PROTEIN-KINASE-C ISOZYME PATTERN IN LIVER HYPERPLASIA

Lead nitrate, a potent activator of protein kinase C, is able to induc e reversible rat liver hyperplasia. This phenomenon shows sex-related growth differences: liver hyperplasia as well as its regression by apo ptosis occurred earlier and was more pronounced in male than in female rats. Dietary choline administration to females causes a shift of gro wth pattern towards the male values. Analysis of protein kinase C isoe nzymes with hydroxylapatite column chromatography at time points cruci al for lead-induced liver proliferation in male, female and choline-tr eated female rats showed a significant down-regulation of beta and a P KC activities and a marked activation of epsilon PKC. The fluctuation of these activities could be related to the rates of DNA synthesis. Th ese data suggest that the observed PKC isoenzymes could be involved in the signal transduction pathway leading to lead-induced liver prolife ration. (C) 1994 Academic Press, Inc.