Manganese induces the overexpression of α-synuclein in PC12 cells via ERK activation

Manganese has been known to induce neurological disorders. In the present study, we determined the effect of manganese on the expression of e-synuclein in PC12 cells and its role in manganese-induced cytotoxicity. We also investigated the relationship between alpha-synuclein expression and the change of ERK1/2 MAPK activity. In our research, manganese exposure induced the overexpression of alpha-synuclein, while siRNA knockdown of alpha-synuclein reversed manganese-induced cytotoxicity. Furthermore, manganese induced the activation of ERK1/2 MAPK. The MEK1 inhibitor PD98059, which inhibits the activation of ERK MAPK, attenuated the overexpression of alpha-synuclein and the cytotoxicity induced by manganese. In conclusion, our studies show that manganese may induce the overexpression of alpha-synuclein via ERK1/2 activation, which may play a role in manganese-induced cytotoxicity. (C) 2010 Elsevier B.V. All rights reserved.