Formation of Reactive Nitrogen Species during Peroxidase-catalyzed Oxidation of Nitrite

Vliet, Albert van der; Eiserich, Jason P.; Halliwell, Barry; Cross, Carroll E.

doi:10.1074/jbc.272.12.7617

Cited by 745 publications

(452 citation statements)

References 75 publications

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“…The reaction product, peroxynitrite anion (ONOO Ϫ ), is a potent oxidant that, when protonated (pK a 7.49; ONOOH), has ⅐OH radical-like reactivity (7). ONOO Ϫ nitrates protein tyrosine residues to form 3-nitrotyrosine (3-NT) in reoxygenated tissues, but alternate pathways of tyrosine nitration utilizing myeloperoxidase and H 2 O 2 exist and probably predominate (122). Thus finding 3-NT in reoxygenated cells does not unequivocally identify ONOO Ϫ as the nitrating species, because nitrite (NO 2 Ϫ ) can react with peroxidase and H 2 O 2 to form nitrogen dioxide (NO 2 ⅐), which also contributes strongly to tyrosine nitration.…”

Section: ⅐No Itself Can Cause Cellular Injurymentioning

confidence: 99%

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Jackson

2002

American Journal of Physiology-Cell Physiology

929

663

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Li, Chuanyu, and Robert M. Jackson. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 282: C227-C241, 2002; 10.1152/ajpcell.00112.2001.-Exacerbation of hypoxic injury after restoration of oxygenation (reoxygenation) is an important mechanism of cellular injury in transplantation and in myocardial, hepatic, intestinal, cerebral, renal, and other ischemic syndromes. Cellular hypoxia and reoxygenation are two essential elements of ischemia-reperfusion injury. Activated neutrophils contribute to vascular reperfusion injury, yet posthypoxic cellular injury occurs in the absence of inflammatory cells through mechanisms involving reactive oxygen (ROS) or nitrogen species (RNS). Xanthine oxidase (XO) produces ROS in some reoxygenated cells, but other intracellular sources of ROS are abundant, and XO is not required for reoxygenation injury. Hypoxic or reoxygenated mitochondria may produce excess superoxide (O 2 Ϫ ) and release H2O2, a diffusible long-lived oxidant that can activate signaling pathways or react vicinally with proteins and lipid membranes. This review focuses on the specific roles of ROS and RNS in the cellular response to hypoxia and subsequent cytolytic injury during reoxygenation.anoxia; ischemia; reperfusion BACKGROUND

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Section: ⅐No Itself Can Cause Cellular Injurymentioning

confidence: 99%

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Jackson

2002

American Journal of Physiology-Cell Physiology

929

663

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“…In the second pathway, myeloperoxidase uses a one-electron reaction to directly oxidize NO 2 Ϫ to nitrogen dioxide radical, NO 2 ⅐ . The radical might then oxidize tyrosine directly or might react with tyrosyl radical that myeloperoxidase also generates (38,53).…”

Section: Myeloperoxidase Generates 3-nitrotyrosine In Hdl Protein Undmentioning

confidence: 99%

“…Overproduction of superoxide by phagocyte and nonphagocyte NADPH oxidases (such as the NOX family of enzymes) and dysregulation of NO synthase might contribute to this pathway (55,56). Moreover, myeloperoxidase, which is enriched in human atherosclerotic lesions (16,17), uses NO 2 Ϫ derived from NO to generate reactive intermediates that form 3-nitrotyrosine in proteins in vitro (38,53). They also peroxidize the lipid moieties of LDL (39,40), converting the lipoprotein to a form that is recognized by the macrophage scavenger receptor (40).…”

Section: Figmentioning

confidence: 99%

Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species

Pennathur

Bergt

Shao

et al. 2004

Journal of Biological Chemistry

253

230

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High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but itis not yet established whether HDL proteins are damaged by reactive nitrogen species in the circulation or artery wall. One pathway that generates such species involves myeloperoxidase (MPO), a major constituent of artery wall macrophages. Another pathway involves peroxynitrite, a potent oxidant generated in the reaction of nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine in vitro. To investigate the involvement of reactive nitrogen species in atherogenesis, we quantified 3-nitrotyrosine levels in HDL in vivo. The mean level of 3-nitrotyrosine in HDL isolated from human aortic atherosclerotic intima was 6-fold higher (619 ؎ 178 mol/mol Tyr) than that in circulating HDL (104 ؎ 11 mol/mol Tyr; p < 0.01). Immunohistochemical studies demonstrated striking colocalization of MPO with epitopes reactive with an antibody to 3-nitrotyrosine. However, there was no significant correlation between the levels of 3-chlorotyrosine, a specific product of MPO, and those of 3-nitrotyrosine in lesion HDL. We also detected 3-nitrotyrosine in circulating HDL, and linear regression analysis demonstrated a strong correlation between the levels of 3-chlorotyrosine and levels of 3-nitrotyrosine. These observations suggest that MPO promotes the formation of 3-chlorotyrosine and 3-nitrotyrosine in circulating HDL but that other pathways also produce 3-nitrotyrosine in atherosclerotic tissue. Levels of HDL isolated from plasma of patients with established coronary artery disease contained twice as much 3-nitrotyrosine as HDL from plasma of healthy subjects, suggesting that nitrated HDL might be a marker for clinically significant vascular disease. The detection of 3-nitrotyrosine in HDL raises the possibility that reactive nitrogen species derived from nitric oxide might promote atherogenesis. Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation.

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“…However, there is disagreement regarding the predominant mechanism by which tyrosyl nitration occurs under these conditions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). The reaction between superoxide (O 2 Ϫ ) and nitric oxide (NO) results in formation of peroxynitrite (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)17).…”

mentioning

confidence: 99%

Direct real-time evaluation of nitration with green fluorescent protein in solution and within human cells reveals the impact of nitrogen dioxide vs. peroxynitrite mechanisms

Espey

Xavier

Thomas

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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3-Nitrotyrosyl adducts in proteins have been detected in a wide range of diseases. The mechanisms by which reactive nitrogen oxide species may impede protein function through nitration were examined by using a unique model system, which exploits a critical tyrosyl residue in the fluorophoric pocket of recombinant green fluorescent protein (GFP). Exposure of purified GFP suspended in phosphate buffer to synthetic peroxynitrite in either 0.5 or 5 M steps resulted in progressively increased 3-nitrotyrosyl immunoreactivity concomitant with disappearance of intrinsic fluorescence (IC 50 Ϸ 20 M). Fluorescence from an equivalent amount of GFP expressed within intact MCF-7 tumor cells was largely resistant to this bolus treatment (IC 50 > 250 M). The more physiologically relevant conditions of either peroxynitrite infusion (1 M͞min) or de novo formation by simultaneous, equimolar generation of nitric oxide (NO) and superoxide (e.g., 3-morpholinosydnonimine; NONOates plus xanthine oxidase͞hypo-xanthine, menadione, or mitomycin C) were examined. Despite robust oxidation of dihydrorhodamine under each of these conditions, fluorescence decrease of both purified and intracellular GFP was not evident regardless of carbon dioxide presence, suggesting that oxidation and nitration are not necessarily coupled. Alternatively, both extra-and intracellular GFP fluorescence was exquisitely sensitive to nitration produced by heme-peroxidase͞hydrogen peroxidecatalyzed oxidation of nitrite. Formation of nitrogen dioxide (NO 2) during the reaction between NO and the nitroxide 2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide indicated that NO 2 can enter cells and alter peptide function through tyrosyl nitration. Taken together, these findings exemplified that heme-peroxidasecatalyzed formation of NO 2 may play a pivotal role in inflammatory and chronic disease settings while calling into question the significance of nitration by peroxynitrite.3-nitrotyrosine ͉ myeloperoxidase ͉ nitric oxide ͉ xanthine oxidase ͉ superoxide T he prevalence of increased 3-nitrotyrosine in both acute inflammatory events and numerous chronic diseases suggests that protein nitration may be an important component in pathophysiologic processes (1-7). However, there is disagreement regarding the predominant mechanism by which tyrosyl nitration occurs under these conditions (1-16). The reaction between superoxide (O 2 Ϫ ) and nitric oxide (NO) results in formation of peroxynitrite (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)17). Numerous studies have concluded that this nitrogen oxide mediates the majority of nitration, on the basis of 3-nitrotyrosine formation after bolus application of synthetically produced peroxynitrite. Nitration by this route is strongly influenced by buffer composition, in particular, the concentration of protons, transition metals, and carbon dioxide (CO 2 ; refs. 1, 6, 20-24). Both neutrophils and macrophages have been shown to elicit nitration reactions through myeloperoxidase (MPO) activity (15-18). Catalysis of nitrite oxidation by heme...

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Formation of Reactive Nitrogen Species during Peroxidase-catalyzed Oxidation of Nitrite

Cited by 745 publications

References 75 publications

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Reactive species mechanisms of cellular hypoxia-reoxygenation injury

Human Atherosclerotic Intima and Blood of Patients with Established Coronary Artery Disease Contain High Density Lipoprotein Damaged by Reactive Nitrogen Species

Direct real-time evaluation of nitration with green fluorescent protein in solution and within human cells reveals the impact of nitrogen dioxide vs. peroxynitrite mechanisms

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