Ia. Shibley et al., ETHANOL DIFFERENTIALLY AFFECTS METABOLIC AND MITOTIC PROCESSES IN CHICK EMBRYONIC-CELLS, Alcoholism, clinical and experimental research, 21(3), 1997, pp. 460-466
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.