Journal article
MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress
Journal of molecular and cellular cardiology, Vol.112, pp.123-130
11/2017
DOI: 10.1016/j.yjmcc.2017.08.007
PMCID: PMC5682927
PMID: 28822805
Abstract
The cardiac transverse (T)-tubule membrane system is the safeguard for cardiac function and undergoes dramatic remodeling in response to cardiac stress. However, the mechanism by which cardiomyocytes repair damaged T-tubule network remains unclear. In the present study, we tested the hypothesis that MG53, a muscle-specific membrane repair protein, antagonizes T-tubule damage to protect against maladaptive remodeling and thereby loss of excitation-contraction coupling and cardiac function. Using MG53-knockout (MG53-KO) mice, we first established that deficiency of MG53 had no impact on maturation of the T-tubule network in developing hearts. Additionally, MG53 ablation did not influence T-tubule integrity in unstressed adult hearts as late as 10months of age. Following left ventricular pressure overload-induced cardiac stress, MG53 protein levels were increased by approximately three-fold in wild-type mice, indicating that pathological stress induces a significant upregulation of MG53. MG53-deficient mice had worsened T-tubule disruption and pronounced dysregulation of Ca2+ handling properties, including decreased Ca2+ transient amplitude and prolonged time to peak and decay. Moreover, MG53 deficiency exacerbated cardiac hypertrophy and dysfunction and decreased survival following cardiac stress. Our data suggest MG53 is not required for T-tubule development and maintenance in normal physiology. However, MG53 is essential to preserve T-tubule integrity and thereby Ca2+ handling properties and cardiac function under pathological cardiac stress.
•MG53 is a muscle specific membrane repair protein. Its role in cardiac T-tubule biology is completely unknown.•MG53 deficiency had no impact on maturation of T-tubule network in developing hearts.•MG53 ablation did not influence T-tubule integrity in unstressed adult hearts.•MG53 protein is upregulated in both compensated hypertrophy and heart failure.•MG53 deficiency exacerbated T-tubule remodeling, Ca2+ handling dysfunction following cardiac stress.
Details
- Title: Subtitle
- MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress
- Creators
- Caimei Zhang - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USABiyi Chen - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAYihui Wang - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAAng Guo - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAYiqun Tang - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USATahsin Khataei - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAYun Shi - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAWilliam J Kutschke - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAKathy Zimmerman - Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USARobert M Weiss - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAJie Liu - Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060, ChinaChristopher J Benson - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAJiang Hong - Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, ChinaJianjie Ma - Department of Surgery, Ohio State University Medical Center, Columbus, OH 43212, USALong-Sheng Song - Division of Cardiovascular Medicine, Department of Internal Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.112, pp.123-130
- DOI
- 10.1016/j.yjmcc.2017.08.007
- PMID
- 28822805
- PMCID
- PMC5682927
- NLM abbreviation
- J Mol Cell Cardiol
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: R01 HL090905, HL130346, AR070752, AR061385; DOI: 10.13039/100000738, name: United States Department of Veterans Affairs Biomedical Laboratory Research, award: I01BX002334, 2I01BX000776; DOI: 10.13039/501100001809, name: China National Natural Science Foundation, award: 31371159, 57201701, 81570293
- Language
- English
- Date published
- 11/2017
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984040255602771
Metrics
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