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Query: UNIPROT:P06889 (Mol)
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In the bovine nodal conduction tissue we have described the existence of a novel cardiac myosin isoform, immunologically related to the myosin types expressed during skeletal muscle development. Using different monoclonal antibodies specific for the embryonic and the neonatal skeletal myosin heavy chain types we investigated the myosin composition of the rat sino-atrial and atrio-ventricular nodes. We find that nodal conduction tissue fibers of the rat heart contain a distinct cardiac myosin isoform antigenically similar to the skeletal embryonic myosin heavy chain. The expression of this myosin isoform in nodal tissue appears to be developmentally regulated and partially controlled by thyroid hormone. Reactive cardiac fibers were detected in the nodal regions only during fetal development and a few days after birth, whereas very rare labelled fibers could be observed in the adult nodes. This myosin type does not represent a primordial cardiac myosin isoform since it was not detected in the embryonic heart before 13.5 days of gestation. When congenital hypothyroidism was induced in rats, the post-natal disappearance of reactive fibers in the nodal regions was delayed. On the other hand, hypothyroidism induced in the adult rats did not change the number of the reactive nodal fibers with respect to the euthyroid hearts.
J Mol Cell Cardiol 1988 Oct
PMID:An embryonic-like myosin heavy chain is transiently expressed in nodal conduction tissue of the rat heart. 321 2

Myosin heavy chain degradation fragments produced in vivo have been identified in chicken pectoralis muscle. The fragments were identified by electrophoresis of unfractionated extracts of chicken pectoralis muscle on sodium dodecyl sulfate/polyacrylamide gels followed by immunoblotting on nitrocellulose sheets. Monoclonal antibodies directed against the S2 and light meromyosin subfragments as well as type II myosin-specific polyclonal antibodies directed against the entire myosin heavy chain were used to characterize the fragments, which range in molecular weight from approximately 80,000 to 180,000. All fragments contain the extreme carboxy-terminal portion of the molecule and are distinct from the classical proteolytic fragments such as heavy and light meromyosin, S1, S2 or rod. These fragments appear to be produced in vivo by proteolytic cleavage of peptides from the amino-terminal (S1) end of the heavy chain while the myosin molecule is still embedded in the thick filament. Fragment concentrations are estimated to be approximately 5 to 10% of that of the intact myosin heavy chain. These fragments are not the result of artifactual damage to myosin, e.g. proteolysis or hydrodynamic shear. The techniques described in this paper provide a probe into the early stages of myosin and thick filament degradation in vivo.
J Mol Biol 1987 Jan 05
PMID:Myosin degradation fragments in skeletal muscle. 329 57

We examined the effects of human recombinant tumor necrosis factor-alpha (TNF) on human primary myoblasts. When added to proliferating myoblasts, TNF inhibited the expression of alpha-cardiac actin, a muscle-specific gene whose expression is observed at low levels in human myoblasts. TNF also inhibited muscle differentiation as measured by several parameters, including cell fusion and the expression of other muscle-specific genes, such as alpha-skeletal actin and myosin heavy chain. Muscle cells were sensitive to TNF in a narrow temporal window of differentiation. Northern (RNA) blot and immunofluorescence analyses revealed that human muscle gene expression became unresponsive to TNF coincident with myoblast differentiation. When TNF was added to differentiated myotubes, there was no effect on muscle gene expression. In contrast, TNF-inducible mRNAs such as interferon beta-2 still responded, suggesting that the signal mediated by TNF binding to its receptor had no effect on muscle-specific genes after differentiation.
Mol Cell Biol 1988 Jun
PMID:Tumor necrosis factor inhibits human myogenesis in vitro. 340 7

We evaluated the extent to which muscle-specific genes display identical patterns of mRNA accumulation during human myogenesis. Cloned satellite cells isolated from adult human skeletal muscle were expanded in culture, and RNA was isolated from low- and high-confluence cells and from fusing cultures over a 15-day time course. The accumulation of over 20 different transcripts was compared in these samples with that in fetal and adult human skeletal muscle. The expression of carbonic anhydrase 3, myoglobin, HSP83, and mRNAs encoding eight unknown proteins were examined in human myogenic cultures. In general, the expression of most of the mRNAs was induced after fusion to form myotubes. However, several exceptions, including carbonic anhydrase and myoglobin, showed no detectable expression in early myotubes. Comparison of all transcripts demonstrated little, if any, identity of mRNA accumulation patterns. Similar variability was also seen for mRNAs which were also expressed in nonmuscle cells. Accumulation of mRNAs encoding alpha-skeletal, alpha-cardiac, beta- and gamma-actin, total myosin heavy chain, and alpha- and beta-tubulin also displayed discordant regulation, which has important implications for sarcomere assembly. Cardiac actin was the only muscle-specific transcript that was detected in low-confluency cells and was the major alpha-actin mRNA at all times in fusing cultures. Skeletal actin was transiently induced in fusing cultures and then reduced by an order of magnitude. Total myosin heavy-chain mRNA accumulation lagged behind that of alpha-actin. Whereas beta- and gamma-actin displayed a sharp decrease after initiation of fusion and thereafter did not change, alpha- and beta-tubulin were transiently induced to a high level during the time course in culture. We conclude that each gene may have its own unique determinants of transcript accumulation and that the phenotype of a muscle may not be determined so much by which genes are active or silent but rather by the extent to which their transcript levels are modulated. Finally, we observed that patterns of transcript accumulation established within the myotube cultures were consistent with the hypothesis that myoblasts isolated from adult tissue recapitulate a myogenic developmental program. However, we also detected a transient appearance of adult skeletal muscle-specific transcripts in high-confluence myoblast cultures. This indicates that the initial differentiation of these myoblasts may reflect a more complex process than simple recapitulation of development.
Mol Cell Biol 1987 Nov
PMID:Differential patterns of transcript accumulation during human myogenesis. 343 50

