Genomes and Genes
adenosine diphosphate ribose
Summary: 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.
Publications277 found, 100 shown here
- ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homologyA L Perraud
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 411:595-9. 2001..These results indicate that intracellular ADPR regulates calcium entry into cells that express LTRPC2...
- A ternary mechanism for NADH oxidation by positively charged electron acceptors, catalyzed at the flavin site in respiratory complex IJames A Birrell
Medical Research Council Mitochondrial Biology Unit, Wellcome Trust MRC Building, Cambridge, UK
FEBS Lett 585:2318-22. 2011..Our mechanism for paraquat reduction defines a new mechanism for superoxide production by complex I (by redox cycling); in contrast to direct O(2) reduction the rate is stimulated, not inhibited, by high NADH concentrations...
- Divalent copper is a potent extracellular blocker for TRPM2 channelBo Zeng
Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University Hull, Hull, HU6 7RX, UK
Biochem Biophys Res Commun 424:279-84. 2012..We concluded that Cu(2+) is a potent TRPM2 channel blocker. The sensitivity of TRPM2 channel to heavy metal ions could be a new mechanism for the pathogenesis of some metal ion-related diseases...
- Structure and biochemical functions of SIRT6Patricia W Pan
Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada
J Biol Chem 286:14575-87. 2011..Collectively, these new insights imply a unique activating mechanism and/or the possibility that SIRT6 could act as an NAD(+) metabolite sensor...
- Structural basis for the mechanism and regulation of Sir2 enzymesJose L Avalos
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA
Mol Cell 13:639-48. 2004..We propose a detailed structure-based mechanism for deacetylation and nicotinamide inhibition of Sir2 consistent with mutagenesis and enzymatic studies...
- Haploid genetic screens in human cells identify host factors used by pathogensJan E Carette
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Science 326:1231-5. 2009..This approach has both conceptual and practical parallels with genetic approaches in haploid yeast...
- TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-riboseFrank J P Kühn
Medical Faculty, RWTH Aachen, Institute of Physiology, Pauwelsstrasse 30, 52057 Aachen, Germany
Pflugers Arch 451:212-9. 2005..Moreover, it plays a decisive role in experimentally induced diabetes mellitus and in the activation of leukocytes...
- ADP-ribosylation of human defensin HNP-1 results in the replacement of the modified arginine with the noncoded amino acid ornithineLinda A Stevens
Translational Medicine Branch and Laboratory of Biochemistry, National Heart, Lung and Blood Institute, Medical Genetics Branch, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 106:19796-800. 2009..Targeted ADP-ribosylation of specific arginines by transferases, resulting in their replacement with ornithine, is an alternative pathway for regulation of protein function through posttranslational modification...
- Photorhabdus luminescens toxins ADP-ribosylate actin and RhoA to force actin clusteringAlexander E Lang
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, 79104 Freiburg, Germany
Science 327:1139-42. 2010..The concerted action of both toxins inhibited phagocytosis of target insect cells and induced extensive intracellular polymerization and clustering of actin. Several human pathogenic bacteria produce related toxins...
- Overexpression of an ADP-ribose pyrophosphatase, AtNUDX2, confers enhanced tolerance to oxidative stress in Arabidopsis plantsTakahisa Ogawa
Department of Advanced Bioscience, Faculty of Agriculture, Kinki University, 3327 204 Nakamachi, Nara 631 8505, Japan
Plant J 57:289-301. 2009....
- A biochemical genomics approach for identifying genes by the activity of their productsM R Martzen
Department of Biochemistry and Biophysics, University of Rochester School of Medicine, Rochester, NY 14642, USA
Science 286:1153-5. 1999....
- TRPM2 functions as a lysosomal Ca2+-release channel in beta cellsIngo Lange
Center for Biomedical Research, The Queen s Medical Center, Honolulu, HI 96813, USA
Sci Signal 2:ra23. 2009..Thus, ADPR and TRPM2 represent multimodal signaling elements regulating Ca2+ mobilization in beta cells through membrane depolarization, Ca2+ influx, and release of Ca2+ from intracellular stores...
- Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microgliaRobert Kraft
Institut fur Pharmakologie, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Thielallee 69 73, 14195 Berlin, Germany
Am J Physiol Cell Physiol 286:C129-37. 2004..The increased sensitivity to H2O2 in LPS-stimulated cells suggests a role for TRPM2 in the calcium signaling of activated microglia...
- Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?Paul O Hassa
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Microbiol Mol Biol Rev 70:789-829. 2006..e., DNA damage response, transcriptional regulation, and insulator function), are described. A potential cross talk between nuclear ADP-ribosylation processes and other NAD(+)-dependent pathways is discussed...
- Nicotinamide adenine dinucleotide: beyond a redox coenzymeHening Lin
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Org Biomol Chem 5:2541-54. 2007..Focus is given to the enzymatic reactions, mechanisms, structures, and biological functions...
- Crystal structure of ADP-ribosylated ribosomal translocase from Saccharomyces cerevisiaeRené Jørgensen
Macromolecular Crystallography, Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK8000 Aarhus, Denmark
J Biol Chem 279:45919-25. 2004..These results provide insight to the inhibitory mechanism and suggest that inhibition may be caused by erroneous interaction of the translation factor with the codon-anticodon area in the P-site of the ribosome...
- Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated lysosomal Ca2+ releaseAdriana Sumoza-Toledo
Laboratory of Cell and Molecular Signaling, Center for Biomedical Research, Queen s Medical Center, Honolulu, Hawaii, USA
FASEB J 25:3529-42. 2011..These results highlight TRPM2 as a key player regulating DC chemotaxis through its function as Ca(2+) release channel and confirm ADP-ribose as a novel second messenger for intracellular Ca(2+) mobilization...
- Transient receptor potential melastatin 2 is required for lipopolysaccharide-induced cytokine production in human monocytesJanine Wehrhahn
Department of Immunobiology, Institute of Biology II, University of Leipzig, 04277 Leipzig, Germany
J Immunol 184:2386-93. 2010..The identification of TRPM2 as a major player in this LPS-dependent process makes it a promising tool in modulating monocyte functions...
- Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn(2+)-dependent ADP-ribose/CDP-alcohol pyrophosphataseJosé Canales
Grupo de Enzimologia, Departamento de Bioquimica y Biologia Molecular y Genetica, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain
FEBS Lett 583:1593-8. 2009..This is similar to the ADP-ribose/cADPR formation ratio by NADases. The product of cADPR phosphohydrolysis by ADPRibase-Mn was N(1)-(5-phosphoribosyl)-AMP, suggesting a novel route for cADPR turnover...
- Combining affinity purification by ADP-ribose-binding macro domains with mass spectrometry to define the mammalian ADP-ribosyl proteomeNadia Dani
Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro Chieti, Italy
Proc Natl Acad Sci U S A 106:4243-8. 2009..This represents an important step toward the discovery of new ADP-ribosyltransferase targets and an understanding of the physiological role and the pharmacological potential of this protein modification...
- A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunitC Locht
Laboratoire de Microbiologie Génétique et Moléculaire, INSERM CJF 9109, Institut Pasteur de Lille, France
Biochimie 77:333-40. 1995..His-35 could increase the nucleophilicity of the cysteine in the G protein or the water molecule to attack the weakened N-glycosidic bond of NAD+ and yield the products of the reaction...
- Botulinum C2 toxin ADP-ribosylates cytoplasmic beta/gamma-actin in arginine 177J Vandekerckhove
Laboratorium voor Genetika, Gent, Belgium
J Biol Chem 263:696-700. 1988..Further digestion of these two peptides with thermolysin yielded the same radioactive peptide, which was in both cases peptide 175-177. Amino acid sequence analysis of peptides 174-183 and 175-177 located the ADP-ribosylation on Arg177...
- Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolitesMaarit Neuvonen
Institute of Biotechnology, University of Helsinki, Helsinki, Finland
J Mol Biol 385:212-25. 2009..The differential activity profiles of the human proteins implicate them in different cellular pathways, some of which may involve RNA rather than ADP-ribose derivatives...
- Structural basis of severe acute respiratory syndrome coronavirus ADP-ribose-1''-phosphate dephosphorylation by a conserved domain of nsP3Kumar Singh Saikatendu
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Structure 13:1665-75. 2005..Sequence and structure comparison of all known macro-H2A domains combined with available functional data suggests that proteins of this superfamily form an emerging group of nucleotide phosphatases that dephosphorylate Appr-1''-p...
- Metabolite of SIR2 reaction modulates TRPM2 ion channelOlivera Grubisha
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon 97239, USA
J Biol Chem 281:14057-65. 2006..ADP-ribose binds TRPM2 with similarly affinity, whereas NAD+ displays almost negligible binding. These studies provide the first evidence for the potential role of sirtuin-generated OAADPr in TRPM2 channel gating...
- Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acidRobert Kraft
Institut fur Pharmakologie, Charite Campus Benjamin Franklin, Thielallee 69 73, Berlin 14195, Germany
Br J Pharmacol 148:264-73. 2006..Owing to its high potency and efficacy ACA can serve, in combination with other blockers, as a useful tool for studying the unknown function of TRPM2 in native cells...
- Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domainsMarie Pierre Egloff
Centre National de la Recherche Scientifique and Universités d Aix Marseille I et II, UMR 6098, Architecture et Fonction des Macromolecules Biologiques, Ecole Supérieure d Ingénieurs de Luminy Case 925, France
J Virol 80:8493-502. 2006..Collectively, these results suggest to further evaluate the role of viral macro domains in host response to viral infection...
- Modulation of redox homeostasis under suboptimal conditions by Arabidopsis nudix hydrolase 7Niranjani Jambunathan
246 Noble Research Center, Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, USA
BMC Plant Biol 10:173. 2010..Secondly, we evaluate the biochemical and molecular consequences of increased NADH levels due to loss of function of AtNUDT7 in Arabidopsis...
- The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility of protein ADP-ribosylationChristoph Mueller-Dieckmann
European Molecular Biology Laboratory Hamburg Outstation, c o Deutsches Elektronen Synchrotron, Institute of Immunology, University Hospital, Hamburg, Germany
Proc Natl Acad Sci U S A 103:15026-31. 2006..Our results underscore the importance of endogenous ADP-ribosylation cycles and provide a basis for structure-based design of ADP-ribosylhydrolase inhibitors...
- The macro domain is an ADP-ribose binding moduleGeorgios I Karras
Gene Expression Programme and Structural and Computational Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany
EMBO J 24:1911-20. 2005..In addition, some macro domain proteins also recognize poly-ADP-ribose as a ligand. Our data suggest an important role for proteins containing macro domains in the biology of ADP-ribose...
- Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferaseGregory Liszt
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Biol Chem 280:21313-20. 2005..These results provide the first characterization of a Sir2 protein from phylogenetic class IV...
- Identification of direct and indirect effectors of the transient receptor potential melastatin 2 (TRPM2) cation channelBalazs Toth
Department of Medical Biochemistry, Semmelweis University, Budapest H 1094, Hungary
J Biol Chem 285:30091-102. 2010..H(2)O(2), cADPR, and NAADP did not enhance activation by ADPR. Considering intracellular concentrations of these compounds, none of them are likely to directly affect the TRPM2 channel protein in a physiological context...
- Extracellular-added ADP-ribose increases intracellular free Ca2+ concentration through Ca2+ release from stores, but not through TRPM2-mediated Ca2+ entry, in rat beta-cell line RIN-5FMasakazu Ishii
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan
J Pharmacol Sci 101:174-8. 2006..H2O2-induced Ca2+ entry through TRPM2 was not affected by extracellular ADP-ribose. These findings suggest that extracellular-added ADP-ribose induces Ca2+ release through the PLC-IP3 pathway and does not act as a TRPM2 activator...
- Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient miceJiro Kato
Pulmonary Critical Care Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC 1590, Bethesda, MD 20892 1590, USA
Mol Cell Biol 27:5534-43. 2007..In disease, toxin-catalyzed ADP-ribosylation overwhelms this potential host defense system, resulting in persistence of ADP-ribosylation and intoxication of the cell...
- SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cellsMarcia C Haigis
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
Cell 126:941-54. 2006..These results indicate that SIRT4 functions in beta cell mitochondria to repress the activity of GDH by ADP-ribosylation, thereby downregulating insulin secretion in response to amino acids, effects that are alleviated during CR...
- Studies on the polypeptide elongation factor 2 from Sulfolobus solfataricus. Interaction with guanosine nucleotides and GTPase activity stimulated by ribosomesG Raimo
Dipartimento di Biochimica e Biotecnologie Mediche, , Italia
J Biol Chem 270:21082-5. 1995..The ADP-ribosylation of SsEF-2 does not significantly affect either the binding of GDP and GTP or the kinetics of the GTPaser. A hypothesis on the stimulation by ribosome of SsEF-2 GTPase is proposed...
- Eukaryotic elongation factor 2 can bind to the synthetic oligoribonucleotide that mimics sarcin/ricin domain of rat 28S ribosomal RNAS Tang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Mol Cell Biochem 223:117-21. 2001..These results indicate that eEF2 is likely to bind directly to the sarcin/ricin domain of 28S ribosomal RNA in the process of protein synthesis...
- Emerging roles of NAD+ and its metabolites in cell signalingFriedrich Koch-Nolte
Institute of Immunology, Diagnostic Department, University Medical Center Hamburg Eppendorf, Martinistrasse 52, Hamburg, Germany
Sci Signal 2:mr1. 2009..A symposium in Hamburg, Germany, brought together 120 researchers from various fields, who were all engaged in the molecular characterization of the key players of NAD(+) signaling (www.NAD2008.de)...
- The new life of a centenarian: signalling functions of NAD(P)Felicitas Berger
Institut fur Biochemie, Freie Universitat Berlin, Thielallee 63, 14195 Berlin, Germany
Trends Biochem Sci 29:111-8. 2004..The comprehensive molecular characterization of NAD biosynthetic pathways over the past few years has further extended the understanding of the multiple roles of pyridine nucleotides in cell biology...
- A role for poly(ADP-ribose) polymerase in the transcriptional regulation of the melanoma growth stimulatory activity (CXCL1) gene expressionC Nirodi
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
J Biol Chem 276:9366-74. 2001..Furthermore, 3-aminobenzamide, an inhibitor of PARP-specific ADP-ribosylation, inhibits CXCL1 promoter activity and reduces levels of CXCL1 mRNA. The data point to the possibility that PARP may be a coactivator of CXCL1 transcription...
- The structure of ADP-ribose pyrophosphatase reveals the structural basis for the versatility of the Nudix familyS B Gabelli
Department of Biophysics and Biophysical Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA
Nat Struct Biol 8:467-72. 2001..This segregation of catalytic and recognition roles provides versatility to the Nudix family...
- Differential regulation of nicotinic acid-adenine dinucleotide phosphate and cADP-ribose production by cAMP and cGMPH L Wilson
University Department of Pharmacology, Oxford University, Mansfield Road, Oxford OX1 3QT, UK
Biochem J 331:837-43. 1998..We suggest that in the sea urchin egg, cADPR and NAADP production may be differentially regulated by receptor-coupled second messengers, with cADPR production being regulated by cGMP and NAADP production modulated by cAMP...
- Structure and function of an ADP-ribose-dependent transcriptional regulator of NAD metabolismNian Huang
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Structure 17:939-51. 2009..By comparing the crystal structures of NrtR in complex with DNA and with ADP-ribose, we identified a "Nudix switch" element that likely plays a critical role in the allosteric regulation of DNA binding and repressor function of NrtR...
- The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesisA Ruf
Institut fur Organische Chemie und Biochemie, Albertstr 21, Freiburg im Breisgau, D 79104, Germany
J Mol Biol 278:57-65. 1998....
- Kinetic determination of the effects of ADP-ribosylation on the interaction of eukaryotic elongation factor 2 with ribosomesO Nygard
Department of Cell Biology, Wenner Gren Institute, University of Stockholm, Sweden
J Biol Chem 265:6030-4. 1990..We conclude that the ADP-ribosylation affects both the association of the modified factor with pretranslocation ribosomes and the hydrolytic capacity of the factor...
- Transient ADP-ribosylation of a 2'-phosphate implicated in its removal from ligated tRNA during splicing in yeastS L Spinelli
Department of Biochemistry and Biophysics, University of Rochester School of Medicine, Rochester, New York 14642, USA
J Biol Chem 274:2637-44. 1999..Step 1 of this reaction is strikingly similar to the ADP-ribosylation of proteins catalyzed by a number of bacterial toxins...
- Redox-dependent change of nucleotide affinity to the active site of the mammalian complex IVera G Grivennikova
Department of Biochemistry, School of Biology, Moscow State University, Moscow 119992, Russian Federation
Biochemistry 46:10971-8. 2007..Possible models to explain the different titration patterns for the forward and reverse reactions are briefly discussed...
- Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeabilityClaudie M Hecquet
Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA
Circ Res 102:347-55. 2008..Thus, TRPM2 mediates H2O2-induced increase in endothelial permeability through the activation of Ca2+ entry via TRPM2. TRPM2 represents a novel therapeutic target directed against oxidant-induced endothelial barrier disruption...
- Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase: a novel metallophosphoesterase family preferentially expressed in rodent immune cellsJosé Canales
Grupo de Enzimologia, Departamento de Bioquimica y Biologia Molecular y Genetica, Facultad de Medicina, Universidad de Extremadura, 06080 Badajoz, Spain
Biochem J 413:103-13. 2008..Furthermore, the influence of ADPRibase-Mn on the CDP-choline or CDP-ethanolamine pathways of phospholipid biosynthesis cannot be discounted...
- Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoSMatthew J Riese
Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
J Biol Chem 277:12082-8. 2002..The 50-kDa protein was determined to be auto-ADP-ribosylated ExoS, whereas the 25-kDa protein appeared to represent a group of proteins that included Ras...
- Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the ratKenny K H Chung
Department of Physiology and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
J Neurophysiol 106:2865-75. 2011..Given the involvement of oxidative stress in degeneration of SNc neurons in Parkinson's disease, further studies are needed to determine the pathophysiological role of these channels in the disease process...
- Structure and mechanism of activity of the cyclic phosphodiesterase of Appr>p, a product of the tRNA splicing reactionA Hofmann
Protein Structure Section, Macromolecular Crystallography Laboratory, Program in Structural Biology, NCI Frederick, Frederick, MD 21702, USA
EMBO J 19:6207-17. 2000....
- Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-riboseEdith Wehage
Institute of Physiology, Medical Faculty, Rheinisch Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, D 52057 Aachen, Germany
J Biol Chem 277:23150-6. 2002..We conclude that activation of LTRPC2 by H(2)O(2) is independent of ADP-ribose and that LTRPC2 may mediate the influx of Na(+) and Ca(2+) during oxidative stress, such as the respiratory burst in granulocytes...
- Precursor ion scanning and sequencing of arginine-ADP-ribosylated peptide by mass spectrometryHarumi Osago
Department of Biochemistry, Shimane University, Faculty of Medicine, Izumo, Japan
Anal Biochem 393:248-54. 2009..We propose that a combination of the precursor ion scanning with ADP-R-carbodiimide as a marker ion and two-step collision is useful in searching for physiological target proteins of Arg-ADP-ribosylation...
- Inactivation of the elongation factor Tu by mosquitocidal toxin-catalyzed mono-ADP-ribosylationJörg Schirmer
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albert Ludwigs Universitat Freiburg, D 79104 Freiburg, Germany
Appl Environ Microbiol 68:4894-9. 2002..The inactivation of EF-Tu by MTX-mediated ADP-ribosylation and the resulting inhibition of bacterial protein synthesis are likely to play important roles in the cytotoxicity of the 27-kDa enzyme fragment of MTX toward E. coli...
- Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8Taisuke Wakamatsu
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
J Bacteriol 190:1108-17. 2008..These results suggest that ADPRase-I and ADPRase-II enzymes have nearly identical catalytic mechanisms but different mechanisms of substrate recognition...
- Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from structural and kinetic studiesManwu Zha
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
J Mol Biol 379:568-78. 2008..Structural comparison of different ADPRases also suggests that most dimeric ADPRases may share a similar catalytic mechanism of ADPR hydrolysis...
- Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functionsRobson Francisco de Souza
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
Mol Biosyst 8:1661-77. 2012..We use the data derived from this analysis to understand the origin and early evolutionary trajectories of key NAD-utilizing enzymes and present targets for future biochemical investigations...
- Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-riboseA H Guse
Department of Enzyme Chemistry, Institute of Physiological Chemistry, University of Hamburg, Germany
Nature 398:70-3. 1999..Thus we show the presence, causal relation and biological significance of the major constituents of the cADPR/calcium-signalling pathway in human T cells...
- TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymeraseElena Fonfria
Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW
Br J Pharmacol 143:186-92. 2004..64+/-0.38; 6.68+/-0.28; 4.78+/-0.05, respectively). 6. These data suggest that oxidative stress causes TRPM2 channel opening in both recombinant and endogenously expressing cell systems via activation of PARP enzymes...
- Flufenamic acid is a pH-dependent antagonist of TRPM2 channelsK Hill
Department of Neurology and GI CEDD, GlaxoSmithKline Research and Development Ltd, New Frontiers Science Park North, Third Avenue, Harlow, Essex CM19 5AW, UK
Neuropharmacology 47:450-60. 2004..These experiments suggest that FFA may be a useful tool antagonist for studies of TRPM2 function...
- Transformation products of extracellular NAD(+) in the rat liver: kinetics of formation and metabolic actionAna Carla Broetto-Biazon
Laboratory of Liver Metabolism, Department of Biochemistry, University of Maringa, Maringa, Brazil
Mol Cell Biochem 307:41-50. 2008..It was concluded that the metabolic and hemodynamic effects of extracellular NAD(+) are caused mainly by interactions with purinergic receptors with a highly significant participation of its main transformation product ADP-ribose...
- Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB)K Togashi
Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Aichi, Japan
Br J Pharmacol 153:1324-30. 2008..Although flufenamic acid, antifungal agents (miconazole and clotrimazole), and a phospholipase A(2) inhibitor (N-(p-amylcinnamoyl)anthranilic acid) inhibit TRPM2, their inhibition was either gradual or irreversible...
- Expression profile of the transient receptor potential (TRP) family in neutrophil granulocytes: evidence for currents through long TRP channel 2 induced by ADP-ribose and NADInka Heiner
Institut fur Physiologie, Universitätsklinikum der RWTH Aachen, Pauwelsstr 30, 52074 Aachen, Germany
Biochem J 371:1045-53. 2003..The results provide evidence that LTRPC2 in neutrophil granulocytes forms an entry pathway for Na(+) and Ca(2+), which is regulated by ADP-ribose and the redox state...
- TRPM2 Ca2+ permeable cation channels: from gene to biological functionAnne Laure Perraud
Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA
Cell Calcium 33:519-31. 2003....
- Identification of an iron-sulfur cluster that modulates the enzymatic activity in NarE, a Neisseria meningitidis ADP-ribosyltransferaseMariangela Del Vecchio
Novartis Vaccines and Diagnostics, Via Fiorentina 1, 53100 Siena, Italy
J Biol Chem 284:33040-7. 2009..This is the first observation suggesting that a member of the ADP-ribosyltransferase family contains an Fe-S cluster implicated in catalysis. This observation may unravel novel functions exerted by this class of enzymes...
- A new detection method for arginine-specific ADP-ribosylation of protein -- a combinational use of anti-ADP-ribosylarginine antibody and ADP-ribosylarginine hydrolaseHarumi Osago
Department of Biochemistry, Faculty of Medicine, Shimane University, Izumo 693 8501, Japan
J Biochem Biophys Methods 70:1014-9. 2008..We applied the method to search endogenously ADP-ribosylated protein in the rat, and detected possible target proteins in the skeletal muscle, which has high Art activity...
- Activation of T cell calcium influx by the second messenger ADP-riboseAndreas Gasser
University Medical Center Hamburg Eppendorf, Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology I Cellular Signal Transduction
J Biol Chem 281:2489-96. 2006..Moreover, gene silencing of TRPM2 abolished the ADPR- and ConA-mediated inward current. Thus, ADPR is a novel second messenger significantly involved in ConA-mediated cell death in T cells...
- Human alpha-defensins neutralize toxins of the mono-ADP-ribosyltransferase familyChun Kim
Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21 22, D 10117 Berlin, Germany
Biochem J 399:225-9. 2006..Our results reveal that toxin neutralization represents a novel biological function of HNPs in host defence...
- ADP-ribosylation of integrin alpha7 modulates the binding of integrin alpha7beta1 to lamininZhefeng Zhao
Department of Biochemistry, Kansas State University, 104 Willard Hall, Manhattan, KS 66506, USA
Biochem J 385:309-17. 2005....
- Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactionsA A Sauve
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
Biochemistry 40:15456-63. 2001..This mechanism is unprecedented in ADP-ribosyl transferase enzymology. The 2'- and 3'-AADPR products are candidate molecules for SIR2-initiated signaling pathways...
- Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neuronesKerstin Hill
Neurology, GlaxoSmithKline Research and Development Ltd, New Frontiers Science Park North, Harlow, Essex, UK
Neuropharmacology 50:89-97. 2006....
- Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metalSachiko Yoshiba
Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Osaka 560 0043, Japan
J Biol Chem 279:37163-74. 2004..This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond...
- Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosisLin Woo Kang
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Structure 11:1015-23. 2003..0 and 2.3 A, showed that there are sequence differences in binding site residues between MT-ADPRase and a human homolog that may be exploited for antituberculosis drug development...
- Spatial control of Ca2+ signaling by nicotinic acid adenine dinucleotide phosphate diffusion and gradientsG C Churchill
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, United Kingdom
J Biol Chem 275:38687-92. 2000..Thus, the range of action of NAADP can be tuned by its concentration from that of a local messenger, like Ca(2+), to that of a global messenger, like IP(3) or cyclic ADP-ribose...
- Glutamic acid 207 in rodent T-cell RT6 antigens is essential for arginine-specific ADP-ribosylationN Hara
Department of Biochemistry, Shimane Medical University, 89 1, Izumo, Shimane 693, Japan
J Biol Chem 271:29552-5. 1996..Moreover, the mouse homologue of rat RT6 lost arginine-specific ADP-ribosyltransferase activity when Glu-207 was replaced with Gln. Thus, Glu-207 in rodent T-cell RT6 antigens is essential for transfer reaction of ADP-ribose to arginine...
- Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine/protein mono(ADPribosyl)transferases and share secondary structure motifs with ADP-ribosylating bacterial toxinsF Koch-Nolte
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA
J Biol Chem 271:7686-93. 1996..4.2.31). They are the first such enzymes to be molecularly characterized in the immune system...
- New functions of a long-known molecule. Emerging roles of NAD in cellular signalingM Ziegler
Freie Universitat Berlin, Institut fur Biochemie, Berlin, Germany
Eur J Biochem 267:1550-64. 2000..Both cADPR and NAADP+ have been reported to be potent intracellular calcium-mobilizing agents. In concert with inositol 1,4,5-trisphosphate, they participate in cytosolic calcium regulation by releasing calcium from intracellular stores...
