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

共 20 条

[11]

Gottlieb RA, 2001, BIOL SIGNAL RECEPT, V10, P147

[12] p53-dependent induction of apoptosis by proteasome inhibitors [J].

Lopes, UG ;

Erhardt, P ;

Yao, RJ ;

Cooper, GM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (20) :12893-12896

[13] A novel in vivo post-translational modification of p53 by PARP-1 in MPTP-induced parkinsonism [J].

Mandir, AS ;

Simbulan-Rosenthal, CM ;

Poitras, MF ;

Lumpkin, JR ;

Dawson, VL ;

Smulson, ME ;

Dawson, TM .

JOURNAL OF NEUROCHEMISTRY, 2002, 83 (01) :186-192

[14] Altered proteasomal function in sporadic Parkinson's disease [J].

McNaught, KS ;

Belizaire, R ;

Isacson, O ;

Jenner, P ;

Olanow, CW .

EXPERIMENTAL NEUROLOGY, 2003, 179 (01) :38-46

[15] Proteasomal function is impaired in substantia nigra in Parkinson's disease [J].

McNaught, KSP ;

Jenner, P .

NEUROSCIENCE LETTERS, 2001, 297 (03) :191-194

[16] Failure of the ubiquitin-proteasome system in Parkinson's disease [J].

McNaught, KSP ;

Olanow, CW ;

Halliwell, B ;

Isacson, O ;

Jenner, P .

NATURE REVIEWS NEUROSCIENCE, 2001, 2 (08) :589-594

[17] Multiple C-terminal lysine residues target p53 for ubiquitin-proteasome-mediated degradation [J].

Rodriguez, MS ;

Desterro, JMP ;

Lain, S ;

Lane, DP ;

Hay, RT .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (22) :8458-8467

[18] p53-dependent apoptosis pathways [J].

Shen, Y ;

White, E .

ADVANCES IN CANCER RESEARCH, VOL 82, 2001, 82 :55-+

[19] The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription [J].

Steffan, JS ;

Kazantsev, A ;

Spasic-Boskovic, O ;

Greenwald, M ;

Zhu, YZ ;

Gohler, H ;

Wanker, EE ;

Bates, GP ;

Housman, DE ;

Thompson, LM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6763-6768

[20] Surfing the p53 network [J].

Vogelstein, B ;

Lane, D ;

Levine, AJ .

NATURE, 2000, 408 (6810) :307-310

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