We have used alpha-chymotrypsin as an enzyme-probe to detect local melting in the subfragment-2 region of the cross-bridges of rigor myofibrils and glycerinated psoas fibers. The kinetics of proteolysis and the sites of cleavage were determined at various temperatures over the range 5 to 40 degrees C by following the decay of the myosin heavy chain and the rates of appearance of light meromyosin fragments, using electrophoresis on sodium dodecyl sulfate-containing polyacrylamide gels. Cleavage occurs primarily at the 72,000 Mr and 64,000 Mr (per polypeptide chain from the C terminus of myosin) sites within the light meromyosin-heavy meromyosin hinge domain of the subfragment-2 region, under all experimental conditions. At pH 8.2 to 8.3 and at low divalent metal ion (0.1 mM), where the actin-bound cross-bridges are thought to be released from the thick filament surface, the intrinsic cleavage rate constant (k) increases markedly as the temperature is raised. This suggests substantial thermal destabilization of the released cross-bridge in the intact contractile apparatus. Addition of divalent metal ion (10 mM) lowers the cleavage rate and shifts the k versus temperature profile to higher temperatures. Normalized rate constants for chymotryptic cleavage within the subfragment-2 hinge region of released cross-bridges (pH 8.2, low divalent metal) of rigor fibers were markedly lower than activated fibers at all temperatures investigated (5 to 40 degrees C). Results show that conformational melting within the subfragment-2 hinge region is amplified on activation and is well above that observed when the actin-attached rigor bridge is passively released from the thick filament surface.
J Mol Biol 1986 Jul 05
PMID:Temperature-dependence of local melting in the myosin subfragment-2 region of the rigor cross-bridge. 353 14

We describe a method for the complete solubilization and quantitative analysis of individual myofibrillar proteins in whole tissue homogenates of ventricular myocardium using gradient dodecyl sulfate polyacrylamide gel electrophoresis and staining with 125I-labeled Coomassie brilliant blue. The procedure allows for the simultaneous quantification of myosin heavy chain, myosin light chain, phosphorylatable myosin light chain and actin from as little as 50 mg of tissue. Within-assay and between-assay variations range from 8.0% to 12.6% for each protein subunit. The method was applied to the determination of the subunit stoichiometry of purified myosin, and to the measurement of myosin and actin concentrations in the neonatal and adult rabbit heart. Furthermore, we provide quantitative biochemical evidence for the existence of large molar excesses of myosin light chains in tissue homogenates of both neonatal and adult rabbit ventricular myocardium.
J Mol Cell Cardiol 1987 Jul
PMID:Quantitative analysis of myofibrillar protein subunits: demonstration of large molar excesses of myosin light chains in rabbit ventricular myocardium. 368 7

Regional ventricular norepinephrine and myosin heavy chain concentrations were measured in two models of healed left ventricular myocardial infarction in cats. One model was characterized by a well-defined dense transmural scar (discrete myocardial infarction), while the other demonstrated a pattern of nontransmural diffuse patchy fibrosis in the infarct area (diffuse myocardial infarction). Norepinephrine and myosin heavy chain concentrations were measured in the scarred area, the non-infarcted zone surrounding the scar(s), and in sites remote from the scar. Corresponding tissue sites from unoperated animals and sham operated animals served as controls. Myosin heavy chain concentration was used as an index of surviving muscle mass to express norepinephrine concentration. Norepinephrine concentration, as a function of crude tissue mass, was significantly reduced in both the scarred tissues and the non-scarred tissues surrounding the scar in the discrete infarction model but was significantly reduced only in non-scarred tissues adjacent to the dense scar when expressed as a function of myosin heavy chain. The heavily scarred area of the discrete preparation approached normal values when corrected for myosin heavy chain content. The diffuse infarct preparation demonstrated normal norepinephrine concentration at all three sites studied, whether expressed as a function of tissue mass or myosin heavy chain. These data indicate a long-term regional reduction in norepinephrine concentration specific to non-infarcted tissues adjacent to a dense transmural myocardial infarction scar. This regional reduction in norepinephrine concentration corresponds to reported regions of increased sensitivity to sympathetic nerve stimulation in the discrete myocardial infarction model.
J Mol Cell Cardiol 1986 Apr
PMID:Regional reduction in ventricular norepinephrine after healing of experimental myocardial infarction in cats. 371 51

Monoclonal antibodies to the fast (high ATPase) alpha-type myosin heavy chain and to the slow (low ATPase) beta-type myosin heavy chain of rabbit heart were used to investigate myosin expression in human fetal, infant and adult heart by immunocytochemical procedures. With the anti-HC alpha antibody human atria always showed homogeneous staining from 14 weeks gestation through to the adult. No staining of ventricles was observed with this antibody between 14 and 18 weeks gestation but in infant ventricle a wide range of staining patterns was found; most hearts (44 out of 53) displayed none or a scattering of stained cells, five hearts showed fairly widespread but mostly weak staining while only two hearts showed strong staining of the majority of the ventricular myocytes. Normal adult ventricles more closely resembled the majority of infant hearts in showing none or a handful of stained cells scattered throughout the left ventricular wall. With the anti-HC beta antibody, all ventricular cells of all hearts stained strongly while a minority of atrial cells also showed staining from 14 weeks gestation. It is concluded that the alpha-type myosin heavy chain only appears in the ventricles around the time of birth but most commonly only ever constitutes a minor proportion of total ventricular myosin.
J Mol Cell Cardiol 1986 Jun
PMID:Isomyosin expression in human heart in early pre- and post-natal life. 373 41

The complete nucleotide sequence and exon/intron structure of the rat embryonic skeletal muscle myosin heavy chain (MHC) gene has been determined. This gene comprises 24 X 10(3) bases of DNA and is split into 41 exons. The exons encode a 6035 nucleotide (nt) long mRNA consisting of 90 nt of 5' untranslated, 5820 nt of protein coding and 125 nt of 3' untranslated sequence. The rat embryonic MHC polypeptide is encoded by exons 3 to 41 and contains 1939 amino acid residues with a calculated Mr of 223,900. Its amino acid sequence displays the structural features typical for all sarcomeric MHCs, i.e. an amino-terminal "globular" head region and a carboxy-terminal alpha-helical rod portion that shows the characteristics of a coiled coil with a superimposed 28-residue repeat pattern interrupted at only four positions by "skip" residues. The complex structure of the rat embryonic MHC gene and the conservation of intron locations in this and other MHC genes are indicative of a highly split ancestral sarcomeric MHC gene. Introns in the rat embryonic gene interrupt the coding sequence at the boundaries separating the proteolytic subfragments of the head, but not at the head/rod junction or between the 28-residue repeats present within the rod. Therefore, there is little evidence for exon shuffling and intron-dependent evolution by gene duplication as a mechanism for the generation of the ancestral MHC gene. Rather, intron insertion into a previously non-split ancestral MHC rod gene consisting of multiple tandemly arranged 28-residue-encoding repeats, or convergent evolution of an originally non-repetitive ancestral MHC rod gene must account for the observed structure of the rod-encoding portion of present-day MHC genes.
J Mol Biol 1986 Aug 05
PMID:Complete nucleotide and encoded amino acid sequence of a mammalian myosin heavy chain gene. Evidence against intron-dependent evolution of the rod. 378 1

The muscle-specific form of creatine kinase (MCK) is induced in differentiating myoblast cultures, and a dramatic increase in mRNA levels precedes and parallels the increase in MCK protein. To study this induction, the complete MCK gene was cloned and characterized. The transcription unit was shown to span 11 kilobases and to contain seven introns. The splice junctions were identified and shown to conform to the appropriate consensus sequences. Close homology with branchpoint consensuses was found upstream of the 3' splice sites in six of seven cases. Transcriptional regulation of the gene in differentiating myoblast cultures was demonstrated by nuclear run-on experiments; increases in transcription accounted for a major part of the increased mRNA levels. Regulated expression of a transfected MCK gene containing the entire transcription unit with 3.3 kilobases of 5'-flanking sequence was also demonstrated during differentiation of the MM14 mouse myoblast cell line. The MCK 5'-flanking region was sufficient to confer transcriptional regulation to a heterologous structural gene, since chloramphenicol acetyl transferase activity was induced during differentiation of cultures transfected with an MCK-chloramphenicol acetyl transferase fusion construct. Examination of the DNA sequence immediately upstream of the transcription start site revealed a 17-nucleotide element which occurred three times. Comparisons with other muscle-specific genes which are also transcriptionally regulated during myogenesis revealed upstream homologies in the alpha-actin and myosin heavy chain genes, but not in the myosin light-chain genes, with the regions containing these repeats. We suggest that coordinate control of a subset of muscle genes may occur via recognition of these common sequences.
Mol Cell Biol 1986 Aug
PMID:Transcriptional regulation of the muscle creatine kinase gene and regulated expression in transfected mouse myoblasts. 378 16


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