Author
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Uthus, Eric |
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ROSS, SHARON - NIH/NCI |
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Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/4/2007 Publication Date: 4/1/2007 Citation: Uthus, E.O., Ross, S.A. 2007. Dietary selenium affects homocysteine metabolism differently in Fisher-344 rats and CD-1 mice. Journal of Nutrition. 137:1132-1136. Interpretive Summary: Our previous work showed that plasma and tissue homocysteine concentrations are decreased by selenium deprivation in rats. 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 key aspects of homocysteine metabolism. A second objective was to determine if there are differences in how selenium status affects homocysteine metabolism in rats vs. mice. We found, as before, that plasma homocysteine was decreased by selenium deficiency in both rats and mice. However, we found that glutathione, a compound that is important in oxidative defense and that can be derived from homocysteine, was increased by selenium deficiency only in the rat. We also found differences between the rat and mouse in the activities of several enzymes important in homocysteine and glutathione metabolism. Based on these findings, it is evident that selenium deficiency can result in different outcomes in mice and rats as related to homocysteine and glutathione metabolism. Thus, the species differences may prove vital in determination of which animal model is used in studies of selenium deficiency or in studies that are designed to ascertain cancer preventive actions of selenium. Furthermore, these results emphasize the dilemma when translating the results of selenium studies from laboratory animals to humans. Technical Abstract: Our previous work showed that plasma and tissue homocysteine concentrations are decreased by selenium deprivation in rats. 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 key aspects of homocysteine metabolism involving methionine recycling and transsulfuration. A second objective was to determine if there are species differences in how selenium status affects homocysteine metabolism. 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. After 72 d (rats) or 60 d (mice) plasma homocysteine was significantly decreased by selenium deprivation. On the other hand, plasma glutathione was increased by selenium deficiency only in the rat. Also, the specific activities of liver betaine homocysteine methyltransferase and glycine N-methyltransferase were decreased by selenium deficiency in the rat, 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 the rat and mouse liver. Gclm, the modifier subunit of glutamate-cysteine ligase, was upregulated by selenium deprivation only in the rat. Based on these findings, it is evident that selenium deficiency can result in different outcomes in mice and rats. These parameters are all related to methionine/methyl metabolism. Thus, the species differences may prove vital in determination of which animal model is used in studies of selenium deficiency or in studies that are designed to ascertain chemopreventive mechanisms of selenium. Furthermore, these results emphasize the dilemma when translating the results of selenium studies from laboratory animals to humans. |
