Inhibition of Peroxynitrite-Mediated Oxidation of Glutathione by Carbon Dioxide

Zhang, Houwen; Squadrito, G; Uppu, Rao M.; Lemercier, Jean-Noël; Cueto, Rafael; Pryor, William A.

doi:10.1006/abbi.1996.9863

Cited by 76 publications

(69 citation statements)

References 26 publications

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“…Alternatively, nucleophilic attack at the nitrogen atom in ONOOH, which is more positively charged than the two partially negatively charged oxygen atoms in the peroxide bond (62) Ϫ are leaving groups). The relatively low yield of S-nitrosation by ONOOH may be due to the fact that HOO Ϫ is a relatively poor leaving group (61) and can also be attributed to competing additional reaction mechanisms such as nitration or hydroxylation by nucleophilic substitution or electron transfer reactions (21,38). Nevertheless, based on experiments performed in the presence of ascorbate, the yield of S-nitrosation by ONOO Ϫ is as high as 5% and may be physiologically significant.…”

Section: Discussionmentioning

confidence: 99%

“…Under similar conditions, oxidation of GSH was only partially inhibited (Ͻ50%), which indicates that the adduct of ONOO Ϫ with CO 2 (ONOOCO 2 Ϫ ; Ref. 32) oxidizes thiols by a mechanism distinct from ONOO Ϫ and may either be unable to directly nitrosate GSH or promote one-electron oxidation reactions (38,58) that enhance decomposition of GSNO. This latter notion was confirmed by the finding that the inhibition of ONOO Ϫ -induced S-nitrosation by HCO 3 Ϫ was abrogated by increasing concentrations of ascorbate (Fig.…”

Section: Fig 3 Effect Of Ascorbate and Buffer Ph On S-nitrosation Bmentioning

confidence: 99%

“…Thiols and other nucleophilic substrates are thought to react with ONOO Ϫ primarily via nucleophilic substitution at the weak peroxide bond with elimination of nitrite (20,36). An alternative mechanism of thiol oxidation by ONOO Ϫ is presumed to involve an electron transfer mechanism with intermediate formation of thionitrate esters (S-nitrothiols; RSNO 2 ) (21,37,38). Thionitrate esters decompose in aqueous systems to release NO ⅐ via homolytic cleavage of a sulfenyl nitrite (RSONO) intermediate, formed by intramolecular rearrangement of RSNO 2 (39 -41).…”

mentioning

confidence: 99%

“…-induced S-nitrosation, we performed experiments with various NO 2 ⅐ -or NO 2 ϩ -generating systems that are presumed to react with GSH via the initial formation of GSNO 2 (37,38,55). The addition of the nitrating agent TNM (at concentrations ranging from 100 to 500 M) to 2 mM GSH resulted in concentration-dependent formation of GSNO, the yield being about 5% relative to the GSH that was oxidized.…”

mentioning

confidence: 99%

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Formation of S-Nitrosothiols via Direct Nucleophilic Nitrosation of Thiols by Peroxynitrite with Elimination of Hydrogen Peroxide

Vliet¹,

Hoen²,

Wong³

et al. 1998

Journal of Biological Chemistry

140

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Peroxynitrite (ONOO ؊ ), a potent oxidant formed by reaction of nitric oxide (NO ⅐ ) with superoxide anion, can activate guanylyl cyclase and is able to induce vasodilation or inhibit platelet aggregation and leukocyte adhesion, via thiol-dependent formation of NO ⅐ . Reaction of ONOO ؊ with thiols is thought to proceed through formation of a S-nitrothiol (thionitrate; RSNO 2 ) intermediate and yields low levels of S-nitrosothiols (thionitrites; RSNO), both of which are theoretical sources of NO (2, 3). An important component of NO ⅐ biochemistry involves the formation of thionitrite esters with cysteine or cysteine-residues (Snitrosothiols; RSNO), and low molecular weight S-nitrosothiols or S-nitrosothiol adducts in proteins such as albumin or hemoglobin are known to be generated in vivo (4 -7). Formation of S-nitrosothiols may provide a buffering system regulating the bioavailability of NO ⅐ and/or serve to increase its range of action, since S-nitrosothiols are more stable and can release NO ⅐ by site-specific regulatory mechanisms, via reactions with transition metal ions or other reducing systems such as thioredoxin or superoxide anion (7-10). Furthermore, S-nitrosation and transnitrosation reactions with protein cysteine residues may regulate the activity of many enzymes and represent an important signaling mechanism (11-13). Despite the growing interest in the role of S-nitrosothiols in the biological actions of NO ⅐ , there is still uncertainty regarding the mechanism of S-nitrosation in vivo, which most likely does not involve direct reaction of NO ⅐ with thiols but requires electrophilic activation to a nitrosyl cation (NO ϩ )-like intermediate. Metabolites formed during NO ⅐ (auto)oxidation, such as dinitrogen trioxide (N 2 O 3 ), are likely candidates in this respect (14 -17). Alternatively, NO ⅐ can be activated to intermediates with NO ϩ character via interaction with ferric heme proteins (18) or via formation of dinitrosyl-iron complexes (19), in both cases leading to more efficient S-nitrosation. Finally, thiols are important physiological targets for peroxynitrite (ONOO Ϫ ) 2 (20), a potent oxidant formed during simultaneous generation of NO ⅐ and superoxide anion (O 2 . ) (4, 21), and formation of S-nitrosothiols has been detected after reaction of ONOO Ϫ with thiols (22,23). This chemistry has been linked to an increasing number of findings that ONOO -is capable of activating guanylyl cyclase (23-25) and can induce vasodilation, inhibition of platelet aggregation, or leukocyte adhesion and activation (26 -29), actions involving (re)generation of NO ⅐ via reaction with * This study was supported by National Institutes of Health Grant HL57452 (to C. E. C.), the Cystic Fibrosis Foundation, the American Lung Association of California, and a Fellowship from the Parker B. Francis Foundation (to A. v. d. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Sectio...

