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Inhibitory effects of tributyltin on dopamine biosynthesis in rat PC12 cells
Yu Mi Kim1, Jae Joon Lee, Shou Yu Yin
1College of Pharmacy, Chungbuk National University, San 48, Kaeshin-Dong, Heungduk-Ku, Cheongju 361-763, South Korea.
Abstract:
The inhibitory effects of tributyltin chloride (TBTC) on dopamine biosynthesis in PC12 cells were investigated. Twenty-four hour exposure to TBTC at 0.5 microM showed 32.9% inhibition of dopamine content: the IC(50) value of TBTC was 0.72 microM. Dopamine content decreased at 6 h and reached a minimal level at 24 h after exposure to TBTC at 0.5 microM. The decreased dopamine level was maintained for up to 48 h. Under these conditions, tyrosine hydroxylase (TH) activity was inhibited at 6 h following the treatment with TBTC and the activity was maintained at a reduced level for up to 48 h (20-35% inhibition at 0.5 microM of TBTC). TH mRNA level also started to decrease at about 6 h and reached a minimal level at 24 h after exposure of PC12 cells to TBTC. In addition, treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) at 20-50 microM increased the intracellular dopamine content in PC12 cells and the increase of dopamine level by L-DOPA was significantly inhibited after exposure to TBTC at 0.5-2.0 microM for 24 h. These results indicate that TBTC decreases dopamine content by the inhibition of TH activity and TH mRNA level in PC12 cells. It is, therefore, proposed that TBTC may exacerbate the Parkinson's symptoms because of the inhibition of dopamine biosynthesis and dopamine increase induced by L-DOPA.
Insights
Tributyltin chloride (TBTC) inhibits dopamine production in PC12 cells by reducing tyrosine hydroxylase (TH) activity and mRNA levels. This neurotoxic effect may worsen Parkinson's disease symptoms.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Dopamine is a crucial neurotransmitter involved in motor control.
- Parkinson's disease is characterized by a loss of dopamine-producing neurons.
- Environmental toxins are suspected contributors to neurodegenerative diseases.
Purpose of the Study:
- To investigate the impact of tributyltin chloride (TBTC) on dopamine biosynthesis in PC12 cells.
- To determine the mechanism by which TBTC affects dopamine production.
- To assess the potential of TBTC to exacerbate Parkinson's-like symptoms.
Main Methods:
- PC12 cells were exposed to varying concentrations of TBTC.
- Dopamine content was measured using biochemical assays.
- Tyrosine hydroxylase (TH) activity and TH mRNA levels were quantified.
- The effect of L-3,4-dihydroxyphenylalanine (L-DOPA) on dopamine levels was assessed in the presence of TBTC.
Main Results:
- TBTC significantly inhibited dopamine content in PC12 cells, with an IC(50) of 0.72 microM.
- Dopamine levels decreased starting at 6 hours and remained low for up to 48 hours.
- TBTC inhibited TH activity and TH mRNA levels in a time-dependent manner.
- TBTC attenuated the dopamine-increasing effect of L-DOPA.
Conclusions:
- TBTC reduces dopamine biosynthesis by inhibiting TH activity and TH mRNA expression in PC12 cells.
- TBTC's neurotoxic effects on dopamine production suggest it may exacerbate Parkinson's disease.
- Further research is warranted to understand the clinical implications of TBTC exposure in neurodegeneration.