Dietary Selenium Supplementation and Whole Blood Gene Expression in Healthy North American Men
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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.
KeywordsSelenium Supplementation Gene expression T lymphocyte Natural killer cell Microarray
U.S. Department of Agriculture CRIS Project Nos. 5306-51530-009-00D and 5306-51530-018-00D supported this research. The authors gratefully acknowledge the excellent technical assistance of the Human Studies Unit of WHNRC and the clinical staff of the UC Davis Cowell Student Health Center for their assistance with the conduct of this study. The UC Davis Cancer Center Gene Expression Resource supported by NCI Cancer Center Support Grant P30 CA93373 performed the microarray labeling, hybridizations, and scanning. Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the U.S. Department of Agriculture or the University of California, nor does it imply approval to the exclusion of other products that may be suitable. The opinions expressed herein represent those of the authors and do not necessarily represent those of the U.S. Department of Agriculture or the University of California. USDA is an equal opportunity provider and employer.
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