TY  - JOUR
PY  - 2004//
TI  - Protein kinase A in postmortem brain of depressed suicide victims: altered expression of specific regulatory and catalytic subunits
JO  - Biological psychiatry
A1  - Dwivedi, Yogesh
A1  - Rizavi, Hooriyah S.
A1  - Shukla, Pradeep K.
A1  - Lyons, Jennifer
A1  - Faludi, Gabor
A1  - Palkovits, Miklos
A1  - Sarosi, Andrea
A1  - Conley, Robert R.
A1  - Roberts, Rosalinda C.
A1  - Tamminga, Carol A.
A1  - Pandey, Ghanshyam N.
SP  - 234
EP  - 243
VL  - 55
IS  - 3
N2  - 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 RIIbeta and the catalytic Cbeta 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 RIIbeta and Cbeta. These abnormalities in PKA may be critical in the pathophysiology of depression.<p /> <p>Language: en</p>
LA  - en
SN  - 0006-3223
UR  - http://dx.doi.org/
ID  - ref1
ER  -