mRNA and Protein Expression of Selective Alpha Subunits of G Proteins are Abnormal in Prefrontal Cortex of Suicide Victims

Abstract

The present investigation was undertaken to examine whether there is an abnormality in the expression of alpha and beta gamma subunits of G proteins both at the transcriptional and translational level in postmortem brain of adult and teenage suicide subjects and whether these abnormalities are related to mental disorders or suicide per se. In addition, an attempt has been made to investigate whether these abnormalities are similar or dissimilar in teenage and adult suicide, because the etiology of teenage suicide may be different than that of adults.A significant decrease in both mRNA and protein levels of G(i2)alpha and G(O)alpha and a significant increase in levels of G(s)alpha(-S) were observed in prefrontal cortex of suicide subjects (n = 43) compared with non-psychiatric control subjects (n = 38). When subjects were grouped according to age, a significantly decreased expression of G(i2)alpha and G(O)alpha and significantly increased expression of G(s)alpha(-S) were observed in adult suicide subjects (age > or = 20 yrs; n = 20) as compared with age-matched controls (n = 27). These changes were present in all adult suicide subjects regardless of psychiatric diagnosis. On the other hand, although there were no significant differences in any alpha or beta gamma subunits in teenage suicide subjects (age < or = 19 yrs; n = 16) when compared with matched control subjects (n = 18); however, mRNA and protein levels of G(i2)alpha and G(O)alpha were significantly decreased and of G(s)alpha(-S) were significantly increased only in those teenage suicide subjects who had a history of mental illness (n = 11). Our results suggest that there are defects in the expression of selective G protein alpha subunits in prefrontal cortex of adult and teenage suicide subjects, which appear to be related to mental disorders.

Brain Region Specific Alterations in the Protein and mRNA Levels of Protein Kinase A Subunits in the Post-Mortem Brain of Teenage Suicide Victims

“…The detailed procedures for determining mRNA levels of various PKA isozymes by quantitative RT-PCR are described in our earlier publications (Dwivedi et al, 2002b. Total RNA was isolated by CsCl 2 ultracentrifugation.…”

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

“…A significant decrease in both [171] PTX, pertussis toxin mRNA and protein levels of G i2 and G o , and a significant increase in levels of 45 kDa G s have been observed in prefrontal cortex of suicide subjects. These alterations were reported to be independent of the retrospective psychiatric diagnosis [49]. On the contrary, several publications have not found alterations in the densities of the different subunits of the heterotrimeric G proteins, both G [47,69] and G [148].…”

“…New York, NY 10029, USA; Tel: +212 241 8691; Fax: +212 289 4107; E-mail: Javier.Maeso@mssm.edu receptor activation (see below). In this context, several discrepancies have been recently reported in density and functional status of the heterotrimeric G proteins both in major depression and bipolar disorder [49,57,62,69,149,186]. The primary focus of this review will be to summarize recent advances in the study of the molecular biology of heterotrimeric G proteins.…”

Lipid Rafts, G Proteins and the Etiology of and Treatment for Depression: Progress toward a Depression Biomarker

“…Dysfunctional cAMP signaling represents a consistent finding in human cerebral cortex tissue from suicide subjects [20][21][22][23][24][25]. Some of these studies demonstrate a consistent decrease in forskolin-stimulated adenylyl cyclase activity without a change in expression or concentration of G sα protein [20,25], while other studies have demonstrated a small increase in G sα protein and mRNA levels in subjects with major depression [21,23].…”

“…Some of these studies demonstrate a consistent decrease in forskolin-stimulated adenylyl cyclase activity without a change in expression or concentration of G sα protein [20,25], while other studies have demonstrated a small increase in G sα protein and mRNA levels in subjects with major depression [21,23]. Downstream in the cAMP signaling pathway, decreased PKA activity was observed in these same suicide subjects [22,24].…”