Behavioral and brain functions : BBF · 2013
The role of autophagy in Parkinson's disease: rotenone-based modeling.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Xiong Nian, Xiong Jing, Jia Min, Liu Ling, Zhang Xiaowei, Chen Zhenzhen, Huang Jinsha, Zhang Zhentao, Hou Lingling, Luo Zhijian, Ghoorah Devina, Lin Zhicheng, Wang Tao
Аннотация
BACKGROUND: Autophagy-mediated self-digestion of cytoplasmic inclusions may be protective against neurodegenerative diseases such as Parkinson's disease (PD). However, excessive autophagic activation evokes autophagic programmed cell death.
METHODS: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD.
RESULTS: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time- and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo.
CONCLUSIONS: These data, along with our previous finding showing rotenone-induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD.
METHODS: In this study, we aimed at exploring the role of autophagy in the pathogenesis of rotenone-induced cellular and animal models for PD.
RESULTS: Reactive oxygen species over-generation, mitochondrial membrane potential reduction or apoptosis rate elevation occurred in a dose-dependent fashion in rotenone-treated human neuroblastoma cell line SH-SY5Y. The time- and dose-dependent increases in autophagic marker microtubule-associated protein1 light chain 3 (LC3) expression and decreases in autophagic adaptor protein P62 were observed in this cellular model. LC3-positive autophagic vacuoles were colocalized with alpha-synuclein-overexpressed aggregations. Moreover, the number of autophagic vacuoles was increased in rotenone-based PD models in vitro and in vivo.
CONCLUSIONS: These data, along with our previous finding showing rotenone-induced toxicity was prevented by the autophagy enhancers and was aggravated by the autophagy inhibitors in SH-SY5Y, suggest that autophagy contributes to the pathogenesis of PD, attenuates the rotenone toxicity and possibly represents a new subcellular target for treating PD.
Предметные рубрики MeSH
ApoptosisAutophagyBlotting, WesternCell DeathCell LineCell ProliferationColoring AgentsDose-Response Relationship, DrugDown-RegulationHumansImmunohistochemistryMembrane Potential, MitochondrialMicroscopy, Electron, TransmissionMicrotubule-Associated ProteinsParkinson Disease, SecondaryReactive Oxygen SpeciesRotenoneTetrazolium SaltsThiazolesUncoupling Agents