Exendin-4 Protects Against Myocardial Ischemia-Reperfusion Injury by Upregulation of SIRT1 and SIRT3 and Activation of AMPK

被引：0
|
作者：
Refaat A. Eid
Mashael Mohammed Bin-Meferij
Attalla Farag El-kott
Samy M Eleawa
Mohamed Samir Ahmed Zaki
Mubarak Al-Shraim
Fahmy El-Sayed
Muhammad Alaa Eldeen
Mahmoud A. Alkhateeb
Samah A. Alharbi
Hussain Aldera
Mohammad A. Khalil
机构：
[1] King Khalid University,Department of Pathology, College of Medicine
[2] Princess Nourah Bint Abdulrahman University,Department of Biology
[3] King Khalid University,Department of Biology, College of Science
[4] Damanhour University,Department of Zoology, Faculty of Science
[5] PAAET,Department of Applied Medical Sciences, College of Health Sciences
[6] King Khalid University,Department of Anatomy, College of Medicine
[7] Zagazig University,Department of Histology, Faculty of Medicine
[8] Zagazig University,Biology Department, Physiology Section, Faculty of Science
[9] King Saud bin Abdulaziz University for Health Sciences,Department of Basic Medical Sciences/College of Medicine
[10] Umm Al-Qura University,Department of Physiology, College of Medicine
[11] King Fahad Medical City,Department of Basic Medical Sciences, Faculty of Medicine
来源：
Journal of Cardiovascular Translational Research | 2021年 / 14卷
关键词：
Exendin-4; Heart; Ischemia; Reperfusion; SIRT1;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
This study evaluated if the cardioprotective effect of Exendin-4 against ischemia/reperfusion (I/R) injury in male rats involves modulation of AMPK and sirtuins. Adult male rats were divided into sham, sham + Exendin-4, I/R, I/R + Exendin-4, and I/R + Exendin-4 + EX-527, a sirt1 inhibitor. Exendin-4 reduced infarct size and preserved the function and structure of the left ventricles (LV) of I/R rats. It also inhibited oxidative stress and apoptosis and upregulated MnSOD and Bcl-2 in their infarcted myocardium. With no effect on SIRTs 2/6/7, Exendin-4 activated and upregulated mRNA and protein levels of SIRT1, increased levels of SIRT3 protein, activated AMPK, and reduced the acetylation of p53 and PGC-1α as well as the phosphorylation of FOXO-1. EX-527 completely abolished all beneficial effects of Exendin-4 in I/R-induced rats. In conclusion, Exendin-4 cardioprotective effect against I/R involves activation of SIRT1 and SIRT3.
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页码：619 / 635
页数：16
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