Title: Dietary selenium supplementation and whole blood gene expression in healthy North American men Authors
Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 5, 2013
Publication Date: August 18, 2013
Citation: Hawkes, W.C., Richter, D., Alkan, Z. 2013. Dietary selenium supplementation and whole blood gene expression in healthy North American men. Biological Trace Element Research. DOI:10.1007/s12011-013-9786-5. Interpretive Summary: The essential trace nutrient selenium (Se) is required for development and function of the immune system. However, we do not understand what functions selenium performs in immune cells. We fed healthy men high-level selenium supplements for one year and measured how that affected which genes were active in blood cells. Se supplements increased activation of genes involved in killing virus-infected cells and cancer cells and decreased activity of immunoglobulin genes. The results suggest that selenium increases the potency of natural killer cells without increasing the number of natural killer cells. This may help explain how selenium, boosts immune function without increasing inflammation.
Technical Abstract: Selenium (Se) is a trace nutrient required in microgram amounts by all animals, with a recommended dietary allowance of 55 µg/d in humans. The biological 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, but the biochemical activities of most selenoproteins remain unknown. Se is essential for development and function of the immune system and its deficiency is associated with decreased humoral and cell-mediated immune responses. We supplemented healthy men for one year with 300 µg Se/d as high-Se yeast and measured the effect on whole blood gene expression using high-density oligonucleotide arrays. Gene ontology analysis was conducted on a set of 339 genes whose mRNA levels responded differently in subjects receiving high-Se yeast compared to subjects consuming low-Se yeast. The highest-ranked gene ontology term was protein phosphorylation and there was a prominent cluster of protein kinases, suggesting protein phosphorylation in leukocytes is sensitive to dietary Se. We found highly-ranked clusters of genes associated with RNA processing and protein transport, suggesting dietary Se may affect protein function at both the post-transcriptional and post-translational levels. The main leukocyte pathway affected by Se supplementation was FAS apoptosis signaling. Expression of genes associated with T cell and natural killer cell cytotoxicity was increased while expression of antigen-specific receptors was decreased.