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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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
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
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
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
Bitran JA, Manji HK, Potter WZ, Gusovsky F . Down-regulation of PKC alpha by lithium in vitro Psychopharmacol Bull 1995 31: 449–452
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
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
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
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
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
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
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
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
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
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4000837
Keywords
This article is cited by
-
Docosahexaenoic fatty acid reduces the pro‐inflammatory response induced by IL-1β in astrocytes through inhibition of NF-κB and AP-1 transcription factor activation
BMC Neuroscience (2021)
-
Omega-3 fatty acids and mood stabilizers alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration
Metabolic Brain Disease (2017)
-
The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders
Molecular Neurobiology (2016)
-
Flaxseed Oil as a Neuroprotective Agent on Lead Acetate-Induced Monoamineric Alterations and Neurotoxicity in Rats
Biological Trace Element Research (2012)
-
Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children
European Journal of Pediatrics (2010)