Shubeita H E, McDonough P M, Harris A N, Knowlton K U, Glembotski C C, Brown J H, Chien K R
Department of Medicine, University of California, San Diego, La Jolla 92093.
J Biol Chem. 1990 Nov 25;265(33):20555-62.
The present study examined the effects of endothelin-1 on phosphoinositide hydrolysis, diacylglycerol formation, and the induction of myocardial cell hypertrophy utilizing a well characterized cultured neonatal rat myocardial cell model. In this system, a hypertrophic response can be assessed by increases in myocardial cell size, an increase in the assembly of an individual contractile protein (myosin light chain-2) into organized contractile units, accumulation of contractile proteins, the activation of a program of immediate early gene expression, and the induction of genes encoding contractile and embryonic proteins (Iwaki, K., Sukhatme, V., Shubeita, H.E., Chien, K.R., (1990) J. Biol. Chem. 265, 13809-13817). Utilizing these criteria, the present study documents that stimulation with endothelin-1 can produce myocardial cell hypertrophy, induce the expression and release of ANF in ventricular cells, and can activate the transcription of cardiac-specific genes. In addition, endothelin-1 stimulates phosphoinositide hydrolysis and the accumulation of diacylglycerol. It is proposed that endothelin-1 stimulation may represent an important paracrine mechanism for the in vivo regulation of cardiac growth and hypertrophy.
本研究利用一个特征明确的培养新生大鼠心肌细胞模型，研究了内皮素-1对磷酸肌醇水解、二酰基甘油形成以及心肌细胞肥大诱导的影响。在这个系统中，肥大反应可以通过心肌细胞大小的增加、单个收缩蛋白（肌球蛋白轻链-2）组装成有组织的收缩单位的增加、收缩蛋白的积累、立即早期基因表达程序的激活以及编码收缩蛋白和胚胎蛋白的基因的诱导来评估（Iwaki, K., Sukhatme, V., Shubeita, H.E., Chien, K.R., (1990) J. Biol. Chem. 265, 13809 - 13817）。利用这些标准，本研究证明内皮素-1刺激可导致心肌细胞肥大，诱导心室细胞中ANF的表达和释放，并可激活心脏特异性基因的转录。此外，内皮素-1刺激磷酸肌醇水解和二酰基甘油的积累。有人提出，内皮素-1刺激可能是体内调节心脏生长和肥大的一种重要旁分泌机制。
