title: Alpha-synuclein overexpression induced mitochondrial damage by the generation of endogenous neurotoxins in PC12 cells.
abstract: Alpha-synuclein is one of the important components of Lewy body which involved in neuropathology of Parkinson's disease (PD). The relationship between α-synuclein and cell death is still unclear. In the study, PC12 cell, stably over expressing α-synuclein model was used, and we investigated the level of intracellular oxidative stress, dopamine and endogenous neurotoxin. The results showed that the level of oxidative stress and intracytoplasmic dopamine (DA) was increased in cells over expressing α-synuclein compared with normal PC12 cells. Simultaneously, additional generation of endogenous neurotoxins 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin (NM-salsolinol) was detected and this phenomenon was exacerbated after exposed to H₂O₂ for 24 h, but mitigated when treated with dopamine synthesis inhibitors. The presence of endogenous neurotoxins exacerbated α-synuclein induced mitochondrial damage. These results suggest that the endogenous neurotoxins may become a bridge between α-synuclein and cell death.
authors.affiliation: School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Bingjie
authors.initials: B
authors.lastname: Xie
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Qing
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D007546:Isoquinolines; D009498:Neurotoxins; D051844:alpha-Synuclein; C036617:salsolinol; D004298:Dopamine