Jing Liu1, Yanming Li1, Yi Tang1, Jinghua Cheng1, Jing Wang1, Jianhua Li1, Xiaohua Ma1, Wei Zhuang1, Jianbin Gong2, Zhihong Liu3. 1. Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. 2. Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. Electronic address: jianbingong@163.com. 3. National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. Electronic address: liuzhihong@nju.edu.cn.
Abstract
BACKGROUND: Rhein, an anthraquinone compound isolated from rhubarb, has been shown to protect the pancreatic β cells from hyperglycemia induced apoptosis in our previous studies. PURPOSE: In the present study, we examined whether rhein can protect myocardial cells against ischemia reperfusion (I/R)-induced apoptosis and investigated the underlying mechanism. METHODS: We used an in vitro model of myocardial hypoxia/reoxygenation (H/R) injury. H9c2 cells were incubated with rhein for 1 h and then subjected to hypoxia for 6 h, followed by reoxygenation for 2 h. Cells viability, apoptosis and ROS were assayed for the treated cells. AKT, p-AKT, GSK3β, p- GSK3β, P38 and p-P38 proteins were analyzed using Western blotting. PI3K/AKT inhibitor, LY294002, and GSK3β siRNA were also used to determine the signaling pathways involved in the protection by rhein. RESULTS: Rhein increased viability, decreased apoptosis and ROS production, of the cells that were exposed to H/R. Rhein also increased the phosphorylation of AKT and GSK3β, an effect that was eliminated by LY294002. GSK3β silencing by siRNA showed similar effect as LY294002. The p-P38 level was upregulated by H/R and downregulated in the presence of rhein; however, the p-P38 downregulation was completely abolished by GSK3β silencing. CONCLUSION: Rhein protects myocardial H9c2 cells against hypoxia/reoxygenation induced injury via AKT/ GSK3β/p38 pathway.
BACKGROUND: Rhein, an anthraquinone compound isolated from rhubarb, has been shown to protect the pancreatic β cells from hyperglycemia induced apoptosis in our previous studies. PURPOSE: In the present study, we examined whether rhein can protect myocardial cells against ischemia reperfusion (I/R)-induced apoptosis and investigated the underlying mechanism. METHODS: We used an in vitro model of myocardial hypoxia/reoxygenation (H/R) injury. H9c2 cells were incubated with rhein for 1 h and then subjected to hypoxia for 6 h, followed by reoxygenation for 2 h. Cells viability, apoptosis and ROS were assayed for the treated cells. AKT, p-AKT, GSK3β, p- GSK3β, P38 and p-P38 proteins were analyzed using Western blotting. PI3K/AKT inhibitor, LY294002, and GSK3β siRNA were also used to determine the signaling pathways involved in the protection by rhein. RESULTS: Rhein increased viability, decreased apoptosis and ROS production, of the cells that were exposed to H/R. Rhein also increased the phosphorylation of AKT and GSK3β, an effect that was eliminated by LY294002. GSK3β silencing by siRNA showed similar effect as LY294002. The p-P38 level was upregulated by H/R and downregulated in the presence of rhein; however, the p-P38 downregulation was completely abolished by GSK3β silencing. CONCLUSION: Rhein protects myocardial H9c2 cells against hypoxia/reoxygenation induced injury via AKT/ GSK3β/p38 pathway.
Authors: Pedro Gonçalves de Oliveira; Lara Termini; Edison Luiz Durigon; Ana Paula Lepique; Andrei C Sposito; Enrique Boccardo Journal: Med Hypotheses Date: 2020-06-01 Impact factor: 1.538