Altered cAMP-dependent protein kinase subunit immunolabeling in post-mortem brain from patients with bipolar affective disorder.
Previous findings of reduced [3H]cAMP binding and increased activities of cAMP-dependent protein kinase (PKA) in discrete post-mortem brain regions from patients with bipolar affective disorder (BD) suggest that PKA, the major downstream target of cAMP, is also affected in this illness. As prolonged elevation of intracellular cAMP levels can modify PKA regulatory (R) and catalytic (C) subunit levels, we sought to determine whether these PKA abnormalities are related to changes in the abundance of PKA subunits in BD brain. Using immunoblotting techniques along with PKA subunit isoform-specific polyclonal antisera, levels of PKA RIalpha, RIbeta, RIIalpha, RIIbeta and Calpha subunits were measured in cytosolic and particulate fractions of temporal, frontal and parietal cortices of post-mortem brain from BD patients and matched, non-neurological, non-psychiatric controls. Immunoreactive levels of cytosolic Calpha in temporal and frontal cortices, as well as that of cytosolic RIIbeta in temporal cortex, were significantly higher in the BD compared with the matched control brains. These changes were independent of age, post-mortem interval or pH and unrelated to ante-mortem lithium treatment or suicide. These findings strengthen further the notion that the cAMP/PKA signaling system is up-regulated in discrete cerebral cortical regions in BD.
Chang
Annisa
A
Laboratory of Cellular and Molecular Pathophysiology, Center for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8.
Li
Peter P
PP
Warsh
Jerry J
JJ
D000918:Antibody Specificity; D001714:Bipolar Disorder / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis*; D003600:Cytosol / Q000737:chemistry / Q000201:enzymology; D003710:Demography; D005625:Frontal Lobe / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D010296:Parietal Lobe / Q000737:chemistry / Q000201:enzymology; D021122:Protein Subunits / Q000032:analysis; D012016:Reference Values; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology; D013405:Suicide; D013702:Temporal Lobe / Q000737:chemistry / Q000201:enzymology
D021122:Protein Subunits; D017868:Cyclic AMP-Dependent Protein Kinases