Induction of autophagy promotes cardiomyocyte survival and confers a cardioprotective effect on acute myocardial infarction (AMI). Our previous study showed that knockdown of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) attenuated myocardial apoptosis in mouse AMI. Herein, this study further investigated whether the mechanisms by which MALAT1 enhanced cardiomyocyte apoptosis involved the autophagy regulation. To address this, cardiomyocytes were isolated from neonatal mice and then stimulated with hypoxia/reoxygenation (H/R) injury to mimic AMI. The cell apoptosis was evaluated using TUNEL staining and Western blot analysis of apoptosis-related proteins. The autophagy level was assessed using GFP-LC3 immunofluorescence and Western blot analysis of autophagy-related proteins. The results showed that H/R injury increased MALAT1 expression. Furthermore, MALAT1 overexpression significantly enhanced apoptosis and regulated autophagy of cardiomyocytes, whereas MALAT1 knockdown exerted the opposite effect. Moreover, rapamycin (an autophagy activator) effectively attenuated the MALAT1-mediated enhancement of cardiomyocyte apoptosis. Overall, our findings demonstrated that the increased MALAT1 expression induced by H/R injury enhances cardiomyocyte apoptosis, at least in part, through autophagy modulation.

中文翻译：

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长的非编码RNA MALAT1通过自噬调节增强心肌细胞的凋亡。

自噬的诱导促进心肌细胞存活并赋予急性心肌梗塞（AMI）心脏保护作用。我们先前的研究表明，敲低长非编码RNA（lncRNA）转移相关的肺腺癌转录本1（MALAT1）可以减弱小鼠AMI中的心肌细胞凋亡。在此，本研究进一步研究了MALAT1增强心肌细胞凋亡的机制是否涉及自噬调节。为了解决这个问题，从新生小鼠中分离出心肌细胞，然后用缺氧/复氧（H / R）损伤刺激以模拟AMI。使用TUNEL染色和凋亡相关蛋白的蛋白质印迹分析评估细胞凋亡。使用GFP-LC3免疫荧光和自噬相关蛋白的Western印迹分析来评估自噬水平。结果表明，H / R损伤增加了MALAT1表达。此外，MALAT1的过表达显着增强了心肌细胞的凋亡并调节了其自噬，而MALAT1的抑制则起相反的作用。此外，雷帕霉素（一种自噬激活剂）有效减弱了MALAT1介导的心肌细胞凋亡的增强。总体而言，我们的发现表明，H / R损伤诱导的MALAT1表达增加至少部分通过自噬调节增强了心肌细胞的凋亡。雷帕霉素（一种自噬激活剂）有效地减弱了MALAT1介导的心肌细胞凋亡的增强。总体而言，我们的发现表明，H / R损伤诱导的MALAT1表达增加至少部分通过自噬调节增强了心肌细胞的凋亡。雷帕霉素（一种自噬激活剂）有效地减弱了MALAT1介导的心肌细胞凋亡的增强。总体而言，我们的发现表明，H / R损伤诱导的MALAT1表达增加至少部分通过自噬调节增强了心肌细胞的凋亡。