Bishopric N H, Simpson P C, Ordahl C P
Department of Anatomy, University of California, San Francisco 94143.
J Clin Invest. 1987 Oct;80(4):1194-9. doi: 10.1172/JCI113179.
Myocardial hypertrophy in vivo is associated with reexpression of contractile protein isogenes characteristic of fetal and neonatal development. The molecular signals for hypertrophy and isogene switching are unknown. We studied alpha (sarcomeric)-actin messenger RNA (mRNA) expression in cultured cardiac myocytes from the neonatal rat. In the cultured cells, as in the adult heart in vivo, expression of cardiac alpha-actin (cACT) predominated over that of skeletal alpha-actin (sACT) mRNA, the fetal/neonatal isoform. alpha 1-Adrenergic receptor stimulation induced hypertrophy of these cells, increasing total RNA and cytoskeletal actin mRNA by 1.8-fold over control, and total alpha-actin mRNA by 4.3 fold. This disproportionate increase in total alpha-actin mRNA was produced by a preferential induction of sACT mRNA, which increased by 10.6-fold over control versus only 2.6-fold for cACT mRNA. The alpha 1-adrenoceptor is the first identified molecular mediator of early developmental isogene reexpression in cardiac myocyte hypertrophy.
体内心肌肥大与胎儿和新生儿发育特有的收缩蛋白同基因的重新表达有关。肥大和同基因转换的分子信号尚不清楚。我们研究了新生大鼠培养心肌细胞中α（肌节）-肌动蛋白信使核糖核酸（mRNA）的表达。在培养细胞中，如同在成年动物心脏中一样，心脏α-肌动蛋白（cACT）的表达高于骨骼肌α-肌动蛋白（sACT）mRNA，即胎儿/新生儿异构体。α1-肾上腺素能受体刺激可诱导这些细胞肥大，使总RNA和细胞骨架肌动蛋白mRNA比对照增加1.8倍，总α-肌动蛋白mRNA增加4.3倍。总α-肌动蛋白mRNA的这种不成比例的增加是由sACT mRNA的优先诱导产生的，sACT mRNA比对照增加了10.6倍，而cACT mRNA仅增加了2.6倍。α1-肾上腺素能受体是首次确定的心肌细胞肥大早期发育同基因重新表达的分子介质。
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