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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

ASC is an adaptor protein which contains two protein-protein interaction domains; N-terminal - pyrin domain (PYC) and C-terminal - caspase recruitment domain (CARD).. ASC plays an important role in inflammation and apoptosis. It is a component of several inflammatory complexes, inflammasomes, which are important for caspase-1 activation, processing and secretion of pro-inflammatory cytokines (IL-1β, IL-18). It promotes pyropoptosis in macrophages and induces caspase-mediated apoptosis (involving caspase-8 and caspase-9).. Additionally, ASC is involved in transcriptional control of cytokine and chemokine expression independent of the inflammasome.. ...
Background: Inflammatory responses play a key role in the pathophysiology of myocardial ischemia-reperfusion (I/R) injury. ASC is an adaptor protein that forms inflammasome whose activation leads to caspase-1-dependent interleukin (IL)-1β generation and subsequent inflammatory responses; however, the role of ASC in myocardial I/R injury remains to be determined.. Methods and Results: ASC deficient (ASC−/−) and wild-type (WT) mice were subjected to 30 min LAD occlusion, followed by reperfusion. ASC−/− mice showed improved LV dysfunction (%FS: 34.0% vs. 25.7% at 14 days p,0.01), reduced infarct area/area at risk (IA/AAR: 18.7% vs. 28.6% at 48 h, p,0.01), and scar formation (scar/LV area: 9.7% vs. 14.6% at 14 days, p,0.01) after myocardial I/R. Immunostaining revealed decreased infiltration of macrophages (Mac3) and neutrophils (Gr-1), but not neovascularization (CD31), in the injured myocardium of the ASC−/− mice. Real-time RT-PCR and ELISA analyses demonstrated that the myocardial ...
Shop NLR family ELISA Kit, Recombinant Protein and NLR family Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
NALP1 antibody [Nalpy1-4] (NLR family, pyrin domain containing 1) for ICC/IF, IHC-P, IP, WB. Anti-NALP1 mAb (GTX16091) is tested in Human samples. 100% Ab-Assurance.
NLRP13 antibody (NLR family, pyrin domain containing 13) for ELISA, ICC/IF, WB. Anti-NLRP13 pAb (GTX31990) is tested in Human samples. 100% Ab-Assurance.
cdna:known chromosome:VEGA66:16:3945610:3976632:-1 gene:OTTMUSG00000042324 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Nlrc3 description:NLR family, CARD domain containing 3 ...
NALP1兔多克隆抗体(ab36852)可与人样本反应并经WB, IHC, ICC/IF实验严格验证,被4篇文献引用。所有产品均提供质保服务,中国75%以上现货。
ASC2兔多克隆抗体(ab47092)可与小鼠, 大鼠, 人, 沙鼠样本反应并经WB, IP, IHC实验严格验证。所有产品均提供质保服务,中国75%以上现货。
I need some help. I have a ASC case where the MD did a cystourethroscopy w/ bilaterial retrograde ureterograms. He also did Litholapaxy with the extra
Inflammasome activation is associated with numerous diseases. However, in vivo detection of the activated inflammasome complex has been limited by a dearth of tools. We developed transgenic mice that ectopically express the fluorescent adaptor protein, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and characterized the formation of assembled inflammasome complexes (specks) in primary cells and tissues. In addition to hematopoietic cells, we found that a stromal population in the lung tissues forms specks during the early phase of influenza infection whereas myeloid cells showed speck formation after two days. In a peritonitis and Group B streptococcus infection models, a higher percentage of neutrophils formed specks at early phases of infection, while dendritic cells formed specks at later time points. Furthermore, speck-forming cells underwent pyroptosis, and extensive release of specks to the extracellular milieu in vivo. These data underscore the ...
The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound conditioned medium activates caspase-1 and induces release of IL-1β and IL-18 in cultured Mp via a reactive oxygen species-mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from pro-inflammatory to healing-associated Mp phenotypes and increased levels of pro-healing growth factors. Furthermore, data ...
Ca2+ or other CaSR agonists activate the NLRP3 inflammasome in the absence of exogenous ATP, whereas knockdown of CaSR reduces inflammasome activation in response to known NLRP3 activators. The CaSR activates the NLRP3 inflammasome through phospholipase C (PLC), which catalyzes inositol trisphosphate (IP3) production and thereby induces release of Ca2+ from endoplasmic reticulum (ER) stores. The increased cytoplasmic Ca2+ promotes the assembly of inflammasome components, and intracellular Ca2+ is required for spontaneous inflammasome activity in cells from CAPS patients. CaSR stimulation also results in reduced intracellular cAMP, which independently activates the NLRP3 inflammasome. cAMP binds to NLRP3 directly to inhibit inflammasome assembly, and downregulation of cAMP relieves this inhibition. The binding affinity of cAMP for CAPS-associated mutant NLRP3 is substantially lower than for wild-type NLRP3, and the uncontrolled mature IL-1β production from CAPS patients peripheral blood ...
NLRP3 inflammasome assembly. CARD, caspase recruitment domain; LRR, leucine-rich repeat; NACHT/NBD, nucleotide binding domain; PYD, pyrin domain; CAP1, caspase-
PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome . NMR structure of full-length ASC: PDB ID 2KN6 [1] This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ...
Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22-82) in association with age. Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas
To the Editor. We read the article of Osuka et al. (1) entitled A Protective Role for Inflammasome Activation Following Injury with great interest. However, we are concerned that the authors have not sufficiently ruled out the possibility that the major effects attributed to inflammasome inhibition were merely due to the solvent used.. The authors describe inflammasome activation in burned mice 1 day after injury as revealed by caspase 1 activation and increased interleukin 1β (IL-1β) production. Interestingly, the data suggest that inhibiting caspase 1 activity-and thereby inhibiting inflammasome activation-with the Ac-YVAD-cmk peptide did not reduce inflammation as expected. On the contrary, it caused a significantly higher mortality and increased expression of the proinflammatory cytokines IL-6 and IL-33 as compared with untreated burned mice. The authors therefore conclude that inflammasome activation might have a protective role following severe injury. Inhibition of (pro)caspase 1 ...
The cytosolic pattern recognition receptor NLRP3 senses host-derived danger signals and certain microbe-derived products in both humans and rodents. NLRP3 activation assembles an inflammasome complex that contains the adapter proteins ASC and caspase-1, whose activation triggers the maturation and release of the proinflammatory cytokines IL-1β and IL-18. S5 phosphorylation of NLRP3 prevents its oligomerization and activation, whereas dephosphorylation of this residue by the phosphatase PP2A allows NLRP3 activation. However, the protein kinase that mediates NLRP3 S5 phosphorylation is unknown. In this study, we show that AKT associates with NLRP3 and phosphorylates it on S5, limiting NLRP3 oligomerization. This phosphorylation event also stabilizes NLRP3 by reducing its ubiquitination on lysine 496, which inhibits its proteasome-mediated degradation by the E3 ligase Trim31. Pharmacologic manipulation of AKT kinase activity reciprocally modulates NLRP3 inflammasome-mediated IL-1β production. ...
Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune signaling and can link neural insult to chronic inflammation. The NLRP3 inflammasome requires two stages to contribute: priming and activation. The priming stage involves upregulation of inflammasome components while the activation stage results in the assembly and activation of the inflammasome complex. The priming step can be rate limiting and can connect insult to chronic inflammation, but our knowledge of the signals that regulate NLRP3 inflammasome priming in sterile inflammation is limited. This study examined the link between mechanical strain and inflammasome priming in neural systems. Transient non-ischemic elevation of intraocular pressure (IOP) increased mRNA for inflammasome components IL-1β, NLRP3, ASC and CASP1 in rat and mouse retinas. The elevation was greater one day after
Chronic inflammation and inflammasome activation play roles in the pathogenesis of type 2 diabetes (2,29,30). NLRP3 is a member of the NLR family, which is responsible for cytosolic inflammasome activation. The NLRP3 inflammasome has been the focus of particular attention with regard to its roles in inflammatory responses, antimicrobial responses, and a variety of human diseases, including hereditary autoinflammatory syndromes, atherosclerosis, and diabetes (7,22,30,31). Recently, obesity-induced danger signals have been reported to activate the NLRP3 inflammasome and induce the production of IL-1β in adipose tissue in type 2 diabetic patients and mice fed a high-fat diet (9). Circulating levels of C-X-C motif chemokine 10 and CCL2, as well as interferon-γ mRNA and protein levels in adipose tissue, were significantly reduced in NLRP3-deficient mice, suggesting that the NLRP3 inflammasome plays a role in the macrophage-T-cell interactions that are associated with sustained levels of chronic ...
The ASC (apoptosis speck-like protein) is a key component of multimeric protein complexes that mediate inflammation and host defence. Comprising a PYD (Pyrin) domain and a CARD (caspase activation and recruitment domain), ASC functions downstream of NLRs (nucleotide-binding domain, leucine-rich repeat-containing receptors) and AIM2 (absent in melanoma 2) through the formation of supramolecular structures termed inflammasomes. However, the mechanism underlying ASC signalling and its dependency on oligomeric arrangements in inflammasome formation remain poorly understood. When expressed in cells, ASC forms discrete foci (called specks) typically with one speck per cell. We employed a BiFC (bimolecular fluorescence complementation) system to investigate and visualize ASC foci formation in living cells. We demonstrated that the CARD of ASC plays a central role in ASC inflammasome assembly, representing the minimal unit capable of forming foci in conjunction with the caspase 1 CARD. Mutational ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
The term pyroptosis (pyro greek for fire or fever) has been originally coined to describe the non‐apoptotic, caspase‐1‐dependent cell death of Salmonella‐infected macrophages that would alarm and recruit neighboring cells to the site of infection (Cookson & Brennan, 2001). Later it became apparent that the activation of caspase‐1 to induce pyroptosis is controlled by a subset of PRRs that can induce inflammasome activation (e.g. NLRP3, AIM2 or NLRC4/NAIP). Upon recognition of their cognate ligands, these sensors seed the prion‐like assembly of the inflammasome adapter ASC into a high molecular weight cytosolic complex to which caspase‐1 becomes recruited and is activated by. Auto‐processed caspase‐1 then matures the cytokines IL‐1β and IL‐18 to render them bioactive and induce pyroptotic cell death. Besides this canonical inflammasome activation leading to caspase‐1 maturation, other pro‐inflammatory caspases, murine caspase‐11 and human caspase‐4 and caspase‐5, ...
On September 21, 2017, Posted by Birgit Rogell , In Press Releases, With Kommentare deaktiviert für EMBL: Visualization of inflammasome formation in real life ...
Exaggerated inflammasome activation in venous thrombosis in CD39-deficient mice. Extracellular release of ATP and ADP through cell death, injury, or activation is a potent stress response, altering the local microenvironment to activate paracrine and autocrine signaling pathways (18, 19). Binding of extracellular ATP to the plasma membrane receptor ionophore P2X7 activates a potent stress-response-signaling pathway characterized by potassium efflux, which triggers assembly and activity of the inflammasome, a multiprotein oligomer that activates highly proinflammatory cytokines including IL-1β (20). Gupta et al. recently reported increased NLRP3 inflammasome assembly in patients at high altitude at risk for DVT (21). Canonical inflammasome activation requires a priming step marked by NF-κB activation and inflammasome component transcription (20). A second signal initiates NLRP3-mediated assembly and oligomerization of inflammasome component fibers, proteolytic cleavage of pro-caspase-1 to ...
