Bisphenol A activates the Nrf1/2-antioxidant response element pathway in HEK 293 cells

Chem Res Toxicol. 2013 Mar 18;26(3):498-506. doi: 10.1021/tx400036v. Epub 2013 Feb 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants, Occupational / metabolism*
  • Antioxidants / metabolism*
  • Benzhydryl Compounds / metabolism*
  • Glutathione / metabolism
  • HEK293 Cells
  • Humans
  • NF-E2-Related Factor 2 / metabolism*
  • Nuclear Respiratory Factor 1 / metabolism*
  • Phenols / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*


  • Air Pollutants, Occupational
  • Antioxidants
  • Benzhydryl Compounds
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • NRF1 protein, human
  • Nuclear Respiratory Factor 1
  • Phenols
  • Reactive Oxygen Species
  • Glutathione
  • bisphenol A