Submitted to: Omics - A Journal Of Integrative Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2016
Publication Date: 3/30/2016
Citation: Sinha, I., Karagoz, K., Fogle, R.L., Hollenbeak, C.S., Zea, A.H., Arga, K.Y., Stanley, A.E., Hawkes, W.C., Sinha, R. 2016. ‘‘Omics’’ of Selenium Biology: A Prospective Study of Plasma Proteome Network Before and After Selenized-Yeast Supplementation in Healthy Men. Omics - A Journal Of Integrative Biology. Vol 20(4), 2016;DOI: 10.1089/omi.2015.0187.

Interpretive Summary: Selenium is an essential mineral and deficiency causes Keshan Disease, a cardiomyopathy found primarily in China. Other muscle tissue abnormalities are also caused by selenium deficiency. Other conditions, including cancer, have been associated with low selenium status but cause-effect associations are not certain. In the present study global proteomic analysis was used to compare plasma samples from a randomized, double-blind, controlled intervention trial among 22 men consuming selenium-enriched yeast versus a control group of 20 men consuming yeast with normal selenium levels for 48 weeks. Yeast was used as the source of selenium to be comparable to natural, dietary sources of selenium from food. The proteomic analysis revealed that the plasma concentrations of several proteins were altered after the interventions. These proteins were involved in blood clotting and other immune function pathways, lipid metabolism and insulin-mediated regulation of blood glucose, suggesting a role for selenium at normal dietary levels in regulating these pathways. These novel observations from a human intervention trial suggest that selenium may have previously unappreciated roles in maintaining health.

Technical Abstract: Low selenium levels have been linked to a higher incidence of cancer and other diseases, including Keshan,Chagas, and Kashin–Beck, and insulin resistance. Additionally, muscle and cardiovascular disorders, immune dysfunction, cancer, neurological disorders, and endocrine function have been associated with mutations in genes encoding for selenoproteins. Selenium biology is complex, and a systems biology approach to study global metabolomics, genomics, and/or proteomics may provide important clues to examining selenium-responsive markers in circulation. In the current investigation, we applied a global proteomics approach on plasma samples collected from a previously conducted, double-blinded placebo controlled clinical study, where men were supplemented with selenized-yeast (Se-Yeast; 300 lg/day, 3.8 lmol/day) or placebo-yeast for 48 weeks. Proteomic analysis was performed by iTRAQ on 8 plasma samples from each arm at baseline and 48 weeks. A total of 161 plasma proteins were identified in both arms. Twenty-two proteins were significantly altered following Se-Yeast supplementation and thirteen proteins were significantly changed after placebo-yeast supplementation in healthy men. The differentially expressed proteins were involved in complement and coagulation pathways, immune functions, lipid metabolism, and insulin resistance. Reconstruction and analysis of protein–protein interaction network around selected proteins revealed several hub proteins. One of the interactions suggested by our analysis,PHLD-APOA4, which is involved in insulin resistance, was subsequently validated by Western blot analysis. Our systems approach illustrates a viable platform for investigating responsive proteomic profile in ‘before and after’condition following Se-Yeast supplementation. The nature of proteins identified suggests that selenium may play an important role in complement and coagulation pathways, and insulin resistance.