PMID: 7536887Apr 1, 1995Paper

Effects of chromium on basal and insulin-induced tyrosine phosphorylation in H4 hepatoma cells: comparison with phorbol-12-myristate-13-acetate and sodium orthovanadate

Molecular Pharmacology
E J Yurkow, G Kim

Abstract

Chromium, in its various forms, is recognized both as a human carcinogen and as a nutrient essential in glucose homeostasis. Although the genotoxicity of this element is associated with its carcinogenic properties, the manner in which chromium mediates its epigenetic effects on cells, including its ability to potentiate insulin action, is not known. In the current studies, Western blotting with antiphosphotyrosine antibodies was used to study the effects of chromium on protein tyrosine phosphorylation in intact H4 rat hepatoma cells. Treatment of cells with hexavalent chromium [Cr(VI)] was found to induce the tyrosine phosphorylation of three prominent sets of proteins, having median molecular masses of 210, 125, and 87 kDa. Cr(VI) pretreatment also inhibited the insulin-induced tyrosine phosphorylation of the major substrate of the insulin receptor kinase, insulin receptor substrate-1, and its subsequent association with the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3'-kinase. Furthermore, Cr(VI) was found to alter the pattern of other p85-binding (insulin-induced) phosphoproteins that were distributed throughout the soluble and particulate fractions of cells. Virtually all of the alterations in basal and insulin...Continue Reading

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