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

Abstract

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 32P-PO4 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 μmol 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.

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Acknowledgements

Financial Support: NARSAD Independent Investigator Award (DJS), NIH R01AT00161–01 (LBM, ALS). These data were presented in part at the Society of Biological Psychiatry Annual Meeting, May 2000.

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Correspondence to L B Marangell.

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Seung Kim, H., Weeber, E., Sweatt, J. et al. Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro. Mol Psychiatry 6, 246–248 (2001). https://doi.org/10.1038/sj.mp.4000837

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