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 alpha-synuclein. Since Ca(2+) plays an important role in cell degeneration, [Ca(2+)] (i) in alpha-synuclein-overexpressed human glioma cells was analyzed by Fura-2 fluorometry. Overexpression of alpha-synuclein increased the basal level of [Ca(2+)] (i) , and a higher Ca(2+) response to hydrogen peroxide was further observed. The effect that alpha-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 alpha-synuclein under oxidative stress may contribute to the glial cell death in MSA.