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Sample records for fish skeletal muscle

  1. Skeletal muscle

    Science.gov (United States)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  2. [Stoichiometry of cytochromes and oxygen tension in skeletal muscles of marine fish].

    Science.gov (United States)

    Soldatov, A A; Parfenova, I A

    2014-01-01

    The character of oxygen tension distribution and peculiarities of cytochromes stoichiometry in skeletal muscles of bottom and pelagic species of marine fish were compared. It is shown, that the limitation of muscle activity increases the number of hypoxic zones in the muscle tissue. The mitochondrial electron-transporting chain then obtain the uncompensated type of organization, expressed in the increase of the share of the terminal complex aa3 on the background of general reduction of cytochromes content in the muscles. The reaction is of an adaptive character and can be implemented by pelagic fish species in conditions of experimental hypokinesia.

  3. Deep RNA sequencing of the skeletal muscle transcriptome in swimming fish.

    Directory of Open Access Journals (Sweden)

    Arjan P Palstra

    Full Text Available Deep RNA sequencing (RNA-seq was performed to provide an in-depth view of the transcriptome of red and white skeletal muscle of exercised and non-exercised rainbow trout (Oncorhynchus mykiss with the specific objective to identify expressed genes and quantify the transcriptomic effects of swimming-induced exercise. Pubertal autumn-spawning seawater-raised female rainbow trout were rested (n = 10 or swum (n = 10 for 1176 km at 0.75 body-lengths per second in a 6,000-L swim-flume under reproductive conditions for 40 days. Red and white muscle RNA of exercised and non-exercised fish (4 lanes was sequenced and resulted in 15-17 million reads per lane that, after de novo assembly, yielded 149,159 red and 118,572 white muscle contigs. Most contigs were annotated using an iterative homology search strategy against salmonid ESTs, the zebrafish Danio rerio genome and general Metazoan genes. When selecting for large contigs (>500 nucleotides, a number of novel rainbow trout gene sequences were identified in this study: 1,085 and 1,228 novel gene sequences for red and white muscle, respectively, which included a number of important molecules for skeletal muscle function. Transcriptomic analysis revealed that sustained swimming increased transcriptional activity in skeletal muscle and specifically an up-regulation of genes involved in muscle growth and developmental processes in white muscle. The unique collection of transcripts will contribute to our understanding of red and white muscle physiology, specifically during the long-term reproductive migration of salmonids.

  4. Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue.

    Science.gov (United States)

    Prohaska, Bianca K; Tsang, Paul C W; Driggers, William B; Hoffmayer, Eric R; Wheeler, Carolyn R; Brown, A Christine; Sulikowski, James A

    2013-01-01

    Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs.

  5. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata

    Directory of Open Access Journals (Sweden)

    Md. Shahidul Haque

    2014-06-01

    Full Text Available Channa punctata varieties of fish are energetic and survive in critical environment although the molecular mechanism is not known. They were exposed to cold (4–8 °C for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle was noted and maximal at 2 h. Groups of fish were exposed to Na2HAsO4 to examine its role on cold-induced protein synthesis in the skeletal muscle and the increased protein in the skeletal muscle was reduced significantly. The results appear to indicate that cold acclimation induces a metabolic change involving cellular protein content tissue specifically and arsenic might be involved in impairment of the cold-induced effect. To clarify the molecular mechanism, groups of fish exposed to cold for 1 h and 2 h had significantly increased RNA in the skeletal muscle compared to control fish, however, a higher level was found after 2 h of treatment and the enhanced RNA induced by cold was almost completely prevented by Na2HAsO4. Our findings will give a new insight into the survival process of this species while toxic arsenic prevents this cellular bioprocess.

  6. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata)

    OpenAIRE

    Md Shahidul Haque; Md. Asraful Haque; Swapan Kumar Roy; M M H Khan; Md Mosharrof Hossain

    2014-01-01

    Channa punctata varieties of fish are energetic and survive in critical environment although the molecular mechanism is not known. They were exposed to cold (4–8 °C) for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle was noted and maximal at 2 h. Groups of fish were exposed to Na2HAsO4 to examine its role on cold-induced protein synthesis in the ...

  7. Deep RNA Sequencing of the Skeletal Muscle Transcriptome in Swimming Fish

    NARCIS (Netherlands)

    Palstra, A.P.; Beltran, S.; Burgerhout, E.; Brittijn, S.A.; Magnoni, L.J.; Henkel, C.V.; Jansen, A.; Thillart, G.E.E.J.M.; Spaink, H.P.; Planas, J.V.

    2013-01-01

    Deep RNA sequencing (RNA-seq) was performed to provide an in-depth view of the transcriptome of red and white skeletal muscle of exercised and non-exercised rainbow trout (Oncorhynchus mykiss) with the specific objective to identify expressed genes and quantify the transcriptomic effects of swimming

  8. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence......, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle...

  9. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

  10. Ultrastructural description of Myxobolus cuneus (Myxosporea) in the skeletal muscle and kidney of tropical farmed fish Piaractus mesopotamicus (Characiformes: Characidae).

    Science.gov (United States)

    Manrique, Wilson Gómez; Figueiredo, Mayra Araguaia Pereira; de Andrade Belo, Marco Antonio; Martins, Maurício Laterça; Azevedo, Carlos

    2016-06-01

    This study characterizes by transmission electron microscopy (TEM) and morphometric features the myxozoan Myxobolus cuneus (Myxosporea) in Piaractus mesopotamicus and reports the skeletal muscle and kidney as site of infection. The register was based in 21 young fish from intensive fish farming in Southeast Brazil and the spores were analyzed in fresh-mounted slides of the infected organs stained with Toluidine blue and processed as usual for TEM. It differs from Myxobolus cunhai from the fish host and different polar capsule size, and from Myxobolus serrasalmi on the pyriform spore shape and an oval macrospore, differently to that reported in this study. Morphometric characteristics and TEM study confirmed the present material as M. cuneus.

  11. At environmental doses, dietary methylmercury inhibits mitochondrial energy metabolism in skeletal muscles of the zebra fish (Danio rerio).

    Science.gov (United States)

    Cambier, S; Bénard, G; Mesmer-Dudons, N; Gonzalez, P; Rossignol, R; Brèthes, D; Bourdineaud, J-P

    2009-04-01

    The neurotoxic compound methylmercury (MeHg) is a commonly encountered pollutant in the environment, and constitutes a hazard for human health through fish eating. To study the impact of MeHg on mitochondrial structure and function, we contaminated the model fish species Danio rerio with food containing 13 microg of MeHg per gram, an environmentally relevant dose. Mitochondria from contaminated zebrafish muscles presented structural abnormalities under electron microscopy observation. In permeabilized muscle fibers, we observed, a strong inhibition of both state 3 mitochondrial respiration and functionally isolated maximal cytochrome c oxidase (COX) activity after 49 days of MeHg exposure. However, the state 4 respiratory rate remained essentially unchanged. This suggested a defect at the level of ATP synthesis. Accordingly, we measured a dramatic decrease in the rate of ATP release by skinned muscle fibers using either pyruvate and malate or succinate as respiratory substrates. However, the amount and the assembly of the ATP synthase were identical in both control and contaminated muscle mitochondrial fractions. This suggests that MeHg induced a decoupling of mitochondrial oxidative phosphorylation in the skeletal muscle of zebrafish. Western blot analysis showed a 30% decrease of COX subunit IV levels, a 50% increase of ATP synthase subunit alpha, and a 40% increase of the succinate dehydrogenase Fe/S protein subunit in the contaminated muscles. This was confirmed by the analysis of gene expression levels, using RT-PCR. Our study provides a basis for further analysis of the deleterious effect of MeHg on fish health via mitochondrial impairment.

  12. Skeletal muscle tissue engineering

    National Research Council Canada - National Science Library

    Bach, A. D; Beier, J. P; Stern‐Staeter, J; Horch, R. E

    2004-01-01

    The reconstruction of skeletal muscle tissue either lost by traumatic injury or tumor ablation or functional damage due to myopathies is hampered by the lack of availability of functional substitution...

  13. Lipolysis in Skeletal Muscle

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck

    and especially the energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK), which is activated during exercise, has received increased attention. However, whether AMPK is an activator or inhibitor of lipolysis in skeletal muscle is not clear. Therefore, we in study I aimed to identify the role...... contraction. Accordingly, AMPK is suggested to be an important regulator of basal IMTG and lipid handling in skeletal muscle as well as an important activator of lipolysis by phosphorylation of ATGL and HSL during muscle contractions. Oversupply of energy and dietary fat leads to obesity and accumulation...... chemical structure of DAG. We took advantage of the fact that insulin sensitivity is increased after exercise, and that mice knocked out (KO) of HSL accumulate DAG after exercise, and measured insulin stimulated glucose uptake after treadmill running in skeletal muscle from HSL KO mice and wildtype control...

  14. Dietary fish oil delays hypoxic skeletal muscle fatigue and enhances caffeine-stimulated contractile recovery in the rat in vivo hindlimb.

    Science.gov (United States)

    Peoples, Gregory E; McLennan, Peter L

    2017-06-01

    Oxygen efficiency influences skeletal muscle contractile function during physiological hypoxia. Dietary fish oil, providing docosahexaenoic acid (DHA), reduces the oxygen cost of muscle contraction. This study used an autologous perfused rat hindlimb model to examine the effects of a fish oil diet on skeletal muscle fatigue during an acute hypoxic challenge. Male Wistar rats were fed a diet rich in saturated fat (SF), long-chain (LC) n-6 polyunsaturated fatty acids (n-6 PUFA), or LC n-3 PUFA DHA from fish oil (FO) (8 weeks). During anaesthetised and ventilated conditions (normoxia 21% O2 (SaO2-98%) and hypoxia 14% O2 (SaO2-89%)) the hindlimb was perfused at a constant flow and the gastrocnemius-plantaris-soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6-12V, 0.05 ms) to established fatigue. Caffeine (2.5, 5, 10 mM) was supplied to the contracting muscle bundle via the arterial cannula to assess force recovery. Hypoxia, independent of diet, attenuated maximal twitch tension (normoxia: 82 ± 8; hypoxia: 41 ± 2 g·g(-1) tissue w.w.). However, rats fed FO sustained higher peak twitch tension compared with the SF and n-6 PUFA groups (P recovery was enhanced in the FO-fed animals (SF: 41 ± 3; n-6 PUFA: 40 ± 4; FO: 52 ± 7% recovery; P < 0.05). These results support a physiological role of DHA in skeletal muscle membranes when exposed to low-oxygen stress that is consistent with the attenuation of muscle fatigue under physiologically normoxic conditions.

  15. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata)

    National Research Council Canada - National Science Library

    Md. Shahidul Haque; Md. Asraful Haque; Swapan Kumar Roy; M.M.H. Khan; Md. Mosharrof Hossain

    2014-01-01

    .... They were exposed to cold (4–8 °C) for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle...

  16. Skeletal muscle sodium channelopathies.

    Science.gov (United States)

    Nicole, Sophie; Fontaine, Bertrand

    2015-10-01

    This is an update on skeletal muscle sodium channelopathies since knowledge in the field have dramatically increased in the past years. The relationship between two phenotypes and SCN4A has been confirmed with additional cases that remain extremely rare: severe neonatal episodic laryngospasm mimicking encephalopathy, which should be actively searched for since patients respond well to sodium channel blockers; congenital myasthenic syndromes, which have the particularity to be the first recessive Nav1.4 channelopathy. Deep DNA sequencing suggests the contribution of other ion channels in the clinical expressivity of sodium channelopathies, which may be one of the factors modulating the latter. The increased knowledge of channel molecular structure, the quantity of sodium channel blockers, and the availability of preclinical models would permit a most personalized choice of medication for patients suffering from these debilitating neuromuscular diseases. Advances in the understanding of the molecular structure of voltage-gated sodium channels, as well as availability of preclinical models, would lead to improved medical care of patients suffering from skeletal muscle, as well as other sodium channelopathies.

  17. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

      The connective tissue content of skeletal muscle is believed to be the major factor responsible for defining the eating quality of different meat cuts, although attempts to correlate quantifications based on traditional histological methods have not as yet been able to prove this relation....... Collagen, being the major protein in connective tissue, has been extensively investigated with regard to its relation to meat tenderness, but the results have been rather conflicting. Meat from older animals is tougher than that from younger animals, and changes in the properties of the collagen due...... that collagen plays a significant role in determining the tenderness of meat. What are we missing? Therefore, fundamental aspects of connective tissue research have been the centre of attention throughout this thesis. A holistic view has been applied, glancing at this complex tissue which has many facets...

  18. [Use of properties and regulation peculiarities of enzymes of glycogenolysis in fish skeletal muscle depending on peculiarities of motor activity of species].

    Science.gov (United States)

    Serebrenikova, T P; Nesterov, V P

    2008-01-01

    Levels of activity, properties, and peculiarities of activation of glycogen phosphorylase (GP; EC 2.4.1.1) and glycogen phosphorylase kinase (GPK; EC 2.7.1.38) were studied in the white skeletal muscle of fish differing in motor behavior. No differences in the GP and GPK activity levels were revealed in laskir Diplodus annularis (L.), horse mackerel Trachurus mediterraneus ponticus, salmon Salmo trutta morphario, scorpena Scorpaena porcus, Scophtalnus maeoticus, and carp Cyprinus carpio; however, properties of the isolated enzymes and peculiarities of formation of their activated forms during swimming in a hydrodynamic tube are determined by functional peculiarities of the muscle tissue and are associated with the motor activity character of the species. In fish capable for the spurt type of swimming (scorpena, salmon) the more rapid ion regulation plays the predominant role. In other species, the glycogenolysis hormonal regulation leading to a change of the GPK activity index has been found.

  19. Skeletal Muscle Na+ Channel Disorders

    Directory of Open Access Journals (Sweden)

    Dina eSimkin

    2011-10-01

    Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

  20. Identification of a novel transforming growth factor-β (TGF-β6 gene in fish: regulation in skeletal muscle by nutritional state

    Directory of Open Access Journals (Sweden)

    Jakowlew Sonia B

    2010-05-01

    Full Text Available Abstract Background The transforming growth factor-β (TGF-β family constitutes of dimeric proteins that regulate the growth, differentiation and metabolism of many cell types, including that of skeletal muscle in mammals. The potential role of TGF-βs in fish muscle growth is not known. Results Here we report the molecular characterization, developmental and tissue expression and regulation by nutritional state of a novel TGF-β gene from a marine fish, the gilthead sea bream Sparus aurata. S. aurata TGF-β6 is encoded by seven exons 361, 164, 133, 111, 181, 154, and 156 bp in length and is translated into a 420-amino acid peptide. The exons are separated by six introns: >643, 415, 93, 1250, 425 and >287 bp in length. Although the gene organization is most similar to mouse and chicken TGF-β2, the deduced amino acid sequence represents a novel TGF-β that is unique to fish that we have named TGF-β6. The molecule has conserved putative functional residues, including a cleavage motif (RXXR and nine cysteine residues that are characteristic of TGF-β. Semi-quantitative analysis of TGF-β6 expression revealed differential expression in various tissues of adult fish with high levels in skin and muscle, very low levels in liver, and moderate levels in other tissues including brain, eye and pituitary. TGF-β6 is expressed in larvae on day of hatching and increases as development progresses. A fasting period of five days of juvenile fish resulted in increased levels of TGF-β6 expression in white skeletal muscle compared to that in fed fish, which was slightly attenuated by one injection of growth hormone. Conclusion Our findings provide valuable insights about genomic information and nutritional regulation of TGF-β6 which will aid the further investigation of the S. aurata TGF-β6 gene in association with muscle growth. The finding of a novel TGF-β6 molecule, unique to fish, will contribute to the understanding of the evolution of the TGF

  1. Simvastatin effects on skeletal muscle

    DEFF Research Database (Denmark)

    Larsen, Steen; Stride, Nis; Hey-Mogensen, Martin;

    2013-01-01

    Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9).......Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9)....

  2. Dietary enrichment with fish oil prevents high fat-induced metabolic dysfunction in skeletal muscle in mice.

    Science.gov (United States)

    Philp, Lisa K; Heilbronn, Leonie K; Janovska, Alena; Wittert, Gary A

    2015-01-01

    High saturated fat (HF-S) diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO) diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus) and white (extensor digitorum longus) muscles of male and female C57BL/6 mice (n = 9-12/group). Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic and gene

  3. Dietary enrichment with fish oil prevents high fat-induced metabolic dysfunction in skeletal muscle in mice.

    Directory of Open Access Journals (Sweden)

    Lisa K Philp

    Full Text Available High saturated fat (HF-S diets increase intramyocellular lipid, an effect ameliorated by omega-3 fatty acids in vitro and in vivo, though little is known about sex- and muscle fiber type-specific effects. We compared effects of standard chow, HF-S, and 7.5% HF-S replaced with fish oil (HF-FO diets on the metabolic profile and lipid metabolism gene and protein content in red (soleus and white (extensor digitorum longus muscles of male and female C57BL/6 mice (n = 9-12/group. Weight gain was similar in HF-S- and HF-FO-fed groups. HF-S feeding increased mesenteric fat mass and lipid marker, Oil Red O, in red and mixed muscle; HF-FO increased interscapular brown fat mass. Compared to chow, HF-S and HF-FO increased expression of genes regulating triacylglycerol synthesis and fatty acid transport, HF-S suppressed genes and proteins regulating fatty acid oxidation, whereas HF-FO increased oxidative genes, proteins and enzymes and lipolytic gene content, whilst suppressing lipogenic genes. In comparison to HF-S, HF-FO further increased fat transporters, markers of fatty acid oxidation and mitochondrial content, and reduced lipogenic genes. No diet-by-sex interactions were observed. Neither diet influenced fiber type composition. However, some interactions between muscle type and diet were observed. HF-S induced changes in triacylglycerol synthesis and lipogenic genes in red, but not white, muscle, and mitochondrial biogenesis and oxidative genes were suppressed by HF-S and increased by HF-FO in red muscle only. In conclusion, HF-S feeding promotes lipid storage in red muscle, an effect abrogated by the fish oil, which increases mediators of lipolysis, oxidation and thermogenesis while inhibiting lipogenic genes. Greater storage and synthesis, and lower oxidative genes in red, but not white, muscle likely contribute to lipid accretion encountered in red muscle. Despite several gender-dimorphic genes, both sexes exhibited a similar HF-S-induced metabolic

  4. Choosing a skeletal muscle relaxant.

    Science.gov (United States)

    See, Sharon; Ginzburg, Regina

    2008-08-01

    Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions.

  5. Effect of dietary fish oil on the expression of genes involved in lipid metabolism in liver and skeletal muscle of lactating sows.

    Science.gov (United States)

    Gessner, D K; Gröne, B; Rosenbaum, S; Most, E; Hillen, S; Becker, S; Erhardt, G; Reiner, G; Eder, K

    2016-04-01

    This study investigated the hypothesis that dietary supplementation of fish oil as a source of n-3 polyunsaturated fatty acids (PUFA) influences the expression of target genes of sterol regulatory element-binding proteins (SREBP)-1 and (SREBP)-2 involved in triacylglycerol (TAG) synthesis and fatty acid and cholesterol metabolism in the liver, and moreover activates the expression of target genes of peroxisome proliferation-activated receptor (PPAR)-α involved in TAG and fatty acid catabolism in liver and skeletal muscle. Twenty lactating sows were fed a control diet or a fish oil diet with either 50 g of a mixture of palm oil and soya bean oil (4:1, w/w) or fish oil per kg. The diet of the fish oil group contained 19.1 g of n-3 PUFA (mainly 20:5 n-3 and 22:6 n-3) per 100 g of total fatty acids, while the diet of the control group contained 2.4 g of n-3 PUFA (mainly 18:3 n-3) per 100 g of total fatty acids. The fish oil group had reduced relative mRNA concentrations of various target genes of SREBP-1 involved in fatty acid and TAG synthesis in comparison with the control group (p oil supplementation. Concentrations of cholesterol and TAG in plasma, fat content of milk and weight gains of litters during the suckling period were not different between the two groups of sows. In conclusion, this study suggests that fish oil has only minor effects on hepatic lipid metabolism, which are non-critical with respect to milk production in sows.

  6. PDH regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian

    is determined by the overall content / activity of the regulatory proteins PDH kinase (PDK), of which there are 4 isoforms, and PDH phosphatase (PDP), of which there are 2 isoforms. The overall aim of the PhD project was to elucidate 4 issues. 1: Role of muscle type in resting and exercise-induced PDH...... in arm than leg muscles during exercise in humans may be the result of lower PDH-E1? content and not a muscle type dependent difference in PDH regulation. Both low muscle glycogen and increased plasma FFA are associated with upregulation of PDK4 protein and less exercise-induced increase in PDHa activity...... in human skeletal muscle. It may be noted that the increased PDK4 protein associated with elevated plasma FFA occurs already 2 hours after different dietary intake. A week of physical inactivity (bed rest), leading to whole body glucose intolerance, does not affect muscle PDH-E1? content, or the exercise...

  7. Muscle Bioenergetic Considerations for Intrinsic Laryngeal Skeletal Muscle Physiology

    Science.gov (United States)

    Sandage, Mary J.; Smith, Audrey G.

    2017-01-01

    Purpose: Intrinsic laryngeal skeletal muscle bioenergetics, the means by which muscles produce fuel for muscle metabolism, is an understudied aspect of laryngeal physiology with direct implications for voice habilitation and rehabilitation. The purpose of this review is to describe bioenergetic pathways identified in limb skeletal muscle and…

  8. The exercised skeletal muscle: a review

    Directory of Open Access Journals (Sweden)

    Marina Marini

    2010-09-01

    Full Text Available The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.

  9. Satellite cells: the architects of skeletal muscle.

    Science.gov (United States)

    Chang, Natasha C; Rudnicki, Michael A

    2014-01-01

    The outstanding regenerative capacity of skeletal muscle is attributed to the resident muscle stem cell termed satellite cell. Satellite cells are essential for skeletal muscle regeneration as they ultimately provide the myogenic precursors that rebuild damaged muscle tissue. Satellite cells characteristically are a heterogeneous population of stem cells and committed progenitor cells. Delineation of cellular hierarchy and understanding how lineage fate choices are determined within the satellite cell population will be invaluable for the advancement of muscle regenerative therapies.

  10. Diagnosis of skeletal muscle channelopathies.

    Science.gov (United States)

    Spillane, Jennifer; Fialho, Doreen; Hanna, Michael G

    2013-11-01

    Skeletal muscle channelopathies are rare disorders of muscle membrane excitability. Their episodic nature may result in diagnostic difficulty and delays in diagnosis. Advances in diagnostic clinical electrophysiology combined with DNA-based diagnosis have improved diagnostic accuracy and efficiency. Ascribing pathogenic status to identified genetic variants in muscle channel genes may be complex and functional analysis, including molecular expression, may help with this. Accurate clinical and genetic diagnosis enables genetic counselling, advice regarding prognosis and aids treatment selection. An approach to accurate and efficient diagnosis is outlined. The importance of detailed clinical evaluation including careful history, examination and family history is emphasised. The role of specialised electrodiagnostics combined with DNA testing and molecular expression is considered. New potential biomarkers including muscle MRI using MRC Centre protocols are discussed. A combined diagnostic approach using careful clinical assessment, specialised neurophysiology and DNA testing will now achieve a clear diagnosis in most patients with muscle channelopathies. An accurate diagnosis enables genetic counselling and provides information regarding prognosis and treatment selection. Genetic analysis often identifies new variants of uncertain significance. In this situation, functional expression studies as part of a diagnostic service will enable determination of pathogenic status of novel genetic variants.

  11. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M

    2016-01-01

    caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial...... respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle....

  12. Sympathetic actions on the skeletal muscle.

    Science.gov (United States)

    Roatta, Silvestro; Farina, Dario

    2010-01-01

    The sympathetic nervous system (SNS) modulates several functions in skeletal muscle fibers, including metabolism, ionic transport across the membrane, and contractility. These actions, together with the sympathetic control of other organ systems, support intense motor activity. However, some SNS actions on skeletal muscles may not always be functionally advantageous. Implications for motor control and sport performance are discussed.

  13. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I

    2014-01-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac......, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), psmooth muscle (222±13; 115±2; 48±2 umol•g(-1)•min(-1), p

  14. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

    2012-01-01

    and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma......Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin...

  15. Redox control of skeletal muscle atrophy.

    Science.gov (United States)

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J

    2016-09-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

  16. Channelopathies of skeletal muscle excitability

    Science.gov (United States)

    Cannon, Stephen C.

    2016-01-01

    Familial disorders of skeletal muscle excitability were initially described early in the last century and are now known to be caused by mutations of voltage-gated ion channels. The clinical manifestations are often striking, with an inability to relax after voluntary contraction (myotonia) or transient attacks of severe weakness (periodic paralysis). An essential feature of these disorders is fluctuation of symptoms that are strongly impacted by environmental triggers such as exercise, temperature, or serum K+ levels. These phenomena have intrigued physiologists for decades, and in the past 25 years the molecular lesions underlying these disorders have been identified and mechanistic studies are providing insights for therapeutic strategies of disease modification. These familial disorders of muscle fiber excitability are “channelopathies” caused by mutations of a chloride channel (ClC-1), sodium channel (NaV1.4), calcium channel (CaV1.1) and several potassium channels (Kir2.1, Kir2.6, Kir3.4). This review provides a synthesis of the mechanistic connections between functional defects of mutant ion channels, their impact on muscle excitability, how these changes cause clinical phenotypes, and approaches toward therapeutics. PMID:25880512

  17. Channelopathies of skeletal muscle excitability.

    Science.gov (United States)

    Cannon, Stephen C

    2015-04-01

    Familial disorders of skeletal muscle excitability were initially described early in the last century and are now known to be caused by mutations of voltage-gated ion channels. The clinical manifestations are often striking, with an inability to relax after voluntary contraction (myotonia) or transient attacks of severe weakness (periodic paralysis). An essential feature of these disorders is fluctuation of symptoms that are strongly impacted by environmental triggers such as exercise, temperature, or serum K(+) levels. These phenomena have intrigued physiologists for decades, and in the past 25 years the molecular lesions underlying these disorders have been identified and mechanistic studies are providing insights for therapeutic strategies of disease modification. These familial disorders of muscle fiber excitability are "channelopathies" caused by mutations of a chloride channel (ClC-1), sodium channel (NaV1.4), calcium channel (CaV1.1), and several potassium channels (Kir2.1, Kir2.6, and Kir3.4). This review provides a synthesis of the mechanistic connections between functional defects of mutant ion channels, their impact on muscle excitability, how these changes cause clinical phenotypes, and approaches toward therapeutics. © 2015 American Physiological Society.

  18. [Molecular mechanisms of skeletal muscle hypertrophy].

    Science.gov (United States)

    Astratenkova, I V; Rogozkin, V A

    2014-06-01

    Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

  19. [In vitro construction of skeletal muscle tissues.

    Science.gov (United States)

    Morimoto, Yuya; Takeuchi, Shoji

    In conventional culture methods using culture dishes, myotubes formed by fusion of myoblasts adhere to the surface of the culture dishes. Because the adherence causes interruption of myotube contractions and immobilization of myotubes from the culture dishes, the conventional culture methods have limitations to applications of the myotubes into drug developments and medical treatments. In order to avoid their adherence, many researchers have proposed in vitro construction of skeletal muscle tissues which both ends are fixed to anchors. The skeletal muscle tissues achieve their contractions freely according to electrical stimulations or optical stimulations, and transfer of them to other experimental setup by releasing them form the anchors. By combining the skeletal muscle tissues with force sensors, the skeletal muscle tissues are available to drug screening tests based on contractile force as a functional index. Furthermore, survival of the skeletal muscle tissues are demonstrated by implantation of them to animals. Thus, in vitro constructed skeletal muscle tissues is now recognized as attractive tools in medical fields. This review will summarize fabrication methods, properties and medical applicability of the skeletal muscle tissues.

  20. Fish muscle: the exceptional case of Notothenioids.

    Science.gov (United States)

    Fernández, Daniel A; Calvo, Jorge

    2009-03-01

    Fish skeletal muscle is an excellent model for studying muscle structure and function, since it has a very well-structured arrangement with different fiber types segregated in the axial and pectoral fin muscles. The morphological and physiological characteristics of the different muscle fiber types have been studied in several teleost species. In fish muscle, fiber number and size varies with the species considered, limiting fish maximum final length due to constraints in metabolites and oxygen diffusion. In this work, we analyze some special characteristics of the skeletal muscle of the suborder Notothenioidei. They experienced an impressive radiation inside Antarctic waters, a stable and cold environment that could account for some of their special characteristics. The number of muscle fibers is very low, 12,700-164,000, in comparison to 550,000-1,200,000 in Salmo salar of similar sizes. The size of the fibers is very large, reaching 600 microm in diameter, while for example Salmo salar of similar sizes have fibers of 220 microm maximum diameter. Evolutionary adjustment in cell cycle length for working at low temperature has been shown in Harpagifer antarcticus (111 h at 0 degrees C), when compared to the closely related sub-Antarctic species Harpagifer bispinis (150 h at 5 degrees C). Maximum muscle fiber number decreases towards the more derived notothenioids, a trend that is more related to phylogeny than to geographical distribution (and hence water temperature), with values as low as 3,600 in Harpagifer bispinis. Mitochondria volume density in slow muscles of notothenioids is very high (reaching 0.56) and since maximal rates of substrate oxidation by mitochondria is not enhanced, at least in demersal notothenioids, volume density is the only means of overcoming thermal constraints on oxidative capacity. In brief, some characteristics of the muscles of notothenioids have an apparent phylogenetic component while others seem to be adaptations to low temperature.

  1. Skeletal muscle regeneration in cancer cachexia.

    Science.gov (United States)

    Bossola, Maurizio; Marzetti, Emanuele; Rosa, Fausto; Pacelli, Fabio

    2016-05-01

    Muscle wasting is the most important phenotypic and clinical feature of cancer cachexia, and the principal cause of impaired physical function, fatigue, and respiratory complications. Muscle loss has been attributed to a variable combination of reduced nutritional intake and an imbalance between anabolic and catabolic processes. It has been suggested that defective skeletal muscle regeneration may also contribute to muscle wasting in cancer patients. However, there is little in vitro or in vivo data available, in either animals or in humans, regarding skeletal muscle regeneration in cancer wasting. The aim of the present review is to define the role of skeletal muscle regeneration in the muscle wasting of cancer patients and to determine possible therapeutic implications.

  2. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  3. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B

    2013-01-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we...... analyze the ability of skeletal muscle to respire lactate by using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from vastus lateralis muscle in 16 human subjects. Samples were...... of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within...

  4. Inflammation induced loss of skeletal muscle.

    Science.gov (United States)

    Londhe, Priya; Guttridge, Denis C

    2015-11-01

    Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".

  5. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  6. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik A.

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  7. Advances and challenges in skeletal muscle angiogenesis

    DEFF Research Database (Denmark)

    Olfert, I Mark; Baum, Oliver; Hellsten, Ylva

    2016-01-01

    during health, but poorly controlled in disease - resulting in either excessive capillary growth (pathological angiogenesis) or losses in capillarity (rarefaction). Given that skeletal muscle comprises nearly 40% of body mass in humans, skeletal muscle capillary density has a significant impact...... on metabolism, endocrine function, and locomotion, and is tightly regulated at many different levels. Skeletal muscle is also high adaptable, and thus one of the few organ systems which can be experimentally manipulated (e.g. by exercise) to study physiologic regulation of angiogenesis. This review will focus...... on 1) the methodological concerns that have arisen in determining skeletal muscle capillarity, and 2) highlight the concepts that are reshaping our understanding of the angio-adaptation process. We also summarize selected new findings (physical influences, molecular changes and ultrastructural...

  8. Engineering skeletal muscle tissue in bioreactor systems

    Institute of Scientific and Technical Information of China (English)

    An Yang; Li Dong

    2014-01-01

    Objective To give a concise review of the current state of the art in tissue engineering (TE) related to skeletal muscle and kinds of bioreactor environment.Data sources The review was based on data obtained from the published articles and guidelines.Study selection A total of 106 articles were selected from several hundred original articles or reviews.The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of engineered muscle tissue in bioreactor.Results Skeletal muscle TE is a promising interdisciplinary field which aims at the reconstruction of skeletal muscle loss.Although numerous studies have indicated that engineering skeletal muscle tissue may be of great importance in medicine in the near future,this technique still represents a limited degree of success.Since tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen,carbon dioxide,nutrients and waste products.Moreover,functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural calls.Third,in order to engineer muscle tissue successfully,it may be beneficial to mimic the in vivo environment of muscle through association with adequate stimuli from bioreactors.Conclusion Vascular system and bioreactors are necessary for development and maintenance of engineered muscle in order to provide circulation within the construct.

  9. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  10. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  11. Aspects of skeletal muscle modelling.

    Science.gov (United States)

    Epstein, Marcelo; Herzog, Walter

    2003-09-29

    The modelling of skeletal muscle raises a number of philosophical questions, particularly in the realm of the relationship between different possible levels of representation and explanation. After a brief incursion into this area, a list of desiderata is proposed as a guiding principle for the construction of a viable model, including: comprehensiveness, soundness, experimental consistency, predictive ability and refinability. Each of these principles is illustrated by means of simple examples. The presence of internal constraints, such as incompressibility, may lead to counterintuitive results. A one-panel example is exploited to advocate the use of the principle of virtual work as the ideal tool to deal with these situations. The question of stability in the descending limb of the force-length relation is addressed and a purely mechanical analogue is suggested. New experimental results confirm the assumption that fibre stiffness is positive even in the descending limb. The indeterminacy of the force-sharing problem is traditionally resolved by optimizing a, presumably, physically meaningful target function. After presenting some new results in this area, based on a separation theorem, it is suggested that a more fundamental approach to the problem is the abandoning of optimization criteria in favour of an explicit implementation of activation criteria.

  12. How sex hormones promote skeletal muscle regeneration.

    Science.gov (United States)

    Velders, Martina; Diel, Patrick

    2013-11-01

    Skeletal muscle regeneration efficiency declines with age for both men and women. This decline impacts on functional capabilities in the elderly and limits their ability to engage in regular physical activity and to maintain independence. Aging is associated with a decline in sex hormone production. Therefore, elucidating the effects of sex hormone substitution on skeletal muscle homeostasis and regeneration after injury or disuse is highly relevant for the aging population, where sarcopenia affects more than 30 % of individuals over 60 years of age. While the anabolic effects of androgens are well known, the effects of estrogens on skeletal muscle anabolism have only been uncovered in recent times. Hence, the purpose of this review is to provide a mechanistic insight into the regulation of skeletal muscle regenerative processes by both androgens and estrogens. Animal studies using estrogen receptor (ER) antagonists and receptor subtype selective agonists have revealed that estrogens act through both genomic and non-genomic pathways to reduce leukocyte invasion and increase satellite cell numbers in regenerating skeletal muscle tissue. Although animal studies have been more conclusive than human studies in establishing a role for sex hormones in the attenuation of muscle damage, data from a number of recent well controlled human studies is presented to support the notion that hormonal therapies and exercise induce added positive effects on functional measures and lean tissue mass. Based on the fact that aging human skeletal muscle retains the ability to adapt to exercise with enhanced satellite cell activation, combining sex hormone therapies with exercise may induce additive effects on satellite cell accretion. There is evidence to suggest that there is a 'window of opportunity' after the onset of a hypogonadal state such as menopause, to initiate a hormonal therapy in order to achieve maximal benefits for skeletal muscle health. Novel receptor subtype selective

  13. PLASTICITY OF SKELETAL MUSCLE STUDIED BY STEREOLOGY

    Directory of Open Access Journals (Sweden)

    Ida Eržen

    2011-05-01

    Full Text Available The present contribution provides an overview of stereological methods applied in the skeletal muscle research at the Institute of Anatomy of the Medical Faculty in Ljubljana. Interested in skeletal muscle plasticity we studied three different topics: (i expression of myosin heavy chain isoforms in slow and fast muscles under experimental conditions, (ii frequency of satellite cells in young and old human and rat muscles and (iii capillary supply of rat fast and slow muscles. We analysed the expression of myosin heavy chain isoforms within slow rat soleus and fast extensor digitorum longus muscles after (i homotopic and heterotopic transplantation of both muscles, (ii low frequency electrical stimulation of the fast muscle and (iii transposition of the fast nerve to the slow muscle. The models applied were able to turn the fast muscle into a completely slow muscle, but not vice versa. One of the indicators for the regenerative potential of skeletal muscles is its satellite cell pool. The estimated parameters, number of satellite cells per unit fibre length, corrected to the reference sarcomere length (Nsc/Lfib and number of satellite cells per number of nuclei (myonuclei and satellite cell nuclei (Nsc/Nnucl indicated that the frequency of M-cadherin stained satellite cells declines in healthy old human and rat muscles compared to young muscles. To access differences in capillary densities among slow and fast muscles and slow and fast muscle fibres, we have introduced Slicer and Fakir methods, and tested them on predominantly slow and fast rat muscles. Discussing three different topics that require different approach, the present paper reflects the three decades of the development of stereological methods: 2D analysis by simple point counting in the 70's, the disector in the 80's and virtual spatial probes in the 90's. In all methods the interactive computer assisted approach was utilised.

  14. Skeletal muscle development and regeneration.

    NARCIS (Netherlands)

    Grefte, S.; Kuijpers-Jagtman, A.M.; Torensma, R.; Hoff, J.W. Von den

    2007-01-01

    In the late stages of muscle development, a unique cell population emerges that is a key player in postnatal muscle growth and muscle regeneration. The location of these cells next to the muscle fibers triggers their designation as satellite cells. During the healing of injured muscle tissue, satell

  15. Skeletal muscle development and regeneration.

    NARCIS (Netherlands)

    Grefte, S.; Kuijpers-Jagtman, A.M.; Torensma, R.; Hoff, J.W. Von den

    2007-01-01

    In the late stages of muscle development, a unique cell population emerges that is a key player in postnatal muscle growth and muscle regeneration. The location of these cells next to the muscle fibers triggers their designation as satellite cells. During the healing of injured muscle tissue,

  16. Vasodilatory mechanisms in contracting skeletal muscle

    DEFF Research Database (Denmark)

    Clifford, Philip S.; Hellsten, Ylva

    2004-01-01

    Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vasoactive substances. Muscle blood flow is increased within the first second after a single contraction...... and stabilizes within 30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise...

  17. The Human Skeletal Muscle Proteome Project

    DEFF Research Database (Denmark)

    Gonzalez-Freire, Marta; Semba, Richard D.; Ubaida-Mohien, Ceereena

    2017-01-01

    Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of ‘sarcopenia’, a condition that impairs mobility, challenges autonomy, and is a risk...... factor for mortality. The mechanisms leading to sarcopenia as well as myopathies are still little understood. The Human Skeletal Muscle Proteome Project was initiated with the aim to characterize muscle proteins and how they change with ageing and disease. We conducted an extensive review...... of the literature and analysed publically available protein databases. A systematic search of peer-reviewed studies was performed using PubMed. Search terms included ‘human’, ‘skeletal muscle’, ‘proteome’, ‘proteomic(s)’, and ‘mass spectrometry’, ‘liquid chromatography-mass spectrometry (LC-MS/MS)’. A catalogue...

  18. Skeletal muscle as an immunogenic organ

    DEFF Research Database (Denmark)

    Nielsen, Søren; Pedersen, Bente Klarlund

    2008-01-01

    During the past few years, a possible link between skeletal muscle contractile activity and immune changes has been established. This concept is based on the finding that exercise provokes an increase in a number of cytokines. We have suggested that cytokines and other peptides that are produced......; expressed and released by muscle fibers and exert either paracrine or endocrine effects should be classified as 'myokines'. Human skeletal muscle has the capacity to express several myokines belonging to distinct different cytokine classes and contractile activity plays a role in regulating the expression...... of cytokines in skeletal muscle. In the present review, we focus on the myokines interleukin (IL)-6, IL-8 and IL-15 and their possible anti-inflammatory, immunoregulatory and metabolic roles....

  19. The benefits of coffee on skeletal muscle.

    Science.gov (United States)

    Dirks-Naylor, Amie J

    2015-12-15

    Coffee is consumed worldwide with greater than a billion cups of coffee ingested every day. Epidemiological studies have revealed an association of coffee consumption with reduced incidence of a variety of chronic diseases as well as all-cause mortality. Current research has primarily focused on the effects of coffee or its components on various organ systems such as the cardiovascular system, with relatively little attention on skeletal muscle. Summary of current literature suggests that coffee has beneficial effects on skeletal muscle. Coffee has been shown to induce autophagy, improve insulin sensitivity, stimulate glucose uptake, slow the progression of sarcopenia, and promote the regeneration of injured muscle. Much more research is needed to reveal the full scope of benefits that coffee consumption may exert on skeletal muscle structure and function.

  20. Role of skeletal muscle in lung development.

    Science.gov (United States)

    Baguma-Nibasheka, Mark; Gugic, Dijana; Saraga-Babic, Mirna; Kablar, Boris

    2012-07-01

    Skeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia. We employed various genetically engineered mice lacking different groups of respiratory muscles or lacking all the skeletal muscle and established the criteria for pulmonary hypoplasia in mice, and therefore established a mouse model for this disease. We followed up this discovery with systematic subtractive microarray analysis approach and revealed novel functions in lung development and disease for several molecules. We believe that our approach combines elements of both in vivo and in vitro approaches and allows us to study the function of a series of molecules in the context of lung development and disease and, simultaneously, in the context of lung's dependence on skeletal muscle-executed FBMs.

  1. Gene Regions Responding to Skeletal Muscle Atrophy

    Science.gov (United States)

    Booth, Frank W.

    1997-01-01

    Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

  2. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole...

  3. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    NARCIS (Netherlands)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal mus

  4. Mechanotransduction pathways in skeletal muscle hypertrophy.

    Science.gov (United States)

    Yamada, André Katayama; Verlengia, Rozangela; Bueno Junior, Carlos Roberto

    2012-02-01

    In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process.

  5. YAP-mediated mechanotransduction in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Martina eFischer

    2016-02-01

    Full Text Available Skeletal muscle is not only translating chemical energy into mechanical work, it is also a highly adaptive and regenerative tissue whose architecture and functionality is determined by its mechanical and physical environment. Processing intra- and extracellular mechanical signaling cues contributes to the regulation of cell growth, survival, migration and differentiation. Yes-associated Protein (YAP, a transcriptional coactivator downstream of the Hippo pathway and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, were recently found to play a key role in mechanotransduction in various tissues including skeletal muscle. Furthermore, YAP/TAZ modulate myogenesis and muscle regeneration and abnormal YAP activity has been reported in muscular dystrophy and rhabdomyosarcoma. Here, we summarize the current knowledge of mechanosensing and -signaling in striated muscle. We highlight the role of YAP signaling and discuss the different routes and hypotheses of its regulation in the context of mechanotransduction.

  6. Spot light on skeletal muscles: optogenetic stimulation to understand and restore skeletal muscle function.

    Science.gov (United States)

    van Bremen, Tobias; Send, Thorsten; Sasse, Philipp; Bruegmann, Tobias

    2017-09-16

    Damage of peripheral nerves results in paralysis of skeletal muscle. Currently, the only treatment option to restore proper function is electrical stimulation of the innervating nerve or of the skeletal muscles directly. However this approach has low spatial and temporal precision leading to co-activation of antagonistic muscles and lacks cell-type selectivity resulting in pain or discomfort by stimulation of sensible nerves. In contrast to electrical stimulation, optogenetic methods enable spatially confined and cell-type selective stimulation of cells expressing the light sensitive channel Channelrhodopsin-2 with precise temporal control over the membrane potential. Herein we summarize the current knowledge about the use of this technology to control skeletal muscle function with the focus on the direct, non-neuronal stimulation of muscle fibers. The high temporal flexibility of using light pulses allows new stimulation patterns to investigate skeletal muscle physiology. Furthermore, the high spatial precision of focused illumination was shown to be beneficial for selective stimulation of distinct nearby muscle groups. Finally, the cell-type specific expression of the light-sensitive effector proteins in muscle fibers will allow pain-free stimulation and open new options for clinical treatments. Therefore, we believe that direct optogenetic stimulation of skeletal muscles is a very potent method for basic scientists that also harbors several distinct advantages over electrical stimulation to be considered for clinical use in the future.

  7. Oxidative proteome alterations during skeletal muscle ageing

    Directory of Open Access Journals (Sweden)

    Sofia Lourenço dos Santos

    2015-08-01

    Full Text Available Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

  8. Tissue engineering skeletal muscle for orthopaedic applications

    Science.gov (United States)

    Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

    2002-01-01

    With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

  9. Training induced adaptation in horse skeletal muscle

    NARCIS (Netherlands)

    Dam, K.G. van

    2006-01-01

    It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transp

  10. Skeletal muscle metastasis from uterine leiomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, J.M.; Brennan, D.D.; Taylor, D.H.; Eustace, S.J. [Cappagh National Orthopaedic Hospital, Department of Radiology, Dublin (Ireland); Holloway, D.P.; O' Keane, J.C. [Cappagh National Orthopaedic Hospital, Department of Pathology, Dublin (Ireland); Hurson, B. [Cappagh National Orthopaedic Hospital, Department of Orthopaedics, Dublin (Ireland)

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature. (orig.)

  11. Skeletal muscle metastasis from uterine leiomyosarcoma.

    Science.gov (United States)

    O'Brien, J M; Brennan, D D; Taylor, D H; Holloway, D P; Hurson, B; O'Keane, J C; Eustace, S J

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature.

  12. Cellular Players in Skeletal Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    Laura Cristina Ceafalan

    2014-01-01

    Full Text Available Skeletal muscle, a tissue endowed with remarkable endogenous regeneration potential, is still under focused experimental investigation mainly due to treatment potential for muscle trauma and muscular dystrophies. Resident satellite cells with stem cell features were enthusiastically described quite a long time ago, but activation of these cells is not yet controlled by any medical interventions. However, after thorough reports of their existence, survival, activation, and differentiation there are still many questions to be answered regarding the intimate mechanism of tissue regeneration. This review delivers an up-to-date inventory of the main known key players in skeletal muscle repair, revealed by various models of tissue injuries in mechanical trauma, toxic lesions, and muscular dystrophy. A better understanding of the spatial and temporal relationships between various cell populations, with different physical or paracrine interactions and phenotype changes induced by local or systemic signalling, might lead to a more efficient approach for future therapies.

  13. Regulation of PDH, GS and insulin signalling in skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    as decreased protein level of HKII and GLUT4 in skeletal muscle. Iαn addition, the ability of acute exercise to increase insulin-stimulated glucose extraction was maintained after 7 days of bed rest. However, acute exercise after bed rest did not fully normalize the ability of skeletal muscle to extract....... Study IV demonstrated that an IL-6 injection reduced PDHa activity in skeletal muscle from fed mice and increased the PDHa activity in skeletal muscle from fasted mice without any change in phosphorylation level. An IL-6 injection increased AMPK and ACC phosphorylation in mouse skeletal muscle only...... with physical inactivity in humans, and physical inactivity did not affect the ability of exercise to enhance insulinmediated skeletal muscle glucose extraction. 2) Exercise training-improved glucose handling in aged human skeletal muscle was associated with increased content of key proteins in glucose...

  14. Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications

    Science.gov (United States)

    Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu

    2014-01-01

    Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined. PMID:24320971

  15. Engineering vascularized skeletal muscle tissue

    NARCIS (Netherlands)

    Levenberg, Shulamit; Rouwkema, Jeroen; Macdonald, Mara; Garfein, Evan S.; Kohane, Daniel S.; Darland, Diane C.; Marini, Robert; van Blitterswijk, Clemens; Mulligan, Richard C.; D'Amore, Patricia A.; Langer, Robert

    2005-01-01

    One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe

  16. Wave biomechanics of the skeletal muscle

    Science.gov (United States)

    Rudenko, O. V.; Sarvazyan, A. P.

    2006-12-01

    Results of acoustic measurements in skeletal muscle are generalized. It is shown that assessment of the pathologies and functional condition of the muscular system is possible with the use of shear waves. The velocity of these waves in muscles is much smaller than the velocity of sound; therefore, a higher symmetry type is formed for them. In the presence of a preferential direction (along muscle fibers), it is characterized by only two rather than five (as in usual media with the same anisotropy) moduli of elasticity. A covariant form of the corresponding wave equation is presented. It is shown that dissipation properties of skeletal muscles can be controlled by contracting them isometrically. Pulsed loads (shocks) and vibrations are damped differently, depending on their frequency spectrum. Characteristic frequencies on the order of tens and hundreds of hertz are attenuated due to actin-myosin bridges association/dissociation dynamics in the contracted muscle. At higher (kilohertz) frequencies, when the muscle is tensed, viscosity of the tissue increases by a factor of several tens because of the increase in friction experienced by fibrillar structures as they move relative to the surrounding liquid; the tension of the fibers changes the hydrodynamic conditions of the flow around them. Finally, at higher frequencies, the attenuation is associated with the rheological properties of biological molecules, in particular, with their conformational dynamics in the wave field. Models that describe the controlled shock dissipation mechanisms are proposed. Corresponding solutions are found, including those that allow for nonlinear effects.

  17. Exercise and the Skeletal Muscle Epigenome.

    Science.gov (United States)

    McGee, Sean L; Walder, Ken R

    2017-03-20

    An acute bout of exercise is sufficient to induce changes in skeletal muscle gene expression that are ultimately responsible for the adaptive responses to exercise. Although much research has described the intracellular signaling responses to exercise that are linked to transcriptional regulation, the epigenetic mechanisms involved are only just emerging. This review will provide an overview of epigenetic mechanisms and what is known in the context of exercise. Additionally, we will explore potential interactions between metabolism during exercise and epigenetic regulation, which serves as a framework for potential areas for future research. Finally, we will consider emerging opportunities to pharmacologically manipulate epigenetic regulators and mechanisms to induce aspects of the skeletal muscle exercise adaptive response for therapeutic intervention in various disease states.

  18. Role of skeletal muscle proteoglycans during myogenesis.

    Science.gov (United States)

    Brandan, Enrique; Gutierrez, Jaime

    2013-08-08

    Skeletal muscle formation during development and the adult mammal consists of a highly organised and regulated the sequence of cellular processes intending to form or repair muscle tissue. This sequence includes, cell proliferation, migration, and differentiation. Proteoglycans (PGs), macromolecules formed by a core protein and glycosaminoglycan chains (GAGs) present a great diversity of functions explained by their capacity to interact with different ligands and receptors forming part of their signalling complex and/or protecting them from proteolytic cleavage. Particularly attractive is the function of the different types of PGs present at the neuromuscular junction (NMJ). This review is focussed on the advances reached to understand the role of PGs during myogenesis and skeletal muscular dystrophies.

  19. Anisotropic photon migration in human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Binzoni, T [Departement de Neurosciences Fondamentales, University of Geneva (Switzerland); Department of Radiology, University Hospital, Geneva (Switzerland); Courvoisier, C [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Giust, R [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Tribillon, G [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Gharbi, T [Departement d' optique PM Duffieux, Institut FEMTO-ST, UMR CNRS 6174, Universite de Franche Comte, Besancon (France); Hebden, J C [Department of Medical Physics and Bioengineering, University College London (United Kingdom); Leung, T S [Department of Medical Physics and Bioengineering, University College London (United Kingdom); Roux, J [Hamamatsu Photonics, Grenoble (France); Delpy, D T [Department of Medical Physics and Bioengineering, University College London (United Kingdom)

    2006-03-07

    It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher ({approx}0.4) than that of travelling along a perpendicular axis ({approx}0.3) while in the adipose tissue the probability is the same ({approx}0.33) in all directions. Considering that the muscle fibre orientation is different depending on the type of muscle considered, and that inside a given skeletal muscle the orientation may change, the present findings in part might explain the intrasubject variability observed in the physiological parameters measured by near infrared spectroscopy techniques. In other words, the observed regional differences might not only be physiological differences but also optical artefacts. (note)

  20. Reactive Oxygen Species in Skeletal Muscle Signaling

    OpenAIRE

    2012-01-01

    Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also—within certain concentrations—useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria genera...

  1. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic enz...... interval exercise). The abundance of signaling proteins and metabolic enzymes are in most cases different in type I and type II muscle fibers, indicating that their glucose metabolism is different.......Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance...

  2. Calpains, skeletal muscle function and exercise.

    Science.gov (United States)

    Murphy, Robyn M

    2010-03-01

    1. Skeletal muscle fibres contain ubiquitous (mu-calpain and m-calpain) and muscle-specific (calpain-3) Ca(2+)-dependent proteases. The physiological roles of the calpains are not well understood, although ubiquitous calpains have been associated with apoptosis and myogenesis and calpain-3 is likely involved in sarcomeric remodelling. A defect in the expression of calpain-3 results in limb-girdle muscular dystrophy Type 2A. 2. At resting [Ca(2+)](i), calpains are present predominantly in their full-length, unautolysed/unactivated forms. Once activated, mu-calpain and calpain-3 appear in their autolysed forms and this measurement can be used to determine when in vivo activation occurs. Endogenously expressed mu-calpain and calpain-3 are activated within a physiological [Ca(2+)] range in a Ca(2+)- and time-dependent manner. 3. In skeletal muscle, mu-calpain is a freely diffusible protein that binds rapidly when [Ca(2+)](i) is increased. Calpain-3 is tightly bound in skeletal muscle fibres at the N2A line of the large elastic protein titin. 4. Overall, neither mu-calpain nor calpain-3 are activated immediately following sprint, endurance or eccentric exercise, despite the frequent episodes of high cytoplasmic [Ca(2+)] that would occur during these types of muscle contractions. Importantly, however, a substantial proportion of calpain-3, but not mu-calpain, is activated 24 h after a single bout of eccentric exercise. 5. In vitro studies have shown that calpain-3 becomes activated if exposed for a prolonged period of time (> 1 h) to resting cytoplasmic [Ca(2+)] that are approximately two- to fourfold higher than normal. This suggests that the small but sustained increase in [Ca(2+)](i) that likely occurs after eccentric contractions is both high and long enough to result in calpain-3 activation and supports the role for calpain-3 in sarcomeric remodelling.

  3. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  4. 3D Cell Printing of Functional Skeletal Muscle Constructs Using Skeletal Muscle-Derived Bioink.

    Science.gov (United States)

    Choi, Yeong-Jin; Kim, Taek Gyoung; Jeong, Jonghyeon; Yi, Hee-Gyeong; Park, Ji Won; Hwang, Woonbong; Cho, Dong-Woo

    2016-10-01

    Engineered skeletal muscle tissues that mimic the structure and function of native muscle have been considered as an alternative strategy for the treatment of various muscular diseases and injuries. Here, it is demonstrated that 3D cell-printing of decellularized skeletal muscle extracellular matrix (mdECM)-based bioink facilitates the fabrication of functional skeletal muscle constructs. The cellular alignment and the shape of the tissue constructs are controlled by 3D cell-printing technology. mdECM bioink provides the 3D cell-printed muscle constructs with a myogenic environment that supports high viability and contractility as well as myotube formation, differentiation, and maturation. More interestingly, the preservation of agrin is confirmed in the mdECM, and significant increases in the formation of acetylcholine receptor clusters are exhibited in the 3D cell-printed muscle constructs. In conclusion, mdECM bioink and 3D cell-printing technology facilitate the mimicking of both the structural and functional properties of native muscle and hold great promise for producing clinically relevant engineered muscle for the treatment of muscular injuries.

