Effects of ethanol on protein kinase C activity induced by filamentous actin

Protein kinase C (PKC) can be activated by interaction with filamentous act in (F-actin) in the absence of membrane lipids (S.J. Slater, S.K. Milano, B .A. Stagliano, K.J. Gergich, J.P. Curry, F.J. Taddeo and C.D. Stubbs, Bioch emistry 39 (2000) 271-280). Here, the effects of ethanol on the F-actin-ind uced activities of a panel of PKC isoforms consisting of 'conventional' (cP KC) alpha, betaI, gamma, 'novel' (nPKC) delta, epsilon and 'atypical' (aPKC ) zeta were investigated using purified PKC and F-actin. Ethanol was found to inhibit the Ca2+- and phorbol ester-dependent activities of cPKC alpha a nd betaI, and the Ca2+- and phorbol ester-independent activity of cPKC gamm a, whereas the activities of nPKC delta, epsilon and aPKC zeta were unaffec ted. Although the activities of cPKC alpha and betaI induced by saturating levels of phorbol ester were inhibited by ethanol, the binding of these iso zymes to F-actin was unaffected within the same phorbol ester concentration range. Conversely, within submaximal levels of phorbol ester, cPKC alpha a nd betaI activities were unaffected by ethanol whereas binding to F-actin w as inhibited. The potency of the inhibition of F-actin-induced cPKC betaI a ctivity increased with n-alkanol chain length up to n-hexanol, after which it declined. The results indicate that PKC activities associated with F-act in, and therefore cellular processes involving the actin cytoskeleton, are potential targets for ethanol action. The effects of ethanol on these proce sses may differ according to the particular regulating PKC isoform, its int racellular localization and the presence of activators and cofactors. (C) 2 001 Elsevier Science B.V. All rights reserved.