ETHANOL DIFFERENTIALLY AFFECTS METABOLIC AND MITOTIC PROCESSES IN CHICK EMBRYONIC-CELLS

Our laboratory has been investigating the mechanisms by which ethanol- induced growth inhibition occurs in a developing embryo, and our studi es have focused on disruption of cellular signaling pathways, Previous work on ethanol-induced changes in signaling systems that regulate or nithine decarboxylase activity indicated that the pathways containing protein kinase A, protein kinase C (PKC), and insulin-dependent tyrosi ne kinase were important for the control of ornithine decarboxylase in chick embryonic cells, Herein, we report ethanol's effect on the regu lation of glucose uptake and thymidine uptake by these same kinase pat hways. A pronounced increase in glucose uptake was associated with PKC downregulation in both vehicle- and ethanol-exposed cells, with the l arger increase occurring in ethanol-exposed cells, An increase in thym idine uptake was associated with an activation of all three kinases, a s well as with downregulation of PKC. Because previous work on signali ng pathways has looked for changes in the insulin signaling pathway, t he work herein focuses on the signaling pathways involving protein kin ase A and PKC, cAMP levels were increased by ethanol treatment, but th e increase was relatively small. Analysis of changes in PKC activity i nduced by ethanol exposure showed a significant suppression of PKC act ivity in the ethanol-treated cells and suggested that, overall, ethano l treatment affects the regulation of glucose uptake in embryonic cell s predominantly by PKC downregulation.