation. (archives-ouvertes.fr)
  • Fluoride-induced headkidney macrophage cell apoptosis involves activation of the CaMKIIg-ERK 1/2-caspase-8 axis: the role of superoxide in initiating the apoptotic cascade. (fluoridealert.org)
  • It is involved in the activation cascade of caspases responsible for apoptosis execution. (medgadget.com)
  • Thus, proapoptotic chemotherapeutic agents stimulate the caspase-8-mediated processing and release of IL-1β, implicating direct effects of such drugs on a noncanonical inflammatory cascade that may modulate immune responses in tumor microenvironments. (jimmunol.org)
  • In contrast, TAK1-deficient mouse embryonic fibroblasts are resistant to TRAIL-induced apoptosis, and treatment of control mouse embryonic fibroblasts with 5Z-7-oxozeaenol did not drastically promote the TRAIL-induced activation of a caspase cascade. (aacrjournals.org)
  • The assembly of the different inflammasomes elicits a common downstream cascade, namely the activation of inflammatory caspases. (adipogen.com)
  • Apoptosome formation results in the activation of executioner caspases including caspase-3, -6, and -7. (biologists.org)