title: Anti-apoptotic effects of myocardin-related transcription factor-A on rat cardiomyocytes following hypoxia-induced injury.
abstract: Myocardin-related transcription factor-A (MRTF-A) can transduce both biomechanical and humoral signals, which can positively modulate cardiac damage induced by acute myocardial infarction. However, the molecular mechanism that underlies the contribution that MRTF-A provides to the myocardium is not completely understood. The objective of this study was to investigate the effects of MRTF-A on myocardium apoptosis and its mechanisms. Our experiment results showed that MRTF-A expression increased and Bcl-2 expression reduced during myocardial ischemia-reperfusion in rat. Meanwhile, primary cardiomyocytes were pretreated with wild-type MRTF-A or siRNA of MRTF-A before exposure to hypoxia. We found that overexpression of MRTF-A in myocardial cells inhibited apoptosis and the release of cytochrome c. MRTF-A enhanced Bcl-2, which contributes to MRTF-A interaction with Bcl-2 in the nuclei of cardiomyocytes. MRTF-A upregulation expression of Bcl-2 in cardiomyocytes induced by hypoxia was inhibited by PD98059, an ERK1/2 inhibitor. In conclusions, MRTF-A improved myocardial cell survival in a cardiomyocyte model of hypoxia-induced injury; this effect was correlated with the upregulation of anti-apoptotic gene Bcl-2 through the activation of ERK1/2.
authors: a The Second Affiliated Hospital (Jiande Branch), Zhejiang University School of Medicine, JianDe 311600, China.
authors: Ze
authors: Z
authors: Zhong
authors: a The Second Affiliated Hospital (Jiande Branch), Zhejiang University School of Medicine, JianDe 311600, China.
authors: Jia-Qing
authors: JQ
authors: Hu
authors: a The Second Affiliated Hospital (Jiande Branch), Zhejiang University School of Medicine, JianDe 311600, China.
authors: Xin-Dong
authors: XD
authors: Wu
authors: b Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors: Yong
authors: Y
authors: Sun
authors: b Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors: Jun
authors: J
authors: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D000099251:Myocardin
chemical_list: D045304:Cytochromes c; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin; C557977:myocardin-related transcription factor-A, rat
keywords: Bcl02; Blc-2; ERK pathway; MRTF-A; apoptose du myocarde; dommage par hypoxie; facteur de transcription; hypoxia injury; ischemia–reperfusion; ischémie-reperfusion; myocardial apoptosis; sentier ERK; transcription factor