DrLinOng. Chan SJ, Esposito E, Hayakawa K, Mandaville E, Smith RAA, Guo S, Niu W, Wong PT-H, Cool SM, Lo EH, Nurcombe V. Vascular Endothelial Growth Factor 165-Binding Heparan Sulfate Promotes Functional Recovery From Cerebral Ischemia. Stroke. 2020;51:2844-2853.. Angiogenesis and neurogenesis are crucial processes for brain recovery after stroke. While the brain has the capacity to form new cerebral blood vessels and to generate new neurons from neural stem cells after stroke, these self-repair mechanisms are limited. Therefore, strategies to promote brain restorative processes beyond the endogenous recovery are highly desirable. In this study, Chan and colleagues demonstrated that an exogenously applied heparan sulfate with increased affinity for vascular endothelial growth factor was able to enhance angiogenesis and neurogenesis within the peri-infarct regions, as well as to promote neurological recovery after experimental stroke.. The team first purified heparan sulfate variant 7, a ...
There is a clear need for interdisciplinary research and publications that bring together scientists who work on the inflammasome. This protein complex, termed the inflammasome and many of its components are implicated in disease disorders, autoimmune and infectious diseases. The structure, activation and regulation of the inflammasome complex have been and are still studied in increasing number of laboratories around the world. Our goal is to provide an issue summarizing every fascinating aspect of inflammasome activation and modulation of the innate immune response to microbial and to danger signals. This issue will bring the experts in inflammasome research up to speed with the most recent findings. However, several reviews are geared towards introducing the new scientists to the inflammasome complex and to the fundamental and essential information that will help them understand and even pursue their studies in this direction. By looking at the two sides of the coin, notably, some authors focused on
AIM2 is a cytosolic DNA sensor of the inflammasome, which induces critical innate immune responses against various invading pathogens. Earlier biochemical studies showed that the binding of AIM2 to DNA triggered the self-oligomerization of AIM2, which is essential for AIM2 inflammasome activation. We recently reported that VP22, a virion tegument protein of herpes simplex virus 1 (HSV-1), inhibited activation of the AIM2 inflammasome in HSV-1-infected cells by preventing AIM2 oligomerization. VP22 binds nonspecifically to DNA; however, its role in HSV-1 replication is unclear. We investigated the role of VP22 DNA binding activity in the VP22-mediated inhibition of AIM2 inflammasome activation. We identified a VP22 domain comprising amino acids 227 to 258 as the minimal domain required for its binding to DNA in vitro. Consecutive alanine substitutions in this domain substantially impaired the DNA binding activity of VP22 in vitro and attenuated the inhibitory effect of VP22 on AIM2 inflammasome ...
THE Fas/APO-1 receptor is one of the major regulators of apoptosis(1-7). We report here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-1 beta-converting enzyme (ICE)(8-10) which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Triggering of Fas/APO-1 rapidly stimulated the proteolytic activity of ICE. Overexpression of ICE, achieved by electroporation and microinjection, strongly potentiated Fas/APO-1-mediated cell death. In addition, inhibition of ICE activity by protease inhibitors, as well as by transient expression of the pox virus-derived serpin inhibitor CrmA or an antisense ICE construct, substantially suppressed Fas/APO-1-triggered cell death. We conclude that activation of ICE or an ICE-related protease is a critical event in Fas/APO-1-mediated cell death.. ...
Active Caspase-1, rat recombinant protein , Interleukin-1 beta convertase, Interleukin-1 beta-converting enzyme, IL-1BC, p45. validated in (PBV11136r-25), Abgent
Cellulose nanocrystal cationic derivative induces NLRP3 inflammasome-dependent IL-1β secretion associated with mitochondrial ROS production
Buy NLRP1 elisa kit, Mouse NLR Family, Pyrin Domain Containing 1 (NLRP1) ELISA Kit (MBS109213) product datasheet at MyBioSource, ELISA Kits
Inflammasomes are large protein complexes formed in response to cellular stresses that are platforms for recruitment and activation of caspase 1
Supervisor: Dr Xuan Li. Title: Identification and characterisation of NLRP3 interactome. Abstract: Aberrant activation of the NLRP3 inflammasome is involved in sterile inflammation in multiple chronic diseases such as atherosclerosis, type 2 diabetes or Alzheimers disease. Identification of novel players regulating the NLRP3 inflammasome could therefore lead to the development of new therapeutic strategies.. Here, we propose to further characterize the NLRP3 interactome during inflammasome activation. We will then select and investigate the identified interaction partners in the NLRP3 inflammasome pathway. These experiments will not only shed light into the NLRP3 regulatory mechanism during inflammasome activation, but also reveal new role players in the NLRP3 inflammasome pathway.. ...
Within the last decade numerous advances have already been manufactured in the part and regulation of inflammasomes during pathogenic and sterile insults. to a number of pathogenic and physiological stimuli. Inflammasome activation can be an essential element of the innate immune system response and is crucial for the clearance of pathogens or broken cells. Nevertheless overt inflammasome activation can be a major drivers of autoimmune and metabolic disorders root the need for understanding this technique in physiological and pathological contexts. The inflammasome detectors are grouped relating with their structural features into nucleotide-binding domain-like receptors (NLRs) absent in melanoma 2-like receptors (ALRs) as well as the lately identified pyrin. The power is got by These receptors to put together inflammasomes and activate the cysteine protease caspase-1. As well as the sensor (NLR ALR or pyrin) and enzymatic element (caspase-1) most inflammasomes also make use of an adaptor ...
TY - CHAP. T1 - Pyroptosis. AU - Lawlor, Kathryn. AU - Conos, Stephanie A.. AU - Vince, James E. PY - 2018/12/9. Y1 - 2018/12/9. N2 - Pyroptosis is considered an inflammatory cell death pathway that can be triggered by caspase‐1 or caspase‐11, or the human caspase‐11 orthologs, caspase‐4 and caspase‐5. The activation of caspase‐1 is mediated by supramolecular cytosolic protein complexes, termed inflammasomes, which sense specific pathogen, host or environmental danger molecules. Prior to causing pyroptotic death, caspase‐1 can also cleave and thereby activate the potent pro‐inflammatory cytokines, interleukin‐1 (IL‐1 ) and IL‐18. In contrast, the activation of caspase‐11 is caused by its direct binding to cytosolic lipopolysaccharide (LPS) derived from gram‐negative bacteria. While caspase‐11 can promote caspase‐1 activity, caspase‐1 is not required for caspase‐11 killing, and caspase‐11 itself does not efficiently activate IL‐1 or IL‐18. Unlike apoptotic ...
The nucleotide-binding site and leucine rich repeat containing family pyrin site containing 3 (NLRP3) inflammasome regulates capase-1-reliant maturation of interleukin-1β during infection with Gram-negative bacterial pathogens such as for example enterohemorrhagic mutant not capable of producing RNase H induced elevated degrees of NLRP3-reliant inflammasome activation. nucleotide-binding site and leucine wealthy repeat containing family members pyrin domain including 3 (NLRP3) inflammasome as an important mediator of EHEC-induced IL-1β. Whereas EHEC-specific virulence elements had been dispensable for NLRP3 activation bacterial nucleic acids such as for example RNA:DNA hybrids and RNA obtained cytosolic gain access to and mediated inflammasome-dependent reactions. Consistent with a primary part for RNA:DNA hybrids in inflammasome activation delivery of artificial EHEC RNA:DNA hybrids in to the cytosol activated NLRP3-reliant reactions and intro of RNase H Edoxaban tosylate which degrades such ...
Supplementary Material for: Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia
Recent study of the CAPS disease spectrum has led to significant advances in our understanding of the NLRP3 inflammasome and IL-1β-mediated inflammation. While translational studies have resulted in vital therapies for patients with CAPS, many questions about the inflammasome and other caspase-1-dependent pathways remain. Inflammasome-mediated IL-18 has largely been overlooked in the context of human disease. In addition, recent studies have demonstrated caspase-1 and inflammasome functions extending beyond cytokine maturation to cellular death pathways, but whether these processes have any bearing on CAPS remains to be seen. Here, we take advantage of mutant NLRP3 knockin mouse lines to investigate these questions.. Our studies demonstrate that dysregulated IL-18 secretion occurs from both patient and Nlrp3 mutant mouse cells in a manner similar to IL-1β. In vitro, a hallmark of CAPS is lack of reliance on the 2-signal paradigm generally required for secretion of active IL-1β. We used this ...
The NFκB pathway is complex and regulates many downstream effects depending on the type of stimulating ligand and cell context. [13] TLR9 can be activated by mycobaterial DNA. Further, intracellular viral ssRNA and dsRNA activate the inflammation that induces cleavage of the pro-form of IL-1β into its mature active form.95 In fact, mice lacking the TLR3, which recognizes dsRNA and activates cytokine synthesis, if infected with mouse-adapted influenzavirus have attenuated increases in NREM sleep, hypothermia, and body weight loss compared to the prototypical responses of normal mice infected with influenza.96 Further, intracellular dsRNA that is produced during viral replication is also recognized by cytoplasmic PAMPs.97 Thus, PAMPs play a crucial role in the recognition of pathogens that lead to the production of sleep regulatory cytokines and the acute phase response to infections. Potentially, mitochondria simply act as a physical scaffold that promotes inflammasome assembly. By continuing ...
Sigma-Aldrich offers abstracts and full-text articles by [Ying Yang, Dong-Mei Zhang, Jia-Hui Liu, Lin-Shui Hu, Qiao-Chu Xue, Xiao-Qin Ding, Ling-Dong Kong].
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Formation of the inflammasome results in the activation of multiple pathways responsible for co-ordinating our immune response, yet interestingly, there are multiple forms of inflammasomes made up and triggered by different sets of proteins. This initial step of activation has been covered very well before, here. The activated inflammsome goes on to trigger key downstream members of our innate immune system through the recruitment of an important regulatory protease (it cuts up other proteins) - caspase 1, which converts inactive molecules to active, pro-inflammatory ones, such as interleukin-1 beta and interleukin-18. This inflammatory cascade functions to initiate an effective local and systemic immune response through the control of the innate and adaptive immune system; for example, IL-beta is responsible for fever and the recruitment of immune cells to the site of infection, and IL-18 induces the development of key T cell responses ...
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NLRP7 - NLRP7 (untagged)-Human NLR family, pyrin domain containing 7 (NLRP7), transcript variant 1 available for purchase from OriGene - Your Gene Company.
Complete information for NLRP12 gene (Protein Coding), NLR Family Pyrin Domain Containing 12, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Protein expression of apoptosis-associated genes by Western blot. K562 cells were treated with different reagents for 24 h. Notes: data were normalized to β-a
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... and a caspase, in this case Caspase-1. In some cases, where the signaling proteins contain their own CARDs, like in NLRP1 and ... Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the ... Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both ... For Caspase-1, genes for specific COPs-ICEBERG, COP1 (ICE/Pseudo-ICE), and INCA (Inhibitory Card)-are all found near its locus ...
Like other caspases, Sf caspase-1 is an aspartate-specific cysteine protease that is produced as an inactive proenzyme and ... The Sf caspase-1 proenzyme is cleaved after the amino acid residues Asp-28 and Asp-195, resulting in a smaller 12 kDa fragment ... The protein Sf caspase-1 is the insect ortholog of the human effector caspases CASP3 (CPP32) and CASP7 (MCH3) in the species ... Some experiments also showed cleavage of Sf caspase-1 at the residue Asp-184, resulting in an 18 kDa instead of 19 kDa fragment ...
