Skip to main content
SpringerLink
Log in

Peroxynitrite Biology

  • Reference work entry
  • First Online:
Systems Biology of Free Radicals and Antioxidants

Abstract

Free radicals possess at least one unpaired electron in the outer electron orbit and usually, but not always, are highly chemically reactive. Molecular dioxygen (O2) is stable; however, the oxygen-centered free radicals, superoxide (O2 •−) and hydroxyl (•OH), are not stable. In biological systems, reactive oxygen species (ROS), such as superoxide (O2 •−) and hydrogen peroxide (H2O2), play important signaling roles but may also contribute to cellular damage and disease development. Nitric oxide (also known as nitrogen oxide, or nitrogen monoxide, or simply NO) is also a free radical, and the existence of an unpaired electron may be reflected by the use of the abbreviation NO• rather than NO. Unless discussing the three-redox forms of nitrogen monoxide (the nitrosonium ion, NO+, the uncharged free radical, NO•, and the nitroxyl anion, NO− or HNO), the abbreviation NO will be used throughout this chapter. Reactive nitrogen species (RNS) are produced in biological systems starting with the reaction of NO with O2 •− to form the highly reactive RNS peroxynitrite (ONOO−) that, unlike NO or O2 •−, is a very strong oxidant and nitrating agent. Thus, despite both NO and O2 •− being free radicals, neither are as reactive as ONOO−, and the toxicity of these two free radicals relates primarily to ONOO−. Understanding how ONOO− modulates different intracellular biochemical pathways and how this may affect normal physiological processes and/or give rise to pathological conditions is an emerging area of great scientific interest. ONOO− exerts its adverse effects by direct interaction with CO2, proteins that contain transition metal centers or thiols, or indirectly by aiding the generation of the highly potent hydroxyl radical. In this chapter, we outline the biochemistry and pathophysiology of ONOO− with a particular reference to cardiovascular disease and diabetes. We also address how scavenging strategies can attenuate the toxic effects of ONOO− and therefore may repress the pathophysiological effects of ONOO− and offer the potential for new therapeutic interventions.

Gnanapragasam Arunachalam and Samson Mathews Samuel contributed equally to the manuscript.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,999.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 2,999.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

(•NO2):

Nitrogen dioxide

(•OH):

Hydroxyl radical

(CO3 •−):

Carbonate radical

(O2 •−):

Superoxide anion

ARE:

Antioxidant response element

BH2 :

Dihydrobiopterin

BH4 :

Tetrahydrobiopterin

cGMP:

Cyclic guanosine monophosphate

eNOS:

Endothelial nitric oxide synthase

ERKs:

Extracellular signal-regulated kinases

H2O2 :

Hydrogen peroxide

HClO:

Hypochlorous acid

HONOO:

Peroxynitrous acid

IκB:

IκB kinase

JNK:

c-Jun N-terminal kinases

NO:

Nitrogen (mon)oxide

NO+ :

Nitrosonium ion

NO− (HNO):

Nitroxyl ion nitrosyl hydride, or hydrogen oxonitrate

NO• :

Nitric oxide free radical

NRF2:

Nuclear factor (erythroid-derived 2)-like 2

ONOO− :

Peroxynitrite

PARP:

Poly(ADP-ribose) polymerase

PKC:

Protein kinase C

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SERCA:

Sarcoendoplasmic reticulum Ca2+-ATPase

SOD:

Superoxide dismutases

TNF-α:

Tumor necrosis factor-alpha

References

  • Acquaviva R, Campisi A, Murabito P, Raciti G, Avola R, Mangiameli S, Musumeci I, Barcellona ML, Vanella A, Li Volti G (2004) Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism. Anesthesiology 101:1363–1371

    CAS  PubMed  Google Scholar 

  • Adachi T, Weisbrod RM, Pimentel DR, Ying J, Sharov VS, Schöneich C, Cohen RA (2004) S-glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. Nat Med 10:1200–1207

    CAS  PubMed  Google Scholar 

  • Adak S, Wang Q, Stuehr DJ (2000) Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase. Implications for mechanism. J Biol Chem 275:33554–33561

    CAS  PubMed  Google Scholar 

  • Ademoglu F, Basgut B, Abacioglu N, Cakici I (2002) The mechanisms of peroxynitrite-induced relaxations in isolated rat anococcygeus muscle. Pharmacology 66:1–4

    CAS  PubMed  Google Scholar 

  • Ahmad R, Rasheed Z, Ahsan H (2009) Biochemical and cellular toxicology of peroxynitrite: implications in cell death and autoimmune phenomenon. Immunopharmacol Immunotoxicol 31:388–396

    CAS  PubMed  Google Scholar 

  • Aljofan M, Ding H (2010) High glucose increases expression of cyclooxygenase-2, increases oxidative stress and decreases the generation of nitric oxide in mouse microvessel endothelial cells. J Cell Physiol 222:669–675

    CAS  PubMed  Google Scholar 

  • Alp NJ, Channon KM (2004) Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 24:413–420

    CAS  PubMed  Google Scholar 

  • Altug S, Demiryurek AT, Cakici I, Kanzik I (1999) The beneficial effects of peroxynitrite on ischaemia-reperfusion arrhythmias in rat isolated hearts. Eur J Pharmacol 384:157–162

    CAS  PubMed  Google Scholar 

  • Alvarez B, Radi R (2003) Peroxynitrite reactivity with amino acids and proteins. Amino Acids 25:295–311

    CAS  PubMed  Google Scholar 

  • Alvarez B, Ferrer-Sueta G, Radi R (1998) Slowing of peroxynitrite decomposition in the presence of mannitol and ethanol. Free Radic Biol Med 24:1331–1337

    CAS  PubMed  Google Scholar 

  • Alvarez B, Demicheli V, Duran R, Trujillo M, Cervenansky C, Freeman BA, Radi R (2004) Inactivation of human Cu, Zn superoxide dismutase by peroxynitrite and formation of histidinyl radical. Free Radic Biol Med 37:813–822

    CAS  PubMed  Google Scholar 

  • Andrews KL, Pannirselvam M, Anderson TJ, Jenkins AJ, Triggle CR, Hill MA (2005) The vascular endothelium in diabetes: a practical target for drug treatment? Expert Opin Ther Targets 9:101–117

    CAS  PubMed  Google Scholar 

  • Aoyama K, Matsubara K, Fujikawa Y, Nagahiro Y, Shimizu K, Umegae N, Hayase N, Shiono H, Kobayashi S (2000) Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann Neurol 47:524–527

    CAS  PubMed  Google Scholar 

  • Arteel GE, Sies H (1999) Protection against peroxynitrite by cocoa polyphenol oligomers. FEBS Lett 462:167–170

    CAS  PubMed  Google Scholar 

  • Arteel GE, Mostert V, Oubrahim H, Briviba K, Abel J, Sies H (1998) Protection by selenoprotein P in human plasma against peroxynitrite-mediated oxidation and nitration. Biol Chem 379:1201–1205

    CAS  PubMed  Google Scholar 

  • Arteel GE, Briviba K, Sies H (1999) Protection against peroxynitrite. FEBS Lett 445:226–230

    CAS  PubMed  Google Scholar 

  • Ascenzi P, Visca P (2008) Scavenging of reactive nitrogen species by mycobacterial truncated hemoglobins. Methods Enzymol 436:317–337

    CAS  PubMed  Google Scholar 

  • Ascenzi P, De Marinis E, Coletta M, Visca P (2008) H2O2 and (.)NO scavenging by Mycobacterium leprae truncated hemoglobin O. Biochem Biophys Res Commun 373:197–201

    CAS  PubMed  Google Scholar 

  • Ascenzi P, di Masi A, Sciorati C, Clementi E (2010) Peroxynitrite – an ugly biofactor? Biofactors 36:264–273

    CAS  PubMed  Google Scholar 

  • Augusto O, Bonini MG, Amanso AM, Linares E, Santos CC, De Menezes SL (2002) Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology. Free Radic Biol Med 32:841–859

    CAS  PubMed  Google Scholar 

  • Bajt ML, Knight TR, Farhood A, Jaeschke H (2003) Scavenging peroxynitrite with glutathione promotes regeneration and enhances survival during acetaminophen-induced liver injury in mice. J Pharmacol Exp Ther 307:67–73

