MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress
| Autor: | Yun Shi, Jie Liu, William J. Kutschke, Kathy Zimmerman, Jiang Hong, Christopher J. Benson, Tahsin Khataei, Jianjie Ma, Robert M. Weiss, Long-Sheng Song, Yihui Wang, Caimei Zhang, Yiqun Tang, Biyi Chen, Ang Guo |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cardiac function curve Down-Regulation chemistry.chemical_element Calcium Sodium-Calcium Exchanger Article T-tubule 03 medical and health sciences Sarcolemma Downregulation and upregulation medicine Animals Myocytes Cardiac Calcium Signaling Molecular Biology Pathological Excitation Contraction Coupling Mice Knockout Sodium-calcium exchanger business.industry Myocardium Membrane Proteins Heart Anatomy Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Cardiac hypertrophy Ventricular pressure Carrier Proteins Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 112:123-130 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/j.yjmcc.2017.08.007 |
| Popis: | 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 10 months 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. |
| Databáze: | OpenAIRE |
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