Peroxynitrite-induced changes of thiol groups in human blood platelets

In this study we investigated sulfhydryl and disulfide metabolism in blood platelets treated with peroxynitrite (ONOO-) at concentrations of 10, 100, and 1000 microM. In platelets incubated with peroxynitrite, a decrease of both protein and low molecular weight thiols (glutathione, cysteine and cysteinylglycine) was observed. The reduction of platelet free thiols caused by ONOO- was dose dependent. We found that peroxynitrite induces the oxidation of platelet free SH-groups. Platelets contain a large fraction of glutathione in reduced form (GSH). We showed that after ONOO- treatment, GSH/GSSG ratio in platelets was distinctly decreased. The presented results suggest that oxidation of thiols and depletion of GSH in platelets caused by peroxynitrite may be responsible for cytotoxic effects of this compound.