Synthetic neuromelanin is toxic to dopaminergic cell cultures.
In the present study, primary cultures of mesencephalic dopaminergic cells were exposed to synthetic dopamine neuromelanin (NM) for 48 hrs at concentrations of 0, 1, 10, 20, 50 and 100 microg NM/ml medium. Differently prepared synthetic NM with or without incorporated iron and NM oxidatively damaged by hydrogen peroxide were used. All NMs affected cellular structures e.g. as swelling of neural processes, rounding of cells, and occasional inclusion of neuromelanin particles. Cell numbers were uniformly and dose dependently reduced. Exposure to MPP(+) and ferric iron led to cytotoxic changes which could be further aggravated by oxidatively damaged NM, suggesting cytotoxicity of soluble compounds of NM in predamaged neurons.
Institute for Medical Chemistry, Veterinary Medical University, Vienna, Austria.
A
A
Nguyen
G
G
Gille
R
R
Moldzio
S-T
ST
Hung
W-D
WD
Rausch
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005290:Ferric Compounds / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D008543:Melanins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism / Q000506:poisoning*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction
D005290:Ferric Compounds; D008543:Melanins; C014121:neuromelanin; D007501:Iron; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine