Action of long-chain fatty acids on protein kinase C activity: comparison of omega-6 and omega-3 fatty acids.

The results presented in this paper indicate that long chain free fatty acids have a dual modulatory effect on Protein Kinase C (PKC) activity purified from rat colon. Saturated (stearic) and monounsaturated (oleic) fatty acids are weak activators of PKC in the absence of phosphatidyl serine (PS) and diolein (DO), but have no significant effect on the PS/DO stimulated activity. Increasing the degree of unsaturation of the fatty acid, such as linolenic, arachidonic and eicosapentaenoic acids, also increases their stimulatory action toward unstimulated PKC, as well as their inhibition of PS/DO stimulated enzyme activity. Within this group of fatty acids there is no significant difference in the response of PKC toward omega-6 versus omega-3 type fatty acids. However, docosahexaenoic acid, a 22 carbon omega-3 polyunsaturated fatty acid found primarily in fish oil affected PKC differently from all other fatty acids studied. This compound was unable to stimulate dormant PKC activity, but was a highly potent inhibitor of PS/DO stimulated PKC. It is hypothesized that the inhibitory action of this omega-3 fatty acid may contribute to the protective role of fish oil consumption on colon tumorigenesis.