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[人死后大脑中GTP结合蛋白的年龄相关变化]

[Age-related alterations on GTP binding proteins in postmortem human brain].

作者信息

Hashimoto E, Ozawa H, Saito T

机构信息

Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Apr;14(2):93-104.

PMID:8042348
Abstract

It is important that natural aging-related alterations are characterized to understand disabilities associated with aging. In this study, age-related alterations of GTP binding (G) proteins were examined in membrane preparations from several regions (frontal cortex, temporal cortex, parietal cortex, occipital cortex, caudate nucleus, amygdaloid body) in postmortem human brain. Subjects were free from neurologic or psychiatric disease. The quantity of G proteins (Gs alpha, Gi alpha, Go alpha, Gq alpha, G beta subunit) was determined by immunoblotting with polyclonal antibody (RM/1, AS/7, GC/2, QL, SW/1, respectively). The function of G proteins was examined by photoaffinity GTP analog [azidoanilido GTP (AAGTP)] binding. The immunoreactivities of Gi alpha and Gq alpha subunits were correlated inversely with age in many areas. In caudate nucleus, the GsL alpha (45 kDa) and Go alpha subunit immunoreactivities were decreased with age. And the G beta subunit immunoreactivities showed a negative correlation with age in temporal and occipital cortex areas. However, AAGTP labeling to Gs alpha and Gi/o alpha and the ratio of Gs alpha to Gi/o alpha AAGTP binding showed no age-dependent changes. Our findings suggest that the functional modulation may compensate for quantitative alterations of G proteins with human senescence.

摘要

为了理解与衰老相关的残疾,对自然衰老相关的改变进行特征描述很重要。在本研究中,对死后人类大脑几个区域(额叶皮质、颞叶皮质、顶叶皮质、枕叶皮质、尾状核、杏仁体)的膜制剂中与年龄相关的GTP结合(G)蛋白改变进行了检测。研究对象无神经或精神疾病。通过用多克隆抗体(分别为RM/1、AS/7、GC/2、QL、SW/1)进行免疫印迹法测定G蛋白(Gsα、Giα、Goα、Gqα、Gβ亚基)的量。通过光亲和GTP类似物[叠氮苯胺基GTP(AAGTP)]结合来检测G蛋白的功能。在许多区域,Giα和Gqα亚基的免疫反应性与年龄呈负相关。在尾状核中,GsLα(45 kDa)和Goα亚基的免疫反应性随年龄降低。并且Gβ亚基的免疫反应性在颞叶和枕叶皮质区域与年龄呈负相关。然而,AAGTP对Gsα和Gi/oα的标记以及Gsα与Gi/oα AAGTP结合的比率未显示出年龄依赖性变化。我们的研究结果表明,功能调节可能补偿人类衰老过程中G蛋白的定量改变。

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