Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients - PubMed (original) (raw)
Comparative Study
Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients
H Y Wang et al. J Psychiatr Res. 1999 Mar-Apr.
Abstract
Background: recent investigations have suggested that the phosphoinositide (PI) signal transduction system may be involved in the pathophysiology of bipolar affective disorders. Earlier studies in our laboratory have implicated altered PKC-mediated phosphorylation in bipolar affective disorder and in the clinical action of lithium. In the present study, we compared PKC activity and its translocation in platelets from subjects with bipolar affective disorder and three other groups.
Methods: subjects included 44 with bipolar disorder (acute manic episode), 25 with acute major depression, 23 with schizophrenia in acute exacerbation and 43 controls free of personal or family history of an Axis I disorder. Blood platelet membrane and cytosol PKC activity was measured before and after in vitro stimulation with serotonin (5-HT), thrombin and the direct PKC activator, PMA. In addition, we examined 5-HT-, thrombin- and PMA-elicited translocations of PKC isozymes from cytosol to the membrane in platelets of control subjects.
Results: in the basal state, manic subjects demonstrated higher membrane PKC activity than depressive and control subjects. The ratio of membrane to cytosol PKC activity was significantly higher in manic (1.10), as compared to control (0.84), depressed (0.93) or schizophrenic (0.93) subjects. Stimulation of platelets with 5-HT in vitro, resulted in greater membrane to cytosol ratio in the manic subjects compared to the three other groups. The responsiveness of platelets to PMA and thrombin was greater for manic subjects than for depressed and schizophrenic subjects, but not greater than the controls. In this measure both the schizophrenic and depressive groups were less active than controls. The results also demonstrate that platelets contain alpha-, beta-, delta- and zeta-PKC isozymes. While alpha- and beta-PKC isoforms were translocated from cytosol to membrane in response to serotonin, PMA and thrombin, serotonin also elicited the redistribution of delta-PKC and thrombin also activated zeta-PKC.
Conclusion: the results demonstrate that a heightened PKC-mediated signal transduction is associated with acute mania and suggest a decreased transduction in patients with unipolar depression or schizophrenia.
Similar articles
- Lithium and valproic acid treatments reduce PKC activation and receptor-G protein coupling in platelets of bipolar manic patients.
Hahn CG, Umapathy, Wang HY, Koneru R, Levinson DF, Friedman E. Hahn CG, et al. J Psychiatr Res. 2005 Jul;39(4):355-63. doi: 10.1016/j.jpsychires.2004.10.007. J Psychiatr Res. 2005. PMID: 16044535 Clinical Trial. - Protein kinase C and phospholipase C activity and expression of their specific isozymes is decreased and expression of MARCKS is increased in platelets of bipolar but not in unipolar patients.
Pandey GN, Dwivedi Y, SridharaRao J, Ren X, Janicak PG, Sharma R. Pandey GN, et al. Neuropsychopharmacology. 2002 Feb;26(2):216-28. doi: 10.1016/S0893-133X(01)00327-X. Neuropsychopharmacology. 2002. PMID: 11790517 Clinical Trial. - Lithium treatment inhibits protein kinase C translocation in rat brain cortex.
Wang HY, Johnson GP, Friedman E. Wang HY, et al. Psychopharmacology (Berl). 2001 Oct;158(1):80-6. doi: 10.1007/s002130100834. Psychopharmacology (Berl). 2001. PMID: 11685387 - Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder.
Hahn CG, Friedman E. Hahn CG, et al. Bipolar Disord. 1999 Dec;1(2):81-6. doi: 10.1034/j.1399-5618.1999.010204.x. Bipolar Disord. 1999. PMID: 11252663 Review. - Intracellular phosphatidylinositol pathway abnormalities in bipolar disorder patients.
Soares JC, Mallinger AG. Soares JC, et al. Psychopharmacol Bull. 1997;33(4):685-91. Psychopharmacol Bull. 1997. PMID: 9493480 Review.
Cited by
- New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.
Bortolozzi A, Fico G, Berk M, Solmi M, Fornaro M, Quevedo J, Zarate CA Jr, Kessing LV, Vieta E, Carvalho AF. Bortolozzi A, et al. Pharmacol Rev. 2024 May 2;76(3):323-357. doi: 10.1124/pharmrev.120.000007. Pharmacol Rev. 2024. PMID: 38697859 Free PMC article. Review. - Protein and mRNA expression of protein kinase C (PKC) in the postmortem brain of bipolar and schizophrenic subjects.
Pandey GN, Rizavi HS, Ren X. Pandey GN, et al. J Psychiatr Res. 2020 Nov;130:362-371. doi: 10.1016/j.jpsychires.2020.07.019. Epub 2020 Aug 9. J Psychiatr Res. 2020. PMID: 32882578 Free PMC article. - Intracellular Signaling Cascades in Bipolar Disorder.
Jones GH, Rong C, Shariq AS, Mishra A, Machado-Vieira R. Jones GH, et al. Curr Top Behav Neurosci. 2021;48:101-132. doi: 10.1007/7854_2020_157. Curr Top Behav Neurosci. 2021. PMID: 32860212 Review. - Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization.
Ronzier E, Parks XX, Qudsi H, Lopes CM. Ronzier E, et al. Sci Rep. 2019 Nov 28;9(1):17747. doi: 10.1038/s41598-019-53700-6. Sci Rep. 2019. PMID: 31780674 Free PMC article. - Valproate for acute mania.
Jochim J, Rifkin-Zybutz RP, Geddes J, Cipriani A. Jochim J, et al. Cochrane Database Syst Rev. 2019 Oct 7;10(10):CD004052. doi: 10.1002/14651858.CD004052.pub2. Cochrane Database Syst Rev. 2019. PMID: 31621892 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous