Nitric oxide protects Cu,Zn-superoxide dismutase from hydrogen peroxide-induced inactivation.
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/H2O2 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 H2O2-induced inactivation of SODI. 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 H2O2-induced inactivation by reducing SOD-Cu2+.OH to the active SOD-Cu2+ with concomitant production of NO+ which reacts with H2O2 to give ONOO-.
Kim
Y S
YS
Department of Biochemistry, Kangwon National University, Chunchon, South Korea.
Han
S
S
D000818:Animals; D002417:Cattle; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D005609:Free Radicals; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1