Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite: A potential additional mechanism of nitric oxide- dependent toxicity

Albert Van Der Vliet, Jason P. Eiserich, Barry Halliwell, Carroll E Cross

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688 Scopus citations

Abstract

Involvement of peroxynitrite (ONOO-) in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues. We show here that nitrite (NO2/-), the primary metabolic end product of nitric oxide (NO·), can he oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase (MPO), and lactoperoxidase (LPO), in the presence of hydrogen peroxide (H2O2), to most likely form NO2/·, which can also contribute to tyrosine nitration during inflammatory processes. Phenolic nitration by MPO- catalyzed NO2/- oxidation is only partially inhibited by chloride (Cl-), the presumed major physiological substrate for MPO. In fact, low concentrations of NO2/- (2-10 μM) catalyze MPO-mediated oxidation of Cl- , indicated by increased chlorination of monochlorodimedon or 4- hydroxyphenylacetic acid, most likely via reduction of MPO compound II. Peroxidase-catalyzed oxidation of NO2/-, as indicated by phenolic nitration, was also observed in the presence of thiocyanate (SCN-), an alternative physiological substrate for mammalian peroxidases. Collectively, our results suggest that NO2/-, at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO2/· via peroxidase-catalyzed oxidation of NO2 - may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO· production.

Original languageEnglish (US)
Pages (from-to)7617-7625
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number12
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Biochemistry

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