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
复制标题
激活的Notch1通过与RISK信号通路的串扰减少缺血后处理过程中的体外心肌缺血再灌注损伤
DOI：
10.3760/cma.j.issn.0366-6999.20130721
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发表时间：
2013-12
影响因子：
6.1
通讯作者：
Liu Ji-chun
中科院分区：
文献类型：
--
作者：
Zhou Xue-liang;Wan Li;Liu Ji-chun
背景缺血后处理（Ischemic postconditioning，IPost）能够显著减轻心肌缺血再灌注损伤，其作用依赖于RISK信号。研究表明Notch信号通路对受损心肌具有修复作用，本研究旨在探讨Notch信号通路在心肌IPost中的作用。方法采用H9 c2细胞建立体外心肌缺血再灌注（IPost）和缺氧/复氧（H/R）模型。随机分为对照组、H/R组、IPost组、HGF +IPost组、DAPT+IPost组、NICD +IPost组、miRNA+IPost组和Mock组。MTT法检测心肌细胞存活率，Annexin V/PI双染及流式细胞仪检测心肌细胞凋亡。Western blotting检测N1 ICD、Hes 1、PTEN Phospho-Akt/Akt、Phospho-GSK-3/GSK-3的表达。最后，我们使用电位敏感染料JC-1评估了m的变化，并使用流式细胞术分析进行了测量。结果在心肌缺血再灌注过程中，HGF激活Notch 1信号通路，N1 ICD异位表达，增加心肌细胞活力，抑制心肌细胞凋亡，减少线粒体膜电位的丢失。然而，当使用DAPT抑制Notch 1信号传导或通过Notch 1-miRNA敲低时，IPost中的心肌缺血再灌注损伤增加。Western blotting发现，当Notch 1被激活时，PTEN被Hes 1下调，从而促进Akt和GSK-3的磷酸化。结论Notch 1与RISK信号通路的相互作用可能依赖于PTEN，PTEN在IPost中起心脏保护作用。这一机制为缺血性心脏病的治疗提供了一个有前景的治疗靶点。
Background Ischemic postconditioning (IPost), able to significantly attenuate myocardial ischemia reperfusion injury, is dependent on RISK signaling. Studies have shown that Notch signaling repairs damaged myocardium, and this study aimed to investigate the effect of Notch signaling in myocardial IPost. Methods 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+IPost, and Mock treatment groups. The myocardial cell viability was assessed by MTT, the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses. The expression of N1ICD, Hes1, PTEN Phospho‐Akt/Akt, Phospho‐GSK‐3&bgr;/GSK‐3&bgr; were detected by Western blotting. Finally, we assessed the changes in &PSgr;m using the potential‐sensitive dye JC‐1 and measured using flow cytometry analyses. Results 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 potential. However, myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1‐miRNA. Western blotting found that PTEN was down‐regulated by Hes1 when Notch1 was activated, which consequently promoted Akt and GSK‐3&bgr; phosphorylation. Conclusions Notch1 crosstalk with RISK signaling may be dependent on PTEN, which plays a cardioprotective role during IPost. This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.
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影响因子：
3.4
作者：
Miura, Tetsuji;Tanno, Masaya
通讯作者：
Tanno, Masaya
影响因子：
2.7
作者：
Guo, Dongmei;Ye, Jingjing;Ji, Chunyan
通讯作者：
Ji, Chunyan
DOI：
10.1016/j.biocel.2011.08.005
发表时间：
2011-11
影响因子：
4
作者：
Wang, Michael M.
通讯作者：
Wang, Michael M.
Notch 激活静止心肌细胞的细胞周期重入和进展。
DOI：
10.1083/jcb.200806104
发表时间：
2008-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Campa VM;Gutiérrez-Lanza R;Cerignoli F;Díaz-Trelles R;Nelson B;Tsuji T;Barcova M;Jiang W;Mercola M
通讯作者：
Mercola M
影响因子：
20.1
作者：
Urbanek K;Cabral-da-Silva MC;Ide-Iwata N;Maestroni S;Delucchi F;Zheng H;Ferreira-Martins J;Ogórek B;D'Amario D;Bauer M;Zerbini G;Rota M;Hosoda T;Liao R;Anversa P;Kajstura J;Leri A
通讯作者：
Leri A