Effects of oxygen on the reactivity of nitrogen oxide species including peroxynitrite

Abstract

This paper describes the O2-dependent control of the reactivity of nitrogen oxide species for the production of biologically important nitrated and nitrosated compounds. In this study, the effects of O2 on the reactivity of NO, NO2, and ONOO-/ONOOH for nitration of tyrosine (Tyr) and nitrosation of glutathione (GSH) and morpholine (MOR) were examined. NO produced S-nitrosoglutathione (GSNO) and N-nitrosomorpholine (NMOR) through the formation of N2O3 under aerobic conditions, and NO2 produced 3-nitrotyrosine (3-NO2Tyr), GSNO, and NMOR. Transnitrosation from GSNO to MOR was observed only in the presence of O2. Although preformed ONOO-/ONOOH produced all the products under aerobic conditions, the formation of 3-NO2Tyr and GSNO was markedly reduced and the formation of NMOR was enhanced under anaerobic conditions. The reactivity of the CO2 adduct of ONOO- was similarly dependent on O2. 3-NO2Tyr was produced effectively by reaction with ONOO-/ONOOH at the O2 concentration of 270 μM and by reaction with its CO2 adduct at O2 concentrations greater than 5 μM. Generation of·OH from ONOO-/ONOOH was suppressed under anaerobic conditions. The reactivity of ONOO-/ONOOH and·OH generation from ONOO- were reversibly controlled by the O2 concentration. © 2004 Pharmaceutical Society of Japan.