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At least 955 records · Page 53Linked to original sources
PubMed1998

Evolutionarily conserved promoter region containing CArG*-like elements is crucial for smooth muscle myosin heavy chain gene expression.

In recent years, significant progress has been made toward understanding skeletal muscle development. However, the mechanisms that regulate smooth muscle development and differentiation are presently unknown. To better understand smooth muscle-specific gene expression, we have focused our studies on the smooth muscle myosin heavy chain (SMHC) gene, a highly specific marker of differentiated smooth muscle cells. The goal of the present study was to isolate and characterize the mouse SMHC gene promoter, since the mouse promoter would be particularly suited for in vivo promoter analyses in transgenic mice and would serve as a tool for targeting genes of interest into smooth muscle cells. We report here the isolation and characterization of the mouse SMHC promoter and its 5' flanking region. DNA sequence analysis of a 2.6-kb portion of the promoter identified several potential binding sites for known transcription factors. Transient transfection analysis of promoter deletion constructs in primary cultures of smooth muscle cells showed that the region between -1208 and -1050 bp is critical for maximal SMHC promoter activity. A comparison of SMHC promoter sequences from mouse, rat, and rabbit revealed the presence of a highly conserved region located between -967 and -1208 bp. This region includes three CArG/CArG*-like elements, two SP-1 binding sites, a NF-1-like element, an Nkx2-5 binding site, and an Elk-1 binding site. Gel mobility shift assay and DNase I footprinting analyses show that all three CArG/CArG*-like elements can form DNA-protein complexes with nuclear extract from vascular smooth muscle cells. Protein binding to the CArG* elements can be competed out by either serum response element or by an authentic CArG element from the cardiac alpha-actin gene. Using a serum response factor (SRF) antibody, we demonstrate that SRF is part of the protein complex. In addition, we show that cotransfection with the SRF dominant-negative mutant expression vector abolishes SMHC promoter activity, suggesting that SRF protein plays a critical role in SMHC gene regulation.

Animals↗
PubMed2002

Effects of weight carrying, exercise and a myo-anabolic supplement on growth and muscle.

Weight training is commonly used by human athletes to increase strength and fitness. This study was performed to examine the effect of weight-carrying and nutritional supplementation on muscle development and growth in young horses. This study examined the effect of weight-carrying and nutritional supplementation on muscle development and growth. Seventeen horses were divided into 3 groups: controls exercised in a free-flow exerciser, a weight group that performed the same exercise, carrying progressively increasing weight up to 45 kg, and a weight-supplement group, that also received a myo-anabolic supplement. Horses were accustomed to handling for 30 days then baseline measurements of weight, body condition score, wither height, hip height, forearm and gaskin circumferences, and cross-sectional area of the longissimus dorsi were taken. Horses were stalled for 108 days then conditioned for 78 days. At the end of conditioning, all measurements were taken again. Supplemented weight-carrying horses increased their lean body tissue, as indicated by greater bodyweight (P<0.05) combined with decreased body condition score (P<0.01). Greater increases in wither height (P = 0.09) and hip height (P<0.01) were seen in weight-carrying horses, probably the result of increased muscle tone. Supplemented weight-carrying horses increased forearm (P<0.01) and gaskin circumferences (P<0.05). It is believed that weight-carrying, when combined with additional dietary protein, enabled greater muscle anabolism. Additional research into the potential additive effect of resistance training and diet are warrented.

Animal Nutritional Physiological Phenomena↗
PubMed2005

Stem cells and their derivatives can bypass the requirement of myocardin for smooth muscle gene expression.

The Serum Response Factor (SRF) coactivator myocardin stimulates the transcription of multiple muscle genes during cardiac and smooth muscle development. Mouse embryos lacking myocardin die during the earliest stages of smooth muscle development and fail to express multiple smooth muscle marker genes in the embryonic dorsal aorta and other vascular structures. In this study, we used mutant embryonic stem cell lines to further define the role of myocardin in smooth muscle differentiation and vascular development. Misexpression of myocardin in undifferentiated muscle stem cells resulted in efficient activation of smooth muscle genes, and weaker activation of genes involved in cardiac and skeletal muscle differentiation. Remarkably, myocardin(-/-) embryonic stem cell lines differentiated into smooth muscle cells in vitro, although these cells expressed significantly decreased levels of smooth muscle contractile genes. Moreover, genetically labeled myocardin(-/-) ES cells were able to contribute to smooth muscle lineages in vivo. These results indicate that while myocardin function is sufficient for activation of SRF-dependent muscle gene expression in multiple cell types, myocardin-independent mechanism(s) can suffice for expression in some smooth muscle lineages.

