title: Protein kinase C isozymes that mediate enhancement of neurite outgrowth by ethanol and phorbol esters in PC12 cells.
abstract: Using PC12 cells to study ethanol's effects on growth of neural processes, we found that ethanol enhances NGF- and basic FGF-induced neurite outgrowth. Chronic ethanol exposure selectively up-regulates delta and epsilon protein kinase C (PKC) and increases PKC-mediated phosphorylation in PC12 cells. Since PKC regulates differentiation, we investigated the role of PKC in enhancement of neurite outgrowth by ethanol. Like ethanol, 0.3-10 nM phorbol 12-myristate, 13-acetate (PMA) increased NGF-induced neurite outgrowth. However, higher concentrations did not, and immunoblot analysis demonstrated that 100 nM PMA markedly depleted cells of beta, delta and epsilon PKC. PMA (100 nM) also down-regulated beta, delta and epsilon PKC in ethanol-treated cells and completely prevented enhancement of neurite outgrowth by ethanol. In contrast, the cAMP analogue 8-bromoadenosine cAMP did not completely mimic the effects of ethanol on neurite outgrowth, and ethanol was able to enhance neurite formation in mutant PC12 cells deficient in protein kinase A (PKA). These findings implicate beta, delta or epsilon PKC, but not PKA, in the neurite-promoting effects of ethanol and PMA. Since chronic ethanol exposure up-regulates delta and epsilon, but not beta PKC, these findings suggest that delta or epsilon PKC regulate neurite outgrowth.
authors.affiliation: Department of Neurology, E. Gallo Clinic and Research Center, University of California, San Francisco.
authors.forename: R
authors.initials: R
authors.lastname: Roivainen
authors.forename: T
authors.initials: T
authors.lastname: McMahon
authors.forename: R O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D015151:Immunoblotting; D007527:Isoenzymes / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000431:Ethanol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate