Impact of selenite and selenate on differentially expressed genes in rat liver examined by microarray analysis.

Sodium selenite and sodium selenate are approved inorganic Se (selenium) compounds in human and animal nutrition serving as precursors for selenoprotein synthesis. In recent years, numerous additional biological effects over and above their functions in selenoproteins have been reported. For greater insight into these effects, our present study examined the influence of selenite and selenate on the differential expression of genes encoding non-selenoproteins in the rat liver using microarray technology. Five groups of nine growing male rats were fed with an Se-deficient diet or diets supplemented with 0.20 or 1.0 mg of Se/kg as sodium selenite or sodium selenate for 8 weeks. Genes that were more than 2.5-fold up- or down-regulated by selenite or selenate compared with Se deficiency were selected. GPx1 (glutathione peroxidase 1) was up-regulated 5.5-fold by both Se compounds, whereas GPx4 was up-regulated by only 1.4-fold. Selenite and selenate down-regulated three phase II enzymes. Despite the regulation of many other genes in an analogous manner, frequently only selenate changed the expression of these genes significantly. In particular, genes involved in the regulation of the cell cycle, apoptosis, intermediary metabolism and those involved in Se-deficiency disorders were more strongly influenced by selenate. The comparison of selenite- and selenate-regulated genes revealed that selenate may have additional functions in the protection of the liver, and that it may be more active in metabolic regulation. In our opinion the more pronounced influence of selenate compared with selenite on differential gene expression results from fundamental differences in the metabolism of these two Se compounds.