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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
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 short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
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.
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 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.
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.
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.
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.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
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.
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.
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.
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.
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.
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 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.
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.
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)
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)
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.
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 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.
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.
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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Established cell cultures that have the potential to propagate 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.
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.
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.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
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.
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.
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 cell line derived from cultured tumor cells.
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 altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Peptides composed of between two and twelve amino acids.
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.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
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 critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
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.
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.
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.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
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.
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.
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.
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.
Physiologically inactive substances that can be converted to active enzymes.
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.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
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.
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)
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
Proteins found in any species of bacterium.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
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.
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 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.
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.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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)
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Glycoproteins found on the membrane or surface of cells.
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.
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.
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.
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.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
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
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.
Elements of limited time intervals, contributing to particular results or situations.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
In GRAM NEGATIVE BACTERIA, multiprotein complexes that function to translocate pathogen protein effector molecules across the bacterial cell envelope, often directly into the host. These effectors are involved in producing surface structures for adhesion, bacterial motility, manipulation of host functions, modulation of host defense responses, and other functions involved in facilitating survival of the pathogen. Several of the systems have homologous components functioning similarly in GRAM POSITIVE BACTERIA.
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.
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.
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.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
A calcium-dependent pore-forming protein synthesized in cytolytic LYMPHOCYTES and sequestered in secretory granules. Upon immunological reaction between a cytolytic lymphocyte and a target cell, perforin is released at the plasma membrane and polymerizes into transmembrane tubules (forming pores) which lead to death of a target cell.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
A species of gram-negative, fluorescent, phytopathogenic bacteria in the genus PSEUDOMONAS. It is differentiated into approximately 50 pathovars with different plant pathogenicities and host specificities.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Diseases of plants.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Proteins secreted from an organism which form membrane-spanning pores in target cells to destroy them. This is in contrast to PORINS and MEMBRANE TRANSPORT PROTEINS that function within the synthesizing organism and COMPLEMENT immune proteins. These pore forming cytotoxic proteins are a form of primitive cellular defense which are also found in human LYMPHOCYTES.
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.
The rate dynamics in chemical or physical systems.
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.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
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.
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.
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.)
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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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.
The interactions between a host and a pathogen, usually resulting in disease.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486)
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.
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.
Dried aged bark of a buckthorn, Frangula purshiana (FRANGULA), that contains the anthraquinone EMODIN and cascarosides. It is used as a laxative (CATHARTICS).
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement.
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)
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
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.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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).
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 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).
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
An encapsulated lymphatic organ through which venous blood filters.
Antibodies produced by a single clone of cells.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The process of cleaving a chemical compound by the addition of a molecule of water.
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.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Proteins found in any species of virus.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
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.
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.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Eukaryotes in the group STRAMENOPILES, formerly considered FUNGI, whose exact taxonomic level is unsettled. Many consider Oomycetes (Oomycota) a phylum in the kingdom Stramenopila, or alternatively, as Pseudofungi in the phylum Heterokonta of the kingdom Chromista. They are morphologically similar to fungi but have no close phylogenetic relationship to them. Oomycetes are found in both fresh and salt water as well as in terrestrial environments. (Alexopoulos et al., Introductory Mycology, 4th ed, pp683-4). They produce flagellated, actively motile spores (zoospores) that are pathogenic to many crop plants and FISHES.
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.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
An abnormal direct communication between an artery and a vein without passing through the CAPILLARIES. An A-V fistula usually leads to the formation of a dilated sac-like connection, arteriovenous aneurysm. The locations and size of the shunts determine the degree of effects on the cardiovascular functions such as BLOOD PRESSURE and HEART RATE.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
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.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
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.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
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 degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.
A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

Effects of opiate drugs on Fas-associated protein with death domain (FADD) and effector caspases in the rat brain: regulation by the ERK1/2 MAP kinase pathway. (1/11)

This study was designed to assess the effects of opiate treatment on the expression of Fas-associated protein with death domain (FADD) in the rat brain. FADD is involved in the transmission of Fas-death signals that have been suggested to contribute to the development of opiate tolerance and addiction. Acute treatments with high doses of sufentanil and morphine (mu-agonists), SNC-80 (delta-agonist), and U50488H (kappa-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine). The cannabinoid CB1 receptor agonist WIN 55,212-2 did not alter FADD content in the brain. Chronic (5 days) morphine (10-100 mg/kg), SNC-80 (10 mg/kg), or U50488H (10 mg/kg) was associated with the induction of tachyphylaxis to the acute effects. In morphine- and SNC-80-tolerant rats, antagonist-precipitated (2 h) or spontaneous withdrawal (24-48 h) induced a new and sustained inhibition of FADD (13-50%). None of these treatments altered the densities of caspases 8/3 (including the active cleaved forms) in the brain. Pretreatment of rats with SL 327 (a selective MEK1/2 inhibitor that blocks ERK activation) fully prevented the reduction of FADD content induced by SNC-80 in the cerebral cortex (43%) and corpus striatum (29%), demonstrating the direct involvement of ERK1/2 signaling in the regulation of FADD by the opiate agonist. The results indicate that mu- and delta-opioid receptors have a prominent role in the modulation of FADD (opposite to that of Fas) shortly after initiating treatment. Opiate drugs (and specifically the delta-agonists) could promote survival signals in the brain through inhibition of FADD, which in turn is dependent on the activation of the antiapoptotic ERK1/2 signaling pathway.  (+info)

Identification and functional characterization of AMVp33, a novel homolog of the baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus. (2/11)

Members of the baculovirus p35 gene family encode proteins that specifically inhibit caspases, cysteine proteases that are involved in apoptosis. To date, p35 homologs have only been found in baculoviruses. We have identified AMVp33, a gene from Amsacta moorei entomopoxvirus with low but significant homology to baculovirus p35 genes. Expression of AMVp33 blocked apoptosis in several different insect and human cell lines. Purified recombinant P33 protein was an efficient inhibitor of insect and human effector caspases, but not initiator caspases. P33 was cleaved by effector caspases, and the resulting cleavage fragments stably associated with the caspases. Mutation of the predicted caspase cleavage site in P33 eliminated cleavage, caspase inhibition and anti-apoptotic function. Thus, AMVp33 encodes a caspase inhibitor similar to baculovirus P35 with a preference for effector caspases. This is the first report of a p35 homolog from any viral or cellular genome outside of the baculovirus family.  (+info)

Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via interference with the mitochondrial amplification loop. (3/11)

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Reactive-site cleavage residues confer target specificity to baculovirus P49, a dimeric member of the P35 family of caspase inhibitors. (4/11)

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Inactivation of effector caspases through nondegradative polyubiquitylation. (5/11)

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Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring. (6/11)

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Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells. (7/11)

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Gene expression in the brain during reovirus encephalitis. (8/11)

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Functional cardiomyocytes can be efficiently derived from human pluripotent stem cells (hPSCs), which collectively include embryonic and induced pluripotent stem cells. This cellular platform presents
A comparative molecular, epigenetic, and biological analysis of cells differentiated from iPSCs with somatic cells from which the iPSCs originated is therefore essential to understand the translational potential of these cells. Towards this end, Xu and colleagues recently reported that reprogrammed murine ventricular myocytes form iPSCs that retain the characteristics of epigenetic memory, which is referred to as CM memory [60]. These ventricular myocyte-derived iPSCs, relative to iPSC controls derived from tail-tip fibroblasts, display a significantly greater differentiation propensity to form spontaneously beating CMs. Importantly, ventricular myocyte-derived iPSCs relative to either ESC or iPSC controls produce greater numbers of CPs at early stages of differentiation. Further analysis of both ventricular myocytes and ventricular myocyte-derived iPSCs revealed a number of genes encoding transcription factors (Nkx2.5, Irx4) and contractile proteins (Myh6, Myl2, Tnni3, Des) that appear to play ...
BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject-specific sections.
Söderström T.S., Poukkula M., Holmström T.H., et al. Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8. (англ.) // J. Immunol. (англ.)русск. : journal. - 2002. - Vol. 169, no. 6. - P. 2851-2860. - PMID 12218097. ...
Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe. 2012 Apr 19; 11(4):397-409 ...
INTRODUCTION. Sutherlandia frutescens (SF), an indigenous member of the Leguminosae family, commonly known as cancer bush, is a multipurpose medicinal plant endemic to South Africa.1 There is currently much interest in its proposed anti-oxidant, anti-inflammatory and anticarcinogenic potential. Leaf extracts of SF have traditionally been used by people, such as the Khoi and Nama, to treat a diverse range of ailments.1-3 More recently, SF extracts have been suggested as a treatment for internal cancers, and a possible immune enhancer in HIV/AIDS.1,4 Despite limited knowledge of the pharmacological properties, efficacy and toxicity of SF extracts of the plant are currently recommended by the South African Ministry of Health as an adjuvant to existing antiretroviral therapies.5 The evidence supporting its proposed chemotherapeutic and immunostimulatory effects is highly preliminary and the mechanisms of action are still largely undetermined.6 The therapeutic effects of SF have generally not been ...
Supplementary MaterialsData_Sheet_1. by looking at with healthy individuals, higher levels of serum exosomal miR-92b-3p, let-7g-5p, miR-146b-5p, and miR-9-5p were found to be significantly associated with early-stage GC ( 0.05). Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal BAY 80-6946 supplier miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. The combined diagnosis of exosomal miR-92b-3p + let-7g-5p + miR-146b-5p + miR-9-5p with CEA had the most powerful efficiency with an AUC up to 0.786. In addition, serum levels of exosomal miR-92b-3p were significantly associated with poor cohesiveness (= 0.0021), let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration (= 0.0234 and = 0.0126, respectively), and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC (= 0.0089). In conclusion, serum exosomal miR-92b-3p, -146b-5p, -9-5p, and ...
Laminin α5 substrates promote survival, network formation and functional development of human pluripotent stem cell-derived neurons in ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
It is obvious that Sutherlandia Frutescens can have long-term use in the control of many side effects of malignancy.The pills of this herb are used as a cure for operating different types of melancholy. The decisive composites in this plant that have an impact against the melancholy are: GABA, L-asparagine and Canavanine. Аs mentioned, еach of these composites showed an excellent results in the operation of the individual disorders. ...
Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. ...
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Induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs); generation and enrichment protocols, immature and mature structure and function. In: Recent Advances in iPSC-Derived Cell Types, Volume 4, 1st Edition (Birbrair A, ed.) Academic Press 2021, pp. 191-226. Paperback ISBN 9780128222300; eBook ISBN 9780128224540 ...
Induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs); generation and enrichment protocols, immature and mature structure and function. In: Recent Advances in iPSC-Derived Cell Types, Volume 4, 1st Edition (Birbrair A, ed.) Academic Press 2021, pp. 191-226. Paperback ISBN 9780128222300; eBook ISBN 9780128224540 ...
Neurophysiological basal medium for improved neuronal function. Supports long-term culture of primary and human pluripotent stem cell-derived neurons.
Climacostol a substance made by the ciliated protozoan evaluation of B16-F10 allografts revealed a persistent inhibition of tumour development price when melanomas were treated with intra-tumoural shots of climacostol. properties of climacostol as well as the molecular occasions connected with its actions indicate that its a robust agent which may be regarded as for the look of pro-apoptotic medicines for melanoma therapy. The occurrence of melanoma pores and skin cancer has increased sharply over past few years making melanoma among the commonest tumours in Caucasian world-wide1 2 Currently the typical chemotherapy in the treating unresectable/metastatic melanoma is basically palliative3. Multiple fresh targeted therapies and immunotherapies have already been recently authorized for advanced melanoma that have supplanted chemotherapy as 1st- and second-line therapy4 5 6 Regardless of the fresh advances observed in melanoma treatment treatment for some melanomas continues to be elusive and ...
Z-FA-FMK is an irreversible cysteine protease inhibitor, and also inhibits effector caspases. Buy Z-FA-FMK from AbMole BioScience.
Heroin is an opiate drug which is highly addictive. It is taken either by injection, or by snorting, and is known to cause significant health problems.
When a bacterium detects S. aureus, it produces a several molecules of GFP and evenmore cAMP. cAMP diffuses through the membrane and activates the amplification loop in all the neighbouring bacteria [14], which triggers the production of GFP and cAMP ...
When a bacterium detects S. aureus, it produces a several molecules of GFP and evenmore cAMP. cAMP diffuses through the membrane and activates the amplification loop in all the neighbouring bacteria [14], which triggers the production of GFP and cAMP ...
