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.

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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. (HEPATOL-OGY 1998;27:794-798.) Selenium exerts biological effects as an essential constituent of selenoproteins. 1 Pathological conditions, such as selenium deficiency and organ damage, which are severe enough to alter selenium metabolism, can be expected to affect the concentrations of selenoproteins and to have biochemical and pathological consequences. Several groups have reported that patients with cirrhosis have plasma selenium concentrations lower than those of healthy controls. [2][3][4][5][6] The pathogenesis of those depressed selenium levels is unknown; therefore it is not known whether a remediable state of selenium deficiency exists in cirrhotics.Virtually all the selenium in plasma is present in the form of seleno-amino acids in the primary structure of proteins. One of these amino acids is selenocysteine, the physiologically active form of the element, which is synthesized in animal cells and is present in stoichiometric amounts in selenoproteins. Glutathione peroxidase (isoform GSHPx-3) and selenoprotein P are the only selenoproteins that have been identified in plasma. 7,8 The other amino acid form of selenium in plasma is selenomethionine, 9 an amino acid that is synthesized by plants and is incorporated randomly into animal proteins as a constituent of the methionine pool.Proteins that contain selenomethionine do not contain the element in stoichiometric amounts and are often referred to as selenium-containing proteins to distinguish them from true selenoproteins. Small molecule forms of uncharacterized selenium are involved in homeostasis of the element. Those forms account for approximately 3% of plasma selenium under steady state conditions. 10

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.