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Biochem. Biophys. Res. Commun. · Sep 2018
Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of cardiomyocytes by regulating GSK-3β/Nrf2/ARE signaling.
- Yuan Fang, Yan Zhao, Shaohua He, Tongshuai Guo, Qing Song, Ning Guo, and Zuyi Yuan.
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta Xi Street, Xi'an, 710061, Shaanxi, China. Electronic address: fang_yuanfy@163.com.
- Biochem. Biophys. Res. Commun. 2018 Sep 18; 503 (4): 2355-2362.
AbstractFibroblast growth factor 19 (FGF19) has emerged as a crucial cytoprotective regulator that antagonizes cell apoptosis and oxidative stress under adverse conditions. However, whether FGF19 plays a cytoprotective role in preventing myocardial damage during myocardial ischemia/reperfusion injury remains unknown. In this study, we aimed to investigate the potential role of FGF19 in regulating hypoxia/reoxygenation (H/R)-induced injury of cardiomyocytes in vitro. We found that FGF19 expression was upregulated in response to H/R treatment in cardiomyocytes. Silencing of FGF19 significantly inhibited viability and increased apoptosis and reactive oxygen species (ROS) generation in cardiomyocytes with H/R treatment. In contrast, overexpression of FGF19 improved viability and inhibited apoptosis and ROS generation induced by H/R treatment, showing a cardioprotective effect. Moreover, we found that FGF19 regulated the phosphorylation of glycogen synthase kinase-3β (GSK-3β) and the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2). In addition, FGF19 promoted the activation of Nrf2-mediated antioxidant response element (ARE) antioxidant signaling. Notably, treatment with a GSK-3β inhibitor significantly abrogated the adverse effects of FGF19 silencing on H/R-induced injury, whereas silencing of Nrf2 partially blocked the FGF19-mediated cardioprotective effect against H/R-induced injury in cardiomyocytes. Taken together, our findings demonstrate that FGF19 alleviates H/R-induced apoptosis and oxidative stress in cardiomyocytes by inhibiting GSK-3β activity and promoting the activation of Nrf2/ARE signaling, providing a potential therapeutic target for prevention of myocardial injury.Copyright © 2018 Elsevier Inc. All rights reserved.
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