Involvement of free radicals in MPP+ neurotoxicity against rat dopaminergic neurons in culture.
To examine the mechanisms of the neurotoxicity of 1-methyl-4-phenylpyridinium (MPP+) against dopaminergic neurons, ventral mesencephalic cells from embryonic rats were cultured and exposed to MPP+ with various antioxidants or glutamate receptor antagonists to investigate the participation of free radicals and glutamate, respectively. Such antioxidants as vitamin E, vitamin C, coenzyme Q10, and catalase, but neither allopurinol nor superoxide dismutase, alleviated the MPP(+) -induced death of dopaminergic neurons, while glutamate receptor antagonists did not alter MPP+ neurotoxicity. These findings suggest the participation of free radicals, particularly hydroxyl radicals rather than superoxides, in the process of dopaminergic neuronal death evoked by MPP+.
Akaneya
Y
Y
Department of Neurology, Kinki University School of Medicine, Osaka, Japan.
Takahashi
M
M
Hatanaka
H
H
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005609:Free Radicals; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D005609:Free Radicals; D016291:Dizocilpine Maleate; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine