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Int J Mol Sci. 2017 Nov 23;18(12). pii: E2507. doi: 10.3390/ijms18122507.

Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson's Disease.

Author information

1
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. chentingting@sklmg.edu.cn.
2
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. jieqiong.tan@gmail.com.
3
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. wanzhengqing@sklmg.edu.cn.
4
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. zouyongyi@gmail.com.
5
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. henokessete@hust.edu.cn.
6
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. henokessete@hust.edu.cn.
7
The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China. henokessete@hust.edu.cn.
8
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. zhangzhuohua@sklmg.edu.cn.
9
State Key Laboratory of Medical Genetics, Xiangya Medical School, Central South University, Changsha 410078, China. zhangtongmei1202@gmail.com.
10
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. zhangtongmei1202@gmail.com.
11
The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China. zhangtongmei1202@gmail.com.

Abstract

Evidence continues to accumulate that pesticides are the leading candidates of environmental toxins that may contribute to the pathogenesis of Parkinson's disease. The mechanisms, however, remain largely unclear. According to epidemiological studies, we selected nine representative pesticides (paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad, trichlorphon and carbaryl) which are commonly used in China and detected the effects of the pesticides on mitochondria and ubiquitin-proteasome system (UPS) function. Our results reveal that all the nine studied pesticides induce morphological changes of mitochondria at low concentrations. Paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced mitochondria fragmentation. Furthermore, some of them (paraquat, rotenone, chlorpyrifos, fenpyroximate and tebufenpyrad) caused a significant dose-dependent decrease of intracellular ATP. Interestingly, these pesticides which induce mitochondria dysfunction also inhibit 26S and 20S proteasome activity. However, two out of the nine pesticides, namely trichlorphon and carbaryl, were found not to cause mitochondrial fragmentation or functional damage, nor inhibit the activity of the proteasome, which provides significant guidance for selection of pesticides in China. Moreover, our results demonstrate a potential link between inhibition of mitochondria and the UPS, and pesticide-induced Parkinsonism.

KEYWORDS:

China; Parkinson’s disease; mitochondria; pesticides; ubiquitin-Proteasome system

PMID:
29168786
PMCID:
PMC5751110
DOI:
10.3390/ijms18122507
[Indexed for MEDLINE]
Free PMC Article

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