Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes
Autor: | Erting Zhang, Bihua Liang, Zhenjie Li, Huilan Zhu, Huiyan Deng, Na Jiang, Runxiang Li, Liqian Peng, Huaping Li, Qing Liu |
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Rok vydání: | 2017 |
Předmět: |
Keratinocytes
0301 basic medicine Programmed cell death Pterostilbene NF-E2-Related Factor 2 Ultraviolet Rays Physiology DNA repair Morpholines Photoaging Clinical Biochemistry Biology Biochemistry Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound Stilbenes medicine Humans Cells Cultured Research Articles Phosphoinositide-3 Kinase Inhibitors chemistry.chemical_classification Reactive oxygen species integumentary system Kinase Biochemistry (medical) Cell Biology medicine.disease Molecular biology Blot Oxidative Stress 030104 developmental biology chemistry Chromones Phosphatidylinositol 3-Kinase Reactive Oxygen Species RNA transfection Signal Transduction |
Zdroj: | Redox Rep |
ISSN: | 1743-2928 1351-0002 |
DOI: | 10.1080/13510002.2017.1329917 |
Popis: | Objective: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. Methods: Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm(2)). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay. Results: Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity. Conclusion: The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway. |
Databáze: | OpenAIRE |
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