Dietary Selenium Affects Homocysteine Metabolism Differently in Fisher-344 Rats and CD-1 Mice ,4

Abstract

In our previous work with rats, plasma and tissue homocysteine concentrations were decreased by selenium deprivation. The purpose of this study was to follow up and expand on that work by determining the effects of selenium status (deficient, adequate, and supranutritional) on several aspects of homocysteine metabolism involving methionine recycling and transsulfuration. A 2nd objective was to determine whether there are differences in how selenium status affects homocysteine metabolism in rats and mice. Male weanling Fischer-344 rats and male weanling CD-1 mice were fed diets containing 0, 0.2, or 2.0 μg selenium (as sodium selenite)/g for 72 d or 60 d, respectively. Plasma homocysteine and cysteine were significantly decreased by feeding rats or mice the selenium-deficient diet compared with feeding adequate or supranutritional selenium. On the other hand, plasma glutathione was increased by selenium deficiency only in rats. Also, the specific activities of liver betaine homocysteine methyltransferase and glycine N-methyltransferase were decreased by selenium deficiency in rats, but were unaffected by selenium status in mice. Real-time RT-PCR was used to determine the expression of the subunits of glutamate-cysteine ligase, which catalyzes the rate-limiting step in glutathione biosynthesis. The expression of Gclc, the catalytic subunit of glutamate-cysteine ligase, was upregulated by selenium deprivation in both rat and mouse liver. Gclm, the modifier subunit of glutamate-cysteine ligase, was downregulated in rats fed 2 μg Se/g compared with rats fed adequate or deficient selenium. Based on these findings, it is evident that selenium deficiency has different outcomes in mice and rats. These variables are all related to methionine/methyl metabolism. Although only one strain of rat was compared with one strain of mouse, this work suggests that differences between species may prove vital in determining which animal model is used in studies of selenium deficiency or in studies that are designed to ascertain chemopreventive mechanisms of selenium.