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Stimulation of map kinases and S6 kinases by sodium selenate and vanadyl sulphate

University of British Columbia

Insulin has a wide range of biological effects on mammalian cells including both metabolic and mitogenic actions. A phosphorylation cascade originating at the insulinreceptor and involving a number of different serine/threonine-protein kinases is believed to mediate, at least in part, some of these effects. The two best studied kinases within this phosphorylation cascade, MAP kinases and S6 kinases, are believed to play pivotal roles in insulin signal transduction. Both selenium and vanadium compounds have been shown to have insulin-mimetic effects on isolated rat adipocytes. In providing further evidence for their insulin-mimetic properties, their effects on the activity of MAP kinases and S6 kinases in isolated rat adipocytes were examined by measuring the phosphorylation of myelin basic protein (MBP) and Ribosomal S6 Protein, respectively. Both MBP kinases and Ribosomal Protein S6 kinases were shown to be activated in response to insulin treatment of adipocytes thus confirming the suitability of this system for the investigation of insulin-mimetic agents. Sodium selenate and vanadyl sulphate treatment of cells led to dose and time-dependent stimulation of both MBP kinases and Ribosomal Protein S6 kinases. Maximal stimulation ofMBP kinases by sodium selenate was ∽2-fold control while Ribosomal Protein S6 kinases were stimulated to over 8-fold control. Vanadyl sulphate treatment led to higher levels of stimulation with MBP kinase activity being ∽5-fold control and Ribosomal Protein S6 kinase activity reaching levels that were greater than 16- fold control. Anion-exchange chromatography of the crude cell extracts revealed several distinct peaks of MBP and Ribosomal Protein S6 kinase activity corresponding to previous reports in the literature, however no distinct kinase families were conclusively identified using immunological techniques. Our results further confirm the insulin-mimetic properties of selenium and vanadium compounds. Both were shown to stimulate kinases within the signal transduction cascade of insulin to a greater degree than insulin itself. The distinct families of MAP- and S6 kinases stimulated by these agents were not identified although the presence more than one family for each group of kinases was indicated.

Thesis/Dissertation

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2009-02-26

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http://hdl.handle.net/2429/5130

Pharmacology

University of British Columbia

UBCV

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