Alzheimer's β-amyloid vasoactivity:: identification of a novel β-amyloid conformational intermediate
Alzheimer's β-amyloid vasoactivity:: identification of a novel β-amyloid conformational intermediate
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DOI：
10.1016/s0014-5793(98)01170-3
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发表时间：
1998-10-09
期刊：
影响因子：
3.5
通讯作者：
Mullan, M
中科院分区：
文献类型：
--
作者：
Crawford, F;Soto, C;Mullan, M
β-淀粉样蛋白（A β）肽先前已显示在体外增强苯肾上腺素或内皮素-1诱导的主动脉环收缩。A β血管活性的特点为了确定A β的哪些性质决定其对血管的生物活性，我们研究了许多A β类似物和片段，单独和组合，包括那些已知与阿尔茨海默病有关的疾病（A β（1-42））和遗传性脑出血伴淀粉样变性-荷兰型（A β（22 Q）（1-40））血管活性似乎与溶液中肽所采用的构象有关。富含β折叠片层的A β（1-42）和A β（22 Q）（1-40）各自的血管活性低于主要为无规卷曲的野生型A β（1-40）。然而，最具血管活性的A β肽是含有无规卷曲和β折叠结构的混合物的组合，这一发现表明，含有低或高水平β-褶皱构象的血管活性低于那些含有中等量的这种结构基序的构象，这使我们能够提出在无规卷曲和β-这是第一次发现A β构象中间体和与它们相关的生物活性。(C)1998年欧洲生物化学学会联合会。
The beta-amyloid (A beta) peptide has previously been shown to enhance phenylephrine or endothelin-l induced constriction of aortic rings in vitro. The characteristics of A beta vasoactivity (dose, fragment length, timing) suggest that the mechanism is distinct from A beta cytotoxicity, To identify which properties of A beta determine its biological activity on vessels, we investigated a number of A beta analogues and fragments, individually and in combination, including those that are known to be associated with Alzheimer's disease (A beta(1-42)) and hereditary cerebral hemorrhage with amyloidosis - Dutch type (A beta(22Q)(1-40)) The vasoactivity appears to be related to the conformation adopted by the peptide in solution. The beta-pleated sheet rich A beta(1-42) and A beta(22Q)(1-40) were each less vasoactive than the mainly random coil wild type A beta(1-40) However, the most vasoactive A beta peptides were combinations which contain mixtures of random coil and beta-sheet structure, The finding that peptides containing low or high levels of beta-pleated conformation are less vasoactive than those containing intermediate amounts of this structural motif allows us to propose the existence of a transitional form between random coil and beta-pleated that is the vasoactive species of A beta, This is the first time that A beta conformational intermediates have been identified and a biological activity associated with them. (C) 1998 Federation of European Biochemical Societies.