- Cloning and characterization of a new member of the Nudix hydrolases from human and mouseH Yang
Department of Microbiology and Molecular Genetics and the Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
J Biol Chem 275:8844-53. 2000..The genomic structures of both NUDT5 and mNudT5 were determined and located on human chromosome 10 and mouse chromosome 2, respectively. The role of NUDT5 in maintaining levels of free ADP-ribose in cells is discussed...
- Purification and characterization of adenosine diphosphate ribose pyrophosphatase from human erythrocytesJ S Kim
Department of Biochemistry, Medical School, Chonbuk National University, Chonju, South Korea
Int J Biochem Cell Biol 30:629-38. 1998..These results suggest that our enzyme is unique, and different from the other ADP-ribose pyrophosphatases reported. ADP-ribose pyrophosphatase may play an important role in the regulation of intracellular steady-state of free ADP-ribose...
- Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificityManwu Zha
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
J Mol Biol 364:1021-33. 2006....
- Molecular mechanisms of the cytotoxicity of ADP-ribosylating toxinsQing Deng
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
Annu Rev Microbiol 62:271-88. 2008..Bacterial toxins have been utilized as vaccines, as tools to dissect host cell physiology, and more recently for the development of novel therapies to treat human disease...
- CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretionI Kato
Department of Biochemistry, Tohoku University School of Medicine, Sendai 980 8575, Miyagi, Japan
J Biol Chem 274:1869-72. 1999..These results indicate that CD38 plays an essential role in intracellular Ca2+ mobilization by cADPR for insulin secretion...
- Conserved cysteine residues in the pore region are obligatory for human TRPM2 channel functionZhu Zhong Mei
Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
Am J Physiol Cell Physiol 291:C1022-8. 2006..These results taken together suggest that the cysteine residues in the pore region are obligatory for TRPM2 channel function...
- Intracellular calcium activates TRPM2 and its alternative spliced isoformsJianyang Du
Department of Cell Biology, Calhoun Cardiology Center, University of Connecticut Health Center, Farmington, CT 06030, USA
Proc Natl Acad Sci U S A 106:7239-44. 2009....
- Processing of ADP-ribosylated integrin alpha 7 in skeletal muscle myotubesA Zolkiewska
Pulmonary Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1434, USA
J Biol Chem 270:9227-33. 1995..Thus, cell surface ADP-ribosylation, in contrast to intracellular ADP-ribosylation, is not readily reversed by ADP-ribosylarginine hydrolase and seems to operate outside the postulated ADP-ribosylation cycle...
- How bacterial ADP-ribosylating toxins recognize substratesJianjun Sun
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA
Nat Struct Mol Biol 11:868-76. 2004..The electrostatic properties of regions A, B, C and E define the substrate specificity of ExoS and ExoT and these interactions can explain how other bacterial ADP-ribosylating toxins recognize their unique substrates...
- Sustained depolarization and ADP-ribose activate a common ionic current in rat peritoneal macrophagesBrice Campo
Institute of Molecular Physiology, University of Sheffield, Sheffield, United Kingdom
J Immunol 170:1167-73. 2003..The results suggest that prolonged depolarization leads to an increased intracellular level of ADP-ribose, which in turn activates this nonselective conductance(s)...
- Actin is ADP-ribosylated by the Salmonella enterica virulence-associated protein SpvBD Tezcan-Merdol
Microbiology and Tumor Biology Center, Karolinska Institute, , 171 77 Stockholm, Sweden
Mol Microbiol 39:606-19. 2001..We conclude that actin is a target for an SpvB-mediated modification, most probably ADP-ribosylation, and that the modification of G actin interferes with actin polymerization...
- Analysis of Arabidopsis growth factor gene 1 (GFG1) encoding a nudix hydrolase during oxidative signalingNiranjani Jambunathan
Department of Biochemistry and Molecular Biology, 246 Noble Research Center, Oklahoma State University, Stillwater, OK 74078, USA
Planta 224:1-11. 2006..Based on rapid transcriptional changes in response to various stresses, substrate specificity of the enzyme, and analysis of the knock out mutant, we propose that GFG1 is a key gene linking cellular metabolism and oxidative signaling...
- Cloning, expression and characterization of YSA1H, a human adenosine 5'-diphosphosugar pyrophosphatase possessing a MutT motifL Gasmi
School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB, U K
Biochem J 344:331-7. 1999..Hence the function of YSA1H might be to remove free ADP-ribose arising from NAD(+) and protein-bound poly- and mono-(ADP-ribose) turnover to prevent the occurrence of non-enzymic protein glycation...
- Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channelsAnne Laure Perraud
Department of Pediatrics, University of Washington and Children s Hospital and Regional Medical Center, 1959 N E Pacific Ave, Seattle, WA 98195, USA
J Biol Chem 280:6138-48. 2005....
- A highly specific phosphatase that acts on ADP-ribose 1''-phosphate, a metabolite of tRNA splicing in Saccharomyces cerevisiaeNeil P Shull
Department of Biochemistry and Biophysics, University of Rochester School of Medicine 601 Elmwood Avenue, Rochester, NY 14642, USA
Nucleic Acids Res 33:650-60. 2005..poa1-Delta mutants have no obvious growth defect at different temperatures in rich media, and analysis of yeast extracts suggests that approximately 90% of Appr1p processing activity originates from Poa1p...
- Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistryAnthony A Sauve
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
Biochemistry 42:9249-56. 2003..Sir2 intermediate. These findings suggest a strategy for increasing Sir2 enzyme catalytic activity in vivo by inhibition of chemical exchange but not deacetylation...
- Characterization of the Saccharomyces cerevisiae cyclic nucleotide phosphodiesterase involved in the metabolism of ADP-ribose 1",2"-cyclic phosphateF Nasr
Friedrich Miescher Institut, PO Box 2543, CH 4002 Basel, Switzerland
Nucleic Acids Res 28:1676-83. 2000..Likewise, overexpression of Cpd1p had no effect on yeast growth. These results do not implicate an important role for Appr>p or Appr-1"p in yeast cells grown under standard laboratory conditions...
- Comprehensive analysis of cytosolic Nudix hydrolases in Arabidopsis thalianaTakahisa Ogawa
Department of Advanced Bioscience, Faculty of Agriculture, Kinki University, 3327 204 Nakamachi, Nara 631 8505, Japan
J Biol Chem 280:25277-83. 2005..coli MutT in A. thaliana and is involved in the prevention of spontaneous mutation. The results obtained here suggest that the plant Nudix family has evolved in a specific manner that differs from that of yeast and humans...
- Structural identification of 2'- and 3'-O-acetyl-ADP-ribose as novel metabolites derived from the Sir2 family of beta -NAD+-dependent histone/protein deacetylasesMichael D Jackson
Oregon Health and Science University, Department of Biochemistry and Molecular Biology, Portland, Oregopn 97201 3098, USA
J Biol Chem 277:18535-44. 2002..Possible mechanisms for the generation of 2'-O-acetyl-ADP-ribose are discussed...
