Amyloid peptides in different assembly states and related effects on isolated and cellular proteasomes
Amyloid peptides in different assembly states and related effects on isolated and cellular proteasomes
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DOI：
10.1016/j.brainres.2008.03.003
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发表时间：
2008-05-13
期刊：
影响因子：
2.9
通讯作者：
Eleuteri, Anna Maria
中科院分区：
文献类型：
--
作者：
Cecarini, Valentina;Bonfili, Laura;Eleuteri, Anna Maria
淀粉样蛋白p蛋白（A β）在阿尔茨海默病（AD）发病机制中的作用已得到广泛研究，淀粉样蛋白聚集体被认为是神经元功能障碍的主要原因。越来越多的证据表明，这种蛋白质与蛋白酶体，细胞蛋白水解机制，特别是泛素-蛋白酶体系统之间的相关性。20 S蛋白酶体是26 S蛋白酶体的催化核心，主要负责清除错误折叠和氧化的蛋白质。在这项工作中，我们研究了两种主要的淀粉样肽A β（1-40）和A β（1-42）的不同组装状态对20 S蛋白酶体功能和泛素依赖的蛋白质降解途径的影响。特别是，我们测试了A β处理后对纯化的20 S复合物和人神经母细胞瘤细胞系裂解物的蛋白酶体活性。我们的研究结果表明，蛋白酶体活性显着下降，更明显的细胞裂解物比分离的复合物，和增加量的泛素-蛋白质结合物和已知的蛋白酶体底物（p27）。此外，蛋白酶体功能的改变与细胞活力的降低无关，但与蛋白质氧化水平的增加有关。(C)2008 Elsevier B. V.保留所有权利。
The role of amyloid-p protein (A beta) in the pathogenesis of Alzheimer's disease (AD) has been widely investigated and amyloid aggregates are considered a major cause of neuronal dysfunction. Increasing evidence has identified a correlation between this protein and the proteasome, the cellular proteolytic machinery, in particular the ubiquitin-proteasome system. The 20S proteasome is the catalytic core of a complex, known as 26S proteasome, and is the main responsible for the clearance of misfolded and oxidized proteins. In this work we have investigated the effects of different assembly states of two major amyloid peptides, A beta (1-40) and A beta (1-42) on the 20S proteasome functionality and on the ubiquitin-dependent pathway of protein degradation. In particular, we have tested proteasome activities after A beta treatment on purified 20S complexes and on lysates of a human neuroblastoma cell line. Our findings show a significant decrease in proteasome activity, more evident in cell lysates than in isolated complexes, and an increased amount of ubiquitin-protein conjugates and of a known proteasome substrate (p27). Furthermore, the altered proteasome functionality is not associated with a decrease in cell viability, but is linked with increased levels of protein oxidation. (C) 2008 Elsevier B.V. All rights reserved.