Dietary Selenium Supplementation and Whole Blood Gene Expression in Healthy North American Men

Selenium (Se) is a trace nutrient required in microgram amounts, with a recommended dietary allowance of 55 μg/day in humans. The nutritional functions of Se are performed by a group of 25 selenoproteins containing the unusual amino acid selenocysteine at their active sites. The selenoproteins with known activities are oxidation–reduction enzymes with roles in antioxidant protection, redox homeostasis and signaling, and thyroid hormone metabolism. Both deficiencies and excesses of Se are associated with impaired innate and adaptive immune responses. We supplemented 16 healthy men for 1 year with 300 μg Se/day as high-Se yeast or placebo yeast and measured whole blood gene expression with DNA microarrays before and after supplementation. Protein phosphorylation was the main biological process in common among the Se-responsive genes, which included a prominent cluster of protein kinases, suggesting that protein phosphorylation in leukocytes is sensitive to Se supplementation. We found highly ranked clusters of genes associated with RNA processing and protein transport, suggesting that dietary Se may regulate protein expression in leukocytes at both the posttranscriptional and posttranslational levels. The main functional pathway affected by Se supplementation was FAS apoptosis signaling, and expression of genes associated with T cell and natural killer cell cytotoxicity was increased. At the same time, the numbers of circulating natural killer and T cells expressing activation markers decreased. These changes are consistent with an anti-inflammatory effect of Se supplementation exerted through regulation of protein phosphorylation.