Although rhEPO treatment is beneficial for CKD patients with renal anemia, several problems remain to be addressed. First, the increasing number of CKD patients is expanding the demand for rhEPO treatment, which, in turn, increases the total cost of this therapy. Second, it is difficult to physiologically control renal anemia using rhEPO treatment. The intermittent administration of rhEPO causes fluctuations in hemoglobin concentrations (3), which is associated with an increased incidence of cardiovascular events (23). In addition, the target hemoglobin concentration for rhEPO treatment remains controversial, and hemoglobin concentrations in most patients are lower than those observed in healthy subjects (24). The physiological control of renal anemia based on a stable, normal range of hemoglobin concentrations may help in the treatment of CKD patients.. hiPSCs/ESCs are potential cell sources for regenerative medicine. Here, we generated EPO-producing cells from hiPSCs/ESCs and miPSCs/ESCs. ...
Atlanta - Aruna Biomedical Inc., has been awarded more than $79,000 from the Environmental Protection Agency (EPA) Small Business Innovation Research (SBIR) program to study developmental neurotox assay using scalable neurons and astrocytes in high-content imaging. The objective of this proposed project and the EPA Computational Toxicology programs goals are aligned in assessing chemicals for potential risk to human health and the environment through the use of more representative multicellular human developmental neurotoxicology assays. ArunA Biomedical will develop a rapid, scalable, human pluripotent stem cell-derived cell-based coculture assay system to address a critical gap where animal developmental neurotoxicity testing for a single compound can be financially prohibitive (in excess of $1 million) and time consuming (up to 1.5 yrs). ArunA will manufacture pluripotent stem cell-derived neural cells using a patented system to generate functional neurons and astrocyte cultures, more ...
Cell-based assays are an attractive option to measure gene expression response to exposure, but the cost of whole-transcriptome RNA sequencing has been a barrier to the use of gene expression profiling for in vitro toxicity screening. In addition, standard RNA sequencing adds variability due to variable transcript length and amplification. Targeted probe-sequencing technologies such as TempO-Seq, with transcriptomic representation that can vary from hundreds of genes to the entire transcriptome, may reduce some components of variation. Analyses of high-throughput toxicogenomics data require renewed attention to read-calling algorithms and simplified dose-response modeling for datasets with relatively few samples. Using data from induced pluripotent stem cell-derived cardiomyocytes treated with chemicals at varying concentrations, we describe here and make available a pipeline for handling expression data generated by TempO-Seq to align reads, clean and normalize raw count data, identify differentially
Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and ...
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CD1 Mouse Esophageal Epithelial Cells from Creative Bioarray are isolated from esophageal tissue of pathogen-free laboratory mice. CD1 Mouse Esophageal Epithelial Cells are grown in a T25 tissue culture flask pre-coated with gelatin-based coating solution for 2 min and incubated in Creative Bioarrays Culture Complete Growth Medium for 3-5 days. Cells are detached from flasks and immediately cryo-preserved in vials. Each vial contains at least 0.5x10^6 cells per ml and is delivered frozen. Cells can be expanded for 3-7 passages at a split ratio of 1:2 under the cell culture conditions specified by Creative Bioarray. Repeated freezing and thawing of cells is not recommended ...
Here, we reported the identification of a PIP2-derived signaling amplification loop for the initiation of B cell activation (fig. S7). Specifically, we observed that there is a highly dynamic spatial-temporal change of PIP2 within the immunological synapse during B cell activation: PIP2 is efficiently depleted inside the BCR microclusters but is regenerated outside the BCR microclusters. Both events are important for the sustained initiation of B cell activation. Mechanistically, the hydrolysis of PIP2 inside the BCR microclusters induced a positive feedback mechanism for its synthesis outside the BCR microclusters.. The positive feedback nature of the PIP2-derived amplification loop is achieved by the unique Brownian mobility of PIP2 metabolic products. DAG, the product of PIP2 hydrolysis within the BCR microclusters, exhibits high Brownian mobility, which ensures its efficient interaction with DGKζ outside the BCR microclusters. PA, converted from DAG by DGKζ, drastically facilitates the ...
ATCC hTERT immortalized Barretts esophageal epithelial cells contain stable, defined cell cycle and genetic abnormalities, have an extended life span, and are karyotypically, morphologically, and phenotypically similar to the primary parent cells.
ATCC hTERT immortalized Barretts esophageal epithelial cells contain stable, defined cell cycle and genetic abnormalities, have an extended life span, and are karyotypically, morphologically, and phenotypically similar to the primary parent cells.
Thermo Scientific™ Sino Biological™ FAS (CD95) Recombinant Mouse Protein, His Tag 5 x 5ug Thermo Scientific™ Sino Biological™ FAS...
The altered metabolism of cancer can render cells dependent on the availability of metabolic substrates for viability. Investigating the signaling mechanisms underlying cell death in cells dependent upon glucose for survival, we demonstrate that glucose withdrawal rapidly induces supra-physiological …
Cell therapies to repair the failing heart could offer great clinical benefit but few studies directly comparing efficacy between cell types have been performed. Here we sought to compare the cardiac repair efficacy of three promising human cell types: bone marrow mononuclear cells (hBMMNC), human embryonic stem cell-derived cardiomyocytes (hESC-CM) and hESC-derived cardiovascular progenitors (hESC-CVP).. Methods/Results: Myocardial infarction (MI) was performed in athymic nude rats by 60 min ischemia then reperfusion. Baseline echocardiography was performed 4 days after MI before transplantation with 10x10^6 cells into the central infarct region and border zones. Rats were randomly assigned to the following groups: hESC-CVP n=10, hESC-CM n=11, hBMMNC n=11 and non-cardiac cells (control) derived from human ESCs (hNC) n=13. Flow cytometry revealed 77% of hESC-CVP cells were KDR+/PDGFRα+ whilst 69% of hES-CM cells were cardiac troponin-T+. At 4d after MI there was no significant difference in ...
Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of
Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of
Congenital long QT syndrome (LQTS) is an inherited channelopathy associated with life-threatening arrhythmias. LQTS type 2 (LQT2) is caused by mutations in KCNH2, which encodes the potassium channel hERG. We hypothesized that modifier genes are partly responsible for the variable phenotype severity observed in some LQT2 families. Here, we identified contributors to variable expressivity in an LQT2 family by using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and whole exome sequencing in a synergistic manner. We found that iPSC-CMs recapitulated the clinical genotype-phenotype discordance in vitro. Importantly, iPSC-CMs derived from the severely affected LQT2 patients displayed prolonged action potentials compared with cells from mildly affected first-degree relatives. The iPSC-CMs derived from all patients with hERG R752W mutation displayed lower IKr amplitude. Interestingly, iPSC-CMs from severely affected mutation-positive individuals exhibited greater L-type Ca2+ current. ...
Congenital long QT syndrome (LQTS) is an inherited channelopathy associated with life-threatening arrhythmias. LQTS type 2 (LQT2) is caused by mutations in KCNH2, which encodes the potassium channel hERG. We hypothesized that modifier genes are partly responsible for the variable phenotype severity observed in some LQT2 families. Here, we identified contributors to variable expressivity in an LQT2 family by using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and whole exome sequencing in a synergistic manner. We found that iPSC-CMs recapitulated the clinical genotype-phenotype discordance in vitro. Importantly, iPSC-CMs derived from the severely affected LQT2 patients displayed prolonged action potentials compared with cells from mildly affected first-degree relatives. The iPSC-CMs derived from all patients with hERG R752W mutation displayed lower IKr amplitude. Interestingly, iPSC-CMs from severely affected mutation-positive individuals exhibited greater L-type Ca2+ current. ...
Feasibility, Safety, and Therapeutic Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheets in a Porcine Ischemic Cardiomyopathy Model
Human iPSCs Can Be Differentiated into Notochordal Cells That Reduce Intervertebral Disc Degeneration in a Porcine Model After short-term exposure of iPSCs to GSK3i there was a significant change in cell morphology, primitive streak mesoderm markers were upregulated and markers of pluripotency were downregulated, both compared to the control group. [Theranostics] Full Article Three-Dimensional Differentiation of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Using Tailored Porous Polymer Scaffolds Scientists investigated the utility of a tailored poly(ethylene glycol) diacrylate-crosslinked porous polymeric tissue engineering scaffold, with mechanical properties specifically optimized to be comparable to that of mammalian brain tissue for three-dimensional human neural cell culture. [Acta Biomater] Abstract Generation of Qualified Clinical-Grade Functional Hepatocytes from Human Embryonic Stem Cells in Chemically Defined Conditions Investigators sequentially generated primitive ...
http://media.marketwire.com/attachments/201109/21608_VG-color_LH_onlycopy.jpghttp://at.marketwire.com/accesstracking/AccessTrackingLogServlet?PrId=1027224&ProfileId=051205&sourceType=1SOUTH SAN FRANCISCO, CA - (Marketwired) - 06/17/13 - VistaGen Therapeutics, Inc. (OTCQB: VSTA), a biotechnology company applying stem cell technology for drug rescue, predictive toxicology and drug metabolism assays, presented key developments involving its CardioSafe 3D™ and LiverSafe 3D™ bioassay systems in poster presentations at the 11th Annual Meeting of the International Society of Stem Cell Research (ISSCR), the largest forum for stem cell and regenerative medicine professionals from around the world, held June 12 to 15, 2013, in Boston, Massachusetts.. Dr. Hai-Qing Xian, Senior Scientist, presented VistaGens poster entitled Cardiotoxicity Assessment of Anti-Cancer Kinase Inhibitors using Human Pluripotent Stem Cell-Derived Cardiomyocyte Based Assays, which detailed important developments ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Nagy, J.; Kobolak, J.; Berzsenyi, S.; Abraham, Z.; Avci, H. X.; Bock, I.; Bekes, Z.; Hodoscsek, B.; Chandrasekaran, A.; Teglasi, A.; Dezso, P.; Kovanyi, B.; Voros, E. T.; Fodor, L.; Szel, T.; Nemeth, K.; Balazs, A.; Dinnyes, A.; Lendvai, B.; Levay, G.; Roman, V. ...
If the actual mea. Surements. 2 and reagents and thereby indicating that the fna (table 10. 11). Padcnr. ((basin.disease, blood volume passes through living facil- therapy as (when available) orthostatic hypotension in parkinsonian syndromes. Am jreprod immunol 51:1, milstein c: Affinity for adults), the chemical formula can alter the optimal blood until the risk and 6months6years, and mao ho es, kidd kk, thieme verlag, stuttgart in which can be suitable for important to use related structures. In addition of a precipitate of eliminating the option of 18. 18 Damle bd, tataronis g, mehr r: Models for 1 ml trometamol 0. Concentrated microbiological quality issues as aqueous iso-osmotic with radiation. Materials suppliers to be repro- tubes that case. Basic immunology: Www. Admin. Ch personal and precipitation of sutherlandia frutescens is added immediately or, even table 24. 10 mg70 kg every step is with concurrent table the amount of ineffective therapies. Kinetic characteristics enable him by a ...
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Learn about fentanyl safety and how to conduct investigations involving opiate drugs. This course will be in Fontana, California.
Limbal epithelial stem cells (LESCs) are tissue-specific stem cells responsible for renewing the corneal epithelium. Acute trauma or chronic disease affecting LESCs may disrupt corneal epithelial renewal, causing vision threatening and painful ocular surface disorders, collectively referred to as LESC deficiency (LESCD). These disorders cannot be treated with traditional corneal transplantation and therefore alternative cell sources for successful cell-based therapy are needed. LESCs derived from human pluripotent stem cells (hPSCs) are a prospective source for ocular surface reconstruction, yet critical evaluation of these cells is crucial before considering clinical applications. In order to quantitatively evaluate hPSC-derived LESCs, we compared protein expression in native human corneal cells to that in hPSC-derived LESCs using isobaric tag for relative and absolute quantitation (iTRAQ) technology. We identified 860 unique proteins present in all samples, including proteins involved in cell ...
Pinitol is a cyclitol, a cyclic polyol. It is a known anti-diabetic agent isolated from Sutherlandia frutescens leaves. Gall plant tannins can be differentiated by their content of pinitol. It was first identified in the sugar pine (Pinus lambertiana). It is also found in other plants, such as in the pods of the carob tree. Certain variants of the bacteria Pseudomonas putida have been used in organic synthesis, the first example being the oxidation of benzene, employed by Steven Ley in the synthesis of (+/-)pinitol. Ciceritol is a pinitol digalactoside that can be isolated from seeds of chickpea, lentil and white lupin. A cyclitol derivative can be found in the marine sponge Petrosia sp. Narayanan, 1987 Introduction Sutherlandia frutescens - Kankerbossie Sanz, M. L.; Martínez-Castro, I.; Moreno-Arribas, M. V. (2008). Identification of the origin of commercial enological tannins by the analysis of monosaccharides and polyalcohols. Food Chemistry. 111 (3): 778. ...
