Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload
Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload
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DOI：
10.1006/jmcc.2000.1269
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发表时间：
2000-12-01
影响因子：
5
通讯作者：
Teyssier, JR
中科院分区：
文献类型：
--
作者：
Ecarnot-Laubriet, A;De Luca, K;Teyssier, JR
心脏 LIM 结构域蛋白 MLP 在心肌细胞的结构和机械功能中起着至关重要的作用。缺乏 MLP 基因的小鼠会出现心脏肥大、扩张性心脏病和心力衰竭。我们研究了 MLP 的下调是否是由压力超负荷引起的，并导致心脏肥大和衰竭的病理生理学。我们在患有肺动脉高压的大鼠右心室中研究了这种机制，因为众所周知，该心室非常容易受到压力过载的有害影响。在 31 天的时间内，心脏肥大进展至衰竭，MLP 转录物水平急剧下降 50%。一致的是，免疫组织化学在衰竭阶段的心肌细胞的细胞质中检测到非常微弱的蛋白质信号，但心肌细胞的细胞核被大量标记。通过对细胞核和细胞质部分进行 MLP 的免疫检测来证实细胞核的重新定位。这种核定位是逆向分化表型的标志，因为它仅在分化的成肌细胞中观察到。这些变化与肌原纤维的超微结构紊乱有关，类似于在 MLP -/- 小鼠中观察到的情况。因此，基因重编程过程中发生的 MLP 下调可能对心肌机械衰竭产生重要影响。 (C) 2000 年学术出版社。
The cardiac LIM domain protein MLP plays a crucial role in the architecture and mechanical function of cardiac myocytes. Mice lacking the MLP gene develop cardiac hypertrophy, dilated cardiopathy and heart failure. We investigated whether downregulation of MLP is induced by pressure overload and contributes to the physiopathology of cardiac hypertrophy and failure. We studied this mechanism in rat right ventricles submitted to pulmonary arterial hypertension, because it is known that this ventricle is very vulnerable to the deleterious effects of pressure overload. During the progression of cardiac hypertrophy to failure over a 31 days period there was a dramatic decrease by 50% of the MLP transcripts level. Consistently, immunohistochemistry detected very weak protein signals in the cytoplasms of cardiomyocytes at the failing stage, but myocytes nuclei were heavily labeled. The nuclear relocation was confirmed by the immunodetection of MLP on the nuclear and cytosolic fractions. This nuclear localization is the hallmark of a retro-differentiated phenotype, since it has been observed only in differentiating myoblasts. These changes were associated with ultrastructural disorganization of the myofibrils similar to that observed in MLP -/- mice. Therefore, MLP dowregulation occurring during gene reprogramming may critically contribute to mechanical failure of the myocardium. (C) 2000 Academic Press.