Fig. 6.

Summarizing scheme of the mechanisms involved in E-cigarette condensate and acrolein-induced oxidative stress and cell death. NADPH oxidase complex is activated via toxic constituents of vapour by translocation of subunits (p47phox, p67phox and Rac1) from cytosol to the membrane-bound gp91phox subunit (NOX2). The activated complex generates superoxide radicals, contributing to the total ROS burden. ROS activates Nrf2 transcription factor responsible for antioxidant defence, which modulates the transcription of enzymes such as heme-oxygenase-1 (HO-1). This compensatory rescue mechanism remains, however, futile. Acrolein, as an electrophile, can activate NADPH oxidase complex directly by forming adducts with cytosolic subunits or activating protein kinase C (PKC), which phosphorylates cytosolic subunits, promoting them to the membrane. In this way, acrolein increases total ROS production. Still, it can also activate Nrf2 pathway directly via electrophilic reaction with the thiols in Keap1 or indirectly via induction of ROS (redox-dependent activation of Keap1) and subsequent translocation to the nucleus. Results from our previous study [13] are shown in blue text fields. Created with BioRender.com