Changes in skeletal muscle gene transcription induced by chronic stimulation

Brownson, Carol A.; Isenberg, Harvey; Brown, W. D.; Salmons, Stanley; Edwards, Yvonne H.

doi:10.1002/mus.880111113

Cited by 59 publications

(36 citation statements)

References 28 publications

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“…The DMDL probes were not found to cross-hybridize with dystrophin mRNA under these conditions. Slot blot analysis involved denaturation of RNA in glyoxal (19) and direct transfer to a membrane using a slot blot apparatus (Schleicher & Schuell) as described (20 DNA Analysis. High molecular weight DNA from various animal species was prepared as previously described (22) or purchased from IBI.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…The DMDL probes were not found to cross-hybridize with dystrophin mRNA under these conditions. Slot blot analysis involved denaturation of RNA in glyoxal (19) and direct transfer to a membrane using a slot blot apparatus (Schleicher & Schuell) as described (20). Following hybridization, membranes were washed twice for 15 min each in 0.2x standard saline citrate (SSC)/0.1% SDS at room temperature and at 500C and finally in 0.1x SSC/0.1% SDS at 50'C for 15 min.…”

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confidence: 99%

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Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.

Love

Morris

Ellis

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

108

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We have previously reported a dystrophinrelated locus (DMDL for Duchenne muscular dystrophy-like) on human chromosome 6 that maps close to the dy mutation on mouse chromosome 10. Here we show that this gene is expressed in a wide range of tissues at varying levels. The transcript is particularly abundant in several human fetal tissues, including heart, placenta, and intestine. Studies with antisera raised against a DMDL fusion protein identify a 400,000 Mr protein in all mouse tissues tested, including those of mdx and dy mice. Unlike the dystrophin gene, the DMDL gene transcript is not differentially spliced at the 3' end in either fetal muscle or brain.Dystrophin has been identified as the protein product defective in Duchenne muscular dystrophy (DMD); however, very little is known about its precise function (1-3). Sequence comparisons have revealed features in common with cytoskeletal proteins. The amino-terminal region of dystrophin shows homology to the actin binding region of a-actinin (4,5) and the central rod domain shows structural similarities to the triple helical configuration of spectrin (6). In contrast, the carboxyl-terminal domain of 420 amino acids does not show homology to any previously characterized proteins. This latter domain is thought to be important in the integration of dystrophin into a glycoprotein complex localized at the muscle membrane surface (7,8). The carboxyl-terminal region of the gene is differentially spliced in muscle and brain, which suggests the production of isoforms with differing interactions with membrane proteins (9). In addition, this region of dystrophin is important for the correct functioning of the molecule in vivo as deletions covering this domain result in DMD rather than the milder Becker muscular dystrophy (10)(11)(12)(13).Recently, we demonstrated the existence of an mRNA in human fetal muscle that shares a high degree of sequence homology with the carboxyl-terminal region of dystrophin (14). The gene encoding this transcript is localized to human chromosome 6 and the locus has been designated DMDL for DMD-like in Human Gene Mapping 10 (15). The DMDL gene shares structural similarities with dystrophin: the transcript is large, 13 kilobases (kb), and is multiexonic with a similar distribution of 3' exons and introns.Although no human disease has yet been attributed to mutations at the DMDL locus, the mouse homologue of this gene, designated Dmdl, has been shown to be syntenic with the dy (dystrophia muscularis) locus on mouse chromosome 10 (16). The dy mutation is recessive and results in a severe neuromuscular disease in the mouse in which skeletal muscle shows degenerative changes (17). These observations suggest that the Dmdl gene may be a candidate for the dy mutation.In this paper, we present the tissue distribution of the DMDL transcript in humans and compare this distribution with the presence of a 400,000 Mr protein in mouse tissues. We also investigate the occurrence ofthe DMDL polypeptide in liver and muscle of mice with mutations in the dy...

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Section: Experimental Methodsmentioning

confidence: 99%

“…The DMDL probes were not found to cross-hybridize with dystrophin mRNA under these conditions. Slot blot analysis involved denaturation of RNA in glyoxal (19) and direct transfer to a membrane using a slot blot apparatus (Schleicher & Schuell) as described (20). Following hybridization, membranes were washed twice for 15 min each in 0.2x standard saline citrate (SSC)/0.1% SDS at room temperature and at 500C and finally in 0.1x SSC/0.1% SDS at 50'C for 15 min.…”

mentioning

confidence: 99%

Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.

Love

Morris

Ellis

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

108

View full text Add to dashboard Cite

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“…In the present study we have met this requirement by taking advantage of an experimental situation in which a major contractile protein, myosin, undergoes a complete change in isoform. Adult mammalian fast muscles that are subjected to chronic stimulation undergo a transformation of type which includes a switch from the expression of myosin heavy and light chain isoforms characteristic of fast muscle to those of slow muscle (Brown et al, 1983(Brown et al, , 1985Brownson et al, 1988). We have used electron microscopy in conjunction with an immunogold-labelling procedure to map the distribution of slow (SM) and fast (FM) muscle myosins as they are exchanged in the sarcomeres of rabbit tibialis anterior muscles undergoing stimulation-induced transformation and recovery.…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of newly incorporated myosin in rabbit fast skeletal muscle undergoing stimulation-induced type transformation

Franchi

Murdoch

Brown

et al. 1990

J Muscle Res Cell Motil

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Immunogold labelling was used to study the distribution of newly synthesized slow muscle myosin (SM) at the ultrastructural level as it replaced fast muscle myosin (FM) in rabbit muscles undergoing stimulation-induced type transformation. Control fast muscle was labelled strongly with antibody to FM and control slow muscle with antibody to SM; label was confined to the A-band. Well-defined differences in the distribution of label within the A-band suggested that the monoclonal antibodies used corresponded to epitopes on different parts of the myosin molecule; this was confirmed by Western blots of subfragments prepared from FM and SM. After 4 weeks of continuous stimulation at 10 Hz, fibres of the tibialis anterior muscle reacted with antibodies to both isoforms; after 6 weeks, labelling was obtained only with antibody to SM. After a 7-week period of stimulation and 3 further weeks of recovery, fibres again reacted with both antibodies. In all positively-labelled sections, the distribution of gold particles was characteristic of the antibody and independent of the origin or history of the fibres. This observation supports the conclusion that newly synthesized myosin is capable of being incorporated throughout the length and cross-section of the A-band.

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“…Increased levels of RNA with electrical stimulation has been documented previously [16] and the presence of increased amounts of mRNA, translating slow isoforms of myosin subunits some time prior to their appearance, has been shown at protein level in rat and rabbit electrostimulation studies [7,13,171 and was demonstrated here in the sheep. Slow isoforms of myosin may have undergone some degradation as a result of the surgery as poststimulation values for myosin slow isoforms were found to be less than the prestimulation control values (Figs.…”

Section: Transformation At Mrna Levelmentioning

confidence: 55%

Electrophoretic and computer analysis of skeletal muscle used for cardiac assistance

et al. 1991

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Skeletal muscle has an inherent plasticity which allows it to undergo fibre type transformation when induced by a specific stimulus. Electrical stimulation has been used here to induce transformation of a predominantly fast type skeletal muscle towards a slow, more fatigue-resistant phenotype, which is more suitable for use in long-term cardiac assistance. Muscle samples from animals electrically stimulated for periods up to 6 months have been analysed by electrophoresis for myosin heavy chain (MHC) and myosin light chain (MLC) fast and slow isoforms. Densitometry and computer analysis have been used to determine the pattern of transformation of the different myosin subunits over this time period. MHC and MLC 2 fast to slow isoform switching preceded that of the alkali light chains (MLC1 and MLC3). After 3 months of stimulation the MHC slow isoform was found to have doubled in concentration relative to the unstimulated control muscle and by 4 months accounted for almost 50% of the total MHC content. The slow isoform accounted for 75% of the MLC2 after 4 months of stimulation. The protein products of mRNA isolated from stimulated muscle samples, translated in vitro and separated by electrophoresis, showed that transformation at the mRNA level preceded that at the protein level. By 2-4 weeks of stimulation MLC2 slow isoform mRNA represented over 60% of the total MLC2 mRNA population. An understanding of the molecular structure of muscle during transformation provides insight into its haemodynamic performance in cardiac assistance.

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Changes in skeletal muscle gene transcription induced by chronic stimulation

Cited by 59 publications

References 28 publications

Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.

Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.

Subcellular localization of newly incorporated myosin in rabbit fast skeletal muscle undergoing stimulation-induced type transformation

Electrophoretic and computer analysis of skeletal muscle used for cardiac assistance

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