Alterations at the intercalated disk associated with the absence of muscle LIM protein.
Alterations at the intercalated disk associated with the absence of muscle LIM protein.
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DOI：
10.1083/jcb.153.4.763
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发表时间：
2001-05-14
期刊：
影响因子：
--
通讯作者：
Perriard JC
中科院分区：
文献类型：
--
作者：
Ehler E;Horowits R;Zuppinger C;Price RL;Perriard E;Leu M;Caroni P;Sussman M;Eppenberger HM;Perriard JC
在这项研究中，我们研究了扩张型心肌病 (DCM) 小鼠模型（肌肉 LIM 蛋白 (MLP) 敲除小鼠）的心肌细胞结构，并在第二种 DCM 模型（原调节蛋白过表达转基因 (TOT) 小鼠）中证实了一些观察结果。与野生型细胞相比，从两种菌株中新鲜分离的心肌细胞的特征是形状更不规则。在闰盘处观察到变化，闰盘是心肌细胞之间机械耦合的特殊区域，而 MLP 敲除小鼠的肌小节中收缩蛋白的亚细胞组织似乎没有变化。闰盘的不同部分受到的影响不同。粘附连接的成分上调，桥粒蛋白不变，间隙连接蛋白下调。此外，N-RAP（一种位于闰盘的包含 LIM 结构域的蛋白质）的表达在 MLP 敲除小鼠和 TOT 小鼠中上调。对出生后发育过程中闰盘组成的详细分析表明，N-RAP 表达的上调可能作为 DCM 发展的早期标志。细胞骨架蛋白表达水平的改变（MLP 的缺乏或原调节蛋白表达的增加）显然会导致肌原纤维装置的功能受损和生理应激，最终导致 DCM，并伴随着闰盘的外观和组成的改变。
In this study, we investigated cardiomyocyte cytoarchitecture in a mouse model for dilated cardiomyopathy (DCM), the muscle LIM protein (MLP) knockout mouse and substantiated several observations in a second DCM model, the tropomodulin-overexpressing transgenic (TOT) mouse. Freshly isolated cardiomyocytes from both strains are characterized by a more irregular shape compared with wild-type cells. Alterations are observed at the intercalated disks, the specialized areas of mechanical coupling between cardiomyocytes, whereas the subcellular organization of contractile proteins in the sarcomeres of MLP knockout mice appears unchanged. Distinct parts of the intercalated disks are affected differently. Components from the adherens junctions are upregulated, desmosomal proteins are unchanged, and gap junction proteins are downregulated. In addition, the expression of N-RAP, a LIM domain– containing protein located at the intercalated disks, is upregulated in MLP knockout as well as in TOT mice. Detailed analysis of intercalated disk composition during postnatal development reveals that an upregulation of N-RAP expression might serve as an early marker for the development of DCM. Altered expression levels of cytoskeletal proteins (either the lack of MLP or an increased expression of tropomodulin) apparently lead to impaired function of the myofibrillar apparatus and to physiological stress that ultimately results in DCM and is accompanied by an altered appearance and composition of the intercalated disks.
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影响因子：
10.8
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