miR-24 regulates intrinsic apoptosis pathway in mouse cardiomyocytes

• Published in: PloS one 2014-01, Vol.9 (1), p.e85389-e85389
• Main Authors: Wang, Li, Qian, Li
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Apoptosis; Apoptosis - physiology; Attenuation; Base Sequence; Bax protein; bcl-2-Associated X Protein - metabolism; Biology; Cardiomyocytes; Cardiovascular disease; Cell cycle; Cell death; Cell size; Cell survival; Coronary artery disease; Cytochrome; Cytochrome c; Cytosol; Disease Models, Animal; DNA Primers; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Flow Cytometry; Growth factors; Heart; Heart attack; Heart cells; Heart diseases; Heart failure; Homology; Laboratories; Medicine; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - physiology; miRNA; Mitochondria; Myocardial infarction; Myocardial Infarction - pathology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Protein Transport; Proteins; Real-Time Polymerase Chain Reaction; Ribonucleic acid; RNA; Target recognition; Transcription Factor CHOP - metabolism; Translocation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0085389

Numerous cardiac diseases, including myocardial infarction (MI) and chronic heart failure, have been associated with cardiomyocyte apoptosis. Promoting cell survival by inhibiting apoptosis is one of the effective strategies to attenuate cardiac dysfunction caused by cardiomyocyte loss. miR-24 has been shown as an anti-apoptotic microRNA in various animal models. In vivo delivery of miR-24 into a mouse MI model suppressed cardiac cell death, attenuated infarct size, and rescued cardiac dysfunction. However, the molecular pathway by which miR-24 inhibits cardiomyocyte apoptosis is not known. Here we found that miR-24 negatively regulates mouse primary cadiomyocyte cell death through functioning in the intrinsic apoptotic pathways. In ER-mediated intrinsic pathway, miR-24 genetically interacts with the CEBP homologous gene CHOP as knocking down of CHOP partially attenuated the induced apoptosis by miR-24 inhibition. In mitochondria-involved intrinsic pathway, miR-24 inhibits the initiation of apoptosis through suppression of Cytochrome C release and Bax translocation from cytosol to mitochondria. These results provide mechanistic insights into the miR-24 mediated anti-apoptotic effects in murine cardiomyocytes.