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.
Itano
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
Kitamura
Y
Y
Nomura
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010302:Parkinson Disease, Secondary / Q000209:etiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine