Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human

Parkinson’s disease is a chronic neurodegenerative disorder characterized by loss of dopaminergic neurons in the sub-stantia nigra. Rotenone, a pesticide, produces selective de-generation of dopaminergic neurons and motor dysfunction in rats. To determine the mechanisms underlying rotenone-induced neuronal death, we investigated whether intracellu-lar dopamine plays a role in rotenone (0.1–0.4 M)-induced apoptosis, using an in vitro model of human dopaminergic SH-SY5Y cells. The 40 % decrease of dopamine content by inhibition of dopamine synthesis suppressed rotenone-induced apoptosis. On the other hand, the 30 % increase of dopamine content by inhibition of dopamine metabolism enhanced rotenone-induced apoptosis. Depletion of intra-cellular dopamine using reserpine (0.1–10 M) also pre