Figure 2.

The regulation of reactive oxygen species. Under normal conditions, glutathione functions in scavenging reactive oxygen species, and levels of NRF2 remain low due to ubiquitin-mediated degradation in the proteasome (left panel). If oxidative stress increases, NRF2 escapes protein degradation upon phosphorylation and separation from KEAP1, and it enters the nucleus to regulate gene expression by binding the antioxidant response element (ARE) as a normal reaction in response to oxidative stress. Flavoring, acrolein, and aldehydes can interfere with the normal oxidative stress response: Acrolein can induce the expression of KEAP1, and aldehydes induce NOX proteins, which can result in high levels of ROS. Copper nanoparticles in e-cig aerosols increase mitochondrial dysfunction, as a consequence of mtROS associated with an electron leak. In the presence of e-cigs, glutathione levels are diminished and ROS created by e-cig exposure, including unvaporized e-liquids and flavorings, cannot be scavenged.