[Iron-dependent cytotoxic effects of dopa on cultured neurons of the dorsal root ganglia].
Although many authors have suggested that dopamine and its metabolites producing free radicals have an harmful effect in the substantia nigra, experimental evidence has not been shown. Using a newly established enzyme immunoassay of the neurofilament protein, a reliable index for the number of survived neurons in tissue culture, we evaluate the effects of Dopa on the neurons of dorsal root ganglia from mice. Neurons were destroyed by the exposure of 0.5 mM Dopa with or without superoxide dismutase and catalase, but they were saved by the pretreatment with 1.0 mM deferoxamine mesylate, a powerful iron-chelating agent. Formation of malondialdehyde, an index of lipid peroxidation, was also observed in the reaction of 0.5 mM Dopa and cerebral cortical neurons from new-born rats only when iron was present. These results indicate that Dopa initiates lipid peroxidation of cell membrane in the presence of a small amount of iron in the culture with little or no participation of reactive oxygen species, leading to the destruction of the neurons. In Parkinson's disease, the cytotoxic mechanism of Dopa and iron may involve the neuronal degeneration in the substantia nigra abundant in iron and dopaminergic neurons.
Tanaka
M
M
Division of Neurology, Gunma University Hospital.
Sotomatsu
A
A
Kanai
H
H
Hirai
S
S
D000818:Animals; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000633:toxicity*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology; D007501:Iron / Q000502:physiology*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology
D004295:Dihydroxyphenylalanine; D007501:Iron