    CAS  PubMed  Google Scholar 

  • Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass JM, Bhatnagar A, Tang XL, Wang O, Cardwell E, Ping P (2002) Nitric oxide (NO) induces nitration of protein kinase Cepsilon (PKCepsilon), facilitating PKCepsilon translocation via enhanced PKCepsilon -RACK2 interactions: a novel mechanism of no-triggered activation of PKCepsilon. J Biol Chem 277:15021–15027

    CAS  PubMed  Google Scholar 

  • Bapat S, Verkleij A, Post JA (2001) Peroxynitrite activates mitogen-activated protein kinase (MAPK) via a MEK-independent pathway: a role for protein kinase C. FEBS Lett 499:21–26

    CAS  PubMed  Google Scholar 

  • Bar-Shai M, Reznick AZ (2006) Peroxynitrite induces an alternative NF-kappaB activation pathway in L8 rat myoblasts. Antioxid Redox Signal 8:639–652

    CAS  PubMed  Google Scholar 

  • Batinic-Haberle I, Cuzzocrea S, Reboucas JS, Ferrer-Sueta G, Mazzon E, Di Paola R, Radi R, Spasojevic I, Benov L, Salvemini D (2009) Pure MnTBAP selectively scavenges peroxynitrite over superoxide: comparison of pure and commercial MnTBAP samples to MnTE-2-PyP in two models of oxidative stress injury, an SOD-specific Escherichia coli model and carrageenan-induced pleurisy. Free Radic Biol Med 46:192–201

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beckman JS (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9:836–844

    CAS  PubMed  Google Scholar 

  • Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271:C1424–C1437

    CAS  PubMed  Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beckman JS, Ischiropoulos H, Zhu L, van der Woerd M, Smith C, Chen J, Harrison J, Martin JC, Tsai M (1992) Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch Biochem Biophys 298:438–445

    CAS  PubMed  Google Scholar 

  • Beckman JS, Carson M, Smith CD, Koppenol WH (1993) ALS, SOD and peroxynitrite. Nature 364:584

    CAS  PubMed  Google Scholar 

  • Boccini F, Herold S (2004) Mechanistic studies of the oxidation of oxyhemoglobin by peroxynitrite. Biochemistry 43:16393–16404

    CAS  PubMed  Google Scholar 

  • Bohle DS, Hansert B, Paulson SC, Smith BD (1994) Biomimetic synthesis of the putative cytotoxin peroxynitrite ONOO-, and its characterization as a tetramethylammonium salt. J Am Chem Soc 116:7423–7424

    CAS  Google Scholar 

  • Borbely A, Toth A, Edes I, Virag L, Papp JG, Varro A, Paulus WJ, van der Velden J, Stienen GJ, Papp Z (2005) Peroxynitrite-induced alpha-actinin nitration and contractile alterations in isolated human myocardial cells. Cardiovasc Res 67:225–233

    CAS  PubMed  Google Scholar 

  • Botti H, Trostchansky A, Batthyany C, Rubbo H (2005) Reactivity of peroxynitrite and nitric oxide with LDL. IUBMB Life 57:407–412

    CAS  PubMed  Google Scholar 

  • Bryk R, Griffin P, Nathan C (2000) Peroxynitrite reductase activity of bacterial peroxiredoxins. Nature 407:211–215

    CAS  PubMed  Google Scholar 

  • Bullen ML, Miller AA, Andrews KL, Irvine JC, Ritchie RH, Sobey CG, Kemp-Harper BK (2011) Nitroxyl (HNO) as a vasoprotective signaling molecule. Antioxid Redox Signal 14:1675–1686

    CAS  PubMed  Google Scholar 

  • Burney S, Caulfield JL, Niles JC, Wishnok JS, Tannenbaum SR (1999) The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res 424:37–49

    CAS  PubMed  Google Scholar 

  • Burns AR, Bowden RA, Abe Y, Walker DC, Simon SI, Entman ML, Smith CW (1999) P-selectin mediates neutrophil adhesion to endothelial cell borders. J Leukoc Biol 65:299–306

    CAS  PubMed  Google Scholar 

  • Butler AR, Megson IL, Wright PG (1998) Diffusion of nitric oxide and scavenging by blood in the vasculature. Biochim Biophys Acta 1425:168–176

    CAS  PubMed  Google Scholar 

  • Cai S, Khoo J, Mussa S, Alp NJ, Channon KM (2005) Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation. Diabetologia 48:1933–1940

    CAS  PubMed  Google Scholar 

  • Castro L, Rodriguez M, Radi R (1994) Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem 269:29409–29415

    CAS  PubMed  Google Scholar 

  • Cena JJ, Lalu MM, Cho WJ, Chow AK, Bagdan ML, Daniel EE, Castro MM, Schulz R (2010) Inhibition of matrix metalloproteinase activity in vivo protects against vascular hyporeactivity in endotoxemia. Am J Physiol Heart Circ Physiol 298:H45–H51

    CAS  PubMed  Google Scholar 

  • Ceriello A (2002) Nitrotyrosine: new findings as a marker of postprandial oxidative stress. Int J Clin Pract Suppl 129:51–58

    CAS  PubMed  Google Scholar 

  • Ceriello A, Quagliaro L, D’Amico M, Di Filippo C, Marfella R, Nappo F, Berrino L, Rossi F, Giugliano D (2002) Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 51:1076–1082

    CAS  PubMed  Google Scholar 

  • Channon KM (2004) Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease. Trends Cardiovasc Med 14:323–327

    CAS  PubMed  Google Scholar 

  • Chen K, Pittman RN, Popel AS (2008) Nitric oxide in the vasculature: where does it come from and where does it go? A quantitative perspective. Antioxid Redox Signal 10:1185–1198

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen CA, Wang TY, Varadharaj S, Reyes LA, Hemann C, Talukder MA, Chen YR, Druhan LJ, Zweier JL (2010) S-glutathionylation uncouples eNOS and regulates its cellular and vascular function. Nature 468:1115–1118

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen CA, Lin CH, Druhan LJ, Wang TY, Chen YR, Zweier JL (2011) Superoxide induces endothelial nitric-oxide synthase protein thiyl radical formation, a novel mechanism regulating eNOS function and coupling. J Biol Chem 286:29098–29107

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi HR, Choi JS, Han YN, Bae SJ, Chung HY (2002) Peroxynitrite scavenging activity of herb extracts. Phytother Res 16:364–367

    CAS  PubMed  Google Scholar 

  • Churchill EN, Mochly-Rosen D (2007) The roles of PKCdelta and epsilon isoenzymes in the regulation of myocardial ischaemia/reperfusion injury. Biochem Soc Trans 35:1040–1042

    CAS  PubMed  Google Scholar 

  • Cooke CL, Davidge ST (2002) Peroxynitrite increases iNOS through NF-kappaB and decreases prostacyclin synthase in endothelial cells. Am J Physiol Cell Physiol 282:C395–C402

    CAS  PubMed  Google Scholar 

  • Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17:1195–1214

    CAS  PubMed  Google Scholar 

  • Cosentino F, Eto M, De Paolis P, van der Loo B, Bachschmid M, Ullrich V, Kouroedov A, Delli Gatti C, Joch H, Volpe M, Luscher TF, Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A (2003a) Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 52:2795–2804

    Google Scholar 

  • Cosentino F, Eto M, De Paolis P, van der Loo B, Bachschmid M, Ullrich V, Kouroedov A, Delli Gatti C, Joch H, Volpe M, Lüscher TF (2003b) High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: role of protein kinase C and reactive oxygen species. Circulation 107:1017–1023

    CAS  PubMed  Google Scholar 

  • Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS (2008) Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol 294:H1530–H1540

    CAS  PubMed Central  PubMed  Google Scholar 

  • Crow JP (2002) Peroxynitrite: scavenging for survival. www.sfrbm.org/frs/CrowONOO.pdf

  • Crow JP, Beckman JS, McCord JM (1995) Sensitivity of the essential zinc-thiolate moiety of yeast alcohol dehydrogenase to hypochlorite and peroxynitrite. Biochemistry 34:3544–3552

    CAS  PubMed  Google Scholar 

  • Cuzzocrea S, Mazzon E, Costantino G, Serraino I, Dugo L, Calabro G, Cucinotta G, De Sarro A, Caputi AP (2000) Beneficial effects of n-acetylcysteine on ischaemic brain injury. Br J Pharmacol 130:1219–1226

    CAS  PubMed Central  PubMed  Google Scholar 

  • Denicola A, Souza JM, Radi R (1998) Diffusion of peroxynitrite across erythrocyte membranes. Proc Natl Acad Sci USA 95:3566–3571

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ding H, Triggle CR (2010) Endothelial dysfunction in diabetes: multiple targets for treatment. Pflugers Arch 459:977–994

    CAS  PubMed  Google Scholar 

  • Ding H, Aljofan M, Triggle CR (2007) Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells. J Cell Physiol 212:682–689

    CAS  PubMed  Google Scholar 

  • Djaman O, Outten FW, Imlay JA (2004) Repair of oxidized iron-sulfur clusters in Escherichia coli. J Biol Chem 279:44590–44599

    CAS  PubMed  Google Scholar 

  • Donzelli S, Espey MG, Thomas DD, Mancardi D, Tocchetti CG, Ridnour LA, Paolocci N, King SB, Miranda KM, Lazzarino G, Fukuto JM, Wink DA (2006) Discriminating formation of HNO from other reactive nitrogen oxide species. Free Radic Biol Med 40:1056–1066

    CAS  PubMed  Google Scholar 

  • Douki T, Cadet J (1996) Peroxynitrite mediated oxidation of purine bases of nucleosides and isolated DNA. Free Radic Res 24:369–380

    CAS  PubMed  Google Scholar 

  • Douki T, Cadet J, Ames BN (1996) An adduct between peroxynitrite and 2′-deoxyguanosine: 4,5-dihydro-5-hydroxy-4-(nitrosooxy)-2′-deoxyguanosine. Chem Res Toxicol 9:3–7

    CAS  PubMed  Google Scholar 

  • Dowell FJ, Martin W (1997) The effects of peroxynitrite on rat aorta: interaction with glucose and related substances. Eur J Pharmacol 338:43–53

    CAS  PubMed  Google Scholar 

  • Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    CAS  PubMed  Google Scholar 

  • Ellis A, Li CG, Rand MJ (2000) Differential actions of L-cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta. Br J Pharmacol 129:315–322

    CAS  PubMed Central  PubMed  Google Scholar 

  • El-Remessy AB, Behzadian MA, Abou-Mohamed G, Franklin T, Caldwell RW, Caldwell RB (2003) Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor. Am J Pathol 162:1995–2004

    CAS  PubMed Central  PubMed  Google Scholar 

  • El-Remessy AB, Tawfik HE, Matragoon S, Pillai B, Caldwell RB, Caldwell RW (2010) Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation. Exp Diabetes Res 2010:247861

    PubMed Central  PubMed  Google Scholar 

  • Favaloro JL, Kemp-Harper BK (2009) Redox variants of NO (NO{middle dot} and HNO) elicit vasorelaxation of resistance arteries via distinct mechanisms. Am J Physiol Heart Circ Physiol 296:H1274–H1280

    CAS  PubMed  Google Scholar 

  • Fehsel K, Jalowy A, Qi S, Burkart V, Hartmann B, Kolb H (1993) Islet cell DNA is a target of inflammatory attack by nitric oxide. Diabetes 42:496–500

    CAS  PubMed  Google Scholar 

  • Félétou M, Vanhoutte PM (2006) Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 291:H985–H1002

    PubMed  Google Scholar 

  • Ferdinandy P (2006) Peroxynitrite: just an oxidative/nitrosative stressor or a physiological regulator as well? Br J Pharmacol 148:1–3

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ferdinandy P, Schulz R (2001) Peroxynitrite: toxic or protective in the heart? Circ Res 88:E12–E13

    CAS  PubMed  Google Scholar 

  • Fernandes DC, Medinas DB, Alves MJ, Augusto O (2005a) Tempol diverts peroxynitrite/carbon dioxide reactivity toward albumin and cells from protein-tyrosine nitration to protein-cysteine nitrosation. Free Radic Biol Med 38:189–200

    CAS  PubMed  Google Scholar 

  • Fernandes E, Gomes A, Costa D, Lima JL (2005b) Pindolol is a potent scavenger of reactive nitrogen species. Life Sci 77:1983–1992

    CAS  PubMed  Google Scholar 

  • Ferrer-Sueta G, Radi R (2009) Chemical biology of peroxynitrite: kinetics, diffusion, and radicals. ACS Chem Biol 4:161–177

    CAS  PubMed  Google Scholar 

  • Flores-Santana W, Salmon DJ, Donzelli S, Switzer CH, Basudhar D, Ridnour L, Cheng R, Glynn SA, Paolocci N, Fukuto JM, Miranda KM, Wink DA (2011) The specificity of nitroxyl chemistry is unique among nitrogen oxides in biological systems. Antioxid Redox Signal 14:1659–1674

    CAS  PubMed Central  PubMed  Google Scholar 

  • Forstermann U, Munzel T (2006) Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 113:1708–1714

    PubMed  Google Scholar 

  • Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, Nadal-Ginard B, Anversa P (2000) Myocardial cell death in human diabetes. Circ Res 87:1123–1132

    CAS  PubMed  Google Scholar 

  • Fukuto JM, Carrington SJ (2011) HNO signaling mechanisms. Antioxid Redox Signal 14:1649–1657

    CAS  PubMed  Google Scholar 

  • Fukuto JM, Bartberger MD, Dutton AS, Paolocci N, Wink DA, Houk KN (2005) The physiological chemistry and biological activity of nitroxyl (HNO): the neglected, misunderstood, and enigmatic nitrogen oxide. Chem Res Toxicol 18:790–801

    CAS  PubMed  Google Scholar 

  • Furchgott RF, Vanhoutte PM (1989) Endothelium-derived relaxing and contracting factors. FASEB J 3:2007–2018

    CAS  PubMed  Google Scholar 

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    CAS  PubMed  Google Scholar 

  • Gao CQ, Sawicki G, Suarez-Pinzon WL, Csont T, Wozniak M, Ferdinandy P, Schulz R (2003) Matrix metalloproteinase-2 mediates cytokine-induced myocardial contractile dysfunction. Cardiovasc Res 57:426–433

    CAS  PubMed  Google Scholar 

  • Garcia Soriano F, Virag L, Jagtap P, Szabo E, Mabley JG, Liaudet L, Marton A, Hoyt DG, Murthy KG, Salzman AL, Southan GJ, Szabo C (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7:108–113

    CAS  PubMed  Google Scholar 

  • Ghiadoni L, Taddei S, Virdis A (2011) Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol 10(1):42–60

    Google Scholar 

  • Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    CAS  PubMed Central  PubMed  Google Scholar 

  • Go YM, Patel RP, Maland MC, Park H, Beckman JS, Darley-Usmar VM, Jo H (1999) Evidence for peroxynitrite as a signaling molecule in flow-dependent activation of c-Jun NH(2)-terminal kinase. Am J Physiol 277:H1647–H1653

    CAS  PubMed  Google Scholar 

  • Gochman E, Mahajna J, Reznick AZ (2011) NF-kappaB activation by peroxynitrite through IkappaBalpha-dependent phosphorylation versus nitration in colon cancer cells. Anticancer Res 31:1607–1617

    CAS  PubMed  Google Scholar 

  • Goldstein S, Merényi G (2008) The chemistry of peroxynitrite: implications for biological activity. Methods Enzymol 436:49–61

    CAS  PubMed  Google Scholar 

  • Goldstein S, Squadrito GL, Pryor WA, Czapski G (1996) Direct and indirect oxidations by peroxynitrite, neither involving the hydroxyl radical. Free Radic Biol Med 21:965–974

    CAS  PubMed  Google Scholar 

  • Granger DL, Hibbs JB Jr (1996) High-output nitric oxide: weapon against infection? Trends Microbiol 4:46–47

    CAS  PubMed  Google Scholar 

  • Graves JE, Lewis SJ, Kooy NW (2005) Loss of K+ATP-channel-mediated vasodilation after induction of tachyphylaxis to peroxynitrite. J Cardiovasc Pharmacol 46:646–652

