EFFECT OF SELENIUM ON SELENOPROTEIN-P EXPRESSION IN CULTURED LIVER-CELLS

Selenoprotein P and glutathione peroxidase are selenoproteins that are synthesized by hepatocytes. The production of these selenoproteins by human and rat liver cell lines has been assessed at several levels of selenium supplementation and compared with one another. HepG2 and H4I IE cells were cultured in serum-free medium without selenium supplemen tation for 48 h; then sodium selenite was added to the medium to give final concentrations of 0, 1, 2.5, 5, or 10 ng selenium/ml medium. Aft er 48 h, selenoprotein P concentration in the medium, cellular glutath ione peroxidase activity, and the mRNA levels of the two selenoprotein s were determined. Selenium deficiency caused a decrease in selenoprot ein mRNA and protein levels. The extent of decrease depended on the ce ll line examined. In selenium-deprived HepG2 cells, selenoprotein P re lease decreased to 10% of the release by selenium-replete cells. Under the same conditions, cellular glutathione peroxidase activity decreas ed to 33%. H4IIE cells showed the opposite results with cellular gluta thione peroxidase activity decreasing to 13% and selenoprotein P relea se decreasing to 40% of selenium-replete cells. The effect of dithioth reitol on secretion of selenoprotein P by H4IIE cells was examined. Se lenoprotein P secretion was inhibited by dithiothreitol, suggesting th at disulfide bond formation is necessary for secretion of the mature p rotein.