Impaired G-protein-stimulated adenylyl cyclase activity in Alzheimer's disease brain is not accompanied by reduced cyclic-AMP-dependent protein kinase A activity
Impaired G-protein-stimulated adenylyl cyclase activity in Alzheimer's disease brain is not accompanied by reduced cyclic-AMP-dependent protein kinase A activity
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DOI：
10.1016/0006-8993(96)00724-x
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发表时间：
1996-10-21
期刊：
影响因子：
2.9
通讯作者：
Cowburn, RF
中科院分区：
文献类型：
--
作者：
Bonkale, WL;Fastbom, J;Cowburn, RF
先前的研究表明，腺苷酸环化酶的活性调节在阿尔茨海默病死后的大脑中被破坏。在本研究中，我们确定是否破坏腺苷酸环化酶是伴随着改变cAMP依赖性蛋白激酶活性在阿尔茨海默病上级颞叶皮层和小脑。GTP γ S-刺激腺苷酸环化酶活性显着降低阿尔茨海默氏病上级颞叶皮层，但不是小脑，从一系列匹配的对照病例的值相比。无论是基础或毛喉素刺激腺苷酸环化酶的活动之间的阿尔茨海默病和控制脑区显着不同。阿尔茨海默病和对照脑区之间的颗粒或可溶性部分cAMP依赖性蛋白激酶活性均无显着差异。它的结论是破坏腺苷酸环化酶信号在阿尔茨海默氏病的大脑中发生具体的G（S）-蛋白质-酶的相互作用的水平，并不伴随着改变cAMP依赖性蛋白激酶活性。
Previous studies have shown that the regulation of adenylyl cyclase activity is disrupted in Alzheimer's disease postmortem brain. In the present study, we determined whether disrupted adenylyl cyclase is accompanied by altered cAMP-dependent protein kinase activity in Alzheimer's disease superior temporal cortex and cerebellum. GTP gamma S-stimulated adenylyl cyclase activity was significantly lower in Alzheimer's disease superior temporal cortex, but not cerebellum, compared to values from a series of matched control cases. Neither basal or forskolin-stimulated adenylyl cyclase activities were significantly different between the Alzheimer's disease and control brain regions. No significant differences were seen in either particulate or soluble fraction cAMP-dependent protein kinase activities between the Alzheimer's disease and control brain regions. It is concluded that disrupted adenylyl cyclase signalling in Alzheimer's disease brain occurs specifically at the level of G(s)-protein-enzyme interactions and is not accompanied by an altered cAMP-dependent protein kinase activity.