  5. GLUT-3 expression in human skeletal muscle

    Science.gov (United States)

    Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

    2000-01-01

    Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

  6. Small teleost fish provide new insights into human skeletal diseases.

    Science.gov (United States)

    Witten, P E; Harris, M P; Huysseune, A; Winkler, C

    2017-01-01

    Small teleost fish such as zebrafish and medaka are increasingly studied as models for human skeletal diseases. Efficient new genome editing tools combined with advances in the analysis of skeletal phenotypes provide new insights into fundamental processes of skeletal development. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. Several unique features of the skeleton relate to the extremely small size of early fish embryos and the small size of adult fish used as models. A detailed analysis of the plethora of interesting skeletal phenotypes in zebrafish and medaka pushes available skeletal imaging techniques to their respective limits and promotes the development of new imaging techniques. Impressive numbers of zebrafish and medaka mutants with interesting skeletal phenotypes have been characterized, complemented by transgenic zebrafish and medaka lines. The advent of efficient genome editing tools, such as TALEN and CRISPR/Cas9, allows to introduce targeted deficiencies in genes of model teleosts to generate skeletal phenotypes that resemble human skeletal diseases. This review will also discuss other attractive aspects of the teleost skeleton. This includes the capacity for lifelong tooth replacement and for the regeneration of dermal skeletal elements, such as scales and fin rays, which further increases the value of zebrafish and medaka models for skeletal research. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Role of microRNAs in skeletal muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Keisuke eHitachi

    2014-01-01

    Full Text Available Skeletal muscle comprises approximately 40% of body weight, and is important for locomotion, as well as for metabolic homeostasis. Adult skeletal muscle mass is maintained by a fine balance between muscle protein synthesis and degradation. In response to cytokines, nutrients, and mechanical stimuli, skeletal muscle mass is increased (hypertrophy, whereas skeletal muscle mass is decreased (atrophy in a variety of conditions, including cancer cachexia, starvation, immobilization, aging, and neuromuscular disorders. Recent studies have determined two important signaling pathways involved in skeletal muscle mass. The insulin-like growth factor-1 (IGF-1/Akt pathway increases skeletal muscle mass via stimulation of protein synthesis and inhibition of protein degradation. By contrast, myostatin signaling negatively regulates skeletal muscle mass by reducing protein synthesis. In addition, the discovery of microRNAs as novel regulators of gene expression has provided new insights into a multitude of biological processes, especially in skeletal muscle physiology. We summarize here the current knowledge of microRNAs in the regulation of skeletal muscle hypertrophy, focusing on the IGF-1/Akt pathway and myostatin signaling.

  8. Regulation of PDH, GS and insulin signalling in skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    The aims of the present thesis were to investigate 1) The impact of physical inactivity on insulinstimulated Akt, TBC1D4 and GS regulation in human skeletal muscle, 2) The impact of exercise training on glucose-mediated regulation of PDH and GS in skeletal muscle in elderly men, 3) The impact...... of inflammation on resting and exercise-induced PDH regulation in human skeletal muscle and 4) The effect of IL-6 on PDH regulation in mouse skeletal muscle. Study I demonstrated that bed rest–induced insulin resistance was associated with reduced insulinstimulated GS activity and Akt signaling as well...... as decreased protein level of HKII and GLUT4 in skeletal muscle. Iαn addition, the ability of acute exercise to increase insulin-stimulated glucose extraction was maintained after 7 days of bed rest. However, acute exercise after bed rest did not fully normalize the ability of skeletal muscle to extract...

  9. Contractile Properties of Esophageal Striated Muscle: Comparison with Cardiac and Skeletal Muscles in Rats

    Directory of Open Access Journals (Sweden)

    Takahiko Shiina

    2010-01-01

    Full Text Available The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis.

  10. Differential adenosine sensitivity of diaphragm and skeletal muscle arterioles.

    Science.gov (United States)

    Aaker, Aaron; Laughlin, M H

    2002-09-01

    The hyperemic response in exercising skeletal muscle is dependent on muscle fiber-type composition and fiber recruitment patterns, but the vascular control mechanisms producing exercise hyperemia in skeletal muscle remain poorly understood. The purpose of this study was to test the hypothesis that arterioles from white, low-oxidative skeletal muscle are less responsive to adenosine-induced dilation than are arterioles from diaphragm (Dia) and red, high-oxidative skeletal muscle. Second-order arterioles (2As) were isolated from the white portion of gastrocnemius muscle (WG; low-oxidative, fast-twitch muscle tissue) and two types of high-oxidative skeletal muscle [Dia and red portion of gastrocnemius muscle (RG)] of rats. Results reveal that 2As from all three types of muscle dilated in response to the endothelium-dependent dilator acetylcholine (WG: 48 +/- 3%, Dia: 51 +/- 3%, RG: 74 +/- 3%). In contrast, adenosine dilated only 2As from WG (48 +/- 4%) and Dia (46 +/- 5%) but not those from RG (5 +/- 5%). Thus adenosine-induced dilator responses differed among 2As of these different types of muscle tissue. However, the results do not support our hypothesis because 2As from Dia and WG dilated in response to adenosine, whereas 2As from RG did not. We conclude that the adenosine responsiveness of 2As from rat skeletal muscle cannot be predicted only by the fiber-type composition or oxidative capacity of the skeletal muscle tissue wherein the arteriole lies.

  11. Measurement of skeletal muscle collagen breakdown by microdialysis

    DEFF Research Database (Denmark)

    Miller, B F; Ellis, D; Robinson, M M;

    2011-01-01

    Exercise increases the synthesis of collagen in the extracellular matrix of skeletal muscle. Breakdown of skeletal muscle collagen has not yet been determined because of technical limitations. The purpose of the present study was to use local sampling to determine skeletal muscle collagen breakdown...... collagen breakdown 17–21 h post-exercise, and our measurement of OHP using GC–MS was in agreement with traditional assays....

  12. Vascular and Skeletal Muscle Function in Gulf War Veterans Illness

    Science.gov (United States)

    2016-07-01

    Page 1 of 14 AWARD NUMBER: W81XWH-15-1-0216 TITLE: Vascular and Skeletal Muscle Function in Gulf War Veterans Illness PRINCIPAL INVESTIGATOR...30 Jun 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Vascular and Skeletal Muscle Function in Gulf War Veterans Illness 5b. GRANT NUMBER 5c...cholinesterases and acetylcholine, which could affect activity at the neuromuscular junction of skeletal muscle, muscarinic receptors affecting vascular smooth

  13. Highly extensible skeletal muscle in snakes.

    Science.gov (United States)

    Close, Matthew; Perni, Stefano; Franzini-Armstrong, Clara; Cundall, David

    2014-07-15

    Many snakes swallow large prey whole, and this process requires large displacements of the unfused tips of the mandibles and passive stretching of the soft tissues connecting them. Under these conditions, the intermandibular muscles are highly stretched but subsequently recover normal function. In the highly stretched condition we observed in snakes, sarcomere length (SL) increased 210% its resting value (SL0), and actin and myosin filaments no longer overlapped. Myofibrils fell out of register and triad alignment was disrupted. Following passive recovery, SLs returned to 82% SL0, creating a region of double-overlapping actin filaments. Recovery required recoil of intracellular titin filaments, elastic cytoskeletal components for realigning myofibrils, and muscle activation. Stretch of whole muscles exceeded that of sarcomeres as a result of extension of folded terminal tendon fibrils, stretching of extracellular elastin and independent slippage of muscle fibers. Snake intermandibular muscles thus provide a unique model of how basic components of vertebrate skeletal muscle can be modified to permit extreme extensibility.

  14. Skeletal muscle disorders of glycogenolysis and glycolysis.

    Science.gov (United States)

    Godfrey, Richard; Quinlivan, Ros

    2016-07-01

    Skeletal muscle disorders of glycogenolysis and glycolysis account for most of the conditions collectively termed glycogen storage diseases (GSDs). These disorders are rare (incidence 1 in 20,000-43,000 live births), and are caused by autosomal or X-linked recessive mutations that result in a specific enzyme deficiency, leading to the inability to utilize muscle glycogen as an energy substrate. McArdle disease (GSD V) is the most common of these disorders, and is caused by mutations in the gene encoding muscle glycogen phosphorylase. Symptoms of McArdle disease and most other related GSDs include exercise intolerance, muscle contracture, acute rhabdomyolysis, and risk of acute renal failure. Older patients may exhibit muscle wasting and weakness involving the paraspinal muscles and shoulder girdle. For patients with these conditions, engaging with exercise is likely to be beneficial. Diagnosis is frequently delayed owing to the rarity of the conditions and lack of access to appropriate investigations. A few randomized clinical trials have been conducted, some focusing on dietary modification, although the quality of the evidence is low and no specific recommendations can yet be made. The development of EUROMAC, an international registry for these disorders, should improve our knowledge of their natural histories and provide a platform for future clinical trials.

  15. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, Steen; Wright-Paradis, C; Gnaiger, E

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...

  16. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...... the role of skeletal muscle transverse tubules as potential modulators of tissue insulin responsiveness....

  17. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

    Larsen, S; Wright-Paradis, C; Gnaiger, E

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain...... functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...... loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples....

  18. Amino acids in healthy aging skeletal muscle.

    Science.gov (United States)

    Riddle, Emily S; Stipanuk, Martha H; Thalacker-Mercer, Anna E

    2016-01-01

    Life expectancy in the U.S. and globally continues to increase. Despite increased life expectancy quality of life is not enhanced, and older adults often experience chronic age-related disease and functional disability, including frailty. Additionally, changes in body composition such as the involuntary loss of skeletal muscle mass (i.e. sarcopenia) and subsequent increases in adipose tissue can augment disease and disability in this population. Furthermore, increased oxidative stress and decreased antioxidant concentrations may also lead to metabolic dysfunction in older adults. Specific amino acids, including leucine, cysteine and its derivative taurine, and arginine can play various roles in healthy aging, especially in regards to skeletal muscle health. Leucine and arginine play important roles in muscle protein synthesis and cell growth while cysteine and arginine play important roles in quenching oxidative stress. Evidence suggests that supplemental doses of each of these amino acids may improve the aging phenotype. However, additional research is required to establish the doses required to achieve positive outcomes in humans.

  19. Overexpression of SMPX in adult skeletal muscle does not change skeletal muscle fiber type or size.

    Directory of Open Access Journals (Sweden)

    Einar Eftestøl

    Full Text Available Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear.

  20. Skeletal muscle regeneration after damage by needle penetration and trauma.

    Science.gov (United States)

    McGeachie, J K

    2000-10-01

    Skeletal muscles actually surround the dento-alveolar area. However, most dentists would be unaware that they damage skeletal muscle during routine procedures. Simple puncturing of buccinator muscle during an inferior alveolar block kills thousands of fibres. What happens to muscle fibres following such trauma? Pathology texts suggest that skeletal muscle does not regenerate and is replaced by fibrous scar tissue. However, for some decades it has been recognized that muscle fibres do in fact regenerate. In the early 1960s the "satellite" cell was discovered, lying between the muscle cell membrane and the external lamina. After 30 years of intensive research it has been clearly demonstrated that satellite cells are reserve mesenchyme cells which, once the adjacent muscle fibres are damaged, proliferate and provide a new population of young muscle cells, called "myoblasts". Myoblasts rapidly produce muscle specific proteins and fuse together in long chains, called "myotubes", which mature into typical muscle fibres.

  1. Osmoregulatory processes and skeletal muscle metabolism

    Science.gov (United States)

    Boschmann, Michael; Gottschalk, Simone; Adams, Frauke; Luft, Friedrich C.; Jordan, Jens

    Prolonged microgravity during space flight is associated with a decrease in blood and extracellular volume. These changes in water and electrolyte balance might activate catabolic processes which contribute finally to the loss of muscle and bone mass and strength. Recently, we found a prompt increase that energy expenditure by about 30% in both normal and overweight men and women after drinking 500 ml water. This effect is mediated by an increased sympathetic nervous system activity, obviously secondary to stimulation of osmosensitive afferent neurons in the liver, and skeletal muscle is possibly one effector organ. Therefore, we tested the hypothesis that this thermogenic response to water is accompanied by a stimulation of aerobic glucose metabolism in skeletal muscle. To this end, 16 young healthy volunteers (8 men) were studied. After an overnight fast (12h), a microdialysis probe was implanted into the right M. quadriceps femoris vastus lateralis and subsequently perfused with Ringer's solution (+50 mM ethanol). After 1h, volunteers were asked to drink 500 ml water (22° C) followed by continuing microdialysis for another 90 min. Dialysates (15 min fractions) were analyzed for [ethanol], [glucose], [lactate], [pyruvate], and [glycerol] in order to assess changes in muscle tissue perfusion (ethanol dilution technique), glycolysis and lipolysis. Blood samples were taken and heart rate (HR) and blood pressure (BP) were monitored. Neither HR and systolic and diastolic BP, nor plasma [glucose], [lactate], [insulin], and [C peptide] changed significantly after water drinking. Also, tissue perfusion and dialysate [glucose] did not change significantly. However, dialysate [lactate] increased by about 10 and 20% and dialysate [pyruvate] by about 100 and 200% in men and women, respectively. In contrast, dialysate [glycerol] decreased by about 30 and 20% in men and women, respectively. Therefore, drinking of 500 ml water stimulates aerobic glucose metabolism and inhibits

  2. Historical Perspectives: plasticity of mammalian skeletal muscle.

    Science.gov (United States)

    Pette, D

    2001-03-01

    More than 40 years ago, the nerve cross-union experiment of Buller, Eccles, and Eccles provided compelling evidence for the essential role of innervation in determining the properties of mammalian skeletal muscle fibers. Moreover, this experiment revealed that terminally differentiated muscle fibers are not inalterable but are highly versatile entities capable of changing their phenotype from fast to slow or slow to fast. With the use of various experimental models, numerous studies have since confirmed and extended the notion of muscle plasticity. Together, these studies demonstrated that motoneuron-specific impulse patterns, neuromuscular activity, and mechanical loading play important roles in both the maintenance and transition of muscle fiber phenotypes. Depending on the type, intensity, and duration of changes in any of these factors, muscle fibers adjust their phenotype to meet the altered functional demands. Fiber-type transitions resulting from multiple qualitative and quantitative changes in gene expression occur sequentially in a regular order within a spectrum of pure and hybrid fiber types.

  3. Stretching skeletal muscle: chronic muscle lengthening through sarcomerogenesis.

    Directory of Open Access Journals (Sweden)

    Alexander M Zöllner

    Full Text Available Skeletal muscle responds to passive overstretch through sarcomerogenesis, the creation and serial deposition of new sarcomere units. Sarcomerogenesis is critical to muscle function: It gradually re-positions the muscle back into its optimal operating regime. Animal models of immobilization, limb lengthening, and tendon transfer have provided significant insight into muscle adaptation in vivo. Yet, to date, there is no mathematical model that allows us to predict how skeletal muscle adapts to mechanical stretch in silico. Here we propose a novel mechanistic model for chronic longitudinal muscle growth in response to passive mechanical stretch. We characterize growth through a single scalar-valued internal variable, the serial sarcomere number. Sarcomerogenesis, the evolution of this variable, is driven by the elastic mechanical stretch. To analyze realistic three-dimensional muscle geometries, we embed our model into a nonlinear finite element framework. In a chronic limb lengthening study with a muscle stretch of 1.14, the model predicts an acute sarcomere lengthening from 3.09[Formula: see text]m to 3.51[Formula: see text]m, and a chronic gradual return to the initial sarcomere length within two weeks. Compared to the experiment, the acute model error was 0.00% by design of the model; the chronic model error was 2.13%, which lies within the rage of the experimental standard deviation. Our model explains, from a mechanistic point of view, why gradual multi-step muscle lengthening is less invasive than single-step lengthening. It also explains regional variations in sarcomere length, shorter close to and longer away from the muscle-tendon interface. Once calibrated with a richer data set, our model may help surgeons to prevent muscle overstretch and make informed decisions about optimal stretch increments, stretch timing, and stretch amplitudes. We anticipate our study to open new avenues in orthopedic and reconstructive surgery and enhance

  4. Reduced HDAC2 in skeletal muscle of COPD patients

    National Research Council Canada - National Science Library

    Masako To; Elisabeth B Swallow; Kenich Akashi; Kosuke Haruki; S Amanda Natanek; Michael I Polkey; Kazuhiro Ito; Peter J Barnes

    2017-01-01

    Background Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated...

  5. Myofibre damage in human skeletal muscle

    DEFF Research Database (Denmark)

    Crameri, R M; Aagaard, P; Qvortrup, K

    2007-01-01

    Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in hum......Disruption to proteins within the myofibre after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation...... but not in humans using voluntary exercise. Untrained males (n=8, range 22-27 years) performed 210 maximal eccentric contractions with each leg on an isokinetic dynamometer, voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior...... to exercise and at 5, 24, 96 and 192 h postexercise. Muscle tenderness rose in VOL and ES after 24 h, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 h after exercise, but not in ES (except at 24 h). In contrast...

  6. Undulatory fish swimming : from muscles to flow

    NARCIS (Netherlands)

    Müller, U.K.; Leeuwen, van J.L.

    2006-01-01

    Undulatory swimming is employed by many fish for routine swimming and extended sprints. In this biomechanical review, we address two questions: (i) how the fish's axial muscles power swimming; and (ii) how the fish's body and fins generate thrust. Fish have adapted the morphology of their axial musc

  7. Undulatory fish swimming : from muscles to flow

    NARCIS (Netherlands)

    Müller, U.K.; Leeuwen, van J.L.

    2006-01-01

    Undulatory swimming is employed by many fish for routine swimming and extended sprints. In this biomechanical review, we address two questions: (i) how the fish's axial muscles power swimming; and (ii) how the fish's body and fins generate thrust. Fish have adapted the morphology of their axial

  8. Skeletal muscle stem cells from animals I. Basic cell biology

    Science.gov (United States)

    Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

  9. Regulation of mechano growth factor in skeletal muscle and heart

    NARCIS (Netherlands)

    Ottens, M.

    2010-01-01

    The mechano growth factor (MGF) is expressed in mechanically overloaded skeletal muscle. MGF was discovered in 1996 as an alternative splice product of the IGF-1 gene. Since then, its significance has been investigated particularly in skeletal muscle, because the local expression of MGF could

  10. Smoking-induced Skeletal Muscle Dysfunction. From Evidence to Mechanisms

    NARCIS (Netherlands)

    Degens, H.; Gayan-Ramirez, G.; Hees, H.W.H. van

    2015-01-01

    Smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from skeletal muscle dysfunction, and it has been suggested that cigarette smoke exposure contributes to the development of skeletal muscle dysfunction

  11. Current opportunities and challenges in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Koning, Merel; Harmsen, Martin C; van Luyn, Marja J A; Werker, Paul M N

    The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high

  12. Influence of age on leptin induced skeletal muscle signaling

    DEFF Research Database (Denmark)

    Guadalupe Grau, Amelia; Larsen, Steen; Guerra, Borja

    2014-01-01

    Age associated fat mass accumulation could be due to dysregulation of leptin signaling in skeletal muscle. Thus, we investigated total protein expression and phosphorylation levels of the long isoform of the leptin receptor (OB-Rb), and leptin signaling through Janus Kinase 2 (JAK2)/signal...... skeletal muscle of different age....

  13. Skeletal muscle as a gene regulatory endocrine organ

    DEFF Research Database (Denmark)

    Karstoft, Kristian; Pedersen, Bente K.

    2016-01-01

    on training status. IL-15 has been established as a cytokine mediating cross-talk between skeletal muscle and skin tissue, and decorin has been characterized as a contraction-induced myokine which apparently is differentially regulated between healthy and dysglycemic individuals. Summary Skeletal muscle...

  14. Regulation of mechano growth factor in skeletal muscle and heart

    NARCIS (Netherlands)

    Ottens, M.

    2010-01-01

    The mechano growth factor (MGF) is expressed in mechanically overloaded skeletal muscle. MGF was discovered in 1996 as an alternative splice product of the IGF-1 gene. Since then, its significance has been investigated particularly in skeletal muscle, because the local expression of MGF could provid

  15. Skeletal muscle adaptation in response to exercise(Ⅰ)

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Zhen Yan

    2004-01-01

    @@ INTRODUCTION Skeletal muscles of adult mammalian species, including humans,are the source of power for locomotion and other daily activities essential for survival. Loss of skeletal musclecontractile function is a major cause of falling,morbidity and mortality,especially in elderly populations [1]. More importantly,skeletal muscles collectively influence total body metabolism of glucose, fat and protein, abnormalities of which are associated with a variety of common diseases[2-3].

  16. Compatibility of hyaluronic acid hydrogel and skeletal muscle myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wang Wei; Zhang Li; Sun Liang; Wang Chengyue [Jinzhou Central Hospital, Jinzhou 121000 (China); Fan Ming; Liu Shuhong, E-mail: Weiwang_Ly@yahoo.com.c [Institute of Basic Medical Sciences, Academy of Military Medical Science, Beijing 100850 (China)

    2009-04-15

    Compatibility of hyaluronic acid hydrogel (HAH) and skeletal muscle myoblasts has been investigated for the first time in the present paper. Skeletal muscle myoblasts were separated from skeletons of rats and incubated with a HAH-containing culture medium. Cell morphology, hydrophilicity and cell adhesion of the HAH scaffold were investigated using optical microscopy, scanning electron microscopy, Hoechest33258 fluorescent staining, the immunocytochemistry method and water adsorption rate measurement. It was found that at a proper concentration (around 0.5%) of hyaluronic acid, the hydrogel possessed good compatibility with skeletal muscle myoblasts. The hydrogel can create a three-dimensional structure for the growth of skeletal muscle myoblasts and benefit cell attachment to provide a novel scaffold material for the tissue engineering of skeletal muscle.

  17. PGC-1α-mediated adaptations in skeletal muscle

    DEFF Research Database (Denmark)

    Olesen, Jesper; Kiilerich, Kristian; Pilegaard, Henriette

    2010-01-01

    Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each...... to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise...... multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle...

  18. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim

    2014-01-01

    . In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo...... insulin levels after 9 and 12 months, respectively, improved intra peritoneal glucose tolerance after 6 months, and a trend towards increased insulin-stimulated glucose uptake in isolated skeletal muscle. Conclusions. The data suggests that overexpression of apoB decreases skeletal muscle lipid......Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design...

  19. Omega-3 Fatty Acids and Skeletal Muscle Health.

    Science.gov (United States)

    Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee

    2015-11-19

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  20. Omega-3 Fatty Acids and Skeletal Muscle Health

    Directory of Open Access Journals (Sweden)

    Stewart Jeromson

    2015-11-01

    Full Text Available Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  1. Localization of nitric oxide synthase in human skeletal muscle

    DEFF Research Database (Denmark)

    Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

    1996-01-01

    The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...... I NO synthase immunoreactivity and NADPH diaphorase activity. Type III NO synthase immunoreactivity was observed both in the endothelium of larger vessels and of microvessels. The results establish that human skeletal muscle expresses two different constitutive isoforms of NO synthase in different...... endothelium is consistent with a role for NO in the control of blood flow in human skeletal muscle....

  2. Osteogenic sarcoma with skeletal muscle metastases

    Energy Technology Data Exchange (ETDEWEB)

    Peh, W.C.G. [Department of Diagnostic Radiology, The University of Hong Kong, Queen Mary Hospital (Hong Kong); Shek, T.W.H. [Department of Pathology, The University of Hong Kong, Queen Mary Hospital (Hong Kong); Wang Shihchang [Department of Diagnostic Imaging, National University of Singapore, National University Hospital (Singapore); Wong, J.W.K.; Chien, E.P. [Department of Orthopaedic Surgery, The University of Hong Kong, Queen Mary Hospital (Hong Kong)

    1999-05-01

    Two cases of osteogenic sarcoma with skeletal muscle metastases are described. A 40-year-old woman presented with progressive swelling of both calves and a soft tissue back lump. She had been diagnosed with mandibular chondroblastic osteogenic sarcoma 6 years earlier. Radiographs showed calcified masses. MRI scans and bone scintigraphy revealed multiple soft tissue masses in both calves. Bone scintigraphy also showed uptake in the back lump, right thigh and left lung base. Biopsy confirmed metastatic chondroblastic osteogenic sarcoma, which initially responded well to chemotherapy. However, the metastatic disease subsequently progressed rapidly and she died 21 months after presentation. The second case concerns a 20-year-old man who presented with a pathologic fracture of the humerus, which was found to be due to osteoblastic osteogenic sarcoma. He developed cerebral metastases 17 months later, followed by metastases at other sites. Calcified masses were subsequently seen on radiographs of the abdomen and chest. CT scans confirmed the presence of densely calcified muscle metastases in the abdominal wall, erector spinae and gluteal muscles. The patient`s disease progressed rapidly and he died 30 months after presentation. (orig.) With 6 figs., 29 refs.

  3. Motor endplate cholinesterase in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Fujii,Masafumi

    1982-08-01

    Full Text Available The activity and properties of cholinesterase (ChE of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.

  4. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Handberg, A; Beck-Nielsen, H

    2000-01-01

    amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation......, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...

  5. Skeletal muscle microvascular function in girls with Turner syndrome

    OpenAIRE

    West, Sarah L.; Clodagh S. O'Gorman; Alyaa H. Elzibak; Jessica Caterini; Noseworthy, Michael D; Tammy Rayner; Jill Hamilton; Wells, Greg D.

    2014-01-01

    Background: Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) s...

  6. Expression of androgen receptor target genes in skeletal muscle

    OpenAIRE

    2014-01-01

    We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR)-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (ARΔZF2 ) versus w...

  7. Skeletal muscle dedifferentiation during salamander limb regeneration.

    Science.gov (United States)

    Wang, Heng; Simon, András

    2016-10-01

    Salamanders can regenerate entire limbs throughout their life. A critical step during limb regeneration is formation of a blastema, which gives rise to the new extremity. Salamander limb regeneration has historically been tightly linked to the term dedifferentiation, however, with refined research tools it is important to revisit the definition of dedifferentiation in the context. To what extent do differentiated cells revert their differentiated phenotypes? To what extent do progeny from differentiated cells cross lineage boundaries during regeneration? How do cell cycle plasticity and lineage plasticity relate to each other? What is the relationship between dedifferentiation of specialized cells and activation of tissue resident stem cells in terms of their contribution to the new limb? Here we highlight these problems through the case of skeletal muscle.

  8. Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis.

    Science.gov (United States)

    Tierney, Matthew T; Sacco, Alessandra

    2016-06-01

    The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity.

  9. Induction of Acute Skeletal Muscle Regeneration by Cardiotoxin Injection.

    Science.gov (United States)

    Guardiola, Ombretta; Andolfi, Gennaro; Tirone, Mario; Iavarone, Francescopaolo; Brunelli, Silvia; Minchiotti, Gabriella

    2017-01-01

    Skeletal muscle regeneration is a physiological process that occurs in adult skeletal muscles in response to injury or disease. Acute injury-induced skeletal muscle regeneration is a widely used, powerful model system to study the events involved in muscle regeneration as well as the mechanisms and different players. Indeed, a detailed knowledge of this process is essential for a better understanding of the pathological conditions that lead to skeletal muscle degeneration, and it aids in identifying new targeted therapeutic strategies. The present work describes a detailed and reproducible protocol to induce acute skeletal muscle regeneration in mice through a single intramuscular injection of cardiotoxin (CTX). CTX belongs to the family of snake venom toxins and causes myolysis of myofibers, which eventually triggers the regeneration events. The dynamics of skeletal muscle regeneration is evaluated by histological analysis of muscle sections. The protocol also illustrates the experimental procedures for dissecting, freezing, and cutting the Tibialis Anterior muscle, as well as the routine Hematoxylin & Eosin staining that is widely used for subsequent morphological and morphometric analysis.