    CAS  PubMed  Google Scholar 

  • Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA (2008) Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem 283:21837–21841

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hagar JM, Hale SL, Kloner RA (1991) Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat. Circ Res 68:61–68

    CAS  PubMed  Google Scholar 

  • Hall ED, Detloff MR, Johnson K, Kupina NC (2004) Peroxynitrite-mediated protein nitration and lipid peroxidation in a mouse model of traumatic brain injury. J Neurotrauma 21:9–20

    PubMed  Google Scholar 

  • Hausladen A, Fridovich I (1994) Superoxide and peroxynitrite inactivate aconitases, but nitric oxide does not. J Biol Chem 269:29405–29408

    CAS  PubMed  Google Scholar 

  • Heitzer T, Krohn K, Albers S, Meinertz T (2000) Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with Type II diabetes mellitus. Diabetologia 43:1435–1438

    CAS  PubMed  Google Scholar 

  • Herold S, Fago A (2005) Reactions of peroxynitrite with globin proteins and their possible physiological role. Comp Biochem Physiol A Mol Integr Physiol 142:124–129

    PubMed  Google Scholar 

  • Herold S, Shivashankar K, Mehl M (2002) Myoglobin scavenges peroxynitrite without being significantly nitrated. Biochemistry 41:13460–13472

    CAS  PubMed  Google Scholar 

  • Herold S, Exner M, Boccini F (2003) The mechanism of the peroxynitrite-mediated oxidation of myoglobin in the absence and presence of carbon dioxide. Chem Res Toxicol 16:390–402

    CAS  PubMed  Google Scholar 

  • Hogg N, Kalyanaraman B (1999) Nitric oxide and lipid peroxidation. Biochim Biophys Acta 1411:378–384

    CAS  PubMed  Google Scholar 

  • Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowski H (1998) Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA 95:675–680

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hou R, Zhang J, Yin T, Cao H, Zhang N, Li X, Wang L, Xing Y, Li D, Ji Q (2010) Upregulation of PTEN by peroxynitrite contributes to cytokine-induced apoptosis in pancreatic beta-cells. Apoptosis 15:877–886

    CAS  PubMed  Google Scholar 

  • Ignarro LJ (1990) Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30:535–560

    CAS  PubMed  Google Scholar 

  • Ihlemann N, Rask-Madsen C, Perner A, Dominguez H, Hermann T, Kober L, Torp-Pedersen C (2003) Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects. Am J Physiol Heart Circ Physiol 285:H875–H882

    CAS  PubMed  Google Scholar 

  • Irvine JC, Favaloro JL, Kemp-Harper BK (2003) NO- activates soluble guanylate cyclase and Kv channels to vasodilate resistance arteries. Hypertension 41:1301–1307

    CAS  PubMed  Google Scholar 

  • Ischiropoulos H, Beckman JS (2003) Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest 111:163–169

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ishii N, Patel KP, Lane PH, Taylor T, Bian K, Murad F, Pollock JS, Carmines PK (2001) Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus. J Am Soc Nephrol 12:1630–1639

    CAS  PubMed  Google Scholar 

  • Joshi MS, Ferguson TB Jr, Han TH, Hyduke DR, Liao JC, Rassaf T, Bryan N, Feelisch M, Lancaster JR Jr (2002) Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions. Proc Natl Acad Sci USA 99:10341–10346

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jourd’heuil D, Jourd’heuil FL, Kutchukian PS, Musah RA, Wink DA, Grisham MB (2001) Reaction of superoxide and nitric oxide with peroxynitrite. Implications for peroxynitrite-mediated oxidation reactions in vivo. J Biol Chem 276:28799–28805

    PubMed  Google Scholar 

  • Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P (2001) IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 50:1414–1424

    CAS  PubMed  Google Scholar 

  • Kang KW, Choi SH, Kim SG (2002) Peroxynitrite activates NF-E2-related factor 2/antioxidant response element through the pathway of phosphatidylinositol 3-kinase: the role of nitric oxide synthase in rat glutathione S-transferase A2 induction. Nitric Oxide 7:244–253

    CAS  PubMed  Google Scholar 

  • Kar S, Kavdia M (2011) Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide production. Free Radic Biol Med 51:1411–1427

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H (1999) Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 34:146–154

    CAS  PubMed  Google Scholar 

  • Kemp-Harper BK (2011) Nitroxyl (HNO): a novel redox signaling molecule. Antioxid Redox Signal 14:1609–1613

    CAS  PubMed  Google Scholar 

  • Keyer K, Imlay JA (1997) Inactivation of dehydratase [4Fe-4S] clusters and disruption of iron homeostasis upon cell exposure to peroxynitrite. J Biol Chem 272:27652–27659

    CAS  PubMed  Google Scholar 

  • Kietadisorn R, Juni RP, Moens AL (2011) Tackling endothelial dysfunction by modulating NOS-uncoupling: new insights in pathogenesis and therapeutic possibilities. Am J Physiol Endocrinol Metab 302:E481–E495

    PubMed  Google Scholar 

  • Kim JY, Song EH, Lee HJ, Oh YK, Park YS, Park JW, Kim BJ, Kim DJ, Lee I, Song J, Kim WH (2010) Chronic ethanol consumption-induced pancreatic {beta}-cell dysfunction and apoptosis through glucokinase nitration and its down-regulation. J Biol Chem 285:37251–37262

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kissner R, Nauser T, Bugnon P, Lye PG, Koppenol WH (1997) Formation and properties of peroxynitrite as studied by laser flash photolysis, high-pressure stopped-flow technique, and pulse radiolysis. Chem Res Toxicol 10:1285–1292

    CAS  PubMed  Google Scholar 

  • Klatt P, Lamas S (2000) Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 267:4928–4944

    CAS  PubMed  Google Scholar 

  • Klotz LO, Sies H (2003) Defenses against peroxynitrite: selenocompounds and flavonoids. Toxicol Lett 140–141:125–132

    PubMed  Google Scholar 

  • Knapp LT, Kanterewicz BI, Hayes EL, Klann E (2001) Peroxynitrite-induced tyrosine nitration and inhibition of protein kinase C. Biochem Biophys Res Commun 286:764–770

    CAS  PubMed  Google Scholar 

  • Kobayashi T (2008) Possible involvement of insulin and oxidative stress in vascular dysfunction of diabetic mellitus. Yakugaku Zasshi 128:1013–1021

    CAS  PubMed  Google Scholar 

  • Kohnen SL, Mouithys-Mickalad AA, Deby-Dupont GP, Deby CM, Lamy ML, Noels AF (2001) Oxidation of tetrahydrobiopterin by peroxynitrite or oxoferryl species occurs by a radical pathway. Free Radic Res 35:709–721

    CAS  PubMed  Google Scholar 

  • Konorev EA, Hogg N, Kalyanaraman B (1998) Rapid and irreversible inhibition of creatine kinase by peroxynitrite. FEBS Lett 427:171–174

    CAS  PubMed  Google Scholar 

  • Kooy NW, Royall JA, Ischiropoulos H, Beckman JS (1994) Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radic Biol Med 16:149–156

    CAS  PubMed  Google Scholar 

  • Koppenol WH (2001) 100 years of peroxynitrite chemistry and 11 years of peroxynitrite biochemistry. Redox Rep 6:339–341

    CAS  PubMed  Google Scholar 

  • Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulos H, Beckman JS (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842

    CAS  PubMed  Google Scholar 

  • Kossenjans W, Eis A, Sahay R, Brockman D, Myatt L (2000) Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia. Am J Physiol Heart Circ Physiol 278:H1311–H1319

    CAS  PubMed  Google Scholar 

  • Kuhn DM, Aretha CW, Geddes TJ (1999) Peroxynitrite inactivation of tyrosine hydroxylase: mediation by sulfhydryl oxidation, not tyrosine nitration. J Neurosci 19:10289–10294

    CAS  PubMed  Google Scholar 

  • Kvietys PR, Granger DN (2011) Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 52(3):556–592

    PubMed Central  PubMed  Google Scholar 

  • Lakey JR, Suarez-Pinzon WL, Strynadka K, Korbutt GS, Rajotte RV, Mabley JG, Szabo C, Rabinovitch A (2001) Peroxynitrite is a mediator of cytokine-induced destruction of human pancreatic islet beta cells. Lab Invest 81:1683–1692

