Development of Strategy of Molecular Cloning of Cardiac-Specific-Gene by use of Adriamycin

阿霉素心脏特异性基因分子克隆策略的开发

基本信息

批准号：
08557048
负责人：
KURABAYASHI Masahiko
金额：
$ 6.46万
依托单位：
Gunma University School of Medicine (1997)The University of Tokyo (1996)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

CARP,a cardiac adriamycin response protein, has been identified as a nuclear protein whose expression is down-regulated in response to adriamycin. In this study, we sought to examine the link between the pathophysiological stress and the regulation of CARP gene expression to specifically test the hypothesis that CARP functions as a nuclear factor mediating genetic response to diverse stress in the heart. CARP expression markedly increased in pressure-overloaded hypertrophy of rat heart. CARP expression increased during rat development, which is in a sharp contrast to the concept that cardiac hypertrophy is accompanied by the reactivation of the "fetal" gene program. Consistent with pressure-depenedent regulation, CARP mRNA was present in greater abundance in left ventricle than in right ventricle. In Dahl salt sensitive rats which exhibits the transition from cardiac hypertrophy to heart failure in a salt dependent manner, CARP mRNA increased during the period of compensatoty cardiac hypertrophy but such an increase in CARP mRNA level was attenuated after overt heart failure developed. Intraperitoneal administration of low dose of lipopolysaccharides(LPS) in rats induced CARP expression in the heart whereas higher dose of LPS repressed its expression despite either equally increased the level of iNOS mRNA.Chronic intravenous injection of adriamycin in rabbits increased CARP mRNA levels in mild heart failure while decreased it when heart failure became severe as assessed by the downregulation of Ca-ATPase mRNA.These results suggest taht CARP expression is differentially regulated depending upon the magnitude of hemodynamic overload and CARP may play a role in regulating gene expression during cardiac adaptation and failure.

鲤鱼是一种心脏阿霉素反应蛋白，已被鉴定为一种核蛋白，其表达因响应adriamycin而被下调。在这项研究中，我们试图研究病理生理应力与鲤鱼基因表达的调节之间的联系，以特别检验鲤鱼作为介导心脏中多种压力遗传反应的核因子的假设。鲤鱼表达在大鼠心脏的压力肥大中显着增加。鲤鱼表达在大鼠发育过程中增加了，这与心脏肥大伴随着“胎儿”基因程序的重新激活的概念形成鲜明对比。与压力调节一致，左心室中的鲤鱼mRNA比右心室更大。在达尔盐敏感大鼠中，以盐依赖性的方式表现出从心脏肥大到心力衰竭的过渡，在补偿性心脏肥大期间，鲤鱼mRNA增加了，但是在明显的心力衰竭发展后，鲤鱼mRNA水平的升高会增加。腹膜内施用大鼠中低剂量的低剂量脂多糖（LPS）在心脏中诱导鲤鱼表达，而较高的LP抑制了其表达，尽管这两种表达均同样增加了INOS mRNA的水平。chronic mRNA的水平。chronic静脉内注射adrononic admycin在兔子中的腹膜肌蛋白在兔中的car虫水平在轻度的心力衰竭中，而在心力衰竭中降低了心力衰竭的降低，而在心力衰竭中降低了car症，而在心力衰竭中降低了car and的car虫，而在心力衰竭中降低了cart的cart虫，而在心力衰竭中降低了cart虫的降低，则在心力衰竭中降低了cart ramn. mrna n Mrne的cart rna。根据血液动力学超负荷的幅度，对TAHT鲤鱼的表达受到差异调节，并且鲤鱼可能在调节心脏适应和衰竭期间调节基因表达方面发挥作用。