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Biphasic effects of MPP+, a possible parkinsonism inducer, on dopamine content and tyrosine hydroxylase mRNA
Y Itano1, Y Kitamura, Y Nomura
1Department of Pharmacology, Faculty of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
Abstract:
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.
Insights
The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) shows dual effects on dopamine (DA) levels in PC12 cells. Initially, MPP+ increases DA, but prolonged exposure or high concentrations lead to a decrease and cell death.
Area of Science:
- Neuroscience
- Cell Biology
- Toxicology
Background:
- The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) is widely used to model Parkinson's disease.
- Understanding the precise mechanisms of MPP+ toxicity on dopaminergic neurons is crucial for therapeutic development.
Purpose of the Study:
- To investigate the biphasic effects of MPP+ on dopamine (DA) content and tyrosine hydroxylase (TH) mRNA expression in PC12 cells.
- To determine the relationship between DA content changes and cell viability under MPP+ treatment.
Main Methods:
- PC12 cells were treated with varying concentrations and durations of MPP+.
- Dopamine (DA) content was measured using biochemical assays.
- Cell viability was assessed to determine toxicity thresholds.
- Tyrosine hydroxylase (TH) mRNA expression was analyzed to understand gene regulation.
Main Results:
- MPP+ exhibited biphasic effects on DA content, increasing it at low concentrations (1-30 microM) and decreasing it at higher concentrations (>100 microM).
- Cell death was observed at 300 microM MPP+, with DA decrease preceding cell demise.
- Short-term exposure (6 h-2 days) to 100 microM MPP+ transiently increased DA, while longer exposure (4-7 days) led to a decrease below control levels.
- TH mRNA expression showed similar biphasic regulation, increasing initially and then decreasing with prolonged MPP+ treatment.
Conclusions:
- MPP+ exerts concentration- and time-dependent biphasic effects on DA content in PC12 cells.
- The observed changes in DA content and TH mRNA expression provide insights into the neurotoxic mechanisms of MPP+.
- These findings contribute to understanding the complex cellular responses to MPP+ relevant to neurodegenerative disease research.