miR-24 regulates intrinsic apoptosis pathway in mouse cardiomyocytes.
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.
Department of Pathology and Laboratory Medicine; University of North Carolina, Chapel Hill, North Carolina, United States of America ; McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Li
L
Wang
Department of Pathology and Laboratory Medicine; University of North Carolina, Chapel Hill, North Carolina, United States of America ; McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Li
L
Qian
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009203:Myocardial Infarction / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D021381:Protein Transport; D060888:Real-Time Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D017931:DNA Primers; C497250:Ddit3 protein, mouse; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D051028:bcl-2-Associated X Protein; D051742:Transcription Factor CHOP