title: MicroRNA-145 protects cardiomyocytes against hydrogen peroxide (H₂O₂)-induced apoptosis through targeting the mitochondria apoptotic pathway.
abstract: MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, has been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia/reperfusion induced cardiac injury. Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂-induced apoptosis through targeting the mitochondrial pathway. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-145 in either ischemia/reperfused mice myocardial tissues or H₂O₂-treated neonatal rat ventricle myocytes (NRVMs) was markedly down-regulated. Over-expression of miR-145 significantly inhibited the H₂O₂-induced cellular apoptosis, ROS production, mitochondrial structure disruption as well as the activation of key signaling proteins in mitochondrial apoptotic pathway. These protective effects of miR-145 were abrogated by over-expression of Bnip3, an initiation factor of the mitochondrial apoptotic pathway in cardiomyocytes. Finally, we utilized both luciferase reporter assay and western blot analysis to identify Bnip3 as a direct target of miR-145. Our results suggest miR-145 plays an important role in regulating mitochondrial apoptotic pathway in heart challenged with oxidative stress. MiR-145 may represent a potential therapeutic target for treatment of oxidative stress-associated cardiovascular diseases, such as myocardial ischemia/reperfusion injury.
authors.affiliation: Department of Cardiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.
authors.forename: Ruotian
authors.initials: R
authors.lastname: Li
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Li
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Sun
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions / Q000187:drug effects / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C508686:BNip3 protein, mouse; C541010:MIRN145 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide