Poly Adenosine Diphosphate Ribose: A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.Nucleoside Diphosphate SugarsRibose: A pentose active in biological systems usually in its D-form.NAD+ NucleosidaseAdenosine Diphosphate Sugars: Esters formed between the aldehydic carbon of sugars and the terminal phosphate of adenosine diphosphate.Cyclic ADP-Ribose: A pyridine nucleotide that mobilizes CALCIUM. It is synthesized from nicotinamide adenine dinucleotide (NAD) by ADP RIBOSE CYCLASE.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.NAD: A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)Periodic Acid: A strong oxidizing agent.Adenosine Diphosphate Ribose: An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Receptor, Adenosine A2A: A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Receptor, Adenosine A1: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Adenine NucleotidesAdenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Receptors, Purinergic P2Y12: A subclass of purinergic P2Y receptors that have a preference for ADP binding and are coupled to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI. The P2Y12 purinergic receptors are found in PLATELETS where they play an important role regulating PLATELET ACTIVATION.Adenosine Diphosphate Glucose: Serves as the glycosyl donor for formation of bacterial glycogen, amylose in green algae, and amylopectin in higher plants.Receptor, Adenosine A3: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.Receptor, Adenosine A2B: A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Purinergic P2Y Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.Platelet Function Tests: Laboratory examination used to monitor and evaluate platelet function in a patient's blood.Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.Receptors, Adenosine A2: A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Alkyl and Aryl Transferases: A somewhat heterogeneous class of enzymes that catalyze the transfer of alkyl or related groups (excluding methyl groups). EC 2.5.Apyrase: A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC 3.6.1.5.Polyisoprenyl Phosphates: Phosphoric or pyrophosphoric acid esters of polyisoprenoids.Ribosemonophosphates: Ribose substituted in the 1-, 3-, or 5-position by a phosphoric acid moiety.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Nucleoside-Diphosphate Kinase: An enzyme that is found in mitochondria and in the soluble cytoplasm of cells. It catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside diphosphate, e.g., UDP, to form ADP and UTP. Many nucleoside diphosphates can act as acceptor, while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.6.Ticlopidine: An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.Blood Platelet Disorders: Disorders caused by abnormalities in platelet count or function.Platelet Adhesiveness: The process whereby PLATELETS adhere to something other than platelets, e.g., COLLAGEN; BASEMENT MEMBRANE; MICROFIBRILS; or other "foreign" surfaces.Kinetics: The rate dynamics in chemical or physical systems.Hemiterpenes: The five-carbon building blocks of TERPENES that derive from MEVALONIC ACID or deoxyxylulose phosphate.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Receptors, Purinergic: Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.Xanthines: Purine bases found in body tissues and fluids and in some plants.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Receptors, Purinergic P2Y1: A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Platelet Membrane Glycoproteins: Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Platelet Storage Pool Deficiency: Disorder characterized by a decrease or lack of platelet dense bodies in which the releasable pool of adenine nucleotides and 5HT are normally stored.Clot Retraction: Retraction of a clot resulting from contraction of PLATELET pseudopods attached to FIBRIN strands. The retraction is dependent on the contractile protein thrombosthenin. Clot retraction is used as a measure of platelet function.Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Platelet Factor 3: A phospholipid from the platelet membrane that contributes to the blood clotting cascade by forming a phospholipid-protein complex (THROMBOPLASTIN) which serves as a cofactor with FACTOR VIIA to activate FACTOR X in the extrinsic pathway of BLOOD COAGULATION.Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.NM23 Nucleoside Diphosphate Kinases: A family of nucleotide diphosphate kinases that play a role in a variety of cellular signaling pathways that effect CELL DIFFERENTIATION; CELL PROLIFERATION; and APOPTOSIS. They are considered multifunctional proteins that interact with a variety of cellular proteins and have functions that are unrelated to their enzyme activity.Megakaryocyte Progenitor Cells: The parent cells that give rise to cells in the MEGAKARYOCYTE lineage, and ultimately BLOOD PLATELETS.Diphosphates: Inorganic salts of phosphoric acid that contain two phosphate groups.Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.Inosine: A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)PentosephosphatesBleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function.Dimethylallyltranstransferase: An enzyme that, in the pathway of cholesterol biosynthesis, catalyzes the condensation of isopentenyl pyrophosphate and dimethylallylpyrophosphate to yield pyrophosphate and geranylpyrophosphate. The enzyme then catalyzes the condensation of the latter compound with another molecule of isopentenyl pyrophosphate to yield pyrophosphate and farnesylpyrophosphate. EC 2.5.1.1.Carbon-Carbon Double Bond Isomerases: Enzymes that catalyze the shifting of a carbon-carbon double bond from one position to another within the same molecule. EC 5.3.3.Phosphates: Inorganic salts of phosphoric acid.Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.Nucleosides: Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Platelet Count: The number of PLATELETS per unit volume in a sample of venous BLOOD.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Thromboxane B2: A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).5'-Nucleotidase: A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.
(1/1280) Activation of Go-proteins by membrane depolarization traced by in situ photoaffinity labeling of galphao-proteins with [alpha32P]GTP-azidoanilide.

Evidence for depolarization-induced activation of G-proteins in membranes of rat brain synaptoneurosomes has been previously reported (Cohen-Armon, M., and Sokolovsky, M. (1991) J. Biol. Chem. 266, 2595-2605; Cohen-Armon, M., and Sokolovsky, M. (1993) J. Biol. Chem. 268, 9824-9838). In the present work we identify the activated G-proteins as Go-proteins by tracing their depolarization-induced in situ photoaffinity labeling with [alpha32P]GTP-azidoanilide (GTPAA). Labeled GTPAA was introduced into transiently permeabilized rat brain-stem synaptoneurosomes. The resealed synaptoneurosomes, while being UV-irradiated, were depolarized. Relative to synaptoneurosomes at resting potential, the covalent binding of [alpha32P]GTPAA to Galphao1- and Galphao3-proteins, but not to Galphao2- isoforms, was enhanced by 5- to 7-fold in depolarized synaptoneurosomes, thereby implying an accelerated exchange of GDP for [alpha32P]GTPAA. Their depolarization-induced photoaffinity labeling was independent of stimulation of Go-protein-coupled receptors and could be reversed by membrane repolarization, thus excluding induction by transmitters release. It was, however, dependent on depolarization-induced activation of the voltage-gated sodium channels (VGSC), regardless of Na+ current. The alpha subunit of VGSC was cross-linked and co-immunoprecipitated with Galphao-proteins in depolarized brain-stem and cortical synaptoneurosomes. VGSC alpha subunit most efficiently cross-linked with guanosine 5'-O-2-thiodiphosphate-bound rather than to guanosine 5'-O-(3-thiotriphosphate)-bound Galphao-proteins in isolated synaptoneurosomal membranes. These findings support a possible involvement of VGSC in depolarization-induced activation of Go-proteins.  (+info)

(2/1280) CD38 signaling in B lymphocytes is controlled by its ectodomain but occurs independently of enzymatically generated ADP-ribose or cyclic ADP-ribose.

CD38 is a type II transmembrane glycoprotein that is expressed by many cell types including lymphocytes. Signaling through CD38 on B lymphocytes can mediate B cell activation, proliferation, and cytokine secretion. Additionally, coligation of CD38 and the B cell Ag receptor can greatly augment B cell Ag receptor responses. Interestingly, the extracellular domain of CD38 catalyzes the conversion of NAD+ into nicotinamide, ADP-ribose (ADPR), and cyclic ADPR (cADPR). cADPR can induce intracellular calcium release in an inositol trisphosphate-independent manner and has been hypothesized to regulate CD38-mediated signaling. We demonstrate that replacement of the cytoplasmic tail and the transmembrane domains of CD38 did not impair CD38 signaling, coreceptor activity, or enzyme activity. In contrast, independent point mutations in the extracellular domain of CD38 dramatically impaired signal transduction. However, no correlation could be found between CD38-mediated signaling and the capacity of CD38 to catalyze an enzyme reaction and produce cADPR, ADPR, and/or nicotinamide. Instead, we propose that CD38 signaling and coreceptor activity in vitro are regulated by conformational changes induced in the extracellular domain upon ligand/substrate binding, rather than on actual turnover or generation of products.  (+info)

(3/1280) Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway.

Lymphocyte extravasation into the brain is mediated largely by the Ig superfamily molecule ICAM-1. Several lines of evidence indicate that at the tight vascular barriers of the central nervous system (CNS), endothelial cell (EC) ICAM-1 not only acts as a docking molecule for circulating lymphocytes, but is also involved in transducing signals to the EC. In this paper, we examine the signaling pathways in brain EC following Ab ligation of endothelial ICAM-1, which mimics adhesion of lymphocytes to CNS endothelia. ICAM-1 cross-linking results in a reorganization of the endothelial actin cytoskeleton to form stress fibers and activation of the small guanosine triphosphate (GTP)-binding protein Rho. ICAM-1-stimulated tyrosine phosphorylation of the actin-associated molecule cortactin and ICAM-1-mediated, Ag/IL-2-stimulated T lymphocyte migration through EC monolayers were inhibited following pretreatment of EC with cytochalasin D. Pretreatment of EC with C3 transferase, a specific inhibitor of Rho proteins, significantly inhibited the transmonolayer migration of T lymphocytes, endothelial Rho-GTP loading, and endothelial actin reorganization, without affecting either lymphocyte adhesion to EC or cortactin phosphorylation. These data show that brain vascular EC are actively involved in facilitating T lymphocyte migration through the tight blood-brain barrier of the CNS and that this process involves ICAM-1-stimulated rearrangement of the endothelial actin cytoskeleton and functional EC Rho proteins.  (+info)

(4/1280) Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus.

Ca2+ released from presynaptic and postsynaptic intracellular stores plays important roles in activity-dependent synaptic plasticity, including long-term depression (LTD) of synaptic strength. At Schaffer collateral-CA1 synapses in the hippocampus, presynaptic ryanodine receptor-gated stores appear to mobilize some of the Ca2+ necessary to induce LTD. Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activator of ryanodine receptors in sea urchin eggs and several mammalian cell types. Here, we provide evidence that cADPR-mediated signaling pathways play a key role in inducing LTD. We show that biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and that blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each prevent the induction of LTD at Schaffer collateral-CA1 synapses. A lack of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site of action.  (+info)

(5/1280) Poly-ADP ribose polymerase activates nuclear proteasome to degrade oxidatively damaged histones.

The 20S proteasome has been shown to be largely responsible for the degradation of oxidatively modified proteins in the cytoplasm. Nuclear proteins are also subject to oxidation, and the nucleus of mammalian cells contains proteasome. In human beings, tumor cells frequently are subjected to oxidation as a consequence of antitumor chemotherapy, and K562 human myelogenous leukemia cells have a higher nuclear proteasome activity than do nonmalignant cells. Adaptation to oxidative stress appears to be one element in the development of long-term resistance to many chemotherapeutic drugs and the mechanisms of inducible tumor resistance to oxidation are of obvious importance. After hydrogen peroxide treatment of K562 cells, degradation of the model proteasome peptide substrate suc-LLVY-MCA and degradation of oxidized histones in nuclei increases significantly within minutes. Both increased proteolytic susceptibility of the histone substrates (caused by modification by oxidation) and activation of the proteasome enzyme complex occur independently during oxidative stress. This rapid up-regulation of 20S proteasome activity is accompanied by, and depends on, poly-ADP ribosylation of the proteasome, as shown by inhibitor experiments, 14C-ADP ribose incorporation assays, immunoblotting, in vitro reconstitution experiments, and immunoprecipitation of (activated) proteasome with anti-poly-ADP ribose polymerase antibodies. The poly-ADP ribosylation-mediated activated nuclear 20S proteasome is able to remove oxidatively damaged histones more efficiently and therefore is proposed as an oxidant-stimulatable defense or repair system of the nucleus in K562 leukemia cells.  (+info)

(6/1280) Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration.

