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Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of cardiomyocytes by regulating GSK-3β/Nrf2/ARE signaling.
Biochem Biophys Res Commun. 2018 09 18; 503(4):2355-2362.BB

Abstract

Fibroblast 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.

Authors+Show Affiliations

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.Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, USA.Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, USA.Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta Xi Street, Xi'an, 710061, Shaanxi, China.Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, USA.Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta Xi Street, Xi'an, 710061, Shaanxi, China.Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta Xi Street, Xi'an, 710061, Shaanxi, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29964017

Citation

Fang, Yuan, et al. "Overexpression of FGF19 Alleviates Hypoxia/reoxygenation-induced Injury of Cardiomyocytes By Regulating GSK-3β/Nrf2/ARE Signaling." Biochemical and Biophysical Research Communications, vol. 503, no. 4, 2018, pp. 2355-2362.
Fang Y, Zhao Y, He S, et al. Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of cardiomyocytes by regulating GSK-3β/Nrf2/ARE signaling. Biochem Biophys Res Commun. 2018;503(4):2355-2362.
Fang, Y., Zhao, Y., He, S., Guo, T., Song, Q., Guo, N., & Yuan, Z. (2018). Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of cardiomyocytes by regulating GSK-3β/Nrf2/ARE signaling. Biochemical and Biophysical Research Communications, 503(4), 2355-2362. https://doi.org/10.1016/j.bbrc.2018.06.161
Fang Y, et al. Overexpression of FGF19 Alleviates Hypoxia/reoxygenation-induced Injury of Cardiomyocytes By Regulating GSK-3β/Nrf2/ARE Signaling. Biochem Biophys Res Commun. 2018 09 18;503(4):2355-2362. PubMed PMID: 29964017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of FGF19 alleviates hypoxia/reoxygenation-induced injury of cardiomyocytes by regulating GSK-3β/Nrf2/ARE signaling. AU - Fang,Yuan, AU - Zhao,Yan, AU - He,Shaohua, AU - Guo,Tongshuai, AU - Song,Qing, AU - Guo,Ning, AU - Yuan,Zuyi, Y1 - 2018/07/04/ PY - 2018/06/26/received PY - 2018/06/28/accepted PY - 2018/7/3/pubmed PY - 2019/1/16/medline PY - 2018/7/3/entrez KW - Cardiomyocyte KW - FGF19 KW - GSK-3β KW - Hypoxia/reoxygenation KW - Nrf2 SP - 2355 EP - 2362 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 503 IS - 4 N2 - Fibroblast 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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/29964017/Overexpression_of_FGF19_alleviates_hypoxia/reoxygenation_induced_injury_of_cardiomyocytes_by_regulating_GSK_3β/Nrf2/ARE_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(18)31480-3 DB - PRIME DP - Unbound Medicine ER -