    CAS  PubMed  Google Scholar 

  • Landino LM, Crews BC, Timmons MD, Morrow JD, Marnett LJ (1996) Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc Natl Acad Sci USA 93:15069–15074

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee WH, Gounarides JS, Roos ES, Wolin MS (2003) Influence of peroxynitrite on energy metabolism and cardiac function in a rat ischemia-reperfusion model. Am J Physiol Heart Circ Physiol 285:H1385–H1395

    CAS  PubMed  Google Scholar 

  • Lefer DJ, Scalia R, Campbell B, Nossuli T, Hayward R, Salamon M, Grayson J, Lefer AM (1997) Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. J Clin Invest 99:684–691

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leffler JE, Grunwald E (1963) Rates and equilibria of organic reactions. Wiley, New York

    Google Scholar 

  • Leiper J, Nandi M (2011) The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nat Rev Drug Discov 10:277–291

    CAS  PubMed  Google Scholar 

  • Li H, Gutterman DD, Rusch NJ, Bubolz A, Liu Y (2004a) Nitration and functional loss of voltage-gated K+ channels in rat coronary microvessels exposed to high glucose. Diabetes 53:2436–2442

    CAS  PubMed  Google Scholar 

  • Li J, Li W, Altura BT, Altura BM (2004b) Peroxynitrite-induced relaxation in isolated canine cerebral arteries and mechanisms of action. Toxicol Appl Pharmacol 196:176–182

    CAS  PubMed  Google Scholar 

  • Li MH, Cha YN, Surh YJ (2006) Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells. Free Radic Biol Med 41:1079–1091

    CAS  PubMed  Google Scholar 

  • Liang JH, Li YN, Qi JS, Jia XX (2010) Peroxynitrite-induced protein nitration is responsible for renal mitochondrial damage in diabetic rat. J Endocrinol Invest 33:140–146

    CAS  PubMed  Google Scholar 

  • Liaudet L, Vassalli G, Pacher P (2009) Role of peroxynitrite in the redox regulation of cell signal transduction pathways. Front Biosci 14:4809–4814

    Google Scholar 

  • Liochev SI, Fridovich I (2003) The mode of decomposition of Angeli’s salt (Na2N2O3) and the effects thereon of oxygen, nitrite, superoxide dismutase, and glutathione. Free Radic Biol Med 34:1399–1404

    CAS  PubMed  Google Scholar 

  • Liu S, Beckman JS, Ku DD (1994) Peroxynitrite, a product of superoxide and nitric oxide, produces coronary vasorelaxation in dogs. J Pharmacol Exp Ther 268:1114–1121

    CAS  PubMed  Google Scholar 

  • Liu P, Xu B, Quilley J, Wong PY (2000) Peroxynitrite attenuates hepatic ischemia-reperfusion injury. Am J Physiol Cell Physiol 279:C1970–C1977

    CAS  PubMed  Google Scholar 

  • Lokuta AJ, Maertz NA, Meethal SV, Potter KT, Kamp TJ, Valdivia HH, Haworth RA (2005) Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure. Circulation 111:988–995

    CAS  PubMed  Google Scholar 

  • Lopez CJ, Qayyum I, Mishra OP, Delivoria-Papadopoulos M (2005) Effect of nitration on protein tyrosine phosphatase and protein phosphatase activity in neuronal cell membranes of newborn piglets. Neurosci Lett 386:78–81

    CAS  PubMed  Google Scholar 

  • Lorch S, Lightfoot R, Ohshima H, Virag L, Chen Q, Hertkorn C, Weiss M, Souza J, Ischiropoulos H, Yermilov V, Pignatelli B, Masuda M, Szabo C (2002) Detection of peroxynitrite-induced protein and DNA modifications. Methods Mol Biol 196:247–275

    CAS  PubMed  Google Scholar 

  • Luiking YC, Engelen MP, Deutz NE (2010) Regulation of nitric oxide production in health and disease. Curr Opin Clin Nutr Metab Care 13:97–104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mabley JG, Pacher P, Bai P, Wallace R, Goonesekera S, Virag L, Southan GJ, Szabo C (2004) Suppression of intestinal polyposis in Apcmin/+ mice by targeting the nitric oxide or poly(ADP-ribose) pathways. Mutat Res 548:107–116

    CAS  PubMed  Google Scholar 

  • Macfadyen AJ, Reiter C, Zhuang Y, Beckman JS (1999) A novel superoxide dismutase-based trap for peroxynitrite used to detect entry of peroxynitrite into erythrocyte ghosts. Chem Res Toxicol 12:223–229

    CAS  PubMed  Google Scholar 

  • Marshall KA, Reist M, Jenner P, Halliwell B (1999) The neuronal toxicity of sulfite plus peroxynitrite is enhanced by glutathione depletion: implications for Parkinson’s disease. Free Radic Biol Med 27:515–520

    CAS  PubMed  Google Scholar 

  • Matata BM, Galinanes M (2002) Peroxynitrite is an essential component of cytokines production mechanism in human monocytes through modulation of nuclear factor-kappa B DNA binding activity. J Biol Chem 277:2330–2335

    CAS  PubMed  Google Scholar 

  • Maulik N, Das DK (2008) Emerging potential of thioredoxin and thioredoxin interacting proteins in various disease conditions. Biochim Biophys Acta 1780:1368–1382

    CAS  PubMed  Google Scholar 

  • Migita K, Maeda Y, Abiru S, Komori A, Yokoyama T, Takii Y, Nakamura M, Yatsuhashi H, Eguchi K, Ishibashi H (2005) Peroxynitrite-mediated matrix metalloproteinase-2 activation in human hepatic stellate cells. FEBS Lett 579:3119–3125

    CAS  PubMed  Google Scholar 

  • Mihm MJ, Bauer JA (2002) Peroxynitrite-induced inhibition and nitration of cardiac myofibrillar creatine kinase. Biochimie 84:1013–1019

    CAS  PubMed  Google Scholar 

  • Mihm MJ, Coyle CM, Schanbacher BL, Weinstein DM, Bauer JA (2001) Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure. Cardiovasc Res 49:798–807

    CAS  PubMed  Google Scholar 

  • Milstien S, Katusic Z (1999) Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. Biochem Biophys Res Commun 263:681–684

    CAS  PubMed  Google Scholar 

  • Miranda KM, Nims RW, Thomas DD, Espey MG, Citrin D, Bartberger MD, Paolocci N, Fukuto JM, Feelisch M, Wink DA (2003a) Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins. A chemical discussion of the differential biological effects of these redox related products of NOS. J Inorg Biochem 93:52–60

    CAS  PubMed  Google Scholar 

  • Miranda KM, Paolocci N, Katori T, Thomas DD, Ford E, Bartberger MD, Espey MG, Kass DA, Feelisch M, Fukuto JM, Wink DA (2003b) A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system. Proc Natl Acad Sci USA 100:9196–9201

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mohr S, Stamler JS, Brune B (1994) Mechanism of covalent modification of glyceraldehyde-3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite and related nitrosating agents. FEBS Lett 348:223–227

    CAS  PubMed  Google Scholar 

  • Moro MA, Darley-Usmar VM, Goodwin DA, Read NG, Zamora-Pino R, Feelisch M, Radomski MW, Moncada S (1994) Paradoxical fate and biological action of peroxynitrite on human platelets. Proc Natl Acad Sci USA 91:6702–6706

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moro MA, Darley-Usmar VM, Lizasoain I, Su Y, Knowles RG, Radomski MW, Moncada S (1995) The formation of nitric oxide donors from peroxynitrite. Br J Pharmacol 116:1999–2004

    CAS  PubMed Central  PubMed  Google Scholar 

  • Naseem KM (2005) The role of nitric oxide in cardiovascular diseases. Mol Aspects Med 26:33–65

    CAS  PubMed  Google Scholar 

  • Niles JC, Wishnok JS, Tannenbaum SR (2006) Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. Nitric Oxide 14:109–121

    CAS  PubMed  Google Scholar 

  • Norris AJ, Sartippour MR, Lu M, Park T, Rao JY, Jackson MI, Fukuto JM, Brooks MN (2008) Nitroxyl inhibits breast tumor growth and angiogenesis. Int J Cancer 122:1905–1910

