Back to Search
Start Over
Fisetin Protects HaCaT Human Keratinocytes from Fine Particulate Matter (PM2.5)-Induced Oxidative Stress and Apoptosis by Inhibiting the Endoplasmic Reticulum Stress Response
- Source :
- Antioxidants, Vol 10, Iss 1492, p 1492 (2021), Antioxidants, Volume 10, Issue 9
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Fine particulate matter (PM2.5) originates from the combustion of coal and is found in the exhaust of fumes of diesel vehicles. PM2.5 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 PM2.5-induced apoptosis in HaCaT human keratinocytes. The results demonstrated that fisetin significantly downregulated PM2.5-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 PM2.5-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 PM2.5. 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 PM2.5-induced apoptosis by inhibiting the ER stress response and production of ROS.
- Subjects :
- PM2.5
Physiology
fisetin
Clinical Biochemistry
RM1-950
medicine.disease_cause
complex mixtures
Biochemistry
Article
chemistry.chemical_compound
medicine
Protein kinase A
Molecular Biology
chemistry.chemical_classification
reactive oxygen species
Reactive oxygen species
biology
Endoplasmic reticulum
apoptosis
Cell Biology
Aryl hydrocarbon receptor
Cell biology
HaCaT
chemistry
Apoptosis
biology.protein
endoplasmic reticulum stress
Therapeutics. Pharmacology
Fisetin
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 20763921
- Volume :
- 10
- Issue :
- 1492
- Database :
- OpenAIRE
- Journal :
- Antioxidants
- Accession number :
- edsair.doi.dedup.....c015d4e7c6c9a4138d8ddb8e72e7bc27