α-Synuclein overexpression during manganese-induced apoptosis in SH-SY5Y neuroblastoma cells
α-Synuclein overexpression during manganese-induced apoptosis in SH-SY5Y neuroblastoma cells
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DOI：
10.1016/j.brainresbull.2009.11.007
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发表时间：
2010-03-16
影响因子：
3.8
通讯作者：
Ye, Liping
中科院分区：
文献类型：
--
作者：
Li, Yan;Sun, Liguang;Ye, Liping
已知慢性无机锰（Mn）暴露可诱发类似于帕金森病（PD）的神经系统疾病。细胞凋亡已被证明参与锰诱导的神经毒性。然而，细胞凋亡的上游分子机制尚未建立。α-突触核蛋白（α-syn）是PD、阿尔茨海默病（AD）和其他神经退行性疾病中细胞内包涵体的主要组分。我们研究了α-syn在氯化锰（MnCl 2）诱导的细胞凋亡中的作用。结果表明，MnCl 2增强转录和翻译的α-syn的过度表达，和细胞凋亡的caspase-3活性和流式细胞术测量。在人神经母细胞瘤SH-SY 5 Y细胞中，过表达α-syn加剧了锰诱导的凋亡，而反义α-syn处理显著逆转了MnCl 2诱导的凋亡。总之，我们的研究结果表明，细胞内α-syn过度表达可能是负责氯化锰诱导的细胞凋亡。(C)2009 Elsevier Inc. All rights reserved.
Chronic inorganic manganese (Mn) exposure has been known to induce neurological disorders similar to Parkinson's disease (PD). Apoptosis has been shown to be involved in manganese-induced neurotoxicity. However, the up-stream molecular mechanisms for cell apoptosis are not established. a-Synuclein (alpha-syn) is a major component of intracellular inclusions in PD, Alzheimer's disease (AD), and other neurodegenerative disorders. We investigated the role of alpha-syn in manganese chloride (MnCl2)-induced apoptosis. Results show that MnCl2 enhanced transcriptional and translational alpha-syn overexpression, and apoptosis as measured by caspase-3 activity and flow cytometry. Overexpressing alpha-syn exacerbated manganese-induced apoptosis, whereas antisense alpha-syn treatment significantly reversed MnCl2-induced apoptosis in human neuroblastoma SH-SY5Y cells. In conclusion, our results imply that intracellular alpha-syn overexpression may be responsible for MnCl2-induced apoptosis. (C) 2009 Elsevier Inc. All rights reserved.