Altered CTX-catalyzed and endogenous [32P]ADP-ribosylation of stimulatory G protein alphas isoforms in postmortem bipolar affective disorder temporal cortex.
Reports of elevated Gs alpha subunit (alpha(s)) immunolabeling and cAMP-mediated hyper-functionality in autopsied cerebral cortical brain regions from bipolar affective disorder (BD) patients suggest signal transduction abnormalities occur in this disorder. Because covalent modification of alpha(s) can affect its turnover and levels, we determined whether CTX-catalyzed and endogenous [(32)P] adenosine diphosphate (ADP)-ribosylation of alpha(s) isoforms are altered in temporal and occipital cortical regions, which show elevated alpha(s) levels in BD as compared to nonpsychiatric subjects. Reduced CTX-catalyzed [(32)P]ADP-ribosylated alpha(s-S) and endogenous [(32)P]ADP-ribosylation of a 39-kDa alpha(s)-like protein were found in BD temporal cortex compared to controls. These findings suggest that clearance of these alpha(s) isoforms through ADP-ribosylation may be decreased in BD temporal cortex. Although no differences were observed in mean levels of endogenous and CTX-catalyzed [(32)P]ADP-ribosylation of alpha(s-L) in BD temporal cortex, alpha(s-L) immunolabeling was elevated significantly and correlated inversely with the degree of endogenous [(32)P]ADP-ribosylation of this subunit. In addition, endogenous [(32)P]ADP-ribosylation of an exogenous substrate, myelin basic protein, was similar in BD and comparison subject temporal cortex. Taken together, these observations suggest that elevations of alpha(s) in BD brain are more likely related to factors affecting the disposition or availability of alpha(s) to this posttranslational enzymatic modification.
Laboratory of Cellular and Molecular Pathophysiology, Center for Addiction and Mental Health, Clarke Site, Toronto, Canada.
Stavroula
S
Andreopoulos
Peter P
PP
Li
Kin Po
KP
Siu
Stephen J
SJ
Kish
Jerry J
JJ
Warsh
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000378:metabolism* / Q000503:physiopathology; D002772:Cholera Toxin / Q000494:pharmacology; D005260:Female; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008094:Lithium / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009778:Occipital Lobe / Q000378:metabolism / Q000503:physiopathology; D010759:Phosphorus Isotopes; D013702:Temporal Lobe / Q000378:metabolism* / Q000503:physiopathology
D004676:Myelin Basic Protein; D010759:Phosphorus Isotopes; D000244:Adenosine Diphosphate; D002772:Cholera Toxin; D008094:Lithium; D020962:Heterotrimeric GTP-Binding Proteins