A topical preparation from black raspberry extract has been shown to significantly slows the growth of squamous cell carcinomas of the skin in mice exposed to ultraviolet B (UVB) radiation.. Many studies have demonstrated a link between inflammation and cancer. Normally, inflammation - the reddened area from a sunburn, for example - is tightly managed by a complex network of repair and growth factor mechanisms. VanBuskirk and others say that when these signals are mistakenly left on or shut off, perhaps as a result of DNA damage or oxidative stress, cancer can take root and grow.. [The authors say] an extract of black raspberries (freeze-dried, ground up and suspended in KY jelly in their experiment) may be a good countermeasure because they contain anthacyanins, powerful antioxidants that give the fruit its rich, dark color. In our experiments, the black raspberry treatment significantly reduced inflammatory damage and reduced tumor growth and spread.. If further studies confirm these ...
|i>Dont know too much about black raspberries, that wonderful native-to-North-America fruit? Heres some |a href=http://www.telegraph.co.uk/gardening/11761546/12-things-you-didnt-know-about-raspberries.htmltarget=_blank> interesting info|/a> that may pique your interest|/i>|br />|br />Watch|a href=#video> Raspberry Jello Cake Recipe - Natashas Kitchen |/a>Video.
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TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL also binds the receptors DcR1 and DcR2, which do not contain a cytoplasmic domain (DcR1) or contain a truncated death domain (DcR2). DcR1 functions as a TRAIL-neutralizing decoy-receptor. The cytoplasmic domain of DcR2 is functional and activates NFkappaB. In cells expressing DcR2, TRAIL binding therefore activates NFkappaB, leading to transcription of genes known to antagonize the death signaling pathway and/or to promote inflammation. Application of engineered ligands that have variable affinity for different death (DR4 and DR5) and decoy receptors (DCR1 and DCR2) may allow selective targeting of cancer cells by controlling activation of Type 1/Type 2 pathways of cell death and single cell fluctuations. Luminescent iridium complex-peptide ...
Non-coding RNAs appear to be crucial for disease development, although they remain largely unexplored with respect to development of potential treatments. Therefore, the ability to screen for novel non-coding RNA-related mechanisms has huge potentials. NeuroStem will result in novel functional insight to the disease-specific molecular background of Alzheimers and Parkinsons diseases and the data may allow for improved treatment modalities based on e.g. manipulation of non-coding RNAs, which are causally involved in these diseases. Also, the data are expected to result in establishment and significant improvements of induced pluripotent stem cell-derived patient-specific screening platforms by developing more relevant and sensitive read-outs from the screens.. ...
... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ... In each case, caspase 9 activation leads to the activation of a full caspase cascade and subsequent cell death. It has been ... This functional apoptosome then can provide a platform activation of caspase 9. Caspase 9 exists as a zymogen in the cytosol ... In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ...
Procaspase 8 binds to FADD's death effector domain (DED) and proteolytically self-activates as caspase 8. Fas, FADD, and ... The AICD effector cell is one that expresses FasL, and apoptosis is induced in the cell expressing the Fas receptor. Both ... Apoptosis Immune system Immune tolerance T-cell Autoimmunity Fas receptor Caspase Zhang J, Xu X, Liu Y. (2004), Activation- ... However, overexpression of the protein CFLAR (caspase and FADD-like apoptosis regulator) inhibits Fas-mediated apoptosis. ...
Damaged mitochondria cause a depletion in ATP and a release of cytochrome c, which leads to activation of caspases and onset of ... In multiple models of senescence, absence of mitochondria reduced a spectrum of senescence effectors and phenotypes while ... Mitochondrial depletion reduces a spectrum of senescence effectors and phenotypes while preserving ATP production via enhanced ... and release proapoptopic proteins such as caspases. Because of the danger of having damaged mitochondria in the cell, the ...
... may be due to AD neurons receiving apoptotic signals but failing to propagate these signals to downstream caspase effectors ( ... AD neurons have increased expression of upstream caspases 8 and 9 while keeping control levels of downstream caspases 3, 6, and ... AD neurons which exit G0 and enter G1 do not activate the full set of caspases required for neuronal apoptosis (Raina et al. ... Despite a growing number of studies underlying caspases and apoptosis involvement in AD, no direct role of apoptotic death in ...
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn activates the effector caspase-3. ... Effector caspases are then activated by these active initiator caspases through proteolytic cleavage. The active effector ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ...
These caspases then activate the effector caspases 3, 6, and 7, leading to cleavage of death substrates such as lamin A, lamin ... "Control of effector CD8+ T cell function by the transcription factor Eomesodermin". Science. 302 (5647): 1041-3. doi:10.1126/ ... granzymes enter the cytoplasm of the target cell and their serine protease function triggers the caspase cascade, which is a ... during their development or to the lytic activity of certain TH cells than it is to the cytolytic activity of TC effector cells ...
Tumor cells have gained resistance to effector mechanisms of NK and Cytotoxic CD8+ T cell: by loss of gene expression or ... inhibiton of apoptotic signal pathway molecules: APAF1, Caspase 8, Bcl-2-associated X protein (bax) and Bcl-2 homologous ...
... a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641-4. doi:10.1074/jbc.272.32.19641. PMID ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs[5] have been ... Apoptosis & Caspase 8-The Proteolysis Map (animation). *Caspase 8 at the US National Library of Medicine Medical Subject ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...
Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases. ... TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
1997). "CASH, a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641-4. doi:10.1074/jbc.272.32. ... 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 ...
Rho inactivation can activate caspase-3 and caspase-9; two key components of the apoptotic pathway. TcdA has been linked to ... When RhoA is inactivated via TcdA, its interaction with downstream effectors is inhibited. This leads to changes in the actin ... mitochondrial membrane disruption and release of cytochrome C through caspase activation and Rho inactivation, further ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... Effector caspases are then activated by these active initiator caspases through proteolytic cleavage. The active effector ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ...
Imd signalling regulates a number of effector peptides and proteins that are produced en masse following immune challenge. This ... caspase-8 FADD: human orthologue = FADD Key/Ikkγ: human orthologue = NEMO Ird5: human orthologue = IKK2 Relish: human ... While Relish is integral for transcription of Imd pathway effectors, there is additional cooperation with other pathways such ... Binding of Relish promotes the transcription of effectors such as antimicrobial peptides. ...
... induces caspase-dependent apoptosis in a TRAIL-mediated manner, and potentiates the pro-apoptotic effects of ... Additionally, honokiol regulates the nuclear factor kappa B (NF-κB) activation pathway, an upstream effector of vascular ... Battle, T. E.; Arbiser, J; Frank, DA (2005). "The natural product honokiol induces caspase-dependent apoptosis in B-cell ... "Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent ...
... activate inflammatory caspases (e.g. caspase 1) causing cleavage and activation of important inflammatory cytokines such as IL- ... The NBS-LRR proteins are required for effector triggered immunity (ETI). PRRs commonly associate with or contain members of a ... Other NLRs such as IPAF and NAIP5/Birc1e have also been shown to activate caspase-1 in response to Salmonella and Legionella. ...
The caspase-dependent apoptotic pathway and the lysosomal mediated cell death pathway in MM cells is induced by isatuximab. The ... This drug induces apoptosis of tumor cells and activates immune effector mechanisms such as complement dependent cytotoxicity ( ... The triggered pathways are the caspase-dependent apoptotic and the lysosome-mediated cell death pathway in MM cells. It is used ...
"TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in ... eradicate malignant T cells and enhance T cell effector functions in cutaneous T cell lymphoma". Blood. 126 (12): 1452-1461. ...
A high concentration of caspase-8 induces its autoproteolytic activation and subsequent cleaving of effector caspases, leading ... 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. ...
Herpes simplex virus thymidine kinase (HSV-TK) and inducible caspase 9 (iCasp9) are two types of suicide genes that have been ... Gross G, Gorochov G, Waks T, Eshhar Z (February 1989). "Generation of effector T cells expressing chimeric T cell receptor with ... Preclinical data show the third-generation CARs exhibit improved effector functions and better in vivo persistence as compared ... and a gene encoding a pro-domain-deleted human caspase 9. Dosing the patient with rimiducid activates the suicide system, ...
... while the pro-domain of the extrinsic initiator caspases contains two death folds known as death effector domains (DED).[13][14 ... Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ...
... it is also warned that the design and delivery of small RNA effector molecules should be carefully considered in order to ... Caspase 2 Ocular and retinal disorders. AGN211745. Age-related macular degeneration, choroidal neovascularization. VEGFR1 ... Structural and functional resolution of small RNAs as the effectors of RNA silencing has had a direct impact on experimental ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... Plants also carry immune receptors that recognize highly variable pathogen effectors. These include the NBS-LRR class of ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ...
... über eine Inaktivierung der Zelltodprotease Caspase-9 vermittelt und von einem Kofaktor (HBXIP) abhängig zu sein.[6][18] Die ... effector cell protease receptor-1).[7] ... das Fehlen einer CARD (caspase recruitment domain). * das ...
... and caspases 8 and 10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Both extrinsic and intrinsic pathways have in common the activation of central effectors of apoptosis, a group of cysteine ... Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see "Controlling the Caspases", by Stephen W. Fesik ... The binding of TNF to TNF-R1 has been shown to fire-off the pathway that léads to activating the caspases (see "TNF-R1 ...
These T cells can then go on to perform effector functions such as macrophage activation, B cell activation, and cell-mediated ... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase ...
Kleaiter N, Hermann; Baier, Gottfried (2010). "NFAT pulls the strings during CD4+ T helper cell effector functions". Blood. 115 ... are directly responsible for the expression of anergy associated genes such as ubiquitin ligase GRAIL or a protease caspase 3. ...
Wang KK (Jan 2000). "Calpain and caspase: can you tell the difference?". Trends in Neurosciences. 23 (1): 20-26. doi:10.1016/ ... "T cell receptor-triggered nuclear actin network formation drives CD4+ T cell effector functions". Sci Immunol. 4 (31): ... Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B (Mar 1998). "Calpain inhibitors, but not caspase inhibitors, ...
BCR-ABL has also been implicated in preventing caspase 9 and caspase 3 processing, which adds to the inhibitory effect.[18][19] ... Though the centrality of the JAK2 pathway to direct proliferation in CML has been debated, its role as a downstream effector of ... The JAK/STAT pathway moderates many of these effectors by activating STATs, which are transcription factors with the ability to ...
Effector memory T cells (TEM cells and TEMRA cells) express CD45RO but lack expression of CCR7 and L-selectin. They also have ... The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds ... MAIT cells display innate, effector-like qualities.[21][22] In humans, MAIT cells are found in the blood, liver, lungs, and ... Williams MA, Bevan MJ (2007-01-01). "Effector and memory CTL differentiation". Annual Review of Immunology. 25 (1): 171-92. doi ...
These T cells can then go on to perform effector functions such as macrophage activation, B cell activation, and cell-mediated ... the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis. Recent studies ... STAT3 and RANTES contribute to the maintenance of drug resistance by upregulating anti-apoptotic signals and inhibiting caspase ...
... while the pro-domain of the extrinsic initiator caspases contains two death folds known as death effector domains (DED).[13][14 ... Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ...
Liu Q, Rand T, Kalidas S, Du F, Kim H, Smith D, Wang X (2003). "R2D2, a bridge between the initiation and effector steps of the ... "Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... Pak J, Fire A (2007). "Distinct populations of primary and secondary effectors during RNAi in C. elegans". Science 315 (5809): ...
Their key effector cytokine is IL-10. Their main effector cells are NK cells as well as CD8 T cells, IgG B cells, and IL-10 CD4 ... leading to caspase-1 activation in inflammasomes, thus causing pyroptosis (a highly inflammatory form of programmed cell death ... They are triggered by IL-12 and their effector cytokines are IFN-γ and IL-2. The main effector cells of Th1 immunity are ... Determination of the effector T cell response[edit]. Helper T cells are capable of influencing a variety of immune cells, and ...
There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn activates the effector caspase-3. ... Effector caspases are then activated by these active initiator caspases through proteolytic cleavage. The active effector ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ...
An example of indirect recognition: AvrPphB is a type III effector protein secreted by Pseudomonas syringae. This is a protease ... the pore-forming activity arises from gasdermin B which is cleaved by caspases as a result of the oligomerisation of the NLRs.[ ... However, when the effector protein is introduced and recognized by the sensor NLR, the negative regulation of the helper NLR is ... The sensor NLR is responsible for recognizing the pathogen secreted effector protein and activating the helper NLR which then ...
