Diethyl dithiocarbamate-induced decomposition of S-nitrosothiols.
Diethyl dithiocarbamate (DDC) has been used extensively as an inhibitor of CuZn superoxide dismutase (SOD) in the study of superoxide and nitric oxide. Addition of DDC to solutions of the endogenous NO adduct S-nitrosoglutathione (GSNO) causes a rapid decrease in GSNO with concomitant formation of nitrite, nitrate, disulfuram, oxidized glutathione, and mixed disulfide. Nitric oxide and superoxide appear to be produced in the process. Product formation is best explained by a radical mechanism in which S-nitrosation of DDC facilitates disulfide formation following homolytic cleavage. S-Nitrosocysteine and S-nitroso-N-acetylpenicillamine are likewise unstable in the presence of DDC. These findings may complicate interpretation of experiments in which DDC is used to alter NO-mediated responses. Some biological actions of DDC may result from SNO elimination rather than SOD inactivation. Moreover, apparent DDC-induced potentiation of superoxide effects may derive from O2- produced during the conversion of SNO to NO.
Arnelle, DR; Day, BJ; Stamler, JS
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