Bisphenol A Activates the Nrf1/2-Antioxidant Response Element Pathway in HEK 293 Cells
| Autor: | Nikolai L. Chepelev, Qixuan Chen, William G. Willmore, Leonid L. Chepelev, Kylie A. Scoggan, Xu-Liang Cao, Melanie C Coughlan, Abdulrahman Almohaisen, Mutiat I Enikanolaiye, Xiaolei Jin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
endocrine system
Bisphenol A Antioxidant NF-E2-Related Factor 2 medicine.medical_treatment Air Pollutants Occupational Toxicology medicine.disease_cause Antioxidants chemistry.chemical_compound Phenols medicine Humans Antioxidant Response Elements NRF1 Benzhydryl Compounds chemistry.chemical_classification Reactive oxygen species Nuclear Respiratory Factor 1 urogenital system HEK 293 cells General Medicine Glutathione HEK293 Cells chemistry Biochemistry Reactive Oxygen Species hormones hormone substitutes and hormone antagonists Oxidative stress Signal Transduction |
| Zdroj: | Chemical Research in Toxicology. 26:498-506 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx400036v |
| Popis: | Bisphenol A (BPA) is used in the production of polycarbonate plastics and epoxy resins for baby bottles, liners of canned food, and many other consumer products. Previously, BPA has been shown to reduce the activity of several antioxidant enzymes, which may contribute to oxidative stress. However, the underlying mechanism of the BPA-mediated effect upon antioxidant enzyme activity is unknown. Antioxidant and phase II metabolizing enzymes protect cells from oxidative stress and are transcriptionally activated by Nrf1 and Nrf2 factors through their cis-regulatory antioxidant response elements (AREs). In this work, we have assessed the effect of BPA on the Nrf1/2-ARE pathway in cultured human embryonic kidney (HEK) 293 cells. Surprisingly, glutathione and reactive oxygen species (ROS) assays revealed that BPA application created a more reduced intracellular environment in cultured HEK 293 cells. Furthermore, BPA increased the transactivation activity of ectopic Nrf1 and Nrf2 and increased the expression of ARE-target genes ho-1 and nqo1 at high (100-200 μM) BPA concentrations only. Our study suggests that BPA activates the Nrf1/2-ARE pathway at high (>10 μM) micromolar concentrations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|