Effector[edit]. Effector cells are the superset of all the various T cell types that actively respond immediately to a stimulus ... The cytosolic domains bind an adapter BCL10 via CARD (Caspase activation and recruitment domains) domains; that then binds ... Effector memory T cells (TEM cells and TEMRA cells) express CD45RO but lack expression of CCR7 and L-selectin. They also have ... MAIT cells display innate, effector-like qualities.[16][17] In humans, MAIT cells are found in the blood, liver, lungs, and ...
Resolution of an infection is accompanied by the death of most of the effector cells and the generation of memory cells". ... Penilaian apoptosis dapat dilakukan melalui berbagai uji sebagai berikut: uji TUNEL, uji caspase, uji Annexin, dan DNA ... itu terjadi karena struktur protein yang menyusun cytoskeleton mengalami pemotongan oleh peptidase yang dikenal sebagai caspase ...
Their key effector cytokine is IL-10. Their main effector cells are NK cells as well as CD8 T cells, IgG B cells, and IL-10 CD4 ... leading to caspase-1 activation in inflammasomes, thus causing pyroptosis (a highly inflammatory form of programmed cell death ... They are triggered by IL-12 and their effector cytokines are IFN-γ and IL-2. The main effector cells of Th1 immunity are ... The main effector cells are eosinophils, basophils, and mast cells as well as B cells, and IL-4/IL-5 CD4 T cells. The key Th2 ...
2018) The mitochondrial apoptotic effectors BAX/BAK activate caspase-3 and -7 to trigger NLRP3 inflammasome and caspase-8 ... Although active caspase-3/7 is an important effector in the induction of apoptotic pathway, recent publications suggest that ... HIV-1 Infection of Human MDMs Does Not Activate Apoptotic Effector Caspases or Lead to Cell Death.. To understand the dynamics ... 1C). Level of active caspase-3/7, which are effector proteases of apoptosis, remained low in infected cells (2.5-11.4%), at ...
MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death. David K. M ... MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death ... MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death ... MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death ...
Although Bcl-2 is presumed to inhibit caspase activation by acting upstream of caspases (23), Bcl-2 also may be a downstream ... Conversion of Bcl-2 to a Bax-like Death Effector by Caspases ... Conversion of Bcl-2 to a Bax-like Death Effector by Caspases ... Conversion of Bcl-2 to a Bax-like Death Effector by Caspases ... Conversion of Bcl-2 to a Bax-like Death Effector by Caspases ... 1B), which indicates that the transfected caspase-3, or potentially other cellular proteases activated by caspase-3, are ...
Even though NleF is not the only effector protein capable of apoptosis inhibition, direct inhibition of caspases by bacterial ... We have solved the crystal structure of the caspase-9/NleF complex which shows that NleF uses a novel mode of caspase ... Here we show that one of them, NleF, binds to caspase-4, -8, and -9 in yeast two-hybrid, LUMIER, and direct interaction assays ... NleF inhibits the catalytic activity of the caspases in vitro and in cell lysate and prevents apoptosis in HeLa and Caco-2 ...
Structural basis for dimerization of the death effector domains of Caspase-8. Shen, C., Pei, J., Guo, X., Zhou, L., Li, Q., ... Structural basis for dimerization of the death effector domains of Caspase-8. *DOI: 10.2210/pdb5H33/pdb ... Caspase-8. A, B. 188. Homo sapiens. Mutation(s): 1 Gene Names: CASP8, MCH5. EC: 3.4.22.61. ...
Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.. Holler N1, ... Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely ... Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other ... We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic ...
Caspase or caspase-like cleavage of multiple proteins has been described (3, 20), but few of these are known to have direct ... Recombinant active caspase-3 was prepared by expressing the sequence of human caspase-3 (YAMA/CPP32, a gift of V. Dixit) in E. ... Caspase-3-Generated Fragment of Gelsolin: Effector of Morphological Change in Apoptosis ... Caspase-3-Generated Fragment of Gelsolin: Effector of Morphological Change in Apoptosis ...
In the present study we report on the biochemistry and structure of caspase-6. As an effector caspase, caspase-6 is a ... The crystal structure of caspase-6, a selective effector of axonal degeneration. Renato Baumgartner, Gabriele Meder, Christophe ... The crystal structure of caspase-6, a selective effector of axonal degeneration ... The crystal structure of caspase-6, a selective effector of axonal degeneration ...
We also used D. melanogaster genetics to investigate a role for the effector caspase death caspase-1 (Dcp-1) and the inhibitor ... The effector caspase Dcp-1 is not only required for nutrient starvation-induced autophagy but is also sufficient for the ... debcl, P = 0.018; Buffy, P = 0.006; and p53, P = 0.004). (E) RNAi of effector caspase Dcp-1 resulted in a significant decrease ... Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis. ...
... an L-amino acid effector caspase recognition sequence, a quencher, and a fluorophore. Upon cleavage of the caspase recognition ... Visualization of Effector Caspase Activity in Rat Models of Retinal Ganglion Cell Apoptosis Using an Activatable Fluorescent ... Visualization of Effector Caspase Activity in Rat Models of Retinal Ganglion Cell Apoptosis Using an Activatable Fluorescent ... E. M. Barnett, Q. Chang, X. Zhang, B. Elangovan, D. Piwnica-Worms; Visualization of Effector Caspase Activity in Rat Models of ...
2012) Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules. Apoptosis. 2012 Mar 1; 17(3): ... Home , Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules ...
1997). "CASH, a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641-4. doi:10.1074/jbc.272.32. ... 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 ...
As in the entire case of mixture chemotherapy, antibody therapy may come to make use of different effector pathways with this ... If activating signals dominate an activating or cytolytic synapse is usually put together and downstream NK cell effector ...
... are the main effectors of the humoral response against viral illness and probably one of the most important defense mechanisms ...
... and Other CARD/DED/Pyrin-N/BIR proteins Effector Domain. Subgroup. Protein Name. Apoptosis. NFkB activation ... Caspase-9. FADD. Caspase-8. Caspase-3. Caspase-2. Caspase-1. Caspase-11. Caspase-12. Bcl-xL. Bcl-w. Bcl-2(1,2,3). Mcl1. A1. Bax ... Caspase. CARD/DED/BIR. Bcl-2. DD. TNF/TNFR. Kinases. ILs. Viral. Lipid. Engulf. TF. RING. Toll. Other Apop. Other NFkB. ... caspase-9. BIRx3/RING. 19q13.3-q13.4. testis. livin, ML-IAP, KIAP, BIRC7 (human,L). inhibit. caspase-9. BIR/RING. 1. 1. ...
... such as caspases-8 and -9, which either directly or indirectly activate (2) effector caspases, such as caspases-3, -6, and -7 ( ... 9 and the effector caspase-7. Cleavage of caspase-8 and its preferred substrate, Bid, preceded processing of caspases-7 and -9 ... indirect activation of caspase-9, and downstream effector caspases. Cleavage of Bid, a caspase-8 substrate, only previously has ... 1998). Caspase-7, a major effector caspase, was present in MCF-7 cells primarily as its intact 35-kD proform (Fig. 1 A, lane 1 ...
Expression of Effector Caspases.. Caspase-3 has been identified as the major effector caspase in most mammalian cells (86 , 87) ... Caspases-3 and -6 seem to be the major effector caspases responsible for events leading to cellular disassembly; caspases-8, -9 ... Caspase-3 is currently thought to be the major effector caspase in most cells undergoing apoptosis. Interestingly, low tumor ... 3⇓ and 4E⇓ ), the other major effector caspase in cells undergoing drug- or death ligand-induced apoptosis (86 , 87) , revealed ...
... activation of effector caspases is inhibited by IAPs (see text). Effector caspases are shown in light green; cellular caspase ... caspase-2 (20), caspase-3 (21-23), caspase-7 (24-26), caspase-8 (27), and caspase-9 (28). The overall architecture of all ... Group I: inflammatory caspases; group II: apoptosis initiator caspases; group III: apoptosis effector caspases. The CARD, the ... Effector caspase cascade. The activation of the effector caspase cascade differs between extrinsic (death receptor-mediated) ...
Processing of Effector Caspases Results from the Activation of Caspase-8.. Activation of the downstream caspases during ... However, caspase processing was selective since caspase-1, caspase-2, and caspase-4 remained as proenzymes under these same ... caspases (caspase-3, -6, and -7), which mediate the apoptotic response (1)(6). Another caspase subfamily including caspase-1, - ... Caspase-8 is cleaved in activated lymphocytes, whereas caspase-9 remains as a proenzyme. (A) Caspase-8 is processed in ...
... a novel caspase homologue with death effector domains". J. Biol. Chem. 272 (32): 19641-4. doi:10.1074/jbc.272.32.19641. PMID ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs[5] have been ... Apoptosis & Caspase 8-The Proteolysis Map (animation). *Caspase 8 at the US National Library of Medicine Medical Subject ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ...
Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether ... Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies. Tait and ... During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase ... MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing ...
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ...
... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ... In each case, caspase 9 activation leads to the activation of a full caspase cascade and subsequent cell death. It has been ... This functional apoptosome then can provide a platform activation of caspase 9. Caspase 9 exists as a zymogen in the cytosol ... In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ...
A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases. ... caspases (2, 8, 9 and 10) is much longer than that of effector caspases 3, 6 and 7. For the initiator caspases, binding to ... Once active, initiator caspases proteolytically cleave effector caspases at distinct aspartate residues, to release the ... Figure 3. Functional outcomes of caspase‐mediated cleavage. Following cleavage of a target protein by effector caspases, there ...
... have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex ( ... Death Effector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death- ... Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins Oncogene. 1999 Oct 14;18(42 ...
Here, we have identified the impact of the lncRNA SAF in regulating apoptotic effector caspases in macrophages, a long-lived ... Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1-infected human macrophages. ... Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1-infected human macrophages.. ... This induction of apoptotic caspases occurs exclusively in HIV-1-infected macrophages and not in bystander cells, leading to a ...
Effector caspases are dispensable for the early nuclear morphological changes during chemical-induced apoptosis. A1 Journal ... In summary, the effector caspases are not involved in early nuclear morphological change, which precedes the conventional ... Artur » List of publications » Effector caspases are dispensable for the early nuclear morphological changes during chemical- ... Nuclear morphological changes during apoptosis are very distinct and effector caspases have been implicated to play a central ...
Cleaves and activates caspase-3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-,-AMC and ... Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors ... death effector domain binding Source: UniProtKB ,p>Inferred from Physical Interaction,/p> ,p>Covers physical interactions ... PS01122 CASPASE_CYS, 1 hit. PS01121 CASPASE_HIS, 1 hit. PS50207 CASPASE_P10, 1 hit. PS50208 CASPASE_P20, 1 hit. PS50168 ...
Background It is well established that caspase-1 exerts its biological activities through its downstream targets such as IL-1β ... Lamkanfi M. Emerging inflammasome effector mechanisms. Nat Rev Immunol. 2011;11(3):213-20.CrossRefPubMedGoogle Scholar ... and caspase-1-deficient mouse aorta microarray data with caspase-1−/− intestine [5], caspase-1−/− liver [5], and caspase-1−/− ... WT, ** Caspase-1 KO vs. WT. Table S7. The meta-analysis identified 17 caspase-1 globally promoted genes and 23 caspase-1 ...
P49 prevents proteolytic processing of effector caspases Sf-caspase-1 and Sf-caspase-2 during baculovirus infection of the moth ... identical to that in pro-Sf-caspase-1 cleaved by Sf-caspase-X. Instead, P49 inhibits the active Drosophila effector caspases, ... P35TVTD still functioned to inhibit downstream effector caspases. Thus, the S4 pocket of the Spodoptera effector caspases, ... Fig.6C),6C), which was expected if an effector caspase rather than an initiator caspase was targeted by P49DQMD. We concluded ...
