Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson's Disease.
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.
['Chen|Tingting|T|', 'Tan|Jieqiong|J|', 'Wan|Zhengqing|Z|', 'Zou|Yongyi|Y|', 'Afewerky|Henok Kessete|HK|', 'Zhang|Zhuohua|Z|', 'Zhang|Tongmei|T|0000-0002-5973-5795']
D000255:Adenosine Triphosphate D017209:Apoptosis D002681:China D004305:Dose-Response Relationship, Drug D006801:Humans D042541:Intracellular Space D008928:Mitochondria D009245:NADH Dehydrogenase D010300:Parkinson Disease D010575:Pesticides D046988:Proteasome Endopeptidase Complex D025801:Ubiquitin D056811:Unfolded Protein Response
pesticides China mitochondria ubiquitin-Proteasome system Parkinson’s disease