Glutathione Peroxidase and Phospholipid Hydroperoxide Glutathione Peroxidase Are Differentially Regulated in Rats by Dietary Selenium

Abstract

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 4–9% in heart, kidney and lung compared with +Se rats; PHGPX activity was reduced only to 25–50% 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.