title: Induction of microRNA-24 by HIF-1 protects against ischemic injury in rat cardiomyocytes.
abstract: 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.
authors.affiliation: Department of Physiology, Second Military Medical University, Shanghai, PR China.
authors.forename: D-F
authors.initials: DF
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Tian
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: L-M
authors.initials: LM
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: C-C
authors.initials: CC
authors.lastname: Wang
authors.forename: J-F
authors.initials: JF
authors.lastname: Wang
authors.forename: A-J
authors.initials: AJ
authors.lastname: Ren
authors.forename: W-J
authors.initials: WJ
authors.lastname: Yuan
authors.forename: L
authors.initials: L
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002470:Cell Survival / Q000235:genetics; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009336:Necrosis / Q000235:genetics; D020011:Protective Agents / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D051793:Hypoxia-Inducible Factor 1; C574736:MIRN24 microRNA, rat; D008565:Membrane Proteins; D035683:MicroRNAs; D020011:Protective Agents; D011518:Proto-Oncogene Proteins; D007770:L-Lactate Dehydrogenase