Chronic ethanol exposure increases levels of protein kinase C delta and epsilon and protein kinase C-mediated phosphorylation in cultured neural cells.
Exposure to ethanol for several days increases the number and function of dihydropyridine-sensitive Ca2+ channels in excitable tissues. In the neural cell line PC12, this process is blocked by inhibitors of protein kinase C (PKC), suggesting that PKC mediates ethanol-induced increases in Ca2+ channels. We report that treatment with 25-200 mM ethanol for 2-8 days increased PKC activity in PC12 cells and NG108-15 neuroblastoma-glioma cells. Detailed studies in PC12 cells showed that ethanol also increased phorbol ester binding and immunoreactivity to PKC delta and PKC epsilon. These changes were associated with increased PKC-mediated phosphorylation. Ethanol did not activate the enzyme directly, nor did ethanol increase levels of diacylglycerol. Ethanol-induced increases in PKC levels may promote up-regulation of Ca2+ channels, and may also regulate the expression and function of other proteins involved in cellular adaptation to ethanol.
Messing
R O
RO
Department of Neurology, University of California, San Francisco.
Petersen
P J
PJ
Henrich
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D015151:Immunoblotting; D007700:Kinetics; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate