Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth.
Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth.
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DOI：
10.1016/s0021-9258(17)46269-7
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发表时间：
1990-09
期刊：
影响因子：
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通讯作者：
S. Sen;Gopal C. Kundu;N. Mekhail;J. Castel;K. Misono;B. Healy
中科院分区：
文献类型：
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作者：
S. Sen;Gopal C. Kundu;N. Mekhail;J. Castel;K. Misono;B. Healy
心肌肥厚发生或消退的机制不能完全解释为对血压控制的反应。我们假设心肌肥大的发展是由一个信号（机械的或体液的）传递给心肌，进而产生一种可溶性因子，触发蛋白质合成并启动心肌生长。利用从正常大鼠心脏分离的心肌细胞中获得的蛋白质合成刺激作为实验系统，我们从自发性高血压大鼠的肥大心肌中鉴定出一种可溶性因子。该因子经纯化后具有明显的同质性，是一个12kda的蛋白。测定了含有7-24个残基的三个内部释放肽的序列。根据确定的这些肽的氨基酸序列，这种因子（称为肌营养因子）似乎是一种新的蛋白质，与任何先前描述的生长因子都没有同源性。肌营养因子存在于人、狗和大鼠肥厚的心脏中（28-35%的蛋白质合成刺激超过控制），少量存在于正常心脏中（5-6%的刺激）。肌营养因子在新生儿心肌细胞中引起两种剂量依赖性效应：心肌细胞表面积的增加和有组织的肌原纤维的出现，这在48小时内变得明显。肌营养因子可能在心肌肥大的发病机制和心肌细胞的正常发育中发挥重要作用。
Mechanisms involved in the development or the regression of myocardial hypertrophy cannot be fully explained as responses to blood pressure control alone. We had hypothesized that the development of hypertrophy is initiated by a signal (mechanical or humoral) to the myocardium, which in turn produces a soluble factor that triggers protein synthesis and initiates myocardial growth. Using the stimulation of protein synthesis in isolated cardiac myocytes obtained from normal rat hearts as an assay system, we have identified a soluble factor from the hypertrophied myocardium of spontaneously hypertensive rats. This factor, which has been purified to apparent homogeneity, is a protein of 12 kDa. The sequence of three internally liberated peptides containing 7-24 residues was determined. Based on the determined amino acid sequences of these peptides, this factor (designated myotrophin) appears to be a novel protein that shows no homology with any previously described growth factors. Myotrophin is present in human, dog, and rat hypertrophied hearts (28-35% stimulation of protein synthesis over control) and in small amounts in normal hearts (5-6% stimulation). Myotrophin causes two dose-dependent effects in neonatal cardiac myocytes: an increase in the surface area of the myocyte and the appearance of organized myofibrils, which become apparent within 48 h. Myotrophin may play an important role in the pathogenesis of cardiac hypertrophy as well as in the normal development of cardiac myocytes.