mRNA and protein expression of selective alpha subunits of G proteins are abnormal in prefrontal cortex of suicide victims.
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.
Dwivedi
Yogesh
Y
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, 60612, USA.
Rizavi
Hooriyah S
HS
Conley
Robert R
RR
Roberts
Rosalinda C
RC
Tamminga
Carol A
CA
Pandey
Ghanshyam N
GN
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2; D044385:GTP-Binding Protein alpha Subunits; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D013405:Suicide; D015854:Up-Regulation / Q000235:genetics
D044385:GTP-Binding Protein alpha Subunits; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C084618:olfactory G protein subunit alpha olf; D019204:GTP-Binding Proteins; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins