Differential effects of omega-3 fish oils on protein kinase activities in vitro.
We studied the in vitro effects of omega-3 fish oils and other fatty acids on the activity of crude protein kinase C from S49 lymphoma cells, on partially purified enzyme from rat cerebrum, on homogeneous protein kinase C from bovine brain, and, for comparison, on type I adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. In the absence of exogenous phospholipid, the fish oils cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and acid (DCHA) enhance the catalytic cis-4,7,10,13,16,19-docosahexaenoic activity of protein kinase C and support the binding of [3H]phorbol 12,13-dibutyrate, both to approximately 50% of the level supported by phosphatidylserine. In the presence of phosphatidylserine, the omega-3 fatty acids reduce catalytic activity and [3H]phorbol 12,13-dibutyrate binding by about one-half. The effects of the omega-3 fatty acids on enzyme activity suggest that fish oils act as partial agonists competitively with phosphatidylserine. EPA, DCHA, and arachidonate (but not a variety of saturated fatty acids) inhibit the cAMP-dependent protein kinase. Thus dietary fish oils and cellular fatty acids mobilized by the action of phospholipase A2 may differentially modulate the activities of protein kinase C and cAMP-dependent protein kinase. These data suggest means by which unsaturated fatty acids mobilized within cells may act as second messengers.
Speizer
L A
LA
Department of Pharmacology, University of California School of Medicine, San Diego, La Jolla 92093.
Watson
M J
MJ
Brunton
L L
LL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D003514:Cyclohexylamines / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008223:Lymphoma; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D003514:Cyclohexylamines; D004791:Enzyme Inhibitors; D015525:Fatty Acids, Omega-3; D010743:Phospholipids; C011769:dicyclohexylamine; D015118:Eicosapentaenoic Acid; D011494:Protein Kinases; D011493:Protein Kinase C; D002118:Calcium