Nitric oxide-mediated protection of endothelial cells from hydrogen peroxide is mediated by intracellular zinc and glutathione.

摘要

Oxidative stress may cause endothelial dysfunction and vascular disease. It has been shown that NO protects endothelial cells (EC) against H(2)O(2)-induced toxicity. In addition, it is known that NO within cells induces a zinc release from proteins containing zinc-sulfur complexes. The aim of this study was to investigate whether zinc released intracellularly by NO plays a signaling role in the NO-mediated protection against H(2)O(2) in rat aortic EC. Our results show that the NO-mediated protection toward H(2)O(2) depends on the activities of glutathione peroxidase and glutamate cysteine ligase (GCL), the rate-limiting enzyme of glutathione (GSH) de novo biosynthesis. Moreover, NO increases the synthesis of the antioxidant GSH by inducing the expression of the catalytic subunit of GCL (GCLC). Chelating intracellular "free