Regionally selective alterations in G protein subunit levels in the Alzheimer's disease brain.
In the present study the relative densities of a number of G protein subunits were quantified in membranes prepared from the hippocampus, temporal cortex and angular gyrus of Alzheimer's disease and control post-mortem brain by immunoblotting with specific polyclonal antisera against Gs alpha, Gi alpha, Gi alpha-1, G(o) alpha and G beta protein subunits. In addition, basal, Gs-stimulated and Gi-inhibited adenylyl cyclase activities were measured in the same hippocampal membrane samples. Densitometric analysis of the immunoblot data revealed a 58% reduction in the levels of Gi alpha, and a 75% reduction in the levels of Gi alpha-1, in the Alzheimer's disease temporal cortex. Gi alpha levels were reduced, by 37% in the angular gyrus of the Alzheimer's disease cases. The ratio of large to small molecular weight isoforms of the Gs alpha subunit was significantly increased in both the hippocampus and the angular gyrus of the Alzheimer's disease samples when compared to control values, although the difference in individual Gs alpha isoform levels did not attain statistical significance when comparing groups. No statistically significant differences were observed in G(o) alpha or G beta levels when comparing control and Alzheimer's disease cases. Gs-stimulated adenylyl cyclase activity was significantly reduced in the Alzheimer's disease samples compared to controls, whereas Gi-inhibited adenylyl cyclase activity was unchanged. No significant differences were observed between the control and Alzheimer's disease samples for either basal or forskolin stimulated adenylyl cyclase activity. The ratio of hippocampal Gs-stimulated to basal adenylyl cyclase activity correlated significantly with the large to small Gs alpha subunit ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Neill
C
C
Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Wiehager
B
B
Fowler
C J
CJ
Ravid
R
R
Winblad
B
B
Cowburn
R F
RF
D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007120:Immunochemistry; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013702:Temporal Lobe / Q000201:enzymology / Q000378:metabolism
D009419:Nerve Tissue Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases