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: Ruotian Li, Guijun Yan, Qiaoling Li, Haixiang Sun, Yali Hu, Jianxin Sun, Biao Xu
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e44907 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23028672 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• BNip3 protein, mouse
• MIRN145 microRNA, human
• Membrane Proteins
• MicroRNAs
• Mitochondrial Proteins
• Reactive Oxygen Species
• Hydrogen Peroxide

Topics

• 3' Untranslated Regions (drug effects, genetics)
• Animals
• Apoptosis (drug effects, genetics)
• Down-Regulation (drug effects, genetics)
• HEK293 Cells
• Humans
• Hydrogen Peroxide (pharmacology)
• Male
• Membrane Proteins (genetics)
• Mice
• MicroRNAs (genetics, metabolism)
• Mitochondria (drug effects, genetics, metabolism, pathology)
• Mitochondrial Proteins (genetics)
• Myocytes, Cardiac (cytology, drug effects, metabolism, pathology)
• Oxidative Stress (drug effects, genetics)
• Rats
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (genetics, metabolism, pathology)