Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain

Mary A. Pacheco, Craig Stockmeier, Herbert Y. Meltzer, James C. Overholser, Ginny E. Dilley, Richard S Jope

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

The function of the phosphoinositide signal transduction system and the levels of heterotrimeric G-protein α-subunits were examined in postmortem prefrontal cortex regions (8/9) and region (10) from suicide victims with major depression and matched control subjects without psychiatric illness. The hydrolysis of [3H]phosphatidylinositol (PI) stimulated by phospholipase C, GTP-γ-S, NaF, and neurotransmitter receptor agonists was measured in membrane preparations from both groups. Phospholipase C-β activity was similar in depressed suicide and control subjects in the two regions of prefrontal cortex. In prefrontal cortex (10), but not in (8/9), the GTP-γ-S concentration-dependent stimulation of [3H]PI hydrolysis was significantly lower (30%) in the depressed suicide group compared to the control group. Receptor-coupled, G-protein-mediated [3H]PI hydrolysis induced with carbachol, histamine, trans-1-aminocyclopentyl-1,3-dicarboxylic acid (ACPD, a glutamatergic metabotropic receptor agonist), serotonin, or 2-methylthio-adenosine triphosphate (2mATP, a purinergic receptor agonist) in the presence of GTP-γ-S stimulated equivalent responses in the two groups of subjects in each brain region. In prefrontal cortex (10) there was a 68% increase in the level of the 45 kDa subtype of Gαs and in prefrontal cortex (8/9) there was a significant decrease (21%) in the level of Gαi2 in the depressed suicide group compared to the control group. Levels of other heterotrimeric G-protein α-subunits (Gαq/11, Gαi1, and Gαo) were not different in depressed suicide and control subjects in either brain region. Moreover, there were no differences in the levels of phospholipase C-β or protein kinase C-α in the two groups of subjects in either brain region examined. These results demonstrate that in the prefrontal cortex of suicide victims with major depression compared to normal control subjects there is a region-specific alteration of G-protein-induced activation of the phosphoinositide signal transduction system and in the levels of G-protein α-subunits involved in cyclic AMP synthesis. These findings provide direct evidence in human brain that these two important signal transduction systems are altered in suicide subjects with major depression.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalBrain Research
Volume723
Issue number1-2
DOIs
StatePublished - Jun 3 1996
Externally publishedYes

Fingerprint

Phosphatidylinositols
GTP-Binding Proteins
Suicide
Prefrontal Cortex
Brain
Protein Subunits
Type C Phospholipases
Guanosine Triphosphate
Heterotrimeric GTP-Binding Proteins
Signal Transduction
Hydrolysis
Depression
Purinergic Agonists
Serotonin Receptor Agonists
Control Groups
Neurotransmitter Receptor
Carbachol
G-Protein-Coupled Receptors
Cyclic AMP
Protein Kinase C

Keywords

  • depression
  • G-protein
  • inositol phosphate
  • phosphoinositide
  • signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pacheco, M. A., Stockmeier, C., Meltzer, H. Y., Overholser, J. C., Dilley, G. E., & Jope, R. S. (1996). Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain. Brain Research, 723(1-2), 37-45. https://doi.org/10.1016/0006-8993(96)00207-7

Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain. / Pacheco, Mary A.; Stockmeier, Craig; Meltzer, Herbert Y.; Overholser, James C.; Dilley, Ginny E.; Jope, Richard S.

In: Brain Research, Vol. 723, No. 1-2, 03.06.1996, p. 37-45.

Research output: Contribution to journalArticle

Pacheco, MA, Stockmeier, C, Meltzer, HY, Overholser, JC, Dilley, GE & Jope, RS 1996, 'Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain', Brain Research, vol. 723, no. 1-2, pp. 37-45. https://doi.org/10.1016/0006-8993(96)00207-7
Pacheco, Mary A. ; Stockmeier, Craig ; Meltzer, Herbert Y. ; Overholser, James C. ; Dilley, Ginny E. ; Jope, Richard S. / Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain. In: Brain Research. 1996 ; Vol. 723, No. 1-2. pp. 37-45.
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