Differential effects of omega-3 fish oils on protein kinase activities in vitro

Abstract

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.

Differential effect of polyunsaturated fatty acids on cell proliferation during human epithelial in vitro carcinogenesis: involvement of epidermal growth factor receptor tyrosine kinase

“…These studies included fatty acids of the n-6, n-7 and n-9 classes. However, studies on the action of n-3 PUFAs on signal transduction are limited, although modulation of the catalytic activity of protein kinase C and type I cAMP-dependent protein kinase has been demonstrated (Speizer et al, 1991).…”

Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro

“…Concentrations of DHA, EPA, and AA ranged from 0.1 M to 400 M, based on concentrations used in prior in vitro studies with omega-3 fatty acids. 8,9,16 Enzyme activity was measured by quantifying incorporation of 32 P-PO 4 into a synthetic peptide substrate. 17 The reaction mixture consisted of 20 ng of the catalytic subunit of PKC, 20 mM Tris-HCl (pH 7.5), 0.5 mM EGTA, 1 mM EDTA, 2 mM Na 2 PO 4 , deionized H 2 O, 20 M protein substrate, 1 mM ATP, 1 Ci ml −1 gamma-32 P-ATP, 10 mM MgCl 2 .…”

“…[1][2][3][4][5][6][7] Preliminary evidence suggests that omega-3 fatty acids may also affect PKC. 8,9 A clinical pilot study, undertaken based on this putative mechanistic commonality, concluded that omega-3 fatty acids may be effective mood stabilizers for patients with bipolar disorder. In a recent 4-month, double-blind, placebo-controlled study, outpatients who received omega-3 fatty acids in addition to stable doses of their baseline medications had a significantly longer period of remaining well than the placebo group, and performed better for nearly every other outcome measure.…”

Triacylglycerol metabolism by lymphocytes and the effect of triacylglycerols on lymphocyte proliferation

“…It seems likely that the effects of fatty acids are due to their incorporation into membrane phospholipids, altering the fatty acid composition and fluidity [42]. In other tissues and cell types such changes have been shown to affect receptor activity (see [44]) and signal transduction mechanisms (see [45,46] (Tables 5 and 6). Such an effect has not been previously reported.…”