Protein kinase C and adaptation to ethanol.
Adaptation to chronic ethanol exposure results in a decrease in sensitivity to the intoxicating effects of ethanol. Recent evidence indicates that changes in the expression and function of certain proteins involved in signal transduction are important for adaptation to ethanol. Using the neural cell line PC12, we found that chronic exposure to ethanol increases the expression and function of L-type voltage-gated calcium channels and enhances neural differentiation induced by nerve growth factor. Both of these responses to ethanol require protein kinase C (PKC). Chronic ethanol exposure activates PKC-mediated phosphorylation, in part, by increasing the expression of two PKC isozymes, delta and epsilon. The PKC family of enzymes may be important targets for the development of drugs that could modify adaptive and toxic consequences of chronic ethanol exposure.
Ernest Gallo Clinic & Research Center, Department of Neurology, University of California, San Francisco 94110.
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Roivainen
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Hundle
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Messing
D000064:Acclimatization; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D007527:Isoenzymes / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015220:Calcium Channels; D007527:Isoenzymes; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium