peroxynitrous acid

Summary

Summary: A potent oxidant synthesized by the cell during its normal metabolism. Peroxynitrite is formed from the reaction of two free radicals, NITRIC OXIDE and the superoxide anion (SUPEROXIDES).

Top Publications

  1. pmc Nitric oxide and peroxynitrite in health and disease
    Pal Pacher
    Section on Oxidative Stress Tissue Injury, Laboratory of Physiologic Studies, National Institutes of Health, National Institute of Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
    Physiol Rev 87:315-424. 2007
  2. ncbi Peroxynitrite: biochemistry, pathophysiology and development of therapeutics
    Csaba Szabo
    Department of Surgery, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, University Heights, Newark, New Jersey 07103 2714, USA
    Nat Rev Drug Discov 6:662-80. 2007
  3. ncbi Peroxynitrite reactivity with amino acids and proteins
    B Alvarez
    Laboratorio De Enzimologia, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay
    Amino Acids 25:295-311. 2003
  4. ncbi Reactive nitrogen species in the chemical biology of inflammation
    Peter C Dedon
    Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Arch Biochem Biophys 423:12-22. 2004
  5. ncbi Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases
    Leszek Kalinowski
    Department of Biochemistry, Ohio University, Athens, OH 45701, USA
    Circulation 109:2511-7. 2004
  6. ncbi Fructose-induced peroxynitrite production is mediated by methylglyoxal in vascular smooth muscle cells
    Hui Wang
    Department of Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5
    Life Sci 79:2448-54. 2006
  7. ncbi Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite
    Krisztina Kupai
    Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary
    Am J Physiol Heart Circ Physiol 297:H1729-35. 2009
  8. ncbi Ibuprofen binding to secondary sites allosterically modulates the spectroscopic and catalytic properties of human serum heme-albumin
    Alessandra di Masi
    Department of Biology, and Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Italy
    FEBS J 278:654-62. 2011
  9. ncbi The impact of metal catalysis on protein tyrosine nitration by peroxynitrite
    A Daiber
    Universitatsklinikum Hamburg Eppendorf, Medizinische Klinik III, Angiologie und Kardiologie, Martinistr 52, 20246 Hamburg, Germany
    Biochem Biophys Res Commun 317:873-81. 2004
  10. ncbi Tetrahydrobiopterin protects soluble guanylate cyclase against oxidative inactivation
    Kurt Schmidt
    Department of Pharmacology and Toxicology, Karl Franzens Universitat Graz, Graz, Austria
    Mol Pharmacol 82:420-7. 2012

Detail Information

Publications257 found, 100 shown here

  1. pmc Nitric oxide and peroxynitrite in health and disease
    Pal Pacher
    Section on Oxidative Stress Tissue Injury, Laboratory of Physiologic Studies, National Institutes of Health, National Institute of Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
    Physiol Rev 87:315-424. 2007
    ..Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review...
  2. ncbi Peroxynitrite: biochemistry, pathophysiology and development of therapeutics
    Csaba Szabo
    Department of Surgery, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, University Heights, Newark, New Jersey 07103 2714, USA
    Nat Rev Drug Discov 6:662-80. 2007
    ..These include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases...
  3. ncbi Peroxynitrite reactivity with amino acids and proteins
    B Alvarez
    Laboratorio De Enzimologia, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay
    Amino Acids 25:295-311. 2003
    ..The preferential protein targets of peroxynitrite and the role of proteins in peroxynitrite detoxifying pathways are discussed...
  4. ncbi Reactive nitrogen species in the chemical biology of inflammation
    Peter C Dedon
    Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Arch Biochem Biophys 423:12-22. 2004
    ....
  5. ncbi Race-specific differences in endothelial function: predisposition of African Americans to vascular diseases
    Leszek Kalinowski
    Department of Biochemistry, Ohio University, Athens, OH 45701, USA
    Circulation 109:2511-7. 2004
    ..We hypothesized that the differences in endothelial NO/O2-/ONOO- metabolism may highlight the potential predisposition to endothelial dysfunction and cardiovascular complications prevalent in blacks...
  6. ncbi Fructose-induced peroxynitrite production is mediated by methylglyoxal in vascular smooth muscle cells
    Hui Wang
    Department of Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5
    Life Sci 79:2448-54. 2006
    ..Our results demonstrated that fructose is capable of inducing a significant increase in ONOO(-) production, which is mediated by an enhanced formation of endogenous MG in VSMCs...
  7. ncbi Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitrite
    Krisztina Kupai
    Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary
    Am J Physiol Heart Circ Physiol 297:H1729-35. 2009
    ..Furthermore, hyperlipidemia blocks the cardioprotective effect of postconditioning at least in part via deterioration of the postconditioning-induced early increase in peroxynitrite formation...
  8. ncbi Ibuprofen binding to secondary sites allosterically modulates the spectroscopic and catalytic properties of human serum heme-albumin
    Alessandra di Masi
    Department of Biology, and Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Italy
    FEBS J 278:654-62. 2011
    ..Thus, tHSA is a valuable model with which to investigate the allosteric linkage between the heme cleft FA1 and the ligand-binding pockets FA2 and FA6, all located in domains I and II of (t)HSA...
  9. ncbi The impact of metal catalysis on protein tyrosine nitration by peroxynitrite
    A Daiber
    Universitatsklinikum Hamburg Eppendorf, Medizinische Klinik III, Angiologie und Kardiologie, Martinistr 52, 20246 Hamburg, Germany
    Biochem Biophys Res Commun 317:873-81. 2004
    ..These results clearly identify peroxynitrite as the nitrating species even at low steady-state concentrations and demonstrate that metal catalysis plays an important role in nitration of protein-bound tyrosine...
  10. ncbi Tetrahydrobiopterin protects soluble guanylate cyclase against oxidative inactivation
    Kurt Schmidt
    Department of Pharmacology and Toxicology, Karl Franzens Universitat Graz, Graz, Austria
    Mol Pharmacol 82:420-7. 2012
    ..Protection of sGC against oxidative inactivation may contribute to the known beneficial effects of BH4 in cardiovascular disorders associated with oxidative stress...
  11. ncbi Contribution of nitric oxide, superoxide anion, and peroxynitrite to activation of mitochondrial apoptotic signaling in hippocampal CA3 subfield following experimental temporal lobe status epilepticus
    Yao Chung Chuang
    Department of Neurology, Chang Gung Memorial Hospital Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan, Republic of China
    Epilepsia 50:731-46. 2009
    ....
  12. ncbi Endogenous peroxynitrite modulates PGHS-1-dependent thromboxane A2 formation and aggregation in human platelets
    Stefan Schildknecht
    Vascular Biology Unit, Boston University School of Medicine, Boston, MA, 02118, USA
    Free Radic Biol Med 45:512-20. 2008
    ..This may provide a molecular explanation for the clinically observed hyperreactivity of platelets in high-risk patients and serve as a basis for novel therapeutic interventions...
  13. pmc Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block, and sudden death
    Imran N Mungrue
    Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada
    J Clin Invest 109:735-43. 2002
    ..This dramatic cardiac phenotype was rescued by specific attenuation of transgene activity. These data implicate cardiomyocyte iNOS overexpression as sufficient to cause cardiomyopathy, bradyarrhythmia, and sudden cardiac death...
  14. ncbi Multiple pathways of peroxynitrite cytotoxicity
    Csaba Szabo
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    Toxicol Lett 140:105-12. 2003
    ....
  15. ncbi Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation
    Francesc X Guix
    Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    Brain 132:1335-45. 2009
    ....
  16. pmc Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning
    Peter Ferdinandy
    Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dom ter 9, Szeged, H 6720 Hungary
    Br J Pharmacol 138:532-43. 2003
    ..Here we review the roles of NO, O(2)(-)*, and ONOO(-) in both ischaemia-reperfusion injury and preconditioning...
  17. ncbi Peroxynitrite and myocardial contractility: in vivo versus in vitro effects
    Tatsuo Katori
    935 Ross, Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Free Radic Biol Med 41:1606-18. 2006
    ..These data demonstrate that the site of generation within the cardiovascular system largely dictates the ability of ONOO- to directly or indirectly modulate cardiac pump function...
  18. ncbi Scavenging of reactive nitrogen species by mycobacterial truncated hemoglobins
    Paolo Ascenzi
    National Institute for Infectious Diseases IRCCS Lazzaro Spallanzani, Rome, Italy
    Methods Enzymol 436:317-37. 2008
    ..Here, mechanisms for scavenging of reactive nitrogen species by mycobacterial trHbs are reviewed, and detailed protocols for assessing pseudoenzymatic kinetics are provided...
  19. pmc Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis
    Graham S Timmins
    College of Pharmacy, Toxicology Program, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA
    Antimicrob Agents Chemother 48:3006-9. 2004
    ..In conclusion, INH-derived NO* has biological activity, which directly contributes to the antimycobacterial action of INH...
  20. ncbi Endothelial NADH/NADPH-dependent enzymatic sources of superoxide production: relationship to endothelial dysfunction
    Leszek Kalinowski
    Department of Clinical Chemistry and Laboratory of Cellular and Molecular Nephrology, Medical Research Centre of the Polish Academy of Science, Medical University of Gdansk, Poland
    Acta Biochim Pol 51:459-69. 2004
    ..It seems that O(2)(*-) generated by NAD(P)H oxidase may trigger eNOS uncoupling and contribute to the endothelial balance between NO and O(2)(*-). That is maintained at diverse levels...
  21. ncbi Hydroxyl radical formation by O-O bond homolysis in peroxynitrous acid
    Sergei V Lymar
    Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 5000, USA
    Inorg Chem 42:5259-66. 2003
    ..These observations resolve major disputes over experimental data existing in the literature; despite extensive investigation of these reactions, no verifiable experimental evidence has been advanced that contradicts the homolysis model...
  22. ncbi Dipeptidyl peptidase-4 inhibition with saxagliptin enhanced nitric oxide release and reduced blood pressure and sICAM-1 levels in hypertensive rats
    R Preston Mason
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    J Cardiovasc Pharmacol 60:467-73. 2012
    ..001) and decreased sICAM-1 levels by 37% (P < 0.01). The results of this study suggest that DPP4 inhibition reduces blood pressure and inflammation in hypertensive rats while increasing NO bioavailability...
  23. ncbi Effects of peroxynitrite dose and dose rate on DNA damage and mutation in the supF shuttle vector
    Min Young Kim
    Biological Engineering Division and Chemistry Department, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Chem Res Toxicol 18:76-86. 2005
    ..Furthermore, the results indicate that the chemistry of SIN-1-induced DNA damage differs substantially from native ONOO-, which suggests the need for caution in interpreting the biological relevance of SIN-1 as a surrogate for ONOO-...
  24. ncbi Peroxynitrite donor SIN-1 alters high-affinity choline transporter activity by modifying its intracellular trafficking
    Leah K Cuddy
    Molecular Brain Research Group, Robarts Research Institute, London, Ontario N6A 5K8, Canada
    J Neurosci 32:5573-84. 2012
    ..Increased oxidative-nitrosative stress in the microenvironment of cholinergic nerve terminals would diminish cholinergic transmission by reducing choline availability for ACh synthesis...
  25. ncbi Proteomic identification of nitrated proteins in Alzheimer's disease brain
    Alessandra Castegna
    Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506 0055, USA
    J Neurochem 85:1394-401. 2003
    ....
  26. ncbi Pro-oxidative effect of peroxynitrite regarding biological systems: a special focus on high-molar-mass hyaluronan degradation
    Eva Hrabarova
    Department of Carbohydrate Enzymology, Slovak Academy of Sciences, Bratislava, Slovak Republic
    Gen Physiol Biophys 30:223-38. 2011
    ..Here we also describe our experimental set-up for studying peroxynitrite-mediated degradation of hyaluronan, a system, which may be suitable for testing prospective pharmacological substances...
  27. ncbi Drug binding to Sudlow's site I impairs allosterically human serum heme-albumin-catalyzed peroxynitrite detoxification
    Paolo Ascenzi
    Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Roma, Italy
    IUBMB Life 62:776-80. 2010
    ..e., the fatty acid site 1, FA1), depending on ligand occupancy of either sites...
  28. ncbi A computational model for free radicals transport in the microcirculation
    Mahendra Kavdia
    Biomedical Engineering Program, University of Arkansas, Fayetteville, 72701, USA
    Antioxid Redox Signal 8:1103-11. 2006
    ..The results will have significant implications for our understanding of these free radical interactions in physiologic and pathophysiologic conditions resulting from endothelial dysfunction...
  29. ncbi Peroxynitrite is an essential component of cytokines production mechanism in human monocytes through modulation of nuclear factor-kappa B DNA binding activity
    Bashir M Matata
    Department of Integrative Human Cardiovascular Physiology and Functional Genomics, Cardiac Surgery, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, United Kingdom
    J Biol Chem 277:2330-5. 2002
    ..These findings indicate ONOO(-) plays an essential role in the mechanism of proinflammatory cytokine release by monocytes and that Rel/NF-kappaB activation is the obligatory pathway...
  30. ncbi Protective effects of cyanidin-3-O-glucoside from blackberry extract against peroxynitrite-induced endothelial dysfunction and vascular failure
    Ivana Serraino
    Dipartimento Clinico e Sperimentale di Medicina e Farmacologia, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy
    Life Sci 73:1097-114. 2003
    ....
  31. ncbi Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury
    Jin Hyup Lee
    Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Taegu 702 701, Korea
    J Biol Chem 278:51360-71. 2003
    ..The peroxynitrite-mediated damage to ICDH may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition...
  32. ncbi Reaction of astaxanthin with peroxynitrite
    Tsutomu Hayakawa
    Faculty of Agriculture, Shizuoka University, Shizuoka, Japan
    Biosci Biotechnol Biochem 72:2716-22. 2008
    ..Here we identify the major remaining reaction products of this reaction and investigate the stabilities of the nitro astaxanthins...
  33. pmc Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors
    Gwen S Scott
    Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 99:16303-8. 2002
    ..The therapeutic effect on animals with active EAE was associated with increased UA, but not inosine, levels in CNS tissue. We, therefore, conclude that the mode of action of inosine and inosinic acid in EAE is via their metabolism to UA...
  34. pmc Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes
    Pal Pacher
    National Institutes of Health, NIAAA, Laboratory of Physiologic Studies, 5625 Fishers Lane MSC 9413, Bethesda, Maryland 20852, USA
    Curr Opin Pharmacol 6:136-41. 2006
    ....
  35. ncbi Enhanced mitochondrial superoxide in hyperglycemic endothelial cells: direct measurements and formation of hydrogen peroxide and peroxynitrite
    Celia Quijano
    Departamento de Bioquimica, Facultad de Medicina, Avenida General Flores 2125, 11800 Montevideo, Uruguay
    Am J Physiol Heart Circ Physiol 293:H3404-14. 2007
    ..Mitochondrial O(2)(.-) formation in hyperglycemic conditions was associated with increased glucose metabolization in the Krebs cycle and hyperpolarization of the mitochondrial membrane...
  36. pmc Peroxynitrite toxicity in Escherichia coli K12 elicits expression of oxidative stress responses and protein nitration and nitrosylation
    Samantha McLean
    Departments of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK
    J Biol Chem 285:20724-31. 2010
    ..Thus, the cellular responses to peroxynitrite and hydrogen peroxide are distinct...
  37. ncbi Nitric oxide and cardioprotection during ischemia-reperfusion
    Bodh I Jugdutt
    Walter Mackenzie Helath Sciences Centre, Cardiology Division, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
    Heart Fail Rev 7:391-405. 2002
    ..Interventions that enhance NO availability by increasing eNOS might be beneficial after ischemia-reperfusion...
  38. pmc Uric acid protects against secondary damage after spinal cord injury
    Gwen S Scott
    Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 102:3483-8. 2005
    ..They also raise the possibility that elevating UA levels may provide a therapeutic approach for the treatment of SCI as well as other neurological diseases with a peroxynitrite-mediated pathological component...
  39. pmc Homocysteine induces cell death in H9C2 cardiomyocytes through the generation of peroxynitrite
    Sandra Levrand
    Department of Intensive Care Medicine, University Hospital Center, 1011 Lausanne, Switzerland
    Biochem Biophys Res Commun 359:445-50. 2007
    ..These results provide the first demonstration that HCY kills cardiomyocytes through the generation of peroxynitrite and can activate key signaling cascades in the myocardium...
  40. ncbi Resveratrol disrupts peroxynitrite-triggered mitochondrial apoptotic pathway: a role for Bcl-2
    Paula M Brito
    Laboratory of Biochemistry, Faculty of Pharmacy, Center of Neurosciences and Cell Biology, University of Coimbra, Couraça dos apóstolos, 51, R C, 3000 295, Coimbra, Portugal
    Apoptosis 13:1043-53. 2008
    ....
  41. ncbi Diabetes-induced nitrative stress in the retina, and correction by aminoguanidine
    Yunpeng Du
    Department of Medicine, Center for Diabetes Research, Case Western Reserve University, University Hospitals, and Veterans Affairs Medical Center, Cleveland, Ohio 44106 4951, USA
    J Neurochem 80:771-9. 2002
    ..Hyperglycemia increases NO production in retinal cells, and aminoguanidine can inhibit this abnormality. Inhibition of diabetic retinopathy by aminoguanidine might be mediated in part by inhibition of sequelae of NO production...
  42. pmc Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins
    Yasuyuki Irie
    Department of Integrative Biology and Pharmacology and the Institute of Molecular Medicine, University of Texas Medical School, 6431 Fannin, MSB 4 100, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 100:5634-9. 2003
    ..The activity was shown to be specific for Histone H1.2, to differ from proteasome activity, and to require no additional cofactors...
  43. ncbi SIN-1 cytotoxicity to PC12 cells is mediated by thiol-sensitive short-lived substances generated through SIN-1 decomposition in culture medium
    Kanako Konishi
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, Japan
    Nitric Oxide 20:270-8. 2009
    ..These results suggest that SIN-1 cytotoxicity in PC12 cells is mediated via the generation of cytotoxic substances in the medium during its decomposition...
  44. ncbi Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins
    Sewite Negash
    Division of Neonatology, Harbor UCLA Medical Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles Biomedical Research Institute, Torrance, California 90502, USA
    Am J Physiol Lung Cell Mol Physiol 293:L1012-20. 2007
    ..However, after 4 h of hypoxia, PKG nitration and decreased PKG expression are involved...
  45. ncbi Peroxynitrite detoxification by horse heart carboxymethylated cytochrome c is allosterically modulated by cardiolipin
    Paolo Ascenzi
    Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, I 00146 Roma, Italy
    Biochem Biophys Res Commun 415:463-7. 2011
    ..1 × 10(-5)M). Although CM-cytc-Fe(III) and CL-cytc-Fe(III) display a different heme distal geometry and heme-Fe(III) reactivity, the heme pocket and the CL cleft are allosterically linked...
  46. pmc Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies
    Pal Pacher
    Laboratory of Physiologic Studies, National Institutes of Health, NIAAA, Bethesda, MD 20892 9413, USA
    Curr Med Chem 12:267-75. 2005
    ....
  47. ncbi Loss of arterial and renal nitric oxide bioavailability in hypertensive rats with diabetes: effect of beta-blockers
    R Preston Mason
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Am J Hypertens 22:1160-6. 2009
    ..In this study, we examined the effects of beta(1)-selective antagonists, nebivolol and metoprolol, on vascular and renal EC function in spontaneously hypertensive (SH) rats with diabetes...
  48. ncbi Mechanistic studies of the isomerization of peroxynitrite to nitrate catalyzed by distal histidine metmyoglobin mutants
    Susanna Herold
    Laboratorium für Anorganische Chemie, Eidgenossische Technische Hochschule, ETH Honggerberg, CH 8093 Zurich, Switzerland
    J Am Chem Soc 126:6945-55. 2004
    ..Again, the extent of nitration of the tyrosine residues of the metMb mutants correlates with the values of k(cat)...
  49. ncbi Isoniazid and rifampicin inhibit allosterically heme binding to albumin and peroxynitrite isomerization by heme-albumin
    Paolo Ascenzi
    Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Viale Guglielmo Marconi 446, Rome, Italy
    J Biol Inorg Chem 16:97-108. 2011
    ..These results highlight the role of drugs in modulating heme-Fe(III) binding to HSA and HSA-heme-Fe(III) reactivity...
  50. ncbi Elevation of mitochondrial glutathione by gamma-glutamylcysteine ethyl ester protects mitochondria against peroxynitrite-induced oxidative stress
    Jennifer Drake
    Department of Chemistry and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506, USA
    J Neurosci Res 74:917-27. 2003
    ....
  51. pmc Attenuated vasodilatation in lambs with endogenous and exogenous activation of cGMP signaling: role of protein kinase G nitration
    Saurabh Aggarwal
    Pulmonary Disease Program, Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia 30912, USA
    J Cell Physiol 226:3104-13. 2011
    ..Together our data reveal that vascular dysfunction can occur, despite elevated levels of cGMP, due to PKG-1α nitration and subsequent attenuation of activity...
  52. ncbi Mechanistic studies on the reaction between cob(II)alamin and peroxynitrite: evidence for a dual role for cob(II)alamin as a scavenger of peroxynitrous acid and nitrogen dioxide
    Riya Mukherjee
    Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA
    Chemistry 17:11805-12. 2011
    Peroxynitrite/peroxynitrous acid (ONOO(-)/ONOOH; pK(a(ONOOH)) =6.8) is implicated in multiple chronic inflammatory and neurodegenerative diseases. Both mammalian B(12)-dependent enzymes are inactivated under oxidative stress conditions...
  53. ncbi Metmyoglobin and methemoglobin catalyze the isomerization of peroxynitrite to nitrate
    Susanna Herold
    Laboratorium für Anorganische Chemie, Eidgenossische Technische Hochschule, ETH Honggerberg, CH 8093 Zurich, Switzerland
    Biochemistry 42:14036-46. 2003
    ..Moreover, the globin offers very little protection, as the heme-free (apoMb) and heme-blocked (metMbCN) forms only partly prevent nitration of free tyrosine...
  54. pmc Peroxynitrite activates ERK via Raf-1 and MEK, independently from EGF receptor and p21Ras in H9C2 cardiomyocytes
    B Pesse
    Division of Critical Care, Department of Internal Medicine, University Hospital, 1011 Lausanne, Switzerland
    J Mol Cell Cardiol 38:765-75. 2005
    ..These results provide the novel concept that peroxynitrite may represent a previously unrecognized signaling molecule in various cardiac pathologies...
  55. ncbi The metalloporphyrin FeTPPS but not by cyclosporin A antagonizes the interaction of peroxynitrate and hydrogen peroxide on cardiomyocyte cell death
    Shaun S Klassen
    University of British Columbia, Vancouver, BC, V5Z 1M9, Canada
    Naunyn Schmiedebergs Arch Pharmacol 379:149-61. 2009
    ..The ability of FeTPPS to reduce reactive nitrogen-induced cell death, and protein nitration suggests that FeTPPS is a useful agent to maintain cell viability and is better than cyclosporin in this situation...
  56. pmc S-nitrosylation of peroxiredoxin II E promotes peroxynitrite-mediated tyrosine nitration
    Maria C Romero-Puertas
    Dipartimento Scientifico e Tecnologico, Universita degli Studi di Verona, 37134 Verona, Italy
    Plant Cell 19:4120-30. 2007
    ....
  57. pmc Targeting of phospholamban by peroxynitrite decreases beta-adrenergic stimulation in cardiomyocytes
    Mark J Kohr
    Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA
    Cardiovasc Res 77:353-61. 2008
    ..Thus, the purpose of this study is to investigate the contribution of phospholamban (PLB), a critical excitation-contraction coupling protein, to the peroxynitrite-induced dysfunction...
  58. ncbi Peroxynitrite-mediated modification of fibrinogen affects platelet aggregation and adhesion
    Pawel Nowak
    Department of General Biochemistry, University of Lodz, Lodz, Poland
    Platelets 13:293-9. 2002
    ..The percentage of ADP-induced platelet aggregation decreased as a function of peroxynitrite-mediated modification of fibrinogen molecule...
  59. ncbi NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity
    Martin L Pall
    School of Molecular Biosciences, Washington State University, Pullman, Washington 99164 4660, USA
    FASEB J 16:1407-17. 2002
    ..Evidence for each of these mechanisms, which may also be involved in Parkinson's disease, is reviewed. These interacting mechanisms provide explanations for diverse aspects of MCS and a framework for hypothesis-driven MCS research...
  60. ncbi Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c
    Paolo Ascenzi
    Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, I 00146 Roma, Italy
    Biochem Biophys Res Commun 404:190-4. 2011
    ..1±0.8)×10(-5) M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively...
  61. ncbi The peroxynitrite donor 3-morpholinosydnonimine induces reversible changes in electrophysiological properties of neurons of the guinea-pig spinal cord
    N Ashki
    Neuroscience Program, The University of Western Ontario, London, Ontario, Canada
    Neuroscience 156:107-17. 2008
    ..The reversal of immune-mediated conduction deficits may contribute to spontaneous neurologic deficits following neurotrauma...
  62. ncbi A peroxynitrite decomposition catalyst: FeTPPS confers cardioprotection during reperfusion after cardioplegic arrest in a working isolated rat heart model
    Benjamin Lauzier
    Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaire Expérimental, IFR n degrees 100, Faculte de Medecine et Pharmacie, 7 bd Jeanne d Arc, BP 87900, 21079 Dijon Cedex, France
    Fundam Clin Pharmacol 21:173-80. 2007
    ..The use of the peroxynitrite decomposition catalyst (FeTPPS) may help to improve myocardial preservation during a prolonged ischemia sequence...
  63. ncbi Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells
    A B El-Remessy
    Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Athens, USA
    FASEB J 21:2528-39. 2007
    ..In conclusion, peroxynitrite is critically involved in transducing VEGF's angiogenic signal via nitration-independent and oxidation-mediated tyrosine phosphorylation...
  64. ncbi Evidence for increased methylglyoxal in the vasculature of women with preeclampsia: role in upregulation of LOX-1 and arginase
    Sowndramalingam Sankaralingam
    Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
    Hypertension 54:897-904. 2009
    ..In conclusion, MG-induced LOX-1 expression is mediated via arginase upregulation likely because of uncoupling of NO synthase, which may have implications in preeclampsia...
  65. ncbi Detection of specific nitrotyrosine-modified proteins as a marker of oxidative stress in cardiovascular disease
    Serena Viappiani
    Am J Physiol Heart Circ Physiol 290:H2167-8. 2006
  66. ncbi Nitric oxide and nitroxidative stress in Alzheimer's disease
    Tadeusz Malinski
    Department of Chemistry and Biochemistry Ohio University, 350 W State Street, Athens, OH 45701, USA
    J Alzheimers Dis 11:207-18. 2007
    ..This article reviews the functions of NO and the potential role of NO/O2-/ONOO- induced nitroxidative stress in neuronal and endothelial degeneration observed in Alzheimer's disease...
  67. ncbi Neuroprotective effects of tempol, a catalytic scavenger of peroxynitrite-derived free radicals, in a mouse traumatic brain injury model
    Ying Deng-Bryant
    Spinal Cord and Brain Injury Research Center and Department of Anatomy and Neurobiology, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536 0509, USA
    J Cereb Blood Flow Metab 28:1114-26. 2008
    ..However, the modest neuroprotective effect of tempol suggests that multitarget combination strategies may be needed to interfere with posttraumatic secondary injury to a degree worthy of clinical translation...
  68. ncbi Fluorescence measurements of steady state peroxynitrite production upon SIN-1 decomposition: NADH versus dihydrodichlorofluorescein and dihydrorhodamine 123
    Francisco Javier Martin-Romero
    Departamento de Bioquimica y Biologia Molecular y Genetica, Facultad de Ciencias and Escuela de Ingenierías Agrarias, Universidad de Extremadura, Avenida de Elvas s n, 06080 Badajoz, Spain
    J Fluoresc 14:17-23. 2004
    ..It is shown that peroxynitrite concentration can be controlled (+/-5%) during predetermined times by using sequential SIN-1 pulses, to simulate chronic exposure of cells or subcellular components to peroxynitrite...
  69. pmc Quantitation of four guanine oxidation products from reaction of DNA with varying doses of peroxynitrite
    Hongbin Yu
    Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 56 731A, Cambridge, Massachusetts 02139, USA
    Chem Res Toxicol 18:1849-57. 2005
    ..The complexity of these dose-response relationships is likely due to the dual role of peroxynitrite as both an oxidant and a nucleophile in competition with water...
  70. pmc Chemical-biological fingerprinting: probing the properties of DNA lesions formed by peroxynitrite
    Sarah Delaney
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Chem Res Toxicol 20:1718-29. 2007
    ..Therefore, while 8-oxoGua itself is nontoxic and only mildly mutagenic in repair-proficient cells, peroxynitrite reveals the promutagenic potential and triggers the covert nature of this DNA lesion...
  71. ncbi Chronic production of peroxynitrite in the vascular wall impairs vasorelaxation function in SHR/NDmcr-cp rats, an animal model of metabolic syndrome
    Satomi Kagota
    Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women s University, Nishinomiya, Japan
    J Pharmacol Sci 109:556-64. 2009
    ....
  72. ncbi The apoprotein is the preferential target for peroxynitrite-induced LDL damage protection by dietary phenolic acids
    Teresa C P Dinis
    Laboratoire de Bioquímica Faculdade de Farmácia, Universidade de Coimbra, Portugal
    Free Radic Res 36:531-43. 2002
    ....
  73. ncbi Contribution of peroxynitrite to fatal cardiovascular depression induced by overproduction of nitric oxide in rostral ventrolateral medulla of the rat
    S H H Chan
    Center for Neuroscience, National Sun Yat Sen University, 804, Kaohsiung, Taiwan, ROC
    Neuropharmacology 43:889-98. 2002
    ..We conclude that the formation of peroxynitrite by a reaction between superoxide anion and NO is primarily responsible for the fatal cardiovascular depression induced by overproduction of NO after activation of iNOS at the RVLM...
  74. ncbi An inhibitor of inducible nitric oxide synthase and scavenger of peroxynitrite prevents diabetes development in NOD mice
    W L Suarez-Pinzon
    Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
    J Autoimmun 16:449-55. 2001
    ..These findings indicate that both superoxide and nitric oxide radicals contribute to islet beta-cell destruction in autoimmune diabetes via peroxynitrite formation in the beta-cells...
  75. ncbi BODIPY-based fluorescent probe for peroxynitrite detection and imaging in living cells
    Zhen Ning Sun
    Morningside Laboratory for Chemical Biology, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, People s Republic of China
    Org Lett 11:1887-90. 2009
    ..This new probe will be a useful tool for studying the roles of peroxynitrite in biological processes...
  76. ncbi Tyrosine nitration of a synaptic protein synaptophysin contributes to amyloid beta-peptide-induced cholinergic dysfunction
    M H Tran
    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Mol Psychiatry 8:407-12. 2003
    ..Our findings suggest that the tyrosine nitration of synaptophysin is related to Abeta-induced impairment of ACh release...
  77. ncbi Mutation of tyrosine 190 to alanine eliminates the inactivation of cytochrome P450 2B1 by peroxynitrite
    Hsia lien Lin
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
    Chem Res Toxicol 16:129-36. 2003
    ..Modeling studies suggest that Tyr 190 may play a structural role in maintaining the integrity of the protein for maximal activity through hydrogen bonding with Glu 149...
  78. ncbi Nitrocapsanthin and nitrofucoxanthin, respective products of capsanthin and fucoxanthin reaction with peroxynitrite
    Makoto Tsuboi
    Graduate of Science and Technology, Shizuoka University, 836 Ohya, Suruga ku, Shizuoka 422 8529, Japan
    J Agric Food Chem 59:10572-8. 2011
    ..Moreover, nitrocapsanthins (3 and 4) inhibited carcinogensis of mouse skin tumors initiated by 7,12-dimethylbenz[a]anthracene (DMBN)...
  79. ncbi Rapid scavenging of peroxynitrous acid by monohydroascorbate
    Christophe R Kurz
    Laboratorium für Anorganische Chemie, Eidgenössische Technische Hochschule Zürich Hönggerberg, Zurich, Switzerland
    Free Radic Biol Med 35:1529-37. 2003
    The reaction of peroxynitrous acid with monohydroascorbate, over the concentration range of 250 microM to 50 mM of monohydroascorbate at pH 5...
  80. pmc Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats
    Meenakshisundaram Thiyagarajan
    Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research NIPER, Sector 67, S A S Nagar, Mohali, Punjab, India
    Br J Pharmacol 142:899-911. 2004
    ....
  81. ncbi Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations
    Margaret M Tarpey
    Department of Anesthesiology, University of Alabama at Birmingham, 35294, USA
    Am J Physiol Regul Integr Comp Physiol 286:R431-44. 2004
    ..This review describes approaches to the direct and indirect measurement of different reactive metabolites of oxygen and nitrogen. Particular attention to a method's applicability for in vivo determinations will be addressed...
  82. ncbi Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction
    Pal Pacher
    Inotek Pharmaceuticals Corp, Beverly, Mass 01915, USA
    Circulation 107:896-904. 2003
    ....
  83. ncbi Oxidative and nitrosative stress in acute renal ischemia
    E Noiri
    Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo 113 8655, Japan 910 1193
    Am J Physiol Renal Physiol 281:F948-57. 2001
    ....
