Activated Notch1 reduces myocardial ischemia reperfusion injury in vitro during ischemic postconditioning by crosstalk with the RISK signaling pathway
Activated Notch1 reduces myocardial ischemia reperfusion injury in vitro during ischemic postconditioning by crosstalk with the RISK signaling pathway作者机构:Department of Cardiac Surgery First Affiliated Hospital Nanchang University Nanchang Jiangxi 330006 China
出 版 物:《Chinese Medical Journal》 (中华医学杂志(英文版))
年 卷 期:2013年第126卷第23期
页 面:4545-4551页
核心收录:
学科分类:0710[理学-生物学] 1002[医学-临床医学] 07[理学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 071002[理学-动物学] 090102[农学-作物遗传育种]
基 金:This work was supported in part by grants from the National Natural Science Foundation of China (No. 81260024) the Natural Science Foundation of Jiangxi Province (No. 20122BAB205026 and No. 20132BAB205033) and the Graduate Innovation Fund of Jiangxi Province (No. YC201 l-B013)
主 题:Notch1 signaling ischemic postconditioning cardioprotection RISK signaling
摘 要:Background Ischemic postconditioning (IPost),able to significantly attenuate myocardial ischemia reperfusion injury,is dependent on RISK *** have shown that Notch signaling repairs damaged myocardium,and this study aimed to investigate the effect of Notch signaling in myocardial *** We used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation (H/R) model in vitro,which were randomly divided into control,H/R,IPost,Hepatocyte growth factor (HGF)+IPost and DAPT+IPost,N1ICD+IPost,miRNA+lPost,and Mock treatment *** myocardial cell viability was assessed by MTT,the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry *** expression of N1ICD,Hes1,PTEN Phospho-Akt/Akt,Phospho-GSK-3β/GSK-3β were detected by Western ***,we assessed the changes in Ψm using the potential-sensitive dye JC-1 and measured using flow cytometry *** The Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost,which increased myocardial cell viability,prevented cardiomyocyte apoptosis,and reduced loss of the mitochondrial membrane ***,myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by *** blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated,which consequently promoted Akt and GSK-3β *** Notch1 crosstalk with RISK signaling may be dependent on PTEN,which plays a cardioprotective role during *** mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.