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

[摘要]

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 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 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⁻.

[学科分类] 生物化学/生物物理

[关键词] Cu;Zn-superoxide dismutase;Hydrogen peroxide;Nitric oxide;DHR123;dihydrorhodamine-1;2;3;DMPO;5;5′-dimethyl-1-pyrroline-N-oxide;DTPA;diethylenetriaminepentaacetic acid;EPR;electron paramagnetic resonance;SNAP;S-nitroso-N-acetylpenicillamine;SOD1;Cu;Zn-superoxide dismutase