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

MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (1/2199)

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.  (+info)

Tumor necrosis factor alpha regulation of the FAS-mediated apoptosis-signaling pathway in synovial cells. (2/2199)

OBJECTIVE: Fas-mediated apoptosis is observed in synoviocytes of patients with rheumatoid arthritis (RA), but not in those of patients with osteoarthritis (OA). The present study was conducted to elucidate the mechanisms that initiate induction of Fas-mediated apoptosis in RA synoviocytes. METHODS: Cultured OA synoviocytes, which are insensitive to Fas-mediated apoptosis in spite of Fas antigen expression, were used in these experiments. Synovial cell proliferation and cytotoxicity studies were performed using MTS and lactate dehydrogenase release assays. Surface expression of Fas antigen was analyzed by flow cytometry. The expression and function of apoptosis-signaling molecules, such as caspase 8 and caspase 3, were examined by immunoblot analysis. RESULTS: Tumor necrosis factor alpha (TNFalpha) induced proliferation of cultured OA synoviocytes. Fas ligation with anti-Fas monoclonal antibody (mAb) resulted in cytotoxic activity against cultured OA synoviocytes that had been pretreated with TNFalpha for 5 days, but not those pretreated for 2 days. In contrast, anti-Fas mAb did not show a cytotoxic effect against untreated cultured OA synoviocytes. A gradual up-regulation of caspase 8 and caspase 3, which played a role in the caspase cascade for Fas-mediated apoptosis, was observed in TNFalpha-treated cultured OA synoviocytes. In addition, Fas ligation to TNFalpha-treated cultured OA synoviocytes induced activation of caspase 8 and caspase 3, with subsequent cleavage of poly(ADP-ribose) polymerase (PARP), a substrate of activated caspase 3. More importantly, Z-IETD-FMK, a caspase 8 inhibitor, and Ac-DEVD-CHO, a caspase 3 inhibitor, almost completely inhibited Fas-mediated apoptosis of TNFalpha-treated cultured OA synoviocytes, whereas Ac-YVAD-CHO, a caspase 1 inhibitor, did not. CONCLUSION: Our results clearly demonstrate that TNFalpha stimulates synovial cells to proliferate as well as sensitizes the cells for Fas-mediated apoptosis, at least in part by up-regulation and activation of caspase 8 and caspase 3. These findings suggest that TNFalpha may be one of the factors providing sensitization of synovial cells to Fas-mediated apoptosis in RA.  (+info)

Solution structure of BID, an intracellular amplifier of apoptotic signaling. (3/2199)

We report the solution structure of BID, an intracellular cross-talk agent that can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after Caspase 8 cleavage. BID contains eight alpha helices where two central hydrophobic helices are surrounded by six amphipathic ones. The fold resembles poreforming bacterial toxins and shows similarity to BCL-XL although sequence homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3 domain-dependent and -independent modes of action in inducing mitochondrial damage.  (+info)

Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. (4/2199)

Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization.  (+info)

Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. (5/2199)

Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems.  (+info)

Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95- and DNA damage-induced apoptosis. (6/2199)

To evaluate the role of ceramide (Cer) in apoptosis signaling, we examined Cer formation induced by CD95, etoposide, or gamma-radiation (IR) in relation to caspase activation and mitochondrial changes in Jurkat T cells. The Cer response to all three stimuli was mapped in between caspases sensitive to benzoyloxycarbonyl-VAD-fluoromethylketone (zVAD-fmk) and acetyl-DEVD-aldehyde (DEVD-CHO). Cer production was independent of nuclear fragmentation but associated with the occurrence of other aspects of the apoptotic morphology. Caspase-8 inhibition abrogated Cer formation and apoptosis induced by CD95 but did not affect the response to etoposide or IR, placing CD95-induced Cer formation downstream from caspase-8 and excluding a role for caspase-8 in the DNA damage pathways. CD95 signaling to the mitochondria required caspase-8, whereas cytochrome c release in response to DNA damage was caspase-independent. These results indicate that the caspases required for the Cer response to etoposide and IR reside at or downstream from the mitochondria. Bcl-2 overexpression abrogated the Cer response to etoposide and IR and reduced CD95-induced Cer accumulation. We conclude that the Cer response to DNA damage fully depends on mitochondrion-dependent caspases, whereas the response to CD95 partially relies on these caspases. Our data imply that Cer is not instrumental in the activation of inducer caspases or signaling to the mitochondria. Rather, Cer formation is associated with the execution phase of apoptosis.  (+info)

Caspase-8 is required for cell death induced by expanded polyglutamine repeats. (7/2199)

We show here that caspase-8 is required for the death of primary rat neurons induced by an expanded polyglutamine repeat (Q79). Expression of Q79 recruited and activated caspase-8. Inhibition of caspase-8 blocked polyglutamine-induced cell death. Coexpression of Q79 with the caspase inhibitor CrmA, a dominant-negative mutant of FADD (FADD DN), Bcl-2, or Bcl-xL, but not an N-terminally tagged Bcl-xL, prevented the recruitment of caspase-8 and inhibited polyglutamine-induced cell death. Furthermore, Western blot analysis revealed the presence of activated caspase-8 in the insoluble fraction of affected brain regions from Huntington's disease (HD) patients but not in those from neurologically unremarkable controls, suggesting the relocation and activation of caspase-8 during the pathogenesis of HD. These results suggest an essential role of caspase-8 in HD-related neural degenerative diseases.  (+info)

Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. (8/2199)

Apoptotic cell suicide initiated by ligation of CD95 (Fas/APO-1) occurs through recruitment, oligomerization and autocatalytic activation of the cysteine protease, caspase-8 (MACH, FLICE, Mch5). An endogenous mammalian regulator of this process, named Usurpin, has been identified (aliases for Usurpin include CASH, Casper, CLARP, FLAME-1, FLIP, I-FLICE and MRIT). This protein is ubiquitously expressed and exists as at least three isoforms arising by alternative mRNA splicing. The Usurpin gene is comprised of 13 exons and is clustered within approximately 200 Kb with the caspase-8 and -10 genes on human chromosome 2q33-34. The Usurpin polypeptide has features in common with pro-caspase-8 and -10, including tandem 'death effector domains' on the N-terminus of a large subunit/small subunit caspase-like domain, but it lacks key residues that are necessary for caspase proteolytic activity, including the His and Cys which form the catalytic substrates diad, and residues that stabilize the P1 aspartic acid in substrates. Retro-mutation of these residues to functional caspase counterparts failed to restore proteolytic activity, indicating that other determinants also ensure the absence of catalytic potential. Usurpin heterodimerized with pro-caspase-8 in vitro and precluded pro-caspase-8 recruitment by the FADD/MORT1 adapter protein. Cell death induced by CD95 (Fas/APO-1) ligation was attenuated in cells transfected with Usurpin. In vivo, a Usurpin deficit was found in cardiac infarcts where TUNEL-positive myocytes and active caspase-3 expression were prominent following ischemia/reperfusion injury. In contrast, abundant Usurpin expression (and a caspase-3 deficit) occurred in surrounding unaffected cardiac tissue, suggesting reciprocal regulation of these pro- and anti-apoptotic molecules in vivo. Usurpin thus appears to be an endogenous modulator of apoptosis sensitivity in mammalian cells, including the susceptibility of cardiac myocytes to apoptotic death following ischemia/ reperfusion injury.  (+info)

Necrosis is a type of cell death that occurs when cells are exposed to excessive stress, injury, or inflammation, leading to damage to the cell membrane and the release of cellular contents into the surrounding tissue. This can lead to the formation of gangrene, which is the death of body tissue due to lack of blood supply.

There are several types of necrosis, including:

1. Coagulative necrosis: This type of necrosis occurs when there is a lack of blood supply to the tissues, leading to the formation of a firm, white plaque on the surface of the affected area.
2. Liquefactive necrosis: This type of necrosis occurs when there is an infection or inflammation that causes the death of cells and the formation of pus.
3. Caseous necrosis: This type of necrosis occurs when there is a chronic infection, such as tuberculosis, and the affected tissue becomes soft and cheese-like.
4. Fat necrosis: This type of necrosis occurs when there is trauma to fatty tissue, leading to the formation of firm, yellowish nodules.
5. Necrotizing fasciitis: This is a severe and life-threatening form of necrosis that affects the skin and underlying tissues, often as a result of bacterial infection.

The diagnosis of necrosis is typically made through a combination of physical examination, imaging studies such as X-rays or CT scans, and laboratory tests such as biopsy. Treatment depends on the underlying cause of the necrosis and may include antibiotics, surgical debridement, or amputation in severe cases.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.

There are several different types of neuroblastoma, including:

1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.

Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:

* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate

Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.

