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.