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MicroRNA-145 protects cardiomyocytes against hydrogen peroxide (H₂O₂)-induced apoptosis through targeting the mitochondria apoptotic pathway.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (9), pp. e44907. Date of Electronic Publication: 2012 Sep 18. - Publication Year :
- 2012
-
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.
- Subjects :
- 3' Untranslated Regions drug effects
3' Untranslated Regions genetics
Animals
Apoptosis genetics
Down-Regulation drug effects
Down-Regulation genetics
HEK293 Cells
Humans
Male
Membrane Proteins genetics
Mice
MicroRNAs genetics
Mitochondria genetics
Mitochondria pathology
Mitochondrial Proteins genetics
Myocytes, Cardiac drug effects
Myocytes, Cardiac pathology
Oxidative Stress drug effects
Oxidative Stress genetics
Rats
Reactive Oxygen Species metabolism
Reperfusion Injury genetics
Reperfusion Injury metabolism
Reperfusion Injury pathology
Apoptosis drug effects
Hydrogen Peroxide pharmacology
MicroRNAs metabolism
Mitochondria drug effects
Mitochondria metabolism
Myocytes, Cardiac cytology
Myocytes, Cardiac metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23028672
- Full Text :
- https://doi.org/10.1371/journal.pone.0044907