Thyroid hormone inhibits slow skeletal TnI expression in cardiac TnI-null myocardial cells
Thyroid hormone inhibits slow skeletal TnI expression in cardiac TnI-null myocardial cells
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DOI：
10.1016/j.tice.2004.10.002
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发表时间：
2005-02-01
期刊：
影响因子：
2.6
通讯作者：
Huang, XP
中科院分区：
文献类型：
--
作者：
Riedel, B;Jia, YY;Huang, XP
建立了心肌肌钙蛋白I （cTnI）基因敲除小鼠模型，cTnI缺失小鼠的表型是由TnI缺乏和舒张功能障碍引起的急性心力衰竭。TnI的两种异构体（胎儿形式的ssTnI和成人形式的cTnl）主要在发育调节程序下在心脏中表达。在我们之前的研究中，我们证明了甲状腺激素可以在ssTnI基因在心脏中表达的时间过程之后。在本研究中，我们成功地培养了野生型和cTnI缺失小鼠心脏的新生心肌细胞。研究了ssTnI基因在这些细胞中的表达模式。通过Western blotting检测，在野生型心肌细胞中观察到TnI亚型的转换。TnI亚型转换的模式与我们之前报道的体内研究非常相似。在第1天至第7天培养的无cTnI心肌细胞中，细胞内ssTnI浓度持续下降。cTnI缺失细胞中ssTnI下降的时间过程与野生型心肌细胞相似，提示ssTnI基因表达不存在对cTnI缺失的显著补偿。这一观察结果与我们之前在整个心脏水平上的发现不同。此外，在培养的无cTnI的心肌细胞中添加甲状腺激素T-3 （20 ng/ml）时，ssTnI浓度下降的时间更早。这与我们之前在体内研究的观察结果不一致。这些数据表明，甲状腺激素可以改变培养心肌细胞中ssTnI基因表达的时间过程，TnI基因的调控也受心肌细胞内一些未知的程序性事件的控制。(C) 2004 Elsevier Ltd.版权所有。
A cardiac troponin I (cTnI) gene knockout mouse model has been created and the phenotype of the cTnI null mice is an acute heart failure resulting from the deficiency of TnI and a diastolic dysfunction. Two isoforrns of TnI (the fetal form ssTnI and the adult form cTnl) are mainly expressed in the heart under a developmentally regulated program. In our previous studies, we demonstrated that thyroid hormone could after the time course of ssTnI gene expression in the heart. In the present study, we have successfully cultured neonatal cardiac myocytes from wild type and cTnI null mouse hearts. The ssTnI gene expression pattern has been investigated in these cells. By using Western blotting assays, a TnI isoform switching has been observed in the wild type cardiac myocytes. The pattern of TnI isoform switching is very similar to that of in vivo study we reported previously. In cTnI null cardiac myocytes cultured from day 1 to day 7, there is a continuous decline in ssTnI concentration in the cells. The time course of ssTnI decline in cTnI null cells is similar to that of wild type cardiac myocytes, suggesting that there is no significant compensation of ssTnI gene expression for the absence of the cTnI. This observation is different from what we found previously at a whole heart level. In addition, when thyroid hormone T-3 (20 ng/ml) is added to cultured cTnI null cardiac myocytes, the decline of ssTnI concentration occurs earlier. This is inconsistent with our observations from previous in vivo studies. The data demonstrate that thyroid hormone can alter the time course of ssTnI gene expression in cultured cardiac myocytes and TnI gene regulation is also controlled by some unknown programmed events inside of cardiac myocytes. (C) 2004 Elsevier Ltd. All rights reserved.