Nitric oxide protects Cu, Zn-superoxide dismutase from hydrogen peroxide- induced inactivation

초록

Reaction of Cu, Zn-superoxide dismutase (SOD1) and hydrogen peroxide generates a putative oxidant SOD-Cu2+-(·)OH that can inactivate the enzyme and oxidize 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) to DMPO-(·)OH. In the presence of nitric oxide ((·)NO), the SOD1/H<inf>2</inf>O<inf>2</inf> system is known to produce peroxynitrite (ONOO-). In contrast to the proposed cytotoxicity of (·)NO conferred by ONOO-, we report here a protective role of (·)NO in the H<inf>2</inf>O<inf>2</inf>-induced inactivation of SOD1. In a dose-dependent manner, (·)NO suppressed formation of DMPO-(·)OH and inactivation of the enzyme. Fragmentation of the enzyme was not affected by (·)NO. Bicarbonate retarded formation of ONOO-, suggesting that (·)NO competes with bicarbonate for the oxidant SOD-Cu2+-(·)OH. We propose that (·)NO protects SOD1 from H<inf>2</inf>O<inf>2</inf>- induced inactivation by reducing SOD-Cu2+-(·)OH to the active SOD-Cu2+ with concomitant production of NO+ which reacts with H<inf>2</inf>O<inf>2</inf> to give ONOO-. © 2000 Federation of European Biochemical Societies.

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