Faculty Opinions recommendation of β-myosin heavy chain is induced by pressure overload in a minor subpopulation of smaller mouse cardiac myocytes.

2011 ◽  
Author(s):  
Nadia Rosenthal ◽  
Enrique Lara-Pezzi
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Pressure Overload ◽  
A Minor

scholarly journals β-Myosin Heavy Chain Is Induced by Pressure Overload in a Minor Subpopulation of Smaller Mouse Cardiac Myocytes

2011 ◽  
Vol 109 (6) ◽  
pp. 629-638 ◽  
Author(s):  
Javier E. López ◽  
Bat-Erdene Myagmar ◽  
Philip M. Swigart ◽  
Megan D. Montgomery ◽  
Stephen Haynam ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Pressure Overload ◽  
A Minor

Abstract 200: Beta-Myosin Heavy Chain Induction after Pressure Overload Is in a Minor Sub-population of Myocytes and Requires the Alpha-1A-Adrenergic Receptor

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Javier E Lopez ◽  
Bat-Erdene Myagmar ◽  
Philip Swigart ◽  
Marty Bigos ◽  
Manoj Rodrigo ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Adrenergic Receptor ◽  
Pressure Overload ◽  
Transverse Aortic Constriction ◽  
Wild Type ◽  
Rt Pcr ◽  
Aortic Constriction ◽  
Double Knockout ◽  
A Minor

Background: Induction of the fetal hypertrophic gene beta-myosin heavy chain (MHC) is a signature feature of pressure overload, and is thought to occur in most hypertrophied myocytes. Beta-MHC mRNA is not induced after transverse aortic constriction (TAC) in a double knockout (KO) model of the alpha-1A and alpha-1B-adrenergic receptor (AR) subtypes, but it is unknown whether the A or B or both are required. Hypothesis: We tested the hypothesis that native beta-MHC protein induction is in a sub-population of myocytes and requires only a single alpha-1 subtype. Methods: TAC was done in wild type (WT) and alpha-1 KO male mice ages 12–14 weeks. Beta-MHC protein was measured in isolated adult myocytes by a novel flow cytometry approach, with antibodies validated for beta-MHC and total sarcomeric MHC. Results: In WT mice, the fraction of myocytes expressing beta-MHC was 3% in shams (SE =1, n =4 hearts), and increased to 26% of myocytes at 1–3 weeks after TAC (SE =4, n =8, p< 0.01 vs. sham). Myocytes expressing beta-MHC were predominantly large cells (see Figure ). In alpha-1A KO mice (AKO), beta-MHC was induced in only 6% of myocytes (SE =2, n =3, p<0.05 vs. WT TAC, p =NS vs. sham), or in only 15% as many myocytes as in WT hearts. Western blotting and quantitative RT-PCR confirmed reduced beta-MHC induction in alpha-1A KO myocytes. Conclusion: Beta-MHC induction after pressure overload is in only a minor sub-population of cardiac myocytes, contrary to common models of fetal hypertrophic gene induction. Furthermore, beta-MHC induction requires a single alpha-1-AR subtype, the alpha-1A, which cannot be compensated by other hypertrophic receptors.

scholarly journals Tissue-Restricted Expression of the Cardiac α-Myosin Heavy Chain Gene Is Controlled by a Downstream Repressor Element Containing a Palindrome of Two Ets-Binding Sites

1998 ◽  
Vol 18 (12) ◽  
pp. 7243-7258 ◽  
Author(s):  
Madhu Gupta ◽  
Radovan Zak ◽  
Towia A. Libermann ◽  
Mahesh P. Gupta
Keyword(s):  
Gene Regulation ◽  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Binding Sites ◽  
Cardiac Myocyte ◽  
Specific Expression ◽  
Tissue Specific Expression ◽  
Nonmuscle Cells ◽  
Muscle Gene

ABSTRACT The expression of the α-myosin heavy chain (MHC) gene is restricted primarily to cardiac myocytes. To date, several positive regulatory elements and their binding factors involved in α-MHC gene regulation have been identified; however, the mechanism restricting the expression of this gene to cardiac myocytes has yet to be elucidated. In this study, we have identified by using sequential deletion mutants of the rat cardiac α-MHC gene a 30-bp purine-rich negative regulatory (PNR) element located in the first intronic region that appeared to be essential for the tissue-specific expression of the α-MHC gene. Removal of this element alone elevated (20- to 30-fold) the expression of the α-MHC gene in cardiac myocyte cultures and in heart muscle directly injected with plasmid DNA. Surprisingly, this deletion also allowed a significant expression of the α-MHC gene in HeLa and other nonmuscle cells, where it is normally inactive. The PNR element required upstream sequences of the α-MHC gene for negative gene regulation. By DNase I footprint analysis of the PNR element, a palindrome of two high-affinity Ets-binding sites (CTTCCCTGGAAG) was identified. Furthermore, by analyses of site-specific base-pair mutation, mobility gel shift competition, and UV cross-linking, two different Ets-like proteins from cardiac and HeLa cell nuclear extracts were found to bind to the PNR motif. Moreover, the activity of the PNR-binding factor was found to be increased two- to threefold in adult rat hearts subjected to pressure overload hypertrophy, where the α-MHC gene is usually suppressed. These data demonstrate that the PNR element plays a dual role, both downregulating the expression of the α-MHC gene in cardiac myocytes and silencing the muscle gene activity in nonmuscle cells. Similar palindromic Ets-binding motifs are found conserved in the α-MHC genes from different species and in other cardiac myocyte-restricted genes. These results are the first to reveal a role of the Ets class of proteins in controlling the tissue-specific expression of a cardiac muscle gene.

