Hashimoto E, Ozawa H, Saito T
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Apr;14(2):105-9.
Qualitative or quantitative alterations of GTP binding (G) proteins in membrane preparations from parietal cortex and temporal cortex in postmortem human brain obtained from patients with dementia of the Alzheimer's type (DAT) and aged and postmortem delay matched controls were investigated by immunoblotting with polyclonal antibodies (RM/1, AS/7, GC/2, QL, SW/1) against specific G protein (Gs alpha, Gi alpha, Go alpha, Gq alpha, G beta, respectively) and the functional photoaffinity GTP analog [azidoanilido GTP (AAGTP)] labeling. Although the quantitative immunoreactivity showed no significant differences between the two groups, a marked reduction in AAGTP binding to Gs alpha was seen in the DAT group compared with controls in both parietal and temporal cortex. Moreover, the ratio of Gs alpha to Gi/o alpha AAGTP binding decreased significantly in the same regions of the DAT group. These results suggest that the disturbances of G protein mediated signal transduction may be involved in the pathophysiology of DAT.
采用针对特定G蛋白(分别为Gsα、Giα、Goα、Gqα、Gβ)的多克隆抗体(RM/1、AS/7、GC/2、QL、SW/1)进行免疫印迹以及功能性光亲和GTP类似物[叠氮苯胺基GTP(AAGTP)]标记,研究了取自阿尔茨海默病型痴呆(DAT)患者及年龄和死后延迟时间匹配的对照者的死后人类大脑顶叶皮质和颞叶皮质膜制剂中GTP结合(G)蛋白的定性或定量改变。尽管两组之间的定量免疫反应性无显著差异,但与对照组相比,DAT组顶叶和颞叶皮质中AAGTP与Gsα的结合均显著减少。此外,DAT组相同区域中Gsα与Gi/oα AAGTP结合的比率显著降低。这些结果表明,G蛋白介导的信号转导紊乱可能参与了DAT的病理生理过程。