  10. A metabolic link to skeletal muscle wasting and regeneration

    Directory of Open Access Journals (Sweden)

    René eKoopman

    2014-02-01

    Full Text Available Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed ‘metabolic reprogramming’.

  11. Exercise and the Regulation of Skeletal Muscle Hypertrophy.

    Science.gov (United States)

    McGlory, Chris; Phillips, Stuart M

    2015-01-01

    Skeletal muscle is a critical organ serving as the primary site for postprandial glucose disposal and the generation of contractile force. The size of human skeletal muscle mass is dependent upon the temporal relationship between changes in muscle protein synthesis (MPS) and muscle protein breakdown. The aim of this chapter is to review our current understanding of how resistance exercise influences protein turnover with a specific emphasis on the molecular factors regulating MPS. We also will discuss recent data relating to the prescription of resistance exercise to maximize skeletal muscle hypertrophy. Finally, we evaluate the impact of age and periods of disuse on the loss of muscle mass and the controversy surround the etiology of muscle disuse atrophy.

  12. Muscle Interstitial Cells: A Brief Field Guide to Non-satellite Cell Populations in Skeletal Muscle.

    Science.gov (United States)

    Tedesco, Francesco Saverio; Moyle, Louise A; Perdiguero, Eusebio

    2017-01-01

    Skeletal muscle regeneration is mainly enabled by a population of adult stem cells known as satellite cells. Satellite cells have been shown to be indispensable for adult skeletal muscle repair and regeneration. In the last two decades, other stem/progenitor cell populations resident in the skeletal muscle interstitium have been identified as "collaborators" of satellite cells during regeneration. They also appear to have a key role in replacing skeletal muscle with adipose, fibrous, or bone tissue in pathological conditions. Here, we review the role and known functions of these different interstitial skeletal muscle cell types and discuss their role in skeletal muscle tissue homeostasis, regeneration, and disease, including their therapeutic potential for cell transplantation protocols.

  13. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

    Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover......, there is now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated...... downstream of changes in intracellular Ca(2+) and energy turnover. In particular, a signaling cascade involving Ca(2+)-calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work...

  14. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  15. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  16. Arginylation of Myosin Heavy Chain Regulates Skeletal Muscle Strength

    Directory of Open Access Journals (Sweden)

    Anabelle S. Cornachione

    2014-07-01

    Full Text Available Protein arginylation is a posttranslational modification with an emerging global role in the regulation of actin cytoskeleton. To test the role of arginylation in the skeletal muscle, we generated a mouse model with Ate1 deletion driven by the skeletal muscle-specific creatine kinase (Ckmm promoter. Ckmm-Ate1 mice were viable and outwardly normal; however, their skeletal muscle strength was significantly reduced in comparison to controls. Mass spectrometry of isolated skeletal myofibrils showed a limited set of proteins, including myosin heavy chain, arginylated on specific sites. Atomic force microscopy measurements of contractile strength in individual myofibrils and isolated myosin filaments from these mice showed a significant reduction of contractile forces, which, in the case of myosin filaments, could be fully rescued by rearginylation with purified Ate1. Our results demonstrate that arginylation regulates force production in muscle and exerts a direct effect on muscle strength through arginylation of myosin.

  17. Diffuse metastatic infiltration of a carcinoma into skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Hundt, W.; Braunschweig, R.; Reiser, M. [Dept. of Diagnostic Radiology, Ludwig-Maximilians-Univ., Muenchen (Germany)

    1999-03-01

    Skeletal muscle is one of the most unusual sites of metastasis from any malignancy. We report a patient with rapidly progressive contractures due to metastatic infiltration of a carcinoma of unknown origin into the skeletal muscle. This 61-year-old man presented with a 1-month history of rapidly evolving, painful restriction of mobility of his right arm and his legs. Computed tomography showed diffuse metastatic nodules in all muscles, particularly in the hip abductors. Muscle biopsy revealed extensive infiltration of the muscle with carcinoma cells. (orig.) With 4 figs., 21 refs.

  18. AMP-Activated Protein Kinase Plays an Important Evolutionary Conserved Role in the Regulation of Glucose Metabolism in Fish Skeletal Muscle Cells

    NARCIS (Netherlands)

    Magnoni, L.J.; Vraskou, Y.; Palstra, A.P.; Planas, J.V.

    2012-01-01

    AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds tha

  19. Peripheral endocannabinoids regulate skeletal muscle development and maintenance

    Directory of Open Access Journals (Sweden)

    Dongjiao Zhao

    2010-12-01

    Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

  20. Genetic architecture of gene expression in ovine skeletal muscle

    DEFF Research Database (Denmark)

    Kogelman, Lisette Johanna Antonia; Byrne, Keren; Vuocolo, Tony

    2011-01-01

    -based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle.Results: The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing...

  1. Role of autophagy in COPD skeletal muscle dysfunction.

    Science.gov (United States)

    Hussain, Sabah N A; Sandri, Marco

    2013-05-01

    Chronic obstructive pulmonary disease (COPD) is a debilitating disease caused by parenchymal damage and irreversible airflow limitation. In addition to lung dysfunction, patients with COPD develop weight loss, malnutrition, poor exercise performance, and skeletal muscle atrophy. The latter has been attributed to an imbalance between muscle protein synthesis and protein degradation. Several reports have confirmed that enhanced protein degradation and atrophy of limb muscles of COPD patient is mediated in part through activation of the ubiquitin-proteasome pathway and that this activation is triggered by enhanced production of reactive oxygen species. Until recently, the importance of the autophagy-lysosome pathway in protein degradation of skeletal muscles has been largely ignored, however, recent evidence suggests that this pathway is actively involved in recycling of cytosolic proteins, organelles, and protein aggregates in normal skeletal muscles. The protective role of autophagy in the regulation of muscle mass has recently been uncovered in mice with muscle-specific suppression of autophagy. These mice develop severe muscle weakness, atrophy, and decreased muscle contractility. No information is yet available about the involvement of the autophagy in the regulation of skeletal muscle mass in COPD patients. Pilot experiments on vastus lateralis muscle samples suggest that the autophagy-lysosome system is induced in COPD patients compared with control subjects. In this review, we summarize recent progress related to molecular structure, regulation, and roles of the autophagy-lysosome pathway in normal and diseased skeletal muscles. We also speculate about regulation and functional importance of this system in skeletal muscle dysfunction in COPD patients.

  2. Expression of androgen receptor target genes in skeletal muscle.

    Science.gov (United States)

    Rana, Kesha; Lee, Nicole K L; Zajac, Jeffrey D; MacLean, Helen E

    2014-01-01

    We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR)-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (AR(ΔZF2)) versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR(∆ZF2) muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57(Kip2), Igf2 and calcineurin Aa, was increased in AR(∆ZF2) muscle, and the expression of all but p57(Kip2) was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

  3. Expression of androgen receptor target genes in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Kesha Rana; Nicole KL Lee; Jeffrey D Zajac; Helen E MacLean

    2014-01-01

    We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor(AR)‑regulated genes ininvitroandinvivomodels. The expression of the myogenic regulatory factormyogenin was signiifcantly decreased in skeletal muscle from testosterone‑treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity(ARΔZF2) versus wildtype mice, demonstrating thatmyogenin is repressed by the androgen/AR pathway. The ubiquitin ligaseFbxo32 was repressed by 12h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, andc‑Myc expression was decreased in testosterone‑treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, Igf2 andcalcineurin Aa, was increased in AR∆ZF2 muscle, and the expression of all butp57Kip2was also decreased in testosterone‑treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase‑mediated atrophy pathways to preserve muscle mass in adult muscle.

  4. Expression of androgen receptor target genes in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Kesha Rana

    2014-10-01

    Full Text Available We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (ARΔZF2 versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57 Kip2, Igf2 and calcineurin Aa, was increased in AR∆ZF2 muscle, and the expression of all but p57 Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

  5. Skeletal Muscle Cell Induction from Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Yusaku Kodaka

    2017-01-01

    Full Text Available Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD. Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

  6. Calprotectin is released from human skeletal muscle tissue during exercise

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian

    2008-01-01

    Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained...... at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold...... in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...

  7. Skeletal Muscle Angiogenesis and Its Relation to Insulin Sensitivity

    DEFF Research Database (Denmark)

    Lindqvist, Anna Maria Charlotte K

    in skeletal muscle capillarization (17.0±2.0%; EDL and 20.1±2.4%; soleus muscle) and whole-body insulin sensitivity increased by 24.0±5.0%. In study II obese Zucker rats were transfected with a VEGF-A overexpression vector. The rats were then subjected to 30 days of swim training (over a period of 6 weeks...... mediator of angiogenesis) are reduced in insulin resistant individuals. Exercise training can improve skeletal muscle capillarization and the angiogenic potential and physical activity has also been proven to enhance muscle insulin sensitivity. Increased skeletal muscle capillarization is associated......). After the intervention period, insulin sensitivity was measured as in study I. VEGF-A transfection caused a normalization of the VEGF levels in the muscle. VEGF transfection in combination with training resulted in an increased capillarization (20.7±4.3%) and insulin-stimulated glucose uptake (124...

  8. Looking Beyond Structure: Membrane Phospholipids of Skeletal Muscle Mitochondria.

    Science.gov (United States)

    Heden, Timothy D; Neufer, P Darrell; Funai, Katsuhiko

    2016-08-01

    Skeletal muscle mitochondria are highly dynamic and are capable of tremendous expansion to meet cellular energetic demands. Such proliferation in mitochondrial mass requires a synchronized supply of enzymes and structural phospholipids. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are generated in skeletal muscle. Herein we describe how each class of phospholipids that constitute mitochondrial membranes are synthesized and/or imported, and summarize genetic evidence indicating that membrane phospholipid composition represents a significant modulator of skeletal muscle mitochondrial respiratory function. We also discuss how skeletal muscle mitochondrial phospholipids may mediate the effect of diet and exercise on oxidative metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Regulation of Metabolic Signaling in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth

    sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle...... enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance...... of human type I muscle fibers is illustrated by the finding of a positive correlation between the relative distribution of type I fibers in the muscle and whole-body insulin sensitivity. This suggests, that type I muscle fibers are more insulin sensitive than type II muscle fibers. Improved insulin...

  10. Potassium initiates vasodilatation induced by a single skeletal muscle contraction in hamster cremaster muscle

    National Research Council Canada - National Science Library

    Marika L. Armstrong; Ashok K. Dua; Coral L. Murrant

    2007-01-01

    ... + ). To test the hypothesis that K + was in part responsible for the rapid dilatation produced by muscle contraction we stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ...

  11. Structure and function of the skeletal muscle extracellular matrix.

    Science.gov (United States)

    Gillies, Allison R; Lieber, Richard L

    2011-09-01

    The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a property that has clinical manifestations and alters muscle function. Here we review the structure, composition, and mechanical properties of skeletal muscle ECM; describe the cells that contribute to the maintenance of the ECM; and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure–function relationships. Detailed structure–function relationships of the ECM have yet to be defined and, as a result, we propose areas for future study.

  12. Carboxylic ester hydrolases in mitochondria from rat skeletal muscle

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Zelander, T

    1990-01-01

    A mitochondrial pellet, prepared from rat skeletal muscle, contained a number of carboxylic ester hydrolase isoenzymes. The esterases which split alpha-naphthyl acetate were organophosphate sensitive, whereas two out of three indoxyl acetate hydrolysing enzymes were resistant to both organophosph......A mitochondrial pellet, prepared from rat skeletal muscle, contained a number of carboxylic ester hydrolase isoenzymes. The esterases which split alpha-naphthyl acetate were organophosphate sensitive, whereas two out of three indoxyl acetate hydrolysing enzymes were resistant to both...

  13. Calpain-6 deficiency promotes skeletal muscle development and regeneration.

    Directory of Open Access Journals (Sweden)

    Kazuo Tonami

    Full Text Available Calpains are Ca(2+-dependent modulator Cys proteases that have a variety of functions in almost all eukaryotes. There are more than 10 well-conserved mammalian calpains, among which eutherian calpain-6 (CAPN6 is unique in that it has amino acid substitutions at the active-site Cys residue (to Lys in humans, strongly suggesting a loss of proteolytic activity. CAPN6 is expressed predominantly in embryonic muscles, placenta, and several cultured cell lines. We previously reported that CAPN6 is involved in regulating microtubule dynamics and actin reorganization in cultured cells. The physiological functions of CAPN6, however, are still unclear. Here, to elucidate CAPN6's in vivo roles, we generated Capn6-deficient mice, in which a lacZ expression cassette was integrated into the Capn6 gene. These Capn6-deficient mouse embryos expressed lacZ predominantly in skeletal muscles, as well as in cartilage and the heart. Histological and biochemical analyses showed that the CAPN6 deficiency promoted the development of embryonic skeletal muscle. In primary cultured skeletal muscle cells that were induced to differentiate into myotubes, Capn6 expression was detected in skeletal myocytes, and Capn6-deficient cultures showed increased differentiation. Furthermore, we found that CAPN6 was expressed in the regenerating skeletal muscles of adult mice after cardiotoxin-induced degeneration. In this experimental system, Capn6-deficient mice exhibited more advanced skeletal-muscle regeneration than heterozygotes or wild-type mice at the same time point. These results collectively showed that a loss of CAPN6 promotes skeletal muscle differentiation during both development and regeneration, suggesting a novel physiological function of CAPN6 as a suppressor of skeletal muscle differentiation.

  14. Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques

    LENUS (Irish Health Repository)

    Ohlendieck, Kay

    2011-02-01

    Abstract Background Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential changes in protein clusters during physiological adaptations or pathological processes. Results Skeletal muscle proteomics attempts to establish the global identification and biochemical characterisation of all members of the muscle-associated protein complement. A considerable number of proteomic studies have employed large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography, and combined them with mass spectrometry as the method of choice for high-throughput protein identification. Muscle proteomics has been applied to the comprehensive biochemical profiling of developing, maturing and aging muscle, as well as the analysis of contractile tissues undergoing physiological adaptations seen in disuse atrophy, physical exercise and chronic muscle transformation. Biomedical investigations into proteome-wide alterations in skeletal muscle tissues were also used to establish novel biomarker signatures of neuromuscular disorders. Importantly, mass spectrometric studies have confirmed the enormous complexity of posttranslational modifications in skeletal muscle proteins. Conclusions This review critically examines the scientific impact of modern muscle proteomics and discusses its successful application for a better understanding of muscle biology, but also outlines its technical limitations and emerging techniques to establish new biomarker candidates.

  15. Resolving Shifting Patterns of Muscle Energy Use in Swimming Fish

    Science.gov (United States)

    Gerry, Shannon P.; Ellerby, David J.

    2014-01-01

    Muscle metabolism dominates the energy costs of locomotion. Although in vivo measures of muscle strain, activity and force can indicate mechanical function, similar muscle-level measures of energy use are challenging to obtain. Without this information locomotor systems are essentially a black box in terms of the distribution of metabolic energy. Although in situ measurements of muscle metabolism are not practical in multiple muscles, the rate of blood flow to skeletal muscle tissue can be used as a proxy for aerobic metabolism, allowing the cost of particular muscle functions to be estimated. Axial, undulatory swimming is one of the most common modes of vertebrate locomotion. In fish, segmented myotomal muscles are the primary power source, driving undulations of the body axis that transfer momentum to the water. Multiple fins and the associated fin muscles also contribute to thrust production, and stabilization and control of the swimming trajectory. We have used blood flow tracers in swimming rainbow trout (Oncorhynchus mykiss) to estimate the regional distribution of energy use across the myotomal and fin muscle groups to reveal the functional distribution of metabolic energy use within a swimming animal for the first time. Energy use by the myotomal muscle increased with speed to meet thrust requirements, particularly in posterior myotomes where muscle power outputs are greatest. At low speeds, there was high fin muscle energy use, consistent with active stability control. As speed increased, and fins were adducted, overall fin muscle energy use declined, except in the caudal fin muscles where active fin stiffening is required to maintain power transfer to the wake. The present data were obtained under steady-state conditions which rarely apply in natural, physical environments. This approach also has potential to reveal the mechanical factors that underlie changes in locomotor cost associated with movement through unsteady flow regimes. PMID:25165858

  16. Resolving shifting patterns of muscle energy use in swimming fish.

    Directory of Open Access Journals (Sweden)

    Shannon P Gerry

    Full Text Available Muscle metabolism dominates the energy costs of locomotion. Although in vivo measures of muscle strain, activity and force can indicate mechanical function, similar muscle-level measures of energy use are challenging to obtain. Without this information locomotor systems are essentially a black box in terms of the distribution of metabolic energy. Although in situ measurements of muscle metabolism are not practical in multiple muscles, the rate of blood flow to skeletal muscle tissue can be used as a proxy for aerobic metabolism, allowing the cost of particular muscle functions to be estimated. Axial, undulatory swimming is one of the most common modes of vertebrate locomotion. In fish, segmented myotomal muscles are the primary power source, driving undulations of the body axis that transfer momentum to the water. Multiple fins and the associated fin muscles also contribute to thrust production, and stabilization and control of the swimming trajectory. We have used blood flow tracers in swimming rainbow trout (Oncorhynchus mykiss to estimate the regional distribution of energy use across the myotomal and fin muscle groups to reveal the functional distribution of metabolic energy use within a swimming animal for the first time. Energy use by the myotomal muscle increased with speed to meet thrust requirements, particularly in posterior myotomes where muscle power outputs are greatest. At low speeds, there was high fin muscle energy use, consistent with active stability control. As speed increased, and fins were adducted, overall fin muscle energy use declined, except in the caudal fin muscles where active fin stiffening is required to maintain power transfer to the wake. The present data were obtained under steady-state conditions which rarely apply in natural, physical environments. This approach also has potential to reveal the mechanical factors that underlie changes in locomotor cost associated with movement through unsteady flow regimes.

  17. Exercise and obesity-induced insulin resistance in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Hyo-Bum Kwak

    2013-12-01

    Full Text Available The skeletal muscle in our body is a major site for bioenergetics and metabolism during exercise. Carbohydrates and fats are the primary nutrients that provide the necessary energy required to maintain cellular activities during exercise. The metabolic responses to exercise in glucose and lipid regulation depend on the intensity and duration of exercise. Because of the increasing prevalence of obesity, recent studies have focused on the cellular and molecular mechanisms of obesity-induced insulin resistance in skeletal muscle. Accumulation of intramyocellular lipid may lead to insulin resistance in skeletal muscle. In addition, lipid intermediates (e.g., fatty acyl-coenzyme A, diacylglycerol, and ceramide impair insulin signaling in skeletal muscle. Recently, emerging evidence linking obesity-induced insulin resistance to excessive lipid oxidation, mitochondrial overload, and mitochondrial oxidative stress have been provided with mitochondrial function. This review will provide a brief comprehensive summary on exercise and skeletal muscle metabolism, and discuss the potential mechanisms of obesity-induced insulin resistance in skeletal muscle.

  18. Estrogen effect on post-exercise skeletal muscle neutrophil infiltration and calpain activity

    National Research Council Canada - National Science Library

    Tiidus P.M; Holden D; Bombardier E; Zajchowski S; Enns D; Belcastro A

    2001-01-01

    We hypothesized that estrogen administration would attenuate skeletal muscle neutrophil infiltration, indices of muscle membrane disruption, and muscle calpain activity shortly after the termination of exercise...

  19. Circadian rhythms, the molecular clock, and skeletal muscle.

    Science.gov (United States)

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A

    2011-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1(-/-) and Clock(Δ19) mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle.

  20. Isolation and Culture of Satellite Cells from Mouse Skeletal Muscle.

    Science.gov (United States)

    Musarò, Antonio; Carosio, Silvia

    2017-01-01

    Skeletal muscle tissue is characterized by a population of quiescent mononucleated myoblasts, localized between the basal lamina and sarcolemma of myofibers, known as satellite cells. Satellite cells play a pivotal role in muscle homeostasis and are the major source of myogenic precursors in mammalian muscle regeneration.This chapter describes protocols for isolation and culturing satellite cells isolated from mouse skeletal muscles. The classical procedure, which will be discussed extensively in this chapter, involves the enzymatic dissociation of skeletal muscles, while the alternative method involves isolation of satellite cells from isolated myofibers in which the satellite cells remain in their in situ position underneath the myofiber basal lamina.In particular, we discuss the technical aspect of satellite cell isolation, the methods necessary to enrich the satellite cell fraction and the culture conditions that optimize proliferation and myotube formation of mouse satellite cells.

  1. A study on the change of autophagy in skeletal muscle of patients with chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    黄娟

    2013-01-01

    Objective To study skeletal muscle atrophy and the change of autophagy in skeletal muscle of patients with chronic kidney disease.Methods Mean muscle cross sectional area,mRNA and protein expression of

  2. Fasting- and Exercise-Induced PDH Regulation in Skeletal Muscle

    DEFF Research Database (Denmark)

    Gudiksen, Anders

    for maintaining short-term metabolic flexibility, as muscle IL-6 was not necessary for exercise-induced switches in substrate utilization and neither lack of skeletal muscle IL-6 or PGC-1α affected fasting–induced switch to fat oxidation. Lack of muscle PGC-1α did however blunt the fasting-induced increase...... on skeletal muscle PDH, whereas muscle IL-6 is not required for fasting-induced substrate switch and skeletal muscle PDH regulation in mice. Study III demonstrated that lack of muscle PGC-1α did not affect the switch from carbohydrate to predominant fat utilization in the transition from the fed to the fasted...... state. Fasting-induced down-regulation of PDHa activity in skeletal muscle of control mice was associated with increased phosphorylation of all four known sites in PDH-E1α as well as with increased PDK4 and SIRT3 protein without changes in total acetylation of PDH-E1α. Lack of muscle PGC-1α reduced PDH...

  3. Xanthine oxidase in human skeletal muscle following eccentric exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik; Orthenblad, N.

    1997-01-01

    1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised and the ......1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one-legged eccentric exercise. Muscle biopsies from both the exercised...... the increase in xanthine oxidase in the muscle there were no detectable changes in the levels of muscle malondialdehyde or in plasma antioxidant capacity up to 4 days post-exercise. 5. It is concluded that eccentric exercise leads to an increased level of xanthine oxidase in human muscle and that the increase...

  4. The expression of HSP in human skeletal muscle. Effects of muscle fiber phenotype and training background

    DEFF Research Database (Denmark)

    Folkesson, Mattias; Mackey, Abigail L; Langberg, Henning;

    2013-01-01

    AIM: Exercise-induced adaptations of skeletal muscle are related to training mode and can be muscle fibre type specific. This study aimed to investigate heat shock protein expression in type I and type II muscle fibres in resting skeletal muscle of subjects with different training backgrounds...... HSPs in human skeletal muscle is influenced by muscle fibre phenotype. The fibre type specific expression of HSP70 is influenced by resistance and endurance training whereas those of αB-crystallin and HSP27 are influenced only by endurance training suggesting the existence of a training......-modality specific action on the adaptive processes including heat shock proteins in human skeletal muscle. This article is protected by copyright. All rights reserved....

  5. Premature aging in skeletal muscle lacking serum response factor.

    Directory of Open Access Journals (Sweden)

    Charlotte Lahoute

    Full Text Available Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor is a crucial transcription factor for muscle-specific gene expression and for post-natal skeletal muscle growth. To assess its role in adult skeletal muscle physiology, we developed a post-mitotic myofiber-specific and tamoxifen-inducible SRF knockout model. Five months after SRF loss, no obvious muscle phenotype was observed suggesting that SRF is not crucial for myofiber maintenance. However, mutant mice progressively developed IIB myofiber-specific atrophy accompanied by a metabolic switch towards a more oxidative phenotype, muscular lipid accumulation, sarcomere disorganization and fibrosis. After injury, mutant muscles exhibited an altered regeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalities encountered in aging skeletal muscle. Interestingly, we also observed an important age associated decrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process.

  6. Action of obestatin in skeletal muscle repair: stem cell expansion, muscle growth, and microenvironment remodeling.

    Science.gov (United States)

    Gurriarán-Rodríguez, Uxía; Santos-Zas, Icía; González-Sánchez, Jessica; Beiroa, Daniel; Moresi, Viviana; Mosteiro, Carlos S; Lin, Wei; Viñuela, Juan E; Señarís, José; García-Caballero, Tomás; Casanueva, Felipe F; Nogueiras, Rubén; Gallego, Rosalía; Renaud, Jean-Marc; Adamo, Sergio; Pazos, Yolanda; Camiña, Jesús P

    2015-06-01

    The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Overall, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration.

  7. Nutritional interventions to preserve skeletal muscle mass

    NARCIS (Netherlands)

    Backx, Evelien M.P.

    2016-01-01

    Muscle mass is the main predictor for muscle strength and physical function. The amount of muscle mass can decline rapidly during periods of reduced physical activity or during periods of energy intake restriction. For athletes, it is important to maintain muscle mass, since the loss of muscle is

  8. Nutritional interventions to preserve skeletal muscle mass

    NARCIS (Netherlands)

    Backx, Evelien M.P.

    2016-01-01

    Muscle mass is the main predictor for muscle strength and physical function. The amount of muscle mass can decline rapidly during periods of reduced physical activity or during periods of energy intake restriction. For athletes, it is important to maintain muscle mass, since the loss of muscle is as

  9. Protein and amino acid metabolism in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guoyao.

    1989-01-01

    Isolated chick extensor digitorum communis (EDC) muscles and, in some experiments, rat skeletal muscles were used to study a number of aspects of protein and amino acid metabolism. (1) Chick EDC muscles synthesize and release large amounts of alanine and glutamine, which indirectly obtain their amino groups from branched-chain amino acids (BCAA). (2) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) decrease (P < 0.01) alanine synthesis and BCAA transamination in EDC muscles from 24-h fasted chicks by decreasing (P < 0.01) intracellular concentrations of pyruvate due to inhibition of glycolysis. (3) Glutamine is extensively degraded in skeletal muscles from both chicks and rats, thus challenging the traditional view that glutamine oxidation is negligible in skeletal muscle. The cytosolic glutamine aminotransferases L and K in the rat and the mitochondrial phosphate-activated glutaminase in the chick play important roles in the conversion of glutamine to {alpha}-ketoglutarate for further oxidation. (4) Although methionine has been reported to be extensively transaminated in rat skeletal muscle preparations in the absence of other amino acids, transamination of methionine is absent or negligible in chick and rat skeletal muscles in the presence of physiological concentrations of amino acids. (5) Glutamine at 1.0-15 mM increases (P < 0.01) protein synthesis ({sup 3}H-phenylalanine incorporation), and at 10.0-15.0 mM decreases (P < 0.05) protein degradation ({sup 3}H-phenylalanine release from prelabelled protein in vivo) in EDC muscles from fed chicks as compared to muscles incubated in the absence of glutamine. (6) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) has a small but significant inhibitory effect (P < 0.05) on the rate of protein synthesis, but has no effect (P > 0.05) on the rate of protein degradation in EDC muscles from fed chicks.

  10. Oxidation of urate in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Tullson, P. C.; Richter, Erik

    1997-01-01

    The purpose of the present study was to investigate whether high metabolic stress to skeletal muscle, induced by intensive exercise, would lead to an oxidation of urate to allantoin in the exercised muscle. Seven healthy male subjects performed short term (4.39 +/- 0.04 [+/-SE] min) exhaustive cy...

  11. Skeletal muscle lipid metabolism in exercise and insulin resistance

    DEFF Research Database (Denmark)

    Kiens, Bente

    2006-01-01

    Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids...... of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed....

  12. Molecular responses to moderate endurance exercise in skeletal muscle

    Science.gov (United States)

    This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 +/- 1 yr, body mass 80 +/- 2 kg, and VO(2peak) 45 +/- 1 ml x kg'¹ x min'¹) immediately (0 hr) and...

  13. Skeletal muscle deiodinase type 2 regulation during illness in mice

    NARCIS (Netherlands)

    J. Kwakkel; H.C. van Beeren; M.T. Ackermans; M. Platvoet-ter Schiphorst; E. Fliers; W.M. Wiersinga; A. Boelen

    2009-01-01

    We have previously shown that skeletal muscle deiodinase type 2 (D2) mRNA (listed as Dio2 in MGI Database) is up-regulated in an animal model of acute illness. However, human Studies on the expression Of muscle D2 during illness report conflicting data. Therefore, we evaluated the expression of skel

  14. Skeletal Muscle as a Peripheral Modifier of Behavior

    Science.gov (United States)

    Jenkins, Robert R.

    1978-01-01

    Discusses how muscle can exert an influence on the behavioral potential of an organism and attempts to refute the "all or none law" by demonstrating that skeletal muscle is not merely a slave of the central nervous system. (Author/MA)

  15. Perlecan and synaptophysin changes in denervated skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Kai Ma; Zhifeng Huang; Jianfeng Ma; Longquan Shao; Huiming Wang; Yanliang Wang

    2012-01-01

    The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix com-ponent, which is located at the skeletal muscle cell surface as acetylcholine esterase, as well as synaptophysin, a synaptic marker. Results showed degeneration and inflammation following transection of the sciatic nerve. In addition, the sciatic nerve-dominated skeletal muscle degen-erated with mild inflammation, indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances. With prolonged injury time (1-4 weeks post-injury), perlecan expression gradually decreased and reached the lowest level at 4 weeks, but synap-tophysin expression remained unchanged after denervation. Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.

  16. Mechanically induced alterations in cultured skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  17. Impact of Conjugated Linoleic Acid (CLA) on Skeletal Muscle Metabolism.

    Science.gov (United States)

    Kim, Yoo; Kim, Jonggun; Whang, Kwang-Youn; Park, Yeonhwa

    2016-02-01

    Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.

  18. Mechanically induced alterations in cultured skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  19. Skeletal muscle metastases: primary tumours, prevalence, and radiological features

    Energy Technology Data Exchange (ETDEWEB)

    Surov, Alexey; Spielmann, Rolf Peter; Behrmann, Curd [Martin-Luther-University Halle-Wittenberg, Department of Radiology, Halle (Germany); Hainz, Michael; Holzhausen, Hans-Juergen [Martin-Luther-University Halle-Wittenberg, Department of Pathology, Halle (Germany); Arnold, Dirk [Martin-Luther-University Halle-Wittenberg, Department of Haematology/Oncology, Halle (Germany); Katzer, Michaela [Martin-Luther-University Halle-Wittenberg, Department of Urology, Halle (Germany); Schmidt, Joerg [Martin-Luther-University Halle-Wittenberg, Department of Medical Statistics and Controlling, Halle (Germany)

    2010-03-15

    Although skeletal muscles comprise nearly 50% of the total human body mass and are well vascularised, metastases in the musculature are rare. The reported prevalence of skeletal muscle metastases from post-mortem studies of patients with cancer is inconstant and ranges from 0.03 to 17.5%. Of 5,170 patients with metastasised cancer examined and treated at our institution during the period from January 2000 to December 2007, 61 patients with muscle metastases (80 lesions) were identified on computed tomography (CT). Genital tumours (24.6%) were the most frequent malignancies metastasising into the skeletal musculature, followed by gastrointestinal tumours (21.3%), urological tumours (16.4%), and malignant melanoma (13.1%). Other primary malignancies were rarer, including bronchial carcinoma (8.2%), thyroid gland carcinoma (4.9%), and breast carcinoma (3.3%). In 8.2%, carcinoma of unknown primary was diagnosed. Skeletal muscle metastases (SMM) were located in the iliopsoas muscle (27.5%), paravertebral muscles (25%), gluteal muscles (16.3%), lower extremity muscles (12.5%), abdominal wall muscles (10%), thoracic wall muscles (5%), and upper extremity muscles (3.8%). Most (76.3%) of the 80 SMM were diagnosed incidentally during routine staging CT examinations, while 23.7% were symptomatic. Radiologically, SMM presented with five different types of lesions: focal intramuscular masses (type I, 52.5% of SMM), abscess-like intramuscular lesions (type II, 32.5%), diffuse metastatic muscle infiltration (type III, 8.8%), multifocal intramuscular calcification (type IV, 3.7%) and intramuscular bleeding (type V, 2.5%). (orig.)

  20. Tirasemtiv amplifies skeletal muscle response to nerve activation in humans

    OpenAIRE

    Hansen,Richard; Saikali, Khalil G; Chou, Willis; Alan J Russell; Chen, Michael M.; Vijayakumar, Vipin; Stoltz, Randall R.; Baudry, Stephane; Enoka, Roger M.; Morgans, David J; Wolff, Andrew A.; Malik, Fady I

    2014-01-01

    Introduction: In this study we tested the hypothesis that tirasemtiv, a selective fast skeletal muscle troponin activator that sensitizes the sarcomere to calcium, could amplify the response of muscle to neuromuscular input in humans. Methods: Healthy men received tirasemtiv and placebo in a randomized, double-blind, 4-period, crossover design. The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot. The force–freque...

  1. Changes in skeletal muscle gene expression following clenbuterol administration

    Directory of Open Access Journals (Sweden)

    McIntyre Lauren M

    2006-12-01

    Full Text Available Abstract Background Beta-adrenergic receptor agonists (BA induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P P Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle.

  2. Decellularized Human Skeletal Muscle as Biologic Scaffold for Reconstructive Surgery

    Directory of Open Access Journals (Sweden)

    Andrea Porzionato

    2015-07-01

    Full Text Available Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation.

  3. Force Transmission between Synergistic Skeletal Muscles through Connective Tissue Linkages

    Directory of Open Access Journals (Sweden)

    Huub Maas

    2010-01-01

    Full Text Available The classic view of skeletal muscle is that force is generated within its muscle fibers and then directly transmitted in-series, usually via tendon, onto the skeleton. In contrast, recent results suggest that muscles are mechanically connected to surrounding structures and cannot be considered as independent actuators. This article will review experiments on mechanical interactions between muscles mediated by such epimuscular myofascial force transmission in physiological and pathological muscle conditions. In a reduced preparation, involving supraphysiological muscle conditions, it is shown that connective tissues surrounding muscles are capable of transmitting substantial force. In more physiologically relevant conditions of intact muscles, however, it appears that the role of this myofascial pathway is small. In addition, it is hypothesized that connective tissues can serve as a safety net for traumatic events in muscle or tendon. Future studies are needed to investigate the importance of intermuscular force transmission during movement in health and disease.

  4. Dietary fat influences the expression of contractile and metabolic genes in rat skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Wataru Mizunoya

    Full Text Available Dietary fat plays a major role in obesity, lipid metabolism, and cardiovascular diseases. To determine whether the intake of different types of dietary fats affect the muscle fiber types that govern the metabolic and contractile properties of the skeletal muscle, we fed male Wistar rats with a 15% fat diet derived from different fat sources. Diets composed of soybean oil (n-6 polyunsaturated fatty acids (PUFA-rich, fish oil (n-3 PUFA-rich, or lard (low in PUFAs were administered to the rats for 4 weeks. Myosin heavy chain (MyHC isoforms were used as biomarkers to delineate the skeletal muscle fiber types. Compared with soybean oil intake, fish oil intake showed significantly lower levels of the fast-type MyHC2B and higher levels of the intermediate-type MyHC2X composition in the extensor digitorum longus (EDL muscle, which is a fast-type dominant muscle. Concomitantly, MyHC2X mRNA levels in fish oil-fed rats were significantly higher than those observed in the soybean oil-fed rats. The MyHC isoform composition in the lard-fed rats was an intermediate between that of the fish oil and soybean oil-fed rats. Mitochondrial uncoupling protein 3, pyruvate dehydrogenase kinase 4, and porin mRNA showed significantly upregulated levels in the EDL of fish oil-fed rats compared to those observed in soybean oil-fed and lard-fed rats, implying an activation of oxidative metabolism. In contrast, no changes in the composition of MyHC isoforms was observed in the soleus muscle, which is a slow-type dominant muscle. Fatty acid composition in the serum and the muscle was significantly influenced by the type of dietary fat consumed. In conclusion, dietary fat affects the expression of genes related to the contractile and metabolic properties in the fast-type dominant skeletal muscle, where the activation of oxidative metabolism is more pronounced after fish oil intake than that after soybean oil intake.

  5. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  6. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

    Describes an experiment using rats that demonstrates contractile characteristics of normal and hypertrophied muscle. Compensatory hypertrophy of the plantaris muscle is induced by surgical removal of the synergistic gastrocnemium muscle. Includes methods for determination of contractile properties of normal and hypertrophied muscle and…

  7. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging...

  8. File list: InP.Myo.10.AllAg.Muscle,_Skeletal [Chip-atlas[Archive

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    Full Text Available NoD.Myo.10.AllAg.Muscle,_Skeletal mm9 No description Muscle Muscle, Skeletal ERX161...919,ERX016334,ERX016328,ERX016330,ERX161925 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Myo.10.AllAg.Muscle,_Skeletal.bed ...

  6. File list: NoD.Myo.05.AllAg.Muscle,_Skeletal [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Myo.05.AllAg.Muscle,_Skeletal mm9 No description Muscle Muscle, Skeletal ERX161...919,ERX016334,ERX016330,ERX016328,ERX161925 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Myo.05.AllAg.Muscle,_Skeletal.bed ...

  7. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  8. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle.

    Science.gov (United States)

    McCarthy, John J; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B; Srikuea, Ratchakrit; Lawson, Benjamin A; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S; Esser, Karyn A; Dupont-Versteegden, Esther E; Peterson, Charlotte A

    2011-09-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca(2+) sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.

  9. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

    Science.gov (United States)

    McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

    2011-01-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

  10. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  11. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-01-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature (P < 0.05). This result indicated that repeated local muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  12. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-07-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature ( P muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  13. Relative appendicular skeletal muscle mass is associated with isokinetic muscle strength and balance in healthy collegiate men.

    Science.gov (United States)

    Kim, Sung-Eun; Hong, Ju; Cha, Jun-Youl; Park, Jung-Min; Eun, Denny; Yoo, Jaehyun; Jee, Yong-Seok

    2016-11-01

    There are few studies on the relationship between skeletal muscle mass and balance in the young ages. We investigated the relationship between appendicular skeletal muscle mass, isokinetic muscle strength of lower extremity, and balance among healthy young men using relative skeletal muscle index. Thirty men were grouped according to relative appendicular skeletal muscle mass index: higher skeletal muscle group (n = 15) and lower skeletal muscle group (n = 15). Static and dynamic balance abilities were measured using the following: a test where participants stood on one leg with eyes closed, a modified Clinical Test of Sensory Interaction on Balance (mCTSIB) with eyes open and eyes closed, a stability test, and limits of stability test. The muscle strength of lower extremities was measured with an isokinetic analyser in hip, knee, and ankle joints. Participants with higher appendicular skeletal muscle mass were significantly more stable in maintaining dynamic balance than those with lower appendicular skeletal muscle mass. Moreover, appendicular skeletal muscle mass index was positively correlated with dynamic balance ability. Participants with higher appendicular skeletal muscle mass had stronger strength in the lower extremity, and there were significant differences in the isokinetic torque ratios between groups. From these results, it can be inferred that higher appendicular skeletal muscle mass relates to muscle strength and the alteration in the peak torque ratio of the lower extremity, contributing to the maintenance of balance.

  14. Control levels of acetylcholinesterase expression in the mammalian skeletal muscle.

    Science.gov (United States)

    Grubic, Z; Zajc-Kreft, K; Brank, M; Mars, T; Komel, R; Miranda, A F

    1999-05-14

    Protein expression can be controled at different levels. Understanding acetylcholinesterase (EC. 3.1.1.7, AChE) expression in the living organisms therefore necessitates: (1) determination and mapping of control levels of AChE metabolism; (2) identification of the regulatory factors acting at these levels; and (3) detailed insight into the mechanisms of action of these factors. Here we summarize the results of our studies on the regulation of AChE expression in the mammalian skeletal muscle. Three experimental models were employed: in vitro innervated human muscle, mechanically denervated adult fast rat muscle, and the glucocorticoid treated fast rat muscle. In situ hybridization of AChE mRNA, combined with AChE histochemistry, revealed that different distribution patterns of AChE, observed during in vitro ontogenesis and synaptogenesis of human skeletal muscle, reflect alterations in the distribution of AChE mRNA (Z. Grubic, R. Komel, W.F. Walker, A.F. Miranda, Myoblast fusion and innervation with rat motor nerve alter the distribution of acetylcholinesterase and its mRNA in human muscle cultures, Neuron 14 (1995) 317-327). To study the mechanisms of AChE mRNA loss in denervated adult rat skeletal muscle, we exposed deproteinated AChE mRNA to various subcellular fractions in vitro. Fractions were isolated from the normal and denervated rat sternomastoideus muscle. We found significantly increased, but non-specific AChE mRNA degradation capacities in the three fractions studied, suggesting that increased susceptibility of muscle mRNA to degradation might be at least partly responsible for the decreased AChE mRNA observed under such conditions (K. Zajc-Kreft, S. Kreft, Z. Grubic, Degradation of AChE mRNA in the normal and denervated rat skeletal muscle, Book of Abstracts, The Sixth International Meeting on Cholinesterases, La Jolla, CA, March 20-24, 1998, p. A3.). In adult fast rat muscle, treated chronically with glucocorticoids, we found the fraction of early

  15. Purinergic receptors expressed in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Bornø, A; Ploug, Thorkil; Bune, L T

    2012-01-01

    Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content...... of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy...... in immunolabelled transverse sections of muscle biopsies. The receptors P2Y(4), P2Y(11) and likely P2X(1) were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X(1) receptors were expressed in intracellular vesicles...

  16. Apoptosis in skeletal muscle and its relevance to atrophy

    Institute of Scientific and Technical Information of China (English)

    Esther E Dupont-Versteegden

    2006-01-01

    Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.

  17. Hypermetabolism of skeletal muscles following sexual activity: a normal variation.

    Science.gov (United States)

    Choi, Byung Wook; Kim, Sung Hoon; Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil

    2010-09-01

    A 46-year-old man with early gastric cancer at the gastric antrum underwent an F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-computer tomography (CT) scan for staging. No definite abnormal FDG uptake of the stomach was shown. Incidentally, variable FDG uptake at the bilateral serratus muscles, abdominal muscles and muscles of both thighs (Fig. 1) was observed. He had no significant past medical history except recently diagnosed stomach cancer. On personal interview, he described having had sexual activity the night before the F-18 FDG PET/CT scan, although he was aware of needing to avoid physical activity before a PET scan. The F-18 FDG PET/CT scan was done at 2:00 p.m. Therefore, the hypermetabolism of individual skeletal muscles following sexual activity lasted over 12 h. This case illustrates the hypermetabolism of skeletal muscles following sexual activity as a normal variation.

  18. Altered cross-bridge properties in skeletal muscle dystrophies

    Directory of Open Access Journals (Sweden)

    Aziz eGuellich

    2014-10-01

    Full Text Available Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal muscle dystrophies and discuss their ultimate impacts on striated muscle function.

  19. Muscle dynamics in fish during steady swimming

    DEFF Research Database (Denmark)

    Shadwick, RE; Steffensen, JF; Katz, SL

    1998-01-01

    position in swimming fish. Quantification of muscle contractile properties in cyclic contractions relies on in vitro experiments using strain and activation data collected in vivo. In this paper we discuss the relation between these parameters and body kinematics. Using videoradiographic data from swimming...... contraction, suggesting that the phase relation between the muscle strain cycle and its activation must vary along the body. Since this phase relation is critical in determining how the muscle performs in cyclic contractions, the possibility has emerged that dynamic muscle function may change with axial...

  20. Comparative Skeletal Muscle Proteomics Using Two-Dimensional Gel Electrophoresis.

    Science.gov (United States)

    Murphy, Sandra; Dowling, Paul; Ohlendieck, Kay

    2016-09-09

    The pioneering work by Patrick H. O'Farrell established two-dimensional gel electrophoresis as one of the most important high-resolution protein separation techniques of modern biochemistry (Journal of Biological Chemistry1975, 250, 4007-4021). The application of two-dimensional gel electrophoresis has played a key role in the systematic identification and detailed characterization of the protein constituents of skeletal muscles. Protein changes during myogenesis, muscle maturation, fibre type specification, physiological muscle adaptations and natural muscle aging were studied in depth by the original O'Farrell method or slightly modified gel electrophoretic techniques. Over the last 40 years, the combined usage of isoelectric focusing in the first dimension and sodium dodecyl sulfate polyacrylamide slab gel electrophoresis in the second dimension has been successfully employed in several hundred published studies on gel-based skeletal muscle biochemistry. This review focuses on normal and physiologically challenged skeletal muscle tissues and outlines key findings from mass spectrometry-based muscle proteomics, which was instrumental in the identification of several thousand individual protein isoforms following gel electrophoretic separation. These muscle-associated protein species belong to the diverse group of regulatory and contractile proteins of the acto-myosin apparatus that forms the sarcomere, cytoskeletal proteins, metabolic enzymes and transporters, signaling proteins, ion-handling proteins, molecular chaperones and extracellular matrix proteins.

  1. Three-dimensional reconstruction of skeletal muscle extracellular matrix ultrastructure.

    Science.gov (United States)

    Gillies, Allison R; Bushong, Eric A; Deerinck, Thomas J; Ellisman, Mark H; Lieber, Richard L

    2014-12-01

    The skeletal muscle extracellular matrix (ECM) supports muscle's passive mechanical function and provides a unique environment for extracellular tissues such as nerves, blood vessels, and a cadre of mononuclear cells. Within muscle ECM, collagen is thought to be the primary load-bearing protein, yet its structure and organization with respect to muscle fibers, tendon, and mononuclear cells is unknown. Detailed examination of extracellular collagen morphology requires high-resolution electron microscopy performed over relatively long distances because multinucleated muscle cells are very long and extend from several millimeters to several centimeters. Unfortunately, there is no tool currently available for high resolution ECM analysis that extends over such distances relevant to muscle fibers. Serial block face scanning electron microscopy is reported here to examine skeletal muscle ECM ultrastructure over hundreds of microns. Ruthenium red staining was implemented to enhance contrast and utilization of variable pressure imaging reduced electron charging artifacts, allowing continuous imaging over a large ECM volume. This approach revealed previously unappreciated perimysial collagen structures that were reconstructed via both manual and semi-automated segmentation methods. Perimysial collagen structures in the ECM may provide a target for clinical therapies aimed at reducing skeletal muscle fibrosis and stiffness.

  2. Comparative Skeletal Muscle Proteomics Using Two-Dimensional Gel Electrophoresis

    Directory of Open Access Journals (Sweden)

    Sandra Murphy

    2016-09-01

    Full Text Available The pioneering work by Patrick H. O’Farrell established two-dimensional gel electrophoresis as one of the most important high-resolution protein separation techniques of modern biochemistry (Journal of Biological Chemistry 1975, 250, 4007–4021. The application of two-dimensional gel electrophoresis has played a key role in the systematic identification and detailed characterization of the protein constituents of skeletal muscles. Protein changes during myogenesis, muscle maturation, fibre type specification, physiological muscle adaptations and natural muscle aging were studied in depth by the original O’Farrell method or slightly modified gel electrophoretic techniques. Over the last 40 years, the combined usage of isoelectric focusing in the first dimension and sodium dodecyl sulfate polyacrylamide slab gel electrophoresis in the second dimension has been successfully employed in several hundred published studies on gel-based skeletal muscle biochemistry. This review focuses on normal and physiologically challenged skeletal muscle tissues and outlines key findings from mass spectrometry-based muscle proteomics, which was instrumental in the identification of several thousand individual protein isoforms following gel electrophoretic separation. These muscle-associated protein species belong to the diverse group of regulatory and contractile proteins of the acto-myosin apparatus that forms the sarcomere, cytoskeletal proteins, metabolic enzymes and transporters, signaling proteins, ion-handling proteins, molecular chaperones and extracellular matrix proteins.

  3. Are antioxidants useful for treating skeletal muscle atrophy?

    Science.gov (United States)

    Bonetto, Andrea; Penna, Fabio; Muscaritoli, Maurizio; Minero, Valerio G; Rossi Fanelli, Filippo; Baccino, Francesco M; Costelli, Paola

    2009-10-01

    Changes in the skeletal muscle protein mass frequently occur in both physiological and pathological states. Muscle hypotrophy, in particular, is commonly observed during aging and is characteristic of several pathological conditions such as neurological diseases, cancer, diabetes, and sepsis. The skeletal muscle protein content depends on the relative rates of synthesis and degradation, which must be coordinately regulated to maintain the equilibrium. Pathological muscle depletion is characterized by a negative nitrogen balance, which results from disruption of this equilibrium due to reduced synthesis, increased breakdown, or both. The current view, mainly based on experimental data, considers hypercatabolism as the major cause of muscle protein depletion. Several signaling pathways that probably contribute to muscle atrophy have been identified, and there is increasing evidence that oxidative stress, due to reactive oxygen species production overwhelming the intracellular antioxidant systems, plays a role in causing muscle depletion both during aging and in chronic pathological states. In particular, oxidative stress has been proposed to enhance protein breakdown, directly or by interacting with other factors. This review focuses on the possibility of using antioxidant treatments to target molecular pathways involved in the pathogenesis of skeletal muscle wasting.

  4. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss......The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...

  5. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...

  6. Establishment of bipotent progenitor cell clone from rat skeletal muscle.

    Science.gov (United States)

    Murakami, Yousuke; Yada, Erica; Nakano, Shin-ichi; Miyagoe-Suzuki, Yuko; Hosoyama, Tohru; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle.

  7. Muscle interleukin-6 and fasting-induced PDH regulation in mouse skeletal muscle.

    Science.gov (United States)

    Gudiksen, Anders; Bertholdt, Laerke; Vingborg, Mikkel Birkkjaer; Hansen, Henriette Watson; Ringholm, Stine; Pilegaard, Henriette

    2017-03-01

    Fasting prompts a metabolic shift in substrate utilization from carbohydrate to predominant fat oxidation in skeletal muscle, and pyruvate dehydrogenase (PDH) is seen as a controlling link between the competitive oxidation of carbohydrate and fat during metabolic challenges like fasting. Interleukin (IL)-6 has been proposed to be released from muscle with concomitant effects on both glucose and fat utilization. The aim was to test the hypothesis that muscle IL-6 has a regulatory impact on fasting-induced suppression of skeletal muscle PDH. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice and floxed littermate controls (control) were either fed or fasted for 6 or 18 h. Lack of muscle IL-6 elevated the respiratory exchange ratio in the fed and early fasting state, but not with prolonged fasting. Activity of PDH in the active form (PDHa) was higher in fed and fasted IL-6 MKO than in control mice at 18 h, but not at 6 h, whereas lack of muscle IL-6 did not prevent downregulation of PDHa activity in skeletal muscle or changes in plasma and muscle substrate levels in response to 18 h of fasting. Phosphorylation of three of four sites on PDH-E1α increased with 18 h of fasting, but was lower in IL-6 MKO mice than in control. In addition, both PDK4 mRNA and protein increased with 6 and 18 h of fasting in both genotypes, but PDK4 protein was lower in IL-6 MKO than in control. In conclusion, skeletal muscle IL-6 seems to regulate whole body substrate utilization in the fed, but not fasted, state and influence skeletal muscle PDHa activity in a circadian manner. However, skeletal muscle IL-6 is not required for maintaining metabolic flexibility in response to fasting. Copyright © 2017 the American Physiological Society.

  8. Bone marrow mesenchymal cells improve muscle function in a skeletal muscle re-injury model.

    Directory of Open Access Journals (Sweden)

    Bruno M Andrade

    Full Text Available Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively. Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model.

  9. Exercise-Induced Skeletal Muscle Damage.

    Science.gov (United States)

    Evans, William J.

    1987-01-01

    Eccentric exercise, in which the muscles exert force by lengthening, is associated with delayed onset muscle soreness. How soreness occurs, how recovery proceeds, and what precautions athletes should take are described. (Author/MT)

  10. [Ontogenetic and phylogenetic analysis of myosin light chain proteins from skeletal muscles of loach Misgurnus fossilis].

    Science.gov (United States)

    Miuge, N S; Tikhonov, A V; Ozerniuk, N D

    2005-01-01

    mRNAs of all three types of myosin light chain proteins are expressed in skeletal muscles of both larval and adult stages of loach Misgurnus fossilis (Cobitidae) and these proteins are encoded by different genes (mlc1, mlc2, and mlc3). No difference was revealed between transcripts from larval stage and adult fish for all three mlc proteins. Our approach (RT-PCR with fish-specific mlc1, mlc2, and mlc3 primers) failed to reveal the larval form of myosin light chain protein found previously by protein electrophoresis of loach fry muscle extract. Comparative analysis of the protein structure shows high homology of MLC1 and MLC3 proteins sharing a large EF-hand calcium-binding domain. Phylogenetic analysis of MLC1 from skeletal muscles of fish and other vertebrate species is concordant with the traditional phylogeny of the group. Within the Teleostei, loach MLC1 had the highest homology with other Cyprinidae, and least with Salmonidae fishes.

  11. Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3

    Science.gov (United States)

    We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the esta...

  12. Growth factor involvement in tension-induced skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  13. STRUCTURAL ALTERATIONS OF SKELETAL MUSCLE IN COPD

    Directory of Open Access Journals (Sweden)

    Sunita eMathur

    2014-03-01

    Full Text Available Background: Chronic obstructive pulmonary disease (COPD is a respiratory disease associated with a systemic inflammatory response. Peripheral muscle dysfunction has been well characterized in individuals with COPD and results from a complex interaction between systemic and local factors. Objective: In this narrative review, we will describe muscle wasting in people with COPD, the associated structural changes, muscle regenerative capacity and possible mechanisms for muscle wasting. We will also discuss how structural changes relate to impaired muscle function and mobility in people with COPD. Key Observations: Approximately 30-40% of individuals with COPD experience muscle mass depletion. Furthermore, muscle atrophy is a predictor of physical function and mortality in this population. Associated structural changes include a decreased proportion and size of type-I fibers, reduced oxidative capacity and mitochondrial density mainly in the quadriceps. Observations related to impaired muscle regenerative capacity in individuals with COPD include a lower proportion of central nuclei in the presence or absence of muscle atrophy and decreased maximal telomere length, which has been correlated with reduced muscle cross-sectional area. Potential mechanisms for muscle wasting in COPD may include excessive production of reactive oxygen species, altered amino acid metabolism and lower expression of peroxisome proliferator-activated receptors-gamma-coactivator 1-alpha mRNA. Despite a moderate relationship between muscle atrophy and function, impairments in oxidative metabolism only seems weakly related to muscle function. Conclusion: This review article demonstrates the cellular modifications in the peripheral muscle of people with COPD and describes the evidence of its relationship to muscle function. Future research will focus on rehabilitation strategies to improve muscle wasting and maximize function.

  14. Pericapillary basement membrane thickening in human skeletal muscles.

    Science.gov (United States)

    Baum, Oliver; Bigler, Marius

    2016-09-01

    The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.

  15. Effects of yessotoxin (YTX) on the skeletal muscle: an update.

    Science.gov (United States)

    Tubaro, A; Bandi, E; Sosa, S; Soranzo, M R; Giangaspero, A; De Ninis, V; Yasumoto, T; Lorenzon, P

    2008-09-01

    Yessotoxins (YTXs) are algal toxins originally included in the diarrheic toxins. After oral intake, YTXs induce only ultra-structural changes (packages of swollen mitochondria) in cardiac cells. The aim of this study was to investigate the possible effects of YTX on the other contractile striated tissue, the skeletal muscle, in vitro and in vivo. In vitro, in skeletal mouse myotubes, YTX (0.01-1.0 microM) influenced cell excitability in a concentration- and time-dependent way. In the in vivo study, transmission electron microscopy analysis did not reveal any ultrastructural alteration of skeletal muscle after acute (1 mg kg(-1)) or repeated (1 and 2mg kg(-1) day(-1), for 7 days) oral administration of YTX to mice. The observation that effects were detected in vitro but not in vivo supports the hypothesis of a low YTX bioavailability to skeletal muscle after oral intake. Therefore, the results seem to exclude a toxic effect in skeletal muscle when YTX is consumed as a food contaminant.

  16. Interleukin-6 myokine signaling in skeletal muscle

    DEFF Research Database (Denmark)

    Muñoz-Cánoves, Pura; Scheele, Camilla; Pedersen, Bente K

    2013-01-01

    been associated with stimulation of hypertrophic muscle growth and myogenesis through regulation of the proliferative capacity of muscle stem cells. Additional beneficial effects of IL-6 include regulation of energy metabolism, which is related to the capacity of actively contracting muscle...

  17. Mitochondrial biogenesis and angiogenesis in skeletal muscle of the elderly

    DEFF Research Database (Denmark)

    Iversen, Ninna; Krustrup, Peter; Rasmussen, Hans N

    2011-01-01

    The aim of this study was to test the hypotheses that 1) skeletal muscles of elderly subjects can adapt to a single endurance exercise bout and 2) endurance trained elderly subjects have higher expression/activity of oxidative and angiogenic proteins in skeletal muscle than untrained elderly people...... in UT PGC-1a mRNA 11-fold and VEGF mRNA 4-fold at 2h of recovery, and AMPK phosphorylation ~5-fold immediately after exercise, relative to Pre, indicating an ability to adapt metabolically and angiogenically to endurance exercise. However, in ET PGC-1a mRNA only increased 5 fold and AMPK phosphorylation...

  18. Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy*

    Science.gov (United States)

    Ebert, Scott M.; Dyle, Michael C.; Kunkel, Steven D.; Bullard, Steven A.; Bongers, Kale S.; Fox, Daniel K.; Dierdorff, Jason M.; Foster, Eric D.; Adams, Christopher M.

    2012-01-01

    Diverse stresses including starvation and muscle disuse cause skeletal muscle atrophy. However, the molecular mechanisms of muscle atrophy are complex and not well understood. Here, we demonstrate that growth arrest and DNA damage-inducible 45a protein (Gadd45a) is a critical mediator of muscle atrophy. We identified Gadd45a through an unbiased search for potential downstream mediators of the stress-inducible, pro-atrophy transcription factor ATF4. We show that Gadd45a is required for skeletal muscle atrophy induced by three distinct skeletal muscle stresses: fasting, muscle immobilization, and muscle denervation. Conversely, forced expression of Gadd45a in muscle or cultured myotubes induces atrophy in the absence of upstream stress. We show that muscle-specific ATF4 knock-out mice have a reduced capacity to induce Gadd45a mRNA in response to stress, and as a result, they undergo less atrophy in response to fasting or muscle immobilization. Interestingly, Gadd45a is a myonuclear protein that induces myonuclear remodeling and a comprehensive program for muscle atrophy. Gadd45a represses genes involved in anabolic signaling and energy production, and it induces pro-atrophy genes. As a result, Gadd45a reduces multiple barriers to muscle atrophy (including PGC-1α, Akt activity, and protein synthesis) and stimulates pro-atrophy mechanisms (including autophagy and caspase-mediated proteolysis). These results elucidate a critical stress-induced pathway that reprograms muscle gene expression to cause atrophy. PMID:22692209

  19. Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD

    NARCIS (Netherlands)

    Remels, A.H.; Schrauwen, P.; Broekhuizen, R.; Willems, J.; Kersten, A.H.; Gosker, H.R.; Schols, A.M.

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence

  20. Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy*

    Science.gov (United States)

    Dyle, Michael C.; Ebert, Scott M.; Cook, Daniel P.; Kunkel, Steven D.; Fox, Daniel K.; Bongers, Kale S.; Bullard, Steven A.; Dierdorff, Jason M.; Adams, Christopher M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. PMID:24719321

  1. Altered cross-bridge properties in skeletal muscle dystrophies.

    Science.gov (United States)

    Guellich, Aziz; Negroni, Elisa; Decostre, Valérie; Demoule, Alexandre; Coirault, Catherine

    2014-01-01

    Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca(2+) through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies (MDs) have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal MDs and discuss their ultimate impacts on striated muscle function.

  2. Altered cross-bridge properties in skeletal muscle dystrophies

    Science.gov (United States)

    Guellich, Aziz; Negroni, Elisa; Decostre, Valérie; Demoule, Alexandre; Coirault, Catherine

    2014-01-01

    Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies (MDs) have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal MDs and discuss their ultimate impacts on striated muscle function. PMID:25352808

  3. Needle muscle biopsy: technique validation and histological and histochemical methods for evaluating canine skeletal muscles

    Directory of Open Access Journals (Sweden)

    Sérgio de Almeida Braga

    2017-05-01

    Full Text Available This study evaluated the needle muscle biopsy technique using a 6G Bergström percutaneous needle combined with histological and histochemical methods to analyze the skeletal muscle of dogs. There are few studies about canine skeletal muscles and a lack of reports in the literature about tissue collection and analysis for canine species. Evaluation of 32 German Shepherd samples collected from the gluteus medius, at a depth of 3 cm, was performed. The choice of gluteus medius and the 3-cm depth provided good quantity fragments with sufficient sizes (3–5 mm, which permitted optimal visualization of muscle fibers. Myosin ATPase, at pH 9.4, 4.6, and 4.3, and SDH reactions revealed that all muscle samples analyzed had fibers in the classic mosaic arrangement, enabling counting and typification. The mean percentages of fibers were 29.95% for type I and 70.05% for type II. On the basis of these results, we concluded that the percutaneous needle biopsy technique for canine skeletal muscles is a safe and easy procedure that obtains fragments of proper sizes, thereby enabling the study of muscle fibers. Standardization of the muscle of choice and the depth of muscle sample collection significantly contributed to this success. This is an important method to evaluate muscle fiber types of dogs and diagnose important diseases affecting the skeletal muscles.

  4. Long-chain n-3 DHA reduces the extent of skeletal muscle fatigue in the rat in vivo hindlimb model.

    Science.gov (United States)

    Peoples, Gregory E; McLennan, Peter L

    2014-03-28

    Dietary fish oil modifies skeletal muscle membrane fatty acid composition and oxygen efficiency similar to changes in the myocardium. Oxygen efficiency is a key determinant of sustained force in mammalian skeletal muscle. Therefore, in the present study, we tested the effects of a fish-oil diet on skeletal muscle fatigue under the stress of contraction using the rat in vivo autologous perfused hindlimb model. For 8 weeks, male Wistar rats were fed a diet rich in saturated fat (SF), a diet rich in n-6 PUFA or a diet rich in long-chain (LC) n-3 PUFA DHA derived from fish oil. In anaesthetised, mechanically ventilated rats, with their hindlimbs perfused with arterial blood at a constant flow, the gastrocnemius-plantaris-soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6-12 V, 0·05 ms) to contract repetitively for 30 min. Rats fed the n-3 PUFA diet developed higher maximum twitch tension than those fed the SF and n-6 PUFA diets (PDHA into skeletal muscle membranes increases the efficiency of oxygen use over a range of contractile force and this is expressed as a higher sustained force and prolonged time to fatigue.

  5. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition

    DEFF Research Database (Denmark)

    Nielsen, Anders Rinnov; Mounier, Remi; Plomgaard, Peter

    2007-01-01

    of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal......The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus...... lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n = 8) not involved...

  6. Skeletal muscle cell apoptosis following motornerve injury versus sensory nerve injury

    Institute of Scientific and Technical Information of China (English)

    Lei Zhao; Ruisheng Xu; Shenyang Jiang; Guangming Lü; Zhiqiang Yan; Junming Sun; Ling Wang; Ye Xue; Donglin Jiang

    2011-01-01

    Skeletal muscle atrophy inevitably occurs in denervated skeletal muscle, and cell apoptosis plays an important role in skeletal muscle atrophy and degeneration. The present study established rat models of simple nerve injury by transecting the ventral or dorsal spinal nerve root and observed rat skeletal muscle cell apoptosis following simple motor nerve injury versus simple sensory nerve injury. Following skeletal muscle denervation for 10 weeks, cell apoptosis was detected in skeletal muscle, which was accompanied by obvious changes in rat behavior and electrophysiological responses. In addition, changes in cross-sectional area and average gray-scale of motor endplates of the gastrocnemius muscle were analyzed following sciatic nerve injury and motor nerve injury.Cell nuclei in denervated skeletal muscle tissue were more densely arranged than in normal skeletal muscle tissue. Cell nuclei were most dense in the sciatic nerve injury group, followed by the motor nerve injury group and the sensory nerve injury group. Fas/Fast expression and the number of apoptotic cells increased in denervated skeletal muscle, and apoptosis-related changes were observed. These findings suggested that motor and sensory nerves provided trophic actions following skeletal muscle and motor nerve injury, resulting in a greater influence on skeletal muscle atrophy than sensory nerve injury. Therefore, reconstruction of motor nerves should be preferentially considered for treating denervation-induced skeletal muscle atrophy.

  7. A novel BDNF gene promoter directs expression to skeletal muscle

    Directory of Open Access Journals (Sweden)

    Heinrich Gerhard

    2003-06-01

    Full Text Available Abstract Background Cell-specific expression of the gene that encodes brain-derived neurotrophic factor (BDNF is required for the normal development of peripheral sensory neurons and efficient synaptic transmission in the mature central and peripheral nervous system. The control of BDNF gene expression involves multiple tissue and cell-specific promoters that are differentially regulated. The molecular mechanisms that are responsible for tissue and cell-specific expression of these promoters are still incompletely understood. Results The cloning and analysis of three additional zebrafish (Danio rerio BDNF gene exons and two associated promoters, is reported. Among them are two exons that generate a novel tripartite mature transcript. The exons were located on the transcription unit, whose overall organization was determined by cloning, Southern blot hybridization and sequence analysis, and compared with the pufferfish (Fugu rubripes and mammalian BDNF loci, revealing a conserved but more compact organization. Structural and functional analysis of the exons, their adjacent promoters and 5' flanks, showed that they are expressed cell-specifically. The promoter associated with the 5' exon of the tripartite transcript is GC-rich, TATA-less and the 5' flank adjacent to it contains multiple Sp1, Mef2, and AP1 elements. A fusion gene containing the promoter and 1.5 KB of 5' flank is directed exclusively to skeletal muscle of transiently transfected embryos. The second promoter, whose associated 5' exon contains a 25-nucleotide segment of identity with a mammalian BDNF gene exon, was transiently expressed in yolk of the early embryo. RT-PCR analysis of total RNA from whole juvenile fish and adult female skeletal muscle revealed tissue-specific expression of the 5' exons but the novel exon could not be detected even after two rounds of nested PCR. Conclusion The zebrafish BDNF gene is as complex as the mammalian gene yet much more compact. Its exons are

  8. A primary reduced TCA flux governs substrate oxidation in T2D skeletal muscle

    DEFF Research Database (Denmark)

    Gaster, Michael

    2012-01-01

    Our current knowledge on substrate oxidation in skeletal muscle in relation to insulin resistance and type 2 diabetes (T2D) originate mainly from in vivo studies. The oxidative capacity of skeletal muscle is highly influenced by physical activity, ageing, hormonal status, and fiber type composition...... further regulatory mechanism to our understanding of substrate oxidation in human skeletal muscle during normo- an pathophysiological conditions, focusing especially on the governing influence of a primary reduced TCA flux for the diabetic phenotype in skeletal muscle....

  9. Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

    OpenAIRE

    Mavalli, Mahendra D.; DiGirolamo, Douglas J; FAN, Yong; Riddle, Ryan C.; Kenneth S Campbell; van Groen, Thomas; Frank, Stuart J; Sperling, Mark A.; Esser, Karyn A.; Bamman, Marcas M.; Clemens, Thomas L.

    2010-01-01

    Skeletal muscle development, nutrient uptake, and nutrient utilization is largely coordinated by growth hormone (GH) and its downstream effectors, in particular, IGF-1. However, it is not clear which effects of GH on skeletal muscle are direct and which are secondary to GH-induced IGF-1 expression. Thus, we generated mice lacking either GH receptor (GHR) or IGF-1 receptor (IGF-1R) specifically in skeletal muscle. Both exhibited impaired skeletal muscle development characterized by reductions ...

  10. Metformin protects skeletal muscle from cardiotoxin induced degeneration.

    Directory of Open Access Journals (Sweden)

    Francesca Langone

    Full Text Available The skeletal muscle tissue has a remarkable capacity to regenerate upon injury. Recent studies have suggested that this regenerative process is improved when AMPK is activated. In the muscle of young and old mice a low calorie diet, which activates AMPK, markedly enhances muscle regeneration. Remarkably, intraperitoneal injection of AICAR, an AMPK agonist, improves the structural integrity of muscles of dystrophin-deficient mdx mice. Building on these observations we asked whether metformin, a powerful anti-hyperglycemic drug, which indirectly activates AMPK, affects the response of skeletal muscle to damage. In our conditions, metformin treatment did not significantly influence muscle regeneration. On the other hand we observed that the muscles of metformin treated mice are more resilient to cardiotoxin injury displaying lesser muscle damage. Accordingly myotubes, originated in vitro from differentiated C2C12 myoblast cell line, become more resistant to cardiotoxin damage after pre-incubation with metformin. Our results indicate that metformin limits cardiotoxin damage by protecting myotubes from necrosis. Although the details of the molecular mechanisms underlying the protective effect remain to be elucidated, we report a correlation between the ability of metformin to promote resistance to damage and its capacity to counteract the increment of intracellular calcium levels induced by cardiotoxin treatment. Since increased cytoplasmic calcium concentrations characterize additional muscle pathological conditions, including dystrophies, metformin treatment could prove a valuable strategy to ameliorate the conditions of patients affected by dystrophies.

  11. Leucine supplementation improves regeneration of skeletal muscles from old rats.

    Science.gov (United States)

    Pereira, Marcelo G; Silva, Meiricris T; da Cunha, Fernanda M; Moriscot, Anselmo S; Aoki, Marcelo S; Miyabara, Elen H

    2015-12-01

    The decreased regenerative capacity of old skeletal muscles involves disrupted turnover of proteins. This study investigated whether leucine supplementation in old rats could improve muscle regenerative capacity. Young and old male Wistar rats were supplemented with leucine; then, the muscles were cryolesioned and examined after 3 and 10 days. Leucine supplementation attenuated the decrease in the expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4E (eIF4E) in young and old muscles on day 3 post-injury and promoted an increase in the cross-sectional area of regenerating myofibers from both young and old soleus muscles on day 10 post-injury. This supplementation decreased the levels of ubiquitinated proteins and increased the proteasome activity in young regenerating muscles, but the opposite effect was observed in old regenerating muscles. Moreover, leucine decreased the inflammation area and induced an increase in the number of proliferating satellite cells in both young and old muscles. Our results suggest that leucine supplementation improves the regeneration of skeletal muscles from old rats, through the preservation of certain biological responses upon leucine supplementation. Such responses comprise the decrease in the inflammation area, increase in the number of proliferating satellite cells and size of regenerating myofibers, combined with the modulation of components of the phosphoinositide 3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and ubiquitin-proteasome system.

  12. The role of hyperplasia on the increase of skeletal muscle

    OpenAIRE

    Victor Hugo Maciel Meloni

    2005-01-01

    Skeletal muscle hypertrophy is resulted from the individual increase of the fiber cross-sectional area. This adaptative phenomenon is normally observed in the muscle tissue submitted to a regimen of physical exercises, like strength training. The degree of muscular hypertrophy is directly related to the type of exercise and its intensity. Strength training normally produces a hypertrophy of greater magnitude when compared to other types of physical exercise. However, it is possible that there...

  13. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review...... will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction....

  14. Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease

    DEFF Research Database (Denmark)

    Berchtold, M W; Brinkmeier, H; Müntener, M

    2000-01-01

    Mammalian skeletal muscle shows an enormous variability in its functional features such as rate of force production, resistance to fatigue, and energy metabolism, with a wide spectrum from slow aerobic to fast anaerobic physiology. In addition, skeletal muscle exhibits high plasticity that is based...... on the potential of the muscle fibers to undergo changes of their cytoarchitecture and composition of specific muscle protein isoforms. Adaptive changes of the muscle fibers occur in response to a variety of stimuli such as, e.g., growth and differentition factors, hormones, nerve signals, or exercise....... Additionally, the muscle fibers are arranged in compartments that often function as largely independent muscular subunits. All muscle fibers use Ca(2+) as their main regulatory and signaling molecule. Therefore, contractile properties of muscle fibers are dependent on the variable expression of proteins...

  15. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats.

    Science.gov (United States)

    Acevedo, Luz M; Raya, Ana I; Martínez-Moreno, Julio M; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats.

  16. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

    Science.gov (United States)

    Acevedo, Luz M.; Raya, Ana I.; Martínez-Moreno, Julio M.

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats. PMID:28253314

  17. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration.

    Science.gov (United States)

    Choi, Ji Suk; Yoon, Hwa In; Lee, Kyoung Soo; Choi, Young Chan; Yang, Seong Hyun; Kim, In-San; Cho, Yong Woo

    2016-01-28

    Exosomes released from skeletal muscle cells play important roles in myogenesis and muscle development via the transfer of specific signal molecules. In this study, we investigated whether exosomes secreted during myotube differentiation from human skeletal myoblasts (HSkM) could induce a cellular response from human adipose-derived stem cells (HASCs) and enhance muscle regeneration in a muscle laceration mouse model. The exosomes contained various signal molecules including myogenic growth factors related to muscle development, such as insulin-like growth factors (IGFs), hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF2), and platelet-derived growth factor-AA (PDGF-AA). Interestingly, exosome-treated HASCs fused with neighboring cells at early time points and exhibited a myotube-like phenotype with increased expression of myogenic proteins (myosin heavy chain and desmin). On day 21, mRNAs of terminal myogenic genes were also up-regulated in exosome-treated HASCs. Moreover, in vivo studies demonstrated that exosomes from differentiating HSkM reduced the fibrotic area and increased the number of regenerated myofibers in the injury site, resulting in significant improvement of skeletal muscle regeneration. Our findings suggest that exosomes act as a biochemical cue directing stem cell differentiation and provide a cell-free therapeutic approach for muscle regeneration.

  18. The effects of ectopic UCP1 expression on gene expression in skeletal muscle [Mus Musculus

    NARCIS (Netherlands)

    Schothorst, van E.M.

    2015-01-01

    This SuperSeries is composed of the following subset Series: GSE45991: Amino acid deprivation due to overexpression of UCP1 in skeletal muscle: signalling via FGF-21 GSE45992: Transgenic overexpression of UCP1 in skeletal muscle in mice fed a HFD: signalling via FGF-21 Skeletal muscle FGF21 secretio

  19. The effects of ectopic UCP1 expression on gene expression in skeletal muscle [Mus Musculus

    NARCIS (Netherlands)

    Schothorst, van E.M.

    2015-01-01

    This SuperSeries is composed of the following subset Series: GSE45991: Amino acid deprivation due to overexpression of UCP1 in skeletal muscle: signalling via FGF-21 GSE45992: Transgenic overexpression of UCP1 in skeletal muscle in mice fed a HFD: signalling via FGF-21 Skeletal muscle FGF21

  20. Globular adiponectin induces differentiation and fusion of skeletal muscle cells

    Institute of Scientific and Technical Information of China (English)

    Tania Fiaschi; Domenico Cirelli; Giuseppina Comito; Stefania Gelmini; Giampietro Ramponi; Maria Serio; Paola Chiarugi

    2009-01-01

    The growing interest in skeletal muscle regeneration is associated with the opening of new therapeutic strategies for muscle injury after trauma, as well as several muscular degenerative pathologies, including dystrophies, muscu-lar atrophy, and cachexia. Studies focused on the ability of extracellular factors to promote myogenesis are therefore highly promising. We now report that an adipocyte-derived factor, globular adiponectin (gAd), is able to induce mus-cle gene expression and cell differentiation, gAd, besides its well-known ability to regulate several metabolic func-tions in muscle, including glucose uptake and consumption and fatty acid catabolism, is able to block cell cycle entry of myoblasts, to induce the expression of specific skeletal muscle markers such as myosin heavy chain or eaveolin-3, as well as to provoke cell fusion into multinucleated syneytia and, finally, muscle fibre formation, gAd exerts its pro-differentiative activity through redox-dependent activation of p38, Akt and 5'-AMP-activated protein kinase path-ways. Interestingly, differentiating myoblasts are autocrine for adiponectiu, and the mimicking of pro-inflammatory settings or exposure to oxidative stress strongly increases the production of the hormone from differentiating cells. These data suggest a novel function of adiponectin, directly coordinating the myogenic differentiation program and serving an autocrine function during skeletal myogenesis.

  1. Regulation of skeletal muscle capillary growth in exercise and disease.

    Science.gov (United States)

    Haas, Tara L; Nwadozi, Emmanuel

    2015-12-01

    Capillaries, which are the smallest and most abundant type of blood vessel, form the primary site of gas, nutrient, and waste transfer between the vascular and tissue compartments. Skeletal muscle exhibits the capacity to generate new capillaries (angiogenesis) as an adaptation to exercise training, thus ensuring that the heightened metabolic demand of the active muscle is matched by an improved capacity for distribution of gases, nutrients, and waste products. This review summarizes the current understanding of the regulation of skeletal muscle capillary growth. The multi-step process of angiogenesis is coordinated through the integration of a diverse array of signals associated with hypoxic, metabolic, hemodynamic, and mechanical stresses within the active muscle. The contributions of metabolic and mechanical factors to the modulation of key pro- and anti-angiogenic molecules are discussed within the context of responses to a single aerobic exercise bout and short-term and long-term training. Finally, the paradoxical lack of angiogenesis in peripheral artery disease and diabetes and the implications for disease progression and muscle health are discussed. Future studies that emphasize an integrated analysis of the mechanisms that control skeletal muscle capillary growth will enable development of targeted exercise programs that effectively promote angiogenesis in healthy individuals and in patient populations.

  2. Impact of placental insufficiency on fetal skeletal muscle growth.

    Science.gov (United States)

    Brown, Laura D; Hay, William W

    2016-11-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal "catch-up" growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population.

  3. Regulation of skeletal muscle glycogenolysis during exercise

    DEFF Research Database (Denmark)

    Hargreaves, M; Richter, Erik

    1988-01-01

    Muscle-glycogen breakdown during exercise is influenced by both local and systemic factors. Contractions per se increase glycogenolysis via a calcium-induced, transient increase in the activity of phosphorylase a, and probably also via increased concentrations of Pi. In fast-twitch muscle, increa...

  4. Regulation of skeletal muscle glycogenolysis during exercise

    DEFF Research Database (Denmark)

    Hargreaves, M; Richter, Erik

    1988-01-01

    Muscle-glycogen breakdown during exercise is influenced by both local and systemic factors. Contractions per se increase glycogenolysis via a calcium-induced, transient increase in the activity of phosphorylase a, and probably also via increased concentrations of Pi. In fast-twitch muscle, increa...

  5. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

    noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro expanded muscle...

  6. Lactate and force production in skeletal muscle

    DEFF Research Database (Denmark)

    Kristensen, Michael; Albertsen, Janni; Rentsch, Maria

    2005-01-01

    +-depressed rat soleus muscle. The pH regulation associated with lactate incubation accelerated the Na+-K+ pump. To study whether the protective effect of lactate/lactic acid is a general mechanism, we stimulated muscles to fatigue with and without pre-incubation. None of the incubation solutions improved force...

  7. In utero undernutrition programs skeletal and cardiac muscle metabolism

    Directory of Open Access Journals (Sweden)

    Brittany eBeauchamp

    2016-01-01

    Full Text Available In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease.

  8. Skeletal muscle bioenergetics in aging and heart failure.

    Science.gov (United States)

    Liu, Sophia Z; Marcinek, David J

    2017-03-01

    Changes in mitochondrial capacity and quality play a critical role in skeletal and cardiac muscle dysfunction. In vivo measurements of mitochondrial capacity provide a clear link between physical activity and mitochondrial function in aging and heart failure, although the cause and effect relationship remains unclear. Age-related decline in mitochondrial quality leads to mitochondrial defects that affect redox, calcium, and energy-sensitive signaling by altering the cellular environment that can result in skeletal muscle dysfunction independent of reduced mitochondrial capacity. This reduced mitochondrial quality with age is also likely to sensitize skeletal muscle mitochondria to elevated angiotensin or beta-adrenergic signaling associated with heart failure. This synergy between aging and heart failure could further disrupt cell energy and redox homeostasis and contribute to exercise intolerance in this patient population. Therefore, the interaction between aging and heart failure, particularly with respect to mitochondrial dysfunction, should be a consideration when developing strategies to improve quality of life in heart failure patients. Given the central role of the mitochondria in skeletal and cardiac muscle dysfunction, mitochondrial quality may provide a common link for targeted interventions in these populations.

  9. Ultrasound guided needle biopsy of skeletal muscle in neuromuscular disease

    DEFF Research Database (Denmark)

    Lindequist, S; Schrøder, H D; Larsen, C

    1990-01-01

    Guided by ultrasonography percutaneous needle biopsy of skeletal muscle was performed in 24 patients, using the one hand held Biopty system and a 2 mm Tru-Cut needle. The specimens were graded with regard to diagnostic quality and utility and almost all specimens (96%) were of highest quality...

  10. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  11. Acute exercise remodels promoter methylation in human skeletal muscle

    DEFF Research Database (Denmark)

    Barrès, Romain; Yan, Jie; Egan, Brendan

    2012-01-01

    DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene ex...

  12. Physical injuries, contractures and rigidity of skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Korenyi-Both, A.L.; Korenyi-Both, I.

    1986-01-01

    The authors condensed their knowledge of physical injuries of skeletal muscle, particularly injuries caused by mechanical energy, atmospheric pressure, radiation, extremes of temperature and electricity. The possible perils, outcomes and consequences are discussed. Special attention is given to the military medical projections.

  13. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Science.gov (United States)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  14. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  15. Redox Signaling in Skeletal Muscle: Role of Aging and Exercise

    Science.gov (United States)

    Ji, Li Li

    2015-01-01

    Skeletal muscle contraction is associated with the production of ROS due to altered O[subscript 2] distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely…

  16. Skeletal muscle training for spinal muscular atrophy type 3

    NARCIS (Netherlands)

    Bartels, Bart; Montes, Jacqueline; van der Pol, W. Ludo; de Groot, Janke F.

