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Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

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Author(s)
Cheol ParkJeong Sook NohYoungmi JungSun-Hee LeemJin Won HyunYoung-Chae ChangTaeg Kyu KwonGi-Young KimHyesook LeeYung Hyun Choi
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Front Pharmacol
Issued Date
2022
Volume
13
Keyword
fisetinhuman retinal pigment epithelial cellsDNA damageapoptosisROSNrf2/HO-1
Abstract
Fisetin is a kind of bioactive flavonol, widely present in various fruits such as strawberries and apples, and is known to act as a potent free radical scavenger. However, the mechanism of action related to the antioxidant activity of this compound in human retinal pigment epithelial (RPE) cells is not precisely known. In this study, we aimed to investigate whether fisetin could attenuate oxidative stress-induced cytotoxicity on human RPE ARPE-19 cells. To mimic oxidative stress, ARPE-19 cells were treated with hydrogen peroxide (H2O2), and fisetin significantly inhibited H2O2-induced loss of cell viability and increase of intracellular reactive oxygen species (ROS) production. Fisetin also markedly attenuated DNA damage and apoptosis in H2O2-treated ARPE-19 cells. Moreover, mitochondrial dysfunction in H2O2-treated cells was alleviated in the presence of fisetin as indicated by preservation of mitochondrial membrane potential, increase of Bcl-2/Bax expression ratio, and suppression of cytochrome c release into the cytoplasm. In addition, fisetin enhanced phosphorylation and nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2), which was associated with increased expression and activity of heme oxygenase-1 (HO-1). However, the HO-1 inhibitor, zinc protoporphyrin, significantly reversed the protective effect of fisetin against H2O2-mediated ARPE-19 cell injury. Therefore, our results suggest that Nrf2-mediated activation of antioxidant enzyme HO-1 may play an important role in the ROS scavenging activity of fisetin in RPE cells, contributing to the amelioration of oxidative stress-induced ocular disorders.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1663-9812
Source
https://www.frontiersin.org/articles/10.3389/fphar.2022.927898/full
DOI
10.3389/fphar.2022.927898
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44377
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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