alpha-Synuclein selectively increases manganese-induced viability loss in SK-N-MC neuroblastoma cells expressing the human dopamine transporter.
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 alpha-synuclein. SK-N-MC neuroblastoma cells stably expressing the human dopamine transporter were transfected with human alpha-synuclein and cell clones with and without alpha-synuclein immunoreactivity were obtained. Cells were exposed for 24-72 h to 1-10 microM dopamine, 0.1-3 microM MPP(+), 0.1-1 mM FeCl(2) or 30-300 microM MnCl(2) added to the culture medium. There was no difference between cells expressing alpha-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 alpha-synuclein after 72 h. These findings suggest that manganese may co-operate with alpha-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.
Pifl
Christian
C
Brain Research Institute, University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. christian.pifl@univie.ac.at
Khorchide
Maya
M
Kattinger
Alexandra
A
Reither
Harald
H
Hardy
John
J
Hornykiewicz
Oleh
O
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000633:toxicity*; D004298:Dopamine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D005296:Ferrous Compounds / Q000633:toxicity; D015870:Gene Expression; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D017895:Manganese Compounds; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D009410:Nerve Degeneration / Q000139:chemically induced; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma; D051843:Synucleins; D014162:Transfection; D051844:alpha-Synuclein
D002712:Chlorides; D050483:Dopamine Plasma Membrane Transport Proteins; D005296:Ferrous Compounds; D006540:Herbicides; D017895:Manganese Compounds; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; C025340:manganese chloride; D015655:1-Methyl-4-phenylpyridinium; C029451:ferrous chloride; D004298:Dopamine