Inhibitory effects of omega-3 fatty acids on protein kinase C activity in vitro. 2001

H F Seung Kim, and E J Weeber, and J D Sweatt, and A L Stoll, and L B Marangell
Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030, USA.

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.

UI MeSH Term Description Entries
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004281 Docosahexaenoic Acids C22-unsaturated fatty acids found predominantly in FISH OILS. Docosahexaenoate,Docosahexaenoic Acid,Docosahexenoic Acids,Docosahexaenoic Acid (All-Z Isomer),Docosahexaenoic Acid Dimer (All-Z Isomer),Docosahexaenoic Acid, 3,6,9,12,15,18-Isomer,Docosahexaenoic Acid, 4,7,10,13,16,19-(All-Z-Isomer),Docosahexaenoic Acid, 4,7,10,13,16,19-(All-Z-Isomer), Cerium Salt,Docosahexaenoic Acid, 4,7,10,13,16,19-(All-Z-Isomer), Cesium Salt,Docosahexaenoic Acid, 4,7,10,13,16,19-(All-Z-Isomer), Potassium Salt,Docosahexaenoic Acid, 4,7,10,13,16,19-(Z,Z,Z,Z,Z,E-Isomer),Docosahexaenoic Acid, 4,7,10,13,16,19-Isomer,Docosahexaenoic Acid, 4,7,10,13,16,19-Isomer, Sodium Salt,Docosahexaenoic Acid, Sodium Salt,Acid, Docosahexaenoic,Acids, Docosahexaenoic,Acids, Docosahexenoic
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001095 Arachidonic Acids Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic
D001714 Bipolar Disorder A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. Affective Psychosis, Bipolar,Bipolar Disorder Type 1,Bipolar Disorder Type 2,Bipolar Mood Disorder,Depression, Bipolar,Manic Depression,Manic Disorder,Manic-Depressive Psychosis,Psychosis, Manic-Depressive,Type 1 Bipolar Disorder,Type 2 Bipolar Disorder,Psychoses, Manic-Depressive,Bipolar Affective Psychosis,Bipolar Depression,Bipolar Disorders,Bipolar Mood Disorders,Depression, Manic,Depressions, Manic,Disorder, Bipolar,Disorder, Bipolar Mood,Disorder, Manic,Manic Depressive Psychosis,Manic Disorders,Mood Disorder, Bipolar,Psychoses, Bipolar Affective,Psychoses, Manic Depressive,Psychosis, Bipolar Affective,Psychosis, Manic Depressive
D015525 Fatty Acids, Omega-3 A group of unsaturated fatty acids occurring mainly in fish oils, with three double bonds at particular positions in the hydrocarbon chain. N-3 Fatty Acid,Omega-3 Fatty Acid,Omega-3 Fatty Acids,n-3 Fatty Acids,n-3 Oil,n3 Oil,Omega 3 Fatty Acids,n-3 Oils,n-3 PUFA,n-3 Polyunsaturated Fatty Acid,n3 Fatty Acid,n3 Oils,n3 PUFA,n3 Polyunsaturated Fatty Acid,Acid, N-3 Fatty,Acid, Omega-3 Fatty,Fatty Acid, N-3,Fatty Acid, Omega-3,Fatty Acid, n3,N 3 Fatty Acid,Oil, n-3,Oil, n3,Omega 3 Fatty Acid,PUFA, n-3,PUFA, n3,n 3 Fatty Acids,n 3 Oil,n 3 Oils,n 3 PUFA,n 3 Polyunsaturated Fatty Acid
D016718 Arachidonic Acid An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. (all-Z)-5,8,11,14-Eicosatetraenoic acid,Arachidonic Acid, (all-Z)-Isomer, 1-(14)C-Labeled,Arachidonic Acid, (all-Z)-isomer, 3H-Labeled,Arachidonic Acid, Ammonium Salt, (all-Z)-Isomer,Arachidonic Acid, Cerium Salt, (all-Z)-Isomer,Arachidonic Acid, Cesium Salt, (all-Z)-Isomer,Arachidonic Acid, Lithium Salt, (all-Z)-Isomer,Arachidonic Acid, Potassium Salt, (all-Z)-Isomer,Arachidonic Acid, Sodium Salt,Arachidonic Acid, Sodium Salt, (all-Z)-Isomer,Arachidonic Acid, Zinc Salt, (all-Z)-Isomer,Sodium Arachidonate,Vitamin F,Arachidonate, Sodium
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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