BIPHASIC EFFECTS OF MPP(+), A POSSIBLE PARKINSONISM INDUCER, ON DOPAMINE CONTENT AND TYROSINE-HYDROXYLASE MESSENGER-RNA 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 mu M but was decreased to less than the control at concentrations above 100 mu M. Cell death was caused by 300 mu M MPP(+), indicating that decrease in DA content proceeds cell death. When the cells were treated with 100 mu M 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 pel iods. Moreover, by treatment with 100 mu M 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.