Al-Salam Suhail, Hashmi Satwat, Jagadeesh Govindan S, Tariq Saeed
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates,
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Cell Physiol Biochem. 2020 Apr 4;54(2):287-302. doi: 10.33594/000000220.
BACKGROUND/AIMS: Galectin 3 (GAL-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. GAL-3 has been associated with heart failure and was linked to increased risk of death in a number of studies. GAL-3 was found to be up regulated in animal models of heart failure as well as myocardial infarction (MI). The objective of his study is to test if high GAL-3 after myocardial infarction has a protective role on the heart through its anti-apoptotic and anti-necrotic functions.
Male C57B6/J mice and GAL-3 knockout (KO) mice were used for permanent ligation of the left anterior descending artery of the heart to create infarction in the anterior myocardium. Heart and plasma samples were collected 24 hours after the induction of MI and were used for immunohistochemistry, Tunnel procedure, electron microscopy and enzyme linked immunosorbent assay (ELISA).
Our results show that the significant increase in GAL-3 levels in the left ventricle at 24-hour following MI is associated with significant lower levels of pro-apoptotic proteins; cytochrome c, Bax, annexin V, cleaved caspase-3 and a higher levels of anti-apoptotic protein Bcl2 in GAL-3 wild MI group than GAL-3 KO group. We also have identified the anti-apoptotic activity of GAL-3 is mediated through a significant increase in Akt-1, NF kappa-B and beta- catenin proteins. In addition, we have identified the antiapoptotic activity is mediated through a significant lower levels of cathepsin-D protein.
We conclude that the increased levels of GAL-3 at 24-hour following MI regulate antiapoptotic mechanisms in the myocardium that will shape the future course of the disease. We also identified that the anti-apoptotic mechanisms are likely mediated through interaction of GAL-3 with Akt-1, NF kappa-B, beta- catenin and cathepsin D proteins.
背景/目的:半乳糖凝集素3(GAL-3)是一种β-半乳糖苷结合凝集素,在正常和病理生理条件下具有不同作用。GAL-3与心力衰竭相关,并且在多项研究中与死亡风险增加有关。在心力衰竭以及心肌梗死(MI)的动物模型中发现GAL-3上调。本研究的目的是测试心肌梗死后高表达的GAL-3是否通过其抗凋亡和抗坏死功能对心脏具有保护作用。
使用雄性C57B6/J小鼠和GAL-3基因敲除(KO)小鼠,对心脏左前降支进行永久性结扎,以在前壁心肌造成梗死。在MI诱导后24小时收集心脏和血浆样本,用于免疫组织化学、TUNEL法、电子显微镜检查和酶联免疫吸附测定(ELISA)。
我们的结果显示,MI后24小时左心室中GAL-3水平的显著升高与促凋亡蛋白水平的显著降低相关;与GAL-3基因敲除组相比,GAL-3野生型MI组中的细胞色素c、Bax、膜联蛋白V、裂解的半胱天冬酶-3水平显著降低,抗凋亡蛋白Bcl2水平升高。我们还确定GAL-3的抗凋亡活性是通过Akt-1、核因子κB和β-连环蛋白水平的显著增加介导的。此外,我们确定抗凋亡活性是通过组织蛋白酶-D蛋白水平的显著降低介导的。
我们得出结论,MI后24小时GAL-3水平的升高调节心肌中的抗凋亡机制,这将决定疾病的未来进程。我们还确定抗凋亡机制可能是通过GAL-3与Akt-1、核因子κB、β-连环蛋白和组织蛋白酶D蛋白的相互作用介导的。