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

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.