Platelet Protein Kinase C alpha Levels in Drug-Free and Lithium-Treated Subjects with Bipolar Disorder

Abstract

Recent studies suggest that protein kinase C (PKC), particularly the α isoform, plays an important role in the action of lithium. There is, however, little evidence from patients with bipolar disorder (BD) to support this effect. The present investigation carried out comparative studies of PKC levels in platelets obtained from BD subjects including those with and without lithium treatment. All subjects met DSM-IV criteria for BD type I confirmed by structured interview (SCID-IV). Levels of PKC-α isoform in platelets from controls and from BD subjects were measured with immunoblotting analysis. No significant differences were found between controls, drug-free or lithium-treated BD subjects on membrane or cytosolic levels of PKC-α or in the membrane-to-cytosol ratio of this protein. The present study suggests that levels of PKC-α do not change in the peripheral tissues of BD subjects with or without lithium treatment.

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

“…Soares et al (2000) found a significant decrease in PKC ␣ but not PKC ␤I, ␤II, ␦, and in platelets of lithiumtreated patients compared with control subjects. Whereas the discrepancy between our results and those of Soares et al (2000) could be attributed to previous treatment with lithium, the reasons for discrepancy in our results and those of Friedman et al (1993) and Young et al (1999) are unclear.…”

“…p values are a, .009; b, .001. Young et al (1999) did not find any differences in PKC ␣ either in membrane or cytosol fractions of platelets between bipolar patients and normal control subjects. Soares et al (2000) found a significant decrease in PKC ␣ but not PKC ␤I, ␤II, ␦, and in platelets of lithiumtreated patients compared with control subjects.…”

“…They attributed this decrease to an increase in the formation of DAG, which is responsible for the activation of PKC. It has also been argued that the activation of PKC is often followed by its rapid proteolytic degradation (Kishimoto et al 1989;Young et al 1999). The overactive PI signaling in platelets of bipolar patients reported by several investigators may result in the increased formation of DAG and the activation and translocation of PKC to membrane and its subsequent proteolytic degradation.…”

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

“…In contrast to putative hyperactive PKC signaling in BD, Young et al [88] did not observe any significant difference in PKCα levels and activity between platelets from control, drug-free BD patients, and lithium-treated BD patients. In another contradictory finding in a recent report, Hayashi et al [61] reported increased PKC activity in response to lithium in cultured adipocytes from patients with BD.…”

A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

“…It seems also relatively clear that treating mania with a mood stabilizer can reverse the enhancement of platelet PKC activity along with improving the mood in the same patients [90,91]. However, data become more discrepant when different mood states are mixed in the same BPD group (manic, mixed, and depressed states) [92][93][94]. Regarding MDD, two out of three studies reported no change in PKC activity, neither in the membrane nor in the cytosolic fractions [89,94].…”