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.
Original language | English (US) |
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Pages (from-to) | 234-243 |
Number of pages | 10 |
Journal | Biological Psychiatry |
Volume | 55 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 2004 |
Keywords
- Depression
- Human
- Postmortem brain
- Protein kinase A
- cAMP signal transduction
ASJC Scopus subject areas
- Biological Psychiatry