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of skeletal muscle training on functional performance in people with spinal muscular atrophy (SMA) type 3 and to identify any adverse effects.

  17. Factors regulating fat oxidation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiens, Bente; Alsted, Thomas Junker; Jeppesen, Jacob

    2011-01-01

    In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin...

  18. Pyruvate carboxylase is expressed in human skeletal muscle

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2010-01-01

    Pyruvate carboxylase (PC) is a mitochondrial enzyme that catalyses the carboxylation of pyruvate to oxaloacetate thereby allowing supplementation of citric acid cycle intermediates. The presence of PC in skeletal muscle is controversial. We report here, that PC protein is easily detectable...

  19. Swimming and muscle structure in fish

    NARCIS (Netherlands)

    Spierts, I.L.Y.

    1999-01-01

    In this series of studies the relations between swimming behaviour of fish in general and extreme swimming responses in particular (called fast starts or escape responses) and the structure and ontogeny of the muscle system was investigated. Special attention was paid to relate functional difference

  20. Swimming and muscle structure in fish

    NARCIS (Netherlands)

    Spierts, I.L.Y.

    1999-01-01

    In this series of studies the relations between swimming behaviour of fish in general and extreme swimming responses in particular (called fast starts or escape responses) and the structure and ontogeny of the muscle system was investigated. Special attention was paid to relate functional

  1. Swimming and muscle structure in fish

    NARCIS (Netherlands)

    Spierts, I.L.Y.

    1999-01-01

    In this series of studies the relations between swimming behaviour of fish in general and extreme swimming responses in particular (called fast starts or escape responses) and the structure and ontogeny of the muscle system was investigated. Special attention was paid to relate functional d

  2. Lifelong physical exercise delays age-associated skeletal muscle decline.

    Science.gov (United States)

    Zampieri, S; Pietrangelo, L; Loefler, S; Fruhmann, H; Vogelauer, M; Burggraf, S; Pond, A; Grim-Stieger, M; Cvecka, J; Sedliak, M; Tirpáková, V; Mayr, W; Sarabon, N; Rossini, K; Barberi, L; De Rossi, M; Romanello, V; Boncompagni, S; Musarò, A; Sandri, M; Protasi, F; Carraro, U; Kern, H

    2015-02-01

    Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977).

  3. Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism

    DEFF Research Database (Denmark)

    Li, Mengyao; Vienberg, Sara G; Bezy, Olivier

    2015-01-01

    levels of insulin. Likewise, in young mice, muscle-specific deletion of PKCδ did not rescue high-fat diet-induced insulin resistance or glucose intolerance. However, with an increase in age, PKCδ levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKCδ improved whole......Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose...... metabolism by generating mice in which PKCδ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCδ in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological...

  4. Androgens regulate gene expression in avian skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Matthew J Fuxjager

    Full Text Available Circulating androgens in adult reproductively active male vertebrates influence a diversity of organ systems and thus are considered costly. Recently, we obtained evidence that androgen receptors (AR are expressed in several skeletal muscles of three passeriform birds, the golden-collared manakin (Manacus vitellinus, zebra finch (Taenopygia guttata, and ochre-bellied flycatcher (Mionectes oleagieus. Because skeletal muscles that control wing movement make up the bulk of a bird's body mass, evidence for widespread effects of androgen action on these muscles would greatly expand the functional impact of androgens beyond their well-characterized effects on relatively discrete targets throughout the avian body. To investigate this issue, we use quantitative PCR (qPCR to determine if androgens alter gene mRNA expression patterns in wing musculature of wild golden-collared manakins and captive zebra finches. In manakins, the androgen testosterone (T up-regulated expression of parvalbumin (PV and insulin-like growth factor I (IGF-I, two genes whose products enhance cellular Ca(2+ cycling and hypertrophy of skeletal muscle fibers. In T-treated zebra finches, the anti-androgen flutamide blunted PV and IGF-I expression. These results suggest that certain transcriptional effects of androgen action via AR are conserved in passerine skeletal muscle tissue. When we examined wing muscles of manakins, zebra finches and ochre-bellied flycatchers, we found that expression of PV and IGF-I varied across species and in a manner consistent with a function for AR-dependent gene regulation. Together, these findings imply that androgens have the potential to act on avian muscle in a way that may enhance the physicality required for successful reproduction.

  5. REDD1 deletion prevents dexamethasone-induced skeletal muscle atrophy.

    Science.gov (United States)

    Britto, Florian A; Begue, Gwenaelle; Rossano, Bernadette; Docquier, Aurélie; Vernus, Barbara; Sar, Chamroeun; Ferry, Arnaud; Bonnieu, Anne; Ollendorff, Vincent; Favier, François B

    2014-12-01

    REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy. Copyright © 2014 the American Physiological Society.

  6. Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ho Cheol Kim

    2009-01-01

    Full Text Available Ho Cheol Kim1, Mahroo Mofarrahi2, Sabah NA Hussain21Department of Internal Medicine, College of Medicine, Gyeongsang National University, Gyeongsang University Hospital, Jinju, Korea; 2Critical Care and Respiratory Divisions, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, CanadaAbstract: Chronic obstructive pulmonary disease (COPD is a debilitating disease characterized by inflammation-induced airflow limitation and parenchymal destruction. In addition to pulmonary manifestations, patients with COPD develop systemic problems, including skeletal muscle and other organ-specific dysfunctions, nutritional abnormalities, weight loss, and adverse psychological responses. Patients with COPD often complain of dyspnea on exertion, reduced exercise capacity, and develop a progressive decline in lung function with increasing age. These symptoms have been attributed to increases in the work of breathing and in impairments in gas exchange that result from airflow limitation and dynamic hyperinflation. However, there is mounting evidence to suggest that skeletal muscle dysfunction, independent of lung function, contributes significantly to reduced exercise capacity and poor quality of life in these patients. Limb and ventilatory skeletal muscle dysfunction in COPD patients has been attributed to a myriad of factors, including the presence of low grade systemic inflammatory processes, nutritional depletion, corticosteroid medications, chronic inactivity, age, hypoxemia, smoking, oxidative and nitrosative stresses, protein degradation and changes in vascular density. This review briefly summarizes the contribution of these factors to overall skeletal muscle dysfunction in patients with COPD, with particular attention paid to the latest advances in the field.Keywords: skeletal muscles, chronic obstructive pulmonary disease, diaphragm, quadriceps, fatigue, disuse, atrophy, smoking, exercise

  7. Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression.

    Directory of Open Access Journals (Sweden)

    Kelly C Clause

    Full Text Available Skeletal muscle derived stem cells (MDSCs transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC and cardiac specific troponin-I (cTn-I positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13 and 20 (ED20, neonatal day 0 (ND0 and 4 (ND4, postnatal day 10 (PND10, and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle.

  8. Preservative solution for skeletal muscle biopsy samples

    Science.gov (United States)

    Kurt, Yasemin Gulcan; Kurt, Bulent; Ozcan, Omer; Topal, Turgut; Kilic, Abdullah; Muftuoglu, Tuba; Acikel, Cengizhan; Sener, Kenan; Sahiner, Fatih; Yigit, Nuri; Aydin, Ibrahim; Alay, Semih; Ekinci, Safak

    2015-01-01

    Context: Muscle biopsy samples must be frozen with liquid nitrogen immediately after excision and maintained at -80°C until analysis. Because of this requirement for tissue processing, patients with neuromuscular diseases often have to travel to centers with on-site muscle pathology laboratories for muscle biopsy sample excision to ensure that samples are properly preserved. Aim: Here, we developed a preservative solution and examined its protectiveness on striated muscle tissues for a minimum of the length of time that would be required to reach a specific muscle pathology laboratory. Materials and Methods: A preservative solution called Kurt-Ozcan (KO) solution was prepared. Eight healthy Sprague-Dawley rats were sacrificed; striated muscle tissue samples were collected and divided into six different groups. Muscle tissue samples were separated into groups for morphological, enzyme histochemical, molecular, and biochemical analysis. Statistical method used: Chi-square and Kruskal Wallis tests. Results: Samples kept in the KO and University of Wisconsin (UW) solutions exhibited very good morphological scores at 3, 6, and 18 hours, but artificial changes were observed at 24 hours. Similar findings were observed for the evaluated enzyme activities. There were no differences between the control group and the samples kept in the KO or UW solution at 3, 6, and 18 hours for morphological, enzyme histochemical, and biochemical features. The messenger ribonucleic acid (mRNA) of β-actin gene was protected up to 6 hours in the KO and UW solutions. Conclusion: The KO solution protects the morphological, enzyme histochemical, and biochemical features of striated muscle tissue of healthy rats for 18 hours and preserves the mRNA for 6 hours. PMID:26019417

  9. Preservative solution for skeletal muscle biopsy samples

    Directory of Open Access Journals (Sweden)

    Yasemin Gulcan Kurt

    2015-01-01

    Full Text Available Context : Muscle biopsy samples must be frozen with liquid nitrogen immediately after excision and maintained at -80 o C until analysis. Because of this requirement for tissue processing, patients with neuromuscular diseases often have to travel to centers with on-site muscle pathology laboratories for muscle biopsy sample excision to ensure that samples are properly preserved. Aim: Here, we developed a preservative solution and examined its protectiveness on striated muscle tissues for a minimum of the length of time that would be required to reach a specific muscle pathology laboratory. Materials and Methods: A preservative solution called Kurt-Ozcan (KO solution was prepared. Eight healthy Sprague-Dawley rats were sacrificed; striated muscle tissue samples were collected and divided into six different groups. Muscle tissue samples were separated into groups for morphological, enzyme histochemical, molecular, and biochemical analysis. Statistical method used: Chi-square and Kruskal Wallis tests. Results: Samples kept in the KO and University of Wisconsin (UW solutions exhibited very good morphological scores at 3, 6, and 18 hours, but artificial changes were observed at 24 hours. Similar findings were observed for the evaluated enzyme activities. There were no differences between the control group and the samples kept in the KO or UW solution at 3, 6, and 18 hours for morphological, enzyme histochemical, and biochemical features. The messenger ribonucleic acid (mRNA of β-actin gene was protected up to 6 hours in the KO and UW solutions. Conclusion: The KO solution protects the morphological, enzyme histochemical, and biochemical features of striated muscle tissue of healthy rats for 18 hours and preserves the mRNA for 6 hours.

  10. Angiotensin II induces differential insulin action in rat skeletal muscle.

    Science.gov (United States)

    Surapongchai, Juthamard; Prasannarong, Mujalin; Bupha-Intr, Tepmanas; Saengsirisuwan, Vitoon

    2017-03-01

    Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia. At the cellular level, insulin-stimulated glucose uptake in the soleus muscle of the ANGII-100 group was 33% lower (P study demonstrates for the first time that chronic infusion with these two pressor doses of ANGII induced differential metabolic responses at both the systemic and skeletal muscle levels.

  11. Exercise-induced phospho-proteins in skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A S; Hawley, J A; Zierath, J R

    2008-01-01

    Efforts to identify exercise-induced signaling events in skeletal muscle have been influenced by ground-breaking discoveries in the insulin action field. Initial discoveries demonstrating that exercise enhances insulin sensitivity raised the possibility that contraction directly modulates insulin...... receptor signaling events. Although the acute effects of exercise on glucose metabolism are clearly insulin-independent, the canonical insulin signaling cascade has been used as a framework by investigators in an attempt to resolve the mechanisms by which muscle contraction governs glucose metabolism....... This review focuses on recent advances in our understanding of exercise-induced signaling pathways governing glucose metabolism in skeletal muscle. Particular emphasis will be placed on the characterization of AS160, a novel Akt substrate that plays a role in the regulation of glucose transport....

  12. Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

    Science.gov (United States)

    Marquette, Michele L.; Sognier, Marguerite A.

    2013-01-01

    An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

  13. Role of glycogen availability in sarcoplasmic reticulum Ca2+ kinetics in human skeletal muscle

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt

    2011-01-01

    Glucose is stored as glycogen in skeletal muscle. The importance of glycogen as a fuel during exercise has been recognized since the 1960s; however, little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. We show that low muscle glycogen is associated...... that links energy utilization, i.e. muscle contraction, with the energy content in the muscle, thereby inhibiting a detrimental depletion of the muscle energy store....

  14. Neuromuscular electrical stimulation for skeletal muscle function.

    Science.gov (United States)

    Doucet, Barbara M; Lam, Amy; Griffin, Lisa

    2012-06-01

    Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle.

  15. Skeletal muscle responses to unweighting in humans

    Science.gov (United States)

    Dudley, Gary A.

    1991-01-01

    An overview of earth-based studies is presented emphasizing the data on muscular strength and size derived from experiments under simulated microgravity. The studies involve the elimination of weight-bearing responsibility of lower-limb human musculature to simulate the unweighting effects of space travel in the absence of exercise. Reference is given to bedrest and unilateral lower-limb suspension, both of which provide data that demonstrate the decreased strength of the knee extensors of 20-25 percent. The response is related to the decrease in cross-sectional area of the knee extensors which is a direct indication of muscle-fiber atrophy. Most of the effects of unweighting are associated with extensor muscles in the lower limbs and not with postural muscles. Unweighting is concluded to cause significant adaptations in the human neuromuscular system that require further investigation.

  16. Skeletal muscle abnormalities in patients with fibromyalgia.

    Science.gov (United States)

    Olsen, N J; Park, J H

    1998-06-01

    Widespread muscle pain and tender points are the most common complaints of fibromyalgia patients, and the underlying mechanisms responsible for these symptoms have been studied intensively during the past decade. It has been suggested that fatigue and pain may lead to decreased levels of physical activity in many patients. The resulting deconditioned state may itself contribute to muscle abnormalities. Associated symptoms such as disturbed sleep, anxiety, depression, or irritable bowel also may have a negative impact on muscle function and level of daily activities. The important interactions between the central nervous and musculoskeletal systems may involve another element, the neuroendocrine stress-response system. This review will consider both the current state of knowledge and also future studies which might be designed to answer more effectively the outstanding questions regarding the underlying pathogenesis of fibromyalgia.

  17. Skeletal muscle dysfunction in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Bozkanat Erkan

    2001-05-01

    Full Text Available Abstract It has become increasingly recognized that skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD. Muscle strength and endurance are decreased, whereas muscle fatigability is increased. There is a reduced proportion of type I fibers and an increase in type II fibers. Muscle atrophy occurs with a reduction in fiber cross-sectional area. Oxidative enzyme activity is decreased, and measurement of muscle bioenergetics during exercise reveals a reduced aerobic capacity. Deconditioning is probably very important mechanistically. Other mechanisms that may be of varying importance in individual patients include chronic hypercapnia and/or hypoxia, nutritional depletion, steroid usage, and oxidative stress. Potential therapies include exercise training, oxygen supplementation, nutritional repletion, and administration of anabolic hormones.

  18. Abnormalities of skeletal muscle in patients with chronic heart failure.

    Science.gov (United States)

    Lipkin, D P; Jones, D A; Round, J M; Poole-Wilson, P A

    1988-02-01

    We have examined muscle strength, mitochondrial enzyme activity, histochemistry and fibre size in the quadriceps muscle of 9 patients with severe chronic heart failure. A needle biopsy of the quadriceps muscle was taken with patients at rest. Maximum oxygen uptake was measured during treadmill exercise. Mean maximal oxygen consumption was 11.7 ml.kg-1.min-1. Isometric maximum voluntary contraction was reduced to 55% of the predicted value for weight. Eight biopsies were abnormal. Findings included increased acid phosphatase, increased interstitial cellularity, excess intracellular lipid accumulation, atrophy of both type I and II fibres and variation in size with hypertrophy and atrophy of fibers. Muscle fibre capillary density and the activity of mitochondrial enzymes were normal. Changes in skeletal muscle strength may play a role in the limitation of exercise capacity seen in patients with congestive heart failure.

  19. Protective Effects of Ciliary Neurotrophic Factor on Denervated Skeletal Muscle

    Institute of Scientific and Technical Information of China (English)

    黄仕龙; 王发斌; 洪光祥; 万圣祥; 康皓

    2002-01-01

    Summary: To study the effects of ciliary neurotrophic factor (CNTF) on denervated skeletal muscle atrophy and to find a new approach to ameliorate atrophy of denervated muscle, a model was estab lished by cutting the right sciatic nerve in 36 Wistar mice, with the left side serving as control. Then they were divided into two groups randomly. CNTF (1 U/ml) 0. 1 ml was injected into the right tib-ial muscle every day in experimental group, and saline was used into another group for comparison.The muscle wet weight, muscle total protein, Ca2+, physiological response and morphology were an alyzed on the 7th, 14th and 28th day after operation. Our results showed that compared to control group, there was a significant increase in muscle wet weight, total protein, Ca2+ , muscle fiber cross section area in CNTF group (P< 0. 05). CNTF could ameliorate the decrease of tetanic tension (PO), post-tetanic twitch potentiation (PTP), and the prolonged muscle relaxation time (RT)caused by denervation (P<0. 05). The motor end-plate areas 7 days and 14 days after denervation was similar (P>0. 05), but significantly larger 28 days after the denervation (P<0.05). Our re-sults suggest that CNTF exerts myotrophic effects by attenuating the morphological and functional changes associated with denervation of rat muscles and has protective effects on denervated muscle and motor end plate.

  20. MicroRNAs Involved in Skeletal Muscle Differentiation

    Institute of Scientific and Technical Information of China (English)

    Wen Luo; Qinghua Nie; Xiquan Zhang

    2013-01-01

    MicroRNAs (miRNAs) negatively regulate gene expression by promoting degradation of target mRNAs or inhibiting their translation.Previous studies have expanded our understanding that miRNAs play an important role in myogenesis and have a big impact on muscle mass,muscle fiber type and muscle-related diseases.The muscle-specific miRNAs,miR-206,miR-1 and miR-133,are among the most studied and best characterized miRNAs in skeletal muscle differentiation.They have a profound influence on multiple muscle differentiation processes,such as alternative splicing,DNA synthesis,and cell apoptosis.Many non-muscle-specific miRNAs are also required for the differentiation of muscle through interaction with myogenic factors.Studying the regulatory mechanisms of these miRNAs in muscle differentiation will extend our knowledge of miRNAs in muscle biology and will improve our understanding of the myogenesis regulation.

  1. Enhanced Myogenesis in adult skeletal muscle by transgenic expression of Myostatin Propeptide

    Science.gov (United States)

    Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-ß, plays a dominant role in the genetic control of muscle mass. Transgenic expression of myostatin propeptide in skeletal muscle showed ...

  2. The influence of estrogen on skeletal muscle: sex matters.

    Science.gov (United States)

    Enns, Deborah L; Tiidus, Peter M

    2010-01-01

    As women enter menopause, the concentration of estrogen and other female hormones declines. This hormonal decrease has been associated with a number of negative outcomes, including a greater incidence of injury as well as a delay in recovery from these injuries. Over the past two decades, our understanding of the protective effects of estrogen against various types of injury and disease states has grown immensely. In skeletal muscle, studies with animals have demonstrated that sex and estrogen may potentially influence muscle contractile properties and attenuate indices of post-exercise muscle damage, including the release of creatine kinase into the bloodstream and activity of the intramuscular lysosomal acid hydrolase, beta-glucuronidase. Furthermore, numerous studies have revealed an estrogen-mediated attenuation of infiltration of inflammatory cells such as neutrophils and macrophages into the skeletal muscles of rats following exercise or injury. Estrogen has also been shown to play a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. Although the mechanisms by which estrogen exerts its influence upon indices of skeletal muscle damage, inflammation and repair have not been fully elucidated, it is thought that estrogen may potentially exert its protective effects by: (i) acting as an antioxidant, thus limiting oxidative damage; (ii) acting as a membrane stabilizer by intercalating within membrane phospholipids; and (iii) binding to estrogen receptors, thus governing the regulation of a number of downstream genes and molecular targets. In contrast to animal studies, studies with humans have not as clearly delineated an effect of estrogen on muscle contractile function or on indices of post-exercise muscle damage and inflammation. These inconsistencies have been attributed to a number of factors, including age and fitness level of subjects, the type and intensity of exercise

  3. Pathology of skeletal muscle in fibromyalgia

    DEFF Research Database (Denmark)

    Drewes, A M; Andreasen, A; Schrøder, H D

    1993-01-01

    The value of muscle biopsy in fibromyalgia is still questioned. In this study we obtained 50 quadriceps biopsies from 20 patients and compared them blindly to 10 biopsies from five normal controls. Using light microscopy, histochemical and immunoenzymatic methods we found no definite evidence...

  4. Image-based modelling of skeletal muscle oxygenation.

    Science.gov (United States)

    Zeller-Plumhoff, B; Roose, T; Clough, G F; Schneider, P

    2017-02-01

    The supply of oxygen in sufficient quantity is vital for the correct functioning of all organs in the human body, in particular for skeletal muscle during exercise. Disease is often associated with both an inhibition of the microvascular supply capability and is thought to relate to changes in the structure of blood vessel networks. Different methods exist to investigate the influence of the microvascular structure on tissue oxygenation, varying over a range of application areas, i.e. biological in vivo and in vitro experiments, imaging and mathematical modelling. Ideally, all of these methods should be combined within the same framework in order to fully understand the processes involved. This review discusses the mathematical models of skeletal muscle oxygenation currently available that are based upon images taken of the muscle microvasculature in vivo and ex vivo Imaging systems suitable for capturing the blood vessel networks are discussed and respective contrasting methods presented. The review further informs the association between anatomical characteristics in health and disease. With this review we give the reader a tool to understand and establish the workflow of developing an image-based model of skeletal muscle oxygenation. Finally, we give an outlook for improvements needed for measurements and imaging techniques to adequately investigate the microvascular capability for oxygen exchange.

  5. The creation of a measurable contusion injury in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Margaret N. Deane

    2014-02-01

    Full Text Available The effect that compressed air massage (CAM has on skeletal muscle has been ascertained by the morphological and morphometric evaluation of healthy vervet monkey and rabbit skeletal muscle. How CAM may influence the process of healing following a contusion injury is not known. To determine how CAM or other physiotherapeutic modalities may influence healing, it is necessary to create a minor injury that is both reproducible and quantifiable at the termination of a pre-determined healing period. An earlier study described changes in the morphology of skeletal muscle following a reproducible contusion injury. This study extended that work in that it attempted to quantify the ‘severity’ of such an injury. A 201 g, elongated oval-shaped weight was dropped seven times through a 1 m tube onto the left vastus lateralis muscle of four New Zealand white rabbits. Biopsies were obtained 6 days after injury from the left healing juxta-bone and sub-dermal muscle and uninjured (control right vastus lateralis of each animal. The tissue was fixed in formal saline, embedded in wax, cut and stained with haematoxylin and phosphotungstic haematoxylin. The muscle was examined by light microscopy and quantification of the severity of injury made using a modified, ‘in-house’ morphological index and by the comparative morphometric measurement of the cross-sectioned epimysium and myofibres in injured and control muscle. The results showed that a single contusion causes multiple, quantifiable degrees of injury from skin to bone – observations of particular importance to others wishing to investigate contusion injury in human or animal models.

  6. Passive stiffness of rat skeletal muscle undernourished during fetal development

    Directory of Open Access Journals (Sweden)

    Ana Elisa Toscano

    2010-01-01

    Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

  7. Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency.

    Directory of Open Access Journals (Sweden)

    Eun-Jeong Lee

    Full Text Available The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT and nebulin deficient (NEB KO mice. Nebulin is a sarcomeric protein that when absent (NEB KO mouse or present at low levels (nemaline myopathy (NM patients with NEB mutations causes muscle weakness. We studied the effect of fast skeletal troponin activation on WT muscle and tested whether it might be a therapeutic mechanism to increase muscle strength in nebulin deficient muscle. We measured tension-pCa relations with and without added CK-2066260. Maximal active tension in NEB KO tibialis cranialis fibers in the absence of CK-2066260 was ∼60% less than in WT fibers, consistent with earlier work. CK-2066260 shifted the tension-calcium relationship leftwards, with the largest relative increase (up to 8-fold at low to intermediate calcium levels. This was a general effect that was present in both WT and NEB KO fiber bundles. At pCa levels above ∼6.0 (i.e., calcium concentrations <1 µM, CK-2066260 increased tension of NEB KO fibers to beyond that of WT fibers. Crossbridge cycling kinetics were studied by measuring k(tr (rate constant of force redevelopment following a rapid shortening/restretch. CK-2066260 greatly increased k(tr at submaximal activation levels in both WT and NEB KO fiber bundles. We also studied the sarcomere length (SL dependence of the CK-2066260 effect (SL 2.1 µm and 2.6 µm and found that in the NEB KO fibers, CK-2066260 had a larger effect on calcium sensitivity at the long SL. We conclude that fast skeletal muscle troponin activation increases force at submaximal activation in both wildtype and NEB KO fiber bundles and, importantly, that this troponin activation is a potential therapeutic mechanism for increasing force in NM and other skeletal muscle diseases with loss of muscle strength.

  8. Specific association of growth-associated protein 43 with calcium release units in skeletal muscles of lower vertebrates

    Directory of Open Access Journals (Sweden)

    G.A. Caprara

    2014-10-01

    Full Text Available Growth-associated protein 43 (GAP43, is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes, and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species.

  9. Skeletal muscle microvascular function in girls with Turner syndrome

    Science.gov (United States)

    West, Sarah L.; O'Gorman, Clodagh S.; Elzibak, Alyaa H.; Caterini, Jessica; Noseworthy, Michael D.; Rayner, Tammy; Hamilton, Jill; Wells, Greg D.

    2014-01-01

    Background Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal responses during recovery from exercise compared to HC. Methods Thirteen TS participants and 8 HC completed testing. BOLD MRI was used to measure skeletal muscle microvascular response during 60 second recovery, following 60 s of exercise at 65% of maximal workload. Exercise and recovery were repeated four times, and the BOLD signal time course was fit to a four-parameter sigmoid function. Results Participants were 13.7 ± 3.1 years old and weighed 47.9 ± 14.6 kg. The mean change in BOLD signal intensity following exercise at the end of recovery, the mean response time of the function/the washout of deoxyhemoglobin, and the mean half-time of recovery were similar between the TS and HC groups. Conclusions Our results demonstrate that compared to HC, peripheral skeletal muscle microvascular function following exercise in girls with TS is not impaired. General significance This study supports the idea that the aerobic energy pathway is not impaired in children with TS in response to submaximal exercise. Other mechanisms are likely responsible for exercise intolerance in TS; this needs to be further investigated. PMID:26676172

  10. Skeletal muscle mitochondrial uncoupling in a murine cancer cachexia model.

    Science.gov (United States)

    Tzika, A Aria; Fontes-Oliveira, Cibely Cristine; Shestov, Alexander A; Constantinou, Caterina; Psychogios, Nikolaos; Righi, Valeria; Mintzopoulos, Dionyssios; Busquets, Silvia; Lopez-Soriano, Francisco J; Milot, Sylvain; Lepine, Francois; Mindrinos, Michael N; Rahme, Laurence G; Argiles, Josep M

    2013-09-01

    Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We subjected mice to in vivo phosphorous-31 nuclear magnetic resonance (31P NMR) spectroscopy and subjected murine skeletal muscle samples to gas chromatography/mass spectrometry (GC/MS). The mice used in both experiments were Lewis lung carcinoma models of cancer cachexia. A novel 'fragmented mass isotopomer' approach was used in our dynamic analysis of 13C mass isotopomer data. Our 31P NMR and GC/MS results indicated that the adenosine triphosphate (ATP) synthesis rate and tricarboxylic acid (TCA) cycle flux were reduced by 49% and 22%, respectively, in the cancer-bearing mice (p<0.008; t-test vs. controls). The ratio of ATP synthesis rate to the TCA cycle flux (an index of mitochondrial coupling) was reduced by 32% in the cancer-bearing mice (p=0.036; t-test vs. controls). Genomic analysis revealed aberrant expression levels for key regulatory genes and transmission electron microscopy (TEM) revealed ultrastructural abnormalities in the muscle fiber, consistent with the presence of abnormal, giant mitochondria. Taken together, these data suggest that mitochondrial uncoupling occurs in cancer cachexia and thus point to the mitochondria as a potential pharmaceutical target for the treatment of cachexia. These findings may prove relevant to elucidating the mechanisms underlying skeletal muscle wasting observed in other chronic diseases, as well as in aging.

