Starvation triggers Aβ42 generation from human umbilical vascular endothelial cells
Starvation triggers Aβ42 generation from human umbilical vascular endothelial cells
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DOI：
10.1016/j.febslet.2010.05.048
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发表时间：
2010-07-16
期刊：
影响因子：
3.5
通讯作者：
Chen, Sheng-Di
中科院分区：
文献类型：
--
作者：
Ma, Jian-Fang;Wang, Hong-Mei;Chen, Sheng-Di
脑淀粉样血管病是阿尔茨海默病（Alzheimer's disease，AD）的常见特征，其特征是淀粉样蛋白在脑血管（包括毛细血管）周围沉积存款。CAA的淀粉样蛋白的起源仍有争议。在我们的工作中，我们提供的数据表明，原代脐静脉内皮细胞（HUVEC）携带APP加工分泌酶，并能在饥饿条件下产生A β（42）。饥饿可以通过改变β-分泌酶（BACE 1）和γ-分泌酶（APH和PEN 2）的表达来增加A β（42）的分泌。这个过程是由macroautophagy调控的。3 MA对巨自噬诱导的抑制进一步增加了HUVEC在饥饿条件下产生的A β（42）水平。这些结果表明，饥饿诱导的A β（42）分泌可能有助于CAA的形成，从而导致AD的血管变性。(C)2010年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Cerebral amyloid angiopathy is a common feature in Alzheimer's disease (AD), which is characterized by amyloid deposit around brain vessels including capillaries. The origin of the amyloid protein of CAA remains controversial. In our work, we provide data to show that primary umbilical vein endothelial cells (HUVEC) harbor APP processing secretases and can produce A beta(42) under starvation. Starvation can increase the secretion of A beta(42) by altering the expression of beta-secretases (BACE1) and gamma-secretases (APH and PEN2). This process is regulated by macroautophagy. Suppression of macroautophagy induction by 3MA further increased the level of A beta(42) produced under starvation in HUVECs. These results suggest that starvation-induced A beta(42) secretion might contribute to the formation of CAA and hence vascular degeneration in AD. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.