Formation of S-nitrosothiols via direct nucleophilic nitrosation of thiols by peroxynitrite with elimination of hydrogen peroxide

Albert Van Der Vliet, Peter A. Peter, Patrick S Y Wong, Aalt Bast, Carroll E Cross

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Peroxynitrite (ONOO-), a potent oxidant formed by reaction of nitric oxide (NO(·)) 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(·). Reaction of ONOO- with thiols is thought to proceed through formation of a S-nitrothiol (thionitrate; RSNO2) intermediate and yields low levels of S-nitrosothiols (thionitrites; RSNO), both of which are theoretical sources of NO(·). Kinetic analysis of NO(·) production after reaction of ONOO- with GSH established that NO(·) originates exclusively from the thionitrite GSNO. Further mechanistic investigations indicated that GSNO formation by ONOO- does not occur via one-electron oxidation mechanisms. Nitrosation of GSH could theoretically proceed via intermediate formation of the thionitrate GSNO2, which, after rearrangement to the corresponding sulfenyl nitrite (GSONO), can react with GSH to form GSNO and GSOH. However, no evidence for such a mechanism was found in experiments with NO2 or with the stable nitrothiol tert-butylthionitrate. Using high performance liquid chromatography with chemiluminescence detection, formation of H2O2 was observed after reaction of ONOO- with GSH under both aerobic and anaerobic conditions, at levels similar to the yield of GSNO, indicative of a direct nucleophilic nitrosation mechanism with elimination of HOO-. Our results indicate that ONOO- may contribute to S-nitrosation in vivo and that direct nitrosation of thiols or other nucleophilic substrates by ONOO- may represent an important and often overlooked component of NO(·) biochemistry.

Original languageEnglish (US)
Pages (from-to)30255-30262
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number46
DOIs
StatePublished - Nov 13 1998

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S-Nitrosothiols
Nitrosation
Peroxynitrous Acid
Sulfhydryl Compounds
Hydrogen Peroxide
Nitric Oxide
Biochemistry
Chemiluminescence
Guanylate Cyclase
High performance liquid chromatography
Nitrites
Platelets
Luminescence
Platelet Aggregation
Oxidants
Vasodilation
Superoxides
Leukocytes
Adhesion
Agglomeration

ASJC Scopus subject areas

  • Biochemistry

Cite this

Formation of S-nitrosothiols via direct nucleophilic nitrosation of thiols by peroxynitrite with elimination of hydrogen peroxide. / Van Der Vliet, Albert; Peter, Peter A.; Wong, Patrick S Y; Bast, Aalt; Cross, Carroll E.

In: Journal of Biological Chemistry, Vol. 273, No. 46, 13.11.1998, p. 30255-30262.

Research output: Contribution to journalArticle

Van Der Vliet, Albert ; Peter, Peter A. ; Wong, Patrick S Y ; Bast, Aalt ; Cross, Carroll E. / Formation of S-nitrosothiols via direct nucleophilic nitrosation of thiols by peroxynitrite with elimination of hydrogen peroxide. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 46. pp. 30255-30262.
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abstract = "Peroxynitrite (ONOO-), a potent oxidant formed by reaction of nitric oxide (NO(·)) 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(·). Reaction of ONOO- with thiols is thought to proceed through formation of a S-nitrothiol (thionitrate; RSNO2) intermediate and yields low levels of S-nitrosothiols (thionitrites; RSNO), both of which are theoretical sources of NO(·). Kinetic analysis of NO(·) production after reaction of ONOO- with GSH established that NO(·) originates exclusively from the thionitrite GSNO. Further mechanistic investigations indicated that GSNO formation by ONOO- does not occur via one-electron oxidation mechanisms. Nitrosation of GSH could theoretically proceed via intermediate formation of the thionitrate GSNO2, which, after rearrangement to the corresponding sulfenyl nitrite (GSONO), can react with GSH to form GSNO and GSOH. However, no evidence for such a mechanism was found in experiments with NO2 or with the stable nitrothiol tert-butylthionitrate. Using high performance liquid chromatography with chemiluminescence detection, formation of H2O2 was observed after reaction of ONOO- with GSH under both aerobic and anaerobic conditions, at levels similar to the yield of GSNO, indicative of a direct nucleophilic nitrosation mechanism with elimination of HOO-. Our results indicate that ONOO- may contribute to S-nitrosation in vivo and that direct nitrosation of thiols or other nucleophilic substrates by ONOO- may represent an important and often overlooked component of NO(·) biochemistry.",
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AU - Cross, Carroll E

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AB - Peroxynitrite (ONOO-), a potent oxidant formed by reaction of nitric oxide (NO(·)) 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(·). Reaction of ONOO- with thiols is thought to proceed through formation of a S-nitrothiol (thionitrate; RSNO2) intermediate and yields low levels of S-nitrosothiols (thionitrites; RSNO), both of which are theoretical sources of NO(·). Kinetic analysis of NO(·) production after reaction of ONOO- with GSH established that NO(·) originates exclusively from the thionitrite GSNO. Further mechanistic investigations indicated that GSNO formation by ONOO- does not occur via one-electron oxidation mechanisms. Nitrosation of GSH could theoretically proceed via intermediate formation of the thionitrate GSNO2, which, after rearrangement to the corresponding sulfenyl nitrite (GSONO), can react with GSH to form GSNO and GSOH. However, no evidence for such a mechanism was found in experiments with NO2 or with the stable nitrothiol tert-butylthionitrate. Using high performance liquid chromatography with chemiluminescence detection, formation of H2O2 was observed after reaction of ONOO- with GSH under both aerobic and anaerobic conditions, at levels similar to the yield of GSNO, indicative of a direct nucleophilic nitrosation mechanism with elimination of HOO-. Our results indicate that ONOO- may contribute to S-nitrosation in vivo and that direct nitrosation of thiols or other nucleophilic substrates by ONOO- may represent an important and often overlooked component of NO(·) biochemistry.

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