Aberrant regulation of smooth muscle cell proliferation and migration is associated with the pathophysiology of vascular disorders such as hypertension, atherosclerosis, restenosis, and graft rejection. To elucidate molecular mechanisms that regulate proliferation and migration of vascular smooth muscle cells, we determined whether signaling through the small G protein Rho is involved in thrombin- and phenylephrine-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). Thrombin and the thrombin peptide SFLLRNP stimulated DNA synthesis of RASMCs as measured by [3H]thymidine incorporation. Both ligands also increased cell migration as measured by the Boyden chamber method. L-Phenylephrine failed to induce either of these responses but increased inositol phosphate accumulation and mitogen-activated protein kinase activation in these cells, which indicated that the cells were responsive to alpha1-adrenergic stimulation. The C3 exoenzyme, which ADP-ribosylates and inactivates Rho, fully inhibited both thrombin-stimulated proliferation and migration but had no effect on inositol phosphate accumulation. In addition, Y-27632, an inhibitor of the Rho effector p160ROCK/Rho kinase, decreased thrombin-stimulated DNA synthesis and migration. To directly examine Rho activation, Rho-[35S]GTPgammaS binding was measured. The addition of the thrombin peptide SFLLRNP, but not phenylephrine, to RASMC lysates resulted in a significant increase in Rho-[35S]GTPgammaS binding. Thrombin and SFLLRNP, but not phenylephrine, also increased membrane-associated Rho in intact RASMCs, consistent with selective activation of Rho by thrombin. These results indicate that thrombin activates Rho in RASMCs and establish Rho as a critical mediator of thrombin receptor effects on DNA synthesis and cell migration in these cells.  (+info)

(7/1280) Identification of critical, conserved vicinal aspartate residues in mammalian and bacterial ADP-ribosylarginine hydrolases.

NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyze opposing arms of a putative ADP-ribosylation cycle. ADP-ribosylarginine hydrolases from mammalian tissues and Rhodospirillum rubrum exhibit three regions of similarity in deduced amino acid sequence. We postulated that amino acids in these consensus regions could be critical for hydrolase function. To test this hypothesis, hydrolase, cloned from rat brain, was expressed as a glutathione S-transferase fusion protein in Escherichia coli and purified by glutathione-Sepharose affinity chromatography. Conserved amino acids in each of these regions were altered by site-directed mutagenesis. Replacement of Asp-60 or Asp-61 with Ala, Gln, or Asn, but not Glu, significantly reduced enzyme activity. The double Asp-60 --> Glu/Asp-61 --> Glu mutant was inactive, as were Asp-60 --> Gln/Asp-61 --> Gln or Asp-60 --> Asn/Asp-61 --> Asn. The catalytically inactive single and double mutants appeared to retain conformation, since they bound ADP-ribose, a substrate analogue and an inhibitor of enzyme activity, with affinity similar to that of the wild-type hydrolase and with the expected stoichiometry of one. Replacing His-65, Arg-139, Asp-285, which are also located in the conserved regions, with alanine did not change specific activity. These data clearly show that the conserved vicinal aspartates 60 and 61 in rat ADP-ribosylarginine hydrolase are critical for catalytic activity, but not for high affinity binding of the substrate analogue, ADP-ribose.  (+info)

(8/1280) An antagonist of cADP-ribose inhibits arrhythmogenic oscillations of intracellular Ca2+ in heart cells.

Oscillations of Ca2+ in heart cells are a major underlying cause of important cardiac arrhythmias, and it is known that Ca2+-induced release of Ca2+ from intracellular stores (the sarcoplasmic reticulum) is fundamental to the generation of such oscillations. There is now evidence that cADP-ribose may be an endogenous regulator of the Ca2+ release channel of the sarcoplasmic reticulum (the ryanodine receptor), raising the possibility that cADP-ribose may influence arrhythmogenic mechanisms in the heart. 8-Amino-cADP-ribose, an antagonist of cADP-ribose, suppressed oscillatory activity associated with overloading of intracellular Ca2+ stores in cardiac myocytes exposed to high doses of the beta-adrenoreceptor agonist isoproterenol or the Na+/K+-ATPase inhibitor ouabain. The oscillations suppressed by 8-amino-cADP-ribose included intracellular Ca2+ waves, spontaneous action potentials, after-depolarizations, and transient inward currents. Another antagonist of cADP-ribose, 8-bromo-cADP-ribose, was also effective in suppressing isoproterenol-induced oscillatory activity. Furthermore, in the presence of ouabain under conditions in which there was no arrhythmogenesis, exogenous cADP-ribose was found to be capable of triggering spontaneous contractile and electrical activity. Because enzymatic machinery for regulating the cytosolic cADP-ribose concentration is present within the cell, we propose that 8-amino-cADP-ribose and 8-bromo-cADP-ribose suppress cytosolic Ca2+ oscillations by antagonism of endogenous cADP-ribose, which sensitizes the Ca2+ release channels of the sarcoplasmic reticulum to Ca2+.  (+info)

