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学科主题临床医学
Activation of Akt/GSK-3 beta signaling pathway is involved in intermedin(1-53) protection against myocardial apoptosis induced by ischemia/reperfusion
Song, Jun-Qiu1; Teng, Xu1; Cai, Yan1; Tang, Chao-Shu1,2,3; Qi, Yong-Fen1,2,3
关键词Intermedin Myocardium Ischemia/reperfusion Apoptosis Akt/gsk-3 Beta
刊名APOPTOSIS
2009-11-01
DOI10.1007/s10495-009-0398-7
14期:11页:1299-1307
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
资助者National Natural Science Foundation of China ; State Major Basic Research Development Program of the People&prime ; s Republic of China ; National Natural Science Foundation of China ; State Major Basic Research Development Program of the People&prime ; s Republic of China
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]ISCHEMIA-REPERFUSION INJURY ; RAT HEARTS ; AKT ; SURVIVAL ; CARDIOPROTECTION ; ADRENOMEDULLIN ; MITOCHONDRIA ; REGULATOR
英文摘要

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. We investigated the cardioprotective mechanism of IMD1-53 in the in vivo rat model of myocardial ischemia/reperfusion (I/R) injury and in vitro primary neonatal cardiomyocyte model of hypoxia/reoxygenation (H/R). Myocardial infarct size was measured by 2,3,5-triphenyl tetrazolium chloride staining. Cardiomyocyte viability was determined by trypan blue staining, cell injury by lactate dehydrogenase (LDH) leakage, and cardiomyocyte apoptosis by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay, Hoechst staining, gel electrophoresis and caspase 3 activity. The translocation of mitochondrial cytochrome c of myocardia and expression of apoptosis-related factors Bcl-2 and Bax, phosphorylated Akt and phosphorylated GSK-3 beta were determined by western blot analysis. IMD1-53 (20 nmol/kg) limited the myocardial infarct size in rats with I/R; the infarct size was decreased by 54%, the apoptotic index by 30%, and caspase 3 activity by 32%; and the translocation of cytochrome c from mitochondria to cytosol was attenuated. IMD1-53 increased the mRNA and protein expression of Bcl-2 and ratio of Bcl-2 to Bax by 81 and 261%, respectively. IMD1-53 (1 x 10(-7) mol/L) inhibited the H/R effect in cardiomyocytes by reducing cell death by 43% and LDH leakage by 16%; diminishing cellular apoptosis; decreasing caspase 3 activity by 50%; and increasing the phosphorylated Akt and GSK-3 beta by 41 and 90%, respectively. The cytoprotection of IMD1-53 was abolished with LY294002, a PI3K inhibitor. In conclusion, IMD1-53 exerts cardioprotective effect against myocardial I/R injury through the activation of the Akt/GSK-3 beta signaling pathway to inhibit mitochondria-mediated myocardial apoptosis.

语种英语
所属项目编号30770869 ; 30871013 ; 2006CB503807
资助者National Natural Science Foundation of China ; State Major Basic Research Development Program of the People&prime ; s Republic of China ; National Natural Science Foundation of China ; State Major Basic Research Development Program of the People&prime ; s Republic of China
WOS记录号WOS:000270540800005
引用统计
被引频次:61[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50744
专题北京大学第一临床医学院_心血管内科
作者单位1.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
3.Peking Univ, Inst Cardiovasc Dis, Hosp 1, Beijing 100034, Peoples R China
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GB/T 7714
Song, Jun-Qiu,Teng, Xu,Cai, Yan,et al. Activation of Akt/GSK-3 beta signaling pathway is involved in intermedin(1-53) protection against myocardial apoptosis induced by ischemia/reperfusion[J]. APOPTOSIS,2009,14(11):1299-1307.
APA Song, Jun-Qiu,Teng, Xu,Cai, Yan,Tang, Chao-Shu,&Qi, Yong-Fen.(2009).Activation of Akt/GSK-3 beta signaling pathway is involved in intermedin(1-53) protection against myocardial apoptosis induced by ischemia/reperfusion.APOPTOSIS,14(11),1299-1307.
MLA Song, Jun-Qiu,et al."Activation of Akt/GSK-3 beta signaling pathway is involved in intermedin(1-53) protection against myocardial apoptosis induced by ischemia/reperfusion".APOPTOSIS 14.11(2009):1299-1307.
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