Effects of postmortem interval, age, and Alzheimer's disease on G-proteins in human brain.
Heterotrimeric G-proteins are critical components in many receptor-coupled signal transduction systems, and altered levels and functions of G-proteins have been implicated in several neurological disorders, including Alzheimer's disease. Investigations in postmortem human brain provide a direct approach to study G-protein involvement in neurological disorders. Therefore, the effects of postmortem interval, aging, and Alzheimer's disease on G-protein levels were determined in postmortem human brain and an assay to measure activation of G-proteins was developed. Within the postmortem interval range of 5 to 21 h, the levels of G alpha i1, G alpha i2, G alpha s, and G beta were stable, whereas G alpha q and G alpha o decreased slightly, in human prefrontal cortex. In subjects aged 19 to 100 y, decreased levels of G alpha q and G alpha o were significantly correlated with increased age, but levels of the other G-protein subunits did not vary. In Alzheimer's disease prefrontal cortex, superior temporal gyrus, and occipital cortex, all G-protein subunit levels were equivalent to those in matched controls except for a slight deficit in G alpha i1. An ELISA assay using selective antibodies was used to measure [35S]GTP gamma S binding to G alpha o and G alpha i1. Binding was proportional to the concentration of GTP-gamma S and was concentration-dependently stimulated by mastoparan equivalently in control and Alzheimer's disease prefrontal cortical membranes.
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Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 35294-0017, USA.
Greenwood
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Powers
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Jope
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D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism*; D001667:Binding, Competitive; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011180:Postmortem Changes; D014862:Wasp Venoms / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan; D019204:GTP-Binding Proteins