MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress.
MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress.
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MG53 对于 T 管成熟来说是可有可无的，但对于在心脏应激后维持 T 管完整性至关重要
DOI：
10.1016/j.yjmcc.2017.08.007
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发表时间：
2017-11
影响因子：
5
通讯作者：
Song LS
中科院分区：
文献类型：
--
作者：
Zhang C;Chen B;Wang Y;Guo A;Tang Y;Khataei T;Shi Y;Kutschke WJ;Zimmerman K;Weiss RM;Liu J;Benson CJ;Hong J;Ma J;Song LS
心脏横（T）小管膜系统是心脏功能的保障，并在心脏应激时发生急剧重塑。然而，心肌细胞修复受损T-小管网络的机制尚不清楚。在本研究中，我们测试了一种假设，即MG 53，一种肌肉特异性膜修复蛋白，拮抗T-小管损伤，以防止适应不良的重塑，从而失去兴奋-收缩偶联和心脏功能。使用MG 53敲除（MG 53-KO）小鼠，我们首先确定了MG 53的缺乏对发育中心脏的T-小管网络的成熟没有影响。此外，MG 53消融不影响迟至10月龄的无应激成人心脏中的T-小管完整性。在左心室压力超负荷诱导的心脏应激后，野生型小鼠的MG 53蛋白水平增加了约3倍，表明病理性应激诱导MG 53的显著上调。MG 53缺陷小鼠的T-小管破坏恶化，Ca 2+处理特性明显失调，包括Ca 2+瞬时振幅降低，达到峰值和衰减的时间延长。此外，MG 53缺乏加剧了心脏肥大和功能障碍，并降低了心脏应激后的存活率。我们的数据表明，MG 53是不需要的T-小管的发展和维护在正常的生理。然而，MG 53对于在病理性心脏应激下保持T-小管完整性以及由此保持Ca 2+处理特性和心脏功能是必不可少的。
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.
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影响因子：
3.7
作者：
Crossman DJ;Ruygrok PN;Soeller C;Cannell MB
通讯作者：
Cannell MB
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1161/circep.111.969733
发表时间：
2012-08-01
期刊：
Circulation. Arrhythmia and electrophysiology
影响因子：
--
作者：
Chen B;Guo A;Gao Z;Wei S;Xie YP;Chen SR;Anderson ME;Song LS
通讯作者：
Song LS
影响因子：
10.8
作者：
Balijepalli, RC;Lokuta, AJ;Kamp, TJ
通讯作者：
Kamp, TJ
影响因子：
10.8
作者：
Chen, Biyi;Guo, Ang;Song, Long-Sheng
通讯作者：
Song, Long-Sheng