... is a protein that in humans is encoded by the CAAP1 gene. Caspase Apoptosis GRCh38: ... 236 (1): 107-13. doi:10.1006/abio.1996.0138. PMID 8619474. Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial ...
... has been shown to interact with Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000138794 - ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene ... "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase". Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct ...
... 2, Caspase 8, Caspase 9, Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases ... Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro-inflammatory ... Pyroptosis by Caspase-4 and Caspase-5 in humans and Caspase-11 in mice These caspases have the ability to induce direct ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ...
Murine caspase-11, and its human homologs caspase-4 and caspase-5, are mammalian intracellular receptor proteases activated by ... Caspase-11 activation by direct binding to LPS represents a novel and unprecedented mechanism for caspase activation. Caspase- ... an inactive precursor to active caspase-11) expression and caspase-11-mediated pyroptosis. Once expressed, caspase-11 is only ... Activation of caspase-11 by LPS is known to cause the activation of other caspase proteins, leading to septic shock, pyroptosis ...
... is a protein that in humans is encoded by the CARD8 gene. Caspase recruitment ... "Entrez Gene: CARD8 caspase recruitment domain family, member 8". Fontalba A, Martinez-Taboada V, Gutierrez O, et al. (2007). " ... 2002). "CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis". J. Biol. Chem. 277 (16): ... 2001). "CARDINAL, a novel caspase recruitment domain protein, is an inhibitor of multiple NF-kappa B activation pathways". J. ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs ... As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after ... Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ... During the caspase cascade, however, caspase-3 functions to inhibit XIAP activity by cleaving caspase-9 at a specific site, ...
CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ... Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ, Megeney LA (March 2010). "Caspase 3/caspase-activated DNase promote ... October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... "Entrez Gene: DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)". Davidson College. "Caspase ...
Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other ... Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating ... Different protein isoforms of caspase-9 are produced due to alternative splicing. Similar to other caspases, caspase-9 has ... Previously activated caspases can cleave caspase-9, causing its dimerization. Caspase-9 has a preferred cleavage sequence of ...
... is a feedback regulator of caspase-1-dependent interleukin-1beta secretion". J. Biol. Chem. 280 (23): 21720-5. doi:10.1074/jbc. ... caspase-1 and PYCARD. ENSG00000281166, ENSG00000182261 GRCh38: Ensembl release 89: ENSG00000276780, ENSG00000281166, ... June 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ... 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ...
... has a similar amino acid sequence to initiator caspases, including caspase 1, caspase 4, caspase 5, and caspase 9. It ... Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction. Caspase 2 has ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 2 proteolytically cleaves other proteins. It belongs to a family of cysteine proteases called caspases that cleave ...
Although this enzyme was originally reported as a human caspase that could be activated by caspase 8, later studies confirmed ... and is the likely orthologue of human caspase 4. Humke EW, Ni J, Dixit VM (1998). "ERICE, a novel FLICE-activatable caspase". J ... Caspase 13 or ERICE ("evolutionarily related interleukin-1β converting enzyme") is a protein that was identified in cattle. It ... Koenig U, Eckhart L, Tschachler E (2001). "Evidence that caspase-13 is not a human but a bovine gene". Biochem. Biophys. Res. ...
April 2002). "Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but ... Full maturation requires cleavage by Caspase-1. IL-37 is known to have immunosuppression properties through two different ... Exons 1, 2, 4, 5, and 6 are expressed and the isoform is 218 amino acids in length. IL-37c is found in the heart, and contains ... 13 (1): 1-7. doi:10.1006/cyto.2000.0799. PMID 11145836. Lin H, Ho AS, Haley-Vicente D, Zhang J, Bernal-Fussell J, Pace AM, et ...
"Caspase 1 deficiency reduces inflammation-induced brain transcription". Proceedings of the National Academy of Sciences of the ... 234 (1): 211-215. doi:10.1006/bbrc.1997.6436. PMID 9168991. Wong, M.-L.; Bongiorno, P. B.; Rettori, V.; McCann, S. M.; Licinio ... 86 (1): 27-31. doi:10.1016/j.pbb.2006.12.003. PMID 17258301. S2CID 41483918. Paz-Filho, G. J.; Babikian, T.; Asarnow, R.; ... 1 (2): 110-115. doi:10.1159/000097143. PMID 7489320. Wong, M.-L.; Rettori, V.; al-Shekhlee, A.; Bongiorno, P. B.; Canteros, G ...
2001). A conserved XIAP-interaction motif in caspase-9 and Smac/Diablo regulates caspase activity and apoptosis. Nature. 410: ... "A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis". Nature. 410 (6824): ... 2001). Isolation and Assay of Caspases. Ch. 1. Methods in Cell Biol. 66:1-27. Profile page at IISER Thiruvananthapuram Faculty ... 19 (1): R17-R19. doi:10.1016/j.cub.2008.11.041. ISSN 0960-9822. Liao, Wentao; Xiao, Qi; Tchikov, Vladimir; Fujita, Ken-ichi; ...
Apaf-1's Drosophila ortholog. The diagram (figure 4) shows functional homologues of apoptotic proteins (colour-coded ... In humans, initiator caspases such as Caspase-2 and Caspase-9 have a prodomain that cleaves caspases to a holoenzyme complex in ... Just as caspase 9 in mammals, caspase Dronc is a protein that has a caspase activation and recruitment domain (CARD). It is the ... Although most human caspases are considered orthologs of caspase Dronc, the one that resembles it the most is Caspase-2. ...
... caspase 1 and caspase 8). In comparison to their mammalian counterparts, viral serpins contain significant deletions of ... 183 (1): 49-59. doi:10.1016/j.ajpath.2013.03.009. PMID 23669344. Scarff KL, Ung KS, Nandurkar H, Crack PJ, Bird CH, Bird PI ( ... 77 (1): 47-57. doi:10.1046/j.1440-1711.1999.00787.x. PMID 10101686. S2CID 44268106. Bird CH, Sutton VR, Sun J, Hirst CE, Novak ... The disorder alpha-1 antitrypsin deficiency is one of the most common hereditary diseases. Since the stressed serpin fold is ...
Lee SH, Stehlik C, Reed JC (Sep 2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 ... 2006). "Dysregulation of receptor interacting protein-2 and caspase recruitment domain only protein mediates aberrant caspase-1 ... Fagol Caspase recruitment domain-containing protein 16 is an enzyme that in humans is encoded by the CARD16 gene. GRCh38: ... "Entrez Gene: COP1 caspase-1 dominant-negative inhibitor pseudo-ICE". Human CARD16 genome location and CARD16 gene details page ...
In 1992, her work on proteases led to the identification of the first caspase, caspase-1/Interleukin-1 converting enzyme (ICE ... In 1992, Thornberry identified the first caspase, Caspase-1/Interleukin-1 converting enzyme (ICE). In 1999, Thornberry ... "The caspase family of cysteine proteases". British Medical Bulletin. 53 (3): 478-490. doi:10.1093/oxfordjournals.bmb.a011625. ... "A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B". Journal of Biological ...
"Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". Journal of Immunology. 170 (7): 3631-6. doi: ... 70 (1): 120-135.e8. doi:10.1016/j.molcel.2018.03.009. PMC 5911935. PMID 29625033. Jia J, Bissa B, Brecht L, Allers L, Choi SW, ... 200 (1-2): 149-56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. Matsumoto R, Matsumoto H, Seki M, Hata M, Asano Y, ... 138 (1-2): 171-4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano ...
Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ... BCL2-like 1 (gene) has been shown to interact with: APAF1, BAK1, BCAP31, BCL2L11, BNIP3, BNIPL, BAD, BAX, BIK, Bcl-2, HRK, ... "Entrez Gene: BCL2L1 BCL2-like 1". Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and ... Weng C, Li Y, Xu D, Shi Y, Tang H (Mar 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related ...
Pan G, O'Rourke K, Dixit VM (1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841-5. ... The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which ... 505 (1): 23-6. doi:10.1016/S0014-5793(01)02768-5. PMID 11557035. Aouacheria A, Arnaud E, Venet S, et al. (2001). "Nrh, a human ... 359 (1): 76-82. doi:10.1016/j.bbrc.2007.05.090. PMID 17532299. Guillemin Y, Lalle P, Gillet G, et al. (2009). "Oocytes and ...
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Caspase activity that is triggered by the NLRP1 inflammasome activates caspase-6, which destroys the axons of neurons. Plants ... NOD-like receptors, in general, activate caspase-1 and assist in the maturation of the proinflammatory cytokines IL-1β and IL- ... However, not every NLRP forms an inflammasome and activates caspase-1; these NLRPs are referred to as non-canonical NLRPs. As ... including K+ efflux and caspase 1 activation. NLRPs are also known to be associated with a number of diseases. Research ...
Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results ... hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner". The Journal of Cell Biology. ... The protein was identified in the lab of Xiaodong Wang as an activator of caspase-3 in the presense of cytochromeC and dATP. ... Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ...
... caspase 4 and the murine caspase 4 homolog caspase 11, and has a role in the immune system. The Proteolysis Map Caspase ... and belongs to a family of cysteine proteases called caspases. It is an inflammatory caspase, along with caspase 1, ... Caspase 5 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue, ... Caspases, All stub articles, Human chromosome 11 gene stubs). ... Martinon F, Tschopp J (2007). "Inflammatory caspases and ...
"Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain ... Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to ... Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM (2000). "TMS1, a novel proapoptotic caspase recruitment ... Moriai R, Tsuji N, Kobayashi D, Yagihashi A, Namiki Y, Takahashi H, Watanabe N (2003). "A proapoptotic caspase recruitment ...
Lee SH, Stehlik C, Reed JC (2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation ... Inohara N, del Peso L, Koseki T, Chen S, Nunez G (Jun 1998). "RICK, a novel protein kinase containing a caspase recruitment ... The encoded protein contains a C-terminal caspase recruitment domain (CARD), and is a component of signaling complexes in both ... Chen YR, Clark AC (2003). "Equilibrium and kinetic folding of an alpha-helical Greek key protein domain: caspase recruitment ...
In human cells, the corresponding caspases of the non-canonical inflammasome are caspase 4 and caspase 5. Traditionally, ... whereas human non-canonical inflammasomes rely on caspase 4 and caspase 5. All of these caspases are able to directly bind ... While the murine caspase-11 is mainly expressed in macrophages, human caspase-4 is also expressed at high levels in intestinal ... The activated caspase-1 finally cleaves the immature pro-inflammatory cytokines pro-IL-1β and pro-IL-18, as well as Gasdermin-D ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 138 (1-2): 247-51. doi:10.1016/0378-1119(94)90817-6. PMID 7510261. Oberg-Welsh C, Welsh M (January 1995). "Cloning of BSK, a ... 91 (1): 53-60. doi:10.1172/JCI116200. PMC 329994. PMID 7678609. Aligayer H, Boyd DD, Heiss MM, Abdalla EK, Curley SA, Gallick ... doi:10.1016/0042-6822(77)90250-1. PMID 190771. Oppermann H, Levinson AD, Varmus HE, Levintow L, Bishop JM (April 1979). " ...
Wang M, Qanungo S, Crow MT, Watanabe M, Nieminen AL (2005). "Apoptosis repressor with caspase recruitment domain (ARC) is ... NOL3 has been shown to interact with SFRS9 and Caspase 8. GRCh38: Ensembl release 89: ENSG00000140939 - Ensembl, May 2017 ... Ekhterae D, Platoshyn O, Zhang S, Remillard CV, Yuan JX (2003). "Apoptosis repressor with caspase domain inhibits cardiomyocyte ... "Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic ...
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In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin- ... Mahalingam S, Ayyavoo V, Patel M, Kieber-Emmons T, Kao GD, Muschel RJ, Weiner DB (Mar 1998). "HIV-1 Vpr interacts with a human ... Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ... 1502 (1): 133-8. doi:10.1016/s0925-4439(00)00039-9. PMID 10899438. Chung, KK; Dawson, VL; Dawson, TM (November 2001). "The role ...
... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... 446 (1): 387-392. doi:10.1016/j.bbrc.2014.02.124. PMID 24613385. Seo JH, Park JH, Lee EJ, Vo TT, Choi H, Kim JY, et al. ( ... 4 (1): 23-30. doi:10.1530/ror.0.0040023. PMID 10051099. S2CID 13035273. Liu J, Xia J, Cho KH, Clapham DE, Ren D (June 2007). " ... 46 (1): 207-215. doi:10.1016/j.ejca.2009.10.020. PMID 19914824. Rohde M, Daugaard M, Jensen MH, Helin K, Nylandsted J, Jäättelä ...
... called Inhibitor of caspase-activated DNase (ICAD). In order for apoptosis to begin, an enzyme called caspase 3 cleaves ICAD so ... "Caspase-activated DNase Is Required for Maintenance of Tolerance to Lupus Nuclear Autoantigens." Arthritis and Rheumatism 64.4 ... Apoptotic DNA fragmentation relies on an enzyme called Caspase-Activated DNase (CAD). CAD is usually inhibited by another ... "Identification of ICAD-derived Peptides Capable of Inhibiting Caspase-activated DNase." FEBS Journal 279.16 (2012): 2917-928. ...
"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 ...
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis ... Wang, J; Chun H J; Wong W; Spencer D M; Lenardo M J (November 2001). "Caspase-10 is an initiator caspase in death receptor ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ...
1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/238040151162165141. PMID 10069390. S2CID 31218178. Scanlan MJ, ... the sensitivity of PS1 to caspases" (PDF). FEBS Lett. ...
If cells receive multiple apoptotic stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the serine at position ... 13 (1): 102-12. doi:10.1089/cmb.2006.13.102. PMID 16472024. Rønningen T, Shah A, Oldenburg AR, Vekterud K, Delbarre E, Moskaug ... ISBN 978-1-4292-3413-9. Molden RC, Bhanu NV, LeRoy G, Arnaudo AM, Garcia BA (2015). "Multi-faceted quantitative proteomics ... 575 (2 Pt 1): 276-84. doi:10.1016/j.gene.2015.09.005. PMID 26343795. "Histone H2B (53H3) Mouse mAb #2934". Cell Signaling ...
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Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of ... J. 417 (1): 149-60. doi:10.1042/BJ20081885. PMID 18939944. Kitson J, Raven T, Jiang YP, Goeddel DV, Giles KM, Pun KT, Grinham ... Wang Y, Wu TR, Cai S, Welte T, Chin YE (July 2000). "Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD ... Wang Y, Wu TR, Cai S, Welte T, Chin YE (2000). "Stat1 as a Component of Tumor Necrosis Factor Alpha Receptor 1-TRADD Signaling ...
... 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, et ... 6 (1): 9-20. doi:10.1038/nri1747. PMID 16493424. S2CID 33505741. Burberry A, Zeng MY, Ding L, Wicks I, Inohara N, Morrison SJ, ...
In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase ... 34 (1): 18-23. doi:10.1016/j.leukres.2009.07.023. PMID 20109966. Jensen SA, Calvert AE, Volpert G, Kouri FM, Hurley LA, Luciano ... 534 (1-3): 61-8. doi:10.1016/S0014-5793(02)03778-X. PMID 12527362. S2CID 7018829. Human BCL2L13 genome location and BCL2L13 ... Two possible explanations propose that either 1) Bcl-rambo performs a different biological role in childhood, or 2) alternative ...
In one such pathway, caspase-independent apoptosis, the E3 ligase C-terminal of Hsc-70 interacting protein (CHIP), a regulator ... Lemarié A, Lagadic-Gossmann D, Morzadec C, Allain N, Fardel O, Vernhet L (Jun 2004). "Cadmium induces caspase-independent ... This protein primarily participates in caspase-independent apoptosis via DNA degradation when translocating from the ... Differential involvement of caspase-3 and endonuclease G". Journal of Neurovirology. 10 (3): 141-51. doi:10.1080/ ...
Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... 10 (1): 55-67. doi:10.1016/S1097-2765(02)00583-X. PMID 12150907. Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, ... 228 (1): 84-91. doi:10.1006/excr.1996.0302. PMID 8892974. Hansen S, Midgley CA, Lane DP, Freeman BC, Morimoto RI, Hupp TR (Nov ... 213 (1): 1-6. doi:10.1006/bbrc.1995.2090. PMID 7639722. Inoue A, Torigoe T, Sogahata K, Kamiguchi K, Takahashi S, Sawada Y, ...
It has also been suggested that S1P kinase 2 (SphK2) is a target of caspase 1, and that a cleaved fragment of SphK2 is what is ... In other forms of apoptosis, caspase-1 is not normally induced, meaning the formation of S1P needs to be further studied. S1P ... S1P generation involved caspase-1-dependent release of sphingosine kinase 2 (SphK2) fragments. CX3CL1 release is mediated ... Release is dependent upon caspase activity. Less than 2% of ATP released from the beginning stages of cell death is released ...
2006). "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway". Oncogene. 25 (30): 4172-82. doi:10.1038/ ... and it plays a role in the increase of cell survival in a caspase 3 dependent pathway. GRCh38: Ensembl release 89: ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Veríssimo F, Jordan P (2001). "WNK kinases, a novel protein kinase subfamily ... 2010). "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no ...
Such substrates have been used to detect caspase activity and cytochrome P450 activity, among others. Luciferase can also be ... 352 (1): 61-67. doi:10.1016/j.ab.2006.02.019. PMID 16564487. Fujii H, Noda K, Asami Y, Kuroda A, Sakata M, Tokida A (Jul 2007 ... 17 (1): 43-74. doi:10.1002/bio.676. PMID 11816060. Lyons SK, Meuwissen R, Krimpenfort P, Berns A (Nov 2003). "The generation of ... 1 (3): 194-205. doi:10.17516/1997-1389-0264. Gould SJ, Subramani S (November 1988). "Firefly luciferase as a tool in molecular ...
Her demonstration that caspases are involved directly in ischaemic brain damage in vivo stimulated the development of caspase ... She assumed her post on 1 July 2010, succeeding Gilbert, who had retired after nearly six years. She became the first woman to ... She patented the use of IL-1 inhibitors to prevent acute neurodegeneration and is leading the first clinical trial of such an ... Her studies have begun to elucidate the mechanisms regulating IL-1 release and its action and her group have conducted the ...
... mitochondrial dysfunction and caspase-3-dependent signaling pathways". International Journal of Oncology. 39 (1): 217-224. doi: ...
... encoding protein Caspase 16, pseudogene CCDC113: encoding protein Coiled-coil domain-containing protein 113 Ccdc78: encoding ... ISBN 978-1-136-84407-2. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly GRCh38.p3). Last ... ISBN 978-1-4673-1921-8. S2CID 16666470. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly ... 20 (1): 140-147. doi:10.1038/mp.2014.145. PMC 4320286. PMID 25421402. Richter, M (21 February 2018). "Altered TAOK2 activity ...
The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase ... 2002). "Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1". ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... J. 381 (Pt 1): 213-9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016. Ota T, Suzuki Y, Nishikawa T, et al. (2004). " ...
... the apoptotic effector caspase, caspase 3, cleaves ICAD and thus causes CAD to become activated. CAD cleaves the DNA at the ... The enzyme responsible for apoptotic DNA fragmentation is the Caspase-activated DNase. CAD is normally inhibited by another ... "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD". Nature. 391 (6662): 43-50. Bibcode: ... 207 (1): 202-205. doi:10.1006/excr.1993.1182. PMID 8391465.{{cite journal}}: CS1 maint: multiple names: authors list (link) ...
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): ...
2005). "Caspase-dependent and independent activation of acid sphingomyelinase signaling". J. Biol. Chem. 280 (28): 26425-26434 ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ... The SN-1 position can contain either an ester bond or an ether bond, with ether LPA being found at elevated levels in certain ... Ceramide-1-phosphate (C1P) is formed by the action of ceramide kinase (CK) enzymes on Cer. C1P carry ionic charge at neutral pH ...
"Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with ... 88: 1-6. doi:10.1016/j.fitote.2013.03.028. ISSN 0367-326X. PMID 23570840. (CS1 Dutch-language sources (nl), CS1 Latin-language ... The smooth, elliptical, yellow to red fruit are 8-15 by 7.5-10 millimeters and have 1-2 seeds. The base of the fruit are wedge- ... Its carpels have ovaries that are 1-3 by 0.3-0.8 millimeter and densely covered in gold to red-brown hairs arranged in rows, ...
The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and ... 112 (1): 138-47. doi:10.1046/j.1365-2141.2001.02491.x. PMID 11167794. S2CID 44981142. Strausberg RL, Feingold EA, Grouse LH, et ...
Caspase-1 causes pyroptosis, a necrotic-like cell death. AIM2 is an inflammasome sensor for cytosolic DNA. The adaptor molecule ... ASC mediates AIM2-dependent caspase-1 activation. To date, no function besides caspase-1 activati … ... The inflammasome is a signalling platform leading to caspase-1 activation. ... AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages Cell Death Differ. 2012 ...
Highly specific and rigorously validated in-house, Cleaved Caspase-1 (Asp296) (E2G2I) Rabbit Monoclonal Antibody (CST #89332) ... which also includes caspases -4, -5, -11, and -12. Caspase-1 cleaves inflammatory cytokines such as pro-IL-1ß and interferon-γ ... Like other caspases, caspase-1 is proteolytically activated from a proenzyme to produce a tetramer of its two active subunits, ... Cleaved Caspase-1 (Asp296) (E2G2I) Rabbit mAb 89332. Toggle Between Dark and Light Modes Filter: *WB ...
Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway Joo-Sung Yang*1, Mathura P. ... Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway. ... Figure 1. Figure 1. West Nile virus capsid (WNV-cp)-DJY protein expression induces apoptosis. Nuclear condensation was observed ... Ramanathan*1, Karuppiah Muthumani*, Andrew Y. Choo*, Sung-Ha Jin*, Qian-Chun Yu*, Daniel S. Hwang*, Daniel K. Choo*, Mark D. ...
... caspase-3, NLRP3, caspase-1, GSDMD and IL-1β) were observed in IMR-32 and SK-N-SH cells again (Fig. 5G-L). All results suggest ... caspase-3, caspase-1, NLRP3, GSDMD and IL-1β, and reduced the Bcl-2 protein expressions in IMR-32 and SK-N-SH cells. Moreover, ... caspase-3, NLRP3, caspase-1, GSDMD and IL-1β, but also increase the secretion of IL-1β, IL-18, caspase-1 and LDH in ... Caspase-3 is the executor caspase of apoptosis. MMP is a vital marker of intrinsic apoptosis (Park et al., 2020). Our results ...
A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing. ... Caspase 8, the initiator caspase for death receptor-induced apoptosis, functions as a negative regulator of receptor ... Caspase 8-mediated pro-IL-1β processing requires intact RIPK1, RIPK3, TRIF, and FADD. In response to LPS, a complex that ... A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing. Journal Article (Journal Article) ...
Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1. ... Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1. ... Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1. Respir Res. 2022 Feb ...
In the new work, the authors showed that caspase-1 inhibition reduced secretion of IL-1α and almost 80 other inflammatory ... Many of the transported proteins were not caspase-1 substrates, yet catalytic activity of the enzyme was required for their ... suggesting caspase-1 is helping to regulate the entire inflammatory response. ... IL-1α is also not a substrate for caspase-1, but its secretion is reduced in macrophages that do not express the protease. ...
Inactivation of caspase-1 in rodent brain: A novel anticonvulsive strategy. Teresa Ravizza, Sian Marie Lucas, Silvia Balosso, ... Inactivation of caspase-1 in rodent brain : A novel anticonvulsive strategy. / Ravizza, Teresa; Lucas, Sian Marie; Balosso, ... Inactivation of caspase-1 in rodent brain : A novel anticonvulsive strategy. In: Epilepsia. 2006 ; Vol. 47, No. 7. pp. 1160- ... Methods: Caspase-1 was selectively blocked by using pralnacasan or VX-765. IL-1β release was induced in mouse organotypic ...
Riboflavin, vitamin B2, attenuates NLRP3, NLRC4, AIM2, and non-canonical inflammasomes by the inhibition of caspase-1 activity ... Figure 1. Extract of roasted coffee beans suppresses LPS-induced NO production and expression of iNOS. RAW264.7 cells were ... B-F) RAW264.7 cells were pretreated with coffee extract (5% (v/v)) for 1 h prior to the LPS stimulation (1 μg/mL) for the ... 1). Thus, we examined the effects of coffee extract on the LPS-induced transcriptional activation of NF-κB using a luciferase ...
Caspase-2+Caspase-9+Caspase-8+Caspase-7+Caspase-1+Caspase-4+Caspase-6/CASP-6+Caspase-5+Caspase-10+Ca (1). ... Caspase-2+Caspase-9+Caspase-8+Caspase-7+Caspase-1+Caspase-6+Caspase-10+Caspase 3 (1). ... Caspase-3, Caspase-8 and Caspase-9 Multiplex Activity Assay Kit (Fluorometric) (ab219915) Specific References (16) ... Caspase-3, Caspase-8 and Caspase-9 Multiplex Activity Assay Kit (Fluorometric) ...
... live cell caspases activity assay kits are based on fluorescent FMK inhibitors of caspases Cat No. 20108 ... Once inside the cell, the caspase inhibitors bind covalently to the active caspases. This Cell Meter™ Live Cell Caspase 1 ... Cell Meter™ Caspase 8 Activity Apoptosis Assay Kit *Red Fluorescence*. Cell Meter™ Caspase 9 Activity Apoptosis Assay Kit *Red ... Cell Meter™ Caspase 3/7 Activity Apoptosis Assay Kit *Blue Fluorescence*. Cell Meter™ Caspase 3/7 Activity Apoptosis Assay Kit ...
By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1-dependent ... Besides caspase-2, the caspase-1-independent pathway involves the activation of caspase-3, -6, and -8 and the release of ... Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. ... We show that caspase-1-deficient macrophages undergo apoptosis within 4-6 h of infection with invasive bacteria. This process ...
CASP1; IL1BC; IL1BCE; Caspase-1; CASP-1; Interleukin-1 beta convertase; IL-1BC; Interleukin-1 beta-converting enzyme; ICE; IL-1 ... Cleaved-Caspase-1 (M211) Polyclonal Antibody detects endogenous levels of fragment of activated Caspase-1 protein resulting ... ELISA: 1/20000. Not yet tested in other applications.. Purification. The antibody was affinity-purified from rabbit antiserum ... Immunohistochemistry analysis of paraffin-embedded human lung carcinoma, using IL-1 beta (Cleaved-Asp210) Antibody. The picture ...
با توجه به نقش ژن-های Caspase-1 و Interleukin-1β درتنظیم اینفلامازوم و ایجاد التهاب، بررسی میزان بیان این دو ژن در بیماران ... پس از سنتز cDNA آنالیز کمّی بیان ژن با روش Real Time PCR برای ژن های IL-1β و Casp-1 صورت پذیرفت. نتایج نشان دادبیان ژن-های IL-1 ... با توجه به نتایج و نقش ژن-های IL-1βو Casp-1 در مسیر فعال-سازی کمپلکس اینفالامازوم از یک طرف و افزایش بیان معنی دار این ژن ها در ... و 1/56(0/052 =p) برابر نمونه های کنترل می-باشد که این تفاوت در مورد ژن Casp-1 معنی دار می-باشد. ...
keywords = "Apoptosis, Caspase-3, Mcl-1, Neutrophil, Trichomonas vaginalis",. author = "Kang, {J. H.} and Song, {H. O.} and Ryu ... The activation of caspase-3 was evident in neutrophils undergoing spontaneous apoptosis but was markedly enhanced during T. ... The activation of caspase-3 was evident in neutrophils undergoing spontaneous apoptosis but was markedly enhanced during T. ... The activation of caspase-3 was evident in neutrophils undergoing spontaneous apoptosis but was markedly enhanced during T. ...
Caspase-1 inflammasome activation *Ear and dLN caspase-1 activation was assayed via Promega Caspase-Glo 1 Inflammasome kit ... Mouse IL-1β Quantikine ELISA Kit (R&D Systems). *Capillary western immunoassay performed according to the ProteinSimple Wes ... Mitochondrial membrane potential was measured via MitoProbe JC-1 Assay Kit (ThermoFisher Scientific) according to ...
... anti-Caspase-1 (p20) (mouse), mAb (Casper-1) , Packing: 100 ug , AdipoGen Life Sciences products available at Bio-Connect ... anti-Caspase-1 (p20) (mouse), mAb (Casper-1). Catalog number:. AG-20B-0042-C100. ... FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes: P. Gurung, et al.; J. ... Caspase-1 is the best-described inflammatory caspase. It processes the cytokines interleukin-1beta (IL-1beta) and IL-18 and ...
Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1. Nature, 490 (7419). pp. 288-291. ... These results indicate that caspase-11-dependent cell death is detrimental to the host in the absence of caspase-1-mediated ... Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1 ... Recently, a new non-canonical inflammasome was described that activates caspase-11, a pro-inflammatory caspase required for ...
Importantly, in either caspase-3 KO neurons or wild-type neurons treated with caspase-3 inhibitor (z-DEVD-FMK) or caspase-9 ... X-linked inhibitor of apoptosis (XIAP) is an E3 ligase that inhibits caspase-3 and caspase-9 directly and targets caspase-3 for ... Caspase-3 KO mice manifest abnormalities in spine density and mEPSCs. A-G, Spine density was measured in caspase-3 KO mice and ... 3G-L, S) or of Mito-KillerRed in caspase-3 KO neurons (Fig. 3M-R,S), indicating the selectivity of the CellEvent caspase-3 ...
This reagent is designed to detect caspase 3/7 activity in live cells. The ability to ... https://www.perkinelmer.com/Product/vs-caspase3-7-for-2d-3d-culture-cs1-v0002-1 ... ViaStain™ Live Caspase 3/7 Detection for 2D/3D Culture - CS1-V0002-1. $ 384.00 Save $ -384 SKU: CS1-V0002-1 ... Home Consumables Reagents ViaStain™ Live Caspase 3/7 Detection for 2D/3D Culture - CS1-V0002-1 ...
View Simple Plex Control for Mouse CXCL12/SDF-1 alpha (898561) datasheet. ... CXCL12/SDF-1 alpha is 89 amino acids (aa) in length with a predicted molecular weight of 10 kDa, CXCL12/SDF-1 beta is 93 aa in ... Reviews for Simple Plex Control for Mouse CXCL12/SDF-1 alpha. There are currently no reviews for this product. Be the first to ... Have you used Simple Plex Control for Mouse CXCL12/SDF-1 alpha?. Submit a review and receive an Amazon gift card.. $25/€18/£15 ...
Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway Joo-Sung Yang*1, Mathura P. ... Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway. ... Figure 1. Figure 1. West Nile virus capsid (WNV-cp)-DJY protein expression induces apoptosis. Nuclear condensation was observed ... Ramanathan*1, Karuppiah Muthumani*, Andrew Y. Choo*, Sung-Ha Jin*, Qian-Chun Yu*, Daniel S. Hwang*, Daniel K. Choo*, Mark D. ...
... caspase recruitment domain family member 9) activation CRISPR was administered with LP17 and TREM-1 activating anti-mouse TREM- ... Caspase Recruitment Domain Family Member 9) Signaling Pathway After Intracerebral Hemorrhage in Mice. ... The aim of this study was to evaluate the role of TREM-1 in neuroinflammatory response after ICH in mice. Methods:. CD1 mice (n ... Receptor Gatilho 1 Expresso em Células Mieloides Limite: Animais Idioma: Inglês Revista: Stroke Ano de publicação: 2021 Tipo de ...
Interleukin-1β (IL-1β) is implicated in gastric cancer development and certain gene polymorphisms play a role in this ... Mature IL-1β production depends on inflammasome activation, and the NLRP3 inflammasome is a major driver in H. pylori- ... In addition to the formation of mature IL-1β or IL-18, inflammasome activation induces pyroptotic death in cells. We ... but secreted only very low amounts of mature IL-1β. However, application of exogenous control activators such as Nigericin ...
The discovery that, in sperm, caspase activation is restricted to the surface of organelles called mitochondria sheds light on ... Caspase enzymes promote cell death, but are also involved in sperm development in fruit flies. ... Writing in Developmental Cell, Aram et al.2 report that the restriction of caspase activity to the surfaces of organelles ... Caspase enzymes promote cell death, but are also involved in sperm development in fruit flies. The discovery that, in sperm, ...
INS-1 cells undergoing caspase-dependent apoptosis enhance the regenerative capacity of neighboring cells. ... Dive into the research topics of INS-1 cells undergoing caspase-dependent apoptosis enhance the regenerative capacity of ...
... cleaved-caspase-1 and cleaved-gasdermin D (0.36-fold decrease), and increased level of anti-inflammatory factors IL-10. MiR-34a ... activity of caspase-1 (0.51-fold decrease) and expression of nucleotide-binding domain and leucine-rich repeat protein-3 (0.48- ... heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. Moreover, miR-34a down... ... heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. Moreover, miR-34a down- ...
Angiotensin I Converting Enzyme 2, ACE-2/Caspase-1 Substrate. Home/Catalog peptide/Angiotensin I Converting Enzyme 2, ACE-2/ ... Angiotensin I Converting Enzyme 2, ACE-2/Caspase-1 SubstrateAdmin2021-01-04T11:12:17+00:00 ...
Caspase 3 Monoclonal Antibody (CPP32 4-1-18). Advanced Verification 14 References ... git-branch: origin/release/1.57.1-2023.01.04-1.1 ...
1 mg/ml. Formulation : Phosphate buffered saline (PBS) solution with 15 mM sodium azide ...
  • Many of the transported proteins were not caspase-1 substrates, yet catalytic activity of the enzyme was required for their secretion, for reasons that are not yet clear. (rupress.org)
  • Both IL-1α and FGF-2 bound to caspase-1, suggesting that the enzyme may carry them directly. (rupress.org)
  • In this study, we investigated whether seizures can be effectively inhibited by blocking the brain production of IL-1β, by using selective inhibitors of interleukin- converting enzyme (ICE/caspase-1) or through caspase-1 gene deletion. (elsevier.com)
  • IL-1β release was induced in mouse organotypic hippocampal slice cultures by proinflammatory stimuli [lipopolysaccaride (LPS) + adenosine triphosphate (ATP)] and measured with enzyme-linked immunosorbent assay (ELISA). (elsevier.com)
  • The enzyme poly (ADP-ribose) polymerase, or PARP, was one of the first proteins identified as a substrate for caspases. (reading.ac.uk)
  • The fragmentation of DNA into nucleosomal units - as seen in DNA laddering assays - is caused by an enzyme known as CAD, or caspase activated DNase. (reading.ac.uk)
  • This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. (immunochemistry.com)
  • The remaining green fluorescent signal is a direct measure of the active caspase-8 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)
  • Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE. (bvsalud.org)
  • Caspase 8, the initiator caspase for death receptor-induced apoptosis, functions as a negative regulator of receptor interacting protein kinase 3 (RIPK3), an essential factor for TNF-, TLR3-, and TLR4-induced necroptosis. (duke.edu)
  • This process requires SipB, implying that this protein can initiate the apoptotic machinery by regulating components distinct from caspase-1. (harvard.edu)
  • Cleaved-Caspase-1 (M211) Polyclonal Antibody detects endogenous levels of fragment of activated Caspase-1 protein resulting from cleavage adjacent to M211. (intolala.com)
  • Trichomonad-induced apoptosis was also associated with reduced expression of the neutrophil anti-apoptotic protein, Mcl-1. (uthscsa.edu)
  • TREM (Triggering Receptor Expressed on Myeloid Cells)-1 Inhibition Attenuates Neuroinflammation via PKC (Protein Kinase C) δ/CARD9 (Caspase Recruitment Domain Family Member 9) Signaling Pathway After Intracerebral Hemorrhage in Mice. (bvsalud.org)
  • To elucidate TREM-1 signaling pathway, CARD9 ( caspase recruitment domain family member 9) activation CRISPR was administered with LP17 and TREM-1 activating anti- mouse TREM-1 monoclonal antibody (mAb) was administered with Rottlerin, a specific PKC ( protein kinase C ) δ inhibitor. (bvsalud.org)
  • The mouse CXCL12/SDF-1 orthologs share 99% aa sequence identity with the human protein. (rndsystems.com)
  • and protein carbonyl, IL-1B, and caspase-1 determination. (cdc.gov)
  • This effect is mediated through the formation of an apoptosome, a multi-protein complex consisting of cytochrome C, Apaf-1, pro-caspase 9 and ATP. (reading.ac.uk)
  • 1 Nevertheless, strategies that target protein misfolding frequently reduce aggregate formation and cell death in parallel. (bmj.com)
  • Huntingtin-interacting protein 1 (HIP1) is a cofactor in clathrin-mediated vesicle trafficking. (jci.org)
  • SWCNT induced a significant activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-kB), and the effect was inhibited by mitogen-activated protein kinase (MAPK) inhibitors. (cdc.gov)
  • Fas ligand binds to the receptor and forms the death-inducing signalling complex, including the Fas-associated death domain, death-domain associated protein, and caspase-10. (smpdb.ca)
  • We further validate 2 downstream candidates (oxidative stress-induced growth inhibitor 1) and (X-ray repair cross-complementing protein 5) and evaluate their functional relationship with PEL cell survival/proliferation and chemoresistance respectively. (biotech2012.org)
  • Particularly, AZD8055 fully inhibited multisite eIF4E-binding protein 1 phosphorylation, subsequently blocking protein translation, which was in contrast to the effects of rapamycin. (crick.ac.uk)
  • Surprisingly, RIPK3-specific kinase inhibitors strongly enhanced caspase 8 activation and pro-IL-1β processing in LPS-stimulated BMDCs. (duke.edu)
  • Our Cell Meter™ live cell caspases activity assay kits are based on fluorescent FMK inhibitors of caspases. (aatbio.com)
  • Once inside the cell, the caspase inhibitors bind covalently to the active caspases. (aatbio.com)
  • It is used for the quantification of activated caspase 1 activities in apoptotic cells, or for screening caspase 1 inhibitors. (aatbio.com)
  • These research bring novel understanding on the experience of PAI-1 inhibitors and offer important information PF-2341066 for future years style of inhibitors concentrating on PAI-1 as healing agents in cancers. (exposed-skin-care.net)
  • The results showed that BPA nonlinearly upregulated the levels of IL-18, ASC, GSDMD and NLRP3 mRNAs and that of NLRP3, caspase-1, GSDMD and IL-1β proteins in IMR-32 and SK-N-SH cells. (researchsquare.com)
  • Meanwhile, Z-YVAD-FMK and ICI182.780 abruptly reduced the levels of Bak1, Bax, Bcl-2 and caspase-3 proteins induced by BPA. (researchsquare.com)
  • In the new work, the authors showed that caspase-1 inhibition reduced secretion of IL-1α and almost 80 other inflammatory response proteins, many of which lack secretion signal peptides, including FGF-2. (rupress.org)
  • The proteins involved trigger detoxification, tissue repair, and cell survival, suggesting caspase-1 is helping to regulate the entire inflammatory response. (rupress.org)
  • However, pharmacological inhibition of inhibitor of apoptosis proteins or proteasome function led to neuronal death, suggesting that caspase activation is spatially restricted by these "molecular brakes" on apoptosis. (jneurosci.org)
  • We present evidence that the restriction of caspase-3 activation to the region of photostimulation-and hence protection against cell death-is mediated by the action of proteasomes and the inhibitor of apoptosis proteins (IAPs). (jneurosci.org)
  • Protease enzymes called caspases are renowned killers, cleaving proteins to execute a program of apoptotic cell death. (nature.com)
  • NF-κB consists of multiple members of the Rel family of proteins that include NF-κB1 (p105/p50), NF-κB2 (pl00/p52), RelA (p65), RelB, and c-Rel ( 1 , 2 ). (aai.org)
  • Rel proteins form hetero- and homodimeric complexes that differ in their transactivating activity ( 1 ). (aai.org)
  • The caspases are a family of proteins that are one of the main executors of the apoptotic process. (reading.ac.uk)
  • These caspases are responsible for the cleavage of the key cellular proteins, such as cytoskeletal proteins, that leads to the typical morphological changes observed in cells undergoing apoptosis. (reading.ac.uk)
  • The caspases play an important role in this process by activating DNases, inhibiting DNA repair enzymes and breaking down structural proteins in the nucleus. (reading.ac.uk)
  • Once activated, caspases -3 and -7 cleave downstream proteins. (smpdb.ca)
  • AT-101 is an oral inhibitor of the antiapoptotic Bcl proteins (Bcl-2, Bcl-XL, Bcl-W, and Mcl-1) and an inducer of the pro-apoptotic proteins noxa and puma. (jto.org)
  • 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. (nih.gov)
  • 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. (nih.gov)
  • As mediated by the estrogen receptor, BPA may induce the pyroptosis of neuroblastoma cells through NLRP3/caspase-1/GSDMD signaling pathway, and caspase-1-dependent pyroptosis may be involved in BPA-induced apoptosis, which is alleviated by EGCG, an anti-oxidation agent. (researchsquare.com)
  • Besides caspase-2, the caspase-1-independent pathway involves the activation of caspase-3, -6, and -8 and the release of cytochrome c from mitochondria, none of a which occurs during caspase-1-dependent apoptosis. (harvard.edu)
  • This study demonstrated that TREM-1 enhanced neuroinflammation by modulating microglia polarization after ICH, and this regulation was partly mediated via PKC δ/CARD9 signaling pathway and increased HMGB1 activation of TREM-1. (bvsalud.org)
  • Long-term depression, a proposed physiological correlate of synapse elimination, requires caspase-3 and the mitochondrial pathway of apoptosis. (jneurosci.org)
  • Local activation of the mitochondrial apoptosis pathway in dendrites is sufficient to cause elimination of spines and dendrite branches that are localized in the vicinity of Mito-KillerRed photostimulation in a manner dependent on caspase-3 activation. (jneurosci.org)
  • Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. (cdc.gov)
  • and (c) the kynuric pathway that produces N 1 -acetyl-N 2 -formyl-5-kynuramine (AFMK) [ 29 - 31 ]. (hindawi.com)
  • To investigate the effects of Banxia Houpo decoction on the renal NLRP3/Caspase-1/IL-1β signaling pathway in chronic intermittent hypoxia mice. (magtech.com.cn)
  • A selective TREM-1 inhibitor, LP17, was administered intranasally 2 hours after ICH. (bvsalud.org)
  • Lastly, to evaluate the role of HMGB1 (high-mobility group box 1) in TREM-1 mediated microglia activation, glycyrrhizin , an inhibitor of HMBG1 was administered with TREM-1 activating mAb. (bvsalud.org)
  • DNA fragmentation was efficiently blocked by the caspase inhibitor Z-VAD-fmk and partially blocked by Ac-DEVD-fmk, suggesting that SN50-mediated apoptosis is caspase-dependent. (aai.org)
  • Our results indicated that all the 5 genes (and (Oxidative stress-induced growth inhibitor 1) one of the highly upregulated genes in SASP-treated KSHV+ PEL cells from microarray data to determine its role in SASP-induced cell apoptosis. (biotech2012.org)
  • Launch Plasminogen activator inhibitor-1 (PAI-1) is certainly a serine protease inhibitor that has an important function in lots of physiological and pathological circumstances, including wound curing, obesity, metabolic symptoms, coronary disease and cancers [1]. (exposed-skin-care.net)
  • Induction of apoptosis via death receptors typically results in the activation of an initiator caspase such as caspase 8 or caspase 10. (reading.ac.uk)
  • Caspase-8 is an initiator caspase that is activated in response to pro-apoptotic stimulus and causes a cascade of further caspase activity by cleaving and activating effector caspases, like caspases -3 and -7. (smpdb.ca)
  • Caspases are are proteases that cleave their substrates. (smpdb.ca)
  • Caspases are cysteine proteases involved in the signalling cascades of programmed cell death in which caspase-3 plays a central role, since it propagates death signals from intrinsic and extrinsic stimuli to downstream targets. (proteopedia.org)
  • This study also highlighted that previously generated caspase-1 knockout mice lack a functional allele of Casp11 (also known as Casp4), making them functionally Casp1 Casp11 double knockouts. (unibas.ch)
  • Francisella tularensis, the agent of tularaemia, triggers AIM2/ASC-dependent caspase-3-mediated apoptosis in caspase-1-deficient macrophages. (nih.gov)
  • Immunoprecipitation of Cleaved Caspase-1 (Asp296) from extracts of acetone precipitated media from mouse bone marrow derived macrophages treated with Lipopolysaccharides (LPS) #14011 (50ng/ml, 4hr) followed by Nigericin (15 μM, 45 min). (cellsignal.com)
  • Western blot analysis of cell extracts from the cells or media from mouse bone marrow derived macrophages (mBMDM), untreated (-) or treated with Lipopolysaccharides (LPS) #14011 (50 ng/ml, 4 hr) followed by Nigericin (15 μM, 45 min) (+), using Cleaved Caspase-1 (Asp296) (E2G2I) Rabbit mAb (upper), or Caspase-1 (E2Z1C) Rabbit mAb (lower). (cellsignal.com)
  • IL-1α is also not a substrate for caspase-1, but its secretion is reduced in macrophages that do not express the protease. (rupress.org)
