散发性和伴有早老素1（PS1）及淀粉样前体蛋白（APP）突变的家族性阿尔茨海默病患者成纤维细胞中腺苷酸环化酶的差异调节

Differential regulation of adenylyl cyclase in fibroblasts from sporadic and familial Alzheimer's disease cases with PS1 and APP mutations.

作者信息

Vestling M, Adem A, Racchi M, Gibson G E, Lannfelt L, Cowburn R F

机构信息

Division of Geriatric Medicine, Karolinska Institute, Novum, Huddinge, Sweden.

出版信息

Neuroreport. 1997 May 27;8(8):2031-5. doi: 10.1097/00001756-199705260-00045.

DOI:10.1097/00001756-199705260-00045

PMID:9223097

Abstract

beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were determined in primary skin fibroblasts established from patients with sporadic Alzheimer's disease (AD) and from individuals with familial APP KM670/671NL, PS1 M146V and PS1 H163Y mutations. Our data showed a significantly decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in fibroblasts from sporadic AD compared with age-matched controls (p < 0.001, Student's unpaired t-test). In contrast, both beta-adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were significantly increased in fibroblasts bearing PS1 M146V and PS1 H163Y mutations compared with controls (p < 0.01 and p < 0.05, respectively). No differences were seen between cell lines with and without the Swedish APP KM670/671NL double mutation. We suggest that various gene mutations associated with AD have different consequences for the regulation of adenylyl cyclase signal transduction in this disorder.

摘要

在从散发性阿尔茨海默病（AD）患者以及携带家族性APP KM670/671NL、PS1 M146V和PS1 H163Y突变的个体中建立的原代表皮成纤维细胞中，测定了β-肾上腺素能受体和福斯高林刺激的腺苷酸环化酶活性。我们的数据显示，与年龄匹配的对照组相比，散发性AD患者成纤维细胞中β-肾上腺素能受体刺激的腺苷酸环化酶活性显著降低（p < 0.001，Student非配对t检验）。相比之下，与对照组相比，携带PS1 M146V和PS1 H163Y突变的成纤维细胞中β-肾上腺素能受体和福斯高林刺激的腺苷酸环化酶活性均显著增加（分别为p < 0.01和p < 0.05）。有无瑞典APP KM670/671NL双突变的细胞系之间未见差异。我们认为，与AD相关的各种基因突变对该疾病中腺苷酸环化酶信号转导的调节有不同的影响。