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Section: Discussionmentioning

confidence: 99%

Section: Fig 3 Effect Of Ascorbate and Buffer Ph On S-nitrosation Bmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Formation of S-Nitrosothiols via Direct Nucleophilic Nitrosation of Thiols by Peroxynitrite with Elimination of Hydrogen Peroxide

Vliet¹,

Hoen²,

Wong³

et al. 1998

Journal of Biological Chemistry

140

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“…Peroxynitrite is also known to undergo additional reactions in the presence of physiological buffered systems and GSH. One of the first observed actions of ONOO Ϫ on thiols was that it caused oxidation reactions, and an analysis of products of these reactions resulted in a hypothesis that nitrated thiols were a key unstable intermediate formed during these reactions (7,8). Recent studies have also provided evidence that thiol radicals seem to be one of the major initial products of the reaction of ONOO Ϫ with thiols (9, 10).…”

Section: Peroxynitrite (Onoomentioning

confidence: 99%

S-Nitroglutathione, a Product of the Reaction between Peroxynitrite and Glutathione That Generates Nitric Oxide

Balazy

Kaminski

Mao

et al. 1998

Journal of Biological Chemistry

133

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Peroxynitrite (ONOO؊ ) has been shown in studies on vascular relaxation and guanylate cyclase activation to react with glutathione (GSH), generating an intermediate product that promotes a time-dependent production of nitric oxide (NO). In this study, reactions of ONOO ؊ with GSH produced a new substance, which was characterized by liquid chromatography, ultraviolet spectroscopy, and electrospray tandem mass spectrometry. The mass spectrometric data provided evidence that the product of this reaction was S-nitroglutathione (GSNO 2 ) and that S-nitrosoglutathione (GSNO) was not a detectable product of this reaction. Further evidence was obtained by comparison of the spectral and chromatographic properties with synthetic standards prepared by reaction of GSH with nitrosonium or nitronium borofluorates. Both the synthetic and ONOO ؊ /GSH-derived GSNO 2 generated a protonated ion, GSNO 2 H ؉ , at m/z 353, which was unusually resistant to decomposition under collision activation, and no fragmentation was observed at collision energy of 25 eV. In contrast, an ion at m/z 337 (GSNOH ؉ ), generated from the synthetic GSNO, readily fragmented with the abundant loss of NO at 9 eV. Reactions of ONOO ؊ with GSH resulted in the generation of NO, which was detected by the head space/ NO-chemiluminescence analyzer method. The generation of NO was inhibited by the presence of glucose and/or CO 2 in the buffers employed. Synthetic GSNO 2 spontaneously generated NO in a manner that was not significantly altered by glucose or CO 2 . Thus, ONOO ؊ reacts with GSH to form GSNO 2 , and GSNO 2 decomposes in a manner that generates NO.Exposure of vascular tissue to peroxynitrite (ONOO Ϫ ) 1 results in a prolonged relaxation (1) that appears to be mediated through a glutathione (GSH)-dependent regeneration of NO (2). Peroxynitrite has also been observed to stimulate guanylate cyclase activity in a thiol-dependent manner in vascular endothelial and smooth muscle preparations (3, 4). Whereas the reaction of ONOO Ϫ with GSH has been reported to form small amounts of S-nitroso-GSH (GSNO) (3, 5), our previous studies detected a different product of this reaction, which was isolated and demonstrated to possess potent vascular relaxant activity (2). Examination of the reaction of nitrogen dioxide (NO 2 ) with GSH detected the formation of what appears to be the same product as that observed in the reaction with ONOO Ϫ (6). Because the biologically active metabolite of these reactions co-migrated on HPLC with a the product of a reaction between nitrosonium borofluorate (NO 2 BF 4 ) and GSH, the vascular relaxant detected was suggested to be a nitrated product of GSH (GSNO 2 ) (6). Thus, additional studies are needed to identify the biologically active substances derived from the reaction of GSH with ONOO Ϫ . Peroxynitrite is also known to undergo additional reactions in the presence of physiological buffered systems and GSH. One of the first observed actions of ONOO Ϫ on thiols was that it caused oxidation reactions, and an analysis of products o...

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Stickstoffmonoxid: die rätselhafte Chemie eines biologischen Botenstoffes

Pfeiffer¹,

Mayer²,

Hemmens³

1999

Angewandte Chemie

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Enorm gestiegen ist das Interesse an der Biologie von Stickstoffmonoxid (NO) in den letzten Jahren. NO wirkt als Signalmolekül in Blutgefäßen und im Gehirn, spielt aber auch eine wichtige Rolle bei der zellulären Immunabwehr. Die chemischen und biologischen Eigenschaften dieses vielseitigen kleinen Moleküls werden vorgestellt und diskutiert, um zu einem besseren Verständnis seiner zahlreichen biologischen Funktionen beizutragen.

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Inhibition of Peroxynitrite-Mediated Oxidation of Glutathione by Carbon Dioxide

Cited by 76 publications

References 26 publications

Formation of S-Nitrosothiols via Direct Nucleophilic Nitrosation of Thiols by Peroxynitrite with Elimination of Hydrogen Peroxide

Formation of S-Nitrosothiols via Direct Nucleophilic Nitrosation of Thiols by Peroxynitrite with Elimination of Hydrogen Peroxide

S-Nitroglutathione, a Product of the Reaction between Peroxynitrite and Glutathione That Generates Nitric Oxide

Stickstoffmonoxid: die rätselhafte Chemie eines biologischen Botenstoffes

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