- Biosynthesis of diphthamide in Saccharomyces cerevisiae. Partial purification and characterization of a specific S-adenosylmethionine:elongation factor 2 methyltransferaseJ Y Chen
Department of Biochemistry, University of Minnesota, Minneapolis 55455
J Biol Chem 263:11692-6. 1988..Evidence is also presented for the existence of an ATP-dependent amidating enzyme which catalyzes the final step in the biosynthesis of diphthamide in EF-2...
- Immunocyte Ca2+ influx system mediated by LTRPC2Y Sano
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305 8585, Japan
Science 293:1327-30. 2001..This activation was suppressed by intracellular adenosine triphosphate. These results reveal that ADPR and NAD act as intracellular messengers and may have an important role in Ca2+ influx by activating LTRPC2 in immunocytes...
- Three-dimensional reconstruction using transmission electron microscopy reveals a swollen, bell-shaped structure of transient receptor potential melastatin type 2 cation channelYuusuke Maruyama
Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology AIST, Umezono 1 1 4, Tsukuba, Ibaraki 305 8568, Japan
J Biol Chem 282:36961-70. 2007..2 (TRPM2) is a redox-sensitive, calcium-permeable cation channel activated by various signals, such as adenosine diphosphate ribose (ADPR) acting on the ADPR pyrophosphatase (ADPRase) domain, and cyclic ADPR...
- A calcium influx pathway regulated separately by oxidative stress and ADP-Ribose in TRPM2 channels: single channel eventsMustafa Naziroglu
Department of Biophysics, Medical Faculty, Suleyman Demirel University, Cunur, Isparta 32260, Turkey
Neurochem Res 33:1256-62. 2008..A second novel result of the present study was that the TRPM2 channels were constitutionally activated by H2O2...
- Chymase-Mediated MMP Activation in Ishemia Reperfusion InjuryLOUIS JOSEPH DELL'ITALIA; Fiscal Year: 2013....
- Multi-targeted Countermeasures against Acute and Delayed Effects of OP ExposureJohn A Butera; Fiscal Year: 2013..This would set the stage for a final lead optimization campaign focused on identifying pre- clinical leads with well-balanced in vivo PK parameters during an SBIR Phase 2 continuing grant. ..
- A Hybrid PARP Inhibitor and Redox Catalyst for Lung TransplantationGARRY JOHN SOUTHAN; Fiscal Year: 2012..At present there are no approved prophylactic measures. We are developing a novel drug that targets the basic mechanisms of this condition and will test this agent in a clinically-relevant animal model. ..
- Peroxynitrite Decomposition Catalyst and Nitric Oxide Donor for EndotoxemiaGARRY JOHN SOUTHAN; Fiscal Year: 2012..We will now test this agent in a series of investigations in order to determine the optimal dose, to confirm the mechanism of action, and to establish the window of opportunity after disease onset within which therapy may be initiated. ..
- A Redox-active PARP Inhibitor for Lung TransplantationANDREW LURIE SALZMAN; Fiscal Year: 2012..At present there are no approved prophylactic measures. We are developing a novel drug that targets the basic mechanisms of this condition and will test this agent in two clinically-relevant animal models. ..
- A Hybrid Katp Channel Opener to Prevent Radiocontrast-Induced NephropathyKanneganti Murthy; Fiscal Year: 2012..We now propose to test this agent in a clinically-relevant small animal model of radiocontrast-induced kidney failure. ..
- Combination drug treatment to inhibit multiple cell death pathways after TBIALAN IRA FADEN; Fiscal Year: 2010....
- A Thioredoxin Mimetic for Radiocontrast NephropathyGARRY JOHN SOUTHAN; Fiscal Year: 2012..We now propose to test this agent in a clinically-relevant small animal model of radiocontrast-induced kidney failure. ..
- Hybrid Katp Channel Opener and Redox Catalyst for Lung TransplantationPrakash Jagtap; Fiscal Year: 2013..R-801 therapy is expected to translate into decreased primary graft dysfunction and mortality after lung transplant. ..
- A Bifunctional Katp Channel Activator and Redox Mimetic for BPDKanneganti Murthy; Fiscal Year: 2013....
- Regulation of LPS-mediated HMGB1 Release by Poly (ADP-ribose) Polymerase-1RAJESH K ANEJA; Fiscal Year: 2013..Additional studies will be performed to determine the therapeutic window for use of PARP-1 inhibitors in murine sepsis. ..
- Neurotrophins in the LungY S Prakash; Fiscal Year: 2012..By establishing the role of neurotrophins in airway narrowing with or without inflammation, the proposed studies will the foundation for better understanding of airway diseases, and potential development of new therapeutic targets. ..
- A Novel Thioredoxin Mimetic Prodrug for Prevention of Bronchopulmonary DysplasiaPrakash Jagtap; Fiscal Year: 2013..The heart will undergo morphometric analysis for evidence of PAH (as shown by right ventricular (RV) hypertrophy). ..
- PARP inhibitor and Redox Catalyst Conjugate for Traumatic Brain InjuryKanneganti Murthy; Fiscal Year: 2012..We are developing a novel drug that targets the basic mechanisms of this condition and will test this agent in a clinically-relevant animal model. ..
- Resuscitation of smoke inhalation and burn injury with a thioredoxin mimeticANDREW LURIE SALZMAN; Fiscal Year: 2012..We are developing a novel drug that targets the basic mechanisms of lung injury in this condition and will test this agent in a clinically-relevant large animal model f trauma. ..
- Local Calcium Signaling in Pulmonary ArteriesJAMES SK SHAM; Fiscal Year: 2012..The information generated by the proposed experiments will be valuable for the development of new treatments for pulmonary vascular diseases. ..
- PARP Inhibitor and Redox Catalyst for Ventilatory TraumaPrakash Jagtap; Fiscal Year: 2013..Lung concentrations of R-503 will be correlated with outcome measures, so as to construct a PD profile. ..
- Role of poly (ADP-ribose) polymerase 1 (PARP-1) in experimental colitisClaire Larmonier; Fiscal Year: 2013..Those specific aims will help address the following hypothesis: PARP1 contributes to aggravated mucosal immune response via modulation of inflammatory signaling pathways within the cells of the innate immune system. ..
- Chemokine Decoy Receptor for Therapy of Autoimmune ArthritisKanneganti Murthy; Fiscal Year: 2012..We will test this agent in a clinically-relevant small animal model and determine the most effective dose, in anticipation of definitive large animal studies to confirm its efficacy and safety. ..
- Novel Therapeutic Targets in Necrotizing EnterocolitisPeter J Giannone; Fiscal Year: 2012....
- NAD Metabolism and SignalingFrances E Lund; Fiscal Year: 2011....
- Pathogenesis of Oxidative Stress in Chagas DiseaseNisha Jain Garg; Fiscal Year: 2013..function during the progression of Chagas disease, and (3) ROS induced DNA oxidative adducts and poly(adenosine diphosphate ribose) polymerase 1 (PARP-1) activation signaled inflammatory cytokine response in infected cardiomyocytes...
