期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 288, 期 2, 页码 H455-H460出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00896.2004
关键词
thyroid hormone; myocardium; gene transcription; actinomycin D; RNA stability; heterogeneous nuclear RNA
资金
- NHLBI NIH HHS [HL-58849] Funding Source: Medline
Triiodothyronine (T-3) regulates cardiac contractility in part by regulating the expression of several important cardiac myocyte genes. In the rat, the T-3-mediated induction of alpha-myosin heavy chain (MHC) transcription in hypothyroid hearts is rapid, exhibiting zero-order kinetics, whereas the repression of beta-MHC in these same hearts is much slower. To elucidate the mechanism for T-3 transcriptional as well as posttranscriptional regulation of both MHC gene isoforms, we used an RT-PCR-based transcription assay and the RNA polymerase II inhibitor actinomycin D in an in vivo model to simultaneously measure specific alpha- and beta-MHC heterogeneous nuclear RNA ( hnRNA), mRNA kinetics, and MHC antisense RNA. In vivo actinomycin D treatment blocked alpha-MHC transcription in euthyroid rats by > 80% at 2 h and suggested a half-life of alpha-MHC hnRNA of similar to 1 h, whereas actinomycin D inhibited beta-MHC transcription in hypothyroid rats by > 75% at 6 h, suggesting a significantly longer hnRNA half-life of similar to 4 h. The effect of actinomycin D on beta-MHC transcription was independent of T-3. T-3 treatment in hypothyroid animals caused beta-MHC mRNA to decline more rapidly than beta-MHC hnRNA, demonstrating, for the first time, a posttranscriptional mechanism(s). The measured change in beta-MHC mRNA half-life indicates a T-3-mediated destabilization of beta-MHC mRNA. To understand the mechanism by which T-3 destabilizes beta-MHC mRNA, we measured beta-MHC antisense RNA. beta-MHC antisense RNA is present in euthyroid myocytes, but levels are not significant in hypothyroid myocytes. This differential expression may explain some of the effects of T-3 on MHC posttranscriptional regulation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据