Biphasic effects of MPP+, a possible parkinsonism inducer, on dopamine content and tyrosine hydroxylase mRNA expression in PC12 cells.

When PC12 cells were treated with 1-methyl-4-phenylpyridinium ion (MPP+) at various concentrations for 1 week, the dopamine (DA) content was increased compared to the control at 1-30 microM but was decreased to less than the control at concentrations above 100 microM. Cell death was caused by 300 microM MPP+, indicating that decrease in DA content proceeds cell death. When the cells were treated with 100 microM MPP+ for various periods, DA content was transiently increased (6 h-2 days) and then gradually decreased below the control (4-7 days). These results suggest that MPP+ possesses biphasic effects on DA content, being dependent on both concentrations and treatment periods. Moreover, by treatment with 100 microM MPP+, tyrosine hydroxylase (TH) mRNA expression was also transiently increased and then gradually decreased below the control, suggesting that MPP+ also possesses biphasic effects on TH mRNA expression.