Han Hu1, Mingyang Jiang2, Yangpo Cao3, Zhuojun Zhang1, Bin Jiang1, Feng Tian4, Juan Feng3, Yali Dou5, Myriam Gorospe6, Ming Zheng3, Lemin Zheng7, Zhongzhou Yang2, Wengong Wang1. 1. >Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. 2. Department of Cardiology, State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China. 3. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road Beijing, 100191, China. 4. Department of Laboratory Animal Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. 5. Department of Pathology and Biological Chemistry, University of Michigan, 1301 Catherine Street, Ann Arbor, MI 48105, USA. 6. Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21224, USA. 7. Institute of Cardiovascular Research, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
Abstract
AIMS: The elevated expression of phospholamban (PLB) has been observed in heart failure and cardiac remodelling, inhibiting the affinity of Ca2+ pump to Ca2+ thereby impairing heart relaxation. However, the mechanisms underlying the regulation of PLB remains to be further studied. The present study aims to test the role of RNA-binding protein HuR in the regulation of PLB and the impact of this regulatory process in cardiac remodelling. METHODS AND RESULTS: A mouse model specifically deleted HuR in cardiomyocytes were used for testing the role of HuR in regulating PLB during isoproterenol (ISO)-induced cardiac remodelling. HuR deficiency did not significantly influence the phenotype and function of mouse heart under static status. However, deletion of HuR in cardiomyocytes mitigated the effect of ISO in inducing PLB expression and reducing β1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and β1-AR mRNAs stabilized PLB mRNA and destabilized β1-AR mRNA, respectively. CONCLUSION: HuR stabilizes PLB mRNA and destabilizes β1-AR mRNA. The HuR-PLB and HuR-β1-AR regulatory processes impact on ISO-induced cardiac remodelling. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: The elevated expression of phospholamban (PLB) has been observed in heart failure and cardiac remodelling, inhibiting the affinity of Ca2+ pump to Ca2+ thereby impairing heart relaxation. However, the mechanisms underlying the regulation of PLB remains to be further studied. The present study aims to test the role of RNA-binding protein HuR in the regulation of PLB and the impact of this regulatory process in cardiac remodelling. METHODS AND RESULTS: A mouse model specifically deleted HuR in cardiomyocytes were used for testing the role of HuR in regulating PLB during isoproterenol (ISO)-induced cardiac remodelling. HuR deficiency did not significantly influence the phenotype and function of mouse heart under static status. However, deletion of HuR in cardiomyocytes mitigated the effect of ISO in inducing PLB expression and reducing β1-AR expression, in turn aggravating ISO-induced myocardial hypertrophy and cardiac fibrosis. In H9C2 cells, association of HuR with PLB and β1-AR mRNAs stabilized PLB mRNA and destabilized β1-AR mRNA, respectively. CONCLUSION:HuR stabilizes PLB mRNA and destabilizes β1-AR mRNA. The HuR-PLB and HuR-β1-AR regulatory processes impact on ISO-induced cardiac remodelling. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Junying Zheng; Danielle M Yancey; Mustafa I Ahmed; Chih-Chang Wei; Pamela C Powell; Mayilvahanan Shanmugam; Himanshu Gupta; Steven G Lloyd; David C McGiffin; Chun G Schiros; Thomas S Denney; Gopal J Babu; Louis J Dell'Italia Journal: Circ Heart Fail Date: 2013-12-02 Impact factor: 8.790
Authors: Daniel B McClatchy; Yuanhui Ma; David A Liem; Dominic C M Ng; Peipei Ping; John R Yates Journal: J Mol Cell Cardiol Date: 2018-07-19 Impact factor: 5.000