Role of quercetin in protecting ARPE‑19 cells against H2O2‑induced injury via nuclear factor erythroid 2 like 2 pathway activation and endoplasmic reticulum stress inhibition

Weng,Sisi; Mao,Lei; Gong,Yuanyuan; Sun,Tao; Gu,Qing

doi:10.3892/mmr.2017.6964

Role of quercetin in protecting ARPE‑19 cells against H2O2‑induced injury via nuclear factor erythroid 2 like 2 pathway activation and endoplasmic reticulum stress inhibition

Authors:
- Sisi Weng
- Lei Mao
- Yuanyuan Gong
- Tao Sun
- Qing Gu
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Affiliations: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Hongkou, Shanghai 200080, P.R. China
Published online on: July 13, 2017 https://doi.org/10.3892/mmr.2017.6964
Pages: 3461-3468

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Abstract

Age‑related macular degeneration (AMD) is a common cause of irreversible blindness in the elderly in the western world. Research has demonstrated that degenerative and progressive conditions of retinal pigmented epithelial (RPE) cells are the key pathogenic mechanisms in AMD. Previous research has indicated the anti‑apoptosis, anti‑oxidant, anti‑inflammatory and anti‑cancer properties of quercetin. Therefore, the present study aimed to investigate the protective effects of quercetin on the ARPE‑19 human retinal pigment epithelial cell line. ARPE‑19 cells were pretreated with various concentrations of quercetin (0‑80 µM) before exposure to 300 µM H2O2. Cell viability was assessed and reactive oxygen species (ROS) were determined. The importance of the NF‑E2‑related factor 2 (Nrf2) signaling pathway was corroborated by western blotting and immunostaining. The protein expression levels of endoplasmic reticulum‑associated stress responsive genes and apoptotic markers were assessed by western blotting. The results demonstrated that in the H2O2 group, cell viability was weakened, but preserved in quercetin group in a dose‑dependent manner, particularly at 20 µM. The level of ROS decreased in the quercetin group compared with the control groups. In the quercetin group, the expression levels of Nrf2 and phase II enzymes (NQO1 and HO‑1) were increased, whereas the levels of ER stress markers (binding of immunoglobulin protein, CCAAT/enhancer‑binding protein homologous protein and phosphorylated eukaryotic translation initiation factor 2α) were reduced. Cell apoptosis‑associated protein expression levels were altered, with the increase of B‑cell lymphoma 2 and reduction of Bcl‑2 X‑associated protein. In conclusion, quercetin protected ARPE‑19 cells from H2O2‑induced cytotoxicity by activating the Nrf2 pathway, inhibiting ER stress and targeting anti‑apoptotic proteins.

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