    CAS  PubMed  Google Scholar 

  • Nossaman BD, Kadowitz PJ (2008) Potential benefits of peroxynitrite. Open Pharmacol J 2:31–53

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nossuli TO, Hayward R, Scalia R, Lefer AM (1997) Peroxynitrite reduces myocardial infarct size and preserves coronary endothelium after ischemia and reperfusion in cats. Circulation 96:2317–2324

    CAS  PubMed  Google Scholar 

  • Nossuli TO, Hayward R, Jensen D, Scalia R, Lefer AM (1998) Mechanisms of cardioprotection by peroxynitrite in myocardial ischemia and reperfusion injury. Am J Physiol 275:H509–H519

    CAS  PubMed  Google Scholar 

  • Nowak P, Wachowicz B (2001) Studies on pig blood platelet responses to peroxynitrite action. Platelets 12:376–381

    CAS  PubMed  Google Scholar 

  • Ohshima H, Virag L, Souza J, Yermilov V, Pignatelli B, Masuda M, Szabo C (2002) Detection of certain peroxynitrite-induced DNA modifications. Methods Mol Biol 186:77–88

    CAS  PubMed  Google Scholar 

  • Okamoto T, Akaike T, Sawa T, Miyamoto Y, van der Vliet A, Maeda H (2001) Activation of matrix metalloproteinases by peroxynitrite-induced protein S-glutathiolation via disulfide S-oxide formation. J Biol Chem 276:29596–29602

    CAS  PubMed  Google Scholar 

  • Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS (2002) Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: effects of ACEI and ARB. Kidney Int 61:186–194

    CAS  PubMed  Google Scholar 

  • Pacher P, Szabo C (2005) Role of poly (ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal 7:1568–1580

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pacher P, Liaudet L, Soriano FG, Mabley JG, Szabo E, Szabo C (2002) The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. Diabetes 51:514–521

    CAS  PubMed  Google Scholar 

  • Pacher P, Schulz R, Liaudet L, Szabo C (2005) Nitrosative stress and pharmacological modulation of heart failure. Trends Pharmacol Sci 26:302–310

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424

    CAS  PubMed Central  PubMed  Google Scholar 

  • Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    CAS  PubMed  Google Scholar 

  • Panasenko OM, Sharov VS, Briviba K, Sies H (2000) Interaction of peroxynitrite with carotenoids in human low density lipoproteins. Arch Biochem Biophys 373:302–305

    CAS  PubMed  Google Scholar 

  • Pannirselvam M, Verma S, Anderson TJ, Triggle CR (2002) Cellular basis of endothelial dysfunction in small mesenteric arteries from spontaneously diabetic (db/db −/−) mice: role of decreased tetrahydrobiopterin bioavailability. Br J Pharmacol 136:255–263

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pannirselvam M, Simon V, Verma S, Anderson T, Triggle CR (2003) Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice. Br J Pharmacol 140:701–706

    CAS  PubMed Central  PubMed  Google Scholar 

  • Paolocci N, Wink DA (2009) The shy Angeli and his elusive creature: the HNO route to vasodilation. Am J Physiol Heart Circ Physiol 296:H1217–H1220

    CAS  PubMed Central  PubMed  Google Scholar 

  • Paolocci N, Saavedra WF, Miranda KM, Martignani C, Isoda T, Hare JM, Espey MG, Fukuto JM, Feelisch M, Wink DA, Kass DA (2001) Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling. Proc Natl Acad Sci USA 98:10463–10468

    CAS  PubMed Central  PubMed  Google Scholar 

  • Patel RP, McAndrew J, Sellak H, White CR, Jo H, Freeman BA, Darley-Usmar VM (1999) Biological aspects of reactive nitrogen species. Biochim Biophys Acta 1411:385–400

    CAS  PubMed  Google Scholar 

  • Ping P, Takano H, Zhang J, Tang XL, Qiu Y, Li RC, Banerjee S, Dawn B, Balafonova Z, Bolli R (1999) Isoform-selective activation of protein kinase C by nitric oxide in the heart of conscious rabbits: a signaling mechanism for both nitric oxide-induced and ischemia-induced preconditioning. Circ Res 84:587–604

    CAS  PubMed  Google Scholar 

  • Pober JS, Min W, Bradley JR (2009) Mechanisms of endothelial dysfunction, injury, and death. Annu Rev Pathol 4:71–95

    CAS  PubMed  Google Scholar 

  • Pryor WA (1966) Free radicals. McGraw-Hill, New York

    Google Scholar 

  • Pryor WA, Squadrito GL (1995) The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 268:L699–L722

    CAS  PubMed  Google Scholar 

  • Pryor WA, Jin X, Squadrito GL (1994) One- and two-electron oxidations of methionine by peroxynitrite. Proc Natl Acad Sci USA 91:11173–11177

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rabini RA, Vignini A, Salvolini E, Staffolani R, Martarelli D, Moretti N, Mazzanti L (2002) Activation of human aortic endothelial cells by LDL from Type 1 diabetic patients: an in vitro study. Atherosclerosis 165:69–77

    CAS  PubMed  Google Scholar 

  • Radi R, Beckman JS, Bush KM, Freeman BA (1991a) Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481–487

    CAS  PubMed  Google Scholar 

  • Radi R, Beckman JS, Bush KM, Freeman BA (1991b) Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem 266:4244–4250

    CAS  PubMed  Google Scholar 

  • Radi R, Cassina A, Hodara R (2002a) Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem 383:401–409

    CAS  PubMed  Google Scholar 

  • Radi R, Cassina A, Hodara R, Quijano C, Castro L (2002b) Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33:1451–1464

    CAS  PubMed  Google Scholar 

  • Reynolds MR, Berry RW, Binder LI (2005) Site-specific nitration and oxidative dityrosine bridging of the tau protein by peroxynitrite: implications for Alzheimer’s disease. Biochemistry 44:1690–1700

    CAS  PubMed  Google Scholar 

  • Romero N, Radi R (2005) Hemoglobin and red blood cells as tools for studying peroxynitrite biochemistry. Methods Enzymol 396:229–245

    CAS  PubMed  Google Scholar 

  • Ronson RS, Nakamura M, Vinten-Johansen J (1999) The cardiovascular effects and implications of peroxynitrite. Cardiovasc Res 44:47–59

    CAS  PubMed  Google Scholar 

  • Rork TH, Hadzimichalis NM, Kappil MA, Merrill GF (2006) Acetaminophen attenuates peroxynitrite-activated matrix metalloproteinase-2-mediated troponin I cleavage in the isolated guinea pig myocardium. J Mol Cell Cardiol 40:553–561

    CAS  PubMed  Google Scholar 

  • Rubbo H (1998) Nitric oxide and peroxynitrite in lipid peroxidation. Medicina (B Aires) 58:361–366

    CAS  Google Scholar 

  • Rubbo H, Freeman BA (1996) Nitric oxide regulation of lipid oxidation reactions: formation and analysis of nitrogen-containing oxidized lipid derivatives. Methods Enzymol 269:385–394

    CAS  PubMed  Google Scholar 

  • Rubbo H, O’Donnell V (2005) Nitric oxide, peroxynitrite and lipoxygenase in atherogenesis: mechanistic insights. Toxicology 208:305–317

    CAS  PubMed  Google Scholar 

  • Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA (1994) Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 269:26066–26075

    CAS  PubMed  Google Scholar 

  • Rusche KM, Spiering MM, Marletta MA (1998) Reactions catalyzed by tetrahydrobiopterin-free nitric oxide synthase. Biochemistry 37:15503–15512

    CAS  PubMed  Google Scholar 

  • Salvemini D, Wang ZQ, Stern MK, Currie MG, Misko TP (1998) Proc Natl Acad Sci USA 95:2659–2663

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sasaki N, Yamashita T, Takaya T, Shinohara M, Shiraki R, Takeda M, Emoto N, Fukatsu A, Hayashi T, Ikemoto K, Nomura T, Yokoyama M, Hirata K, Kawashima S (2008) Augmentation of vascular remodeling by uncoupled endothelial nitric oxide synthase in a mouse model of diabetes mellitus. Arterioscler Thromb Vasc Biol 28:1068–1076

