Dopa and dopamine cause cultured neuronal death in the presence of iron.
We examined the cytotoxicity of dopa and dopamine for cultured neurons by using a newly developed enzyme immunoassay for neurofilament protein to determine surviving neuronal numbers. Each of the two catechols caused neuronal death in the presence of iron with or without superoxide dismutase and catalase, while deferoxamine mesylate prevented neuronal loss. Lipid peroxidation of phospholipid liposomes was confirmed to be produced by the combination of the catechols and iron (Fe3(+)-ADP complex). Thus, it was strongly suggested that cultured neurons were killed via the peroxidative cleavage of cell membrane components provoked by the catechols and iron. This mechanism of neuronal loss may play an important role in the degeneration in the substantia nigra of Parkinson's disease, because the catechols and iron are abundant in this region.
Tanaka
M
M
Department of Neurology, Gunma University, School of Medicine, Maebashi, Japan.
Sotomatsu
A
A
Kanai
H
H
Hirai
S
S
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D007381:Intermediate Filament Proteins / Q000032:analysis; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016900:Neurofilament Proteins; D009474:Neurons / Q000187:drug effects*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000473:pathology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D007381:Intermediate Filament Proteins; D008081:Liposomes; D016900:Neurofilament Proteins; D000244:Adenosine Diphosphate; D004295:Dihydroxyphenylalanine; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D004298:Dopamine