  84. pmc Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration
    You Yang Zhao
    Department of Pharmacology and 2Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA
    J Clin Invest 119:2009-18. 2009
    ..Thus, targeting of PKG nitration represents a potential novel therapeutic strategy for the treatment of PH...
  85. ncbi Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death via activation of calpains
    Matthew Whiteman
    Department of Biochemistry, Faculty of Medicine, National University of Singapore, 8 Medical Dr, Republic of Singapore 117597
    FASEB J 18:1395-7. 2004
    ..Our data show, for the first time, that peroxynitrite induces mitochondrial dysfunction in cells via a calcium-dependent process that leads to caspase-independent apoptosis mediated by calpains...
  86. ncbi Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology
    Ohara Augusto
    Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Brazil
    Free Radic Biol Med 32:841-59. 2002
    ..In this review, we provide a framework for this hypothesis and discuss the potential sources and properties of these radicals that are likely to become increasingly recognized as important mediators of biological processes...
  87. ncbi Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts
    Annamaria Onody
    Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged, Dom ter 9, H 6720 Szeged, Hungary
    Cardiovasc Res 58:663-70. 2003
    ..We investigated the influence of experimental hyperlipidemia on the formation of cardiac NO, superoxide, and peroxynitrite (ONOO(-)) in rat hearts...
  88. pmc Role of proinflammatory cytokines and redox homeostasis in exercise-induced delayed progression of hypertension in spontaneously hypertensive rats
    Deepmala Agarwal
    Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Dr, Baton Rouge, LA 70803, USA
    Hypertension 54:1393-400. 2009
    ....
  89. pmc Role of peroxynitrite in the redox regulation of cell signal transduction pathways
    Lucas Liaudet
    Department of Intensive Care Medicine, University Medical Center and Faculty of Biology and Medicine, Lausanne, Switzerland
    Front Biosci (Landmark Ed) 14:4809-14. 2009
    ....
  90. ncbi Peroxynitrite detoxification and its biologic implications
    Madia Trujillo
    Departamento de Bioquimica, Universidad de la Republica, Montevideo, Uruguay
    Antioxid Redox Signal 10:1607-20. 2008
    ..Flavonoids, nitroxides, and tyrosine-containing peptides decreased peroxynitrite-mediated toxicity under different conditions, but their mechanism of action is indirect...
  91. ncbi Scavenging of peroxynitrite reduces renal ischemia/reperfusion injury
    Ahmet Guven
    Department of Pediatric Surgery, Gulhane Military Medical Academy, Ankara, Turkey
    Ren Fail 30:747-54. 2008
    ....
  92. ncbi Superoxide radical- and peroxynitrite-scavenging activity of anthocyanins; structure-activity relationship and their synergism
    M Mamunur Rahman
    Niigata University of Pharmacy and Applied Life Sciences, Faculty of Applied Life Sciences, 265 1 Higashijima, Niigata, Japan
    Free Radic Res 40:993-1002. 2006
    ..It was confirmed that methylation of 4'-OH markedly reduced the antioxidant activity of anthocyanin. Further, it was revealed that synergism occurred in both - and ONOO- -scavenging activities among the anthocyanins in the mixture...
  93. ncbi Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia
    Yasemin Gursoy-OZdemir
    Department of Neurology, Faculty of Medicine, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey
    Stroke 35:1449-53. 2004
    ..However, depending on their cellular origin and interactions between them, these molecules may exert protective or deleterious actions, neither of which is characterized in the intact brain...
  94. ncbi Neuronal NOS-mediated nitration and inactivation of manganese superoxide dismutase in brain after experimental and human brain injury
    Hulya Bayir
    Safar Center for Resuscitation Research, Pittsburgh, Pennsylvania 15260, USA
    J Neurochem 101:168-81. 2007
    ..Nitration and inactivation of MnSOD could lead to self-amplification of oxidative stress in the brain progressively enhancing peroxynitrite production and secondary damage...
  95. ncbi Peroxynitrite-mediated oxidative damage to brain mitochondria: Protective effects of peroxynitrite scavengers
    Indrapal N Singh
    Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536 0509, USA
    J Neurosci Res 85:2216-23. 2007
    ....
  96. pmc Redox regulation of the AMP-activated protein kinase
    Yingying Han
    Department of Biochemistry and Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States of America
    PLoS ONE 5:e15420. 2010
    ..Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death...
  97. pmc Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes
    Viktor R Drel
    Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
    Int J Mol Med 20:783-92. 2007
    ..The findings provide rationale for development of potent peroxynitrite decomposition catalysts for the treatment of diabetic neuropathy...
  98. ncbi Degradation of extracellular matrix by peroxynitrite/peroxynitrous acid
    Eleanor C Kennett
    The Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown, NSW 2050, Australia
    Free Radic Biol Med 45:716-25. 2008
    ..Peroxynitrite/peroxynitrous acid, which is generated at elevated levels at sites of inflammation, is believed to play a role in ECM damage; ..
  99. pmc Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages
    Carolina Muscoli
    Faculty of Pharmacy, University of Catanzaro Magna Graecia, Roccelletta di Borgia, Catanzaro, Italy
    BMC Neurosci 3:13. 2002
    ..Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M)...
  100. ncbi The chemistry of peroxynitrite: implications for biological activity
    Sara Goldstein
    Department of Physical Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
    Methods Enzymol 436:49-61. 2008
    ....
  101. pmc Stimulation of peroxynitrite catalysis improves insulin sensitivity in high fat diet-fed mice
    Herve Duplain
    Department of Internal Medicine and Botnar Center for Clinical Research, University Hospital Center and University of Lausanne, Switzerland
    J Physiol 586:4011-6. 2008
    ..Stimulation of peroxynitrite catalysis attenuates HFD-induced insulin resistance in mice by restoring insulin signalling and insulin-stimulated glucose uptake in skeletal muscle tissue...

Research Grants65

  1. Molecular Basis for Microbicidal Action in Phagocytes
    James Hurst; Fiscal Year: 2005
    ..enzyme, myeloperoxidase, and the microbicidal competence of the putative macrophage-generated toxin, peroxynitrous acid (ONOOH)...
  2. NITRIC OXIDE TOXICITY--OXIDATIONS VIA PEROXYNITRITE
    WILLIAM PRYOR; Fiscal Year: 1999
    ..Nitric oxide itself is a weak oxidant, but it reacts with O2-. in the lung to produce peroxynitrite and peroxynitrous acid. HOONO, potent oxidants and toxins...
  3. Ultrapotent PARS inhibitor for CNS trauma
    Csaba Szabo; Fiscal Year: 2003
    ..Estimated worldwide revenues after market entry and maturation (ca. 4 years after FDA approval)=$750 million (annual). ..
  4. Peroxynitrate neutralizing agents for stroke therapy
    Csaba Szabo; Fiscal Year: 2003
    ....
