title: MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway.
abstract: Myocardial ischemia reperfusion (I/R) can induce altered expression of microRNAs (miRNAs). The miRNAs-miR-15a, miR-15b and miR-16 have been shown to play a role in apoptosis, although not in cardiac-related models. We investigated the roles of miR-15b in hypoxia/reoxygenation (H/R)-induced apoptosis of cardiomyocytes. Quantitative real time polymerase chain reaction results showed that the expression of miR-15a and miR-15b were up-regulated in Sprague-Dawley rat hearts subjected to I/R. Expression levels of miR-15b increased more than four fold above basal levels. Similar results were obtained for cardiomyocytes exposed to H/R. Recombinant adenoviral vectors were generated to explore the functional role of miR-15b in cultured cardiomyocytes exposed to H/R. Overexpression of miR-15b enhanced cell apoptosis and the loss of mitochondrial membrane potential, as determined by flow cytometric analysis. Conversely, down-regulated expression was cytoprotective. The effects of miR-15b can by mimicked by Bcl-2 short-interfering RNAs. The inhibition of miR-15b increased expression levels of the Bcl-2 protein without affecting Bcl-2 mRNA levels, suppressed the release of mitochondrial cytochrome c to the cytosol and decreased the activities of caspase-3 and 9. It is possible that miR-15b is the upstream regulator of a mitochondrial signaling pathway for H/R induced apoptosis.
authors.affiliation: Department of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China, liulifeng301@126.com.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
authors.forename: Guoming
authors.initials: G
authors.lastname: Zhang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liang
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Liu
authors.forename: Tiande
authors.initials: T
authors.lastname: Li
authors.forename: Jiao
authors.initials: J
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C534110:mirn15 microRNA, rat; D053148:Caspase 3; D053453:Caspase 9; D010100:Oxygen