SELECTIVE CHANGES IN PROTEIN-KINASE-C ISOFORMS AND PHOSPHORYLATION OFENDOGENOUS SUBSTRATE PROTEINS IN RAT CEREBRAL-CORTEX DURING PRENATAL AND POSTNATAL ETHANOL EXPOSURE

The effect of pre- and postnatal ethanol exposure on protein kinase C (PKC) activity, immunochemical analysis of PKC alpha, beta I, beta II, gamma, delta, epsilon, eta, and zeta by isoform-specific antibodies, and in vitro phosphorylation of endogenous substrate proteins was inve stigated in rat cerebral cortex. The PKC activity was increased throug hout the development. However, the activity at the age of 8 days was s ignificantly high in cytosolic and membrane fractions from ethanol-tre ated rats. Immunochemical analysis showed increased levels of PRC beta I and beta II at the age of 8 days, and a decrease in delta isoform a t 8, 30, and 90 days of age. PKC isoforms alpha, gamma, epsilon, and e ta showed no appreciable change in ethanol-treated rats. PKC zeta leve ls were high in the cytosolic fraction from ethanol-treated samples of 90 days age. lit vitro phosphorylation of endogenous substrate protei ns in the presence of Ca2+/phospholipid showed increased phosphorylati on of selective membrane and cytosolic proteins with 87, 65, 50, 43, 3 6, and 29 kDa in ethanol-treated rats. The phosphorylation of these pr oteins decreased in the presence of staurosporine, which also supporte d PKC-mediated phosphorylation. Increased PKC activity, activation of beta I and beta II isoforms, decreased levels of delta isoform, and ph osphorylation of selective substrate proteins in cerebral cortex due t o alcohol exposure might be relevant in ethanol-induced central nervou s system dysfunction and fetal alcohol syndrome. (C) 1998 Academic Pre ss.