title: α-Synuclein increases U251 cells vulnerability to hydrogen peroxide by disrupting calcium homeostasis.
abstract: Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by glial cytoplasmic inclusions containing insoluble α-synuclein. Since Ca(2+) plays an important role in cell degeneration, [Ca(2+)]( i ) in α-synuclein-overexpressed human glioma cells was analyzed by Fura-2 fluorometry. Overexpression of α-synuclein increased the basal level of [Ca(2+)]( i ), and a higher Ca(2+) response to hydrogen peroxide was further observed. The effect that α-synuclein overexpression caused U251 cells to be more vulnerable to hydrogen peroxide was eliminated by Ca(2+) chelator BAPTA-AM or transient receptor potential channels blocker SKF 96365 but not by L-type Ca(2+) channel blocker nimodipine. These findings suggest that the dysregulation of cellular Ca(2+) homeostasis caused by α-synuclein under oxidative stress may contribute to the glial cell death in MSA.
authors.affiliation: School of Life Science, Beijing Institute of Technology, No. 5 Zhongguancun Nandajie, Haidian District, Beijing, 100081, People's Republic of China.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Ying
authors.forename: Fankai
authors.initials: F
authors.lastname: Lin
authors.forename: Weihong
authors.initials: W
authors.lastname: Gu
authors.forename: Yang
authors.initials: Y
authors.lastname: Su
authors.forename: Abida
authors.initials: A
authors.lastname: Arshad
authors.forename: Hong
authors.initials: H
authors.lastname: Qing
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
mesh_terms: D002118:Calcium / Q000037:antagonists & inhibitors* / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D051844:alpha-Synuclein; D006861:Hydrogen Peroxide; D002118:Calcium