- Chemokine Decoy Receptor: a novel therapy of IBDKanneganti Murthy; Fiscal Year: 2012..We are developing a novel drug that specifically blocks the inflammatory process in this condition. We will test this agent in a series of clinically-relevant animal models of autoimmune colitis. ..
- REGULATION OF NUCLEAR ENVELOPE ASSEMBLY AND DISASSEMBLYKatherine L Wilson; Fiscal Year: 2012..Aim 3 is a whole-genome and promoter-specific analysis of BAF function in C. elegans, which is expected to identify genes relevant to its roles in muscle and DNA- damage responses. ..
- Chemical approaches for studying the biology of CD38Hening Lin; Fiscal Year: 2013..The enzymatic activity can convert nicotinamide adenine dinucleotide (NAD) to adenosine diphosphate ribose (ADPR) and cyclic ADPR (cADPR), and NAD phosphate (NADP) to nicotinic acid adenine dinucleotide ..
- The Role of hPso4 in DNA Repair and Chemotherapy ResistanceMontaser Shaheen; Fiscal Year: 2013..We will deplete this E2 and evaluate if this will achieve the same chemosensitivity as depleting hPso4. This will open the opportunity to identify Ubc3 small molecule inhibitors as cancer therapy. ..
- Abnormal Bone Marrow Cells and Diabetic NeuropathyLawrence Chan; Fiscal Year: 2013..The proposed research on the role and mechanism of high glucose-induced PI-BMDCs and PI-BMDC-neuron cell fusion may lead to a fundamental change in our understanding of the pathogenesis of diabetic neuropathy. ..
- Mechanisms of Coronary Arteriolar Dysfunction in Type 2 DiabetesKhalid Matrougui; Fiscal Year: 2013..The goal of our studies is to determine how increased Epidermal Growth Factor Receptor tyrosine kinase activity compromises coronary arteriolar function in type 2 diabetes. ..
- Role of The Jak-Stat Pathway in Ischemic PreconditioningYu Ting Xuan; Fiscal Year: 2010..This proposal will provide important new insights into the signaling and molecular mechanisms whereby the late phase of ischemic PC reprograms the heart in the intact animal. ..
- Therapeutic Potential of PARP inhibitor for Acute PancreatitisLatha Paka; Fiscal Year: 2010..Our therapeutic strategy in the current project is to test our lead PARP inhibitors in two invivo models of AP and identifify one of the best PARP inhibitor to further studies in Phase II and potentially a clinical product. ..
- Radiocontrast Nephropathy: Redox Degradation Catalyst and Nitric Oxide DonorZSUZSANNA KINGA ZSENGELLER; Fiscal Year: 2013..The proposed studies will provide a rational foundation for advanced commercial development of R-100, with the intent that this product will serve as first-line prophylaxis in high-risk diabeic patients undergoing CM injection. ..
- Cardiac Autonomic Neuropathy and Myocardial Dysfunction in Type 1 DiabetesRODICA BUSUI POP-BUSUI; Fiscal Year: 2013..These studies will help elucidate mechanisms of myocardial dysfunction in T1DM with ultimate goal of designing future studies implementing therapeutic strategies aimed at preventing increased cardiovascular risk in patients with T1DM. ..
- Effect of cardioplegia and cardiopulmonary Bypass on coronary microvascular reactFrank W Sellke; Fiscal Year: 2013..The results of these studies may have significant implications regarding the recovery of diabetic and other patients after cardiac surgery involving cardioplegia and CPB. ..
- The differential regulation of poly(ADP-ribose) in cancer and its role in proteinKRISTIN ANNE KRUKENBERG; Fiscal Year: 2013..This study will also determine the potential of pADPr levels in predicting drug sensitivity and identify possible new strategies for the use of PARP inhibitors in the clinic. ..
- The role of two-pore channels in integrative calcium signalingMichael X Zhu; Fiscal Year: 2013....
- Defining the role of proteostasis pathways in cancer drug resistanceERICA LYNN CAIN; Fiscal Year: 2013..The components and pathways identified by this work will provide proof- of-concept mechanisms that may be exploited in developing new treatment strategies to prevent the escape of drug resistant populations of cancer cells. ! ..
- Regulation of IL4 signal transduciton by poly (ADP-ribose) polymerase-1.Rahul Datta; Fiscal Year: 2011..Given the data demonstrating that PARP-1 inhibition abates of pulmonary inflammation in the mouse model of asthma, it is important to study the role of PARP-1 in inflammation in order to develop strategies in dealing with the disease. ..
- Molecular and functional properties of the TRPM2 catioin channelReinhold Penner; Fiscal Year: 2010....
- The role of a novel AIF-associated nuclease PAAN1 in neuronal injuryYingfei Wang; Fiscal Year: 2013..This training will allow me to expand my expertise and help my transition into a successful independent academic researcher. ..
- Diphthamide biosynthesisHening Lin; Fiscal Year: 2012..These toxins catalyze the transfer of an adenosine diphosphate ribose (ADP-ribose) from nicotinamide adenine dinucleotide (NAD) to one of the nitrogen atoms in the imidazole ..
- PARTICIPATION OF PARP-1 IN THE PATHOGENESIS OF ASTHMAHamid Boulares; Fiscal Year: 2013....
- The role of cell death in Lupus NephritisRoberto Caricchio; Fiscal Year: 2013..The rationale for our project is that a better understanding of the pathways regulating the tissue damage in lupus GN pathophysiologies in males and females will lead to a tailored and better treatment for each gender. ..
- Targeted Therapy of Triple Negative Breast Cancer Using Theranostic NanoparticlesLily Yang; Fiscal Year: 2013..Clinical impact: The proposed study addresses the urgent need in clinical management of TNBC to improve the survival of patients afflicted with TNBC. ..
- Mechanisms and Modulation of Cell Death in Traumatic Brain InjuryALAN IRA FADEN; Fiscal Year: 2012..A better understanding of the mechanisms underlying TBI would offer the possibility of improving survival and insuring a more complete recovery. ..
- Targeting PCSK9 Transcription to Combat Hypercholesterolemia by BerberineJingwen Liu; Fiscal Year: 2013....
- Role of poly (ADP-ribose)in the Repair of Ultraviolet Induced DNA DamageBRENEE SHEMEIR KING; Fiscal Year: 2012..UVR is the major environmental agent contributing to skin cancer and this project is aimed at gaining a molecular understanding of PARP's role in DNA repair activities. ..
- The Role of PARP-1 in Hormone-Regulated TranscriptionWILLIAM L KRAUS; Fiscal Year: 2013..Given the important role of PARP-1 in human disease, as well as its potential "drugability", our studies could lead to new ways to exploit these factors as therapeutic targets. ..
- NEUROTROPHIC FACTOR MODULATION OF CORNEAL ENDOTHELIUMShay Whey Koh; Fiscal Year: 2009..abstract_text> ..
- Novel approaches to enhance tumor cell cytotoxicity of alkylating agentsRobert W Sobol; Fiscal Year: 2013..Insights gained from these studies have the potential to identify novel targets for adjuvant therapies including BER inhibitors and NAD+ biosynthesis modulators that can be combined with alkylators to improve anticancer drug efficacy. ..
