Citations to this article
Abstract
Cardiac hypertrophy produced in vivo by pressure overload is characterized by selective up-regulation of the fetal/neonatal beta-cardiac myosin heavy chain (MHC) isogene. However, a molecular signal for beta-MHC isogene induction has not been identified. We examined cardiac MHC isogene expression in a cell culture model for hypertrophy. alpha-MHC and beta-MHC iso-protein and iso-mRNA levels in cultured cardiac myocytes were quantified during hypertrophy stimulated by the alpha 1-adrenergic agonist, norepinephrine (NE). beta-MHC iso-protein content was increased 3.2-fold vs. control (P less than 0.001), whereas alpha-MHC isoprotein content was not changed significantly (1.4-fold vs. control, P = NS). MHC iso-mRNA levels were quantified by nuclease S1 analysis, using a single oligonucleotide probe. NE increased beta-MHC iso-mRNA content by 3.9-fold vs. control (P less than 0.001), but there was no change in alpha-MHC iso-mRNA (1.1-fold vs. control, P = NS). The NE-stimulated increase in beta-MHC iso-mRNA preceded in time the increase in beta-MHC isoprotein accumulation. The EC50 for NE induction of beta-MHC was 40 nM, and pharmacologic experiments indicated alpha 1-adrenergic receptor specificity. alpha-MHC isogene expression was predominant in control myocytes (68% alpha-isoprotein and 60% alpha-iso-mRNA). In contrast, beta-MHC expression was equal to alpha-MHC or predominant after treatment with NE (51% beta-isoprotein and 69% beta-iso-mRNA). Thus, alpha 1-adrenergic receptor stimulation increases the cellular contents of beta-MHC iso-mRNA and beta-MHC isoprotein during hypertrophy of cultured neonatal rat cardiac myocytes, but does not change the levels of alpha-MHC iso-mRNA or isoprotein. The effect on beta-MHC is mediated primarily at the level of mRNA steady-state level (pretranslational). Activation of the alpha 1-adrenergic receptor is the first identified molecular signal for increased beta-MHC isogene expression in a model of cardiac hypertrophy.
Authors
L E Waspe, C P Ordahl, P C Simpson
Total citations by year
Citations to this article in year 2003 (6)
| Title and authors | Publication | Year |
|---|---|---|
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In vivo regulation of the chicken cardiac troponin T gene promoter in zebrafish embryos
WE Tidyman, AJ Sehnert, A Huq, J Agard, F Deegan, DY Stainier, CP Ordahl |
Developmental Dynamics | 2003 |
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Progressive Development of Pulmonary Hypertension Leading to Right Ventricular Hypertrophy Assessed by Echocardiography in Rats
Y KATO, M IWASE, H KANAZAWA, N KAWATA, Y YOSHIMORI, K HASHIMOTO, T YOKOI, A NODA, K TAKAGI, Y KOIKE, T NISHIZAWA, M NISHIMURA, M YOKOTA |
Experimental Animals | 2003 |
|
The myocardial protein S100A1 plays a role in the maintenance of normal gene expression in the adult heart
JN Tsoporis, A Marks, DB Zimmer, C McMahon, TG Parker |
Molecular and Cellular Biochemistry | 2003 |
|
Yin Yang 1 Is Increased in Human Heart Failure and Represses the Activity of the Human α-Myosin Heavy Chain Promoter
CC Sucharov, P Mariner, C Long, M Bristow, L Leinwand |
The Journal of biological chemistry | 2003 |
|
Regulation of the S100B gene by α 1 -adrenergic stimulation in cardiac myocytes
JN Tsoporis, A Marks, LJ van Eldik, D O'Hanlon, TG Parker |
American journal of physiology. Heart and circulatory physiology | 2003 |
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