Caspase-10, Caspase-2, Caspase-3, Caspase-6, Caspase-7, Caspase-9, DEDD, FADD, FasL, FasR, IFT57, NOL3, PEA15, RIPK1, TNFRSF10B ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Cowling V, Downward J (October 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis ... Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 ( ...
... (CEDS) is a very rare genetic disorder of the immune system. It is caused by mutations in the CASP8 gene ... Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 ( ... Caspase-8 is involved in the initiation of the cell death signal cascade. Cell death counters proliferation of lymphocytes, ... CEDS is caused by homozygous mutations in caspase-8. Caspase-8 is a 51 kb gene with 13 exons encoding for a 496 amino acid ...
... 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). " ... 2001). "CARDINAL, a novel caspase recruitment domain protein, is an inhibitor of multiple NF-kappa B activation pathways". J. ... an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer". J Biol Chem. 276 (34): 32220-9 ...
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, ...
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 ... Caspase 6 has been shown to interact with Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000138794 - ...
... 9, Caspase 10) Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases are activated, they ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro- ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... Apoptopic caspases are subcategorised as: Initiator Caspases (Caspase 2, Caspase 8, ...
Gly Caspase-10 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-8 (EC 3.4.22.61) and caspase-9 (EC 3.4.22.62 ... Caspase-10 (EC 3.4.22.63, FLICE2, Mch4, CASP-10, ICE-like apoptotic protease 4, apoptotic protease Mch-4, FAS-associated death ... Caspase-10 at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC 3.4.22). ... Shikama Y, Yamada M, Miyashita T (July 2003). "Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK and IKKalpha ...
The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and ... Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved ... Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner ... Caspase 7 has been shown to interact with: Caspase 8, Survivin and XIAP. The Proteolysis Map Caspase GRCh38: Ensembl release 89 ...
... 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 ... Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species of ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...
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 ...
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 ...
1] Apoptosis, Trail & Caspase 8 - The Proteolysis Map-animation PDB: 1D2Q​ TRAIL+Protein at the US National Library of Medicine ... TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... Feb 2016 Song JJ, Lee YJ (May 2008). "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation ... doi:10.1016/S0083-6729(04)67001-4. ISBN 978-0-12-709867-8. PMID 15110168. Song C, Jin B (2005). "TRAIL (CD253), a new member of ...
... caspase-11 (caspase-4 in humans), which is responsible for many of the effects previously attributed to caspase-1, including ... The 2011 paper showed that mice lacking the gene that encodes caspase-1 also carry a mutation in a neighboring caspase gene, ... They showed that these mechanisms did not depend on TLR4, but were rather mediated by caspase-11. This was significant, because ... By 2002, Dixit was among the first scientists to demonstrate that pro-inflammatory caspases are part of a molecular complex ...
2003 nomenclature IA - Fas IB - Fas ligand IIA - Caspase 10 IIB - Caspase 8 III - unknown IV - Neuroblastoma RAS viral oncogene ... Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... 20% of patients CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder RALD: NRAS, KRAS ... 3 reported cases ALPS-CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients ALPS-U: Undefined. ...
... has been shown to interact with Caspase 8. GRCh38: Ensembl release 89: ENSG00000114446 - Ensembl, May 2017 GRCm38: ... "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol ... "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol ... "Interaction of HIPPI with putative promoter sequence of caspase-1 in vitro and in vivo". Biochem. Biophys. Res. Commun. 353 (1 ...
Caspase-3, caspase-8, and caspase-9 have been reported to be modified by O-GlcNAc. Caspase-8 is modified near its cleavage/ ... Hyper-O-GlcNAcylation in PDAC cells appeared to be anti-apoptotic, inhibiting cleavage and activation of caspase-3 and caspase- ... deoxy-GlcNAc Reveals O-GlcNAc Modification of the Apoptotic Caspases That Can Block the Cleavage/Activation of Caspase-8". ... GlcNAc with 5S-GlcNAc accelerated caspase activation while pharmacological raising of O-GlcNAc with thiamet-G inhibited caspase ...
... initiating the caspase cascade. The activated caspases can go on to cleave intracellular proteins such as inhibitor of caspase- ... "Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8". Journal of ... Since activation of caspase 8 requires FADD in order to bring the procaspase 8 molecules into close proximity to one another to ... Caspase 8 then cleaves RIPK1, leading to inhibition of this signalling, inhibiting cell death. FADD knockout in mouse embryos ...
"The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8". Proceedings of the National Academy of Sciences. ...
Hu WH, Johnson H, Shu HB (April 2000). "Activation of NF-kappaB by FADD, Casper, and caspase-8". J. Biol. Chem. 275 (15): 10838 ... In 2000, he and his colleagues showed that FADD, Casper (caspase-8-related protein), and caspase-8 play important roles in NF- ... They also cloned and identified a novel AIF-homologous molecule called AMID, which can lead the way to caspase-independent ... induces caspase-independent apoptosis". J. Biol. Chem. 277 (28): 25617-23. doi:10.1074/jbc.M202285200. PMID 11980907. Xu LG, ...
