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

We show here tnhitarticniotrxiitdee(N(NOO2؊1⁄7)), the primary metabolic end product of can be oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase, and lactoperoxidase, in the presence of hydrogen peroxide, to most likely form NO21⁄7, which can contribute to tyrosine nitration during inflammatory processes

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

2002

Scholarcy highlights

  • Involvement of peroxynitrite in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues
  • The results presented demonstrate that the peroxidases horseradish peroxidase, MPO, and LPO can oxidize NO2Ϫ in the presence of H2O2 or H2O2-generating systems to form reactive nitrogen intermediate(s) capable of nitrating phenolic compounds such as tyrosine
  • In addition to being oxidized to more reactive nitrogen species, NO2Ϫ was found to catalyze MPO-mediated oxidation of Thio-2-nitrobenzoic acid or chlorination of MCD or hydroxyphenylacetic acid. These results confirm and extend a recent study by Shibata et al, who demonstrated that HRP and H2O2 oxidize NO2Ϫ to form an intermediate that is capable of causing chlorophyll degradation and tyrosine nitration
  • They postulated that HRP oxidizes NO2Ϫ to NO21⁄7 in the presence of H2O2 according to the following reaction scheme: HRP ϩ H2O2 3 Compound I ϩ H2O
  • The notion that NO2Ϫ can act as a substrate for MPO/H2O2 in the presence of physiological levels of ClϪ is further supported by our studies with MCD chlorination or HPA oxidation, which demonstrated that low concentrations of NO2Ϫ markedly enhanced MPO-catalyzed chlorination of these substrates
  • We have recently demonstrated that oxidation of NO2Ϫ by hypochlorous acid results in formation of reactive intermediates capable of inducing phenolic nitration, and both mechanisms of NO2Ϫ oxidation may contribute to tyrosine nitration observed in tissues undergoing inflammatory responses and where high levels of MPO are present
  • Peroxidase-catalyzed oxidation of NO2Ϫ results in formation of NO21⁄7 or a related species, which can contribute to tyrosine nitration and could be involved in cell and tissue injury during situations of increased NO1⁄7 production

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