Animals↗
PubMed2003

Eye muscle force development and saccadic velocity in thyroid-associated ophthalmopathy.

BACKGROUND: Ocular motility disturbances are very common in patients with thyroid-associated ophthalmopathy (TAO). The force duction test has demonstrated that limitations of eye movements may be caused by mechanical restrictions in the muscles. A quantitative evaluation of isometric force production and ocular motility in all directions of gaze could further elucidate the mechanism of the movement disorder. METHODS: In eight patients with TAO and eight controls of the same age range, horizontal and vertical saccadic movements of both eyes were recorded by means of electro-oculography (EOG). The corresponding force development in muscles of the more affected eye in patients and the non-dominant eye in normals was measured, using a suction contact lens/strain gauge technique. RESULTS: Steady-state tension in the patients was increased in all directions of gaze both horizontally and vertically, most markedly for vertical fixations in the upper field of gaze. However, peak tension was increased only for the downward movements in the upper field of gaze and for the horizontal movements in the abduction field of gaze. Vertical saccadic velocity was slower than normal in downward movements, and horizontal saccadic velocity was reduced in the abduction field of gaze. CONCLUSION: The increased active eye muscle tension in different directions of gaze could represent an adaptational mechanism of the ocular motor system to overcome the eye movement restriction in TAO.

Aged↗
PubMed1990

Myosin isoforms and cell heterogeneity in vascular smooth muscle. I. Developing and adult bovine aorta.

Monoclonal anti-smooth muscle (SM-E7, SM-F11, and BF-48) and anti-nonmuscle (NM-A9 and NM-G2) myosin antibodies, Western blotting, and immunocytochemical procedures were used to study myosin isoform composition and distribution in the smooth muscle (SM) cells of bovine aorta differentiating in vivo and in vitro. Two myosin heavy chain (MHC) isoforms were identified by SM-E7 in adult aorta: SM-MHC-1 (Mr = 205 kDa) and SM-MHC-2 (Mr = 200 kDa), respectively. When tested with the SM-F11 antibody, SM-MHC-2 isoform showed distinct antigenic properties compared to SM-MHC-1. Two bands of 205 and 200 kDa were also present in the aortic SM tissue from 3-month-old fetus and were equally recognized by the BF-48 antibody. The 200-kDa SM myosin isoform was labeled by SM-F11 but not by SM-E7, thus indicating the existence of a fetal-specific SM-MHC-2 isoform. At the cellular level, both developing and adult bovine aortic tissues showed the existence of distinct patterns of myosin isoform expression. Three or even more aortic cell populations are differently distributed in areas which appear as (1) a network of interconnecting sheet-like or compact tissue (early fetus) and (2) enriched of collagenous-elastic or muscular tissue (adult animal). In addition, the SM-MHC-2 isoform of the fetal type appears to be uniquely distributed in cultured SM cells grown in vitro from adult bovine aortic explants. Our data indicate that in bovine aorta (1) MHC isoform expression is developmentally regulated and (2) the distribution of myosin isoforms is heterogenous both among and within aortic cells. These findings may be related to the distinct physiological properties displayed by SM during vascular myogenesis.

Animals↗
PubMed1998

Ontogenesis of nitric oxide synthases in the ventilatory muscles.

