A COMPARISON OF THE EFFECTS OF DIETARY SELENIUM ON SELENOPROTEIN EXPRESSION IN RAT-BRAIN AND LIVER

In studies with rodents, when dietary supplies of the essential nutrie nt Se are restricted, in most tissues there are parallel substantial l osses of the element and the important antioxidant selenoenzyme glutat hione peroxidase (GPx) for which it is a cofactor. In brain, however, there appears to be both a sequestration of Se and a conservation of G Px activity when dietary Se is limited. To further explore the relatio n between these phenomena, we have undertaken a comparison of the effe cts of diets low, normal and high in Se on GPx activity, and labeling of selenoproteins following short-term (72 h) in vivo exposure to Se-7 5, in subcellular fractions from rat brain and liver, the latter servi ng as a representative tissue which does not retain Se and is depleted of most GPx activity following dietary restriction. Brains and livers from animals on the three diets showed different patterns of response with respect to both GPx activity and retention of the Se-75 dose. Th e low-Se diet (0.006 ppm) substantially reduced GPx activity in liver but not brain, while high levels (1 ppm) did not increase GPx in eithe r tissue relative to a normal (0.1 ppm) intake. The Se-75 was retained in brain homogenates and subcellular fractions to the greatest extent by rats on the restricted diet, while in liver, retention was greater in rats fed the normal supplement than in animals on either the low- or high-Se diets. Levels of non-protein-bound Se-75 were higher in bra in than liver and increased with dietary Se in both tissues. When prot eins in brain and liver homogenates and subcellular fractions where se parated by one-dimensional SDS-PAGE and exposed to X-ray film, the res ulting autoradiograms revealed the existence of seven distinct selenop rotein bands in brain and eight in liver. Different patterns of seleno protein expression were observed in subcellular fractions isolated fro m both tissues. Dependence of levels of individual selenoproteins on d iet paralleled the effects on Se-75 retention. Dietary influences on e xpression of protein bands tentatively identified as GPx were more pro nounced in liver than brain. All of these observations provide further evidence of the unique nature of Se metabolism in brain.