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The cardiac beta-myosin heavy chain isogene is induced selectively in alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes.

L E Waspe, … , C P Ordahl, P C Simpson

Published April 1, 1990
Citation Information: J Clin Invest. 1990;85(4):1206-1214. https://doi.org/10.1172/JCI114554.

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Research Article

The cardiac beta-myosin heavy chain isogene is induced selectively in alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes.

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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.

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L E Waspe, C P Ordahl, P C Simpson

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Citations to this article (163)

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An E-box/M-CAT hybrid motif and cognate binding protein(s) regulate the basal muscle-specific and cAMP-inducible expression of the rat cardiac alpha-myosin heavy chain gene MP Gupta, M Gupta, R Zak	The Journal of biological chemistry	1994
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Myocardial alpha-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression CC Glembotski, CE Irons, KA Krown, SF Murray, AB Sprenkle, CA Sei	The Journal of biological chemistry	1993
Transcriptional enhancer factor-1 in cardiac myocytes interacts with an alpha 1-adrenergic- and beta-protein kinase C-inducible element in the rat beta-myosin heavy chain promoter K Kariya, IK Farrance, PC Simpson	The Journal of biological chemistry	1993
Hemodynamic regulation of myosin heavy chain gene expression. Studies in the transplanted rat heart I Klein, K Ojamaa, AM Samarel, R Welikson, C Hong	Journal of Clinical Investigation	1992
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Mapping of mRNA isoforms with an oligonucleotide probe: exonuclease VII compared with endonucleases C Chassagne, K Schwartz	Nucleic Acids Research	1992
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Positive regulation of the skeletal alpha-actin gene by Fos and Jun in cardiac myocytes NH Bishopric, V Jayasena, KA Webster	The Journal of biological chemistry	1992
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Contribution of both ?- and ?-adrenoceptors to the inotropic effects of catecholamines in the rabbit heart U Jahnel, B Kaufmann, M Rombusch, H Nawrath	Naunyn-Schmiedeberg's Archives of Pharmacology	1992
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Activation of alpha-myosin heavy chain gene expression by cAMP in cultured fetal rat heart myocytes MP Gupta, M Gupta, A Stewart, R Zak	Biochemical and Biophysical Research Communications	1991
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Molecular Mechanisms of Cellular Growth HE Morgan		1991
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Expression of a constitutively activated mutant of the beta-isozyme of protein kinase C in cardiac myocytes stimulates the promoter of the beta-myosin heavy chain isogene K Kariya, LR Karns, PC Simpson	The Journal of biological chemistry	1991
Characterization of a promoter element required for transcription in myocardial cells RC Iannello, JH Mar, CP Ordahl	The Journal of biological chemistry	1991
Adrenergic hormones and control of cardiac myocyte growth P Simpson, C Simpson, K Kariya, LR Karns, CS Long, JS Karliner	Molecular and Cellular Biochemistry	1991
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The cardiac beta-myosin heavy chain isogene is induced selectively in alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes.

The cardiac beta-myosin heavy chain isogene is induced selectively in alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes.

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