title: "Omics" of Selenium Biology: A Prospective Study of Plasma Proteome Network Before and After Selenized-Yeast Supplementation in Healthy Men.
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 μg/day, 3.8 μmol/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.
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Penn State University College of Medicine , Hershey, Pennsylvania, USA .
authors.forename: Indu
authors.initials: I
authors.lastname: Sinha
authors.affiliation: 2 Department of Bioengineering, Marmara University , Istanbul, Turkey .
authors.forename: Kubra
authors.initials: K
authors.lastname: Karagoz
authors.affiliation: 3 Department of Surgery, Penn State University College of Medicine , Hershey, Pennsylvania, USA .
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Fogle
authors.affiliation: 3 Department of Surgery, Penn State University College of Medicine , Hershey, Pennsylvania, USA .
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hollenbeak
authors.affiliation: 4 Stanley S, Scott Cancer Center and Department of Microbiology, Immunology, and Parasitology, LSU Health Sciences Center , New Orleans, Louisiana, USA .
authors.forename: Arnold H
authors.initials: AH
authors.lastname: Zea
authors.affiliation: 2 Department of Bioengineering, Marmara University , Istanbul, Turkey .
authors.forename: Kazim Y
authors.initials: KY
authors.lastname: Arga
authors.affiliation: 5 Department of Mass Spectrometry Core, Penn State University College of Medicine , Hershey, Pennsylvania, USA .
authors.forename: Anne E
authors.initials: AE
authors.lastname: Stanley
authors.affiliation: 6 United State Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, University of California Davis , California, USA .
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hawkes
authors.affiliation: 1 Department of Biochemistry and Molecular Biology, Penn State University College of Medicine , Hershey, Pennsylvania, USA .
authors.forename: Raghu
authors.initials: R
authors.lastname: Sinha
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010919:Placebos; D011446:Prospective Studies; D012643:Selenium / Q000008:administration & dosage*; D015003:Yeasts / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D010919:Placebos; D012643:Selenium