Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone.
Mitochondrial complex I activity is partially suppressed in patients with Parkinson's disease, which is characterized by dopaminergic neuronal death. However, the precise relationship between neuronal death and mitochondrial complex I suppression has been unresolved. We investigated the involvement of superoxide and endogenous dopamine in neurotoxicity by rotenone, a complex I inhibitor. A short exposure to rotenone at high concentrations reduced the viability of both dopaminergic and non-dopaminergic neurons. The toxicity was significantly prevented by a membrane-permeable superoxide dismutase mimetic and alpha-methyl-p-tyrosine (alpha-MT), a tyrosine hydroxylase inhibitor. Chronic treatment with low-concentration rotenone caused selective toxicity to dopaminergic neurons, and this toxicity was attenuated by alpha-MT. These data suggest that superoxide and endogenous dopamine play an important role in dopaminergic neuronal loss.
Sakka
Noriko
N
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Sawada
Hideyuki
H
Izumi
Yasuhiko
Y
Kume
Toshiaki
T
Katsuki
Hiroshi
H
Kaneko
Shuji
S
Shimohama
Shun
S
Akaike
Akinori
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000633:toxicity*; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D012402:Rotenone; D019805:alpha-Methyltyrosine; D004298:Dopamine