Consequences of MnSOD interactions with nitric oxide: nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide.
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 H2O2. 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.
Filipović
Milos R
MR
Department of Chemistry, University of Belgrade, Studentski Trg 12-16, Belgrade, Serbia.
Stanić
Dragana
D
Raicević
Smiljana
S
Spasić
Mihajlo
M
Niketić
Vesna
V
D004591:Electrophoresis, Polyacrylamide Gel; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D030421:Peroxynitrous Acid / Q000378:metabolism*; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000378:metabolism*
D006454:Hemoglobins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase