title: ERK5 knock down aggravates detrimental effects of hypothermal stimulation on cardiomyocytes via Bim upregulation.
abstract: Mechanism of cold induced myocardial injury remained unclear. Our study investigated the role of ERK5/Bim pathway in hypothermal stimulation-induced apoptosis or damage of cardiomyocytes (CMs). Results showed that in CMs which under hypothermal stimulation, ERK5 siRNA promoted expression of Bim protein. Bim siRNA did not influence ERK5 expression but attenuated production of p-ERK5. ERK5 siRNA induced higher apoptosis rate; intracellular Ca(2+) overload; ROS activity; ΔΨm damage in hypothermia stimulated CMs, when compared with hypothermal stimulation solely treated group, while Bim siRNA effected oppositely and canceled pro-apoptotic effect of ERK5 siRNA. In conclusion, ERK5 knock down releases inhibition to Bim expression, induces aggravated apoptosis in CMs under hypothermal stimulation, which related to higher intracellular Ca(2+) overload, ROS activity, and more severe ΔΨm damage. Results revealed regulative role of ERK5/Bim pathway in hypothermal stimulation-induced injure or apoptosis of cardiomyocytes.
authors.affiliation: Department of Cardiology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: Yao-Sheng
authors.initials: YS
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Health Sciences, Shanghai, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, PR China.
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, PR China. Electronic address: chengxiaoshu01@gmail.com.
authors.forename: Xiao-Shu
authors.initials: XS
authors.lastname: Cheng
authors.affiliation: Department of Cardiology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China. Electronic address: changzhengxnk@163.com.
authors.forename: Zong-Gui
authors.initials: ZG
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D007036:Hypothermia, Induced; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000172:deficiency* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D048054:Mitogen-Activated Protein Kinase 7; D002118:Calcium
keywords: Bim; Cardiomyocytes; Extracellular regulated protein kinases 5; Hypothermal stimulation