α-Synuclein increases U251 cells vulnerability to hydrogen peroxide by disrupting calcium homeostasis

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.