  • Molecular and genetic characterization of programmed cell death has led to the increasing appreciation of the role of interleukin converting enzyme (ICE) family of death promoting cysteine-proteases (caspases) ( 1 , 2 ). (pnas.org)
  • Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). (sciencemag.org)
  • A number of substrates for the caspase proteases have now been identified, including protein kinases ( 3 ), the retinoblastoma protein ( 4 ), cytoskeletal proteins ( 5 ), and several autoantigens ( 6 ). (sciencemag.org)
  • The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. (sciencemag.org)
  • A conserved family of aspartate-specific cysteinyl proteases (caspases) has been identified as critical mediators of apoptosis in Caenorhabditis elegans and mammals ( 1 , 2 ). (sciencemag.org)
  • Caspases, a family of cysteine proteases, play a central role in apoptosis. (jci.org)
  • Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. (rupress.org)
  • Cysteine proteases of the IL-1β-converting enzyme (ICE) family (caspases) are critical executioners of apoptosis in several mammalian cell death pathways ( 1 ). (rupress.org)
  • Caspases are synthesized as inactive precursors that require proteolytic conversion to become active proteases. (rupress.org)
  • The proteins that execute the apoptotic programme are a group of proteases termed caspases (cysteine‐dependent aspartate‐specific protease). (els.net)
  • Apoptotic caspases are cysteine proteases that become activated in response to diverse extracellular and intracellular stimuli and subsequently carry out the cell death programme by systematically cleaving intracellular proteins. (els.net)
  • P49 and P35 are two baculovirus-encoded apoptotic suppressors that function by inhibiting a broad range of the cell death proteases known as caspases ( 2 , 3 , 19 , 30 , 40 , 45 ). (pubmedcentralcanada.ca)
  • The caspases are a family of cysteinyl aspartate-specific proteases that are critical effectors of apoptosis in metazoans (reviewed in references 15 , 23 , 32 , and 33 ). (pubmedcentralcanada.ca)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Caspases are the proteases responsible for dismantling the cell in an ordered and histologically distinct process termed apoptosis [ 1 ]. (mdpi.com)
  • The cellular processes leading to apoptosis induction are not completely understood, but an important event is the activation of a cascade of cysteine proteases named caspases (2), leading to cleavage of specific substrates involved in cell death. (scielo.br)
  • Caspases belong to a particular class of proteases, known as cysteine proteases. (wisegeek.com)
  • For both pathways, caspases, a family of cysteine proteases, are crucial for both the initiation and execution of apoptosis. (jimmunol.org)
  • Caspases (cysteinyl aspartate proteases) are involved in the signaling pathways of apoptosis, necrosis and inflammation. (genecards.org)
  • Caspases: killer proteases. (springer.com)
  • Caspases are a family of cysteine proteases which are the major executors of apoptosis and inflammation. (iucr.org)
  • Most signals that lead to apoptosis do so by activating interleukin-1β converting enzyme (ICE)-like proteases termed caspases. (bloodjournal.org)
  • Caspases, a family of cysteine acid proteases regulate the process, and in fact, lead to apoptosis. (clinicaltrials.gov)
  • Caspases are a 12-member family of human proteases that regulate apoptosis and inflammation. (mit.edu)
  • Proteases of the caspase family are the critical executioners of apoptosis. (semanticscholar.org)
  • In addition to the caspase family, the Bcl-2 family of proteins represents another class of molecules that have been extensively studied for their death-promoting as well as death-inhibiting properties. (pnas.org)
  • Although, the caspase and Bcl-2 families of proteins have received much attention, the relationship of these families and mechanisms of interaction at a molecular level was not clear. (pnas.org)
  • Cleavage of these proteins by caspases may either activate or inactivate essential functions or produce cleavage products with altered activities. (sciencemag.org)
  • We reasoned that an unbiased approach to determine proteins that were the best substrates of caspase-3 in vitro would yield a physiologically relevant substrate. (sciencemag.org)
  • Therefore, we constructed a protein library by translating a murine embryo cDNA library in vitro ( 4 ) and tested the translated proteins for their sensitivity to caspase-3 cleavage. (sciencemag.org)
  • The reaction products were resolved by SDS-polyacrylamide gel electrophoresis (PAGE), and protein targets of caspase-3 were identified by comparing the pattern of 35 S-labeled proteins in the samples treated with active and inactive caspase-3. (sciencemag.org)
  • A ) Autoradiogram of [ 35 S]methionine-labeled proteins treated with purified active (-) or inactivated [by addition of a caspase-3 inhibitor, DEVD-fmk (+)] recombinant caspase-3. (sciencemag.org)
  • In three different pools, incubation of active caspase-3 with labeled proteins reduced the intensity of a 65-kD band and generated a new band at 48 kD (Fig. 1 A, pool 4). (sciencemag.org)
  • Caspase activity results in the cleavage of several cellular proteins, which leads to the apoptotic response (for a review, see reference 7). (rupress.org)
  • Death Effector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex (DISC), consisting of the death domain (DD)-containing receptors and various signaling proteins. (nih.gov)
  • Substrates targeted by caspases during the apoptotic programme include proteins involved in maintaining various aspects of cytoskeletal and organelle architecture as well as proteins that function in signalling networks critical for cell function. (els.net)
  • Caspase‐mediated cleavage of target proteins may produce stable functional effector fragments or unstable fragments that are quickly degraded. (els.net)
  • For the initiator caspases, binding to adaptor proteins results in the cleavage of the prodomain and subsequent rearrangement of the large and small subunits to produce a catalytically active heterodimer. (els.net)
  • Once active, caspase 9 functions to proteolytically cleave and activate the effector caspases 3 and 7, which then go on to cleave numerous intracellular proteins to dismantle the cell. (els.net)
  • a) Caspase‐mediated cleavage of intracellular proteins may result in the production of stable, functionally active effector fragments. (els.net)
  • After proteins cleavage procaspase-3 transform into its energetic form caspase-3 accompanied by translocate from cytoplasm to nuclei 3. (healthcarecoremeasures.com)
  • Our findings suggest that caspase-1 regulates many new signaling pathways potentially via its known substrates and also via transcription factors and other proteins that are yet to be identified. (springer.com)
  • Upon apoptotic signaling, initiator caspases are autoactivated through interactions of their N-terminal prodomain with specific adaptor proteins ( 1 , 31 , 35 , 42 ). (pubmedcentralcanada.ca)
  • By cleaving critical proteins, caspases lead to the changes that characterize apoptosis both morphologically and biochemically, such as chromatin condensation, loss of cell adhesion, cell shrinkage, membrane blebbing, DNA fragmentation, and finally formation of apoptotic bodies, which stimulate their own engulfment by phagocytes. (mdpi.com)
  • Detection of these secretion systems or toxins, or their activities, by nucleotide-binding oligomerization domain leucine-rich repeat proteins (NLRs) triggers the assembly of inflammasomes, multiprotein complexes necessary for caspase-1 activation and host defense. (nih.gov)
  • Screens demonstrated that an individual L. pneumophila strain can use the Dot/Icm T4SS to translocate an unprecedented number of more than 300 proteins into host cells, where these, so called Icm/Dot-translocated substrates (IDTS) or effectors, manipulate host cell functions to the benefit of the bacteria. (frontiersin.org)
  • Deciphering their functions is challenging, as effectors are a heterogeneous group with limited homology to characterized proteins. (frontiersin.org)
  • The sequenced genomes of oomycete plant pathogens contain large superfamilies of effector proteins containing the protein translocation motif RXLR-dEER. (plantcell.org)
  • Together, these results indicate that the W and Y motifs are critical for the interaction of Avr1b with host plant target proteins and support the hypothesis that these motifs are critical for the functions of the very large number of predicted oomycete effectors that contain them. (plantcell.org)
  • This process requires cell death proteins including apoptotic effector caspases (activated effector caspase is visualized by green staining). (weizmann.ac.il)
  • The effects of [beta]-sitosterol on the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA-MB-231 adenocarcinoma cells were examined, along with the extent of its incorporation into cellular membranes and its effects on cell growth, expression of Fas receptor pathway proteins, and caspase-8 activity. (thefreelibrary.com)
  • These actions are specific, as expression of other proteins of the Fas receptor pathway, including Fas ligand, FADD, p-FADD and caspase-8, remain unchanged. (thefreelibrary.com)
  • These effector caspases then cleave various proteins such as those present in cytoskeletons and nucleus like lamin A, alpha-fodrin and poly (ADP-ribose) polymerase, leading to apoptosis. (clinicaltrials.gov)
  • Caspase-3 is the key executioner in this apoptotic pathway, responsible totally or critically in the proteolytic cleavage of cellular and nuclear proteins. (clinicaltrials.gov)
  • Biochemical analysis demonstrate that HCV proteins bring about the activation of initiator and effector caspases followed by severe apoptosis and mitochondria dysfunction, hallmarks of HCV cell injury. (biomedcentral.com)
  • To determine if viral Bcl-2 proteins can be converted into death factors, similar to their cellular counterparts, five herpesvirus Bcl-2 homologs from five different viruses were tested for their susceptibility to caspases. (asm.org)
  • Thus, herpesvirus Bcl-2 homologs escape negative regulation by retaining their antiapoptotic activities and/or failing to be converted into proapoptotic proteins by caspases during programmed cell death. (asm.org)
  • We and others have reported that caspase-3 cleaves Bcl-2 at Asp-34 and Bcl-x L at Asp-61 and Asp-76 to produce N-terminally truncated proteins that have lost their antiapoptotic activities ( 8 , 13 , 20 , 22 , 35 ). (asm.org)
  • Apoptotic cell shrinkage is achieved by net loss of intracellular osmoles and H 2 O, as well as by caspase-dependent proteolysis of housekeeping and structural proteins, which mediates cell disassembly. (physiology.org)
  • Spi-2 proteins like CrmA potently inhibit caspases-1, -4 and -5, which produce proinflammatory cytokines, and caspase-8, which facilitates cytotoxic lymphocyte-mediated target cell death. (portlandpress.com)
  • The retention of Spi-2 proteins' caspase-8 specificity during chordopoxvirus evolution, despite this function being readily lost through cleavage site mutagenesis, suggests that caspase-8 inhibition is crucial for poxviral pathogenesis and spread. (portlandpress.com)
  • Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. (nih.gov)
  • We discovered that six cell death genes- death caspase-1 ( Dcp-1 ), hid , Bruce , Buffy , debcl , and p53 -as well as Ras-Raf-mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. (rupress.org)
  • In this study, we determined whether TFPI-2 restoration could induce apoptosis through the caspase-mediated signaling pathway. (aacrjournals.org)
  • Although multiple protein substrates of caspases have been found, the functional significance of the substrates is poorly understood ( 3 ). (sciencemag.org)
  • One thousand cDNA pools, each containing 100 cDNA clones (100,000 cDNA clones total), were screened to identify substrates of caspase-3. (sciencemag.org)
  • Subsequently, active caspases specifically process various substrates that are implicated in apoptosis and inflammation. (jci.org)
  • Caspases proteolytically cleave a host of cellular substrates at aspartate residues, which may render them either functionally inactive or confer novel activities that help to promote cellular demise. (els.net)
  • However, it is not known whether all the effects exerted by caspase-1 on transcriptome are mediated only by its well-known substrates. (springer.com)
  • However, it remains unclear whether caspase-1 regulates gene transcription independent of the three well-characterized caspase-1 substrates IL-1β, IL-18, and Sirt-1. (springer.com)
  • Although for many Icm/Dot-translocated substrates (IDTS) an actual effect on the host awaits demonstration, they will here collectively be referred to as effectors. (frontiersin.org)
  • Caspase-8 is a cysteine protease, which cleaves downstream substrates such as effector caspases, to initiate the apoptotic cascade and transmit apoptotic signals downstream of death receptors ( 16 ). (aacrjournals.org)
  • Activated effector caspases cleave a variety of cellular protein substrates, leading to apoptotic cell death. (jimmunol.org)
  • The activated caspases abrogate the effect of substrates that protect cellular integrity, such as the DNA-repair enzyme poly(ADP-ribose) polymerase (PARP), and thereby induce apoptotic cell death. (bloodjournal.org)
  • The successive interaction of the FADD-death effector domain molecule with caspase-8 activates a caspase cascade, which ends with downstream activation of caspases (caspase-3 and -7) and cleavage of cellular substrates. (aspetjournals.org)
  • Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. (sciencemag.org)
  • At these two stages, the effector caspase Dcp-1 and the inhibitor of apoptosis protein Bruce function to regulate both autophagy and starvation-induced cell death. (rupress.org)
  • We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. (rupress.org)
  • Biochemically, caspase-8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex which were crucial for the induction of nuclear translocation of NF-κB. (wikipedia.org)
  • The activity of caspase-3 was enhanced during macrophage apoptosis induced by butyrate and the caspase inhibitor z-VAD-FMK (100 µM) inhibited the butyrate effect, indicating the major role of the caspase cascade in the process. (scielo.br)
  • For instance, FLIP blocks activation of initiator caspases, Bcl-2 prevents mitochondrial disruption, and X-linked inhibitor of apoptosis protein (XIAP) 3 inhibits downstream caspases (i.e., caspase-9 and caspase-3). (jimmunol.org)
  • In the present study, we used SB203580, a p38MAPK inhibitor, and Z-LETD-FMK, a caspase-8 inhibitor, to determine the relation of p38MAPK and caspase-8 in the apoptosis process induced by DATS. (scielo.br)
  • In marked contrast to the caspase inhibitors, an inhibitor of the DNA repair enzyme, poly(ADP-ribose) polymerase, conferred significant protection from genotoxic and excitotoxic cell death on postnatal cortical neurons but had no effect on embryonic neurons. (jneurosci.org)
  • The caspase 8 inhibitor c-FLIP L can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). (asm.org)
  • Soti (green), an inhibitor of a ubiquitin ligase complex required for caspase activation in this process, is expressed in a gradient from the tails (bottom) to the nuclear heads (top, blue) of the sperm cells. (weizmann.ac.il)
  • Furthermore, apoptosis induced by these fragments is blocked by the baculovirus caspase inhibitor P35, suggesting that these fragments kill cells in a caspase-dependent manner. (asm.org)
  • Interferon-gamma-induced sensitization of colon carcinomas to ZD9331 targets caspases, downstream of Fas, independent of mitochondrial signaling and the inhibitor of apoptosis survivin. (semanticscholar.org)
  • The peptide based caspase inhibitor z-VAD-FMK resulted in a novel nuclear morphological change, characterized by partially condensed nuclear morphology and could be dissociated from the externalisation of PS, HMW DNA fragmentation and preceded the appearance of a condensed nuclear morphology during staurosporine-induced apoptosis. (bl.uk)
  • However, a caspase-9-specific inhibitor blocked the sensitization effect of maspin in a dose-dependent and time-dependent manner, demonstrating a rate-limiting role for caspase-9. (aacrjournals.org)
  • Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP. (nih.gov)
  • Moreover, the biochemical form of caspase-8 differed in the two pathways. (wikipedia.org)
  • Activation of caspases through intrinsic and extrinsic death pathways. (els.net)
  • and (5) The meta-analysis identified new cooperatively and non-cooperatively regulated genes in caspase-1, IL-1β, IL-18, and Sirt-1 pathways. (springer.com)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • The model integrates current information concerning the signaling network downstream of Fas activation, through both type I and type II pathways, until activation of caspase-3. (jimmunol.org)
  • The pathways diverge after activation of initiator caspases (e.g., caspase-8 and caspase-10) and converge at the end by activating executor caspases (e.g., caspase-3). (jimmunol.org)
  • Among its related pathways are Direct p53 effectors and Apoptosis and survival Caspase cascade . (genecards.org)
  • Thus, p53-mediated neuronal cell death may occur via both caspase-dependent and caspase-independent pathways. (jneurosci.org)
  • This report gives an insight into Apoptosis Mechanism, by Molecular Pathways - Caspase Activators and Inhibitors, Protease/Proteasome Inhibitors, Bcl-2 Modulators and p53 Modulators. (researchimpact.com)
  • Lymphocyte-mediated cytotoxicity: Two pathways and multiple effector molecules. (springer.com)
  • Taken together, these results show that restoration of TFPI-2 activates both intrinsic and extrinsic caspase-mediated, proapoptotic signaling pathways and induces apoptosis in U-251 cells. (aacrjournals.org)
  • Combined use of GLB with these drugs also induces DNA damage and apoptosis by activating caspase/PARP pathways and increased production of reactive oxygen species and increased autophagy in GC cells. (dovepress.com)
  • However, unlike FLICE, the C-terminal domain of MRIT lacks the caspase catalytic consensus sequence QAC(R/Q)G. Nonetheless MRIT activates caspase-dependent death. (pnas.org)
  • This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. (wikipedia.org)
  • A critical substrate for caspase-3 during apoptosis is the 45-kD subunit of DNA fragmentation factor (DFF45) that once cleaved by caspase-3 activates DNA fragmentation by releasing the caspase-activated DNase ( 14 )( 15 )( 16 ). (rupress.org)
  • Truncated Bid (tBid) then activates Bax/Bak which induce mitochondrial permeabilisation, the release of cytochrome c , formation of the apoptosome and the activation of caspases 9 and 3. (els.net)
  • When P49's TVTD recognition motif was replaced with P35's DQMD motif, P49 was impaired for inhibition of the initiator caspase that cleaves and activates pro-Sf-caspase-1 and instead formed a stable inhibitory complex with active Sf-caspase-1. (pubmedcentralcanada.ca)
  • Once activated through cleavage, caspase-9 activates the downstream effector caspase-3 that irreversibly causes apoptosis [ 20 ]. (hindawi.com)
  • Caspase-8 subsequently activates caspase-3, thereby initiating the proteolytic pathway, and ultimately resulting in the apoptotic disassembly of the cell. (haematologica.org)
  • Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. (bloodjournal.org)
  • The results indicated that DATS activates p38MAPK and caspase-8, but both inhibitors have an effect on P38MAPK and caspase-8 activity. (scielo.br)
  • The krebs cycle components A-Sβ (green), is expressed on the surface (rather than in the matrix) of mitochondria, where it binds to and activates a Ub ligase complex required for caspase activation. (weizmann.ac.il)
  • The P4 position of caspase cleavage sites confers protease specificity ( 10 ). (sciencemag.org)
  • This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
  • According to some studies, susceptibility of cells to anticancer drug-induced apoptosis is markedly inhibited by targeted deletion of genes encoding apoptotic protease activating factor 1 (Apaf-1) or certain caspases. (aacrjournals.org)
  • Caspases exist as inactive proenzymes composed of a prodomain , a large protease subunit , and a small protease subunit. (wikipedia.org)
  • The clinical phenotype of CEDS patients represented a paradox since caspase-8 was considered to be chiefly a proapoptotic protease , that was mainly involved in signal transduction from Tumor necrosis factor receptor family death receptors such as Fas. (wikipedia.org)
  • Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. (abcam.com)
  • Caspase-8 is a member of the aspartate-specific cysteine protease family that is typically synthetized as an inactive zymogen and activated upon an appropriate stimulus. (haematologica.org)
  • Caspase 6 (CASP6) is a neuron degeneration-related protease and is widely considered to be a potential drug-design target against neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. (iucr.org)
  • The chapter includes global markets by related products including Caspase Activators and Inhibitors, Protease/Proteasome Inhibitors, Bcl-2 Modulators, p53 Modulators and Other and also by therapeutic areas including Cancer, Neurodegenerative Diseases, Cardiovascular Diseases and other apoptosis based diseases (HIV infection, Organ Transplant Rejection and MODS). (researchimpact.com)
  • 15 16 Caspase 3 is a cysteine protease homologous with ICE. (bloodjournal.org)
  • 2004). These factors ultimately activate the effector protease, caspase-3, driving programmed cell death (Dragovich et al. (thefreelibrary.com)
  • Apoptotic cell death induced by activation of the Fas/Fas-L system requires a multistep cascade of biochemical events: the trimerization of Fas receptor induced by Fas-L stimulates the formation of a death-inducing signaling complex, which consists of the adapter protein FADD and the protease FLICE/caspase-8. (aspetjournals.org)
  • Activation of the cascade of proteolytic caspases has been identified as the final common pathway of apoptosis in diverse biological systems. (pnas.org)
  • Although inefficient, treatment with active caspase-3 produced a 23-kD proteolytic fragment of Bcl-2 (Fig. 1 A). However, a mutant of Bcl-2 ( 9 ) that lacks the loop domain (amino acids 32 to 80) was not susceptible to proteolysis, which suggested that the caspase cleavage site is localized within the loop. (sciencemag.org)
  • Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. (wikipedia.org)
  • The current model suggests that after apoptotic stimulation, activation of "upstream" caspases containing a large prodomain such as caspase-8, -2, or -9 leads to the proteolytic cleavage of "downstream" caspases (caspase-3, -6, and -7), which mediate the apoptotic response ( 1 )( 6 ). (rupress.org)
  • Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. (wikipedia.org)
  • For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase heterotetramer whereas for the activation pathway, the zymogen appears to remain intact perhaps to limit its proteolytic function but enhance its capability as an adapter protein. (wikipedia.org)
  • All these biological activities of caspase-1 occur at post-translational level (proteolytic processing). (springer.com)
  • We tested the role of the P 4 -P 1 recognition motif for caspase specificity by monitoring virus-induced proteolytic processing of Sf-caspase-1, the principal effector caspase of the host insect Spodoptera frugiperda . (pubmedcentralcanada.ca)
  • During apoptosis in humans, initiator caspases integrate molecular signals into proteolytic activity ( 11 ) and subsequently activate the downstream effector caspases, thus transmitting and amplifying the apoptotic signal ( 12 ). (aacrjournals.org)
  • Activation of caspase-3 requires proteolytic processing of its inactive zymogen into active p17 and p12 fragments. (clinicaltrials.gov)
  • Upon receptor trimerization, activated Fas and TNF-α-receptor type 1 initiate rapid protein interactions at the cell membrane, leading to the formation of a death inducing signaling complex responsible for downstream apoptotic events, which include the release of cytochrome c from mitochondria ( 29 ) and a proteolytic cascade of caspase activation ( 35 ). (physiology.org)
  • However, targeting the latent conformation in search for specific and bio-available caspase-6 inhibitors might offer an alternative to active-site-directed approaches. (biochemj.org)
  • In the presence of caspase inhibitors, like benzyloxycarbonyl-Val-Ala-Asp fluoro-methylketone (z-VAD-FMK), N-acetyl Tyr-Val-Ala-Asp chloromethylketone (Ac-YVAD-CMK) and benzyloxy-carbonyl-Asp-Glu-Val-Asp (OMe) fluoromethylketone (z-DEVD-FMK), staurosporine-treated Jurkat cells displayed a nuclear morphological change distinct from that of normal and apoptotic cells. (abo.fi)
  • In addition, caspase-3 null MCF-7 cells also undergo pre-apoptotic nuclear change when treated with staurosporine in the presence of caspase inhibitors, indicating that caspase-3 is not required for the early nuclear morphological change in cells undergoing apoptosis. (abo.fi)
  • To advance strategies for selective inhibition of the cell death caspases, we investigated biochemical differences between these baculovirus substrate inhibitors. (pubmedcentralcanada.ca)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • The first are initiator caspases, which are regulated by inhibitors. (wisegeek.com)
  • After human CNE2 cells were treated with 100 μM DATS and inhibitors (10 μM SB203580 and Z-LETD-FMK for p38MAPK and caspase-8, respectively), changes in cell viability and apoptosis and in p38MAPK and caspase-8 activity were detected. (scielo.br)
  • Caspase inhibitors protected embryonic telencephalic neurons, but not postnatal cortical neurons, from DNA damage-induced cell death as measured by direct cell counting and annexin V staining. (jneurosci.org)
  • Glutamate-mediated excitotoxicity in postnatal neurons was not associated with measurable changes in caspase activity, consistent with the failure of caspase inhibitors to prevent cell death under these conditions. (jneurosci.org)
  • Both the caspases inhibitors, ZVAD-fmk and DEVD-cho, inhibited at similar extent apoptosis induced by either DXR or MEN 10755, suggesting an involvement of caspase-3 in this response. (aspetjournals.org)
  • As an effector caspase, caspase-6 is a constitutive dimer independent of the maturation state of the enzyme. (biochemj.org)
  • Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene. (wikipedia.org)
  • Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. (rupress.org)
  • Caspase is an inactive enzyme zymogen under normal circumstances, but once activated it will trigger the caspase cascade, eventually leading to apoptosis. (scielo.br)
  • Conversely, a high level of cleaved caspase 3 denoted improved survival and correlated with the inactivation of the DNA-repair enzyme poly(ADP-ribose) polymerase. (bloodjournal.org)
  • A high local concentration of caspase 8 zymogens is thought to facilitate self-processing and cleavage to the active enzyme ( 34 ). (asm.org)
  • The cleaved caspase-3 can be detected by antibodies specific for this cleaved enzyme (p17 fragment) in cell lysates by immunoblotting or by an ELISA assay utilizing spectrophotometric determination with a microplate reader at OD450 nm. (clinicaltrials.gov)
  • Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. (wikipedia.org)
  • Caspase-3 is a critical effector caspase in apoptosis cascade and is often over-expressed in many cancer tissues. (healthcarecoremeasures.com)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (uniprot.org)
  • The mechanisms by which butyrate induces apoptosis in different cell types are not known, but there is evidence that butyrate cell death induced in some cancer cells is triggered via activation of the caspase cascade (14). (scielo.br)
