Protective role of intracellular glutathione against oxidized low density lipoprotein in cultured endothelial cells.

We examined the role of intracellular glutathione (GSH) in the defense of endothelial cells against oxidized low density lipoprotein (OX-LDL). Incubation of cultured bovine endothelial cells with OX-LDL produced a loss of intracellular GSH, followed by lysis. A decrease in the cellular stores of GSH by treating the endothelial cells with buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, increased the susceptibility of endothelial cells to lysis by OX-LDL. In contrast, an increase in cellular GSH level by treatment with L-2-oxothiazolidine-4-caboxylate, an effective intracellular cysteine delivery agent, reduced the toxicity of OX-LDL. These findings suggest that intracellular GSH plays an important role in the defense of endothelial cells against OX-LDL, and that the mechanism of OX-LDL toxicity is related to the depletion of intracellular GSH.