Elevation of glutathione levels in bovine pulmonary artery endothelial cells by N-acetylcysteine.

N-Acetylcysteine (NAC), a cysteine derivative with chemoprotective and radioprotective effects, was found to elevate bovine pulmonary artery endothelial cell (EC) glutathione after in vitro incubation. The elevation in glutathione was associated with enhanced uptake of radioactivity of cystine from the medium. Because cystine in medium was converted rapidly to cysteine and cysteinyl-NAC in the presence of NAC and given that cysteine has a higher affinity for uptake by EC than cystine, we conclude that the enhanced uptake of radioactivity was in the form of cysteine and at least part of the stimulatory effect of NAC on EC glutathione was due to a formation of cysteine by a mixed disulfide reaction of NAC with cystine similar to that previously reported for Chinese hamster ovarian cells (R. D. Issels et al. 1988. Biochem. Pharmacol. 37:881-888). However, NAC was more effective than cysteine in elevating cellular glutathione at equimolar concentrations, and at higher concentrations of NAC an elevation of EC glutathione occurred even in the absence of cystine in the medium through a currently unknown mechanism. Thus, at least two mechanisms are operative in the elevation of endothelial cellular glutathione by NAC. NAC may be a useful compound for elevating glutathione of the pulmonary vasculature for protection against oxidant stress.