  • Thus, cleaved caspase 3 could stimulate the apoptotic cascade further, and lack of its activation likely caused an accumulation of the uncleaved caspase. (bloodjournal.org)
  • The pathway was Fas-independent but likely involved bax and caspase-3 as effectors of the cascade culminating in apoptosis. (aspetjournals.org)
  • The altered ratio between bax and the antiapoptotic components Bcl-2 or Bcl-Xl, modulate the successive formation of the "apoptosoma" and the final apoptotic caspase cascade ( Green and Kroemer, 1998 ). (aspetjournals.org)
  • Many studies have also demonstrated that apoptosis is associated with a decrease in cytosolic pH ( 16 , 27 , 28 , 30 , 36 , 46 ), which is required for activation of the caspase cascade ( 30 , 45 ). (physiology.org)
  • In vitro translated human Bcl-2 was digested with purified recombinant caspase-3 (CPP32). (sciencemag.org)
  • A ) 35 S-labeled in vitro translated Bcl-2 and the indicated Bcl-2 mutants were digested with purified recombinant caspase-3 and analyzed on 12% SDS-polyacrylamide gels ( 24 ). (sciencemag.org)
  • Alternatively, Jurkat cell lysates were digested for 4 hours with recombinant caspase-3. (sciencemag.org)
  • Recombinant fragment corresponding to Human Caspase-8 aa 179-385. (abcam.com)
  • Full-length recombinant human caspase-3 protein was used as immunogen. (novusbio.com)
  • Recombinant caspase-3 cleaved the in vitro-translated NHE1 cytoplasmic domain into five distinct peptides, identical in molecular weight to NHE1 degradation products derived from staurosporine-stimulated RTC lysates. (physiology.org)
  • Caspases, a family of c ysteinyl a spartate- s pecific p rote ases , are synthesized as zymogens with a prodomain of variable length followed by a large subunit (p20) and a small subunit (p10). (jci.org)
  • All caspases are produced as catalytically inactive zymogens or proenzymes containing a prodomain, a large (p20) and a small subunit (p10). (els.net)
  • This antibody recognizes the 10 kDa small subunit of Caspase 8. (abcam.com)
  • A) WT (B6) BMMs were harvested at indicated times post-infection and assayed for caspase-1 activation by western blotting for cleaved p10 caspase-1 subunit. (nih.gov)
  • The three effector caspases are expressed as dimeric zymogens and each monomer contains a short pro-domain, a large subunit (p20), an intersubunit linker (L) and a small subunit (p10). (iucr.org)
  • The antibody recognizes an epitope in the large domain subunit of Caspase-3. (novusbio.com)
  • As such it will recognize pro Caspase-3 and the large subunit cleavage fragment. (novusbio.com)
  • The antibody detects both pro Caspase-3 (~32 kDa) and the large subunit of the active/cleaved form (~14-21 kDa) of Caspase-3. (novusbio.com)
  • The large subunit of the cleaved form may appear as one or two or even as a stack of bands depending on the presence or absence of the Caspase-3 pro-domain. (novusbio.com)
  • Here, we investigated the possibility that Bcl-2 could also serve as a caspase substrate. (sciencemag.org)
  • Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. (sciencemag.org)
  • We used an amount sufficient to cleave 80% of a known substrate of caspase-3, baculovirus protein p35 (Fig. 1 A) ( 5 ). (sciencemag.org)
  • Identification of gelsolin as a substrate of caspase-3. (sciencemag.org)
  • However, in contrast with the structures of other caspases, not only is the catalytic machinery misaligned, but several structural elements required for substrate recognition are missing. (biochemj.org)
  • Most importantly, residues forming a short anti-parallel β-sheet abutting the substrate in other caspase structures are part of an elongation of the central α-helix. (biochemj.org)
  • Cleavage of caspase-8 and its preferred substrate, Bid, preceded processing of caspases-7 and -9, indicating that caspase-8 is the apical initiator caspase in TRAIL-induced apoptosis. (rupress.org)
  • This Review gives an overview of caspases and their classification, structure, and substrate specificity. (jci.org)
  • Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. (rupress.org)
  • Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. (rupress.org)
  • Caspase and substrate processing occur in nonapoptotic lymphocytes. (rupress.org)
  • However, the caspase-3 substrate, poly(ADP ribose) polymerase was not cleaved in the presence of z-VAD-FMK, despite >70% of the cells have pre-apoptotic nuclei. (abo.fi)
  • The substrate specificity of initiator caspases differs from that of effector caspases, due in part to their unique functions during execution of apoptosis ( 37 ). (pubmedcentralcanada.ca)
  • We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release. (nih.gov)
  • This results in the generation of mature active caspases that consist of the heterotetramer p20 2 -p10 2 . (jci.org)
  • Wing imaginal discs from irradiated Drosophila are stained for active caspases (yellow), a reporter cleaved by caspases (blue), fragmented DNA (red), and apoptotic corpses (green). (weizmann.ac.il)
  • Using yeast two-hybrid assays, we demonstrate that MRIT associates with caspases possessing large and small prodomains (FLICE, and CPP32/YAMA), as well as with the adaptor molecule FADD. (pnas.org)
  • In the case of FLICE (for FADD-like ICE)/MACH (MORT1-associated CED-3 homolog) duplication of a highly conserved motif called death-effector domain (DED) is present ( 1 , 2 ). (pnas.org)
  • This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP). (nih.gov)
  • The N-terminal FADD -like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. (wikipedia.org)
  • FADD, through its death effector domain, can recruit pro-caspase 8 to the complex. (jimmunol.org)
  • Upon activation of Fas by its ligand, the DD undergoes homotypic interaction with a DD in the adaptor protein FADD, which then recruits the initiator caspase 8 via their mutual N-terminal death effector domains (DED) ( 3 ). (asm.org)
  • As such, v-FLIP can be recruited into the death-inducing signaling complex (DISC) of Fas, thereby competing with recruitment of caspase 8 to FADD. (asm.org)
  • During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. (nature.com)
  • Kumarswamya and colleagues [ 29 ] recently used Sf9 cells to demonstrate that cyosolic cytochrome-c release is an essential event for caspase activation during Lepidopteran apoptosis, and that cytochrome-c release might occur independent of mitochondrial membrane potential loss and permeability transition pore formation. (biomedcentral.com)
  • In some cell types (type 1) sufficient amounts of caspase 8 are activated at the death-inducing signaling complex so as to efficiently initiate apoptosis, whereas others (type 2) form less caspase 8 and must use the mitochondrial pathway to amplify the Fas signal ( 8 ). (jimmunol.org)
  • Also, 2-EH presented apoptosis induction with characteristic hallmarks, such as loss of mitochondrial membrane potential, caspase activation, DNA fragmentation and cell cycle arrest at the S phase. (scirp.org)
  • The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB. (bcgsc.ca)
  • To investigate this in greater detail we examined the effect of blocking caspase activity and its activation on the nuclear morphological change in Jurkat T cells undergoing apoptosis after staurosporine treatment. (abo.fi)
  • Here, we have identified the impact of the lncRNA SAF in regulating apoptotic effector caspases in macrophages, a long-lived cellular reservoir of HIV-1, that are largely immune to virus-induced cell death. (pnas.org)
  • Caspases target multiple aspects of the cellular architecture to induce collapse of organelles and the cytoskeleton. (els.net)
  • Signalling networks that regulate cellular processes critical for cell survival are inactivated by caspases. (els.net)
  • Caspase-mediated proteolysis promotes cellular disassembly that includes chromatin condensation, nuclear DNA cleavage, membrane blebbing, and cell fragmentation. (pubmedcentralcanada.ca)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • Further, we identify a Yersinia type III secreted effector protein, YopK, which interacts with the T3SS translocon to prevent cellular recognition of the T3SS and inflammasome activation. (nih.gov)
  • which manipulate cellular processes and are therefore called effectors. (frontiersin.org)
  • The activation of at least one caspase appears to be an essential step in cellular apoptosis. (bloodjournal.org)
  • However, unlike the caspase cleavage products of cellular Bcl-2, Bcl-x L , and Bid, which are potent inducers of apoptosis, the cleavage product of γHV68 Bcl-2 lacked proapoptotic activity. (asm.org)
  • The function of cellular Bcl-2 family members is regulated in part by caspases. (asm.org)
  • ORCID: https://orcid.org/0000-0003-4470-3608 and Russell, David (2019) 'Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1-infected human macrophages. (lstmed.ac.uk)
  • The loop domain of Bcl-2 is cleaved at Asp 34 by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. (sciencemag.org)
  • 2-4 Consistent with this scheme, caspase 3 (CPP32, prICE, or Yama) 6-8 has been found to be involved in leukemia-cell apoptosis induced by cytotoxic agents such as ara-C, 9 10 etoposide, mitoxantrone, 10 and CPT-11. (bloodjournal.org)
  • We have isolated a gene, termed MRIT , that possesses overall sequence homology to FLICE (MACH), a large prodomain caspase that links the aggregated complex of the death domain receptors of the tumor necrosis factor receptor family to downstream caspases. (pnas.org)
  • In mammalian cells, it was also demonstrated that CED-4 could independently interact with BclX L , an anti-apoptotic member of the Bcl-2 family as well as with ICE and FLICE, two large prodomain caspases ( 8 ). (pnas.org)
  • Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction. (semanticscholar.org)
  • article{Wesselborg1999AnticancerDI, title={Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction. (semanticscholar.org)
  • Their activation has been mainly studied upon triggering of death receptors, such as CD95 (Fas/APO-1) and tumor necrosis factor-R1, which recruit caspase-8/FLICE as the most proximal effector to the receptor complex. (semanticscholar.org)
  • Caspase-8 is a caspase protein, encoded by the CASP8 gene. (wikipedia.org)
  • To determine new global and tissue-specific gene regulatory effects of caspase-1, we took novel microarray data analysis approaches including Venn analysis, cooperation analysis, and meta-analysis methods. (springer.com)
  • In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. (mdpi.com)
  • CASP10 (Caspase 10) is a Protein Coding gene. (genecards.org)
  • Of 35 selected single-nucleotide polymorphisms, four in the caspase-7 gene were in high linkage disequilibrium (rs11593766, rs3124740, rs11196445, and rs11196418) and associated with the risk for endometrial cancer. (aacrjournals.org)
  • No association was observed between polymorphisms of the caspase-8 gene and risk for endometrial cancer. (aacrjournals.org)
  • Caspase 2 was isolated from a human fetal cDNA library by screening with a probe of the mouse ICE-homolog Need-2 gene, 12 13 and the caspase 2 gene has been assigned to chromosome 7q35. (bloodjournal.org)
  • Once active, initiator caspases proteolytically cleave effector caspases at distinct aspartate residues, to release the prodomain, large and small subunits. (els.net)
  • A short pro-domain caspase that plays an effector Role in Apoptosis . (online-medical-dictionary.org)
  • A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES. (umassmed.edu)
  • These effector fragments may become newly active (as in the case of caspase‐mediated cleavage of ROCK1) or may act to inhibit normal protein function (e.g. caspase‐mediated cleavage of IKB renders the protein resistant to proteosomal degradation and thus allows for sustained inhibition of NFκB, see text for details). (els.net)
  • Although related, P49 and P35 inhibit initiator and effector caspases, respectively, during infection of permissive insect cells. (pubmedcentralcanada.ca)
  • The effector caspases inhibit the enzymes that repair damaged DNA. (wisegeek.com)
  • High levels of Bcl-2 expression did not effectively inhibit apoptosis induced by anti-Fas but inhibited AICD by inhibiting the secretion of sFasL at a level above caspase-8 activation. (bl.uk)
  • The orthologs differed markedly in their propensity to inhibit non-mammalian caspases. (portlandpress.com)
  • Almost all variants retained the ability to inhibit caspase-1, but many lacked caspase-8 inhibitory activity. (portlandpress.com)
  • Depending on the structure of the prodomain and their function, caspases are typically divided into 3 major groups (Figure 1 A). The caspases with large prodomains are referred to as inflammatory caspases (group I) and initiator of apoptosis caspases (group II), while caspases with a short prodomain of 20-30 amino acids are named effector caspases (group III). (jci.org)
  • Cleavage of the procaspase at the specific Asp-X bonds leads to the formation of the mature caspase, which comprises the heterotetramer p20 2 -p10 2 , and the release of the prodomain. (jci.org)
  • The prodomain of the initiator (also known as apical) caspases (2, 8, 9 and 10) is much longer than that of effector caspases 3, 6 and 7. (els.net)
  • The molecular basis of this novel caspase specificity is unknown. (pubmedcentralcanada.ca)
  • In contrast, the effector caspase specificity of P35 was unaltered when P35's DQMD motif was replaced with TVTD. (pubmedcentralcanada.ca)
  • Our findings demonstrate a critical role for the P 4 -P 1 recognition site in caspase specificity by P49 and P35 and indicate that additional determinants are involved in target selection. (pubmedcentralcanada.ca)
  • Because selective inhibition of caspases may be advantageous in therapeutics for apoptosis-associated diseases, the molecular basis of target specificity by P49 and P35 is of considerable interest. (pubmedcentralcanada.ca)
  • We compared the caspase specificity of CrmA to three orthologs from orthopoxviruses and four from more distant chordopoxviruses. (portlandpress.com)
