Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro.
Preliminary clinical data indicate that omega-3 fatty acids may be effective mood stabilizers for patients with bipolar disorder. Both lithium and valproic acid are known to inhibit protein kinase C (PKC) activity after subchronic administration in cell culture and in vivo. The current study was undertaken to determine the effects of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on protein kinase C phosphotransferase activity in vitro. Various concentrations of DHA, EPA, and arachidonic acid (AA) were incubated with the catalytic domain of protein kinase C beta from rat brain. Protein kinase C activity was measured by quantifying incorporation of (32)P-PO(4) into a synthetic peptide substrate. Both DHA and EPA, as well as the combination of DHA and EPA, inhibited PKC activity at concentrations as low as 10 micromol l(-1). In contrast, arachidonic acid had no effect on PKC activity. Thus, PKC represents a potential site of action of omega-3 fatty acids in their effects on the treatment of bipolar disorder.
Seung Kim
H F
HF
Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030, USA.
Weeber
E J
EJ
Sweatt
J D
JD
Stoll
A L
AL
Marangell
L B
LB
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D001095:Arachidonic Acids; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D011493:Protein Kinase C