Induction of MicroRNA-24 by HIF-1 Protects Against Ischemic Injury in Rat Cardiomyocytes

Physiological Research - Trang 555-565 - 2012
Dong Li1, Jing Tian1, Xin Guo2, Longtai Huang2, Yungen Xu1, Chih‐Chieh Wang1, Jia Wang2, Anmin Ren1, Wei Yuan2,1, Longxin Lin1
1Department of Physiology and the Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, P. R. China,
2Department of Physiology and Neurobiology, Basic Medical College, Ningxia Medical University, Yinchuan, P. R. China

Tóm tắt

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.

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Physiological Research

555-565

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