The induction of amyloid precursor protein and α-synuclein in rat hippocarnpal astrocytes by diethyldithiocarbamate and copper with or without glutathione
The induction of amyloid precursor protein and α-synuclein in rat hippocarnpal astrocytes by diethyldithiocarbamate and copper with or without glutathione
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DOI：
10.1016/j.toxlet.2003.09.009
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发表时间：
2004-01-15
影响因子：
3.5
通讯作者：
Trombetta, LD
中科院分区：
文献类型：
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作者：
Cheng, SY;Trombetta, LD
α-突触核蛋白是路易体的主要成分。它的聚集可以被铜、铁或β-淀粉样蛋白(Abeta)加速，并被认为在淀粉样斑块的形成过程中提供了一个成核中心。淀粉样斑块的主要结构成分是Abeta，它来自一种更大的蛋白质，即淀粉样前体蛋白(APP)。外源生物与这种神经退行性疾病的病因学有关。二乙基二硫代氨基甲酸酯(DDC)的神经毒性机制包括铜的络合和与SH基团的相互作用导致氧化应激。在本研究中，用DDC(75um)、CuCl2(0.2um)或DDC(75um)+CuCl2(0.2um)处理大鼠海马星形胶质细胞1h，并允许细胞在有或没有10 mM GSH的情况下恢复。结果表明，APP和α-突触核蛋白的产生呈时间依赖性增加。处理后4h，APP胞浆内可见少量阳性染色物质沉积，8h后APP和α-突触核蛋白表达均增加。免疫印迹支持免疫细胞化学结果。谷胱甘肽(GSH)处理后8h，这些蛋白的积聚减少。(C)2003爱思唯尔爱尔兰有限公司。保留所有权利。
alpha-Synuclein is the major component of Lewy bodies. Its aggregation can be accelerated by copper, iron, or beta-amyloid (Abeta) and has been thought to provide a nucleation center during the formation of amyloid plaques. The main structural component of amyloid plaque is Abeta, which is derived from a larger protein, amyloid precursor protein (APP). Xenobiotics have been implicated in the etiology of the neurodegenerative disease. Mechanisms of diethyldithiocarbamate (DDC) neurotoxicity involve copper chelation and interactions with SH groups resulting in oxidative stress. In this study, rat hippocampal astrocytes were treated with DDC (75 muM), CuCl2 (0.2 muM), or DDC (75 muM) Plus CuCl2 (0.2 muM) for 1 h. Cells were allowed to recover with or without 10 mM GSH. Results showed an increase of APP and alpha-synuclein production occurring in a time-dependent manner. At 4 h post-treatment, cells contained small positively stained material deposited throughout the cytosol for APP and by 8 h post-treatment increases were seen in both APP and alpha-synuclein. Immunoblots supported immunocytochemical results. Glutathione (GSH) decreased the accumulation of these proteins at 8 h post-treatment. (C) 2003 Elsevier Ireland Ltd. All rights reserved.