PROTOONCOGENE INDUCTION AND REPROGRAMMING OF CARDIAC GENE-EXPRESSION PRODUCED BY PRESSURE OVERLOAD
PROTOONCOGENE INDUCTION AND REPROGRAMMING OF CARDIAC GENE-EXPRESSION PRODUCED BY PRESSURE OVERLOAD
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DOI：
10.1073/pnas.85.2.339
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发表时间：
1988-01-01
影响因子：
11.1
通讯作者：
MAHDAVI, V
中科院分区：
文献类型：
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作者：
IZUMO, S;NADALGINARD, B;MAHDAVI, V
肥大是细胞大小增加而无细胞分裂，是有丝分裂后心肌和骨骼肌细胞的基本适应过程。心肌肌球蛋白在各种肥大模型中经历成人至胎儿亚型转变。使用基因特异性cDNA探针，我们在此表明，在成人心肌中，编码α-SMA的胎儿（骨骼肌型）同种型的mRNA肌动蛋白和肌节原肌球蛋白在2天内响应压力超负荷而重新表达。此外，心钠素mRNA，迄今认为主要在心房表达，是很容易检测到的新生儿心室，并诱导显着高水平的压力超载的成人心室。相反，甲状腺激素过多引起的心脏肥大与心房利钠因子基因或胎儿收缩蛋白同源基因的诱导无关。此外，c-fos和c-myc原癌基因和一个主要的热休克蛋白基因（HSP 70）诱导在心室肌后1小时内施加压力超负荷。这些结果表明，诱导细胞原癌基因和热休克（应激）蛋白基因是压力超负荷的早期反应，而通常只在围产期表达的基因，如胎儿收缩蛋白和心房利钠因子亚型的再诱导，是一个较晚的事件。这两种类型的反应可能代表了生长诱导的一般模式，以工作负荷的终末分化细胞已经失去了进行DNA复制的能力。
Hypertrophy, an increase in cell size without cell division, is a fundamental adaptive process employed by postmitotic cardiac and skeletal muscle cells. Cardiac myosins undergo an adult-to-fetal isoform transition in various models of hypertrophy. Using gene-specific cDNA probes, we show here that in the adult myocardium the mRNAs encoding the fetal (skeletal muscle type) isoforms of .alpha.-actin and sarcomeric tropomyosin are re-expressed within 2 days in response to pressure overload. In addition, atrial natriuretic factor mRNA, so far believed to be expressed primarily in the atria, was readily detectable in the ventricles of neonates and was induced to markedly high levels in pressure-overloaded adult ventricles. In contrast, cardiac hypertrophy produced by thyroid hormone excess was not associated with induction of the atrial natriuretic factor gene or fetal contractile protein isogenes. Furthermore, the c-fos and c-myc protooncogenes and a major heat shock protein gene (hsp70) are induced in the ventricular myocardium within 1 hr after imposition of pressure overload. These result suggest that induction of cellular protooncogenes and heat shock (stress) protein genes is an early response to pressure overload, whereas reinduction of the genes normally expressed only in perinatal life, such as fetal isoforms of contractile proteins and atrial natriuretic factor, is a later event. These two types of responses might represent the general pattern of growth induction to work overload by terminally differentiated cells that have lost the ability to undergo DNA replication.