Effects of oxidant stress on the hexose monophosphate shunt pathway of platelets

Abstract

Platelet function may be altered by the oxygen metabolites generated by phagocytic cells. This raised the question whether oxidant injury to platelets is associated with a depletion of reduced glutathione, since this compound is known to be important in the protection of other blood cells against oxidant damage. We studied the effects of the oxygen metabolites generated by the enzyme system xanthine-xanthine oxidase on the glutathione (GSH) stability and the metabolism of the hexose monophosphate pathway (HMPS) of platelets. Platelet suspensions incubated with the enzyme system had marked stimulation of the HMPS pathway and did not have GSH instability. In spite of this, the platelet suspensions had impaired aggregation to adenosine diphosphate (ADP). By using specific scavengers, we found that this altered metabolism and function was related to H2O2 and not O2- or hydroxyl radical. In order to determine if cellular catalase was degrading H2O2 we studied the oxidation of 14C-formate by platelet suspensions exposed to the xanthine-xanthine oxidase system. As expected, no oxidation of 14C-formate occurred, suggesting that H2O2 was preferentially degraded by the HMPS pathway via glutathione peroxidase. These data indicate that oxidant injury to platelets occurs in spite of active degradation of H2O2 and suggest that these cells may not be able to protect some sensitive cellular sites during exposure of exogenous H2O2. Our studies also suggest that platelets produce O2 and that this oxygen radical cannot react directly with HMPS of platelets.