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MPP+诱导的 SH-SY5Y 细胞凋亡的蛋白质组学分析。

Proteomics analysis of MPP+-induced apoptosis in SH-SY5Y cells.

机构信息

Department of Neurology, The First Hospital, Jilin University, 71 Xinmin Street, Changchun, 130021, People's Republic of China.

出版信息

Neurol Sci. 2011 Apr;32(2):221-8. doi: 10.1007/s10072-010-0340-3. Epub 2010 Jun 19.

Abstract

Accumulating evidence suggests that oxidative stress plays a pivotal role in dopaminergic neurodegeneration. However, the kinds of proteins involved in the response to oxidative stress remain unclear. In the present study, SH-SY5Y cells were treated with neurotoxin 1-methyl-4-phenyl-pyridinium ion (MPP+) to induce apoptotic neuronal injury. 2D-DIGE followed by MALDI-TOF-MS was used to determine the changing protein levels. Proteomics analysis revealed that 22 proteins were differentially altered in MPP(+)-treated SH-SY5Y cells, of which 7 were up-regulated proteins and 15 were down-regulated proteins, respectively. Three protein spots were unambiguously identified as sorcin, annexin V, and ribosomal protein P0. The three proteins showed a significant increase in level, suggesting a role in MPP(+)-induced apoptosis. The functional roles of these three proteins collectively indicate that multiple mechanisms are pertinent in the underlying pathogenesis of Parkinson's disease (PD), such as apoptosis, calcium homeostasis, and DNA insults.

摘要

越来越多的证据表明,氧化应激在多巴胺能神经元退行性变中起着关键作用。然而,涉及氧化应激反应的蛋白质种类仍不清楚。在本研究中,我们用神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPP+)处理 SH-SY5Y 细胞,诱导凋亡性神经元损伤。用 2D-DIGE 结合 MALDI-TOF-MS 来确定蛋白表达水平的变化。蛋白质组学分析显示,在 MPP+处理的 SH-SY5Y 细胞中有 22 种蛋白发生了差异改变,其中 7 种为上调蛋白,15 种为下调蛋白。有 3 个蛋白斑点被明确鉴定为钙结合蛋白 Sorcin、膜联蛋白 V 和核糖体蛋白 P0。这三种蛋白的水平显著增加,提示它们在 MPP+诱导的细胞凋亡中起作用。这三种蛋白的功能作用共同表明,多种机制与帕金森病(PD)的潜在发病机制有关,如细胞凋亡、钙稳态和 DNA 损伤。

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