Catecholamines and cardiac growth.

Catecholamines and cardiac growth.
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儿茶酚胺和心脏生长。

DOI:
10.1007/bf00408659
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发表时间:
1996
影响因子:
4.3
通讯作者:
Zak,R
Zak,R
中科院分区:
生物学3区
文献类型:
--
作者:
Gupta,MP;Gupta,M;Jakovcic,S;Zak,R

文献摘要

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本文就α和β肾上腺素能系统在心脏生长和基因表达调控中的作用作一综述。为了研究CAMP调节心脏基因表达的机制,我们使用了来自胎鼠心脏的培养心肌细胞。我们以前已经证明,在培养基中加入Br cAMP可使α-肌球蛋白重链(α-MHC)mRNA水平、转录速率以及V1异肌球蛋白量增加。为了表征参与α-MHC表达的cAMP应答调节的启动子元件,我们用一系列α-MHC基因启动子-CAT构建体进行瞬时转染分析。我们鉴定了一个13 × E-box/M-CAT杂合基序(EM元件),它赋予α-MHC基因的基底肌特异性和cAMP诱导性表达。利用迁移率变动分析,我们已经证明了EM元件结合蛋白之一是TEF-1。此外,通过将心脏核提取物与PK-A的催化亚基孵育,我们发现与EM元件结合的因子是cAMP依赖性磷酸化的底物。
The present knowledge concerning the α- and β-adrenergic systems in the regulation of cardiac growth and gene expression in reviewed. To investigate the mechanism by which CAMP regulates the expression of cardiac genes we have used cultured myocytes derived from fetal rat hearts. We have shown previously that the addition of Br cAMP to the culture medium produced an increase in α-myosin heavy chain (α-MHC) mRNA level, in its rate of transcription as well as in the amount of V1 isomyosin. To characterize the promoter element(s) involved in cAMP responsive regulation of a-MHC expression we performed transient transfection analysis with a series of α-MHC gene promoter-CAT constructs. We have identified a 13 by E-box/M-CAT hybrid motif (EM element) which conferred a basal muscle specific and cAMP inducible expression of the α-MHC gene. Using mobility shift assay we have documented that one of the EM element binding protein is TEF-1. Moreover, by incubating cardiac nuclear extracts with the catalytic subunit of PK-A we have found that factor(s) binding to the EM element is a substrate for CAMP dependent phosphorylation.