Fisetin inhibits PM2.5-induced apoptosis by inhibiting the ER stress response and production of ROS. - GreenMedInfo Summary

Fine particulate matter (PM) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PMreadily penetrates the skin via the aryl hydrocarbon receptor, causing skin senescence, inflammatory skin diseases, DNA damage, and carcinogenesis. In this study, we investigated whether fisetin, a bioactive flavonoid, prevents PM-induced apoptosis in HaCaT human keratinocytes. The results demonstrated that fisetin significantly downregulated PM-induced apoptosis at concentrations below 10μM. Fisetin strongly inhibited the production of reactive oxygen species (ROS) and the expression of pro-apoptotic proteins. The PM-induced apoptosis was associated with the induction of the endoplasmic reticulum (ER) stress response, mediated via the protein kinase R-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP) axis. Additionally, the cytosolic Calevels were markedly increased following exposure to PM. However, fisetin inhibited the expression of ER stress-related proteins, including 78 kDa glucose-regulated protein (GRP78), phospho-eIF2α, ATF4, and CHOP, and reduced the cytosolic Calevels. These data suggest that fisetin inhibits PM-induced apoptosis by inhibiting the ER stress response and production of ROS.