Protein kinase a in postmortem brain of depressed suicide victims: Altered expression of specific regulatory and catalytic subunits

Academic Article

Abstract

  • Background: We recently reported reduced [3H]cyclic adenosine monophosphate binding and catalytic activity of protein kinase A in prefrontal cortex of depressed suicide victims. Here we examined the molecular basis of these alterations and whether these findings can be replicated in another cohort. Methods: Prefrontal cortex from depressed suicide victims and nonpsychiatric controls were obtained from the Lenhossek Human Brain Program, Budapest and the Maryland Brain Collection Program. [3H]cyclic adenosine monophosphate binding and protein kinase A activity were determined by radioligand binding and enzymatic assay, respectively. Expression of catalytic and regulatory subunits was determined by quantitative reverse transcription polymerase chain reaction and Western blot, respectively. Results: [3H]cyclic adenosine monophosphate binding and total and endogenous protein kinase A activity were significantly decreased in membrane and cytosol fractions of prefrontal cortex of depressed suicide victims from the Budapest cohort, with a similar magnitude (33%-40% reduction) as reported for the Maryland cohort. In both cohorts, selective reduction (36%-41%) in mRNA and protein expression of the regulatory RIIβ and the catalytic Cβ was observed. Conclusions: Our results suggest abnormalities in [ 3H]cyclic adenosine monophosphate binding and catalytic activity kinase A in brain of depressed suicide victims, which could be due to reduced expression of RIIβ and Cβ. These abnormalities in PKA may be critical in the pathophysiology of depression.
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    Digital Object Identifier (doi)

    Author List

  • Dwivedi Y; Rizavi HS; Shukla PK; Lyons J; Faludi G; Palkovits M; Sarosi A; Conley RR; Roberts RC; Tamminga CA
  • Start Page

  • 234
  • End Page

  • 243
  • Volume

  • 55
  • Issue

  • 3