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Published on: July 9, 2016
Methyl methacrylate activates the Gsta1 promoter
1Department of Periodontology, School of Dentistry, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan. srp-psho@dpc.agu.ac.jp
Journal of Dental Research
|November 26, 2008
Summary
Methyl methacrylate (MMA) in biomaterials can be toxic. This study shows MMA activates the glutathione S-transferase alpha 1 (Gsta1) gene promoter via the anti-oxidant responsive element (ARE), suggesting a mechanism for MMA-induced gene expression.
Area of Science:
- Biomaterials Science
- Molecular Toxicology
- Gene Regulation
Background:
- Residual monomers in resin-based biomaterials can cause cytotoxicity.
- Methyl methacrylate (MMA) is a common residual monomer.
- MMA exposure is linked to the induction of glutathione S-transferase alpha 1 (Gsta1) gene expression.
Purpose of the Study:
- To investigate the hypothesis that MMA activates the Gsta1 promoter through the anti-oxidant responsive element (ARE).
- To elucidate the molecular mechanism underlying MMA-induced Gsta1 gene transcription.
Main Methods:
- HepG2 cells were transfected with luciferase reporter vectors containing the Gsta1 promoter and ARE sequences.
- Cells were treated with varying concentrations of MMA (1-30 mM).
- Luciferase activity was measured to quantify promoter activation.
Main Results:
- MMA significantly activated the Gsta1 promoter in a dose-dependent manner.
- Promoter activation by MMA reached a plateau between 6 and 12 hours of exposure.
- Reporter expression increased 2.6-fold with 10 mM MMA and 2.8-fold with a vector containing two AREs.
Conclusions:
- MMA increases Gsta1 transcription through ARE-mediated promoter activation.
- This finding provides insight into the molecular mechanisms of MMA-induced cytotoxicity.
- Understanding this pathway is crucial for developing safer biomaterials.
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