  • 2000. "Salmonella-Induced Caspase-2 Activation in Macrophages. (harvard.edu)
  • We show that caspase-1-deficient macrophages undergo apoptosis within 4-6 h of infection with invasive bacteria. (harvard.edu)
  • By using caspase-2 knockout macrophages and chemical inhibition, we establish a role for caspase-2 in both caspase-1-dependent and -independent apoptosis. (harvard.edu)
  • LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition: J. Jin, et al. (bio-connect.nl)
  • Toll-like receptor 4 (TLR4)-dependent and TIR-domain-containing adaptor-inducing interferon-β (TRIF)-dependent interferon-β production is crucial for caspase-11 activation in macrophages, but is only partially required for pro-caspase-11 expression, consistent with the existence of an interferon-inducible activator of caspase-11. (unibas.ch)
  • In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19 -deficient mice ( Card19 lxcn ) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. (plos.org)
  • The ability of PARP to repair DNA damage is prevented following cleavage of PARP by caspase-3. (reading.ac.uk)
  • Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. (proteopedia.org)
  • It inhibits urokinase plasminogen activator (uPA) and tissues plasminogen activator (tPA) to avoid plasminogen cleavage into energetic plasmin and blocks fibrinolysis [1, 2]. (exposed-skin-care.net)
  • By photostimulation of Mito-KillerRed, we induced caspase-3 activity in defined dendritic regions of cultured neurons. (jneurosci.org)
  • A highly fluorescent substrate for caspase 1. (bestbiochem.com)
  • The atomic resolution (1.06 Angstroms) crystal structure of the caspase-3 DEVD-cmk complex reveals the structural basis for substrate selectivity in the S4 pocket. (proteopedia.org)
  • Ganesan R, Mittl PR, Jelakovic S, Grutter MG. Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis. (proteopedia.org)
  • Mice with caspase-1 gene deletion showed a 70% reduction in seizures and an approximate fourfold delay in their onset. (elsevier.com)
  • The aim of this study was to evaluate the role of TREM-1 in neuroinflammatory response after ICH in mice . (bvsalud.org)
  • Previous studies have shown that these mice are more susceptible to infections with microbial pathogens, including the bacterial pathogen Salmonella enterica serovar Typhimurium (S. typhimurium), but the individual contributions of caspase-1 and caspase-11 to this phenotype are not known. (unibas.ch)
  • Caspase-3 knock-out mice have increased spine density and altered miniature EPSCs, confirming a physiological involvement of caspase-3 in the regulation of spines in vivo . (jneurosci.org)
  • Caspase-3-deficient neurons in culture fail to show spine shrinkage in response to NMDA stimulation (chemical LTD). Finally, we show that caspase-3 knock-out (KO) mice have increased spine density and synaptic strength, which is consistent with an essential role of caspase-3 in spine elimination in vivo . (jneurosci.org)
  • Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. (cdc.gov)
  • MiR-34a down-regulation also decreased reactive oxygen species accumulation (0.36-fold decrease), and promoted superoxide dismutase activity and the expression of SIRT1 (1.24-fold increase), heme oxygenase-1 and nuclear factor erythroid 2 like 2 to inhibit oxidative stress in septic mice. (frontiersin.org)
  • FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes: P. Gurung, et al. (bio-connect.nl)
  • The NLRP3 gene is found on chromosome 1 . (medlineplus.gov)
  • This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6. (reading.ac.uk)
  • However, studies in BMDCs expressing the kinase-inactive RIPK3-K51A mutant or RIPK1-K45A mutant showed that the kinase activity of neither RIPK1 nor RIPK3 is required for LPS-induced caspase 8 activation and IL-1β secretion. (duke.edu)
  • Determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers in tumor tissue, by using microwestern to assess decrease in drug targets IAP1/2 and increase in apoptosis/necroptosis markers caspase 3 and mixed lineage kinase domain like pseudokinase gene (MLKL). (clinicaltrials.gov)
  • TREM-1 mAb increased neurobehavior deficits, proinflammatory cytokines , and reduced M2 microglia after ICH, which was reversed with Rottlerin. (bvsalud.org)
  • Caspase-1 activation leads to the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18, as well as lytic inflammatory cell death known as pyroptosis. (unibas.ch)
  • Recent advances have indicated that inflammasomes contribute the etiology of MS. Inflammasomes are multiprotein complexes of the innate immune response involved in the processing of caspase-1, the activation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as the cell death-mediated mechanism of pyroptosis and the activation of the adaptive immune response. (springer.com)
  • These cytokines are also released from activated γδ T cells and jointly combine to initiate pro-inflammatory feedback loops that augment the production of IL-1β, IL-6, and IL-23 by antigen presenting cells (APC), leading to enhanced Th17 responses and continued γδ T cell activation of the effector phase. (springer.com)
  • Recent studies suggest that the pathogenesis of different inflammatory diseases also involves the inflammasomes, intracellular multiprotein complexes that mediate activation of inflammatory caspases thereby inducing the secretion of proinflammatory cytokines. (hindawi.com)
  • Noticeably, the mRNA levels of caspase-1 and IL-1β were changed differently in the two cell lines: the level of caspase-1 mRNA was enhanced in IMR-32 cells but suppressed in SK-N-SH cells, and that of IL-1β was suppressed in IMR-32 cells but enhanced in SK-N-SH cells. (researchsquare.com)
  • In this study, we show that RIPK3 is crucial for caspase 1- and caspase 8-mediated pro-IL-1β and pro-IL-18 processing in bone marrow-derived dendritic cells (BMDCs) in response to LPS stimulation. (duke.edu)
  • This Cell Meter™ Live Cell Caspase 1 Activity Assay Kit is designed to detect cell apoptosis by measuring caspase 1 activation in live cells. (aatbio.com)
  • FAM-YVAD-FMK, the green label reagent, allows for direct detection of activated caspase 1 in apoptotic cells by fluorescence microscopy, flow cytometer, or fluorescent microplate reader. (aatbio.com)
  • Treating Jurkat cells with 1 µM staurosporine for 3 hours. (aatbio.com)
  • Treating HL-60 cells with 1 µM staurosporine for 4 hours. (aatbio.com)
  • Add 150X FAM-YVAD-FMK stock solution into the cell solution at a 1:150 ratio, and incubate the cells in a 37°C, 5% CO 2 incubator for 1 hour. (aatbio.com)
  • Spin down the cells at ~ 200g for 5 minutes, and wash cells with 1 mL Washing Buffer (Component B) twice. (aatbio.com)
  • The results showed that the expression of IL-1β and Casp-1 genes in the peripheral blood mononuclear cells of patients with glomerulonephritis is different from control samples. (aejournal.ir)
  • TREM (triggering receptor expressed on myeloid cells )-1 is a key regulator of inflammation . (bvsalud.org)
  • This reagent is designed to detect caspase 3/7 activity in live cells. (nexcelom.com)
  • In HepG2 cells bortezomib markedly increased AP-1 activity and the expression of its transcriptional targets such as c-Jun, FasL, BimEL, which are involved in apoptosis. (unipa.it)
  • Differently, in Chang liver cells the different composition of AP-1 complex as well as the failure of JNK activation seemed to be responsible for the low susceptibility to apoptosis. (unipa.it)
  • Granzyme B can be delivered into cells by cytotoxic T lymphocytes and is able to directly activate caspases 3, 7, 8 and 10. (reading.ac.uk)
  • Degradation of lamins by caspase 6 results in the chromatin condensation and nuclear fragmentation commonly observed in apoptotic cells. (reading.ac.uk)
  • Multiple sclerosis (MS) and the animal model of MS, experimental autoimmune encephalomyelitis (EAE), are autoimmune demyelinating diseases of the central nervous system (CNS) characterized by the development of myelin-reactive CD4 T cells, Th1, Th17, T reg , γδ T cells and B cells (Fig. 1 ). (springer.com)
  • In the induction phase of EAE, inflammation is initiated by the binding of pathogen-associated molecular patterns (PAMP) or danger-associated molecular patterns (DAMP) to pattern recognition receptors (PRR) on innate immune cells, including inflammatory dendritic cells and monocytes (Fig. 1 ). (springer.com)
  • PRR receptor binding results in production of interleukin (IL)-1, IL-6, IL-12, IL-18, and IL-23 that promote the induction and expansion of Th1 and Th17 cells (Fig. 1 ) [ 1 ]. (springer.com)
  • This process is further amplified by IL-1β- and IL-23-activated γδ T cells that secrete IL-17 and IL-21 that act in a feedback loop to enhance the Th17 response as part of the effector phase. (springer.com)
  • In addition, resident microglia of the CNS, infiltrating monocytes and neutrophils secrete IL-1β and IL-23 to further activate and expand these cells (Fig. 2 ). (springer.com)
  • Key pathological processes within blood and central nervous system (CNS) during EAE and MS. (1) Danger associate molecular patterns (DAMP) and Pathogen-Associated molecular patterns (PAMP) released into the peripheral blood activate inflammatory myeloid and T cells that migrate into the CNS after blood-brain barrier (BBB) breakdown. (springer.com)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • Add diluted FLICA to each sample at 1:30 (e.g., add 10 μL to 290 μL of cultured cells). (immunochemistry.com)
  • A short recovery period of 6h of cells from SWCNT exposure resulted in reversal of caspase-3 and caspase-7, and a partial reversal of PARP-1 activation. (cdc.gov)
  • The results of this study show that the molecular mechanism for raw SWCNT-mediated toxicity in BEAS-2B cells is through the activation of caspase-3, caspase-7, and PARP-1. (cdc.gov)
  • Notably BC-1 cells which are also EBV+ had a much higher number of uniquely altered genes than BCBL-1 and Edivoxetine HCl BCP-1. (biotech2012.org)
  • ABL-N administration induced apoptosis of PC3 cells in a dose-dependent manner, along with the enhanced activity of caspases and increased Bax/Bcl-2 ratio. (cusabio.com)
  • Expression of KLF5, Stat5b and ICAM-1 was significantly downregulated in PC3 cells. (cusabio.com)
  • Caspase 3/7 activity assay Cells had been plated as referred to for cell viability and treated with raising concentrations of TM5275 or TM5441 for 48 hours. (exposed-skin-care.net)
  • Significantly, AZD8055 decreased AML blast cell proliferation and cell cycle progression, reduced the clonogenic growth of leukemic progenitors and induced caspase-dependent apoptosis in leukemic cells but not in normal immature CD34+ cells. (crick.ac.uk)
  • The comparisons of RCC1 levels in cell cycleCsynchronized HeLa and HFF-1 cells were obtained from data shown in Fig. HFF-1 cells created cells with steep mitotic RanGTP gradients much like HeLa cells, indicating that chromosomal gain can promote mitosis in aneuploid tumor cells via Went. (globaltechbiz.com)
  • Outcomes and dialogue Cell typeCspecific variety from the mitotic RanGTP and importin- cargo gradients To find out if the RanGTP gradient helps mitosis in every human being somatic cells or can be an version specific to particular forms of cells, we assessed RanGTP gradients inside a -panel of human being cells, including major cells, immortalized regular cells, cancer-derived cells, and tumorigenic cells (Fig. 1 and Desk S1). (globaltechbiz.com)
  • 2011), where the donor REF = 2,519 ps may be the mean donor of mTFP-1 indicated in cells within the lack of the acceptor (Fig. S1, F) and E. Open in another window Shape 1. (globaltechbiz.com)
  • Bellido T, Huening M, Raval-Pandya M, Manolagas SC, Christakos S. Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase-3 activity. (uams.edu)
