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Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients
Journal article   Peer reviewed

Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients

Hoau-Yan Wang, Philip Markowitz, Douglas Levinson, Ashiwel S Undie and Eitan Friedman
Journal of psychiatric research, v 33(2), pp 171-179
1999
DOI: https://doi.org/10.1016/S0022-3956(98)90057-7
PMID: 10221749
Featured in Collection :   UN Sustainable Development Goals @ Drexel

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 α-, β-, δ- and ζ-PKC isozymes. While α- and β-PKC isoforms were translocated from cytosol to membrane in response to serotonin, PMA and thrombin, serotonin also elicited the redistribution of δ-PKC and thrombin also activated ζ-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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Psychiatry
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