Piceatannol Protects Human Retinal Pigment Epithelial Cells against Hydrogen Peroxide Induced Oxidative Stress and Apoptosis through Modulating PI3K/Akt Signaling Pathway

• Published in: Nutrients 2019-07, Vol.11 (7), p.1515
• Main Authors: Hao, Yiming, Liu, Jie, Wang, Ziyuan, Yu, Liangli Lucy, Wang, Jing
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation; AKT protein; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; ARPE-19 cell; Cell death; Cell Line; Cytoprotection; Epithelial Cells - drug effects; Epithelial Cells - enzymology; Epithelial Cells - pathology; Heme Oxygenase-1 - metabolism; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Kinases; Macular degeneration; Mitochondria; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nutrition; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinase - metabolism; PI3K/Akt signaling pathway; Piceatannol; Proto-Oncogene Proteins c-akt - metabolism; Retina; Retinal pigment epithelium; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - enzymology; Retinal Pigment Epithelium - pathology; Signal Transduction; Stilbenes - pharmacology; Vitamin A
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11071515

This study investigated the protective effect and the molecular mechanism of piceatannol on hydrogen peroxide (H O )-induced retinal pigment epithelium cell (ARPE-19) damage. Piceatannol treatment significantly inhibited H O -induced RPE cell death and reactive oxygen species (ROS) generation by 64.4% and 75.0%, respectively. Results of flow cytometry showed that H O -induced ARPE-19 cells apoptosis was ameliorated by piceatannol supplementation, along with decreased relative protein expressions of Bax/Bcl-2, Cleave-Caspase-3, and Cleave-PARP. Moreover, piceatannol treatment induced NF-E2-related factor 2 (Nrf2) signaling activation, which was evidenced by increased transcription of anti-oxidant genes, glutamate-cysteine ligase catalytic subunit (GCLc), SOD, and HO-1. Knockdown of Nrf2 through targeted siRNA alleviated piceatannol-mediated HO-1 transcription, and significantly abolished piceatannol-mediated cytoprotection. LY294002 (PI3K inhibitor) dramatically blocked piceatannol-mediated increasing of Nrf2 nuclear translocation, HO-1 expression, and cytoprotective activity, indicating the involvement of PI3K/Akt pathway in the cytoprotective effect of piceatannol. The results from this suggest the potential of piceatannol in reducing the risk of age-related macular degeneration.