Protein kinase a in postmortem brain of depressed suicide victims

Altered expression of specific regulatory and catalytic subunits

Yogesh Dwivedi, Hooriyah S. Rizavi, Pradeep Kumar Shukla, Jennifer Lyons, Gabor Faludi, Miklos Palkovits, Andrea Sarosi, Robert R. Conley, Rosalinda C. Roberts, Carol A. Tamminga, Ghanshyam N. Pandey

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Background: We recently reported reduced [ 3 H]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. [ 3 H]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: [ 3 H]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 [ 3 H]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 languageEnglish (US)
Pages (from-to)234-243
Number of pages10
JournalBiological Psychiatry
Volume55
Issue number3
DOIs
StatePublished - Feb 1 2004
Externally publishedYes

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Cyclic AMP
Protein Kinases
Suicide
Catalytic Domain
Cyclic AMP-Dependent Protein Kinases
Prefrontal Cortex
Brain
Radioligand Assay
Enzyme Assays
Cytosol
Reverse Transcription
Carrier Proteins
Phosphotransferases
Western Blotting
Depression
Polymerase Chain Reaction
Messenger RNA
Membranes
Proteins

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

Protein kinase a in postmortem brain of depressed suicide victims : Altered expression of specific regulatory and catalytic subunits. / Dwivedi, Yogesh; Rizavi, Hooriyah S.; Shukla, Pradeep Kumar; Lyons, Jennifer; Faludi, Gabor; Palkovits, Miklos; Sarosi, Andrea; Conley, Robert R.; Roberts, Rosalinda C.; Tamminga, Carol A.; Pandey, Ghanshyam N.

In: Biological Psychiatry, Vol. 55, No. 3, 01.02.2004, p. 234-243.

Research output: Contribution to journalArticle

Dwivedi, Y, Rizavi, HS, Shukla, PK, Lyons, J, Faludi, G, Palkovits, M, Sarosi, A, Conley, RR, Roberts, RC, Tamminga, CA & Pandey, GN 2004, 'Protein kinase a in postmortem brain of depressed suicide victims: Altered expression of specific regulatory and catalytic subunits', Biological Psychiatry, vol. 55, no. 3, pp. 234-243. https://doi.org/10.1016/j.biopsych.2003.11.003
Dwivedi, Yogesh ; Rizavi, Hooriyah S. ; Shukla, Pradeep Kumar ; Lyons, Jennifer ; Faludi, Gabor ; Palkovits, Miklos ; Sarosi, Andrea ; Conley, Robert R. ; Roberts, Rosalinda C. ; Tamminga, Carol A. ; Pandey, Ghanshyam N. / Protein kinase a in postmortem brain of depressed suicide victims : Altered expression of specific regulatory and catalytic subunits. In: Biological Psychiatry. 2004 ; Vol. 55, No. 3. pp. 234-243.
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