LEVELS OF TROPONIN I AND MYOSIN HEAVY CHAIN IN DEDIFFERENTIATED ADULT RABBIT CARDIAC MYOCYTES

1994 ◽  
pp. 619-621
Author(s):  
I. McPhee ◽  
K.A. Kane ◽  
C. MacDonald
Keyword(s):  
Myosin Heavy Chain ◽  
Cardiac Myocytes ◽  
Heavy Chain ◽  
Troponin I ◽  
Adult Rabbit

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

Morphometry and muscle gene expression in hypertrophied hearts from polyomavirus large T antigen transgenic mice

1995 ◽  
Vol 269 (1) ◽  
pp. H86-H95 ◽  
Author(s):  
E. Holder ◽  
B. Mitmaker ◽  
L. Alpert ◽  
L. Chalifour
Keyword(s):  
Transgenic Mice ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Troponin I ◽  
T Antigen ◽  
Large T Antigen ◽  
Cross Sectional

Transgenic mice expressing polyomavirus large T antigen (PVLT) in cardiomyocytes develop a cardiac hypertrophy in adulthood. Morphometric analysis identified cardiomyocytes enlarged up to ninefold in cross-sectional area in the adult transgenic hearts compared with normal age-matched nontransgenic hearts. Most enlarged cardiomyocytes were found in the subendocardium, whereas normal-sized cardiomyocytes were localized to the midmyocardium. Transgenic hearts did not express detectable skeletal muscle actin mRNA or protein, or skeletal troponin I isoform mRNA. Some, but not all, transgenic hearts expressed an increase in the beta-myosin heavy chain mRNA. All five transgenic mice tested had increased expression of atrial natriuretic factor (ANF) mRNA. Whereas normal hearts expressed three myosin light chain proteins of 19, 16, and 15 kDa, we found that the 19-kDa myosin light chain was not observed in the transgenic hearts. We conclude that adult, PVLT-expressing, transgenic mice developed enlarged cardiomyocytes with an increase in beta-myosin heavy chain and ANF mRNA expression, but a widespread skeletal isoform usage was not present in these transgenic mice. The adult transgenic hearts thus display histological and molecular changes similar to those found in hypertrophy induced by a pressure overload in vivo.

scholarly journals Specific Myosin Heavy Chain Mutations Suppress Troponin I Defects in Drosophila Muscles

1999 ◽  
Vol 144 (5) ◽  
pp. 989-1000 ◽  
Author(s):  
William A. Kronert ◽  
Angel Acebes ◽  
Alberto Ferrús ◽  
Sanford I. Bernstein
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Thin Filament ◽  
Troponin I ◽  
Point Mutations ◽  
Thick Filament ◽  
Actin Binding ◽  
Filament Protein ◽  
Phenotypic Rescue

We show that specific mutations in the head of the thick filament molecule myosin heavy chain prevent a degenerative muscle syndrome resulting from the hdp2 mutation in the thin filament protein troponin I. One mutation deletes eight residues from the actin binding loop of myosin, while a second affects a residue at the base of this loop. Two other mutations affect amino acids near the site of nucleotide entry and exit in the motor domain. We document the degree of phenotypic rescue each suppressor permits and show that other point mutations in myosin, as well as null mutations, fail to suppress the hdp2 phenotype. We discuss mechanisms by which the hdp2 phenotypes are suppressed and conclude that the specific residues we identified in myosin are important in regulating thick and thin filament interactions. This in vivo approach to dissecting the contractile cycle defines novel molecular processes that may be difficult to uncover by biochemical and structural analysis. Our study illustrates how expression of genetic defects are dependent upon genetic background, and therefore could have implications for understanding gene interactions in human disease.

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

Abstract 19086: Myofilament Proteins of the Naked Mole-rat Heart Reflect Low Basal Species Cardiac Function

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Kelly M Grimes ◽  
David Barefield ◽  
Mohit Kumar ◽  
Pieter P de Tombe ◽  
Sakthivel Sadayappan ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Troponin I ◽  
Myocardial Contraction ◽  
Myosin Heavy Chain Isoform ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
And Function

The naked mole-rat (NMR) is a mouse-sized rodent with a maximum longevity of >31 years. The species exhibits low basal heart rate (256 bpm) and cardiac output (7 ml/min) for its body size, as well as low fractional shortening (28%) for a rodent. However unlike other well-studied mammals, the NMR maintains cardiac reserve and diastolic function for at least 75% of its maximum lifespan - at ages equivalent to 90 year old humans. We questioned if this low basal cardiac function was due to NMR myofilament composition and function. NMR ventricles are comprised primarily of the β-myosin heavy chain isoform, which is associated with slowed myocardial contraction and increased efficiency. This is in stark contrast to mouse ventricles, which express predominately the α-isoform, and switch to the β-isoform upon experimental induction of heart failure. Compared to mice, NMR myofilament proteins such as cardiac troponin I and cardiac myosin binding protein-C display lower levels of phosphorylation. Such levels are indicative of decreased activation of myofilament proteins and may relate to the species’ low basal cardiac function. Both the NMR’s predominance of β-myosin heavy chain and the low basal level of myofilament phosphorylation present a phenotype much closer to that seen in human ventricles than in those of mice. Intriguingly, maximal force developed by skinned NMR cardiomyocytes is not significantly different to that of mouse cardiomyocytes (NMR: 70.9 ± 9.3mN/mm2 vs. mouse: 87.7 ± 0.6 mN/mm2). This is likely a reflection of the NMR’s ability to enhance cardiac function to the level of a mouse when stimulated, as is evident when both species are treated in vivo with dobutamine (3 μg/g i.p.). Such low basal cardiac function may put less overall strain on the heart over time and could be critical to the NMR’s ability to maintain cardiac function with age.

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