Effect of selenium on selenoprotein P expression in cultured liver cells

摘要

Selenoprotein P ami glutalhione peroxidase are selenoproteins that are synthesized by hepatoeytes. The production of these selenoproteins by human and ral liver cell lines has been assessed at several levels of selenium supplementation and compared with one another. HcpG2 and H4IIE cells were cultured in serum-free medium without selenium supplementation Tor 48 h; then sodium selenite was added lo the medium to give final concentrations of 0, 1, 2.5, 5, or It) ng selenium/ml medium. After 48 h, selenoprotein P concentration in the medium, cellular glutathione pemxidase activity, and the inRNA levels of the two selenoproteins were determined. Selenium deficiency caused a decrease in selenoprotein mRNA and protein levels. The extent of decrease depended on the cell line examined. In selenium-deprived HepG2 cells, selenoprotein P release decreased to 10% of the release by selenium-replete cells. Under the same conditions, cellular glutathione peroxidase activity decreased to 33%. H4I1E cells showed the opposite results with cellular glutathione peroxidase activity decreasing to 13% and selenoprotein P release decreasing to 40% of selenium-replete cells. The effect of dithiothreitol on secretion of selenoprotein P by H41IE cells was examined, Selenoprotein P secretion was inhibited by dithiothreitol, suggesting that disull'ide bond formation is necessary for secretion of the mature protein.