Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro (original) (raw)

Molecular Psychiatry volume 6, pages 246–248 (2001)Cite this article

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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References

  1. Casebolt TL, Jope RS . Effects of chronic lithium treatment on protein kinase C and cyclic AMP dependent protein phosphorylation Biol Psychiatry 1991 29: 233–243
    Article CAS PubMed Google Scholar
  2. Lenox RH, Watson DG, Patel J, Ellis J . Chronic lithium administration alters a prominent PKC substrate in rat hippocampus Brain Res 1992 570: 333–340
    Article CAS PubMed Google Scholar
  3. Manji HK, Etcheberrigaray R, Chen G, Olds JL . Lithium decreases membrane-associated protein kinase C in hippocampus: selectivity for the alpha isozyme J Neurochem 1993 61: 2303–2310
    Article CAS PubMed Google Scholar
  4. Chen G, Manji HK, Hawver DB, Wright CB, Potter WZ . Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro J Neurochem 1994 63: 2361–2364
    Article CAS PubMed Google Scholar
  5. Bitran JA, Manji HK, Potter WZ, Gusovsky F . Down-regulation of PKC alpha by lithium in vitro Psychopharmacol Bull 1995 31: 449–452
    CAS PubMed Google Scholar
  6. Manji HK, Chen G, Hsiao JK, Risby ED, Masana MI, Potter WZ . Regulation of signal transduction pathways by mood-stabilizing agents: implications for the delayed onset of therapeutic efficacy J Clin Psychiatry 1996 57: 34–46
    CAS PubMed Google Scholar
  7. Manji HK, Bebchuk JM, Moore GJ, Glitz D, Hasanat KA, Chen G . Modulation of CNS signal transduction pathways and gene expression by mood-stabilizing agents: therapeutic implications J Clin Psychiatry 1999 60: (suppl 2) 27–39
    PubMed Google Scholar
  8. Speizer LA, Watson MJ, Brunton LL . Differential effects of omega-3 fish oils on protein kinase activities in vitro Am J Physiol 1991 261: E109–E114
    CAS PubMed Google Scholar
  9. Holian O, Nelson R . Action of long-chain fatty acids on protein kinase C activity: comparison of omega-7 and omega-3 fatty acids Anticancer Res 1992 12: 975–980
    CAS PubMed Google Scholar
  10. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E et al. Omega 3 fatty acids in bipolar disorder Arch Gen Psychiatry 1999 56: 407–412
    Article CAS PubMed Google Scholar
  11. Stoll AL, Locke CA, Marangell LB, Severus WE . Omega-3 fatty acids and bipolar disorder: a review Prostaglandins, Leukotrienes and Essential Fatty Acids 1999 60: 329–337
    Article CAS Google Scholar
  12. Manji HK, Lenox RH . Ziskind-Somerfeld Research Award. Protein kinase C signaling in the brain: molecular transduction of mood stabilization in the treatment of manic-depressive illness Biol Psychiatry 1999 15: 1328–1351
    Article Google Scholar
  13. Chen G, Zeng WZ, Yuan PX, Huang LD, Jiang YM, Zhao ZH et al. The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein Bcl-2 in the CNS J Neurochem 1999 72: 879–882
    Article CAS PubMed Google Scholar
  14. Chen RW, Chuang DM . Long-term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity J Biol Chem 1999 275: 6039–6042
    Article Google Scholar
  15. Manji HK, Moore GJ, Chen G . Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness J Clin Psychiatry 2000 61: (suppl9) 82–96
    CAS PubMed Google Scholar
  16. Hardy SJ, Ferrante A, Robinson BS, Johnson DW, Poulos A, Clark KJ et al. In vitro activation of rat brain protein kinase C by polyenoic very-long-chain fatty acids J Neurochem 1994 62: 1546–1551
    Article CAS PubMed Google Scholar
  17. Chen SJ, Klann E, Gower MC, Powell CM, Sessoms JS, Sweatt JD . Studies with synthetic peptide substrates derived from the neuronal protein neurogranin reveal structural determinants of potency and selectivity for protein kinase C Biochemistry 1993 2: 1032–1039
    Article Google Scholar

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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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Authors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, 77030, Texas, USA
    H F Seung Kim & L B Marangell
  2. Department of Neuroscience, Baylor College of Medicine, Houston, 77030, Texas, USA
    E J Weeber & J D Sweatt
  3. Psychopharmacology Research Laboratory, McLean Hospital, Belmont, MA, USA
    A L Stoll
  4. Department of Psychiatry, Harvard Medical School, Boston, MA, USA
    A L Stoll

Authors

  1. H F Seung Kim
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  2. E J Weeber
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  3. J D Sweatt
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  4. A L Stoll
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  5. L B Marangell
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Correspondence toL 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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