Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response
Fine particulate matter (PM<sub>2.5</sub>) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PM<sub>2.5</sub> readily penetrates the skin via the aryl hydrocarbon receptor, causing skin senescence, inflammatory skin diseases, DNA...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/9/1492 |
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| author | Ilandarage Menu Neelaka Molagoda Mirissa Hewage Dumindu Kavinda Yung Hyun Choi Hyesook Lee Chang-Hee Kang Mi-Hwa Lee Chang-Min Lee Gi-Young Kim |
| author_facet | Ilandarage Menu Neelaka Molagoda Mirissa Hewage Dumindu Kavinda Yung Hyun Choi Hyesook Lee Chang-Hee Kang Mi-Hwa Lee Chang-Min Lee Gi-Young Kim |
| author_sort | Ilandarage Menu Neelaka Molagoda |
| collection | DOAJ |
| description | Fine particulate matter (PM<sub>2.5</sub>) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PM<sub>2.5</sub> 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<sub>2.5</sub>-induced apoptosis in HaCaT human keratinocytes. The results demonstrated that fisetin significantly downregulated PM<sub>2.5</sub>-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<sub>2.5</sub>-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 Ca<sup>2+</sup> levels were markedly increased following exposure to PM<sub>2.5</sub>. 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 Ca<sup>2+</sup> levels. These data suggest that fisetin inhibits PM<sub>2.5</sub>-induced apoptosis by inhibiting the ER stress response and production of ROS. |
| first_indexed | 2024-03-10T07:56:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T07:56:17Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-9c9688daf52b46ec98513f30d6e03d2f2023-11-22T11:49:38ZengMDPI AGAntioxidants2076-39212021-09-01109149210.3390/antiox10091492Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress ResponseIlandarage Menu Neelaka Molagoda0Mirissa Hewage Dumindu Kavinda1Yung Hyun Choi2Hyesook Lee3Chang-Hee Kang4Mi-Hwa Lee5Chang-Min Lee6Gi-Young Kim7Department of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaDepartment of Biochemistry, College of Korean Medicine, Dong-Eui University, Busan 47227, KoreaNakdonggang National Institute of Biological Resources, Sangju 37242, Gyeongsanbuk-do, KoreaNakdonggang National Institute of Biological Resources, Sangju 37242, Gyeongsanbuk-do, KoreaDepartment of Molecular Microbiology and Immunology, Brown University, 185 Meeting Street, Box G-L, Providence, RI 02913, USADepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaFine particulate matter (PM<sub>2.5</sub>) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PM<sub>2.5</sub> 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<sub>2.5</sub>-induced apoptosis in HaCaT human keratinocytes. The results demonstrated that fisetin significantly downregulated PM<sub>2.5</sub>-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<sub>2.5</sub>-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 Ca<sup>2+</sup> levels were markedly increased following exposure to PM<sub>2.5</sub>. 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 Ca<sup>2+</sup> levels. These data suggest that fisetin inhibits PM<sub>2.5</sub>-induced apoptosis by inhibiting the ER stress response and production of ROS.https://www.mdpi.com/2076-3921/10/9/1492fisetinPM<sub>2.5</sub>apoptosisendoplasmic reticulum stressreactive oxygen species |
| spellingShingle | Ilandarage Menu Neelaka Molagoda Mirissa Hewage Dumindu Kavinda Yung Hyun Choi Hyesook Lee Chang-Hee Kang Mi-Hwa Lee Chang-Min Lee Gi-Young Kim Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response Antioxidants fisetin PM<sub>2.5</sub> apoptosis endoplasmic reticulum stress reactive oxygen species |
| title | Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response |
| title_full | Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response |
| title_fullStr | Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response |
| title_full_unstemmed | Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response |
| title_short | Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM<sub>2.5</sub>)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response |
| title_sort | fisetin protects hacat human keratinocytes from fine particulate matter pm sub 2 5 sub induced oxidative stress and apoptosis by inhibiting the endoplasmic reticulum stress response |
| topic | fisetin PM<sub>2.5</sub> apoptosis endoplasmic reticulum stress reactive oxygen species |
| url | https://www.mdpi.com/2076-3921/10/9/1492 |
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