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发酵木瓜制剂可减轻β-淀粉样前体蛋白:β-淀粉样蛋白介导的β-淀粉样前体蛋白和过表达β-淀粉样前体蛋白瑞典突变体的SH-SY5Y细胞中的铜神经毒性。

Fermented papaya preparation attenuates beta-amyloid precursor protein: beta-amyloid-mediated copper neurotoxicity in beta-amyloid precursor protein and beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells.

作者信息

Zhang J, Mori A, Chen Q, Zhao B

机构信息

State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Chaoyang District, Beijing, 100101, PR China.

出版信息

Neuroscience. 2006 Nov 17;143(1):63-72. doi: 10.1016/j.neuroscience.2006.07.023. Epub 2006 Sep 8.

Abstract

Recent studies indicate that the deposition of beta-amyloid (Abeta) is related in the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is still not clear. The abnormal interactions of Abeta with metal ions such as copper are implicated in the process of Abeta deposition and oxidative stress in AD brains. In the present study, we established a new AD model, using which we found that copper triggered the Abeta neurotoxicity in SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw) in a concentration dependent manner. Fermented papaya preparation (FPP) has shown high free radical scavenging ability in vivo and in vitro. FPP post-treatment increased cell viability and decreased the intracellular [Ca2+]i, reactive oxygen species (ROS) generation such as hydroxyl free radical and superoxide anion and nitric oxide (NO) accumulation in the cell. Our results also show that FPP prevents the cell apoptosis through bax/bcl-2 sensitive pathway.

摘要

最近的研究表明,β-淀粉样蛋白(Aβ)的沉积与阿尔茨海默病(AD)的发病机制有关,但其潜在机制仍不清楚。Aβ与金属离子如铜的异常相互作用与AD大脑中Aβ沉积和氧化应激过程有关。在本研究中,我们建立了一种新的AD模型,利用该模型我们发现铜以浓度依赖性方式触发了过表达人APP瑞典突变体形式(APPsw)的SH-SY5Y细胞中的Aβ神经毒性。发酵木瓜制剂(FPP)在体内和体外均表现出高自由基清除能力。FPP后处理增加了细胞活力,降低了细胞内[Ca2+]i、活性氧(ROS)如羟基自由基和超氧阴离子的生成以及细胞内一氧化氮(NO)的积累。我们的结果还表明,FPP通过bax/bcl-2敏感途径预防细胞凋亡。

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