Nitric oxide (NO) acts as an endogenous mediator in mature skeletal muscle. In this study, we investigated the regulation of the endothelial (eNOS) and neuronal (nNOS) isoforms of nitric oxide synthase (NOS) in skeletal-muscle development (rat diaphragm). Muscle NOS activity, nNOS and eNOS protein, and mRNA expressions were markedly increased during the late gestational and early postnatal periods. Expression of both isoforms, however, declined progressively thereafter. Similarly, argininosuccinate lyase and argininosuccinate synthetase, both involved in the recycling of L-citrulline to L-arginine, were expressed at high levels in rat embryonic and neonatal diaphragms, with gradual reduction in their expression during late postnatal development. Immunostaining revealed extensive nNOS expression at the sarcolemma in neonatal and mature diaphragms, whereas eNOS expression was limited to the endothelium. Both neonatal and adult diaphragms expressed an alternatively spliced nNOS isoform with an insert of 34 amino acids between exons 16 and 17. In vitro-generated muscle force rose significantly after NOS inhibition in both neonatal and adult diaphragms, but the magnitude of force augmentation was larger in adult than in neonatal diaphragm. These results indicate that constitutive NOS isoforms are developmentally regulated in skeletal muscles, suggesting multiple roles for NO in developing and mature skeletal-muscle fibers.

Aging↗
PubMed1999

Development of muscle pathology in canine X-linked muscular dystrophy. I. Delayed postnatal maturation of affected and normal muscle as revealed by myosin isoform analysis and utrophin expression.

Canine X-linked muscular dystrophy (CXMD) is genetically homologous to Duchenne muscular dystrophy and shares the severe myopathy and lethal clinical development of the human disease. We used immunohistochemistry to characterize the time course of postnatal expression of adult fast, adult slow and developmental myosin in the muscle of CXMD dogs, carriers and healthy controls. We also characterized the expression of utrophin and dystrophin. This detailed immunolocalization study confirmed that postnatal muscle maturation is delayed in normal dogs compared to other animals and humans, and is only achieved at around 60 days. In CXMD dogs major derangement of myosin expression became evident from about 15 days; there was a selective loss of fibers expressing fast myosin and persistence of developmental fibers compared to controls. In carriers, the proportion of dystrophin-deficient fibers, which mainly expressed fast myosin, decreased with age. In controls and carriers utrophin was absent from muscle fiber surfaces in 2-day-old animals but present between 15 and 30 days, to mostly disappear by 60 days. In dystrophic animals, sarcolemmal expression of utrophin was more marked and persistent. That immature neonatal muscle from control dogs normally contains sarcolemmal utrophin may have implications for the success of utrophin up-regulation therapy to correct the dystrophic phenotype. The data of this study provide important baseline information for further studies on the development and progression of pathological changes in the muscle of CXMD dogs.

Aging↗
PubMed1993

Dystrophin protects the sarcolemma from stresses developed during muscle contraction.

The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse.

Animals↗
PubMed2005

[Familial amyotrophic lateral sclerosis with rapid progression].

We report a family with autosomal dominant (AD) motor neuron disease. A 41-year-old man developed muscle weakness and fasciculation of the lower extremities. The weakness progressed to the upper extremities and bulbar muscles. The cerebrospinal fluid (CSF) protein level was slightly elevated. A nerve conduction study revealed reduced compound muscle action potentials, but conduction block was not observed. Electromyogram showed acute and chronic neurogenic changes. He was treated with intravenous immunoglobulin (IVIg) and methylprednisolone pulse therapy, but his condition rapidly deteriorated. He developed respiratory failure necessitating artificial ventilation within three months after the onset of the disease. His father developed muscle weakness and atrophy of the upper extremities at age 70, and his cousin developed muscle weakness of the legs at age 41. Their conditions rapidly progressed to quadriplegia. CSF and electrophysiological findings were similar to those of the proband. Treatments by steroid pulse therapy, IVIg, and plasmapheresis were not effective. The father and cousin also required artificial ventilation within 3-4 months from the onset of symptoms, and became locked-in state. Autosomal dominant amyotrophic lateral sclerosis (AD-ALS) was considered, but SOD1 gene mutation was not detected. The present pedigree may have familial ALS caused by a gene mutation other than SOD1.

Adult↗
PubMed2002

Development of muscle fatigue as assessed by electromyography and mechanomyography during continuous and intermittent low-force contractions: effects of the feedback mode.

The goal of the present study was to investigate the significance of low-force continuous or intermittent static contraction and feedback mode (visual or proprioceptive) on the development of muscle fatigue as assessed by electromyography (EMG) and mechanomyography (MMG). Visual (force control) and proprioceptive (displacement control) feedback was investigated during intermittent (6 s contraction, 4 s rest) and continuous static contractions at 10% and 30% of the maximum voluntary contraction (MVC). Mean force, force fluctuation, rating of perceived exertion and root mean square (RMS) and mean power frequency (MPF) of the EMG and MMG signals were analysed. The general pattern for MMG RMS and EMG RMS values and the rating of perceived exertion was an increase with contraction time, while the EMG MPF values decreased ( P<0.05). The increase in RMS values was generally more pronounced for the MMG compared with the EMG, while the decrease in MPF values was more consistent for the EMG compared with the MMG signal. During the intermittent contractions, the main effect was on MPF for both EMG and MMG. Lower force fluctuation and larger rating of perceived exertion ( P<0.05), greater slopes of EMG and MMG RMS and MPF values versus time were observed with proprioceptive feedback compared with visual feedback. The findings suggest that (1) the EMG and MMG signals give complementary information about localised muscle fatigue at low-level contraction: they responded differently in terms of changes in the time and frequency domain during continuous contraction, while they responded in concert in the frequency domain during intermittent contractions, and (2) the different centrally mediated motor control strategies used during fatiguing contraction may be dependent upon the feedback modality.

Adult↗
PubMed1998

Unlike tenascin-X, tenascin-C is highly up-regulated in pig cutaneous and underlying muscle tissue developing fibrosis after necrosis induced by very high-dose gamma radiation.

Fibrosis is characterized by proliferation of fibroblasts and deposition of extracellular matrix (ECM). As alterations in the composition of ECM may account for its chronic extension, we studied the expression of the tenascin-C (TN-C) and tenascin-X (TN-X) ECM glycoproteins in our pig model of the effects of accidental exposures to radiation, in which cutaneous and muscle fibrosis developed after the induction of necrosis after a high single dose (160 Gy at the skin surface) of gamma rays. We found that, in the healed fibrotic dermis and underlying muscle fibrosis, the amount of TN-C mRNA was increased up to 18- and 39-fold, respectively, compared to normal dermis, whereas the level of TN-X mRNA remained almost unchanged. In analyses by Western blotting, the two main TN-C isoforms of 235-240 and 190-200 kDa increased up to 45- and 105-fold in fibrotic tissues, respectively. The large isoform was expressed more strongly than the smaller, although in healed fibrotic scar tissues their ratio was lower in protein than in RNA. Compared to unirradiated skin, an immunohistological study revealed stronger TN-C staining at the dermo-epidermal junction and in areas of remodeling in healed skin. An intense extracellular staining was observed around myofibroblasts in muscle fibrosis. Therefore, the gene encoding TN-C is highly up-regulated in fibrotic tissues, and mechanisms regulating the levels of TN-C variants occur at both the RNA and protein levels. Each isoform might play a distinct role in the chronic activation of fibrosis by differentially regulating mechanisms like cell adhesion, migration or proliferation.

Alternative Splicing↗
PubMed1988

Transcriptional repression of an embryo-specific muscle gene.

Skeletal muscle involves both the induction and repression of gene expression. Although activation and up-regulation of several contractile protein genes has been shown to occur via transcriptional mechanisms, the mechanisms by which contractile protein genes are repressed during muscle development remain unknown. However, a post-transcriptional mechanism has been implicated in the repression of thymidine kinase expression during muscle development. The chicken cardiac troponin T (cTNT) gene is expressed in early embryonic skeletal muscle but is abruptly repressed in late embryonic/fetal development. Using run-on transcription assays we demonstrate here that cTNT gene repression occurs at the level of transcription. Thus, transcriptional as well as post-transcriptional mechanisms operate both to activate and repress gene expression during skeletal muscle development.

Actins↗
PubMed1989

Development of smooth muscle: ultrastructural study of the chick embryo gizzard.

The growth and differentiation of smooth muscle in the chicken gizzard were studied by electron microscopy from the 10th day in ovo to 6 months after hatching; during this period the organ grows 1000-fold in weight. At the earliest stage studied, smooth muscle cells, interstitial cells, and fibroblasts are immature but can already be clearly distinguished. The structural components of muscle cells develop in a characteristic sequence. Mitochondria are more abundant in immature muscle cells (8% in 14 days embryos and 7% in 19 days embryos) than in the adult (5%). Caveolae are virtually absent in the 11 day embryo; they become more common at the end of embryonic life, but continue to increase in relative frequency after hatching. Gap junctions appear around the 16th day in ovo as minute aggregates of connexons, which then grow in size, probably by addition of new connexons. In the earliest stages studied, myofilaments occupy 25% of the cell profile and are assembled into bundles accompanied by dense bodies and surrounded by loosely arranged intermediate filaments. By contrast, membrane-bound dense bands are scarce until the latter part of embryonic life, an observation suggesting that myofilament formation and alignment is not a process initiated near the cell membrane or directed by the cell membrane, and that only late in development bundles of myofilaments become extensively anchored to dense bands over the entire cell surface: at that time myofilaments occupy more than 75% of the cell volume. The muscle cells increase about four-fold in volume over the period studied; the 1000-fold increase in muscle volume is mainly accounted for by an increase in muscle cell number. Mitoses are found in the gizzard musculature at all embryonic ages with a peak at 17-19 days; they occur in muscle cells with a high degree of differentiation. These cells divide at a stage when they are packed with myofilaments and form junctions with neighbouring cells: the mitotic process affects the middle portion of the cell, which takes up an ovoid shape and eventually divides, whereas the remaining portions of the cell do not differ in appearance from the surrounding muscle cells. At all stages of development the population of muscle cells has a uniform appearance (apart from the cells in mitosis), and the growth and differentiation seem to proceed at the same pace in all the cells. There are no undifferentiated cells left behind in the tissue for later development.

Animals↗
PubMed2005

Insulin-like growth factor-I (IGF-1) mRNA levels and chicken muscle growth.

Insulin-like Growth Factor-1 is a key regulator of muscle development and metabolism in birds and other vertebrate species. In a first part, the present paper sums up the specificities of the IGF system in birds and especially those related to muscle development. In a second part, it reviews available data obtained with avian genetic or nutritional models. Data obtained by comparing genetic models with large variations of overall body growth show a positive relation between endocrine IGF-1 and growth rate. Data obtained using both genetic and nutritional models show a positive relation between muscle IGF-1 mRNA levels, which determine paracrine IGF-1 levels, and post hatch muscle growth.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Expression of myostatin pro domain results in muscular transgenic mice.

Myostatin, a member of the TGF-beta family, negatively regulates skeletal muscle development. Depression of myostatin activity leads to increased muscle growth and carcass lean yield. In an attempt to down-regulate myostatin, transgenic mice were produced with a ribozyme-based construct or a myostatin pro domain construct. Though the expression of the ribozyme was detected, muscle development was not altered by the ribozyme transgene. However, a dramatic muscling phenotype was observed in transgenic mice carrying the myostatin pro domain gene. Expression of the pro domain transgene at 5% of beta-actin mRNA levels resulted in a 17-30% increase in body weight (P < 0.001). The carcass weight of the transgenic mice showed a 22-44% increase compared with nontransgenic littermates at 9 weeks of age (16.05 +/- 0.67 vs. 11.16 +/- 0.28 g in males; 9.99 +/- 0.38 vs. 8.19 +/- 0.19 g in females, P < 0.001). Extreme muscling was present throughout the whole carcass of transgenic mice as hind and fore limbs and trunk weights, all increased significantly (P < 0.001). Epididymal fat pad weight, an indicator of body fat, was significantly decreased in pro domain transgenic mice (P < 0.001). Analysis of muscle morphology indicated that cross-sectional areas of fast-glycolytic fibers (gastrocnemius) and fast-oxidative glycolytic fibers (tibialis) were larger in pro domain transgenic mice than in their controls (P < 0.01), whereas fiber number (gastrocnemius) was not different (P > 0.05). Thus, the muscular phenotype is attributable to myofiber hypertrophy rather than hyperplasia. The results of this study suggest that the over-expression of myostatin pro domain may provide an alternative to myostatin knockouts as a means of increasing muscle mass in other mammals.

Adipose Tissue↗
PubMed1994

[Main steps in the skeletal myogenesis in man].

During the metabolic differentiation of developing human skeletal muscle fibers, two different generations of fibers can be characterised by their profiles of protein expression (in particular of the myosin heavy chains). This differentiation is regulated by both genetic and epigenetic factors (motor innervation, levels of thyroid hormone). The anomalies in different muscle pathologies can be better understood by comparison with the modifications occurring during normal skeletal muscle development.

Embryonic and Fetal Development↗