Fig. 8.

A schematic diagram illustrating the role of APE1 in activating NRF2 under reflux conditions. Exposure of cells to reflux conditions (acidic bile salts, ABS) generates high levels of ROS. High ROS and oxidative stress levels induce APE1-dependent increase in NRF2, leading to its release and translocation into the nucleus. In the nucleus, NRF2 is stabilized and regulated by APE1 redox function that inactivates GSK-3β dependent degradation of NRF2. Loss of redox function of APE1 mediates inactivation of GSK-3-β to promote accumulation and activation of NRF2.