Oleic acid promotes changes in the subcellular distribution of protein kinase C in isolated hepatocytes.

The effect of oleate on the subcellular distribution of protein kinase C (PKC) was studied in isolated hepatocytes and in perfused rat liver in the presence of physiological concentrations of serum albumin. A time- and dose-dependent translocation of PKC from the cytosol towards the membranes was observed at oleate concentrations that fell within the range of concentrations reached under several physiological conditions. Analysis of the membrane-bound isoenzymes of PKC by hydroxylapatite chromatography revealed that the beta isoenzyme was preferentially translocated to this compartment in hepatocytes incubated with oleate. Activation of PKC after incubation of hepatocytes with oleate involved at least three different effectors of the enzyme: the fatty acid itself, the diacylglycerol synthesized from oleate, and the rise in the cytosolic calcium concentration elicited by oleate. As a result of PKC activation, protein phosphorylation of intact hepatocytes in response to oleate exhibited an enhancement in the phosphate content of a protein of 82 kDa, similar to that phosphorylated in the presence of phorbol dibutyrate.