DIETARY MODULATION OF EPIDERMAL PROTEIN-KINASE-C - MEDIATION BY DIACYLGLYCEROL

Studies on the mechanism of dietary fat and energy modulation of skin carcinogenesis suggest that these diets may act through the cellular b inding site of the phorbol ester tumor promoters, protein kinase C (PK C). High-fat diets increase the activity of PKC but have no impact on the steady-state protein levels. Energy restriction reduces the activi ty of PKC, presumably through reduction in the steady-state levels of particular isoenzymes (PKC alpha and PKC xi). Phorbol-binding studies with epidermal cells from mice fed energy-restricted diets indicated a reduction of phorbol-binding sites in these cells. Investigations int o lipid metabolism showed that both dietary fat and energy restriction increased epidermal cell diacylglycerol (DAG). The increase in DAG in cells from energy-restricted mice may be due to increased turnover of phosphatidylinositol, as was evident in the reduced phosphatidylinosi tol-4-phosphate and phosphatidylphositol-4,5-biphosphate and elevated inositol biphosphinate and inositol triphosphate in these cells.