Myotrophin in human cardiomyopathic heart.
Myotrophin in human cardiomyopathic heart.
复制标题
人类心肌病心脏中的肌营养蛋白。
DOI：
10.1161/01.res.73.1.98
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发表时间：
1993
影响因子：
20.1
通讯作者：
Sen,S
中科院分区：
文献类型：
--
作者：
Sil,P;Misono,K;Sen,S
早些时候，肌营养因子，一个因素，已被分离，纯化，并部分测序自发性高血压大鼠心脏刺激心肌细胞生长。为了评估肌营养素在人类扩张型心肌病心脏的启动中的作用，我们分离并纯化了肌营养素，通过反相高效液相色谱法和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）确定其均一性（约50，000倍）。在纯化过程中，我们使用了一个生物测定系统，在该系统中，成人心肌细胞保持在文化中被用来评估蛋白质合成的[3 H]亮氨酸纳入肌细胞蛋白。从人扩张的心肌病心脏中纯化的肌营养素由单链多肽组成，其表观分子量为12 kD，通过SDS-PAGE测定。人肌营养素的部分内部氨基酸序列与大鼠肌营养素肽T9非常相似。使用大鼠肌营养肽（T26）抗体，我们确定了人类肌营养蛋白的免疫印迹。这些结果表明，人肌营养素具有大鼠肌营养素的T9和T26区。人肌营养因子刺激心肌蛋白质合成和细胞生长，类似于大鼠肌营养因子刺激这些因子的方式。蛋白质印迹分析表明，扩张的心肌病和正常人的心脏肌营养因子的存在。此外，与年龄和性别匹配的正常对照心脏相比，我们观察到扩张型心肌病患者心脏中肌营养素水平显著升高。从这些观察结果，我们得出结论，肌营养因子是存在于正常人的心脏，被发现在扩张的心肌病的人的心脏在较高的水平，并可能发挥作用，在启动心脏肥大以及在正常生长的心肌细胞在人类。
Earlier, myotrophin, a factor, has been isolated, purified, and partially sequenced from spontaneously hypertensive rat hearts that stimulated myocyte growth. To evaluate the role of myotrophin in the initiation of the human dilated cardiomyopathic heart, we have isolated and purified myotrophin to homogeneity (approximately 50,000-fold) as defined by reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). During purification, we used a bioassay system in which adult myocardial cells maintained in culture were used to evaluate protein synthesis by the incorporation of [3H]leucine into myocyte protein. Myotrophin purified from human dilated cardiomyopathic hearts is composed of a single polypeptide chain having an apparent molecular mass of 12 kD, determined by SDS-PAGE. The partial internal amino acid sequence of human myotrophin is very similar to that of rat myotrophin peptide T9. Using a rat myotrophin peptide (T26) antibody, we identified human myotrophin on an immunoblot. These results showed that human myotrophin possesses the T9 and T26 regions of rat myotrophin. Human myotrophin stimulated myocardial protein synthesis and cell growth, similar to the way in which rat myotrophin stimulated these factors. Western blot analysis showed the presence of myotrophin in both dilated cardiomyopathic and normal human hearts. In addition, we observed significantly elevated levels of myotrophin in dilated cardiomyopathic human hearts when compared with age- and sex-matched normal control hearts. From these observations, we conclude that myotrophin is present in normal human hearts, is found at higher levels in dilated cardiomyopathic human hearts, and may play a role in the initiation of cardiac hypertrophy as well as in normal growth of cardiac myocytes in humans.