... caspase 1 and caspase 8). In comparison to their mammalian counterparts, viral serpins contain significant deletions of ... 92 (8): 2696-2706. doi:10.1182/blood.V92.8.2696. PMID 9763552. Gooptu B, Hazes B, Chang WS, Dafforn TR, Carrell RW, Read RJ, ... 204 (8): 1901-1909. doi:10.1084/jem.20070494. PMC 2118684. PMID 17664292. Antalis TM, La Linn M, Donnan K, Mateo L, Gardner J, ... 134 (8): 2076-2079. doi:10.1038/jid.2014.156. PMID 25029323. Dahlen JR, Jean F, Thomas G, Foster DC, Kisiel W (January 1998). " ...
Initiator caspases: responsible for the activation of effector caspases. These caspases are activated through oligomerization ... FLIPL's pseudo-caspase has two tandem DEDs that are very similar to the N-terminus of capase-8, but in which there is an ... Studying caspases is important since they don't only control apoptosis but also inhibit it, depending on the necessity of the ... This type of apoptosis depends on the pDED of the HIP-1, and it consists in the activation of caspase-3, an enzyme that is ...
... the activation of caspase-9, caspase-3 and the decrease of Bcl-2. Those phenomena indicate the role of mitochondrial in the ... This can stimulate the apoptosis by activating downstream caspase-3 or by cleaving Bid. As a result, the cleavage of Bid (tBid ... Furthermore, the increase in caspase-8 activation is also observed. ... 148 (2): 203-8. doi:10.1007/s12011-012-9364-2. PMID 22367705. S2CID 16035022. Li GQ, Chen XG, Wu XP, Xie JD, Liang YJ, Zhao XQ ...
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 ...
A latest study indicated that ECP caused cytotoxicity in HL-60 and HeLa cells via caspase-3 like activity. Accordingly, ... ECP triggers apoptosis by caspase-8 activation through mitochondria-independent pathway. Increases in chromatin condensation, ... 8 (12): 1778-95. doi:10.1111/j.1600-0854.2007.00650.x. PMID 17944807. S2CID 23093550. Chang KC, Lo CW, Fan TC, Chang MD, Shu CW ... 267 (3): 391-5. doi:10.1007/s00405-009-1103-8. PMID 19760211. S2CID 8311866. Yuksel H, Yilmaz O, Sogut A, et al. (2009). " ...
The caspase-independence of necroptosis allows the cell to bypass caspase activation, decreasing the time during which the ... in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to ... Conversely, caspase 8 inhibition of necroptosis can be bypassed by the necroptotic machinery through the anti-apoptotic protein ... The best characterized example of this co-regulation is the ability of caspase 8 to inhibit the formation of the necrosome by ...
"RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3". Cell. 157 (5): 1189-202. doi:10.1016/j.cell.2014.04. ...
"AID and Caspase 8 Shape the Germinal Center Response through Apoptosis". The Journal of Immunology. 191 (12): 5840-5847. doi: ...
On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... 8: 1675. doi:10.3389/fimmu.2017.01675. PMC 5712345. PMID 29234328. Probert L (2015). "TNF and its receptors in the CNS: The ... 66 (8): 1403-8. doi:10.1016/S0006-2952(03)00490-8. PMID 14555214. Ghada A. Abd El Latif, Tumor necrosis factor alpha and ...
Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). "Activation of the NF-kappaB pathway by caspase 8 and its ... 13 (1): 13-8. PMID 11801527. Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV (1997). "A novel interaction between ... 22 (8): 2536-43. doi:10.1128/MCB.22.8.2536-2543.2002. PMC 133739. PMID 11909948. Gajate C, Mollinedo F (2005). "Cytoskeleton- ... 57 (2-3): 117-8. doi:10.1159/000133127. PMID 1655358. Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GH, Gatanaga T, ...
Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). "Activation of the NF-kappaB pathway by caspase 8 and its ... 19 (3): 2180-8. doi:10.1128/MCB.19.3.2180. PMC 84010. PMID 10022904. Lin X, Cunningham ET, Mu Y, Geleziunas R, Greene WC (1999 ... doi:10.1016/S1074-7613(00)80027-8. PMID 10072079. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (1999 ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 58 (8): 872-9. doi:10.1016/j.neuint.2011.02.014. PMC 3100427. PMID 21334414. Zan L, Zhang X, Xi Y, Wu H, Song Y, Teng G, Li H, ... 180 (4): 383-8. doi:10.1002/(SICI)1096-9896(199612)180:4. 3.0.CO;2-N. PMID 9014858. S2CID 26892937. Slamon DJ, Clark GM, Wong ... Researchers have shown that Src expression is 5 to 8 fold higher in premalignant polyps than normal mucosa. The elevated c-Src ...
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 ...
Granzymes usually cause apoptosis of the infected cell through initiation of the caspase cascade. However, apoptosis can also ... 5 (8): 1789-1792. doi:10.1111/j.1600-6143.2005.00970.x. PMID 15996224. S2CID 19946195. Walch M, Dotiwala F, Mulik S, Thiery J, ... 12 (8): e0183610. Bibcode:2017PLoSO..1283610D. doi:10.1371/journal.pone.0183610. PMC 5565109. PMID 28827826. Harris V, Jackson ...
In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin- ... 272 (13): 8145-8. doi:10.1074/jbc.272.13.8145. PMID 9079628. Mahalingam S, Ayyavoo V, Patel M, Kieber-Emmons T, Kao GD, Muschel ... 8 (7): 307-15. doi:10.1016/s1359-6446(03)02647-3. PMID 12654543. Karin, M; Delhase, M (February 2000). "The I kappa B kinase ( ... 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 ... 20 (8): 1367-1379. doi:10.1002/pro.663. PMC 3189522. PMID 21608060. Eddy EM (January 1999). "Role of heat shock protein HSP70-2 ... doi:10.1007/s00018-016-2236-8. PMID 27137183. S2CID 14824854. Mohanan V, Grimes CL (July 2014). "The molecular chaperone HSP70 ...
"Relationship between Caspase Activity and Apoptotic Markers in Human Sperm in Response to Hydrogen Peroxide and Progesterone". ... 21 (5): 1465-8. doi:10.1002/hep.1840210534. PMID 7737654. Negoescu A, Lorimier P, Labat-Moleur F, Drouet C, Robert C, ... 52 (6): 252-8. doi:10.1016/S0753-3322(98)80010-3. PMID 9755824. Li X, Darzynkiewicz Z (1995). "Labeling DNA strand breaks with ...
1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter ... the sensitivity of PS1 to caspases" (PDF). FEBS Lett. 445 (1): 149-54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/ ...
"Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". Journal of Immunology. 170 (7): 3631-6. doi: ... 11 (8): 2962-8. doi:10.1158/1078-0432.CCR-04-0861. PMID 15837748. Zhang ZY, Dong JH, Chen YW, Wang XQ, Li CH, Wang J, Wang GQ, ... 169 (10): 5912-8. doi:10.4049/jimmunol.169.10.5912. PMID 12421975. Kashio Y, Nakamura K, Abedin MJ, Seki M, Nishi N, Yoshida N ... 11 (8): 2962-8. doi:10.1158/1078-0432.CCR-04-0861. PMID 15837748. Kasamatsu A, Uzawa K, Nakashima D, Koike H, Shiiba M, Bukawa ...
If cells receive multiple apoptotic stimuli, caspase-3 activates the Mst1 kinase, which phosphorylates the serine at position ... 8 (15): 15. doi:10.1186/s13072-015-0006-8. PMC 4411797. PMID 25922622. Wu J, Mu S, Guo M, Chen T, Zhang Z, Li Z, Li Y, Kang X ( ...
Hayashi Y, Arakaki R, Ishimaru N (2003). "The role of caspase cascade on the development of primary Sjögren's syndrome". J. Med ... 8 (1): 1-9. doi:10.1128/MCB.8.1.1. PMC 363070. PMID 3336352. Leto, T. L.; Fortugno-Erikson, D.; Barton, D.; Yang-Feng, T. L.; ... 8 (1): 1-9. doi:10.1128/MCB.8.1.1. PMC 363070. PMID 3336352. McMahon AP, Giebelhaus DH, Champion JE, Bailes JA, Lacey S, ... 274 (46): 32904-8. doi:10.1074/jbc.274.46.32904. PMID 10551855. Sridharan D, Brown M, Lambert WC, McMahon LW, Lambert MW (March ...
Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of ... 162 (2): 1042-8. PMID 9916731. Schütze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, Krönke ... 277 (37): 34343-8. doi:10.1074/jbc.M204169200. PMID 12107169. Inada H, Izawa I, Nishizawa M, Fujita E, Kiyono T, Takahashi T, ... doi:10.1016/S1074-7613(00)80400-8. PMID 9430227. Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, Vincenz C, Aggarwal BB, Ni J ...
In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase ... 437 (7062): 1173-8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026. Olsen JV, Blagoev B, ... 534 (1-3): 61-8. doi:10.1016/S0014-5793(02)03778-X. PMID 12527362. S2CID 7018829. Human BCL2L13 genome location and BCL2L13 ...
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- ... Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in ... 22 (8): 2536-43. doi:10.1128/MCB.22.8.2536-2543.2002. PMC 133739. PMID 11909948. Ajuh P, Kuster B, Panov K, Zomerdijk JC, Mann ... 3 (8): 781-93. doi:10.1016/j.molmet.2014.08.003. PMC 4216407. PMID 25379403. Bozidis P, Hyphantis T, Mantas C, Sotiropoulou M, ...
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: ... 67 (8): 1265-76. doi:10.1007/s00018-010-0261-6. PMID 20094755. S2CID 32790065. Talmud PJ, Drenos F, Shah S, et al. (2009). " ...
Such substrates have been used to detect caspase activity and cytochrome P450 activity, among others. Luciferase can also be ... At pH 8, it can be seen that the unprotonated histidine residues are involved in a network of hydrogen bonds at the interface ... Luciferase and its domains are not active at pH 8 but they are extremely active at the optimum pH of 6.3 whereas LBP binds ... There is a large pocket in the β-barrel of the dinoflagellate luciferase at pH 8 to accommodate the tetrapyrrole substrate but ...
Her demonstration that caspases are involved directly in ischaemic brain damage in vivo stimulated the development of caspase ... doi:10.1007/s00330-008-1202-8. PMID 18987865. S2CID 417275. Selvarajah, J. R.; Smith, C. J.; Hulme, S.; Georgiou, R.; ...
... mitochondrial dysfunction and caspase-3-dependent signaling pathways". International Journal of Oncology. 39 (1): 217-224. doi: ... 254 (3): 221-8. doi:10.1016/j.taap.2011.03.016. PMID 21457722. Park HG, Yoon SY, Choi JY, Lee GS, Choi JH, Shin CY, Son KH, Lee ...
... encoding protein Caspase 16, pseudogene CCDC113: encoding protein Coiled-coil domain-containing protein 113 Ccdc78: encoding ... ISBN 978-1-4673-1921-8. S2CID 16666470. Genome Decoration Page, NCBI. Ideogram data for Homo sapience (850 bphs, Assembly ... Inflammatory bowel disease 8 IHPS2: Pyloric stenosis, infantile hypertrophic, 2 ITFG3: encoding protein Protein ITFG3 KDM8: ... encoding protein Lysine demethylase 8 LINC00273 encoding protein Long intergenic non-protein coding RNA 273 LOC124220: encoding ...
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 ... recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via ...
... 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: ... Retrieved 8 April 2013. "DNA Forensics". U.S. Department of Energy Genome Programs. Retrieved 8 April 2013. Gong JP, Traganos F ...
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 ... 1851 (5): 620-8. doi:10.1016/j.bbalip.2015.01.011. PMC 4540326. PMID 25633344. Irvine, R. (1992). "Inositol lipids in cell ... 8 (5): 198-202. doi:10.1016/s0962-8924(98)01249-5. PMID 9695839. D'Angelo, G.; et al. (2007). "Glycosphingolipid synthesis ...
"Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with ... 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- ... The pedicels are hairless or sparsely hairy and have 3-8 bracts. It has 3 greenish-red to purple, oval to triangular sepals ...
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 ... 170 (11): 5354-8. doi:10.4049/jimmunol.170.11.5354. PMID 12759408. Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete ... recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via ...
Mukerjee N, McGinnis KM, Gnegy ME, Wang KK (August 2001). "Caspase-mediated calcineurin activation contributes to IL-2 release ...
... caspase cleavage and nuclear fragmentation". Cell Death Differ. 9 (11): 1172-84. doi:10.1038/sj.cdd.4401094. PMID 12404116. ... 446 (1): 6-8. doi:10.1016/S0014-5793(99)00173-8. PMID 10100603. Soldani C, Scovassi AI (2003). "Poly(ADP-ribose) polymerase-1 ... 7 (4): 321-8. doi:10.1023/A:1016119328968. PMID 12101391. S2CID 23227862. Bouchard VJ, Rouleau M, Poirier GG (2003). "PARP-1, a ... 428 (6982): 522-8. Bibcode:2004Natur.428..522D. doi:10.1038/nature02379. PMC 2665288. PMID 15057823. Liu Y, Snow BE, Kickhoefer ...