*  Adenosine diphosphate ribose
... is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. It binds to and ... Adenosine diphosphate Ribose Fonfria E, Marshall IC, Benham CD, et al. (September 2004). "TRPM2 channel opening in response to ... oxidative stress is dependent on activation of poly(ADP-ribose) polymerase". Br. J. Pharmacol. 143 (1): 186-92. doi:10.1038/sj. ...
*  NAD+ nucleosidase
"Nicotinamide adenine dinucleotide glycohydrolases and poly adenosine diphosphate ribose synthesis in rat liver". Biochem. ... ADP-ribose + nicotinamide Thus, the two substrates of this enzyme are NAD+ and H2O, whereas its two products are ADP-ribose and ...
*  DNA repair
PARP1 synthesizes polymeric adenosine diphosphate ribose (poly (ADP-ribose) or PAR) chains on itself. Next the chromatin ... Li D, Bi FF, Cao JM, Cao C, Li CY, Liu B, Yang Q (2014). "Poly (ADP-ribose) polymerase 1 transcriptional regulation: a novel ... In further steps, Poly (ADP-ribose) polymerase 1 (PARP1) is required and may be an early step in MMEJ. There is pairing of ... The PARP1 protein, attached to both DDB1 and DDB2, then PARylates (creates a poly-ADP ribose chain) on DDB2 that attracts the ...
*  Parthanatos
Noncovalent Interactions of Poly(adenosine diphosphate ribose) with Histones. Biochemistry-US. 31: 1397-1385. Fatokun AA, ... ADP-ribose) glycohydrolase. Biochemistry 50: 2850-2859. Wang Y, Dawson VL, Dawson TM. 2009. Poly(ADP-ribose) signals to ... Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Natl Acad Sci. 103: 18308-18313 Yu SW, Wang H, Poitras MF, Coombs C, ... Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci U S A 96: 13978-13982 ...
*  NADH dehydrogenase (ubiquinone)
Complex I is also blocked by adenosine diphosphate ribose - a reversible competitive inhibitor of NADH oxidation - by binding ... by ADP-ribose". Biochimica et Biophysica Acta. 1320 (3): 256-64. doi:10.1016/S0005-2728(97)00029-7. PMID 9230920. Viollet B, ...
*  Poly(ADP-ribose) glycohydrolase
ADP-ribose). Miwa, M.; Sugimura, T. (1971). "Splitting of the ribose-ribose linkage of poly(adenosine diphosphate-ribose) by a ... linkage of ribose-ribose bond to produce free ADP-ribose Specific to (1-2') linkage of ribose-ribose bond of poly( ... ADP-ribose) glycohydrolase". J. Biol. Chem. 272: 11895-11901. doi:10.1074/jbc.272.18.11895. PMID 9115250. Poly(ADP-ribose) ... Poly(ADP-ribose) glycohydrolase (EC 3.2.1.143) is an enzyme. This enzyme catalyses the following chemical reaction hydrolyses ...
*  Ribose-5-phosphate adenylyltransferase
Stern AI, Avron M (1966). "An adenosine 5'-diphosphate ribose:orthophosphate adenylyltransferase from Euglena gracilis". ... D-ribose-5-phosphate adenylyltransferase. Other names in common use include ADP ribose phosphorylase, and adenosine ... ADP-ribose Thus, the two substrates of this enzyme are ADP and D-ribose 5-phosphate, whereas its two products are phosphate and ... In enzymology, a ribose-5-phosphate adenylyltransferase (EC 2.7.7.35) is an enzyme that catalyzes the chemical reaction ADP + D ...
*  Poly (ADP-ribose) polymerase
... and begins the synthesis of a polymeric adenosine diphosphate ribose (poly (ADP-ribose) or PAR) chain, which acts as a signal ... ADP-ribose) glycohydrolase (PARG). NAD+ is required as substrate for generating ADP-ribose monomers. It has been thought that ... Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, ... Bürkle A, Brabeck C, Diefenbach J, Beneke S (May 2005). "The emerging role of poly(ADP-ribose) polymerase-1 in longevity". Int ...
*  Adenosine diphosphate receptor inhibitor
The sugar ribose unit was also replaced with a cyclopentyl group to avoid possible unstability of the glycosidic bond. The ... Adenosine diphosphate (ADP) receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute ... P2Y12 receptor is a G-coupled receptor and is activated by adenosine diphosphate. ADP binds to the P2Y12 receptor that leads to ... "Platelet Adenosine Diphosphate P2Y12 Receptor Antagonism: Benefits and Limitations of Current Treatment Strategies and Future ...
*  Adenosine diphosphate
... a sugar backbone attached to adenine and two phosphate groups bonded to the 5 carbon atom of ribose. The diphosphate group of ... Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is ... ADP in the blood is converted to adenosine by the action of ecto-ADPases, inhibiting further platelet activation via adenosine ... ADP can be interconverted to adenosine triphosphate (ATP) and adenosine monophosphate (AMP). ATP contains one more phosphate ...
*  List of MeSH codes (D09)
... adenosine diphosphate glucose MeSH D09.408.620.569.070.125 --- adenosine diphosphate ribose MeSH D09.408.620.569.070.125.040 ... cyclic adp-ribose MeSH D09.408.620.569.070.125.600 --- poly adenosine diphosphate ribose MeSH D09.408.620.569.200 --- cytidine ... nucleoside diphosphate sugars MeSH D09.408.620.569.070 --- adenosine diphosphate sugars MeSH D09.408.620.569.070.075 --- ... uridine diphosphate n-acetylglucosamine MeSH D09.408.620.569.727.150 --- uridine diphosphate n-acetylmuramic acid MeSH D09.408. ...
*  List of MeSH codes (D13)
... adenosine diphosphate glucose MeSH D13.695.667.138.124.070.125 --- adenosine diphosphate ribose MeSH D13.695.667.138.124.070. ... adenosine diphosphate glucose MeSH D13.695.827.068.124.070.125 --- adenosine diphosphate ribose MeSH D13.695.827.068.124.070. ... adenosine diphosphate glucose MeSH D13.695.827.708.070.125 --- adenosine diphosphate ribose MeSH D13.695.827.708.070.125.040 ... cyclic adp-ribose MeSH D13.695.827.708.070.125.600 --- poly adenosine diphosphate ribose MeSH D13.695.827.708.260 --- cytidine ...
*  Adenosine 3',5'-bisphosphate
This is distinct from adenosine diphosphate, where the two phosphate groups are attached in a chain to the 5' carbon atom in ... bisphosphate is a form of an adenosine nucleotide with two phosphate groups attached to different carbons in the ribose ring. ... Adenosine 3',5'-bisphosphate is produced as a product of sulfotransferase enzymes from the donation of a sulfate group from the ... This product is then hydrolysed by 3'(2'),5'-bisphosphate nucleotidase to give adenosine monophosphate, which can then be ...
*  NUDT9
ADP-ribose pyrophosphatase, mitochondrial is an enzyme that in humans is encoded by the NUDT9 gene. GRCh38: Ensembl release 89 ... "Entrez Gene: NUDT9 nudix (nucleoside diphosphate linked moiety X)-type motif 9". Lin S, Gasmi L, Xie Y, et al. (2002). "Cloning ... expression and characterisation of a human Nudix hydrolase specific for adenosine 5'-diphosphoribose (ADP-ribose)". Biochim. ... 2004). "Interaction of C17orf25 with ADP-ribose pyrophosphatase NUDT9 detected via yeast two-hybrid method". Sheng Wu Hua Xue ...
*  Cytidine monophosphate
As a substituent it takes the form of the prefix cytidylyl-. CMP can be phosphorylated to cytidine diphosphate by the enzyme ... CMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase cytosine; hence, a ribonucleoside ... CMP kinase, with adenosine triphosphate or guanosine triphosphate donating the phosphate group. Since cytidine triphosphate is ...
*  Adenosine thiamine triphosphate
In E. coli AThTP is synthesized from thiamine diphosphate (ThDP) according to the following reaction catalyzed by thiamine ... ADP-ribose) polymerase-1(PARP-1) activity". J Nutr Sci Vitaminol (Tokyo). 57 (2): 192-6. PMID 21697640. Makarchikov AF, Brans A ... Adenosine thiamine triphosphate (AThTP), or thiaminylated adenosine triphosphate, is a natural thiamine adenine nucleotide. It ... diphosphate adenylyl transferase: ThDP + ATP (ADP) ↔ AThTP + PPi (Pi) The molecule is made up of thiamine and adenosine joined ...
*  Adenosine
... and adenosine diphosphate (ADP)-as well as in signal transduction as cyclic adenosine monophosphate (cAMP). Adenosine itself is ... Adenosine is a purine nucleoside composed of a molecule of adenine attached to a ribose sugar molecule (ribofuranose) moiety ... In the US, Adenosine is marketed as Adenocard. In India Adenosine is sold as Adenoscan (Cipla) All adenosine receptor subtypes ... When adenosine enters the circulation, it is broken down by adenosine deaminase, which is present in red cells and the vessel ...
*  Outline of cell biology
Important molecules: ADP - Adenosine diphosphate (ADP) (Adenosine pyrophosphate (APP)) is an important organic compound in ... a sugar backbone attached to a molecule of adenine and two phosphate groups bonded to the 5 carbon atom of ribose. ATP - A ... Often called "cellular power plants", mitochondria generate most of cells' supply of adenosine triphosphate (ATP), the body's ... and mediating biochemical reactions that produce adenosine triphosphate (ATP), which is a major energy intermediate in living ...
*  ATP phosphoribosyltransferase
ATP and diphosphate, whereas its two products are ATP and 5-phospho-alpha-D-ribose 1-diphosphate. This enzyme belongs to the ... Other names in common use include phosphoribosyl-ATP pyrophosphorylase, adenosine triphosphate phosphoribosyltransferase, ... diphosphate ⇌ {\displaystyle \rightleftharpoons } ATP + 5-phospho-alpha-D-ribose 1-diphosphate Thus, the two substrates of this ... The systematic name of this enzyme class is 1-(5-phospho-D-ribosyl)-ATP:diphosphate phospho-alpha-D-ribosyl-transferase. ...
*  Adenosine monophosphate deaminase deficiency type 1
Cellular processes, especially muscles, then convert the ATP into adenosine diphosphate (ADP), freeing the energy to do work.[ ... nucleotidase removes the ribose and phosphorus from AMP, increasing levels of adenosine measured in muscle cells by ~16-25×, ... Adenosine mediates pain through adenosine receptors. MADD causes an increase of free adenosine during heavy activity which may ... In the brain, excess adenosine decreases alertness and causes sleepiness. In this way, adenosine may play a role in fatigue ...
*  Thiamine
Adenosine thiamine diphosphate (AThDP) or thiaminylated adenosine diphosphate exists in small amounts in vertebrate liver, but ... a major route for the biosynthesis of the pentose sugars deoxyribose and ribose. The mitochondrial PDH and OGDH are part of ... and adenosine thiamine diphosphate (AThDP). While the coenzyme role of thiamine diphosphate is well-known and extensively ... Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recently been discovered in Escherichia ...
*  Vidarabine
... is an analog of adenosine with the D-ribose replaced with D-arabinose. As you can see from figure 1.1 that it is a ... This prevents the reduction of nucleotide diphosphates, causing a reduction of viral replication. Vidarabine is more toxic and ... The use of an inhibitor of adenosine deaminase to increase the half-life of vidarabine has also been tried, and drugs such as ... This is where ara-ATP is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention ...
*  Nucleoside-diphosphatase
Horecker BL, Hurwitz J, Heppel LA (1957). "The synthesis of ribose 5-pyrophosphate and ribose 5-triphosphate". J. Am. Chem. Soc ... The systematic name of this enzyme class is nucleoside-diphosphate phosphohydrolase. Other names in common use include ... thiaminpyrophosphatase, UDPase, inosine diphosphatase, adenosine diphosphatase, IDPase, ADPase, adenosinepyrophosphatase, ... GIBSON DM, AYENGAR P, SANADI DR (1955). "A phosphatase specific for nucleoside diphosphates". Biochim. Biophys. Acta. 16 (4): ...
*  Nucleic acid metabolism
The nucleoside, adenosine, is then deaminated and hydrolyzed to form hypoxanthine via adenosine deaminase and nucleosidase ... The conversion of a nucleoside-diphosphate (NDP) to a nucleoside-triphosphate (NTP) is catalyzed by nucleoside diphosphate ... DNA, however, requires deoxyribose, which is missing the 2'-hydroxyl (-OH group) on the ribose. The reaction to remove this -OH ... This enzyme converts NDPs (nucleoside-diphosphate) to dNDPs (deoxynucleoside-diphosphate). The nucleotides must be in the ...
*  Ticagrelor
Like the thienopyridines prasugrel, clopidogrel and ticlopidine, ticagrelor blocks adenosine diphosphate (ADP) receptors of ... Ticagrelor is a nucleoside analogue: the cyclopentane ring is similar to the sugar ribose, and the nitrogen rich aromatic ring ... system resembles the nucleobase purine, giving the molecule an overall similarity to adenosine. The substance has low ...
*  Metabolism
... causing the active site of the synthase domain to change shape and phosphorylate adenosine diphosphate - turning it into ATP. ... Each nucleotide is composed of a phosphate attached to a ribose or deoxyribose sugar group which is attached to a nitrogenous ... Individual nucleosides are made by attaching a nucleobase to a ribose sugar. These bases are heterocyclic rings containing ... One central coenzyme is adenosine triphosphate (ATP), the universal energy currency of cells. This nucleotide is used to ...
Abstract: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian cancer, leading both the US Food and Drug Administration (FDA) and the European Medicines Agency to approve olaparib for tumors characterized by BRCA1 and BRCA2 mutations. However, it is becoming increasingly evident that tumors that share molecular features with BRCA-mutant tumors-a concept known as BRCAness-also may exhibit defective homologous recombination DNA repair, and therefore will respond to PARP inhibition. A number of strategies have been proposed to identify BRCAness, including identifying defects in other genes that modulate homologous recombination and characterizing the mutational and transcriptional signatures of BRCAness. In addition to olaparib, a number of other PARP inhibitors are in clinical development. This article reviews the development of PARP inhibitors other than olaparib, and discusses the evidence for PARP inhibitors beyond BRCA1/2-mutant ...
Poly(ADP-ribose) polymerase activity in nuclei isolated from differentiating cardiac muscle of the rat has been characterized and its activity measured during development. Optimum enzyme activity is observed at pH 8.5. Poly(ADP-ribose) polymerase is inhibited by ATP, thymidine, nicotinamide, theophylline, 3-isobutyl-1-methylxanthine and caffeine and stimulated by actinomycin D. The activity measured under optimal assay conditions increases during differentiation of cardiac muscle and is inversely related to the rate of DNA synthesis and to the activities of DNA polymerase α and thymidine kinase. When DNA synthesis and the activity of DNA polymerase α are inhibited in cardiac muscle of the 1-day-old neonatal rat by dibutyryl cyclic AMP or isoproterenol, the specific activity of poly(ADP-ribose) polymerase measured in isolated nuclei is increased. The concentration of NAD+ in cardiac muscle increases during postnatal development. In the adult compared with the 1-day-old neonatal rat the ...
Treatments with Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have offered patients carrying cancers with mutated BRCA1 or BRCA2 genes a new and in many cases effective option for disease control. There is potentially a large patient population that may also benefit from PARP inhibitor treatment, either in monotherapy or in combination with chemotherapy. Here, we describe the multifaceted role of PARP inhibitors and discuss which treatment options could potentially be useful to gain disease control without potentiating side effects.
8-Bromo-7-deaza-cyclic adenosine diphosphate ribose(8-br-7-ch-cadpr)/ACM189876060 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
20762-30-5 - PWJFNRJRHXWEPT-AOOZFPJJSA-N - Adenosine diphosphate ribose - Similar structures search, synonyms, formulas, resource links, and other chemical information.
Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors- Pipeline Insights, 2015, provides the in-depth analysis of the pipeline assets across the Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors. The main objective of this report to track competitor pipeline molecules, related research activities, technology, collaborations, in-licensing and out-licensing deals.
Recent evidence obtained with transgenic knockout mice suggests that the enzyme poly(ADP-ribose)polymerase (PARP) does not play a direct role in DNA break processing [1, 2]. Nevertheless,...
BACKGROUND AND PURPOSE: Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues. EXPERIMENTAL APPROACH: cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells. KEY RESULTS: Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5-diphosphoribose (N1-cIDPR) was not
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A Membrane-bound or cytosolic enzyme that catalyzes the synthesis of Cyclic ADP-Ribose (cADPR) from Nicotinamide Adenine Dinucleotide (NAD). This enzyme generally catalyzes the Hydrolysis of cADPR to ADP-Ribose, as well, and sometimes the synthesis of Cyclic ADP-Ribose 2 phosphate (2-P-cADPR) from NADP ...
Ladénosine diphosphate ribose (ADP-ribose, ADPR), est un composé biochimique synthétisé sous forme de chaînes par la poly(ADP-ribose) polymérase. Elle peut être décrite comme une molécule dadénosine diphosphate estérifiée par un ribose terminal. Elle active, en sy liant, le canal ionique TRPM2, au rôle encore mal compris mais qui interviendrait dans la sécrétion de linsuline, dans la modulation dune partie de la réponse au facteur de nécrose tumorale dans les leucocytes, ainsi que dans la toxicité, dans le cerveau, de la bêta-amyloïde, une protéine associée à la maladie dAlzheimer. LADP-ribose est polymérisé par des enzymes formant la série des poly(ADP-ribose) polymérases (PARP) et dont le rôle est de signaler la présence dADN monocaténaire au système enzymatique chargé de restaurer lADN bicaténaire. Une fois la réparation de lADN achevée, le poly(ADP-ribose) est dégradé par une poly(ADP-ribose) glycohydrolase (PARG). ↑ Masse molaire calculée ...
Nowadays it has become evident that a chronic systemic inflammation is present in patients suffering from chronic obstructive pulmonary disease (COPD).. The role of the nuclear enzyme poly(adenosine diphosphate-ribose)polymerase (PARP) as a key mediator within these systemic inflammatory processes as well as in COPD associated exercise intolerance and muscle weakness could recently been identified. The attenuating effect of dietary ingredients with PARP inhibiting activity on systemic inflammation was supported by data from in vitro and in vivo studies, from other groups as well as from our own lab. We identified several caffeine metabolites as potent inhibitors of the most abundant PARP-isoform PARP-1 in-vitro, in animal models as well as in ex-vivo experiments with whole blood from COPD patients.. However, clinical data with respect to their anti-inflammatory effects in COPD patients are currently not available for none of these substances. Therefore, the current clinical pilot study is ...
Poly-ADP-ribose (PAR) is a polymer of up to 400 ADP-ribose units synthesized by poly-ADP-ribose-polymerases (PARPs) and degraded by poly-ADP-ribose-glycohydrolase (PARG). Nuclear PAR modulates chromatin compaction, affecting nuclear functions (gene expression, DNA repair). Diverse defined PARP cytoplasmic allocation patterns contrast with the yet still imprecise PAR distribution and still unclear functions. Based on previous evidence from other models, we hypothesized that PAR could be present in epithelial cells where cadherin-based adherens junctions are linked with the actin cytoskeleton (constituting the adhesion belt). In the present work, we have examined through immunofluorescence and confocal microscopy, the subcellular localization of PAR in an epithelial monkey kidney cell line (VERO). PAR was distinguished colocalizing with actin and vinculin in the epithelial belt, a location that has not been previously reported. Actin filaments disruption with cytochalasin D was paralleled by PAR belt
Finite element model (FEM) is a broadly used numerical tool in structural damage detection. In such applications, damage parameters in FEM are estimated by minimizing the differences between experimental modal analysis data and the corresponding FEM model prediction. Very limited works exist on analyzing the identifiability of the FEM used in such applications. In this paper, the identifiability of FEM-based structural damage detection is investigated for undamped elastic beams. We theoretically proved that damage severity at a given location in a uniform beam is identifiable by reformulating the FEM into a linear time invariant (LTI) system. A numerical algorithm is also proposed for checking the identifiability issue of multiple damage locations. Numerical case studies are provided to validate the effectiveness and usefulness of the proposed framework.. ...
IL-4 is survival factor for lymphocytes and other hematopoietic cells. Whether there are mechanisms of pro-survival signaling induced by IL-4 apart from PI3K-Akt activation is not fully clear. Our laboratory identified PARP-14, a poly-ADP-ribose polymerase subfamily member, as a Stat6-interacting protein. PARP-14 is highly expressed in lymphoid organs, influences B cell subset ratios as well as the IgA response to antigen, and has intrinsic ADP-ribosyltransferase activity. ADP-ribosyltransferases and PARPs catalyze mono- and poly-ADP-ribosylation, transferring ADP from NAD+ to target proteins. ADP-ribosylation is a post-translational modification used by bacterial exotoxins to impact signal transduction, or, in the case of the mammalian PARP-1, to influence gene transcription and DNA repair or trigger apoptosis. Almost nothing is known about biological roles or mechanisms of action of other mammalian PARPs. We now show that PARP-14 is essential for full survival signaling despite normal Akt ...
Poly-ADP-Ribose (PAR), 0.1 ml. PADPR (Poly(ADP-ribose)) is a polymer synthesized by a class of enzymes named poly(ADP-ribose) polymerases (PARP).
Looking for online definition of ADP-ribosyl cyclase 2 in the Medical Dictionary? ADP-ribosyl cyclase 2 explanation free. What is ADP-ribosyl cyclase 2? Meaning of ADP-ribosyl cyclase 2 medical term. What does ADP-ribosyl cyclase 2 mean?
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits potent antitumor activity via membrane receptors on cancer cells without deleterious side effects for normal tissue. Unfortunately, breast cancer cells, as many other cancer types, develop resistance to TRAIL; therefore, TRAIL sensitizing agents are currently being explored. 2-Tellurium-bridged β-cyclodextrin (2-TeCD) is a synthetic organotellurium compound, with both glutathione peroxidase-like catalytic ability and thioredoxin reductase inhibitor activity. In the present study, we reported that 2-TeCD sensitized TRAIL-resistant human breast cancer cells and xenograft tumors to undergo apoptosis. In vitro, 2-TeCD efficiently sensitized MDA-MB-468 and T47D cells, but not untransformed human mammary epithelial cells, to TRAIL-mediated apoptosis, as evidenced by enhanced caspase activity and poly (adenosine diphosphate-ribose) polymerase cleavage. From a mechanistic standpoint, we showed that 2-TeCD treatment of breast ...
article{1cb77357-aca8-4b11-9d70-6a2e46c89bc9, abstract = {We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval ...
To investigate how the nucleotide excision repair initiator XPC locates DNA damage in mammalian cell nuclei we analyzed the dynamics of GFP-tagged XPC. Photobleaching experiments showed that XPC constantly associates with and dissociates from chromatin in the absence of DNA damage. DNA-damaging agents retard the mobility of XPC, and UV damage has the most pronounced effect on the mobility of XPC-GFP. XPC exhibited a surprising distinct dynamic behavior and subnuclear distribution compared with other NER factors. Moreover, we uncovered a novel regulatory mechanism for XPC. Under unchallenged conditions, XPC is continuously exported from and imported into the nucleus, which is impeded when NER lesions are present. XPC is omnipresent in the nucleus, allowing a quick response to genotoxic stress. To avoid excessive DNA probing by the low specificity of the protein, the steady-state level in the nucleus is controlled by nucleus-cytoplasm shuttling, allowing temporally higher concentrations of XPC in ...
Background: In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown.. Methods: Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively.. Results: Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in ...
Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 23rd Feburary 2018. Apply now!. ...
Poly(ADP-ribose) polymerase 1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) regulate transcriptional activity by modifying target nuclear proteins with the addition and removal of ADP-ribose polymers, respectively. While the role of PARP-1 has been established, the exact function of PARG in the nucleus is less clear, although its assumed that PARP-1 and PARG have opposing functions in gene regulation. In this article, however, the authors show that this is not the case. Combining short hairpin RNA (shRNA) knockdown with microarray analysis in MCF-7 cells, they determined that these two enzymes often act in a similar, rather than antagonistic, manner. PARP-1 and PARG generally localized to similar target promoters, most notably in genes for stress response and metabolism, and, in about half of the genes tested, PARP-1 binding was dependent on PARG. In addition, studies using shRNA-resistant catalytic mutants revealed that enzymatic activity was not required in some target genes. So, rather ...
In this paper, a damage detection method based on a combination of wavelet analysis and an interval type-2 fuzzy logic system (IT-2FLS) is proposed. Firstly, synthesizing IT-2FLSs as a data-driven model is proposed. The structure is then divided into elements and excited to be vibrated to measure vibration signal. Average quantity signal of wavelet transform coefficient (AQWTC) of vibration signal with a used-scale-sheet is established. The IT-2FLS is utilized to identify the structure at its undamaged time via AQWTC signal. At each surveying time, AQWTC at each element is calculated to estimate difference of corresponding AQWTCs between two cases: undamaged status and the status at the checked time. By applying the AQWTCs contrast at two these times, a damage coefficient is described which is used to estimate status of the structure. Besides, in order to predict structures status, the time-series prediction using the IT-2FLS and the calculated damage coefficient are also presented. The ...
Poly(ADP-ribosyl)ation of proteins is an important switch in cellular processes including differentiation. In particular, recent advances reveal emerging role in differentiation of cancer cells. Here we described the effect of poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide on a morphological feature of differentiation in transformed endothelial cells GM7373. Exposed to this drug, the cells displayed a 40% growth inhibition due to apoptosis, valued by time-lapse videomicroscopy and TUNEL assay. At the same time, cells showed enhanced motility and, when cultured on Matrigel enriched with FGF2 plus 3-aminobenzamide, began to organize a capillary network, in an Akt phosphorylation dependent manner, accompanied by a cyclooxygenase-2 induction. These results validate the role of poly(ADP-ribose) polymerase activity in cell differentiation and confirm the hypothesis that PARP may be a useful target for anticancer drugs.. ...
Conference (2017, October). Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux États-Unis avec un programme sur ... [more ▼]. Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux États-Unis avec un programme sur lintelligence artificielle dispensé par luniversité de Stanford, ces cours en ligne accessibles gratuitement font miroiter la possibilité dune démocratisation maximale des savoirs. A ce titre, les MOOC bénéficient des innovations issues du Web 2.0 : ils tirent le meilleur de la rencontre entre les nouveaux usages induits par les réseaux sociaux et les apports de la pédagogique active. Ces cinq dernières années, nous avons dispensé les travaux pratiques en Histologie aux 500 étudiants de première année détude de la faculté de Médecine de ...
Conference (2017, November). Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux Etats-Unis dans de grandes universités ... [more ▼]. Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux Etats-Unis dans de grandes universités, ces cours en ligne accessibles gratuitement laissent espérer une démocratisation maximale des savoirs. Ces cinq dernières années, nous avons dispensé les travaux pratiques en Histologie aux 500 étudiants de première année détude de la faculté de Médecine de lUniversité de Liège par une méthodologie hybride alliant e-learning et présentiel (Multon et al., 2015). Forte de cette expérience réussie, notre équipe a réalisé un MOOC qui fait partie intégrante du cursus de nos étudiants depuis cette ...
Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca(2+) fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca(2+) influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca(2+) fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates ...
2-Hydroxyglutarate (2HG) exists as two enantiomers, (R)-2HG and (S)-2HG, and both are implicated in tumor progression via their inhibitory effects on α-ketoglutarate (αKG)-dependent dioxygenases. The former is an oncometabolite that is induced by the neomorphic activity conferred by isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations, whereas the latter is produced under pathologic processes such as hypoxia. We report that IDH1/2 mutations induce a homologous recombination (HR) defect that renders tumor cells exquisitely sensitive to poly(adenosine 5′-diphosphate-ribose) polymerase (PARP) inhibitors. This "BRCAness" phenotype of IDH mutant cells can be completely reversed by treatment with small-molecule inhibitors of the mutant IDH1 enzyme, and conversely, it can be entirely recapitulated by treatment with either of the 2HG enantiomers in cells with intact IDH1/2 proteins. We demonstrate mutant IDH1-dependent PARP inhibitor sensitivity in a range of clinically relevant models, including ...
The poly-ADP-ribosylation (PARsylation) activity of tankyrase (TNKS) regulates diverse physiological processes including energy metabolism and wnt/β-catenin signaling. This TNKS activity uses NAD+ as a co-substrate to post-translationally modify various acceptor proteins including TNKS itself. PARsylation by TNKS often tags the acceptors for ubiquitination and proteasomal degradation. Whether this TNKS activity is regulated by physiological changes in NAD+ levels or, more broadly, in cellular energy charge has not been investigated. Because the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) in vitro is robustly potentiated by ATP, we hypothesized that nutritional energy might stimulate cellular NAMPT to produce NAD+ and thereby augment TNKS catalysis. Using insulin-secreting cells as a model, we showed that glucose indeed stimulates the autoPARsylation of TNKS and consequently its turnover by the ubiquitin-proteasomal system. This glucose effect on TNKS is mediated primarily by
TY - JOUR. T1 - Poly(ADP-ribose) polymerase is a regulator of chemokine production. T2 - Relevance for the pathogenesis of shock and inflammation. AU - Haskó, György. AU - Mabley, Jon G.. AU - Németh, Zoltán H.. AU - Pacher, Pál. AU - Deitch, Edwin A.. AU - Szabo, Csaba. PY - 2002. Y1 - 2002. N2 - Background: Chemokines are key regulators of leukocyte traffic in various forms of inflammation and reperfusion injury. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the up-regulation of a variety of proinflammatory signal transduction pathways and associated genes. Materials and Methods: We tested whether the expression of the chemokines macrophage inflammatory protein (MIP)-1α and MIP-2 are under the control of PARP during inflammation. Results: Pharmacologic inhibition of PARP and genetic deletion of PARP suppressed the expression of MIP-1α and MIP-2 protein and mRNA in immunostimulated cultured murine ...
Ated statistic is the odds ratio (instead of fold-change). Matching 95 CIs were calculated as described . f p-values were calculated using the Fishers exact
TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intracellular calcium concentration ([Ca2+]i), but the mechanisms involved are not understood. Using short interfering RNA and a knockout mouse, we report that TRPM2, in addition to its role as a plasma membrane channel, also functions as a Ca2+-release channel activated by intracellular ADPR in a lysosomal compartment. We show that both functions of TRPM2 are critically linked to hydrogen peroxide-induced β cell death. Additionally, extracellular ADPR production by the ectoenzyme CD38 from its substrates NAD+ (nicotinamide adenine dinucleotide) or cADPR causes IP3-dependent Ca2+ release via P2Y and adenosine receptors. Thus, ADPR and TRPM2 represent multimodal signaling elements ...
Rationale: TRPM2 (Transient Receptor Potential Melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca2+ entry in response to intracellular generation of adenosine diphosphoribose (ADPR), the TRPM2 ligand. Objective: Because polymorphonuclear leukocytes (PMN) interaction with endothelial cells (ECs) generates ROS, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. Methods and Results: We observed defective PMN transmigration in response to LPS challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2iΔEC). PMN interaction with ECs induced the entry of Ca2+ in ECs via the EC-expressed TRPM2. Prevention of generation of ADPR in ECs significantly reduced Ca2+ entry in response to PMN activation of TRPM2 in ECs. PMNs isolated from gp91phox-/- mice significantly reduced Ca2+ entry in ECs via TRPM2 as compared to WT PMNs and failed to induce PMN transmigration. Overexpression of the ...
Poly(ADP-ribose) synthesized after DNA damage is only present transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase (PubMed:23102699). PARG acts both as an endo- and exoglycosidase, releasing PAR of different length as well as ADP-ribose monomers (PubMed:23102699). Required for retinoid acid-dependent gene transactivation, probably by dePARsylating histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters (PubMed:23102699). Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257 ...
Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here, we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and whether this mechanism is involved in its sensitizing effect in BRCA-competent models of ovarian and colon cancer. Notably, we found that hyperthermia delayed the repair of DNA damage caused by cisplatin or doxorubicin, acting upstream of different repair pathways to block histone polyADP-ribosylation (PARylation), a known effect of chemotherapy. Furthermore, hyperthermia blocked this histone modification as efficiently as pharmacologic inhibitors of PARP (PARPi), producing comparable delay in DNA repair, induction of double-strand breaks (DSB), and cell cytotoxicity after chemotherapy. ...
The recognition of DNA Double Strand Breaks (DSBs) using a phospho-specific antibody to the histone 2A variant has become the gold standard assay for DNA damage detection. Here we report on the development of the first monoclonal antibody to the phospho-specific form of Drosophila H2AV and characterize the specificity of this antibody to programmed DSBs in oocytes and rereplication sites in endocycling cells by immunofluorescence assays and to DSBs resulting from irradiation in both cell culture and whole tissue by Western blot assays. These studies show that the antibody derived in the study is highly specific for this modification that occurs at DSB sites, and therefore will be a new useful tool within the Drosophila community for the study of DNA damage response, DSB repair, meiotic recombination and chemical agents that cause DNA damage. ...
Talazoparib, also known as BMN-673 and MDV-3800, is an orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential antineoplastic activity (PARP1 IC50 = 0.57 nmol/L). BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.
Modular domains of proteins are important in cellular signaling processes. Eukaryotic cells are constantly undergoing DNA damage due to exogenous and endogenous sources of damage. The DNA damage response (DDR) involves a complex network of signaling events mediated by modular domains such as the BRCT (BRCA1 C-terminal) domains. Therefore, proteins containing BRCT domains are important for DNA damage detection and signaling. In this dissertation, we focus on two BRCT-containing proteins BRCA1 and PAXIP1. BRCA1 is a gene that is known to be associated with increased risk of hereditary breast and ovarian cancer. Germline variants of BRCA1 are assessed to determine lifetime risk of developing breast and ovarian cancer. This is performed by genetic testing of the BRCA1 sequence and the variants can be classified as pathogenic, non-pathogenic or variants of unknown significance (VUS). Using family history, segregation analysis, co-occurrence and tumor pathology, certain variants have been classified as either
Removes ADP-ribose from asparatate and glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.
The process of poly(ADP-ribosyl)ation has been shown to be important for the repair of DNA damage in proliferating cells and for the maintenance of genomic stability, which is the basis for the role of PARP-1 as a cytoprotective survival factor (Jacobson and Jacobson, 1999; Shall and de Murcia, 2000; Bürkle, 2001b,2001c). The previously observed positive correlation between cellular poly(ADP-ribosyl)ation capacity and species-specific life span (Grube and Bürkle, 1992) is in perfect agreement with such cellular function of poly(ADP-ribosyl)ation.. Several laboratories have observed life span-extending and neuroprotective properties of the anti-Parkinson drug l-selegiline (Knoll et al., 1989; Freisleben et al., 1994; Semkova et al., 1996; Ruehl et al., 1997; Stoll et al., 1997; Kitani et al., 1999; Maruyama and Naoi, 1999; Klegeris and McGeer, 2000; Naoi et al., 2000; Kitani et al., 2001; Ebadi et al., 2002). These effects were recorded at concentrations below MAO-B inhibition (≤1 μM), ...
Mammalian target of rapamycin (mTOR) is a serine and threonine protein kinase that regulates numerous cellular functions, in particular, the initiation of protein translation. Rapamycin is a natural product macrolide that induces G|sub>1|/sub> growth arrest in yeast, Drosophila, and mammalian cells. mTOR has a long list of synonyms including FK506 binding protein12 - rapamycin associated protein 1, FK506 binding protein12 - rapamycin associated protein 2, FRAP1, FRAP2, RAFT1, RAPT1 and/or FKBP12-rapamycin associated protein (FRAP). mTOR is one of a family of proteins involved in cell cycle progression, DNA recombination, and DNA damage detection. In rat, mTOR is a 245-kD protein referred to as RAFT1 with significant homology to the Saccharomyces cerevisiae protein TOR1 and has been shown to associate with the immunophilin FKBP12 in a rapamycin-dependent fashion. The FKBP12-rapamycin complex is known to inhibit progression through the G|sub>1|/sub> cell cycle stage by interfering with mitogenic
Increasing evidence has indicated that NAD+ and NADH play critical roles not only in energy metabolism, but also in cell death and various cellular functions including regulation of calcium homeostasis and gene expression. It has also been indicated that NAD+ and NADH are mediators of multiple major biological processes including aging. NAD+ and NADH produce the biological effects by regulating numerous NAD+/NADH-dependent enzymes, including dehydrogenases, poly(ADP-ribose) polymerases, Sir2 family proteins (sirtuins), mono(ADP-ribosyl)transferases, and ADP-ribosyl cyclases. Of particular interest, NAD+-dependent generation of ADP-ribose, cyclic ADP-ribose and O-acetyl-ADP-ribose can mediate calcium homeostasis by affecting TRPM2 receptors and ryanodine receptors; and sirtuins and PARPs appear to play key roles in aging, cell death and a variety of cellular functions. It has also been indicated that NADH and NAD+ can be transported across plasma membranes of cells, and that extracellular NAD+ ...
According to one aspect of the disclosure and a particular example application directed to a flip-chip packaged die, a method for detecting a defect in a surface of the die includes directing light through a first beam splitter; directing light of a known wavelength at the beam splitter, wherein the first beam splitter is adapted to direct a first beam of light into the back side of the semiconductor die which reflects a second beam of light back; and redirecting the second beam to a second beam splitter, the second beam splitter generating third and fourth beams of light. Analysis of the third and fourth beams of light is then performed, and this analysis can include using detectors in respective paths of the third and fourth beams of light to generate an arrival time differential and then comparing the differential with a reference previously generated using a nondefective die.
It is shown that an inorganic ionic polymer (sodium polyphosphate) exhibits the same type of glass transition temp. versus average chain length behavior as non-ionic organic polymers. If the chain ends resemble the terminal units, specifically in terms of the number of anions per phosphorus atom, the material is entirely analogous in its behavior to the organic materials, as shown, for instance, by the applicability of the Gibbs-DiMarzio theory. By contrast, if the terminal units possess two anions per phosphorus atom, a profound change in behavior is observed. (Author)(*INORGANIC POLYMERS
Disclosed are oral compositions comprising one or more linear polyphosphates having an average chain length of about 4 or more, sodium monofluorophosphate, a buffering agent, an abrasive polishing material containing less than 23% calcium, and one or more aqueous carriers, wherein the oral composition has a total water content of from about 5% to about 20%.
Methodology/Principal Findings: Immunofluorescence and electron microscopy were performed to characterise the sub-cellular localisation of ARTD15, which was found to be associated with membranes of the nuclear envelope and endoplasmic reticulum. The orientation of ARTD15 was determined using protease protection assay, and is shown to be a tail-anchored protein with a cytosolic catalytic domain. Importantly, by combining immunoprecipitation with mass spectrometry and using cell lysates from cells over-expressing FLAG-ARTD15, we have identified karyopherin-ß1, a component of the nuclear trafficking machinery, as a molecular partner of ARTD15. Finally, we demonstrate that ARTD15 is a mono-ADP-ribosyltransferase able to induce the ADP-ribosylation of karyopherin-ß1, thus defining the first substrate for this enzyme ...
Sindbis computer virus (SINV) the prototype alphavirus contains a macro area in the highly conserved N-terminal area of nonstructural proteins 3 (nsP3). 10 happened during replication of dual mutant SINV in vitro and in Prkwnk1 vivo. The nsP3 macro area is very important to SINV age-dependent and replication susceptibility to encephalomyelitis. (Fig. 1A) predicted that asparagines at proteins 10 and 24 of nsP3 are in matching Granisetron Hydrochloride positions to both proteins in close connection with ADP-ribose in (Fig. 1B) (10). These asparagines had been transformed to alanines to create SINV using a dual mutation (SINV DM) or with one mutations at amino acidity 10 (SINV SM10) or 24 (SINV SM24) (Fig. 1C). To measure the aftereffect of these mutations on PAR binding his-tagged WT and mutant proteins had been tested for relationship with PAR at different concentrations (Fig. 1D). Simply no impact was had with the mutations in binding of PAR. Fig. 1 Mutation from the nsP3 macro area will not ...
Protein mono-ADP-ribosylation is a reversible post-translational modification that has been implicated in the regulation of different cell functions, including signal transduction, protein trafficking, and immune responses. In mammals, three families of proteins catalyse this reaction: the ecto-monoARTs/ARTCs, some members of the PARP/ARTD family and some members of the sirtuin family. In this study, I have been focused on the characterisation of human P ARP 161 ARTD 15 and hamster cARTC2.1. Moreover, I have set up novel technologies for the study of intracellular ADP- ribosylation reactions. I have shown that PARP16/ARTD15 is a mono-ADP-ribosyl transferase that localises to the endoplasmic reticulum, where it binds karyopherin-B 1, a pivotal nuclear transport receptor. Moreover, I have also shown that PARP16/ARTD15 induces the mono-ADP-ribosylation of karyopherin-B 1, defining the first substrate for this enzyme. These data suggest a novel regulatory mechanism of karyopherin-Bl functions ...
Cell adhesion-mediated drug resistance is an important factor that influences the effects of chemotherapy in multiple myeloma. DTX3L, a ubiquitin ligase, plays a key role in cell-cycle-related process. Here, we found that the expression of DTX3L gradually increased during the proliferation of myeloma cells, which resulted in arrest of the cell cycle in the G1 phase and promoted the adherence of myeloma cells to fibronectin or bone marrow stromal cells. In addition, silencing of DTX3L improved sensitivity to chemotherapy drugs in multiple myeloma cell lines adherent to bone marrow stromal cells and increased the expression of caspase-3 and poly-adenosine diphosphate-ribose polymerase, two markers of apoptosis ...
A cytotoxic cycle triggered by DNA single-strand breakage and poly (ADP-ribose) synthetase activation has been shown to contribute to the cellular injury during various forms of oxidant stress in vitro. The aim of this study was to investigate the role of poly (ADP-ribose) synthetase (PARS) in the process of neutrophil recruitment and in development of local and systemic inflammation. In pharmacological studies, PARS was inhibited by 3-aminobenzamide (10-20 mg/kg) in rats and mice. In other sets of studies, inflammatory responses in PARS?/? mice were compared with the responses in corresponding wild-type controls. Inhibition of PARS reduced neutrophil recruitment and reduced the extent of edema in zymosan- and carrageenan-triggered models of local inflammation. Moreover, inhibition of PARS prevented neutrophil recruitment, and reduced organ injury in rodent models of inflammation and multiple organ failure elicited by intraperitoneal injection of zymosan. Inhibition of PARS also reduced the ...
Transcriptional regulation is mediated in large part by posttranslational modifications of chromatin-remodeling enzymes. Wright and colleagues investigated the contribution of poly-(ADP-ribose) polymerase-1 (PARP-1)-driven chromatin modification in hormone-regulated gene expression in the absence of DNA damage, a known activator of PARP-1. Progestin treatment of breast cancer cells led to a rapid and transient increase in PARP-1 activity, as measured by poly-(ADP)-ribosylation (PARylation) of nuclear proteins, and decreased levels of the PARP-1 substrate NAD. In addition, hormone stimulation enhanced the expression of progesterone target genes and induced proliferation, and these effects were dependent on the progestin-driven increase in PARP-1 activity. Inhibition of cyclin-dependent kinase 2 (CDK2), a hormone-activated kinase that regulates progesterone target genes, significantly diminished PAR accumulation and PARP-1-stimulated gene expression in response to progestin, suggesting that CDK2 ...
Poly(ADP-ribose) polymerases (PARP) comprise a family of enzymes which catalyse poly(ADP-ribosyl)ation of DNA-binding proteins. Multiple researches indicate the importance of PARP in promoting cell recruitment and thereby inducing organ injury in various forms of inflammation, such as colitis. We have evaluated the effects of two PARP inhibitors, nicotinamide and 1,5-dihydroxyisoquinoline, in acute colitis induced by trinitrobenzensulfonic acid (TNBS) in rats. Nicotinamide (20-40 mg/kg) and 1,5-dihydroxyisoquinoline (4-8 mg/kg) were administered 48, 24 and 1 h prior to the induction of colitis as well as 24 h later. 48 h after colitis induction the lesions were blindly scored and quantified as ulcer index. Histological study and colonic inflammation were assessed by gross appearance and myeloperoxidase (MPO) activity. Prostaglandin E2 (PGE2) synthesis and, cyclooxygenase-1 and cyclooxygenase-2 expressions by Western blotting and immunohistochemistry were also performed. Inflammation following TNBS
Poly(ADP-ribose)polymerase-1 (PARP-1) is a NAD-consuming enzyme with an emerging key role in epigenetic regulation of gene transcription. Although PARP-1 expression is classically restricted to the nucleus, a few studies report the mitochondrial localization of the enzyme and its ability to regulate organelle functioning. Here, we show that, in spite of exclusive nuclear localization of PARP-1, mitochondrial homeostasis is compromised in neuroblastoma cells exposed to PARP-1 pharmacological inhibitors or siRNA. PARP-1 suppression reduces integrity of mtDNA, as well as expression of mitochondria-encoded respiratory complex subunits COX-1, COX-2 and ND-2. Accordingly, PARP-1 localizes at promoters of nuclear genes encoding both the mtDNA repair proteins UNG1, MYH1 and APE1, and the mtDNA transcription factors TFB1M and TFB2M. Notably, poly(ADP-ribosyl)ation is required for nuclear gene expression of these mitochondrial proteins. Consistent with these findings, PARP-1 suppression impairs ...
View Notes - Lecture 3B from CHEM CHEM 2204 at Carleton. Carbonyls and Enol (Enolate) Reactions . euterium xchange 9. Deuterium exchange 10. α- Halogen ation 11. α-alkylation 12. Ald ol formation
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TMZ also generates N-methylated bases (N3 and N7) which may be removed by the 13292-46-1 supplier bottom excision fix (BER) program (5) robust BER activity can lead to TMZ level of resistance (5 11 Central to BER and removing methylated N3 and N7 adducts may 13292-46-1 supplier be the enzyme poly(ADP-ribose) polymerase (PARP) an enormous nuclear enzyme that senses both single-stranded DNA and dsDNA breaks. histones starting chromatin for DNA fix; PARP also recruits BER protein to sites of single-stranded DNA breaks initiating DNA fix (12). Hence PARP inhibitors (PARPi) may get over TMZ level of resistance in MMR-deficient cells by preventing BER leading to cytotoxicity from N3- and N7-methyl adducts (11 13 PARP inhibitors have already been examined in a number of tumor types and also have been shown to 13292-46-1 supplier improve the antitumor ramifications of TMZ in leukemia (13) glioma (14-16) lung (17 18 and digestive tract carcinoma both in vitro (16 18 and in xenograft versions (17 21 Prior ...
Parkinsons disease is a common neurodegenerative disorder and the Dawson lab is studying the genetic basis of PD by investigating the mechanisms by which mutations in familial-linked genes cause PD, with hopes of identifying potential therapeutic targets for developing PD treatments. Current projects include the study of alpha-synuclein, LRRK2, parkin and PINK1.. Nitric oxide is a major player in neuronal cell death and the Dawson team has discovered parthanatos, a caspase-independent programmed cell death pathway involving apoptosis inducing factor (AIF) downstream of NO and its major target poly (ADP-ribose) polymerase (PARP). The team now is further characterizing that pathway to identify targets of AIF and the roles of other cell death effectors with the hope of identifying new signaling pathways that might be amenable to therapeutic intervention. In addition they are investigating the role of poly (ADP-ribose) as signaling molecule.. Representative Publications:. ...
This paper describes an ongoing project investigating embedded networked sensing for structural health monitoring applications. The vision is of many low-power sensor motes embedded throughout the structure with a smaller number fo nodes that can provide local excitation. The challenge is to develop both the networking algorithms to reliably communicate within the network, and distributed algorithms to monitor the state of the structure. A wireless data acquisition network is described, including the methods of storing and transmitting the data. A damage detection scheme is described that uses extremely low transmission bandwidth, and is shown to be effective in detecting damage in a simulated structure. Finally, a large-scale structural testbed that is being used for this project is described. The outcome of this work-in-progress is expected to be strong recommendations and algorithms for distributed wireless sensor/actuator structural health monitoring networks. ...
r\nJimi Hendrix, par Arsen. Photo : Jonas Jacquel. \r\nLassociation a en effet donné « carte blanche » à ARSEN, un street artist prometteur de lagglomération dijonnaise, pour que celui-ci fasse vivre les locaux. Arsen sera donc en résidence jusquà la fin de lannée 2014 à la STA. Quoi de plus normal en effet pour une association dont lobjectif est de promouvoir la création artistique par la mise à disposition de moyens adaptés, et qui est en outre hébergée sur une friche industrielle ?\r\n\r\nCela permet à la STA daméliorer la qualité esthétique des locaux en renforçant son identité « musicale », tout donnant accès à Arsen à un vaste espace adapté à la création graphique et au graffiti, qui pourra également lui servir de « book » pour les mois à venir !\r\n\r\nPar le biais de lopération « Carte Blanche à Arsen », lassociation STA investit donc le créneau de la création graphique et du graffiti et améliore sa qualité daccueil, en offrant ...
Poly (ADP-ribose) polymerase (PARP-1) over-activation may lead to depletion of NAD+ and ATP within the cell and proceed to necrotic cell death. Recently, published reports demonstrate high levels of PARP-1 activity in a model of porcine hemorrhagic shock. There is also increased interest in hypotensive resuscitation used for battlefield-wounded soldiers and trauma patients. We wished to evaluate PARP-1 activity during a model of porcine hemorrhagic shock with the hypothesis that PARP-1 activity will be increased using a hypotensive resuscitation strategy. ...
The development of new clinical treatment options that can improve outcomes for patients with ovarian cancer is a major focus of clinical research. Several options that target the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) family are in different stages of development/approval. This family comprises 17 enzymes that play an important role in numerous cellular functions, including DNA transcription and repair, genomic stability maintenance, cell cycle regulation, cell signaling, and cell death. [Anwar, 2015; Benafif and Hall, 2015] d DNA. PARP inhibition may keep tumor cells from repairing their DNA, leading to their death. Several PARP inhibitors have demonstrated efficacy in the treatment of patients with ovarian cancer in clinical trials, and this class of medications has begun to make the transition from laboratory investigation to clinical application. FDA approval has been granted for two agents, with several others in late clinical development in 2017, altering the treatment ...
GenDR A curated database of genes associated with dietary restriction in model organisms either from genetic manipulation experiments or gene expression profiling.. ...
Refworld is the leading source of information necessary for taking quality decisions on refugee status. Refworld contains a vast collection of reports relating to situations in countries of origin, policy documents and positions, and documents relating to international and national legal frameworks. The information has been carefully selected and compiled from UNHCRs global network of field offices, Governments, international, regional and non-governmental organizations, academic institutions and judicial bodies.
54 injection, which will kill the animal without producing gametes. Once animals have been placed in appropriate gender ca tegories they can be added to spawning tanks in a gender equal fashion. At least three tanks were pr e set up to hold animals. One tank was at ambient temperature and two tanks were equippe d with heaters. One of the heated tanks should have its temperature elev ated to at lest 85 degrees F. The other heated tank should have its temperature elevated to 85 degrees F or hotter up to a temperature of 90 degrees F. It has been observed that almost all spawni ng occur in water that is at least 85 degrees F. As animals are being placed into tanks at least 2-3 suspected males should be reserved for KCL injection and sperm harvest. A sy ringe containing 0.5 1.0 M KCL should be inserted into the central disk / appendage junction of each suspected male. KCL should be slowly injected until there is a visible release of sperm (usually 1 3 ml of KCL). Often times it is necessary to ...
usr/bin/perl -w use Crypt::OpenPGP; use Crypt::OpenPGP::KeyRing; my($keyfile, $email) = @ARGV; my $ring = Crypt::OpenPGP::KeyRing-,new(Filename =, $keyfile); my $pgp = Crypt::OpenPGP-,new(PubRing =, $ring); my $kb = $ring-,find_keyblock_by_uid($email); my $alg = $kb-,preferred_sk_alg; my $crypt = $pgp-,encrypt( Data =, squeamish ossifrage, Recipients =, [ $email ], Armour =, 1, ($alg ? (Cipher =, $alg) : ()), # use default if no preference loc +ated ); print $crypt; exit 0; { package Crypt::OpenPGP::KeyBlock; sub preferred_sk_alg { my $self = shift; use Crypt::OpenPGP::Cipher; my $supported = Crypt::OpenPGP::Cipher-,supported; my @prefs; for my $sig (@{ $self-,get(Crypt::OpenPGP::Signature) }) { if ($sig-,is_primary) { unshift @prefs, @{ $sig-,preferred_sk_alg }; } else { push @prefs, @{ $sig-,preferred_sk_alg }; } } for (@prefs) { return $_ if $supported-,{$_}; } return; } } { package Crypt::OpenPGP::Signature; sub is_primary { my $self = shift; my $packet = $self-,find_subpacket(25); # ...
2-Hydroxy-N-(4-hydroxyphenyl)-benzamide 526-18-1 safety info, 2-Hydroxy-N-(4-hydroxyphenyl)-benzamide chemical safety search, Chemical 2-Hydroxy-N-(4-hydroxyphenyl)-benzamide safety technical specifications ect.
A molecular strategy that could make a much larger variety of tumors treatable with PARP inhibitors, a promising new class of cancer drugs, has been demonstrated
Sigma-Aldrich offers abstracts and full-text articles by [Huan Xu, Xixi Zhou, Xia Wen, Fredine T Lauer, Ke Jian Liu, Laurie G Hudson, Lauren M Aleksunes, Scott W Burchiel].
The gain level should stto adjusted to a point where the known fluid is just echo-free and then the lesion should be re-examined. Molecular cytogenetic evalu- ation of 10 chi ГЁ stato a cipro melanoma cell lines. The subjectвs full name should not be required, to maintain subject confi- dentiality 2. 16 Glaucoma пппппA B Fig.
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Complete information for MACROD1 gene (Protein Coding), MACRO Domain Containing 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
This group is dedicated to the Korg Mono/poly. There are links, patches and also mp3 recordings of patches in action! These patches are writen down on patch sheets with descriptions of how to modulate the sound. Remember to share your patches. : )
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Definition of Guanosine diphosphate sugars with photos and pictures, translations, sample usage, and additional links for more information.
dTDP-L-rhamnose is the activated sugar that is used in the synthesis of capsular polysaccharides in gram positive bacteria and O-antigens of gram negative bacteria. This molecule is synthesized by a series of four enzymes in the dTDP-L-rhamnose biosynthetic pathway. The last enzyme of the pathway, dTDP-4-dehydrorhamnose reductase, catalyzes the production of NADP and dTDP-L-rhamnose from NADPH and dTDP-4-dehydro-6-deoxy L-mannose. There are 6 molecules in the P21 asymmetric unit of the 2.65 Å resolution crystal structure of the dTDP-4-dehydrorhamnose reductase from Bacillus anthracis. Six subunits form two head-to-head trimers. Larger Rossmann-fold catalytic domains are at the oligomerization interface in each timer, whereas smaller hood domains of one timer face these domains in another trimer. Pairwise structural alignment of the subunits reveals movement of the hood domains. When two trimers are superimposed, the biggest rmsd value is 0.9 between two individual chains from each of the ...
Uridine Diphosphate Sugars information including symptoms, causes, diseases, symptoms, treatments, and other medical and health issues.
The rhamnolipid pathway in P. aeruginosa comprises three key enzymes and is based on the two precursors rhamnose and β-hydroxy-fatty acid (Fig. 1). The activated β-hydroxy-fatty acid hydroxyacyl-ACP is generated in the fatty acid de novo synthesis. Subsequently the first rhamnolipid specific enzyme 3-hydroxyacyl-ACP:3-hydroxyacyl-ACP O-3-hydroxy-acyl-transferase (RhlA) connects two hydroxyacyl-ACP molecules to form a dimer called hydroxyalkanoyloxy alkanoate (HAA). This molecule does not contain a rhamnose unit and thus is not a rhamnolipid. Due to its ester, carboxyl, and hydroxy groups and resulting amphiphilic structure, it nevertheless is a biosurfactant. The second precursor originates in six reactions from glucose. Activated dTDP-l-rhamnose is then fused by rhamnosyltransferase I (RhlB) to the HAA molecule to yield a mono-rhamnolipid. The second rhamnosyltransferase (RhlC) adds a second sugar to the mono-rhamnolipid, finally leading to the di-rhamnolipid biosurfactant.. The environmental ...
CDP-glycerol | C12H21N3O13P2 | CID 439249 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
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Arginine adenosine-5′-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed potentially reversible posttranslational changes where the ADP-ribose moiety is transferred from NAD+ towards the guanidino CHR2797 moiety of arginine. proteins with binding companions e.g. toxin-catalyzed ADP-ribosylation of actin at R177 blocks actin polymerization sterically. In case there is the nucleotide-gated P2X7 ion route ADP-ribosylation at R125 near the ligand-binding site causes route Rabbit Polyclonal to SF3B3. gating. Arginine-specific ADP-ribosyltransferases (ARTs) bring a quality R-S-EXE theme that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of additional amino acid part chains DNA or little substances. Arginine-specific ADP-ribosylation could be inhibited by little molecule arginine analogues such as for example CHR2797 agmatine or meta-iodobenzylguanidine (MIBG) which themselves can serve as focuses on for arginine-specific ARTs. ...
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. Improper ADP-ribosylation has been implicated in some forms of cancer. It is also the basis for the toxicity of bacterial compounds such as cholera toxin, diphtheria toxin, and others. The first suggestion of ADP-ribosylation surfaced during the early 1960s. At this time, Pierre Chambon and coworkers observed the incorporation of ATP into hen liver nuclei extract. After extensive studies on the acid insoluble fraction, several different research laboratories were able to identify ADP-ribose, derived from NAD+, as the incorporated group. Several years later, the enzymes responsible for this incorporation were identified and given the name poly (ADP-ribose) polymerase. Originally, this group was thought to be a linear sequence of ADP-ribose units ...
Definition of cytidine diphosphate choline. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Recognized as one of the 100 most technologically significant products introduced to the marketplace in the past year. The Remote Methane Leak Detector can quickly and efficiently detect leaks up to one hundred feet away. Using laser technology, remote detection allows the user to safely survey areas that may be difficult to reach, such as busy roadways, yards with large dogs, locked gates, pipe suspended under a bridge and other hard to access places. In the independent validation tests, the RMLD has proven to be a highly effective leak survey instrument, compared to flame ionization and similar equipment, but with the added advantage of remote detection. By design the RMLD is capable of achieving significant productivity gains and drastically reduce operations and maintenance costs ...
Certain microbial toxins are ADP-ribosyltransferases, acting on specific substrate proteins. Although these toxins have been of great utility in studies of cellular regulatory processes, a simple procedure to directly study toxin-catalyzed ADP-ribosy
... is an acid degradation product produced by selective hydrolysis of the more labile forosamine saccharide in the 17-position in spinosyn D, the minor component of commercial product, Spinosad. Spinosyn D 17-pseudoaglycone is only weakly active as an insecticide as the forosamine moiety is considered essential for potent activity. Despite the importance of spinosyns as agro-chemical insecticides and more recently as animal health products, there are few published reports of the biological activity or the levels of spinosyn D 17-pseudoaglycone in animals or in the environment ...
La GDP-6-deossi-D-talosio 4-deidrogenasi è un enzima appartenente alla classe delle ossidoreduttasi, che catalizza la seguente reazione: GDP-6-deossi-D-talosio + NAD(P)+ ⇄ GDP-4-deidro-6-deossi-D-mannosio + NAD(P)H + H+ Markovitz, A., Biosynthesis of guanosine diphosphate D-rhamnose and guanosine diphosphate D-talomethylose from guanosine diphosphate α-D-mannose, in J. Biol. Chem., vol. 239, 1964, pp. 2091-2098 ...
1 ]Dong C, Beis K, Giraud MF, Blankenfeldt W, Allard S, Major LL, Kerr ID, Whitfield C, Naismith JH. A structural perspective on the enzymes that convert dTDP-d-glucose into dTDP-l-rhamnose. Biochem Soc Trans. 2003 Jun;31(Pt 3):532-6. PMID 12773151 ...
Lactobacillus rhamnosus strain ATCC 9595 Wzd (wzd), Wze (wze), Wzx (wzx),WelF (welF), WelG (welG), WelH (welH), WelI (welI), Wzy (wzy), WelJ (welJ),Wzm (wzm), RmlA (rmlA), RmlC (rmlC), RmlB (rmlB), RmlD (rmlD), WelE (welE),Wzr (wzr), Wzb (wzb), ClpL (clpL), and Nrp (nrp) genes, complete ...
NAD glycohydrolases are enzymes that catalyze the hydrolysis of NAD to produce ADP-ribose and nicotinamide. Regulation of these enzymes has not been fully elucidated. We have identified a NAD-glycohydrolase activity associated with the outer surface of the plasma membrane in human lung epithelial cell line A549. This activity is negatively regulated by its substrate beta-NAD but not by alpha-NAD. Partial restoration of NADase activity after incubation of the cells with arginine or histidine, known ADP-ribose acceptors, suggests that inhibition be regulated by ADP-ribosylation. A549 do not undergo to apoptosis upon NAD treatment indicating that this effect be likely mediated by a cellular component(s) lacking in epithelial cells. ...
Looking for hexulose? Find out information about hexulose. A ketose made from a six-carbon-chain monosaccharide Explanation of hexulose
Enzymatic synthesis of cytidine diphosphate 3,6-dideoxyhexoses. II. Reversible 2-epimerization of cytidine diphosphate paratose ...
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
Pooley HM, Abellan FX, Karamata D (1992) CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase, which is involved in the synthesis of the major wall teichoic acid in Bacillus subtilis 168, is encoded by tagF (rodC). J Bacteriol 174:646-9.[PMID:1309530 ...
Mingji Dai and co-workers at Purdue reported in JACS on the synthesis of spinosyn A through a carbonylative macrolactonization. JACS paper
Spinosad is a member of the spinosyns class of insecticides, which are non-antibacterial tetracyclic macrolides. Spinosad contains two major factors, spinosyn A and spinosyn D, derived from the naturally occurring bacterium, Saccharopolyspora spinosa. Spinosyn A and spinosyn D have the chemical compositions 2-[(6-deoxy-2,3,4-tri-O-methyl- -L-mannopyranosyl)oxy]-13-[[5-dimethylamino)-tetrahydro-6-methyl-2H-pyran-2-yl]oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14,16a,16b-tetradecahydro-14-methyl-1 H-as-Indaceno[3,2-d]oxacyclododecin-7, 15-dione and 2-[(6-deoxy-2,3,4-tri-O-methyl- -L-mannopyranosyl)oxy]-13-[[5-dimethylamino)-tetrahydro-6-methyl-2H-pyran-2-yl] oxy]-9-ethyl-2,3,3a,5a,5b,6,9,10,11,12,13,14, 16a,16b-tetradecahydro-4,14-dimethyl-1 H-as-Indaceno[3,2-d] oxacyclododecin-7,15-dione, respectively ...
Creative-Proteomics offer cas 50468-56-9 4-O-β-D-galactopyranosyl-D-[1-13C]mannose. We are specialized in manufacturing Stabel Isotope Labeled Analytical Standard products.
A configuration-inverting rhamnosyltransferase that converts flavonol 3-O-glucosides to 3-O-rutinosides. Also acts, more slowly, on rutin, quercetin 3-O-galactoside and f
BFA induces the ADP-ribosylation of BARS-50 and GAPDH in permeabilized cells. (A) RBL cells were permeabilized with 3 U/ml SLO and exposed to 10 μg/ml BFA
Myc-DDK-tagged ORF clone of Homo sapiens ADP-ribosylation factor-like 5C (ARL5C) as transfection-ready DNA - 10 µg - OriGene - cdna clones
Background: Poly (ADP-ribosyl) polymerase 1 (PARP1) is important in maintaining genomic stability, repairing DNA damage, and regulating transcriptional processe
[120 Pages Report] Check for Discount on Poly (ADP-Ribose) Polymerase 1 (PARP) Inhibitor -Pipeline Insights, 2017 report by Delve Insight. DelveInsight s, Poly (ADP-Ribose) Polymerase 1 (PARP) Inhibitor-Mechanism...
A simple and efficient protocol for the preparative-scale synthesis of various lengths of oligo-N-acetyllactosamine (oligo-LacNAc) and its multi-sialylated extensions is described. The strategy utilizes one thermophilic bacterial thymidylyltransferase (RmlA) coupled with corresponding sugar-1-phosphate kinas
INTRODUCTION Sebum is a hallmark characteristic of oily skin, which typifies or is usually associ- ated with acne-prone skin. The goal of this chapter is to present recent findings regarding ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Poly (ADP-ribose) Polymerases (PARPs) are abundant and ubiquitous proteins that regulate crucial processes of the cell cycle, DNA repair, genomic
Creative Biogene offers challenging job opportunities for people looking for career growth in an entrepreneurial environment that recognizes individual contributions ...
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
They have pushed regime forces into around a third of the city pretty much in the southeastern portion of the city, and that is where most of the front lines lie. The military here for the most part is forced to airdrop supplies to its troops that are stuck on these bases. On many occasions because of fire coming from rebel forces, those air drops miss their targets entirely. They are seeing a growing number of defections. They most certainly do feel despite the fact that it is an incredibly dangerous and very intense front line and there are multiple ones, I must say that, but they do feel that right now, they have the upper hand ...
Biomolecules | Free Full-Text | Strategies for the Use of Poly(adenosine diphosphate ribose) Polymerase (PARP) Inhibitors in...  Biomolecules | Free Full-Text | Strategies for the Use of Poly(adenosine diphosphate ribose) Polymerase (PARP) Inhibitors in...
... adenosine diphosphate ribose) polymerase (PARP) inhibitors have offered patients carrying cancers with mutated BRCA1 or BRCA2 ... Strategies for the Use of Poly(adenosine diphosphate ribose) Polymerase (PARP) Inhibitors in Cancer Therapy. Cecilia E. Ström. ... Treatments with Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have offered patients carrying cancers with ... Ström, C.E.; Helleday, T. Strategies for the Use of Poly(adenosine diphosphate ribose) Polymerase (PARP) Inhibitors in Cancer ...
more infohttp://mdpi.com/2218-273X/2/4/635
Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle ...  Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle ...
Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle ... Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle ... Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle ... Poly(adenosine diphosphate ribose) polymerase activity and nicotinamide adenine dinucleotide in differentiating cardiac muscle ...
more infohttp://www.biochemj.org/content/154/2/387
The Status of Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 2: Extending the Scope...  The Status of Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 2: Extending the Scope...
The best example of this to date is the use of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors for the ... Abstract: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian ... The status of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in ovarian cancer, part 1: olaparib. Clin Adv ... The Status of Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 2: Extending the Scope ...
more infohttp://www.hematologyandoncology.net/archives/september-2016/the-status-of-polyadenosine-diphosphate-ribose-polymerase-parp-inhibitors-in-ovarian-cancer-part-2-extending-the-scope-beyond-olaparib-and-brca12-mutations/
Ryanodine receptor subtype 2 encodes Ca2+ oscillations activated by acetylcholine via the M2 muscarinic receptor/cADP-ribose...  Ryanodine receptor subtype 2 encodes Ca2+ oscillations activated by acetylcholine via the M2 muscarinic receptor/cADP-ribose...
RYRs can be activated by cyclic adenosine diphosphate ribose (cADPR) synthesized by ADP-ribosyl cyclase (Kuemmerle and Makhlouf ... Prakash, Y. S., Kannan, M. S., Walseth, T. F. and Sieck, G. C. (1998). Role of cyclic ADP-ribose in the regulation of [Ca2+]i ... Ge, Z. D., Zhang, D. X., Chen, Y. F., Yi, F. X., Zou, A. P., Campbell, W. B. and Li, P. L. (2003). Cyclic ADP-ribose ... Lee, H. C. (2004). Multiplicity of Ca2+ messengers and Ca2+ stores: a perspective from cyclic ADP-ribose and NAADP. Curr. Mol. ...
more infohttp://jcs.biologists.org/content/118/10/2261
EC 3.2.2.5  EC 3.2.2.5
Glossary: ADP-D-ribose = adenosine 5′-(5-deoxy-D-ribofuranos-5-yl diphosphate). Other name(s): NAD glycohydrolase; nicotinamide ... Reaction: NAD+ + H2O = ADP-D-ribose + nicotinamide. ... bifunctional ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase). ...
more infohttp://www.sbcs.qmul.ac.uk/iubmb/enzyme/EC3/2/2/5.html
Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38  Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38
CD38 exhibits a structural homology to Aplysia adenosine diphosphate (ADP)-ribosyl cyclase. This enzyme catalyzes the synthesis ... Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38 Academic Article ... of cyclic ADP-ribose (cADPR), a metabolite of nicotinamide adenine dinucleotide (NAD +) with calcium-mobilizing activity. A ...
more infohttp://scholars.uab.edu/display/pub767464
Livestock Metabolome Database: Showing metabocard for Adenosine (LMDB00019)  Livestock Metabolome Database: Showing metabocard for Adenosine (LMDB00019)
Adenosine. Description. Adenosine is a nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives ... For instance, adenosine plays an important role in energy transfer - as adenosine triphosphate (ATP) and adenosine diphosphate ... When administered intravenously, adenosine causes transient heart block in the AV node. Because of the effects of adenosine on ... ADP). It also plays a role in signal transduction as cyclic adenosine monophosphate, cAMP. Adenosine itself is both a ...
more infohttp://lmdb.ca/metabolites/LMDB00019
Adenosine deaminase conjugated with polyethylene glycol synonyms, adenosine deaminase conjugated with polyethylene glycol...  Adenosine deaminase conjugated with polyethylene glycol synonyms, adenosine deaminase conjugated with polyethylene glycol...
Antonyms for adenosine deaminase conjugated with polyethylene glycol. 2 words related to adenosine: biochemistry, nucleoside. ... What are synonyms for adenosine deaminase conjugated with polyethylene glycol? ... Synonyms for adenosine deaminase conjugated with polyethylene glycol in Free Thesaurus. ... adenosine diphosphate receptor antagonist. *Adenosine diphosphate ribose. *Adenosine diphosphate sugars. *Adenosine diphosphate ...
more infohttps://www.freethesaurus.com/adenosine+deaminase+conjugated+with+polyethylene+glycol
Adenosine Diphosphate Ribose Cyclase - Medical Dictionary online-medical-dictionary.org  Adenosine Diphosphate Ribose Cyclase - Medical Dictionary online-medical-dictionary.org
Adenosine Diphosphate Ribose Cyclase. A Membrane-bound or cytosolic enzyme that catalyzes the synthesis of Cyclic ADP-Ribose ( ... cADPR) from Nicotinamide Adenine Dinucleotide (NAD). This enzyme generally catalyzes the Hydrolysis of cADPR to ADP-Ribose, as ... well, and sometimes the synthesis of Cyclic ADP-Ribose 2 phosphate (2-P-cADPR) from NADP. ...
more infohttp://www.online-medical-dictionary.org/definitions-a/adenosine-diphosphate-ribose-cyclase.html
Adenosine diphosphate ribose - Wikipedia  Adenosine diphosphate ribose - Wikipedia
Adenosine diphosphate ribose is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. It binds to and ... Adenosine diphosphate Ribose Fonfria E, Marshall IC, Benham CD, et al. (September 2004). "TRPM2 channel opening in response to ... oxidative stress is dependent on activation of poly(ADP-ribose) polymerase". Br. J. Pharmacol. 143 (1): 186-92. doi:10.1038/sj. ...
more infohttps://en.wikipedia.org/wiki/Adenosine_diphosphate_ribose
Novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor  AZD2461 down-regulates VEGF and 
induces apoptosis in...  Novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor AZD2461 down-regulates VEGF and induces apoptosis in...
Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells ... Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells ... Novel poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, AZD2461, down-regulates VEGF and induces apoptosis in ...
more infohttp://ibj.pasteur.ac.ir/browse.php?a_id=2652&&
Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+ release in T lymphocyte cell lines. - Department of...  Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+ release in T lymphocyte cell lines. - Department of...
Recently, a metabolite of nicotinamide adenine dinucleotide+ (NAD+), termed cyclic adenosine diphosphate-ribose (cADPr), has ... Adenosine Diphosphate Ribose, Calcium, Cell Line, Chromatography, High Pressure Liquid, Cyclic ADP-Ribose, Humans, Signal ... Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+ release in T lymphocyte cell lines. ... Characterization of cyclic adenosine diphosphate-ribose-induced Ca2+ release in T lymphocyte cell lines. ...
more infohttps://pharm.ox.ac.uk/publications/678622
Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors -Pipeline Insights, 2015 | Global Market Research Reports  Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors -Pipeline Insights, 2015 | Global Market Research Reports
... provides the in-depth analysis of the pipeline assets across the Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) ... Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors- Pipeline Insights, 2015, ... Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors Overview. • Poly Adenosine Diphosphate (ADP) Ribose ... Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors Assessment by Molecule Type • Poly Adenosine Diphosphate ( ...
more infohttp://www.gosreports.com/poly-adenosine-diphosphate-adp-ribose-polymerase-parp-inhibitors-pipeline-insights-2015/
Cyclic adenosine 5-diphosphate ribose analogs without a southern ribose inhibit ADP-ribosyl cyclase-hydrolase CD38. -...  Cyclic adenosine 5'-diphosphate ribose analogs without a "southern" ribose inhibit ADP-ribosyl cyclase-hydrolase CD38. -...
... diphosphate ribose (cADPR) analogs based on the cyclic inosine 5-diphosphate ribose (cIDPR) template were synthesized by ... Replacing the base N9-ribose with a butyl chain generates inhibitors of cADPR hydrolysis by the human ADP-ribosyl cyclase CD38 ... Taken together, these analogs confirm that the northern ribose is critical for CD38 activity and inhibition, provide new ... catalytic domain (shCD38), illustrating the nonessential nature of the southern ribose for binding. Butyl substitution ...
more infohttps://pharm.ox.ac.uk/publications/677784
this molecule can interfere with next messenger pathways by performing as an adenosine diphosphate (ADP)-ribose acceptor...  this molecule can interfere with next messenger pathways by performing as an adenosine diphosphate (ADP)-ribose acceptor...
this molecule can interfere with next messenger pathways by performing as an adenosine diphosphate (ADP)-ribose acceptor ... this molecule can interfere with 2nd messenger pathways by performing as an adenosine diphosphate (ADP)-ribose acceptor thereby ...
more infohttp://urat1inhibitor.com/2016/03/23/this-molecule-can-interfere-with-next-messenger-pathways-by-performing-as-an-adenosine-diphosphate-adp-ribose-acceptor-therefore-inhibiting-adp-ribosylation-of-proteins-9/
Intracellular Calcium Homeostasis and Signaling | SpringerLink  Intracellular Calcium Homeostasis and Signaling | SpringerLink
cyclic adenosine diphosphate ribose. CaM. calmodulin. CaMK. calmodulin dependent kinase. cAMP. cyclic adenosine monophosphate ...
more infohttps://link.springer.com/chapter/10.1007%2F978-94-007-5561-1_5
Pregnancy-related modifications of rat myometrial Gs proteins: ADP ribosylation, immunoreactivity and gene expression studies.  Pregnancy-related modifications of rat myometrial Gs proteins: ADP ribosylation, immunoreactivity and gene expression studies.
Adenosine Diphosphate Ribose / metabolism. Adenylate Cyclase / metabolism. Animals. Base Sequence. Cholera Toxin / metabolism. ... 0/DNA Probes; 0/RNA, Messenger; 20762-30-5/Adenosine Diphosphate Ribose; 50-28-2/Estradiol; 57-83-0/Progesterone; 84371-65-3/ ...
more infohttp://www.biomedsearch.com/nih/Pregnancy-related-modifications-rat-myometrial/7999253.html
Plus it  Plus it
ABBREVIATIONS: ADPR, adenosine diphosphate ribose; APP, amyloid precursor protein; NAMN, nicotinic acid mononucleotide; nampt, ... ADP-ribose) polymerase; PBEF, pre-B-cell colony-enhancing factor; PRPP, 5-phosphoryl-ribose-1-pyrophosphate; QA, quinolinic ... NAD+ exerts potent effects through the poly(ADP-ribose) polymerases, mono-ADP-ribosyltransferases, and the recently ...
more infohttp://jpet.aspetjournals.org/content/324/3/883
A novel approach to detect toxin-catalyzed ADP-ribosylation in intact cells: its use to study the action of Pasteurella...  A novel approach to detect toxin-catalyzed ADP-ribosylation in intact cells: its use to study the action of Pasteurella...
20762-30-5/Adenosine Diphosphate Ribose; 9012-63-9/Cholera Toxin; 98-92-0/Niacinamide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases ... Adenosine Diphosphate Ribose / metabolism. Animals. Bacterial Proteins*. Bacterial Toxins / metabolism*. Cholera Toxin / ... ADP-ribose from the labeled protein by mercuric acetate. Cholera toxin catalyzed the [3H]-labeling of a 46-kD protein in the [2 ...
more infohttp://www.biomedsearch.com/nih/novel-approach-to-detect-toxin/1835459.html
  • 1. Cloning of cDNA coding for poly (ADP-ribose) synthetase : A complete amino acid sequence of bovine poly (ADP-ribose) synthetase was determined by cDNA cloning. (nii.ac.jp)
  • The modification of the 40-kD protein was ascribed to ADP-ribosylation of a cysteine residue on the basis of inhibition of labeling by nicotinamide and the release of [3H]ADP-ribose from the labeled protein by mercuric acetate. (biomedsearch.com)
  • ADP-ribosylarginine specific hydrolases (ARHs) can restore target protein function by hydrolytic removal of the entire ADP-ribose moiety. (nih.gov)
  • ADP-ribosylation of arginine is a reversible posttranslational modification (PTM) of proteins in which the ADP-ribose moiety is transferred from NAD+ to the guanidino group of arginine under release of nicotinamide (Fig. 1). (nih.gov)