Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM_2.5)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response

• Main Authors: Ilandarage Menu Neelaka Molagoda (Author), Mirissa Hewage Dumindu Kavinda (Author), Yung Hyun Choi (Author), Hyesook Lee (Author), Chang-Hee Kang (Author), Mi-Hwa Lee (Author), Chang-Min Lee (Author), Gi-Young Kim (Author)
• Format: Book
• Published: MDPI AG, 2021-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Fine particulate matter (PM_2.5) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PM_2.5 readily 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_2.5-induced apoptosis in HaCaT human keratinocytes. The results demonstrated that fisetin significantly downregulated PM_2.5-induced apoptosis at concentrations below 10 μM. Fisetin strongly inhibited the production of reactive oxygen species (ROS) and the expression of pro-apoptotic proteins. The PM_2.5-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 Ca²⁺ levels were markedly increased following exposure to PM_2.5. 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 Ca²⁺ levels. These data suggest that fisetin inhibits PM_2.5-induced apoptosis by inhibiting the ER stress response and production of ROS.

Item Description

10.3390/antiox10091492
2076-3921