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Published on: May 5, 2009
Effects of chlorpyrifos on transglutaminase activity in differentiating rat C6 glioma cells
D Muñoz1, P L R Bonner, A J Hargreaves
1School of Science & Technology, Nottingham Trent University, Clifton Lane, Nottingham NG118NS, UK.
Abstract:
The organophosphorothioate compound chlorpyrifos (CPF) is a widely used pesticide, which is known to inhibit the differentiation of mouse N2a neuroblastoma and rat C6 glioma cells. This study in focused on the possible effects of CPF in the activity and expression of tissue transglutaminase (TGase 2) in differentiating C6 cells. Cells exposed for 24 h to 10 μM CPF, which had no effect on cell viability, exhibited a significant increase in cytosolic TGase 2 activity. Western blotting analysis indicated that there was no change in the cytosolic TGase 2 protein levels, suggesting that the enzyme was activated under these conditions. When commercially available TGase 2 was incubated with CPF in vitro, an increase in activity was also observed, suggesting that CPF might interact directly with TGase 2.
Insights
The pesticide chlorpyrifos (CPF) significantly increases tissue transglutaminase 2 (TGase 2) activity in rat C6 glioma cells. This occurs without altering protein levels, suggesting CPF directly activates TGase 2.
Area of Science:
- Neurotoxicology
- Biochemistry
- Cell Biology
Background:
- Organophosphorothioate pesticides like chlorpyrifos (CPF) are widely used globally.
- CPF is known to inhibit the differentiation of neural and glioma cell lines.
- Tissue transglutaminase 2 (TGase 2) plays a role in cellular processes.
Purpose of the Study:
- To investigate the effects of CPF on TGase 2 activity and expression in differentiating C6 glioma cells.
- To determine if CPF directly interacts with TGase 2.
Main Methods:
- Rat C6 glioma cells were exposed to 10 μM CPF for 24 hours.
- Cytosolic TGase 2 activity was measured.
- Western blotting was used to assess TGase 2 protein levels.
- Purified TGase 2 was incubated with CPF in vitro.
Main Results:
- CPF exposure significantly increased cytosolic TGase 2 activity in C6 cells.
- CPF did not affect cell viability or TGase 2 protein levels.
- In vitro incubation of TGase 2 with CPF also resulted in increased enzyme activity.
Conclusions:
- CPF activates TGase 2 in C6 glioma cells, likely through direct interaction.
- This finding suggests a novel mechanism for CPF's neurotoxic effects.