- Structural Biochemistry of PARP-1John Pascal; Fiscal Year: 2013..The studies in this proposal will advance our understanding of PARP-1 mechanism of action and regulation to improve current models of PARP-1 biological functions and to reveal novel strategies for inhibiting PARP-1. ..
- Poly (ADP-Ribose) and AIF in Neuronal InjuryRAYMOND CHARLES KOEHLER; Fiscal Year: 2013....
- BBB Protection in HIV Infection: Barrier-shielding effects of PARP inhibitionYuri Persidsky; Fiscal Year: 2013..PARP inhibitors have now reached the stage of clinical testing for cancer treatment, assuring quick translation to therapy of immune/inflammatory disorders. ..
- Role of peroxynitrite in morphine hyperalgesia and toleranceDaniela Salvemini; Fiscal Year: 2012....
- Poly ADP-ribose Polymerase in Chromatin and Transcriptional RegulationAlexei V Tulin; Fiscal Year: 2012....
- A novel role for PARP1 in regulation of autophagyGen Sheng Wu; Fiscal Year: 2013..Significant efforts are being made to use inhibitors of PARP1 and autophagy to potentiate the therapeutic effectiveness of cytotoxic drugs. Our studies investigate a potentially novel function for PARP1 that links it to autophagy. ..
- SpyA, a novel S. pyogenes ADP-ribosyltransferaseSTEPHEN L MOSELEY; Fiscal Year: 2010..The goals of this grant are (1) to determine the role of SpyA in streptococcal infections, (2) to characterize its novel entry mechanism and (3) to characterize the structure and biochemical activity of this toxin. ..
- Targeting EWS/FLI1-driven pathways to improve therapeutic gains in Ewing's SarcomVicente Notario; Fiscal Year: 2012..abstract_text> ..
- PARP-1 is a Negative Modulator of the Heart Shock ResponseRAJESH K ANEJA; Fiscal Year: 2010..Aim 2 examines the effect of PARP-1 inhibition on HSF-1-mediated transactivation. Aim 3 seeks to study these phenomena in an in vivo setting, specifically examining the effects of heat shock in wt and PARP-/- animals. ..
- Targeting nucleotide excision repair in combination cancer therapyJohn J Turchi; Fiscal Year: 2013..Our previous data identified two classes of RPA inhibitors, both of which decrease ..
- Poly(ADP-ribose)Polymerase 1 Regulates Nucleolar Structure and FunctionsERNEST KOJO BOAMAH; Fiscal Year: 2012..This proposal will uncover a novel and exciting role for PARP1, which may have significant impact on cancer treatment regimens. ..
- Penn Center for Study of Epigenetics in ReproductionMarisa S Bartolomei; Fiscal Year: 2013..abstract_text> ..
- Targeting Tumorigenic Pathways in Glioblastoma with Oncolytic HSVSAMUEL DAVID RABKIN; Fiscal Year: 2013..Our long-term goal is to develop oHSV vectors that are safe and effective for clinical use and to elucidate combination strategies that will enhance efficacy. ..
- PARP inhibitor therapy for septic shockAndrew Salzman; Fiscal Year: 2004..Based on pre-clinical porcine shock models and clinical safety studies, we expect INO-1001 to be a safe, well-tolerated and effective therapeutic in patients with septic shock. ..
- NAD & CD38 Form a Communication System in the RetinaRobert Miller; Fiscal Year: 2006..If this hypothesis can be experimentally established, it will form the basis of an entirely new method by which neurons and glia support each other to stabilize retinal function. ..
- Significance of Caspase-Mediated Cleavage of PARP-1 in Cell DeathKAREN DAVID; Fiscal Year: 2007..We believe that understanding the functional significance of this cleavage will help in developing therapeutic intervention to combat aging-related diseases and cell death. [unreadable] [unreadable] [unreadable]..
- SIGNAL TRANSDUCTION IN T CELLSCONSTANTINE TSOUKAS; Fiscal Year: 1991..We'll measure the effects of these agents on IP3 and Ca++ accumulation using a permeabilized cell system and electroporation...
- MECHANISM OF CORONARY ENDOTHELIUM MEDIATED VASODILATIONPin Lan Li; Fiscal Year: 2000..These studies will demonstrate a new signaling pathway for the action of endothelium-derived vasodilators and contribute to our understanding of cellular and molecular mechanism gating K+ channels and regulating coronary vascular tone. ..
- PARS inhibitor therapy of smoke inhalation injuryPrakash Jagtap; Fiscal Year: 2001..Estimated worldwide gross sales revenues after market entry and maturation (ca. 4 years after FDA approval) equal $250 million (annual). ..
- CYCLIC ADP RIBOSE METABOLISM IN OXIDATIVE CELL DEATHMYRON JACOBSON; Fiscal Year: 2002....
- PARS inhibitor therapy for smoke inhalationAndrew Salzman; Fiscal Year: 2004..The proposed clinical trial is expected to provide the foundation for FDA orphan drug approval of INO-1001 for treatment of acute smoke inhalation injury. ..
- ADP RIBOSYLATION OF A POTENT INDUCER OF PROLIFERATIONMark Francis; Fiscal Year: 2002..Using NAD as a source, bacterial toxins add adenosine diphosphate ribose (ADP-ribose) to proteins, a process called ADP-ribosylation...
- Nitric Oxide--Neurotoxic Mechanisms of MPTPAllen Mandir; Fiscal Year: 2002..In this study we demonstrate that NMDA excitotoxicity is dramatically reduced in PARP-1 knockout mice whereas PARP-1 knockout mice are sensitive to AMPA excitotoxicity. ..
- Volatile Anesthesic Inhibition of Ca2+ Release in AirwayGary Sieck; Fiscal Year: 2006..The studies will initially focus on the effects of halothane; however, when significant effects are observed, the effects of isoflurane and sevoflurane will also be explored. ..
- Poly(ADP-ribose) polymerase in diabetic nephropathyIRINA OBROSOVA; Fiscal Year: 2006..abstract_text> ..
- Role of poly(ADP-ribosyl)ation in diabetic neuropathyIRINA OBROSOVA; Fiscal Year: 2004..The studies are of direct relevance to the pathogenesis of PDN and may provide the rationale for development of PARS inhibitors for its prevention and treatment. ..
- REGULATION OF MACROPHAGE DEPENDENT ANGIOGENIC ACTIVITYSAMUEL LEIBOVICH; Fiscal Year: 2002..abstract_text> ..
- REVERSIBLE ADP-RIBOSYLATION OF NITROGENASEPAUL LUDDEN; Fiscal Year: 2003..ADP-ribosylation is increasingly recognized as an important mechanism of regulation in eucaryotes and procaryotes. A number of pathogenic bacteria produce toxins that ADP-ribosylate crucial protein targets in their eucaryotic hosts. ..