    CAS  PubMed  Google Scholar 

  • Schroeder P, Klotz LO, Sies H (2003) Amphiphilic properties of (−)-epicatechin and their significance for protection of cells against peroxynitrite. Biochem Biophys Res Commun 307:69–73

    CAS  PubMed  Google Scholar 

  • Scott-Burden T (1995) Regulation of nitric oxide production by tetrahydrobiopterin. Circulation 91:248–250

    CAS  PubMed  Google Scholar 

  • Selley ML (2005) Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice. Brain Res 1037(1–2):1–6

    CAS  PubMed  Google Scholar 

  • Sharma A, Bernatchez PN, de Haan JB (2012) Targeting endothelial dysfunction in vascular complications associated with diabetes. Int J Vasc Med 2012:750126

    PubMed Central  PubMed  Google Scholar 

  • Sies H (1963) Strategies of antioxidant defense. Eur J Biochem 215:213–219

    Google Scholar 

  • Sies H, Masumoto H (1997) Ebselen as a glutathione peroxidase mimic and as a scavenger of peroxynitrite. Adv Pharmacol 38:229–246

    CAS  PubMed  Google Scholar 

  • Sies H, Sharov VS, Klotz LO, Briviba K (1997) Glutathione peroxidase protects against peroxynitrite-mediated oxidations. A new function for selenoproteins as peroxynitrite reductase. J Biol Chem 272:27812–27817

    CAS  PubMed  Google Scholar 

  • Singh IN, Sullivan PG, Hall ED (2007) Peroxynitrite-mediated oxidative damage to brain mitochondria: protective effects of peroxynitrite scavengers. J Neurosci Res 85:2216–2223

    CAS  PubMed  Google Scholar 

  • Skinner KA, White CR, Patel R, Tan S, Barnes S, Kirk M, Darley-Usmar V, Parks DA (1998) Nitrosation of uric acid by peroxynitrite. Formation of a vasoactive nitric oxide donor. J Biol Chem 273:24491–24497

    CAS  PubMed  Google Scholar 

  • Solodkin A, Traub RJ, Gebhart GF (1992) Neuroscience 51:495–499

    CAS  PubMed  Google Scholar 

  • Song P, Wu Y, Xu J, Xie Z, Dong Y, Zhang M, Zou MH (2007) Reactive nitrogen species induced by hyperglycemia suppresses Akt signaling and triggers apoptosis by upregulating phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome 10) in an LKB1-dependent manner. Circulation 116:1585–1595

    CAS  PubMed  Google Scholar 

  • Soriano FG, Virag L, Szabo C (2001) Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly- (ADP-ribose) polymerase activation. J Mol Med 79:437–448

    CAS  PubMed  Google Scholar 

  • Souza JM, Giasson BI, Chen Q, Lee VM, Ischiropoulos H (2000) Dityrosine cross-linking promotes formation of stable alpha -synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J Biol Chem 275:18344–18349

    CAS  PubMed  Google Scholar 

  • Squadrito GL, Cueto R, Splenser AE, Valavanidis A, Zhang H, Uppu RM, Pryor WA (2000) Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid. Arch Biochem Biophys 376:333–337

    CAS  PubMed  Google Scholar 

  • Stadler K (2011) Peroxynitrite-driven mechanisms in diabetes and insulin resistance – the latest advances. Curr Med Chem 18:280–290

    CAS  PubMed  Google Scholar 

  • Stadtman ER, Levine RL (2003) Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids 25:207–218

    CAS  PubMed  Google Scholar 

  • Stadtman ER, Moskovitz J, Levine RL (2003) Oxidation of methionine residues of proteins: biological consequences. Antioxid Redox Signal 5:577–582

    CAS  PubMed  Google Scholar 

  • Stuehr DJ, Nathan CF (1989) Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169:1543–1555

    CAS  PubMed  Google Scholar 

  • Su J, Groves JT (2010) Mechanisms of peroxynitrite interactions with heme proteins. Inorg Chem 49:6317–6329

    CAS  PubMed Central  PubMed  Google Scholar 

  • Szabo C (1996) DNA strand breakage and activation of poly-ADP ribosyltransferase: a cytotoxic pathway triggered by peroxynitrite. Free Radic Biol Med 21:855–869

    CAS  PubMed  Google Scholar 

  • Szabo C (2003) Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett 140–141:105–112

    PubMed  Google Scholar 

  • Szabo C, Ohshima H (1997) DNA damage induced by peroxynitrite: subsequent biological effects. Nitric Oxide 1:373–385

    CAS  PubMed  Google Scholar 

  • Szabo C, Zingarelli B, O’Connor M, Salzman AL (1996) DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci USA 93:1753–1758

    CAS  PubMed Central  PubMed  Google Scholar 

  • Szabo C, Zanchi A, Komjati K, Pacher P, Krolewski AS, Quist WC, LoGerfo FW, Horton ES, Veves A (2002) Poly(ADP-ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity. Circulation 106:2680–2686

    CAS  PubMed  Google Scholar 

  • Szabo C, Ischiropoulos H, Radi R (2007) Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat Rev Drug Discov 6:662–680

    CAS  PubMed  Google Scholar 

  • Takakura K, Beckman JS, MacMillan-Crow LA, Crow JP (1999) Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite. Arch Biochem Biophys 369:197–207

    CAS  PubMed  Google Scholar 

  • Tannous M, Rabini RA, Vignini A, Moretti N, Fumelli P, Zielinski B, Mazzanti L, Mutus B (1999) Evidence for iNOS-dependent peroxynitrite production in diabetic platelets. Diabetologia 42:539–544

    CAS  PubMed  Google Scholar 

  • Tao RR, Ji YL, Lu YM, Fukunaga K, Han F (2012) Targeting nitrosative stress for neurovascular protection: new implications in brain diseases. Curr Drug Targets 13:272–284

    CAS  PubMed  Google Scholar 

  • Thomas CE, Morehouse LA, Aust SD (1985) Ferritin and superoxide-dependent lipid peroxidation. J Biol Chem 260:3275–3280

    CAS  PubMed  Google Scholar 

  • Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S, Hussain P, Vecoli C, Paolocci N, Ambs S, Colton CA, Harris CC, Roberts DD, Wink DA (2008) The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med 45:18–31

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thomson L, Trujillo M, Telleri R, Radi R (1995) Kinetics of cytochrome c2+ oxidation by peroxynitrite: implications for superoxide measurements in nitric oxide-producing biological systems. Arch Biochem Biophys 319:491–497

    CAS  PubMed  Google Scholar 

  • Thuraisingham RC, Nott CA, Dodd SM, Yaqoob MM (2000) Increased nitrotyrosine staining in kidneys from patients with diabetic nephropathy. Kidney Int 57:1968–1972

    CAS  PubMed  Google Scholar 

  • Tocchetti CG, Stanley BA, Murray CI, Sivakumaran V, Donzelli S, Mancardi D, Pagliaro P, Gao WD, van Eyk J, Kass DA, Wink DA, Paolocci N (2011) Playing with cardiac “redox switches”: the “HNO way” to modulate cardiac function. Antioxid Redox Signal 14:1687–1698

    CAS  PubMed Central  PubMed  Google Scholar 

  • Torreilles F, Salman-Tabcheh S, Guerin M, Torreilles J (1999) Neurodegenerative disorders: the role of peroxynitrite. Brain Res Brain Res Rev 30:153–163

    CAS  PubMed  Google Scholar 

  • Triggle CR, Ding H (2010) A review of endothelial dysfunction in diabetes: a focus on the contribution of a dysfunctional eNOS. J Am Soc Hypertens 4:102–115

    CAS  PubMed  Google Scholar 

  • Triggle CR, Samuel SM, Ravishankar S, Marei I, Arunachalam G, Ding H (2012) The endothelium: influencing vascular smooth muscle in many ways. Can J Physiol Pharmacol 90:713–738

    CAS  PubMed  Google Scholar 

  • Tsai J-HM, Hamilton TP, Harrison JG, Jablowski M, van der Woerd M, Martin JC, Beckman JS (1994) Role of peroxynitrite conformation with its stability and toxicity. J Am Chem Soc 116:4115–4116

