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心肌肥大中的信号转导

Signal transduction in myocardial hypertrophy.

作者信息

Morgan H E

机构信息

Weis Center for Research, Geisinger Clinic, Danville, PA 17822-2601.

出版信息

Keio J Med. 1990 Mar;39(1):1-5. doi: 10.2302/kjm.39.1.

DOI:10.2302/kjm.39.1
PMID:2162446
Abstract

Transduction of stretch of the ventricular wall into accelerated growth and ultimately hypertrophy of cardiac muscle cells is a cyclic AMP (cAMP) dependent phenomenon. When stretch was induced in isolated perfused rat hearts by an increase in aortic pressure from 60 to 120 mmHg, protein synthesis was accelerated during the second hour of perfusion. Only a brief exposure to higher aortic pressure (2 min) was required to elicit this effect. Elevation of aortic pressure also increased cAMP content. Other interventions that increased cAMP content such as glucagon increased second hour rates of protein synthesis. Stretch of the ventricular wall had a more rapid effect on ribosome formation. During the first hour of perfusion, increased aortic pressure raised rates of 60S ribosomal subunit formation by 38% in the absence of added insulin and 35% in the presence of the hormone. Ribosome formation was also accelerated by addition of glucagon. The muscarinic cholinergic agonist, methacholine blocked the effects of elevated aortic pressure on protein synthesis, ribosome formation, and cAMP content. These studies indicate that stretch of the ventricular wall is transduced into greater cAMP content and that this intracellular messenger is one of the substances responsible for accelerated ribosome formation and protein synthesis.

摘要

心室壁的拉伸转化为心肌细胞的加速生长并最终肥大是一种依赖环磷酸腺苷(cAMP)的现象。当通过将主动脉压力从60 mmHg升高到120 mmHg在离体灌注大鼠心脏中诱导拉伸时,在灌注的第二个小时蛋白质合成加速。仅需短暂暴露于较高的主动脉压力(2分钟)即可引发此效应。主动脉压力升高也会增加cAMP含量。其他增加cAMP含量的干预措施,如胰高血糖素,会增加第二个小时的蛋白质合成速率。心室壁的拉伸对核糖体形成有更快的影响。在灌注的第一个小时内,在未添加胰岛素的情况下,主动脉压力升高使60S核糖体亚基的形成速率提高了38%,在存在该激素的情况下提高了35%。添加胰高血糖素也会加速核糖体的形成。毒蕈碱型胆碱能激动剂乙酰甲胆碱可阻断主动脉压力升高对蛋白质合成、核糖体形成和cAMP含量的影响。这些研究表明,心室壁的拉伸转化为更高的cAMP含量,并且这种细胞内信使是负责加速核糖体形成和蛋白质合成的物质之一。

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