Plasma selenium in patients with cirrhosis.

Plasma selenium concentration is decreased in patients with cirrhosis and, based on this finding, it has been suggested that patients with cirrhosis are selenium deficient. We measured plasma selenium concentration and the two plasma selenoproteins, glutathione peroxidase (GSHPx-3) and selenoprotein P, in the plasma of patients with cirrhosis of Child classes A, B, and C and in control subjects. Plasma selenium declined in proportion to the severity of the cirrhotic condition, as indicated by the Child class. Selenoprotein P, which originates largely in the liver, declined in a similar manner. Plasma glutathione peroxidase activity increased, and GSHPx-3 originates in the kidney. Selenium in the non-selenoprotein pool, shown by others to be largely selenomethionine in albumin, declined. Thus, although plasma selenium is decreased in patients with cirrhosis, the increase in plasma glutathione peroxidase activity, which occurs in them, suggests that patients with cirrhosis do not have selenium deficiency.

Selenoprotein P associates with endothelial cells in rat tissues.

Selenoprotein P is an extracellular heparin-binding protein that has been implicated in protecting the liver against oxidant injury. Its location in liver, kidney, and brain was determined by conventional immunohistochemistry and confocal microscopy using a polyclonal antiserum. Selenoprotein P is associated with endothelial cells in the liver and is more abundant in central regions than in portal regions. It is also present in kidney glomeruli associated with capillary endothelial cells. Staining of selenoprotein P in the brain is also confined to vascular endothelial cells. The heparin-binding properties of selenoprotein P could be the basis for its binding to tissue. Its localization to the vicinity of endothelial cells is potentially relevant to its oxidant defense function.

Thioredoxin reductase activity is decreased by selenium deficiency.

Animal thioredoxin reductase is a selenoprotein. In this study, thioredoxin reductase activities in liver, kidney, and brain have been compared in rats fed selenium-deficient and control diets for 14 weeks following weaning. Selenium deficiency caused a decrease in thioredoxin reductase activity from control to 4.5% in liver and 11% in kidney. However, brain thioredoxin reductase activity was not affected by selenium deficiency of this severity. Gold inhibited thioredoxin reductase activity in the liver in a manner typical of its effect on selenoenzymes. Repletion of selenium-deficient rats with injections of selenium caused thioredoxin reductase activity to increase more rapidly in the liver than glutathione peroxidase activity but more slowly than selenoprotein P. These results indicate that thioredoxin reductase activity in liver and kidney is sensitive to selenium nutritional status but that brain thioredoxin reductase activity is less sensitive.

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 H4IIE cells were cultured in serum-free medium without selenium supplementation 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. After 48 h, selenoprotein P concentration in the medium, cellular glutathione peroxidase activity, and the mRNA 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%. H4IIE 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 H4IIE cells was examined. Selenoprotein P secretion was inhibited by dithiothreitol, suggesting that disulfide bond formation is necessary for secretion of the mature protein.

Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects.

Selenoprotein P, a selenium-rich plasma protein, is an index of selenium status in rats. Antibodies against human selenoprotein P were raised to study the protein and to develop a radioimmunoassay for it. A single collection of plasma from a healthy person in the United States contained 1.84 mumol selenium/L and was defined as containing 1 Unit (U) selenoprotein P/L. Removal of selenoprotein P from the reference plasma by an antibody column indicated that 0.81 mumol selenium/L, or 44% of the plasma selenium, was present as selenoprotein P. Work by others had determined that glutathione peroxidase accounted for 12% of plasma selenium. Stored plasma samples from selenium-deficient (Dechang County) and selenium-supplemented (Mianning County) populations in China were assayed for selenoprotein P. Boys aged 8-12 y had selenoprotein P concentrations of 0.10 +/- 0.04 U/L (n = 22) in Dechang and 0.39 +/- 0.17 U/L (n = 17) in Mianning. Supplementation with 100 micrograms selenium as selenate per day for 14 d raised those levels to 0.51 +/- 0.13 U/L in Dechang and to 0.76 +/- 0.27 U/L in Mianning. Similar results were obtained in men, and plasma selenium concentrations correlated with selenoprotein P concentrations. A study comparing indices of selenium status was conducted in the two counties. Selenoprotein P concentration in Dechang subjects (n = 79) was 36% of that in Mianning subjects (n = 117). For plasma glutathione peroxidase activity the value was 54%; for plasma selenium, 47%; and for whole blood selenium, 64%. We conclude that selenoprotein P is the major selenoprotein in human plasma and that its concentration is an index of selenium nutritional status that appears to be as sensitive as other indices in common use.