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Nutritional Sciences Group, and Departments of Biochemistry, and Food Science and Human Nutrition, University of Missouri, Columbia, MO 65211
Phospholipid hydroperoxide glutathione peroxidase (PHGPX) and classical glutathione peroxidase (GPX1) are encoded by separate genes with only about 40% amino acid and nucleic acid sequence identity. To determine the response of tissue PHGPX expression to dietary Se level and to compare these responses with those for GPX1, weanling male rats were fed amino acid diets containing from 2 (-Se) to 130 (+Se) µg Se/kg diet or a torula diet containing 5 and 190 µg Se/kg diet as Na2SeO3 for 28 d. Tissues were analyzed for PHGPX and GPX1 activity and mRNA. There was no effect of Se on growth. In -Se rats, GPX1 activity was reduced to 1% in liver and 49% in heart, kidney and lung compared with +Se rats; PHGPX activity was reduced only to 2550% in these four tissues. The Se response curves indicated that the dietary Se requirement to reach plateau liver PHGPX activity was half that required for plateau GPX activity. In -Se rats, liver and heart GPX1 mRNA levels were reduced to 6 and 12%, respectively, whereas PHGPX mRNA was not significantly affected by Se deficiency. Notably, 65 µg Se/kg diet resulted in plateau liver GPX1 mRNA levels but not plateau GPX activity. Testis had the lowest GPX activity and GPX1 mRNA of all tissues examined, but had 15-fold higher PHGPX activity and 45-fold higher PHGPX mRNA levels when compared with liver. There was no significant effect of dietary Se on testis GPX1 and PHGPX mRNA levels. This study demonstrates that these two selenoperoxidases are differentially regulated by dietary Se. Differences in Se regulation of mRNA levels in liver and heart were even more pronounced than for enzyme activity. The lack of any significant effect of reduced dietary Se on PHGPX mRNA levels suggests that there are detailed underlying molecular mechanisms whereby Se status regulates GPX1 mRNA levels but not PHGPX mRNA levels.
KEY WORDS: gene expression glutathione peroxidase selenium deficiency mRNA rats
1 A preliminary report of this work was presented at Experimental Biology 94, April, 1994, Anaheim, CA [Lei, X. G., Evenson, J. K., Thompson, K. M. & Sunde, R. A. (1994) Effect of dietary selenium on phospholipid hydroperoxide glutathione peroxidase activity and gene expression in rats. FASEB J. 8: A540 (abs.)].
2 Supported by the University of Missouri Agricultural Experiment Station and the Food for the 21st Century program, and by NIH grants no. DK 43491 and no. CA 45164.
3 The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
4 Current address: Department of Animal Science, Cornell University, Ithaca, NY 14853.
5 To whom correspondence should be addressed.
Manuscript received 1 September 1994. Revision accepted 5 January 1995.
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