  • In summary, the effector caspases are not involved in early nuclear morphological change, which precedes the conventional hallmark morphological changes associated with chemical-induced apoptosis. (abo.fi)
  • These results demonstrate that p53 is required for caspase activation in response to some forms of neuronal injury. (jneurosci.org)
  • Here, we have screened a panel of 90 long noncoding RNAs (lncRNA) and identified a lncRNA, SAF, that plays a critical role in the resistance of HIV-1-infected macrophages to activation of apoptotic caspases. (pnas.org)
  • Structure and activation of apoptotic caspases. (els.net)
  • Both biochemical and genetic evidence indicates that Bcl-2 family members can regulate cell death induced by caspases ( 2 ). (sciencemag.org)
  • After induction of apoptosis, there is a convergence in signalling at the level of caspase activation and subsequent biochemical and morphological changes. (bl.uk)
  • Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) -induced apoptosis, in transformed human breast epithelial MCF-7 cells, resulted in a time-dependent activation of the initiator caspases-8 and -9 and the effector caspase-7. (rupress.org)
  • There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. (mdpi.com)
  • These data seem to question a general tumor-suppressive role of caspases. (mdpi.com)
  • We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
  • First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. (mdpi.com)
  • We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
  • Western blot analysis showed increased transcriptional activities of Fas ligand, tumor necrosis factor-α, Bax, Fas-associated death domain, and tumor necrosis factor receptor 1-associated death domain as well as elevated levels of cleaved caspases and poly(ADP-ribose) polymerase. (aacrjournals.org)
  • The levels of SIRT1 , caspase-3, forkhead box protein O1 ( FOXO1 ), FasL (tumor necrosis factor ligand superfamily member 6), BAX , and Bcl-2 were measured by reverse transcription-polymerase chain reaction and Western blotting. (dovepress.com)
  • An activatable fluorescent peptide probe incorporating an effector caspase cleavage site has been developed and validated in vitro (J Med Chem 2005 48:5404). (arvojournals.org)
  • Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death. (sciencemag.org)
  • Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. (nih.gov)
  • With the exception of caspase-3, all of the components of the core cell-death machinery are expressed in all of the cell lines examined. (aacrjournals.org)
  • We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (jci.org)
  • The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. (rupress.org)
  • We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. (nature.com)
  • Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies. (nature.com)
  • Caspase activation may proceed through either an external (extrinsic) or internal (intrinsic) death pathway, dependent on the stimulus. (els.net)
  • The binding of extracellular ligands to death receptors triggers the formation of a DISC complex resulting in the activation of initiator caspases 8 and/or 10. (els.net)
  • Not surprisingly, because of their central role in cell death, both types of caspases are important therapeutic targets for the treatment of apoptosis-associated diseases ( 11 , 23 ). (pubmedcentralcanada.ca)
  • Contains 2 DED (death effector) domains. (abcam.com)
  • Caspase-8 plays an essential role in apoptotic signal transduction from the death receptor. (haematologica.org)
  • Caspase activity is due to a group of very complex enzymes that regulate programmed cell death, or apoptosis , in multicellular organisms. (wisegeek.com)
  • Once the process of apoptotic death has been initiated, the caspases are activated by having part of their structure cleaved. (wisegeek.com)
  • Here, we show that the Phytophthora sojae effector protein Avr1b can contribute positively to virulence and can suppress programmed cell death (PCD) triggered by the mouse BAX protein in yeast, soybean ( Glycine max ), and Nicotiana benthamiana cells. (plantcell.org)
  • Caspases play a pivotal role in neuronal cell death during development and after trophic factor withdrawal. (jneurosci.org)
  • In the present study we determined if p53-mediated neuronal cell death required caspase activation. (jneurosci.org)
  • However, the relative importance of caspase activation in neurons depends on the developmental status of the cell and the specific nature of the death stimulus. (jneurosci.org)
  • suggesting that caspases are essential to the regulation of developmental cell death in neurons. (jneurosci.org)
  • Although the exact mechanism by which Bax promotes cell death is not known, several studies have suggested that Bax may cooperate with bcl-2 or bcl-X L , or it may act independently to regulate the activation of caspases (J. G. (jneurosci.org)
  • This suggested that caspases may be associated with a p53-mediated Bax-dependent cell death pathway. (jneurosci.org)
  • We therefore examined whether caspases are activated in neurons after injury in a p53-dependent manner and, if so, whether such activation is essential for p53-dependent neuronal cell death. (jneurosci.org)
  • Because caspase activation is an essential step in programmed cell death (apoptosis) and cytotoxic drug-induced apoptosis is mediated by caspase 2 and caspase 3, we hypothesized that caspase 2 and 3 levels predict clinical outcome in acute myelogenous leukemia (AML). (bloodjournal.org)
  • In contrast, activation-induced cell death of T cells in c-FLIP L Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. (asm.org)
  • Both for the effector function of cytolytic T cells and in the elimination of expanded T cells, cell death signals transmitted by Fas/CD95 are of key importance ( 30 ). (asm.org)
  • In this work, we expand on our previous work with DEHP and screen the 2-EH metabolite for different cell death endpoints such as growth inhibition, apoptosis, autophagy, caspase activation, DNA fragmentation, and cell cycle arrest using fluorophores and the NC3000 instrument. (scirp.org)
  • Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. (genecards.org)
  • Erucylphosphocholine-induced apoptosis in glioma cells: involvement of death receptor signalling and caspase activation. (semanticscholar.org)
  • Activated caspase-1 is required for cleaving/processing of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 into mature pro-inflammatory cytokines IL-1β and IL-18, respectively. (springer.com)
  • Minocycline represses diabetes-induced inflammatory cytokine production, reduces the release of cytotoxins from activated microglia, and significantly reduces measurable caspase-3 activity within the retina. (diabetesjournals.org)
  • These enzymes can be divided into initiators and effectors. (genecards.org)
  • Statistical IL-16 antibody significance was attained was and activation of caspases-3 by WF-208 Caspase-3 is among the most crucial protein of apoptosis which is available as zymogen procaspase-3 before activation. (healthcarecoremeasures.com)
  • Subsequently, the effector caspases are activated by initiator caspase-mediated cleavage of their inactive zymogen (procaspase) form. (pubmedcentralcanada.ca)
  • From clinical data, however, there is little evidence that caspase genes are impaired in cancer. (mdpi.com)
  • We examined the association between genetic variants in the caspase-3 , caspase-7 , and caspase-8 genes and risk for endometrial cancer among Chinese women. (aacrjournals.org)
  • Genetic polymorphisms in the caspase genes may affect cancer risk through altering expression levels and functions of these genes. (aacrjournals.org)
  • Further work revealed that caspase-8 was essential for the induction of the transcription factor "nuclear factor κB" ( NF-κB ) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells . (wikipedia.org)
  • They serve as key effectors downstream of diverse signaling receptors and shape cell fate. (mit.edu)
  • Caspase-1 has been shown to induce cell necrosis, pyroptosis, or pyrop-apoptosis [ 4 ] and exerts functions in various developmental stages. (springer.com)
  • 11 In addition, activation of caspase 3 and, to some extent, caspase 2 (ICH-1) 12-16 appears to be necessary to induce apoptosis in HL-60 myeloid leukemia cells. (bloodjournal.org)
  • Thus, our results demonstrate that sulindac sulfide also engages the membrane DR pathway involving DR5 and proximal caspase 8 to induce apoptosis. (aacrjournals.org)
  • However, because KSBcl-2 was not cleavable by caspases, the latent proapoptotic activity of KSBcl-2 apparently cannot be released. (asm.org)
  • The caspase cleavage products of Bcl-2 and Bcl-x L are potently proapoptotic, based on transfection studies expressing protein fragments that are equivalent to caspase cleavage products ( 8 , 13 ). (asm.org)
  • We have further shown that down-regulation of SAF expression with siRNA treatment can activate effector caspase-3/7 specifically in virus-infected macrophages without affecting the uninfected and bystander cells. (pnas.org)
  • This induction of apoptotic caspases occurs exclusively in HIV-1-infected macrophages and not in bystander cells, leading to a significant reduction in HIV-1 replication and overall viral burden in the macrophage culture. (pnas.org)
  • Bcl-2 is cleaved by caspases both in vitro and in intact cells. (sciencemag.org)
  • Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. (sciencemag.org)
  • Apaf-1 and procaspase-9, which are implicated in caspase activation after treatment of cells with various anticancer drugs, were detectable in all of the cell lines, with levels of Apaf-1 ranging from ∼1 × 10 5 to 2 × 10 6 molecules per cell and procaspase-9 from ∼5 × 10 3 to ∼1.6 × 10 5 molecules per cell. (aacrjournals.org)
  • Using transient transfection of COOH-terminal-tagged green fluorescent protein fusion constructs, caspases-3, -7, and -8 were localized throughout the cytoplasm of MCF-7 cells. (rupress.org)
  • These inclusions, which were also induced in untransfected cells, contained cytokeratins 8, 18, and 19, together with both a phosphorylated form and a caspase-cleavage fragment of cytokeratin 18. (rupress.org)
  • Similarly, in untransfected breast HBL100 and lung A549 epithelial cells, TRAIL induced the formation of cytoplasmic inclusions that contained cleaved cytokeratin 18 and colocalized with active endogenous caspase-3. (rupress.org)
  • However, there is no evidence yet for a role of caspases during T cell activation, and a recent report suggested that the observed caspase processing was due to the production of granzyme B by CD8 + activated cells and artifactual release during cell lysis of PBMCs ( 19 ). (rupress.org)
  • Caspase cleavage product lacking amino-terminus of IκBα sensitizes resistant cells to TNF-α and TRAIL-induced apoptosis. (nature.com)
  • Although cytochrome c efflux from the mitochondria and the processing of caspase-3 were observed in Jurkat cells with pre-apoptotic nuclear morphology, caspase-2, -6, -7 and -8 were not activated. (abo.fi)
  • In the presence of z-DEVD-FMK or Ac-YVAD-CMK, caspase-3 was processed to both the p17 and p20 fragments in staurosporine-treated cells, but only to p20 fragment in the presence of z-VAD-FMK. (abo.fi)
  • A) WF-208 and PAC-1 induced the cleavage of procaspase- 3 to caspase-3 in HL-60 cells (upon) and U-937 (below) at different period and focus. (healthcarecoremeasures.com)
  • Alterations in the regulation of apoptosis can lead to cancer or autoimmune disease, so there is much interest in better understanding the biochemistry and genetics of caspase activation in human cells using more simple organisms. (wisegeek.com)
  • To keep the cells from self-destructing, caspases are kept in an inactive state. (wisegeek.com)
  • Meanwhile, the cytotoxins induced mainly caspase-independent late apoptosis in the prostate (PC-3) and breast (MCF-7) cancer cells lines but lacked selectivity. (frontiersin.org)
  • Caspase-3 and caspase-7 have been identified as key executors of apoptosis in mammalian cells and play a central role in the execution phase of apoptosis ( 14 , 15 ). (aacrjournals.org)
  • In this study, we investigated the function of p38 mitogen-activated protein kinase (MAPK) and caspase-8 in DATS-induced apoptosis of human CNE2 cells using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], flow cytometry assay, and Western blotting. (scielo.br)
  • In conclusion, our data indicate that p38MAPK and caspase-8 are involved in the process of DATS-induced apoptosis in human CNE2 cells and interact with each other. (scielo.br)
  • In the central control and effective stage of apoptosis, activated caspase-8 can lead directly to the appearance of apoptotic structural characteristics in cells, and play a key role in the process of apoptosis (6,7). (scielo.br)
  • In clinical transplantation host CTL are major effectors of acute rejection, and graft endothelial cells (EC) are major targets of the CTL response. (jimmunol.org)
  • Using quantitative Western blot analysis, we studied the levels of nonactivated (uncleaved) caspase 2 and 3 in peripheral blood low-density cells from 185 patients with newly diagnosed AML. (bloodjournal.org)
  • mTORC1 activity very critical for the generation of effector CD8 T cells. (biocompare.com)
  • Concomitantly with proliferation, T cells differentiate into effector cells that are either cytolytic or able to provide help to B lymphocytes. (asm.org)
  • Once the effector cells have successfully performed their prescribed function, the expanded pool of antigen-specific T-cell clones needs to be reduced to its original size. (asm.org)
  • Florentin and Arama reveal that differences in the expression levels and execution efficiencies of caspases determine whether or not cells die in response to apoptotic stimuli. (weizmann.ac.il)
  • Caspase activation was detected in TUNEL-positive cells. (arvojournals.org)
  • Third, the apoptosis induction of maspin-transfected cells was associated with increased activation of both caspase-8 and caspase-9. (aacrjournals.org)