  • Outcomes HHT and ETP display synergistic cytotoxicity in AML cells ETP and HHT are cytotoxic reagents for AML cells.21,22 To check whether ETP and HHT possess synergistic cytotoxicity in AML cells, the chemosensitive AML super model tiffany livingston cell lines (THP1 MK-8776 inhibition and HL60) were treated with HHT and ETP alone or in combination (10/1 and 20/2, nM/M) for 48 hours. (ecologicalsgardens.com)
  • During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. (plos.org)
  • The cytokine interleukin-1α (IL-1α) has no secretion signal peptide but is nonetheless secreted as part of the inflammatory response. (rupress.org)
  • These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host's apoptotic machinery by targeting caspase-1. (harvard.edu)
  • Inflammasome Activators Induce Interleukin-1alpha Secretion via Distinct Pathways with Differential Requirement for the Protease Function of Caspase-1: O. Gross, et al. (bio-connect.nl)
  • Caspase-1 causes pyroptosis, a necrotic-like cell death. (nih.gov)
  • He, L;Wei, T;Huang, Y;Zhang, X;Zhu, D;Liu, H;Wang, Z. miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury . (immunochemistry.com)
  • Immunohistochemistry analysis of paraffin-embedded human lung carcinoma, using IL-1 beta (Cleaved-Asp210) Antibody. (intolala.com)
  • UV treatment using anti-Cleaved Caspase 8 antibody (RM442) at 1:2000 dilution. (revmab.com)
  • Based on, the role of Caspase-1 and Interleukin-1β in regulation of inflammation, investigating the gene expression of them in glomerulonephritis patients can be useful in determining the role of Inflammasome in glomerulonephritis. (aejournal.ir)
  • Interleukin-1β (IL-1β) is implicated in gastric cancer development and certain gene polymorphisms play a role in this scenario. (mdpi.com)
  • 1 HD is caused by a tract of more than 37 uninterrupted polyglutamines in exon 1 of the HD gene product, huntingtin. (bmj.com)
  • In addition to the β-lactam resistance genes detected by PCR ( bla SHV-1 , bla OXA-48 and bla OXA-1 ), WGS of five representative isolates revealed the presence of genes encoding aminoglycoside resistance, aadA2 and aph3-Ia , fluoroquinolone resistance determinants aac(6)Ib-c , oqxA and oqxB , the sulfonamide resistance gene sul1 , and fosA (fosfomycin resistance). (microbiologyresearch.org)
  • Within the common gene set the top 20 upregulated or downregulated candidate genes in SASP-treated BCP-1 BC-1 and BCBL-1 cell-lines are listed in Table ?Table11 and Table ?Table2 2 respectively including gene description and the altered level of transcription in these cell-lines. (biotech2012.org)
  • Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. (harvard.edu)
  • In addition, bortezomib caused activation of JNK1, which in turn increased the level of phospho-c-Jun as well as stimulated the activation of caspase-3 and t-Bid, two fundamental apoptotic factors. (unipa.it)
  • Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. (jbc.org)
  • The FLICA reagent FAM-LETD-FMK enters each cell and irreversibly binds to activated caspase-8. (immunochemistry.com)
  • The increase in apoptosis was associated with activation of caspase-3, caspase-7, and poly (ADP-ribose) polymerase-1 (PARP-1). (cdc.gov)
  • CXCL12/Stromal Cell-derived Factor 1 (SDF-1) is a member of the CXC chemokine ligand superfamily. (rndsystems.com)
  • We've also proven that PAI-1 protects EC from Fas ligand (Fas-L)-reliant extrinsic apoptosis [8]. (exposed-skin-care.net)
  • A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. (bvsalud.org)
  • Results: Caspase-1 inhibition reduced the release of IL-1β in organotypic slices exposed to EPS+ATP. (elsevier.com)
  • Organic solvent-induced proximal tubular cell apoptosis via caspase-9 activation. (cdc.gov)
  • This paradoxical aftereffect of PAI-1 provides since been described by its pro-angiogenic activity and its own protective influence on cell apoptosis. (exposed-skin-care.net)
  • Caspase 8-mediated pro-IL-1β processing requires intact RIPK1, RIPK3, TRIF, and FADD. (duke.edu)
  • Caspase-8 activity is regulated by CASP8 and FADD-like apoptosis regulator. (smpdb.ca)
  • Recently, a new non-canonical inflammasome was described that activates caspase-11, a pro-inflammatory caspase required for lipopolysaccharide-induced lethality. (unibas.ch)
  • Cleaves and activates caspase-6, -7 and -9. (proteopedia.org)
  • The adaptor molecule ASC mediates AIM2-dependent caspase-1 activation. (nih.gov)
  • To date, no function besides caspase-1 activation has been ascribed to the AIM2/ASC complex. (nih.gov)
  • 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. (nih.gov)
  • 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. (nih.gov)
  • Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop: C. Juruj, et al. (bio-connect.nl)
  • Activation of caspase-3, an executioner caspase that lies downstream of both extrinsic and intrinsic (mitochondrial) pathways of apoptosis, plays a central role in programmed cell death of many cell types, including neurons ( Fuchs and Steller, 2011 ). (jneurosci.org)
  • Hence, RIPK3 is an unexpected positive regulator of caspase 8 activity that promotes IL-1β maturation in BMDCs. (duke.edu)
  • Here, we show that caspase-3 activity is essential-and can act locally within neurons-for regulation of spine density and dendrite morphology. (jneurosci.org)
  • This concept also implies the existence of mechanisms that limit the activity of caspase-3 and prevent complete destruction of the cell. (jneurosci.org)
  • The ability to perform kinetic apoptosis assays allows researchers to continuously measure the caspase 3/7 activity within the cell population. (nexcelom.com)
  • 2 report that the restriction of caspase activity to the surfaces of organelles called mitochondria allows the enzymes to exert this alternative effect. (nature.com)
  • Interestingly, siRNA silencing of c-Jun or JNK1 reduced HepG2 cell susceptibility to apoptosis and prevented the increase in AP-1 activity. (unipa.it)
  • In addition to the antioxidant properties of melatonin, AFMK and N 1 -acetyl-5-methoxykinuramine (AMK) are two important melatonin metabolites that have excellent radical scavenging activity [ 5 , 32 , 33 ]. (hindawi.com)
  • Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. (immunochemistry.com)
  • Research using physiological degrees of PAI-1 uncovered it stimulates endothelial cell (EC) migration and proliferation through its anti-protease activity and its own capability to bind to vitronectin leading to EC to migrate in the vitronectin-rich perivascular space towards fibronectin-rich tumor stroma [6, 7]. (exposed-skin-care.net)
  • Inflammasomes are cytosolic multiprotein complexes assembled by intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and they initiate innate immune responses to invading pathogens and danger signals by activating caspase-1 (ref. 1). (unibas.ch)
  • These results indicate that caspase-11-dependent cell death is detrimental to the host in the absence of caspase-1-mediated innate immunity, resulting in extracellular replication of a facultative intracellular bacterial pathogen. (unibas.ch)
  • Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. (medlineplus.gov)
  • Numerous studies show a paradoxical positive correlation between raised degrees of plasminogen activator inhibitior-1 (PAI-1) in tumors and blood of cancer individuals with poor scientific outcome, suggesting that PAI-1 is actually a healing target. (exposed-skin-care.net)
  • TREM-1 knockout CRISPR was administered intracerebroventricularly to evaluate the role of TREM-1 after ICH. (bvsalud.org)
  • TREM-1 knockout reduced ICH-induced neurobehavioral deficits and neuroinflammatory response. (bvsalud.org)
  • Caspase-1 is activated by multiprotein complexes called Inflammasomes in response to numerous stimuli that are detected through distinct inflammasomes. (bio-connect.nl)
  • A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing. (duke.edu)
  • However, the biochemical complex that mediates caspase 8-mediated processing is not defined. (duke.edu)
  • We previously found that intracerebral administration of interleukin-1 (IL-1)-β has proconvulsant effects, whereas its endogenous receptor antagonist (IL-1Ra) mediates potent anticonvulsant actions in various models of limbic seizures. (elsevier.com)
  • Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1. (umassmed.edu)
  • Caspases play important roles in apoptosis and inflammation. (immunochemistry.com)
  • Caspasa de prodominio largo con especificidad por la forma precursora de la INTERLEUCINA 1 BETA. (bvsalud.org)
  • La caspasa 1 se denomina también enzima convertidora de la interleucina 1 beta y con frecuencia se abrevia como ICE. (bvsalud.org)
  • Particularly, activation of caspase-1 during fast Salmonella-induced apoptosis partially relies on caspase-2. (harvard.edu)
  • The activation of PARP-1, caspase-3, and caspase-7 was only partially diminished after a recovery of 6h from the exposure to crocidolite. (cdc.gov)
  • Mitochondrial membrane potential was measured via MitoProbe JC-1 Assay Kit (ThermoFisher Scientific) according to manufacturer's instructions. (cdc.gov)
  • dissipation of mitochondrial potential with cytochrome c release and activation of caspase-3. (unipa.it)
  • C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis. (biomedcentral.com)
  • Mitochondrial depolarization was evaluated using the MitoProbe 5,5,6,6-tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) assay package (Life Systems) based on the producers suggestions. (exposed-skin-care.net)
  • Previous studies have used genetic or pharmacologic manipulations to investigate the functions of caspases in neurons and synapses but, by their nature, such approaches cannot address local actions of caspases within specific neuronal compartments or longitudinally follow the changes in the same neuron after caspase activation. (jneurosci.org)
  • CASP3_HUMAN ] Involved in the activation cascade of caspases responsible for apoptosis execution. (proteopedia.org)
  • Release of cytochrome C from mitochondria can lead to the activation of caspase 9, and then of caspase 3. (reading.ac.uk)
  • Recognizes endogenous full-length and activated (p20 fragment) mouse caspase-1. (bio-connect.nl)
  • Melatonin (N-acetyl-5-methoxytryptamine) is an endogenous indoleamine widely distributed in plants, unicellular organisms, algae, bacteria, invertebrates, and vertebrates [ 1 - 3 ]. (hindawi.com)
  • The ability of Salmonella to induce caspase-1-independent macrophage apoptosis may play a role in situations in which activation of this protease is either prevented or uncoupled from the induction of apoptosis. (harvard.edu)
  • Here we show that non-canonical caspase-11 activation contributes to macrophage death during S. typhimurium infection. (unibas.ch)
  • Invasive Salmonella typhimurium targets caspase-2 simultaneously with, but independently of, caspase-1. (harvard.edu)
  • There is growing evidence that NF-κB regulates the susceptibility of certain cell types to apoptosis through the transcriptional control of protective genes ( 1 , 14 , 15 ). (aai.org)
  • Here, using non-small cell lung cancer and glioblastoma multiforme cell line models, we show that two alternatively spliced, functional truncated isoforms of p53 (p53β and p53γ, comprising exons 1 to 9β or 9γ, respectively) and that lack the C-terminal MDM2-binding domain have markedly reduced susceptibility to MDM2-mediated degradation but are highly susceptible to nonsense-mediated decay (NMD), a regulator of aberrant mRNA stability. (jbc.org)
  • The level of GSDMD expression in situ was along with the increase in the release of IL-1β, IL-18, caspase-1 and lactate dehydrogenase (LDH). (researchsquare.com)