Putative function of ADAM9, ADAM10, and ADAM17 as APP α-secretase
Putative function of ADAM9, ADAM10, and ADAM17 as APP α-secretase
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DOI：
10.1016/s0006-291x(02)02999-6
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发表时间：
2003-01-31
影响因子：
3.1
通讯作者：
Ishiura, S
中科院分区：
文献类型：
--
作者：
Asai, M;Hattori, C;Ishiura, S
假定的α-分泌酶在淀粉样β肽（Abeta）结构域的中间切割阿尔茨海默病的淀粉样前体蛋白（APP）。通常认为α-分泌酶途径减轻正常脑中的Abeta形成。一些研究表明，ADAM 9、ADAM 10和ADAM 17是属于ADAM（去整合素和金属蛋白酶）家族的候选α-分泌酶，其是膜锚定的细胞表面蛋白。在对ADAM 9、ADAM 10和ADAM 17的比较研究中，我们通过在COS-7细胞中表达这些亚当斯来检查亚当斯的生理作用，并测定这些亚当斯的“组成型”和“调节型”α-分泌酶活性。我们试图通过脂质体转染编码这些亚当斯的双链RNA（dsRNA）来抑制这些亚当斯在含有大量内源性α-分泌酶的人胶质母细胞瘤A172细胞中的表达。结果表明，ADAM 9、ADAM 10和ADAM 17催化α-分泌裂解，因此在A172细胞中充当α-分泌酶。这是第一个报告，表明内源性α-分泌酶是由几个ADAM酶。(C)2002 Elsevier Science（美国）。All rights reserved.
The putative alpha-secretase cleaves the amyloid precursor protein (APP) of Alzheimer's disease in the middle of the amyloid beta peptide (Abeta) domain. It is generally thought that the alpha-secretase pathway mitigates Abeta formation in the normal brain. Several studies have suggested that ADAM9, ADAM 10, and ADAM 17 are candidate alpha-secretases belonging to the ADAM (a disintegrin and metalloprotease) family, which are membrane-anchored cell surface proteins. In this comparative study of ADAM9, ADAM 10, and ADAM 17, we examined the physiological role of ADAMs by expressing these ADAMs in COS-7 cells, and both "constitutive" and "regulated" alpha-secretase activities of these ADAMs were determined. We tried to suppress the expression of these ADAMs in human glioblastoma A172 cells, which contain large amounts of endogenous alpha-secretase, by lipofection of the double-stranded RNA (dsRNA) encoding each of these ADAMs. The results indicate that ADAM9, ADAM 10, and ADAM 17 catalyze alpha-secretory cleavage and therefore act as alpha-secretases in A172 cells. This is the first report that to suggest the endogenous alpha-secretase is composed of several ADAM enzymes. (C) 2002 Elsevier Science (USA). All rights reserved.