PD (Parkinson's disease) is a complex disorder that is associated with neuronal loss or dysfunction caused by genetic risks, environmental factors and advanced aging. It has been reported that DJ-1 mutations rendered neurons sensitive to oxidative damage, which led to the onset of familiar PD. However, the molecular mechanism is still unclear. In the present study we show that DJ-1 interacts with RACK1 (receptor of activated C kinase 1) and increases its dimerization and protein stability. The DJ-1 transgene protects cortical neurons from H2O2-induced apoptosis, and this protective effect is abrogated by knocking down RACK1. Similarly, deletion of DJ-1 in cortical neurons increases the sensitivity to H2O2, and the damage can be significantly rescued by DJ-1 or DJ-1/RACK1 co-transfection, but not by RACK1 alone. We observed further that the interaction of DJ-1 and RACK1 is disrupted by H2O2 or MPP+ (1-methyl-4-phenylpyridinium) treatment, and the protein levels of DJ-1 and RACK1 decreased in neurodegenerative disease models. Taken together, the DJ-1–RACK1 complex protects neurons from oxidative stress-induced apoptosis, with the implication that DJ-1 and RACK1 might be novel targets in the treatment of neurodegenerative diseases.
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Research Article|
August 22 2014
DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis
Jun Ma;
Jun Ma
*State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
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Rong Wu;
Rong Wu
*State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
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Qiang Zhang;
Qiang Zhang
*State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
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Jun-bing Wu;
Jun-bing Wu
*State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
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Jizhong Lou;
Jizhong Lou
*State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
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Zheng Zheng;
Zheng Zheng
†Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
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Jian-qing Ding;
Jian-qing Ding
‡Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
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Zengqiang Yuan
Zengqiang Yuan
1
*State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
1To whom correspondence should be addressed (email zqyuan@sun5.ibp.ac.cn).
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Publisher: Portland Press Ltd
Received:
February 25 2014
Revision Received:
June 05 2014
Accepted:
June 20 2014
Accepted Manuscript online:
June 20 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 462 (3): 489–497.
Article history
Received:
February 25 2014
Revision Received:
June 05 2014
Accepted:
June 20 2014
Accepted Manuscript online:
June 20 2014
Connected Content
A correction has been published:
Correction: DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis
Citation
Jun Ma, Rong Wu, Qiang Zhang, Jun-bing Wu, Jizhong Lou, Zheng Zheng, Jian-qing Ding, Zengqiang Yuan; DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis. Biochem J 15 September 2014; 462 (3): 489–497. doi: https://doi.org/10.1042/BJ20140235
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