  5. Adenosine-3 agonists for the suppression of arthritis
    Csaba Szabo; Fiscal Year: 2003
    ..A novel A3 receptor agonist may represent a useful anti-inflammatory adjunct to current therapeutic regimens; funding of the current SBIR Phase II will allow for starting human safety trials in 2 years. ..
  6. Novel preservation fluid for organ transplantation
    Jon Mabley; Fiscal Year: 2003
    ..abstract_text> ..
  7. Poly(ADP-ribose)and diabetic erectile dysfunction
    FANGMING ZUO; Fiscal Year: 2004
    ..If these studies confirm that Inotek's PARP inhibitor is effective in improving erectile function in diabetes, a Phase II component will be triggered, which will focus on formal preclinical safety testing. ..
  8. Myicardial injury: role of poly (ADP-ribose) synthetase
    Csaba Szabo; Fiscal Year: 2005
    ..Further, based on exciting preliminary data, the final, fifth aim is focusing in establishing the role of PARS in myocardial preconditioning. ..
  9. PARS INHIBITOR FOR THE THERAPY OF CIRCULATORY SHOCK
    Ludmila Belayev; Fiscal Year: 2003
    ..The current project will enable the applicants to move forward in two years, near to the level of the beginning of Phase II efficacy trial in septic patients. PROPOSED COMMERCIAL APPLICATION: Not Available ..
  10. NEUROSCIENCE TRAINING IN DRUG ABUSE
    DONALD KUHN; Fiscal Year: 2004
    ..abstract_text> ..
  11. Poly(ADP-ribose) synthetase inhibition and diabetes
    Csaba Szabo; Fiscal Year: 2004
    ....
  12. Molecular Neurobiology of Drug Abuse
    DONALD KUHN; Fiscal Year: 2006
    ..Kuhn will remain extensively engaged in scientific mentoring activities. ..
  13. PARS and peroxynitrite induced cell death
    Csaba Szabo; Fiscal Year: 2009
    ..4 To establish the role of Bel family proteins in the regulation of calcium homeostasis during peroxynitrite-induced cell death. The studies proposed here have broad pathophysiological relevance. ..
  14. Poly(ADP-ribose)Polymerase & Doxorubicin Cardiotoxicity
    Jon Mabley; Fiscal Year: 2002
    ..PROPOSED COMMERCIAL APPLICATIONS: The annual anticipated revenues for an effective therapeutic to prevent anti-cancer-drug induced cardiodepression is over $100 million in the US alone. ..
  15. MICROARRAY ANALYSIS OF HUMAN COCAINE ADDICTS
    DONALD KUHN; Fiscal Year: 2002
    ..Microarray-based scanning of the human genome has the potential to establish those genes or gene clusters that define the addictive phenotype, leading the way to proteomic-based studies of the bases of addiction. ..
  16. Methamphetamine Neurotoxicity and Microglial Activation
    DONALD KUHN; Fiscal Year: 2009
    ..A better understanding of the mechanisms by which METH causes persistent damage to the DA neuronal system could lead to more targeted therapies and would open newer lines of investigation into this and other neurotoxic drugs of abuse. ..
  17. Mechanisms of cardiovascular dysfunction in diabetes
    Csaba Szabo; Fiscal Year: 2005
    ..The final aim of the study is to investigate the activation of PARP in human microvasculature, and to correlate the degree of PARP activation with the degree of endothelial dysfunction in humans. ..
  18. PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
    DONALD KUHN; Fiscal Year: 2002
    ....
  19. Peroxynitrite-Induced Oxidative Damage in TBI
    Edward Hall; Fiscal Year: 2007
    ..abstract_text> ..
  20. 26th National Neurotrauma Symposium, 2008
    Edward Hall; Fiscal Year: 2008
    ..Particular efforts are made to actively engage students to participate and interact with leading basic and clinical scientists. [unreadable] [unreadable] [unreadable] [unreadable]..
  21. Poly(ADP-ribose) polymerase in diabetic nephropathy
    IRINA OBROSOVA; Fiscal Year: 2006
    ..abstract_text> ..
  22. Novel Neuroprotectants for TBI
    Edward Hall; Fiscal Year: 2008
    ..Thousands experience long lasting brain injury that interferes with their ability to lead productive and full lives. We plan to test a promising new class of therapeutics for traumatic brain injury. [unreadable] [unreadable] [unreadable]..
  23. Peroxynitrite decomposition catalyst:diabetic neuropathy
    IRINA OBROSOVA; Fiscal Year: 2006
    ..abstract_text> ..
  24. Bicarbonate Enhances Peroxidation of SOD/ALS Mutants
    Balaraman Kalyanaraman; Fiscal Year: 2008
    ....
  25. DNA RADICAL KINETICS
    Martin Newcomb; Fiscal Year: 2001
    ....
  26. Peroxide, NO and Iron Signaling in Endothelial Damage
    Balaraman Kalyanaraman; Fiscal Year: 2007
    ..Novelty: This proposal presents a new insight on peroxide-induced iron signaling in endothelial apoptosis and on the role of NO and antioxidants in mitigating these effects. ..
  27. ENOS & THE RADICAL MECHANISM OF ANTITUMOR ANTHRACYCLINES
    Balaraman Kalyanaraman; Fiscal Year: 2006
    ..Understanding the relationship between DOX-induced apoptosis and ROS formation may help discover novel antioxidant/antiapoptotic therapy in oxidant-induced disease processes. ..
  28. iNOS Posttranslational Regulation in Cardiac Rejection
    GALEN PIEPER; Fiscal Year: 2009
    ..A better understanding of this molecular process may lead to better strategies to prevent injury cardiac cells in these patients. ..
  29. NO-MEDIATED MODIFICATION OF NMDA RECEPTOR DURING HYPOXIA
    Om Mishra; Fiscal Year: 2006
    ..abstract_text> ..
  30. Ethanol Effects on Antigen Presentation in Liver Cells
    Natalia Osna; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  31. NO-MEDIATED MODIFICATION OF NMDA RECEPTOR DURING HYPOXIA
    Om Mishra; Fiscal Year: 2008
    ..abstract_text> ..
  32. MECHANISTIC PROBES FOR ENZYME-CATALYZED OXIDATIONS
    MARTIN E NEWCOMB; Fiscal Year: 2010
    ..A better understanding of the fundamental nature of the reactive species formed in the enzymes and the mechanisms of their reactions is expected to lead to lead ultimately to health-related advances in disease treatment and drug design. ..
  33. MOLECULAR TARGETS OF NITRIC OXIDE IN CARDIAC TRANSPLANTS
    GALEN PIEPER; Fiscal Year: 2004
    ..These studies will provide a novel mechanism to explain the pathogenesis of dyskinesis and graft failure during cardiac transplant rejection. ..
