P53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic SH-SY5Y

被引：31

作者：

Nakaso, K ^{[1
]}

Yoshimoto, Y ^{[1
]}

Yano, H ^{[1
]}

Takeshima, T ^{[1
]}

Nakashima, K ^{[1
]}

机构：

[1] Tottori Univ, Fac Med, Inst Neurol Sci, Dept Neurol, Yonago, Tottori 6838504, Japan

来源：

NEUROSCIENCE LETTERS | 2004年 / 354卷 / 03期

关键词：

p53; Bax; mitochondria; JC-1; ubiquitin-proteasome system; Parkinson's disease;

D O I：

10.1016/j.neulet.2003.10.048

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

引用

页码：213 / 216

页数：4

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