title: Selenium: potent stimulator of tyrosyl phosphorylation and activator of MAP kinase.
abstract: Selenium, an essential biological trace element, is an integral component of several enzymes, and its use as a nutritional supplement has been popularized recently due to its potential role in low concentrations as an antioxidant and in higher concentrations as an anticancer agent. Selenium has also been reported to act as an insulin-mimetic agent with regard to normalization of blood glucose levels and regulation of some insulin-mediated metabolic processes. Little work, however, has been done concerning the pathway(s) by which this insulin-mimetic action occurs. In this study, we investigated the mechanism by which selenate exhibits insulin-mimetic properties in two different insulin responsive cell types, primary rat hepatocytes and 3T3 L1 adipocytes. We found that two proteins associated with the insulin signal cascade, the beta-subunit of the insulin receptor and IRS-1, increased in tyrosyl phosphorylation in the presence of selenium. The third identified selenium activated signal protein, MAP kinase, has been implicated not only in the insulin signal transduction pathway but also in other growth factor-mediated responses. Using an in-gel activity assay for MAP kinase, we demonstrated that both the p42 and p44 MAP kinases are activated when either hepatocytes or adipocytes are incubated in the presence of selenate. In addition to the activation of these specific proteins, we found that selenium also eventually profoundly affected overall tyrosyl phosphorylation. Our results therefore show that selenium not only increased the phosphorylation of proteins identified in the insulin signal cascade but also affected the overall phosphorylation state of the cell.
authors.affiliation: Department of Chemistry, Western Michigan University, Kalamazoo, USA. susan.stapleton@wmich.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Stapleton
authors.forename: G L
authors.initials: GL
authors.lastname: Garlock
authors.forename: L
authors.initials: L
authors.lastname: Foellmi-Adams
authors.forename: R F
authors.initials: RF
authors.lastname: Kletzien
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D019000:Phosphotyrosine; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D064429:Fatty Acid Synthases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D012643:Selenium; D005947:Glucose