    CAS  Google Scholar 

  • Turko IV, Li L, Aulak KS, Stuehr DJ, Chang JY, Murad F (2003) Protein tyrosine nitration in the mitochondria from diabetic mouse heart. Implications to dysfunctional mitochondria in diabetes. J Biol Chem 278:33972–33977

    CAS  PubMed  Google Scholar 

  • Uppu RM, Nossaman BD, Greco AJ, Fokin A, Murthy SN, Fonseca VA, Kadowitz PJ (2007) Cardiovascular effects of peroxynitrite. Clin Exp Pharmacol Physiol 34:933–937

    CAS  PubMed  Google Scholar 

  • Vallance P, Leiper J (2004) Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 24:1023–1030

    CAS  PubMed  Google Scholar 

  • van der Vliet A, Eiserich JP, O’Neill CA, Halliwell B, Cross CE (1995) Tyrosine modification by reactive nitrogen species: a closer look. Arch Biochem Biophys 319:341–349

    PubMed  Google Scholar 

  • van der Vliet A, Hoen PA, Wong PS, Bast A, Cross CE (1998) Formation of S-nitrosothiols via direct nucleophilic nitrosation of thiols by peroxynitrite with elimination of hydrogen peroxide. J Biol Chem 273:30255–30262

    PubMed  Google Scholar 

  • Vasquez-Vivar J, Martasek P, Whitsett J, Joseph J, Kalyanaraman B (2002) The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study. Biochem J 362:733–739

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vegh A, Szekeres L, Parratt J (1992) Preconditioning of the ischaemic myocardium; involvement of the L-arginine nitric oxide pathway. Br J Pharmacol 107:648–652

    CAS  PubMed Central  PubMed  Google Scholar 

  • Verge VMK, Xu Z, Xu XJ, Wiesenfeld-Hallin Z, Hökfelt T (1992) Proc Natl Acad Sci USA 89:11617–11621

    CAS  PubMed Central  PubMed  Google Scholar 

  • Verma S, Lovren F, Dumont AS, Mather KJ, Maitland A, Kieser TM, Triggle CR, Anderson TJ (2000) Tetrahydrobiopterin improves endothelial function in human saphenous veins. J Thorac Cardiovasc Surg 120:668–671

    CAS  PubMed  Google Scholar 

  • Viappiani S, Nicolescu AC, Holt A, Sawicki G, Crawford BD, Leon H, van Mulligen T, Schulz R (2009) Activation and modulation of 72 kDa matrix metalloproteinase-2 by peroxynitrite and glutathione. Biochem Pharmacol 77:826–834

    CAS  PubMed  Google Scholar 

  • Villa LM, Salas E, Darley-Usmar VM, Radomski MW, Moncada S (1994) Peroxynitrite induces both vasodilatation and impaired vascular relaxation in the isolated perfused rat heart. Proc Natl Acad Sci USA 91:12383–12387

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vinten-Johansen J (2000) Physiological effects of peroxynitrite: potential products of the environment. Circ Res 87:170–172

    CAS  PubMed  Google Scholar 

  • Virag L, Szabo C (2002) The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54:375–429

    CAS  PubMed  Google Scholar 

  • Wang J, Alexanian A, Ying R, Kizhakekuttu TJ, Dharmashankar K, Vasquez-Vivar J, Gutterman DD, Widlansky ME (2011) Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for AMP kinase. Arterioscler Thromb Vasc Biol 32(3):712–720

    PubMed Central  PubMed  Google Scholar 

  • Wanstall JC, Jeffery TK, Gambino A, Lovren F, Triggle CR (2001) Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide and nitroxyl ion. Br J Pharmacol 134:463–472

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wei EP, Kontos HA, Beckman JS (1996) Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite. Am J Physiol 271:H1262–H1266

    CAS  PubMed  Google Scholar 

  • Whiteman M, Kaur H, Halliwell B (1996) Protection against peroxynitrite dependent tyrosine nitration and alpha 1-antiproteinase inactivation by some anti-inflammatory drugs and by the antibiotic tetracycline. Ann Rheum Dis 55:383–387

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wiseman H, Halliwell B (1996) Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 313(Pt 1):17–29

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wolin MS (2000) Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 20:1430–1442

    CAS  PubMed  Google Scholar 

  • Wu M, Pritchard KA Jr, Kaminski PM, Fayngersh RP, Hintze TH, Wolin MS (1994) Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite. Am J Physiol 266:H2108–H2113

    CAS  PubMed  Google Scholar 

  • Xu S, Ying J, Jiang B, Guo W, Adachi T, Sharov V, Lazar H, Menzoian J, Knyushko TV, Bigelow D, Schoneich C, Cohen RA (2006) Detection of sequence-specific tyrosine nitration of manganese SOD and SERCA in cardiovascular disease and aging. Am J Physiol Heart Circ Physiol 290:H2220–H2227

    CAS  PubMed  Google Scholar 

  • Yamakura F, Ikeda K (2006) Modification of tryptophan and tryptophan residues in proteins by reactive nitrogen species. Nitric Oxide 14:152–161

    CAS  PubMed  Google Scholar 

  • Yamakura F, Matsumoto T, Ikeda K, Taka H, Fujimura T, Murayama K, Watanabe E, Tamaki M, Imai T, Takamori K (2005) Nitrated and oxidized products of a single tryptophan residue in human Cu, Zn-superoxide dismutase treated with either peroxynitrite-carbon dioxide or myeloperoxidase-hydrogen peroxide-nitrite. J Biochem 138:57–69

    CAS  PubMed  Google Scholar 

  • Yasmin W, Strynadka KD, Schulz R (1997) Generation of peroxynitrite contributes to ischemia-reperfusion injury in isolated rat hearts. Cardiovasc Res 33:422–432

    CAS  PubMed  Google Scholar 

  • Ye Y, Quijano C, Robinson KM, Ricart KC, Strayer AL, Sahawneh MA, Shacka JJ, Kirk M, Barnes S, Accavitti-Loper MA, Radi R, Beckman JS, Estevez AG (2007) Prevention of peroxynitrite-induced apoptosis of motor neurons and PC12 cells by tyrosine-containing peptides. J Biol Chem 282:6324–6337

    CAS  PubMed  Google Scholar 

  • Yin K, Lai PS, Rodriguez A, Spur BW, Wong PY (1995) Antithrombotic effects of peroxynitrite: inhibition and reversal of aggregation in human platelets. Prostaglandins 50:169–178

    CAS  PubMed  Google Scholar 

  • Yuill KH, Yarova P, Kemp-Harper BK, Garland CJ, Dora KA (2011) A novel role for HNO in local and spreading vasodilatation in rat mesenteric resistance arteries. Antioxid Redox Signal 14:1625–1635

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zingarelli B, O’Connor M, Wong H, Salzman AL, Szabo C (1996) Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol 156:350–358

    CAS  PubMed  Google Scholar 

  • Zou MH, Shi C, Cohen RA (2002) High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Diabetes 51:198–203

    CAS  PubMed  Google Scholar 

  • Zou MH, Cohen R, Ullrich V (2004) Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium 11:89–97

    CAS  PubMed  Google Scholar 

  • Zouki C, Zhang SL, Chan JS, Filep JG (2001) Peroxynitrite induces integrin-dependent adhesion of human neutrophils to endothelial cells via activation of the Raf-1/MEK/Erk pathway. FASEB J 15:25–27

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the generous support of the Qatar Foundation in part via a project grant through the National Priorities Research Program (NPRP: 08-165-3-054; 4-910-3-244) as well as a BMRP establishment grant.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Weill Cornell Medical College in Qatar, Education City – Qatar Foundation, # 24144, Doha, Qatar

    Gnanapragasam Arunachalam, Samson Mathews Samuel, Hong Ding & Chris R. Triggle

  2. Department of Medical Education, Weill Cornell Medical College in Qatar, Education City – Qatar Foundation, # 24144, Doha, Qatar

    Hong Ding & Chris R. Triggle

Authors
  1. Gnanapragasam Arunachalam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samson Mathews Samuel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chris R. Triggle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chris R. Triggle .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Arunachalam, G., Samuel, S.M., Ding, H., Triggle, C.R. (2014). Peroxynitrite Biology. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_5

Download citation

Publish with us

Policies and ethics

Search

Navigation