蛋白酶体抑制介导p53导致多巴胺能SH-SY5Y细胞的线粒体功能障碍

p53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic SH-SY5Y cells.

作者信息

Nakaso Kazuhiro, Yoshimoto Yuko, Yano Hidetaka, Takeshima Takao, Nakashima Kenji

机构信息

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan.

出版信息

Neurosci Lett. 2004 Jan 16;354(3):213-6. doi: 10.1016/j.neulet.2003.10.048.

DOI:10.1016/j.neulet.2003.10.048

PMID:14700734

Abstract

Decreased proteasome activity is an important pathology in Parkinson's disease (PD), which is related to cell death and Lewy body formation. In this study, we show that p53-activity may correlate with neuronal death via the mitochondrial pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of p53 in human dopaminergic neuroblastoma SH-SY5Y cells. The increased stabilization of p53 upregulated the level of Bax and mitochondrial depolarization. These events were inhibited by the p53 inhibitor, pifithrin-alpha (PFT). Cell viability analyzes demonstrated that PFT partially prevented MG132-induced cell death. These results suggest that p53 is a candidate as an intermediary between the proteasome system and mitochondria-related neuronal death in PD.

摘要

蛋白酶体活性降低是帕金森病（PD）的一个重要病理特征，这与细胞死亡和路易小体形成有关。在本研究中，我们表明p53活性可能通过PD模型中的线粒体途径与神经元死亡相关。蛋白酶体抑制剂MG132诱导人多巴胺能神经母细胞瘤SH-SY5Y细胞中p53的积累。p53稳定性增加上调了Bax水平和线粒体去极化。这些事件被p53抑制剂pifithrin-α（PFT）抑制。细胞活力分析表明，PFT部分预防了MG132诱导的细胞死亡。这些结果表明，p53作为蛋白酶体系统与PD中线粒体相关神经元死亡之间的中介物是一个候选者。