TROPONIN-T ISOFORM EXPRESSION IN HUMANS - A COMPARISON AMONG NORMAL AND FAILING ADULT HEART, FETAL HEART, AND ADULT AND FETAL SKELETAL-MUSCLE
TROPONIN-T ISOFORM EXPRESSION IN HUMANS - A COMPARISON AMONG NORMAL AND FAILING ADULT HEART, FETAL HEART, AND ADULT AND FETAL SKELETAL-MUSCLE
复制标题
DOI：
10.1161/01.res.69.5.1226
复制
发表时间：
1991-11-01
影响因子：
20.1
通讯作者：
ALLEN, PD
中科院分区：
文献类型：
--
作者：
ANDERSON, PAW;MALOUF, NN;ALLEN, PD
我们检测了正常和衰竭成人左心室心肌中肌钙蛋白（Tn） T的表达。由于正常心肌和衰竭心肌同种异构体表达的差异，我们研究了人横纹肌中TnT的致瘤性表达。左心室样本取自接受心脏移植的严重心力衰竭患者和正常成人器官供体。胎儿肌肉取自妊娠14-15周后流产的胎儿，成人骨骼肌取自手术活检。正常和衰竭成人心脏蛋白的Western blot结果显示，两种异构体TnT1和TnT2的表达量不同，其中TnT2在衰竭心脏中表达量显著增加（p < 0.004）。这些蛋白的二维凝胶的Western blots可以分辨出TnT1和TnT2的两个主要斑点和几个次要的TnT物种。碱性磷酸酶处理将每个同工异构体的两个主要点转化为单个更基本的点。在个体衰竭和正常成人心脏中，atp酶活性与TnT2占总TnT的比例呈负相关（r = 0.7, p < 0.02）。在胎儿心脏中，发现了四种TnT亚型，其中两种与成人心脏亚型TnT1和TnT2具有相同的电泳迁移率。胎儿骨骼肌表达四种胎儿心脏TnT亚型中的两种，其中一种与成人心脏TnT1同源。与7种快速骨骼肌TnT亚型相比，这些心脏亚型在胎儿骨骼肌中表达的丰度较低。成人骨骼肌中不存在心脏同种异构体。由于许多病因导致移植患者心力衰竭，我们提出疾病相关的TnT异构体TnT2表达增加是对心力衰竭状态的适应，也是胎儿心脏TnT异构体表达的部分再现。
The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between normal and failing myocardium led us to examine the ontogenic expression of TnT in human striated muscle. Left ventricular samples were obtained from patients with severe heart failure undergoing cardiac transplantation and normal adult organ donors. Fetal muscle was obtained from aborted fetuses after 14-15 weeks of gestation, and adult skeletal muscle was obtained from surgical biopsies. Western blots of normal and failing adult heart proteins demonstrated that two isoforms, TnT1 and TnT2, are expressed in different amounts, with TnT2 being significantly greater in failing hearts (p < 0.004). Western blots of two-dimensional gels of these proteins resolved two predominant spots of both TnT1 and TnT2 and several minor TnT species. Alkaline phosphatase treatment converted the two major spots of each isoform into the single more basic spots. A comparison of the ATPase activities and the TnT2 percentage of total TnT in individual failing and normal adult hearts demonstrated an inverse and negative relation (r = 0.7, p < 0.02). In the fetal heart, four TnT isoforms were found, two of which had the same electrophoretic mobilities as the adult cardiac isoforms TnT1 and TnT2. Fetal skeletal muscle expressed two of the four fetal cardiac TnT isoforms, one of which comigrated with adult cardiac TnT1. These cardiac isoforms were expressed in low abundance in fetal skeletal muscle relative to seven fast skeletal muscle TnT isoforms. No cardiac isoforms were present in adult skeletal muscle. Because many etiologies caused heart failure in the transplant patients, we propose that the disease-associated increased expression of the TnT isoform TnT2 is an adaptation to the heart failure state and a partial recapitulation of the fetal expression of cardiac TnT isoforms.