  34. Elucidation of nitric oxide resistance mechanisms in motor neurons
    Amy Bishop; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  35. PINEAL OPIOID RECEPTORS & ANALGESIC ACTION OF MELATONIN
    Manuchair Ebadi; Fiscal Year: 2002
    ..Therefore, future research must synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics. ..
  36. Basis for sequence selective guanine oxidation in DNA
    Peter Dedon; Fiscal Year: 2008
    ..Guanine lesions in the oligos will be characterized by LC-MS for single G sequences and by exonuclease digestion/MALDI-MS for localizing damage in sequences with multiple G's. ..
  37. The role of ADMA in the pathology of asthma
    Sandra Wells; Fiscal Year: 2008
    ..To ensure that the candidate accomplishes her research and training goals, she will have an excellent mentor and advisors, rich academic surroundings, and strong institutional commitment. [unreadable] [unreadable] [unreadable]..
  38. UV-induced and NOS-mediated Zn elevation, translation regulatin and apoptosis.
    Shiyong Wu; Fiscal Year: 2007
    ..g., reperfusion, wound healing, diabetes) that are affected by NO and translation inhibition. ..
  39. Renal tubular 20-HETE and EETs on sodium retention in
    Mong Heng Wang; Fiscal Year: 2009
    ..abstract_text> ..
  40. Mathematical Model of Vascular and Tubular Transport in the Rat Outer Medulla
    AURELIE EDWARDS; Fiscal Year: 2008
    ..We will simulate the effects of renal perfusion pressure-induced elevations in medullary CO concentrations on mTAL sodium reabsorption, so as to gain some insight into the mechanisms underlying pressure natriuresis. ..
  41. OXIDATION OF MACROMOLECULES IN SPINAL CORD INJURY
    Danxia Liu; Fiscal Year: 2001
    ..This will directly test whether free radicals damage neurons by inducing oxidation of major cell components and will provide strategies for therapy. ..
  42. Endothelial reactivity and nitric oxide synthetase activity in the ALMS (Aspreva
    Robert Clancy; Fiscal Year: 2009
    ..Relevance to public health: The association of markers/indices of NOS2 expression with mechanism of action of a successful drug treatment in lupus nephritis would be a major advance. ..
  43. Biochemical Characterization of Opioid Receptors
    Gavril W Pasternak; Fiscal Year: 2010
    ..Together, these studies should give a better understanding of the actions of opioids and their pharmacology. ..
  44. Characterization of Pancreatic Disease in a Novel Porcine Cystic Fibrosis Model
    Aliye Uc; Fiscal Year: 2010
    ..The goal of this application is to fully characterize pancreatic involvement in our novel CF pig model and to better understand the pathophysiological mechanisms leading to PI in CF. ..
  45. Mitochondrial Dysfunction and Drug Hepatotoxicity
    HARTMUT W JAESCHKE; Fiscal Year: 2010
    ..This new insight into the signaling mechanism of AAP-induced cell death holds the promise of establishing novel therapeutic approaches for preventing AAP-induced liver failure and potentially other forms of drug toxicity in humans. ..
  46. Mechanisms of Neutrophil-induced Liver Toxicity
    Hartmut Jaeschke; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  47. NOVEL THERAPIES FOR ACETAMINOPHEN TOXICITY
    Laura James; Fiscal Year: 2004
    ..abstract_text> ..
  48. SYNUCLEIN AND NIGRAL DOPAMINERGIC NEURON DEGENERATION
    Serge Przedborski; Fiscal Year: 2003
    ....
  49. 20-HETE and its interaction with NO in pregnant rats
    Mong Heng Wang; Fiscal Year: 2005
    ..Ultimately, this knowledge can uncover new therapeutic targets and provide novel loci for the control and treatment of pregnancy-induced hypertension. ..
  50. Evaluation of a Biomarker for Acetaminophen Toxicity
    Laura James; Fiscal Year: 2005
    ..The data generated from this study will lead to enhanced recognition of APAP hepatotoxicity, thus allowing for better identification of "at risk" populations and the creation of prevention strategies. ..
  51. Oxidants, Mitochondria,and Renal Ischemia/Reperfusion
    LEE MACMILLAN CROW; Fiscal Year: 2005
    ..This information will be helpful in determining possible therapeutic interventions for improving current techniques in renal preservation and transplantation. ..
  52. Counterblance in Inflammation
    MARION CHAN; Fiscal Year: 2005
    ..If feedback mechanisms become a new focus then a groundbreaking paradigm shift would have been made for the development of treatment for arthritis and other inflammation-induced tissue damages. ..
  53. NO& Epithelial Repair in Cryptosporidiosis
    Jody Gookin; Fiscal Year: 2006
    ..abstract_text> ..
  54. Molecular Probes of the Mechanisms of Cytochrome P450
    JOHN GROVES; Fiscal Year: 2006
    ..Synthetic and semi-synthetic phospholipid assemblies are used to model and understand the larger scale events in P450 and NOS action and to probe the permeability of membranes to reactive oxygen and nitrogen species. ..
  55. DNA OXIDATION BY ENDOGENOUS METALS
    Peter Dedon; Fiscal Year: 2003
    ..As a complement to base damage antibodies, the phosphoglycolate antibodies will be used to characterize DNA damage products in Aim number 1 and to quantify deoxyribose degradation in Aims number 2-5. ..
  56. UBIQUINONE AND MITOCHONDRIAL OXIDATIVE DISORDERS OF AGIN
    Manuchair Ebadi; Fiscal Year: 2003
    ..The completion of these studies will undoubtedly provide additional items of information on reactive oxygen species-induced damage of mitochondrial DNA and the protective effects of coenzyme Q10(ubiquinol) to minimize it. ..
  57. Oxidants, eicosanoids, and endothelium in diabetes
    Richard Cohen; Fiscal Year: 2002
    ..abstract_text> ..
  58. Regulation of heme uptake in intestinal epithelial cells
    Aliye Uc; Fiscal Year: 2007
    ..heme uptake pathways will have a great impact in understanding disorders associated with iron overload (hereditary hemochromatosis, iron overload secondary to blood transfusions) and nutritional iron deficiency [unreadable] [unreadable]..
  59. Cardiac myofibroblasts in autoimmune-associated CHB
    Robert Clancy; Fiscal Year: 2002
    ....
  60. MOLECULAR IMAGING OF MELANOMA BY EPR
    Graham Timmins; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  61. Antimycobacterial NO from KatG Activation of Isoniazid
    Graham Timmins; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  62. NITRIC OXIDE INHIBITOR AND LEISHMANIA PATHOGENESIS
    MARION CHAN; Fiscal Year: 2004
    ..Presently, only limited studies addressing this area have been performed. Our proposal fills this gap of knowledge. ..
  63. Ethanol Effects on Hepatic Proteolytic Systems
    TIANA CURRY MCCOY; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  64. Oxidative Stress and Myocardial Remodeling Following MI
    Yao Sun; Fiscal Year: 2008
    ..abstract_text> ..