Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates. Chemical aspects involved in the balance between oxidative and nitrosative stress

• Published in: The Journal of biological chemistry 1997-04, Vol.272 (17), p.11147
• Main Authors: Wink, D A, Cook, J A, Kim, S Y, Vodovotz, Y, Pacelli, R, Krishna, M C, Russo, A, Mitchell, J B, Jourd'heuil, D, Miles, A M, Grisham, M B
• Format: Article
• Language: English
• Subjects: Free Radicals; Glutathione - analogs & derivatives; Glutathione - analysis; Glutathione - chemistry; Glutathione - metabolism; Glutathione Disulfide; Hydrazines; Models, Chemical; Nitrates - chemistry; Nitric Oxide - chemistry; Nitrogen Oxides; Nitroso Compounds; Oxidation-Reduction; S-Nitrosoglutathione; Sulfhydryl Compounds - chemistry; Superoxides - chemistry; Triazoles; Xanthine Oxidase - metabolism
• ISSN: 0021-9258
• DOI: 10.1074/jbc.272.17.11147

Thiol-containing proteins are key to numerous cellular processes, and their functions can be modified by thiol nitrosation or oxidation. Nitrosation reactions are quenched by O-2, while the oxidation chemistry mediated by peroxynitrite is quenched by excess flux of either NO or O-2. A solution of glutathione (GSH), a model thiol-containing tripeptide, exclusively yielded S-nitrosoglutathione when exposed to the NO donor, Et2NN(O)NONa. However, when xanthine oxidase was added to the same mixture, the yield of S-nitrosoglutathione dramatically decreased as the activity of xanthine oxidase increased, such that there was a 95% reduction in nitrosation when the fluxes of NO and O-2 were nearly equivalent. The presence of superoxide dismutase reversed O-2-mediated inhibition, while catalase had no effect. Increasing the flux of O-2 yielded oxidized glutathione (GSSG), peaking when the flux of NO and O-2 were approximately equivalent. The results suggest that oxidation and nitrosation of thiols by superoxide and NO are determined by their relative fluxes and may have physiological significance.