Consequences of MnSOD interactions with nitric oxide: Nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide

Abstract

The present study demonstrates that manganese superoxide dismutase (MnSOD) Escherichia coli, binds nitric oxide (NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed NO disproportionation (dismutation) into nitrosonium (NO + ) and nitroxyl (NO - ) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to NO, MnSOD-derived NO - species initiate the formation of peroxynitrite (ONOO - ) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO - decomposition and ONOO - -dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO - is accompanied by the formation of substantial amounts of H 2 O 2 . MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of NO.