α-Synuclein selectively increases manganese-induced viability loss in SK-N-MC neuroblastoma cells expressing the human dopamine transporter

Abstract

The established or potentially toxic agents implicated in the nigral cell death in Parkinson's disease, dopamine, 1-methyl-4-phenylpyridinium (MPP +), iron, and manganese, were examined as to their effects on the viability of cells overexpressing α-synuclein. SK-N-MC neuroblastoma cells stably expressing the human dopamine transporter were transfected with human α-synuclein and cell clones with and without α-synuclein immunoreactivity were obtained. Cells were exposed for 24–72 h to 1–10 μM dopamine, 0.1–3 μM MPP +, 0.1–1 mM FeCl 2 or 30–300 μM MnCl 2 added to the culture medium. There was no difference between cells expressing α-synuclein and control cells after exposure to dopamine, MPP + or FeCl 2. However, MnCl 2 resulted in a significantly stronger decreased viability of cells overexpressing α-synuclein after 72 h. These findings suggest that manganese may co-operate with α-synuclein in triggering neuronal cell death such as seen in manganese parkinsonism. The relevance of our observations for the pathoetiology of Parkinson's disease proper remains to be determined.