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.
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.
Wink
D A
DA
Tumor Biology Section, Radiation Biology Branch, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. wink@box-w.nih.gov
Cook
J A
JA
Kim
S Y
SY
Vodovotz
Y
Y
Pacelli
R
R
Krishna
M C
MC
Russo
A
A
Mitchell
J B
JB
Jourd'heuil
D
D
Miles
A M
AM
Grisham
M B
MB
D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D019803:Glutathione Disulfide; D006834:Hydrazines; D008956:Models, Chemical; D009566:Nitrates / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry*; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D010084:Oxidation-Reduction; D026422:S-Nitrosoglutathione; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013481:Superoxides / Q000737:chemistry*; D014230:Triazoles; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D006834:Hydrazines; D009566:Nitrates; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D013438:Sulfhydryl Compounds; D014230:Triazoles; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D014969:Xanthine Oxidase; D005978:Glutathione; D019803:Glutathione Disulfide