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 studies have focused on disruption of cellular signaling pathways. Previous work on ethanol-induced changes in signaling systems that regulate ornithine decarboxylase activity indicated that the pathways containing protein kinase A, protein kinase C (PKC), and insulin-dependent tyrosine kinase were important for the control of ornithine decarboxylase in chick embryonic cells. Herein, we report ethanol's effect on the regulation of glucose uptake and thymidine uptake by these same kinase pathways. A pronounced increase in glucose uptake was associated with PKC downregulation in both vehicle- and ethanol-exposed cells, with the larger increase occurring in ethanol-exposed cells. An increase in thymidine uptake was associated with an activation of all three kinases, as well as with downregulation of PKC. Because previous work on signaling pathways has looked for changes in the insulin signaling pathway, the work herein focuses on the signaling pathways involving protein kinase A and PKC. cAMP levels were increased by ethanol treatment, but the increase was relatively small. Analysis of changes in PKC activity induced by ethanol exposure showed a significant suppression of PKC activity in the ethanol-treated cells and suggested that, overall, ethanol treatment affects the regulation of glucose uptake in embryonic cells predominantly by PKC downregulation.
Shibley
I A
IA
Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina, USA.
Carver
F M
FM
Pennington
S N
SN
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism
D000431:Ethanol; D011493:Protein Kinase C; D005947:Glucose