Selenite protects human endothelial cells from oxidative damage and induces thioredoxin reductase

The ability of selenium to protect cultured human coronary artery endotheli al cells (HCAEC), human umbilical vein endothelial cells (HUVEC) and bovine aortic endothelial cells (BAEC) from oxidative damage induced by 100 muM t -butyl hydroperoxide (t-BuOOH) was compared. Preincubation of human endothe lial cells for 24 h with sodium selenite at concentrations as low as 5 nM p rovided significant protection against the harmful effects of 100 muM t-BuO OH, with complete protection bei ng achieved with 40 n M selenite. The prei ncubation period was required for selenite to exert this protective effect on endothelial cells. When compared with selenium-deficient cells, the acti vities of cytoplasmic glutathione peroxidase (GPX-1), phospholipid hydroper oxide glutathione peroxidase (GPX-4) and thioredoxin reductase (TR) were ea ch induced approx. 3-4-fold by 40 nM selenite. HCAEC and HUVEC showed great similarity in their relative abilities to resist oxidative damage in the p resence and absence of selenite, and the activities of TR and the GPXs were also similar in these cell types. BAEC were more susceptible to damage by 100 muM t-BuOOH than were human endothelial cells, and could not be protect ed completely by incubation with selenite at concentrations up to 160 nM. T he activity of TR in human endothelial cells was approx. 25-fold greater th an that in BAEC of a similar selenium status, but GPX-1 and GPX-4 activitie s were not significantly different between the human and bovine cells. Thes e studies, although performed with a small number of cultures, show for the first time that selenium at low doses can provide significant protection o f the human coronary artery endothelium against damage by oxidative stress. TR may be an important antioxidant selenoprotein in this regard, in additi on to the GPXs. The data also suggest that HUVEC, but not BAEC, represent a suitable model system in which to study the effects of selenium on the end othelium of human coronary arteries.