Cystine uptake and glutathione level in endothelial cells exposed to oxidative stress.

The uptake of L-cystine into cultured human umbilical vein endothelial cells was Na+ independent and inhibited competitively by glutamate. It is concluded that the uptake of cystine in endothelial cells is mediated by system x-c. The contents of glutathione in endothelial cells decreased when the cells were cultured in cystine-free medium or in glutamate-enriched medium, suggesting that the glutathione level in endothelial cells is regulated by the cystine uptake via system x-c. The uptake rate of cystine increased three times the normal rate when the cells were exposed to H2O2 generated by glucose and glucose oxidase. This increase required protein synthesis. The cystine transport activity was also enhanced when the cells were cocultured with activated polymorphonuclear leukocytes. Intracellular glutathione levels were decreased when the cells were exposed to H2O2 despite an increase in the cystine uptake. The extracellular glutathione levels were increased at that time, suggesting the efflux of glutathione. In endothelial cells, cystine transport activity seems to be involved in the cell defense against oxidative stress.