alpha-Synuclein overexpression during manganese-induced apoptosis in SH-SY5Y neuroblastoma cells

Brain Research Bulletin
Yan LiLiping Ye

Abstract

Chronic inorganic manganese (Mn) exposure has been known to induce neurological disorders similar to Parkinson's disease (PD). Apoptosis has been shown to be involved in manganese-induced neurotoxicity. However, the up-stream molecular mechanisms for cell apoptosis are not established. alpha-Synuclein (alpha-syn) is a major component of intracellular inclusions in PD, Alzheimer's disease (AD), and other neurodegenerative disorders. We investigated the role of alpha-syn in manganese chloride (MnCl(2))-induced apoptosis. Results show that MnCl(2) enhanced transcriptional and translational alpha-syn overexpression, and apoptosis as measured by caspase-3 activity and flow cytometry. Overexpressing alpha-syn exacerbated manganese-induced apoptosis, whereas antisense alpha-syn treatment significantly reversed MnCl(2)-induced apoptosis in human neuroblastoma SH-SY5Y cells. In conclusion, our results imply that intracellular alpha-syn overexpression may be responsible for MnCl(2)-induced apoptosis.

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