The reaction of S-nitrosoglutathione with superoxide

Abstract

The nitric oxide (NO)-dependent S-nitrosation of thiols to generate S-nitrosothiols has been proposed as an important pathway for the metabolism of NO in vivo. Although it has been suggested that these S-nitrosated compounds are resistant to decomposition by reactive oxygen metabolites (ROMs), very little information is available regarding the interaction between S-nitrosothiols and ROMs. We found that S-nitrosoglutathione (GSNO) rapidly reacted with O2- to generate glutathione disulfide and equimolar quantities of nitrite and nitrate. The reaction was second order with respect of GSNO and first order with respect of O2- with a rate equation of -d[GSNO]/dt = 2k3[GSNO]2[O2-], where k3 = 3 - 6 x 10(8) M-2s-1. In addition, the reaction of GSNO with O2- generated a strong oxidant as an intermediate capable of oxidizing dihydrorhodamine in the absence of the apparent generation of NO. We conclude that O2- may act as a physiological modulator of S-nitrosation reactions by directly promoting the decomposition of S-nitrosothiols.