... an investigational drug targeting caspases and caspase-like proteases: the clinical trials in sight and recent anti- ... May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute ... The substance acts as a pan-caspase inhibitor and has antiapoptotic and antiinflammatory effects. It was developed for the ... November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal ...
It is known as the initiating caspase for the apoptotic cascade. Caspase-8 acts on procaspases-3, 4, 6, 7, 9 and 10, in ... Citations for Human Caspase-8 Antibody. R&D Systems personnel manually curate a database that contains references using R&D ... Detection of Human Caspase8 by Western Blot. Western blot shows lysates of Jurkat human acute T cell leukemia cell line ... Background: Caspase-8. Caspase-8 (Cysteine-aspartic acid protease 8/Casp8; also MCH5 and FLICA) is a 28 kDa member of the ...
Intra- and interdimeric caspase-8 self-cleavage controls strength and timing of CD95-induced apoptosis. ... Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by ... We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an ... Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by ...
This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. ... Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. ... FLICA Caspase-8 Reagent (FAM-LETD-FMK), 1 vial, #656. * 10X ... FAM-FLICA® Caspase-8 Assay Kit. from ImmunoChemistry Technologies Product Manual Safety Data Sheet 11 Citations ... Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. This in vitro assay employs the fluorescent inhibitor probe FAM- ...
The DN caspase-9 specifically blocked the cleavage of pro-caspase-9 in pcWNV-Cp-DJY and pcWNV-CpWT cotransfected cell lysates ... Caspase-3 (Pharmingen, San Diego, CA), caspase-8 (FADD-like interleukin-1 beta-converting enzyme) and caspase-9-like Mch6 (MBL ... The cell lysates (100 μg/100 μl protein) were incubated with specific substrate Ac-DEVD-AMC for caspase-3, IETD-pNA for caspase ... Furthermore, to confirm that this apoptosis-induction pathway is through caspase-9, a domant negative (DN) caspase-9 construct ...
Knockout of caspase-7 gene improves the expression of recombinant protein in CHO cell line through the cell cycle arrest in G2/ ... Knockout of caspase-7 gene improves the expression of recombinant protein in CHO cell line through the cell cycle arrest in G2/ ... b) Caspase 8 activity in cell lysates of control (uninduced) and apoptosis-induced (induced) 892-7 and parental cells (**p , . ... Knockout of the caspase 8-associated protein 2 gene improves recombinant protein expression in HEK293 cells through up- ...
Association of caspase 8 promoter variants and haplotypes with the risk of breast cancer and its molecular profile in an ... Dive into the research topics of Association of caspase 8 promoter variants and haplotypes with the risk of breast cancer and ...
Return to Article Details The Effect of Caspase-8 as an Apoptotic Marker in Relation to COVID-19 Patients Severity Download ...
CASP8base: Mutation registry for Caspase 8 deficiency Lunds Universitet. Department of Experimental Medical Science ...
In the Caspase 8 Formulation oocyte could be the CDK1/Cyclin B complex. These follicle/oocyte proteins are vitally crucial. ... In the Caspase 8 Formulation oocyte could be the CDK1/Cyclin B complex. These follicle/oocyte proteins. ack1 inhibitor ... In the Caspase 8 Formulation oocyte could be the CDK1/Cyclin B complex. These follicle/oocyte proteins are vitally crucial. ... HomeIn the Caspase 8 Formulation oocyte could be the CDK1/Cyclin B complex. These follicle/oocyte proteinsIn the Caspase 8 ...
Antibody Details for caspase 8 Ab-1. WBI Title. Validation Status. Band Result. Date. Dilution. ...
caspase 8. multiple interactions. ISO. N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide affects the localization of and ... NCBI chr 8:4,968,856...4,989,325 Ensembl chr 8:4,968,842...4,988,732 G. Casp8. ... N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide. go back to main search page ... N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide results in decreased activity of CSNK1A1 protein. CTD. PMID:15520213. NCBI ...
Cited in 8 publications. View Rabbit Polyclonal anti-bcl-x Antibody [Unconjugated] (AF800). Validated Applications: WB, Simple ... Showing Publications 1 - 8 of 8.. Publications using AF800. Applications. Species. M Kimsa-Dude, A Synowiec-W, A Krawczyk, A ... Publications for bcl-x Antibody (AF800)(8). We have publications tested in 2 confirmed species: Human, Mouse.. We have ... 1 month, 2 to 8 °C under sterile conditions after reconstitution.. *6 months, -20 to -70 °C under sterile conditions after ...
... pretreatment with IL-1β induces increased caspase-3 activity but keeps cells alive. We now report that IL-1β and TNFα ... pretreatment with IL-1β induces increased caspase-3 activity but keeps cells alive. We now report that IL-1β and TNFα ... sensitized to FasL-induced caspase-3 activation and cell death. However, when TNFα action was blocked by neutralizing ... sensitized to FasL-induced caspase-3 activation and cell death. However, when TNFα action was blocked by neutralizing ...
... caspase 8-dependent activation of the inflammasome. We treated 2 IL10R-deficient patients with severe and treatment-refractory ... Caspase 8/metabolism; Cells, Cultured; Child, Preschool; Colitis/genetics; Colitis/immunology*; Colitis/metabolism; Gene ...
B) Caspase-3 and caspase-8 colorimetric assay kits were used to determine the activities of caspase-3 and -8 in each group. (C ... the expression of caspase-3 is negatively regulated by Bcl-2, caspase-3 subsequently hydrolyzes Bcl-2 and the hydrolyzed ... 4B, the caspase-3 and -8 activities in the I/R group was significantly increased when compared with that observed in the sham ... The caspase reaction was initiated by adding 200 μM N-acetyl-Asp-Glu-Val-Asp-7-amino-4-trifluoromethylcoumarine and incubated ...
Regulation of Proinflammatory Cytokine Responses by a Caspase-8-N4BP1 Axis. GRAJALES-REYES, GARY E. ...
Caspase-dependent apoptosis of the HCT-8 epithelial cell line induced by the parasite Giardia intestinalis. FEMS Immunol Med ...
The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) ... performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine ...
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. N Kayagaki, IB Stowe, BL Lee, K ORourke, K Anderson ... ASC-and caspase-8-dependent apoptotic pathway diverges from the NLRC4 inflammasome in macrophages. BL Lee, KM Mirrashidi, IB ...
Title: BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8- ... BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated ... BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated ...
Western-blot analysis showed an activation of caspase-8, caspase-3, Bid and Bax, and a decrease of Bcl-2, in JB6 cells treated ... In conclusion, we have determined that caspase-8/Bid signaling may play a major role in TiO2-induced apoptosis and that ... Titanium dioxide nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid pathway. ...
The researchers now also describe how the gene, caspase 8, works.. The findings, published in the January 5 issue of the ... January 8, 2006. By DeryaIn Alzheimers, Biotechnology, Brain, nanoparticles, Nanotech, Nanotechnology, Neuroscience1 Comment ... By DeryaIn *Commentaries, Bioengineering, Biotech, Biotechnology, DNA, Genes, Genetic engineering, Genome, synthetic biology8 ...
Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells. ... PLoS One 2013;8:e61271. View abstract.. *Lee MH, Kwak JH, Jeon G, Lee JW, Seo JH, Lee HS, Lee JH. Red ginseng relieves the ... Arch Androl 1982;8:261-3. View abstract.. *Salvati G, Genovesi G, Marcellini L, Paolini P, De Nuccio I, Pepe M, Re M. Effects ... 2021:1-8. English. View abstract.. *Ban MS, Kim Y, Lee S, et al. Pharmacokinetics of Ginsenoside Compound K From a Compound K ...
We improved recombinant protein expression from HEK293 cells by knocking out the Caspase 8-associated protein 2 gene, which was ... 8:30 a.m.. to 5 p.m.. ET, Monday - Friday Email: [email protected] Phone: +1-800-860-8747 TTY: +711 Chat. Live Chat ...
Smac mimetic bypasses apoptosis resistance in FADD- or caspase-8-deficient cells by priming for tumor necrosis factor α-induced ... Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: Implications for Smac-dependent anti-apoptotic ... The Drosophila inhibitor of apoptosis D-IAP1 suppresses cell death induced by the caspase drICE ... Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf ...
... caspase-3; caspase-8; cell proliferation; cell viability; cytotoxicity; dose response; drug therapy; fluorescence; growth ... 8. A 2-year field trial reveals no significant effects of GM high-methionine soybean on the rhizosphere bacterial communities ... 7,8-Dihydroxyflavone attenuates the virulence of Staphylococcus aureus by inhibiting alpha-hemolysin ... 8-Hydroxyquinoline a natural chelating agent from Streptomyces spp. inhibits A549 lung cancer cell lines via BCL2/STAT3 ...
One strategy under investigation is the genetic engineering of p16 so that it induces caspase 8 and promotes the death of p16- ... Bernard welcomed members to the open session of the 131st NACA meeting and called the meeting to order at 8:00 a.m. on ... For those costing $500,000 or more, the paylines are 8 percent for established investigators, 11 percent for new investigators ...
  • Detects human Caspase-8 precursor in Western blots and a 42 kDa doublet generated during apoptosis. (rndsystems.com)
  • Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). (ebi.ac.uk)
  • The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis. (ebi.ac.uk)
  • Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. (cdc.gov)
  • We observed that the WNV-Cp protein is a pathogenic protein, which drives apoptosis in vitro through the mitochodrial/caspase-9 pathway. (cdc.gov)
  • Caspases play important roles in apoptosis and inflammation. (immunochemistry.com)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • Peng, Z;Gillissen, B;Richter, A;Sinnberg, T;Schlaak, MS;Eberle, J. Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins . (immunochemistry.com)
  • The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. (proteopedia.org)
  • Titanium dioxide nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid pathway. (cdc.gov)
  • In conclusion, we have determined that caspase-8/Bid signaling may play a major role in TiO2-induced apoptosis and that mitochondrial and lysosomal injury may also be involved. (cdc.gov)
  • BECLIN-1-Mediated Autophagy Suppresses Silica Nanoparticle-Induced Testicular Toxicity via the Inhibition of Caspase 8-Mediated Cell Apoptosis in Leydig Cells. (nih.gov)
  • Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES . (nih.gov)
  • Metallic nickel nano- and fine particles induce JB6 cell apoptosis through a caspase-8/AIF mediated cytochrome c-independent pathway. (cdc.gov)
  • After 4 h treatment, the intracellular pool of Caspase-8 (an indicator of early apoptosis) was significantly higher in cells treated with 5000 nm particles compared to cells treated with same surface functionalized 50 - 200 nm particles (p (usda.gov)
  • Regulates Fas-mediated apoptosis in neurons by interfering with caspase-8 activation. (nih.gov)
  • In additional experiments, the team found that the NSAID inhibition of caspase was independent of COX enzymes. (nih.gov)
  • PVDF membrane was probed with 1 µg/mL of Human Caspase-8 Monoclonal Antibody (Catalog # MAB704), followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF007 ). (rndsystems.com)
  • For a caspase-9-specific test, 5 μg of pcWNV-Cp-DJY or pcWNV-CpWT was cotransfected with a dominant negative caspase-9 (DN caspase-9) construct, and cleavage of procaspase-9 protein was determined by Western blot analysis with antihuman caspase-9 antibody (MBL, Nagoya, Japan). (cdc.gov)
  • The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. (immunochemistry.com)
  • The treatment of hepatocytes with the BMDM supernatant, which contains both IL-1β and TNFα, sensitized to FasL-induced caspase-3 activation and cell death. (frontiersin.org)
  • Western-blot analysis showed an activation of caspase-8, caspase-3, Bid and Bax, and a decrease of Bcl-2, in JB6 cells treated with TiO2 particles. (cdc.gov)
  • Activation of caspase-3, caspase-9, and caspase-8 was investigated using western blot analysis at the end of the propofol treatment. (nih.gov)
  • In the mechanistic studies, effects of propofol, amyloid-β protein (Aβ), and GABA receptor antagonist flumazenil on caspase-3 activation and opening of the mitochondrial permeability transition pore were assessed in H4 human neuroglioma and mouse neuroblastoma cells by western blot analysis and flow cytometry. (nih.gov)
  • Here we showed that the propofol treatment improved cognitive function and attenuated brain caspase-3 and caspase-9 activation in both aged WT and AD Tg mice. (nih.gov)
  • Propofol attenuated Aβ-induced caspase-3 activation and opening of the mitochondrial permeability transition pore in the cells, and flumazenil inhibited the propofol's effects. (nih.gov)
  • These results suggested that propofol might improve cognitive function via attenuating the Aβ-induced mitochondria dysfunction and caspase activation, which explored the potential that anesthetic propofol could improve cognitive function in elderly and AD patients. (nih.gov)
  • 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)
  • The team first ranked the drugs by their ability to inhibit the activity of the caspase-4 enzyme. (nih.gov)
  • Human procaspase-8 alpha 4 is a 58 kDa (predicted), 496 amino acid (aa) protein and contains two N-terminal death domains plus a catalytic site that utilizes His334Gly335 plus Cys377. (rndsystems.com)
  • In addition, the present study indicated that treatment with GP suppressed the I/R-induced increase in the pro-apoptotic protein levels of Bax and cytochrome c and the activity of caspase-3/8, as well as the I/R-induced decrease in the levels of anti-apoptotic protein Bcl‑2. (spandidos-publications.com)
  • We improved recombinant protein expression from HEK293 cells by knocking out the Caspase 8-associated protein 2 gene, which was originally identified by siRNA screening. (nih.gov)
  • To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. (ebi.ac.uk)
  • In the Caspase 8 Formulation oocyte could be the CDK1/Cyclin B complex. (ack1inhibitor.com)
  • The adapter molecule FADD recruits caspase-8 to the activated receptor. (proteopedia.org)
  • 8. Aberrant methylation and silencing of ARHI, an imprinted tumor suppressor gene in which the function is lost in breast cancers. (nih.gov)
  • 14. Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma. (nih.gov)
  • It is known as the initiating caspase for the apoptotic cascade. (rndsystems.com)
  • DN caspase-9 (provided courtesy of Emad S. Alnmeri, Thomas Jefferson University, Philadelphia, PA) has been reported to inhibit the caspase cascade ( 5 ). (cdc.gov)
  • 9. Caspase-8 gene expression in neuroblastoma. (nih.gov)
  • 8. Altered transcriptional regulation of the insulin-like growth factor 2 gene in human hepatocellular carcinoma. (nih.gov)
  • Whereas TNFα preincubation leads to elevated levels of caspase-3 activity and cell death, pretreatment with IL-1β induces increased caspase-3 activity but keeps cells alive. (frontiersin.org)
  • Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. (immunochemistry.com)
  • Bulk Order Inquiry for FAM-FLICA® Caspase-8 Assay Kit ------- (please add any order requirements, including desired quantity, timing, etc. (immunochemistry.com)
  • The FLICA reagent FAM-LETD-FMK enters each cell and irreversibly binds to activated caspase-8. (immunochemistry.com)
  • The approach involves preparation in the patient's blood sample of plasma with a concentration of platelets higher than physiological after which its injection into pathological tissues[2,6-8]. (ack1inhibitor.com)
  • Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. (ebi.ac.uk)
  • We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. (ebi.ac.uk)
  • The team focused on another group of enzymes called caspases that are known to be important for inflammation and thus might also serve as useful therapeutic targets. (nih.gov)
  • Furthermore, GP exhibits a therapeutic effect on chronic hepatic injury, fibrosis, as well as fatty liver disease, which were induced by a high fat, high cholesterol diet and alcohol in mice ( 5 , 8 ). (spandidos-publications.com)
  • Propofol was administrated to the WT and AD Tg mice once a week for 8 or 12 weeks, respectively. (nih.gov)
  • Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. (ebi.ac.uk)
  • This newly discovered mechanism of NSAID activity suggests future studies into how these drugs affect caspases in the human body. (nih.gov)
  • Association with another p18/p10 heterodimer generates active caspase-8. (rndsystems.com)
  • Caspases are known to play a role in inflammatory diseases such as rheumatoid arthritis and heart disease. (nih.gov)
  • RD cells transfected with pcWNV-Cp-DJY or pcDNA3.1 plasmid DNA were processed for transmission electron microscope analysis as described ( 7 , 8 ). (cdc.gov)
  • In human cells, the caspases were inhibited by the same NSAIDs in the same rank order as in the high-throughput screen. (nih.gov)
  • A long pro-domain caspase that contains a death effector domain in its pro-domain region. (nih.gov)
  • Dr. Freeman, SACATM Chair, called the meeting to order at 8:30 a.m. (nih.gov)
  • Dr. Bernard welcomed members to the open session of the 131st NACA meeting and called the meeting to order at 8:00 a.m. on Wednesday, May 17, 2017. (nih.gov)
  • Aloe emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), which belongs to the anthraquinones as one of the class from quinone family of the polyketide group characterized by an amazing structural diversity of compounds, is a naturally occurring phenolic compound mainly found in Aloe , Rheum , and Rhamnus genera plants. (hindawi.com)