Mechanism of S-nitrosothiol formation and degradation mediated by copper ions

Experimental evidence is presented supporting a mechanism of S-nitrosothiol formation and degradation mediated by copper ions using bovine serum album in, human hemoglobin and glutathione as models. We found that Cu2+, but not Fe3+, induces in the presence of NO a fast S-nitrosation of bovine serum a lbumin and human hemoglobin, and the reaction is prevented by thiol blockin g reagents. During the reaction, Cu is accumulated and accounts for destabi lization of the S-nitrosothiol formed. In contrast, glutathione rapidly dim erizes in the presence of Cu2+, the reaction competing with S-nitrosation a nd therefore preventing the formation of S-nitrosoglutathione. We have comb ined the presented role of Cu2+ in S-nitrosothiol formation with the known destabilizing effect of Cu+, providing a unique simple picture where the re dox state of copper determines either the NO release from S-nitrosothiols o r the NO scavenging by thiol groups. The reactions described are fast, effi cient, and may occur at micromolar concentration of all reactants, We propo se that the mechanism presented may provide a general method for in vitro S -nitrosation.