scholarly journals GATA-5 Is Involved in Leukemia Inhibitory Factor-responsive Transcription of the β-Myosin Heavy Chain Gene in Cardiac Myocytes

1999 ◽  
Vol 274 (18) ◽  
pp. 12811-12818 ◽  
Author(s):  
Tatsuya Morimoto ◽  
Koji Hasegawa ◽  
Satoshi Kaburagi ◽  
Tsuyoshi Kakita ◽  
Hiroshi Masutani ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene

Differential regulation by thyroid hormones of myosin heavy chain α and β mRNAs in the rat ventricular myocardium

1989 ◽  
Vol 122 (1) ◽  
pp. 193-200 ◽  
Author(s):  
N. K. Green ◽  
J. A. Franklyn ◽  
J. A. O. Ahlquist ◽  
M. D. Gammage ◽  
M. C. Sheppard
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Ventricular Myocardium ◽  
Mhc Genes ◽  
Specific Effects ◽  
Dependent Inhibition ◽  
Dose Dependent

ABSTRACT The effect of tri-iodothyronine (T3) treatment on myocardial levels of α and β myosin heavy chain (MHC) mRNAs in the rat was defined in vivo and in vitro. Dose–response experiments were performed in intact hypothyroid and euthyroid rats; in addition, studies in vitro examined the effect of T3 on MHC mRNAs in neonatal cardiac myocytes in primary culture. Specific α and β MHC mRNAs were determined by Northern blot and dot hybridization to oligonucleotide probes complementary to the 3′ untranslated regions of the MHC genes. An increase in myocardial β MHC mRNA was demonstrated in hypothyroidism, accompanied by a reduction in α MHC mRNA. Marked differences in the sensitivity of α and β MHC mRNAs to T3 replacement were found; a dose-dependent increase in α mRNA was evident at 6 h after T3 treatment, in the absence of consistent effects on β mRNA, whereas 72 h after T3 replacement was commenced, stimulatory effects of T3 on α MHC mRNA, evident at all doses, were accompanied by a dose-dependent inhibition of β MHC mRNA. No effect of thyroid status on actin mRNA was found, indicating the specificity of MHC gene regulation. T3 treatment of cardiac myocytes in vitro exerted similar actions on MHC mRNAs to those found in vivo, with a more marked influence on α than β MHC mRNA. These studies of the action of T3 in vivo and in vitro have thus demonstrated specific effects of T3 on pretranslational regulation of the α and β MHC genes, influences which differ not only in terms of stimulation or inhibition, but also in magnitude of effect. Journal of Endocrinology (1989) 122, 193–200

Gonadectomy Alters Myosin Heavy Chain Composition in Isolated Cardiac Myocytes

Endocrine ◽  
2004 ◽  
Vol 24 (2) ◽  
pp. 137-140 ◽  
Author(s):  
Kish L. Golden ◽  
James D. Marsh ◽  
Yang Jiang ◽  
Jerome Moulden
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Chain Composition ◽  
Isolated Cardiac Myocytes ◽  
Myosin Heavy Chain Composition

Control of beta-myosin heavy chain expression in systemic hypertension and caloric restriction in the rat heart

1995 ◽  
Vol 269 (4) ◽  
pp. C1025-C1033 ◽  
Author(s):  
S. J. Swoap ◽  
F. Haddad ◽  
P. Bodell ◽  
K. M. Baldwin
Keyword(s):  
Myosin Heavy Chain ◽  
Caloric Restriction ◽  
Heavy Chain ◽  
Pressure Overload ◽  
Nuclear Extract ◽  
Systemic Hypertension ◽  
Sprague Dawley ◽  
Mobility Shift ◽  
Concomitant Decrease

In the rat left ventricle, both pressure overload induced by abdominal aortic constriction (Abcon) and caloric restriction (CR) induce an increase in the steady-state level of the beta-myosin heavy chain (MHC) protein and mRNA. Both models also induce a concomitant decrease in the alpha-MHC protein and mRNA. The goals of this study were to 1) determine if the changes in MHC expression in the models are due to altered transcription and 2) identify the relative levels of some key factors interacting with the regulatory regions of these genes. Female Sprague-Dawley rats were randomly assigned to the following groups: 1) normal control (NC), 2) Abcon, and 3) CR. After 5 wk of experimental manipulations, myocardial nuclei were isolated. These nuclei were used for 1) nuclear run-on assays or 2) nuclear extract, which was prepared and used for gel mobility shift assays (GMSAs). Nuclear run-on assays demonstrated that the increase in beta-MHC mRNA and protein expression in both Abcon and CR can be at least partially attributed to increased transcription. The concomitant decrease in alpha-MHC content can similarly be attributed to a decrease in transcription of this gene. Furthermore, GMSAs demonstrate that nuclear extract from each group interact differently with certain elements known to be important for expression in vitro. CR nuclear extracts have a 25.6 +/- 7.2% decrease (P < 0.05 vs. NC) in interaction with a thyroid-responsive element, a potential repressor of beta-MHC transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

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