Induction of MicroRNA-24 by HIF-1 Protects Against Ischemic Injury in Rat Cardiomyocytes
Induction of MicroRNA-24 by HIF-1 Protects Against Ischemic Injury in Rat Cardiomyocytes
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HIF-1 诱导 MicroRNA-24 可预防大鼠心肌细胞缺血性损伤
DOI：
10.33549/physiolres.932270
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发表时间：
2012-01-01
影响因子：
2.1
通讯作者：
Lin, L.
中科院分区：
文献类型：
--
作者：
Li, D. F.;Tian, J.;Lin, L.
MicroRNA正在成为心脏功能的重要调节因子。本研究基于大鼠缺血心肌中miR-24表达显著增强的观察，探讨了miR-24在缺血心肌细胞中的作用。使用原代培养的大鼠心肌细胞，细胞损伤诱导缺血条件下，和细胞的乳酸脱氢酶（LDH）的释放，细胞活力，细胞凋亡和坏死的变化进行了评价。结果显示，暴露于缺血的心肌细胞中miR-24增加。当使用模拟RNA序列在缺血心肌细胞中进一步过表达miR-24时，LDH释放减少，细胞活力增强，凋亡和坏死率均降低。相比之下，miR-24缺陷导致正常和缺血心肌细胞中最大的LDH释放、最低的细胞活力和最高的凋亡和坏死率，与未转染的心肌细胞相比具有显著变化。此外，促凋亡基因BCL 2L 11的mRNA和蛋白水平通过miR-24过表达下调，通过miR-24缺陷上调。荧光素酶报告基因测定证实BCL 2L 11是miR-24的靶标。总体而言，这项研究显示了miR-24通过抑制BCL 2L 11对心肌缺血的保护作用，并可能代表缺血性心脏病的潜在新治疗方法。
MicroRNAs are emerging as important regulators of cardiac function. This study investigated the role of microRNA-24 (miR-24) in ischemic cardiomyocytes, based on the observation that miR-24 expression was significantly enhanced in the ischemic myocardium of rats. Using primary cultured rat cardiomyocytes, cell injury was induced by ischemic conditions, and the cells were evaluated for changes in lactate dehydrogenase (LDH) release, cell viability, apoptosis and necrosis. The results showed that miR-24 was increased in myocytes exposed to ischemia. When miR-24 was further overexpressed in ischemic myocytes using the mimic RNA sequence, LDH release was reduced, cell viability was enhanced, and apoptosis and necrosis rates were both decreased. By contrast, a deficiency in miR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes, with significant changes compared to that of non-transfected myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. Overall, this study showed a protective role for miR-24 against myocardial ischemia by inhibiting BCL2L11, and may represent a potential novel treatment for ischemic heart disease.