  11. Purinergic effects on Na,K-ATPase activity differ in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten; Nordsborg, Nikolai Baastrup; Bangsbo, Jens

    2014-01-01

    P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle.......P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle....

  12. Sarcocystis fayeri in skeletal muscle of horses with neuromuscular disease.

    Science.gov (United States)

    Aleman, Monica; Shapiro, Karen; Sisó, Silvia; Williams, Diane C; Rejmanek, Daniel; Aguilar, Beatriz; Conrad, Patricia A

    2016-01-01

    Recent reports of Sarcocystis fayeri-induced toxicity in people consuming horse meat warrant investigation on the prevalence and molecular characterization of Sarcocystis spp. infection in horses. Sarcocysts in skeletal muscle of horses have been commonly regarded as an incidental finding. In this study, we investigated the prevalence of sarcocysts in skeletal muscle of horses with neuromuscular disease. Our findings indicated that S. fayeri infection was common in young mature horses with neuromuscular disease and could be associated with myopathic and neurogenic processes. The number of infected muscles and number of sarcocysts per muscle were significantly higher in diseased than in control horses. S. fayeri was predominantly found in low oxidative highly glycolytic myofibers. This pathogen had a high glycolytic metabolism. Common clinical signs of disease included muscle atrophy, weakness with or without apparent muscle pain, gait deficits, and dysphagia in horses with involvement of the tongue and esophagus. Horses with myositis were lethargic, apparently painful, stiff, and reluctant to move. Similar to humans, sarcocystosis and cardiomyopathy can occur in horses. This study did not establish causality but supported a possible association (8.9% of cases) with disease. The assumption of Sarcocysts spp. being an incidental finding in every case might be inaccurate.

  13. Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    M Carmen Valero

    Full Text Available Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1 positive, non-hematopoetic (CD45⁻ cells were evaluated in wild type (WT and α7 integrin transgenic (α7Tg mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1⁺CD45⁻ stem cells were increased 2-fold in WT muscle post-exercise. The α7 integrin regulated the presence of Sca-1⁺ cells, with expansion occurring in α7Tg muscle and minimal cells present in muscle lacking the α7 integrin. Sca-1⁺CD45⁻ cells isolated from α7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs, predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7⁺ cells and facilitated formation of eMHC⁺DiI⁻ fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an α7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the α7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy.

  14. Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

    DEFF Research Database (Denmark)

    Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.;

    2008-01-01

    The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... (n = 11) received a single Epo injection of 15,000 IU (double blinded, cross over, placebo). A single Epo injection reduced myoglobin and increased transferrin receptor and MRF-4 mRNA content within 10 h after injection. Plasma hormones remained unaltered. Capillarization and fiber hypertrophy...

  15. Exercise, GLUT4, and skeletal muscle glucose uptake.

    Science.gov (United States)

    Richter, Erik A; Hargreaves, Mark

    2013-07-01

    Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions. Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose uptake relies on GLUT4 translocation, glucose uptake also depends on muscle GLUT4 expression which is increased following exercise. AMPK and CaMKII are key signaling kinases that appear to regulate GLUT4 expression via the HDAC4/5-MEF2 axis and MEF2-GEF interactions resulting in nuclear export of HDAC4/5 in turn leading to histone hyperacetylation on the GLUT4 promoter and increased GLUT4 transcription. Exercise training is the most potent stimulus to increase skeletal muscle GLUT4 expression, an effect that may partly contribute to improved insulin action and glucose disposal and enhanced muscle glycogen storage following exercise training in health and disease.

  16. Effect of VEGF on the Regenerative Capacity of Muscle Stem Cells in Dystrophic Skeletal Muscle

    Science.gov (United States)

    Deasy, Bridget M; Feduska, Joseph M; Payne, Thomas R; Li, Yong; Ambrosio, Fabrisia; Huard, Johnny

    2009-01-01

    We have isolated a population of muscle-derived stem cells (MDSCs) that, when compared with myoblasts, display an improved regeneration capacity, exhibit better cell survival, and improve myogenesis and angiogenesis. In addition, we and others have observed that the origin of the MDSCs may reside within the blood vessel walls (endothelial cells and pericytes). Here, we investigated the role of vascular endothelial growth factor (VEGF)–mediated angiogenesis in MDSC transplantation–based skeletal muscle regeneration in mdx mice (an animal model of muscular dystrophy). We studied MDSC and MDSC transduced to overexpress VEGF; no differences were observed in vitro in terms of phenotype or myogenic differentiation. However, after in vivo transplantation, we observe an increase in angiogenesis and endogenous muscle regeneration as well as a reduction in muscle fibrosis in muscles transplanted with VEGF-expressing cells when compared to control cells. In contrast, we observe a significant decrease in vascularization and an increase in fibrosis in the muscles transplanted with MDSCs expressing soluble forms-like tyrosine kinase 1 (sFlt1) (VEGF-specific antagonist) when compared to control MDSCs. Our results indicate that VEGF-expressing cells do not increase the number of dystrophin-positive fibers in the injected mdx muscle, when compared to the control MDSCs. Together the results suggest that the transplantation of VEGF-expressing MDSCs improved skeletal muscle repair through modulation of angiogenesis, regeneration and fibrosis in the injected mdx skeletal muscle. PMID:19603004

  17. The mechanics of mouse skeletal muscle when shortening during relaxation.

    Science.gov (United States)

    Barclay, C J; Lichtwark, G A

    2007-01-01

    The dynamic properties of relaxing skeletal muscle have not been well characterised but are important for understanding muscle function during terrestrial locomotion, during which a considerable fraction of muscle work output can be produced during relaxation. The purpose of this study was to characterise the force-velocity properties of mouse skeletal muscle during relaxation. Experiments were performed in vitro (21 degrees C) using bundles of fibres from mouse soleus and EDL muscles. Isovelocity shortening was applied to muscles during relaxation following short tetanic contractions. Using data from different contractions with different shortening velocities, curves relating force output to shortening velocity were constructed at intervals during relaxation. The velocity component included contributions from shortening of both series elastic component (SEC) and contractile component (CC) because force output was not constant. Early in relaxation force-velocity relationships were linear but became progressively more curved as relaxation progressed. Force-velocity curves late in relaxation had the same curvature as those for the CC in fully activated muscles but V(max) was reduced to approximately 50% of the value in fully activated muscles. These results were the same for slow- and fast-twitch muscles and for relaxation following maximal tetani and brief, sub-maximal tetani. The measured series elastic compliance was used to partition shortening velocity between SEC and CC. The curvature of the CC force-velocity relationship was constant during relaxation. The SEC accounted for most of the shortening and work output during relaxation and its power output during relaxation exceeded the maximum CC power output. It is proposed that unloading the CC, without any change in its overall length, accelerated cross-bridge detachment when shortening was applied during relaxation.

  18. Aetiology of skeletal muscle 'cramps' during exercise: a novel hypothesis.

    Science.gov (United States)

    Schwellnus, M P; Derman, E W; Noakes, T D

    1997-06-01

    The aetiology of exercise-associated muscle cramps (EAMC), defined as 'painful, spasmodic, involuntary contractions of skeletal muscle during or immediately after physical exercise', has not been well investigated and is therefore not well understood. This review focuses on the physiological basis for skeletal muscle relaxation, a historical perspective and analysis of the commonly postulated causes of EAMC, and known facts about EAMC from recent clinical studies. Historically, the causes of EAMC have been proposed as (1) inherited abnormalities of substrate metabolism ('metabolic theory') (2) abnormalities of fluid balance ('dehydration theory'), (3) abnormalities of serum electrolyte concentrations ('electrolyte theory') and (4) extreme environmental conditions of heat or cold ('environmental theory'). Detailed analyses of the available scientific literature including data from recent studies do not support these hypothesis for the causes of EAMC. In a recent study, electromyographic (EMG) data obtained from runners during EAMC revealed that baseline activity is increased (between spasms of cramping) and that a reduction in the baseline EMG activity correlates well with clinical recovery. Furthermore, during acute EAMC the EMG activity is high, and passive stretching is effective in reducing EMG activity. This relieves the cramp probably by invoking the inverse stretch reflex. In two animal studies, abnormal reflex activity of the muscle spindle (increased activity) and the Golgi tendon organ (decreased activity) has been observed in fatigued muscle. We hypothesize that EAMC is caused by sustained abnormal spinal reflex activity which appears to be secondary to muscle fatigue. Local muscle fatigue is therefore responsible for increased muscle spindle afferent and decreased Golgi tendon organ afferent activity. Muscles which cross two joints can more easily be placed in shortened positions during exercise and would therefore decrease the Golgi tendon organ

  19. Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

    Directory of Open Access Journals (Sweden)

    JA DeQuach

    2012-06-01

    Full Text Available Peripheral artery disease (PAD currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI, which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold’s degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 µL of skeletal muscle matrix or collagen 1 week post-injury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue-specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.

  20. Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy.

    Science.gov (United States)

    Bongers, Kale S; Fox, Daniel K; Kunkel, Steven D; Stebounova, Larissa V; Murry, Daryl J; Pufall, Miles A; Ebert, Scott M; Dyle, Michael C; Bullard, Steven A; Dierdorff, Jason M; Adams, Christopher M

    2015-01-15

    Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy.

  1. Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy

    Science.gov (United States)

    Bongers, Kale S.; Fox, Daniel K.; Kunkel, Steven D.; Stebounova, Larissa V.; Murry, Daryl J.; Pufall, Miles A.; Ebert, Scott M.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy. PMID:25406264

  2. Validation of shear wave elastography in skeletal muscle.

    Science.gov (United States)

    Eby, Sarah F; Song, Pengfei; Chen, Shigao; Chen, Qingshan; Greenleaf, James F; An, Kai-Nan

    2013-09-27

    Skeletal muscle is a very dynamic tissue, thus accurate quantification of skeletal muscle stiffness throughout its functional range is crucial to improve the physical functioning and independence following pathology. Shear wave elastography (SWE) is an ultrasound-based technique that characterizes tissue mechanical properties based on the propagation of remotely induced shear waves. The objective of this study is to validate SWE throughout the functional range of motion of skeletal muscle for three ultrasound transducer orientations. We hypothesized that combining traditional materials testing (MTS) techniques with SWE measurements will show increased stiffness measures with increasing tensile load, and will correlate well with each other for trials in which the transducer is parallel to underlying muscle fibers. To evaluate this hypothesis, we monitored the deformation throughout tensile loading of four porcine brachialis whole-muscle tissue specimens, while simultaneously making SWE measurements of the same specimen. We used regression to examine the correlation between Young's modulus from MTS and shear modulus from SWE for each of the transducer orientations. We applied a generalized linear model to account for repeated testing. Model parameters were estimated via generalized estimating equations. The regression coefficient was 0.1944, with a 95% confidence interval of (0.1463-0.2425) for parallel transducer trials. Shear waves did not propagate well for both the 45° and perpendicular transducer orientations. Both parallel SWE and MTS showed increased stiffness with increasing tensile load. This study provides the necessary first step for additional studies that can evaluate the distribution of stiffness throughout muscle. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Exercise-induced AMPK activity in skeletal muscle

    DEFF Research Database (Denmark)

    Friedrichsen, Martin; Mortensen, Brynjulf; Pehmøller, Christian

    2013-01-01

    The energy/fuel sensor 5'-AMP-activated protein kinase (AMPK) is viewed as a master regulator of cellular energy balance due to its many roles in glucose, lipid, and protein metabolism. In this review we focus on the regulation of AMPK activity in skeletal muscle and its involvement in glucose me...... metabolism, including glucose transport and glycogen synthesis. In addition, we discuss the plausible interplay between AMPK and insulin signaling regulating these processes.......The energy/fuel sensor 5'-AMP-activated protein kinase (AMPK) is viewed as a master regulator of cellular energy balance due to its many roles in glucose, lipid, and protein metabolism. In this review we focus on the regulation of AMPK activity in skeletal muscle and its involvement in glucose...

  4. Insulin resistance and mitochondrial function in skeletal muscle

    DEFF Research Database (Denmark)

    Dela, Flemming; Helge, Jørn Wulff

    2013-01-01

    are used in the attempt to resolve the mechanisms of insulin resistance. In this context, a dysfunction of mitochondria in the skeletal muscle has been suggested to play a pivotal role. It has been postulated that a decrease in the content of mitochondria in the skeletal muscle can explain the insulin...... resistance. Complementary to this also specific defects of components in the respiratory chain in the mitochondria have been suggested to play a role in insulin resistance. A key element in these mechanistic suggestions is inability to handle substrate fluxes and subsequently an accumulation of ectopic...... intramyocellular lipids, interfering with insulin signaling. In this review we will present the prevailing view-points and argue for the unlikelihood of this scenario being instrumental in human insulin resistance. This article is part of a Directed Issue entitled: Bioenergetic dysfunction....

  5. Human skeletal muscle glycogen utilization in exhaustive exercise

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Holmberg, Hans-Christer; Schrøder, Henrik Daa

    2011-01-01

    to be influenced by fibre type prior to exercise, as well as carbohydrate availability during the subsequent period of recovery. These findings provide insight into the significance of fibre type-specific compartmentalization of glycogen metabolism in skeletal muscle during exercise and subsequent recovery. .......Although glycogen is known to be heterogeneously distributed within skeletal muscle cells, there is presently little information available about the role of fibre types, utilization and resynthesis during and after exercise with respect to glycogen localization. Here, we tested the hypothesis...... contained more intramyofibrillar and subsarcolemmal glycogen than the latter. In highly glycogen-depleted fibres, the remaining small intermyofibrillar and subsarcolemmal glycogen particles were often found to cluster in groupings. In the recovery period, when the athletes received either a carbohydrate...

  6. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... sympathetic vasoconstriction. ATP is released into plasma from erythrocytes and endothelial cells and the plasma concentration increases in both the feeding artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine...... and endothelial cells. In the interstitium, both ATP and adenosine stimulate the formation of NO and prostaglandins, but ATP has also been suggested to induce vasoconstriction and stimulate afferent nerves that signal to increase sympathetic nerve activity. Adenosine has been shown to contribute to exercise...

  7. Intense and exhaustive exercise induce oxidative stress in skeletal muscle

    Directory of Open Access Journals (Sweden)

    T Thirumalai

    2011-03-01

    Full Text Available Objective: To assess the oxidative stress and antioxidant defense system in the skeletal muscle of male albino rats subjected to strenuous exercise programme. Methods: Wistar strain albino rats were subjected to exhaustive swimming exercise programme daily for a period of five days. The thiobarbituric acid reactive substances (TBARS, conjugated dienes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase were measured in the gastrocnemius muscle of the exercised animals. Results: The elevated levels of TBARS and conjugated dienes indicated the oxidative stress in the gastrocemius muscle of the exercised animals. The depleted activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the exercise animals indicated the increased oxidative stress and decreased antioxidative defense system in the muscle. Conclusions: The study suggests that prolonged strenuous exercise programme can induce oxidative stress and therefore an optimal level of exercise schedule should be advocated to obtain the maximum benefit of exercise programme.

  8. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was perfo...... recovery of human skeletal muscle.......The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  9. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte;

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  10. Exploring the whereabouts of GLUT4 in skeletal muscle (review)

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Ralston, Evelyn

    2002-01-01

    The glucose transporter GLUT4 is expressed in muscle, fat cells, brain and kidney. In contrast to other glucose transporters, GLUT4 in unstimulated cells is mostly intracellular. Stimuli such as insulin and muscle contractions then cause the translocation of GLUT4 to the cell surface. Questions...... related to GLUT4 storage compartments, trafficking to the surface membrane, and nature of the intracellular pools, have kept many groups busy for the past 20 years. Yet, one of the main questions in the field remains the universality of GLUT4 features. Can one extrapolate work done on fat cells to muscle...... or brain? Or vice-versa? Can one use cultures to predict GLUT4 behaviour in fully differentiated tissues? This review summarizes the authors' knowledge of GLUT4 biology in skeletal muscle, which is the predominant tissue for glucose homeostasis. The results are compared to those obtained with the fat cell...

  11. Skeletal muscle substrate metabolism during exercise: methodological considerations

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; González-Alonso, J; Sacchetti, M

    1999-01-01

    and metabolites may be both taken up and released by muscle at rest and during exercise, isotopes can be used to determine uptake and/or release and also fractional uptake can be accounted for. Furthermore, the use of isotopes opens up further possibilities for the estimation of oxidation rates of various......The aim of the present article is to evaluate critically the various methods employed in studies designed to quantify precisely skeletal muscle substrate utilization during exercise. In general, the pattern of substrate utilization during exercise can be described well from O2 uptake measurements...... and the respiratory exchange ratio. However, if the aim is to quantify limb or muscle metabolism, invasive measurements have to be carried out, such as the determination of blood flow, arterio-venous (a-v) difference measurements for O2 and relevant substrates, and biopsies of the active muscle. As many substrates...

  12. Dynamics of the skeletal muscle secretome during myoblast differentiation

    DEFF Research Database (Denmark)

    Henningsen, Jeanette; Rigbolt, Kristoffer T G; Blagoev, Blagoy

    2010-01-01

    of the intracellular levels of members of the semaphorin family and their corresponding secretion dynamics demonstrated that the release of secreted proteins is tightly regulated by the secretory pathway, the stability of the protein, and/or the processing of secreted proteins. Finally, we provide 299 unique...... proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics...

  13. Computed tomography of skeletal muscles in neuromuscular disease

    Energy Technology Data Exchange (ETDEWEB)

    Rodiek, S.O.; Kuether, G.

    1985-06-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

  14. An in vitro model of skeletal muscle volume regulation.

    Directory of Open Access Journals (Sweden)

    Anna Wibberley

    Full Text Available Hypertonic media causes cells to shrink due to water loss through aquaporin channels. After acute shrinkage, cells either regulate their volume or, alternatively, undergo a number of metabolic changes which ultimately lead to cell death. In many cell types, hypertonic shrinkage is followed by apoptosis. Due to the complex 3D morphology of skeletal muscle and the difficulty in obtaining isolated human tissue, we have begun skeletal muscle volume regulation studies using the human skeletal muscle cell line TE671RD. In this study we investigated whether hypertonic challenge of the human skeletal muscle cell line TE671RD triggered cell death or evoked a cell volume recovery response.The cellular volume of TE671RD cells was calculated from the 2D surface area. Cell death was assessed by both the trypan blue live/dead assay and the TUNEL assay.Medium osmolality was increased by addition of up to 200 mM sucrose. Addition of 200 mM sucrose resulted in mean cell shrinkage of 44±1% after 30 mins. At later time points (2 and 4 hrs two separate cell subpopulations with differing mean cell volume became apparent. The first subpopulation (15±2% of the total cell number continued to shrink whereas the second subpopulation had an increased cell volume. Cell death was observed in a small proportion of cells (approximately 6-8%.We have established that a substantial proportion of TE671RD cells respond to hypertonic challenge with RVI, but that these cells are resistant to hypertonicity triggered cell death.

  15. Skeletal muscle responses to negative energy balance: effects of dietary protein.

    Science.gov (United States)

    Carbone, John W; McClung, James P; Pasiakos, Stefan M

    2012-03-01

    Sustained periods of negative energy balance decrease body mass due to losses of both fat and skeletal muscle mass. Decreases in skeletal muscle mass are associated with a myriad of negative consequences, including suppressed basal metabolic rate, decreased protein turnover, decreased physical performance, and increased risk of injury. Decreases in skeletal muscle mass in response to negative energy balance are due to imbalanced rates of muscle protein synthesis and degradation. However, the underlying physiological mechanisms contributing to the loss of skeletal muscle during energy deprivation are not well described. Recent studies have demonstrated that consuming dietary protein at levels above the current recommended dietary allowance (0.8 g · kg(-1) · d(-1)) may attenuate the loss of skeletal muscle mass by affecting the intracellular regulation of muscle anabolism and proteolysis. However, the specific mechanism by which increased dietary protein spares skeletal muscle through enhanced molecular control of muscle protein metabolism has not been elucidated. This article reviews the available literature related to the effects of negative energy balance on skeletal muscle mass, highlighting investigations that assessed the influence of varying levels of dietary protein on skeletal muscle protein metabolism. Further, the molecular mechanisms that may contribute to the regulation of skeletal muscle mass in response to negative energy balance and alterations in dietary protein level are described.

  16. Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients

    Directory of Open Access Journals (Sweden)

    Godard MP

    2012-11-01

    Full Text Available Michael P Godard,1 Samantha A Whitman,2 Yao-Hua Song,3 Patrice Delafontaine41Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO, USA; 2Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA; 3Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou, China; 4Tulane University School of Medicine, Section of Cardiology, New Orleans, LA, USABackground: Heart failure (HF, a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1 and insulin-like growth factor-binding protein-5 (IGFB-5 appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single–skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure.Materials and methods: To investigate these molecules during “early” events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size.Results: There were more (P < 0.05 single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7% compared to the control subjects (13% ± 2%. IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05, respectively. Strikingly

  17. Receptor Expression in Rat Skeletal Muscle Cell Cultures

    Science.gov (United States)

    Young, Ronald B.

    1996-01-01

    One on the most persistent problems with long-term space flight is atrophy of skeletal muscles. Skeletal muscle is unique as a tissue in the body in that its ability to undergo atrophy or hypertrophy is controlled exclusively by cues from the extracellular environment. The mechanism of communication between muscle cells and their environment is through a group of membrane-bound and soluble receptors, each of which carries out unique, but often interrelated, functions. The primary receptors include acetyl choline receptors, beta-adrenergic receptors, glucocorticoid receptors, insulin receptors, growth hormone (i.e., somatotropin) receptors, insulin-like growth factor receptors, and steroid receptors. This project has been initiated to develop an integrated approach toward muscle atrophy and hypertrophy that takes into account information on the populations of the entire group of receptors (and their respective hormone concentrations), and it is hypothesized that this information can form the basis for a predictive computer model for muscle atrophy and hypertrophy. The conceptual basis for this project is illustrated in the figure below. The individual receptors are shown as membrane-bound, with the exception of the glucocorticoid receptor which is a soluble intracellular receptor. Each of these receptors has an extracellular signalling component (e.g., innervation, glucocorticoids, epinephrine, etc.), and following the interaction of the extracellular component with the receptor itself, an intracellular signal is generated. Each of these intracellular signals is unique in its own way; however, they are often interrelated.

  18. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  19. Nanosecond electric pulses modulate skeletal muscle calcium dynamics and contraction

    Science.gov (United States)

    Valdez, Chris; Jirjis, Michael B.; Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.

    2017-02-01

    Irreversible electroporation therapy is utilized to remove cancerous tissues thru the delivery of rapid (250Hz) and high voltage (V) (1,500V/cm) electric pulses across microsecond durations. Clinical research demonstrated that bipolar (BP) high voltage microsecond pulses opposed to monophasic waveforms relieve muscle contraction during electroporation treatment. Our group along with others discovered that nanosecond electric pulses (nsEP) can activate second messenger cascades, induce cytoskeletal rearrangement, and depending on the nsEP duration and frequency, initiate apoptotic pathways. Of high interest across in vivo and in vitro applications, is how nsEP affects muscle physiology, and if nuances exist in comparison to longer duration electroporation applications. To this end, we exposed mature skeletal muscle cells to monopolar (MP) and BP nsEP stimulation across a wide range of electric field amplitudes (1-20 kV/cm). From live confocal microscopy, we simultaneously monitored intracellular calcium dynamics along with nsEP-induced muscle movement on a single cell level. In addition, we also evaluated membrane permeability with Yo-PRO-1 and Propidium Iodide (PI) across various nsEP parameters. The results from our findings suggest that skeletal muscle calcium dynamics, and nsEP-induced contraction exhibit exclusive responses to both MP and BP nsEP exposure. Overall the results suggest in vivo nsEP application may elicit unique physiology and field applications compared to longer pulse duration electroporation.

  20. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  1. Passive heat acclimation improves skeletal muscle contractility in humans.

    Science.gov (United States)

    Racinais, S; Wilson, M G; Périard, J D

    2017-01-01

    The aim of this study was to investigate the effect of repeated passive heat exposure (i.e., acclimation) on muscle contractility in humans. Fourteen nonheat-acclimated males completed two trials including electrically evoked twitches and voluntary contractions in thermoneutral conditions [Cool: 24°C, 40% relative humidity (RH)] and hot ambient conditions in the hyperthermic state (Hot: 44-50°C, 50% RH) on consecutive days in a counterbalanced order. Rectal temperature was ~36.5°C in Cool and was maintained at ~39°C throughout Hot. Both trials were repeated after 11 days of passive heat acclimation (1 h per day, 48-50°C, 50% RH). Heat acclimation decreased core temperature in Cool (-0.2°C, P heat acclimation improved skeletal muscle contractility as evidenced by an increase in evoked peak twitch amplitude both in Cool (20.5 ± 3.6 vs. 22.0 ± 4.0 N·m) and Hot (20.5 ± 4.7 vs. 22.0 ± 4.0 N·m) (+9%, P heat acclimation improves skeletal muscle contractile function during electrically evoked and voluntary muscle contractions of different intensities both in Cool and Hot. These results suggest that repeated heat exposure may have important implications to passively maintain or even improve muscle function in a variety of performance and clinical settings. Copyright © 2017 the American Physiological Society.

  2. Skeletal muscle metabolism in hypokinetic rats

    Science.gov (United States)

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  3. Methods for the Organogenesis of Skeletal Muscle in Tissue Culture

    Science.gov (United States)

    Vandenburgh, Herman; Shansky, Janet; DelTatto, Michael; Chromiak, Joseph

    1997-01-01

    Skeletal muscle structure is regulated by many factors, including nutrition, hormones, electrical activity, and tension. The muscle cells are subjected to both passive and active mechanical forces at all stages of development and these forces play important but poorly understood roles in regulating muscle organogenesis and growth. For example, during embryogenesis, the rapidly growing skeleton places large passive mechanical forces on the attached muscle tissue. These forces not only help to organize the proliferating mononucleated myoblasts into the oriented, multinucleated myofibers of a functional muscle but also tightly couple the growth rate of muscle to that of bone. Postnatally, the actively contracting, innervated muscle fibers are subjected to different patterns of active and passive tensions which regulate longitudinal and cross sectional myofiber growth. These mechanically-induced organogenic processes have been difficult to study under normal tissue culture conditions, resulting in the development of numerous methods and specialized equipment to simulate the in vivo mechanical environment.These techniques have led to the "engineering" of bioartificial muscles (organoids) which display many of the characteristics of in vivo muscle including parallel arrays of postmitotic fibers organized into fascicle-like structures with tendon-like ends. They are contractile, express adult isoforms of contractile proteins, perform directed work, and can be maintained in culture for long periods. The in vivo-like characteristics and durability of these muscle organoids make them useful for long term in vitro studies on mechanotransduction mechanisms and on muscle atrophy induced by decreased tension. In this report, we described a simple method for generating muscle organoids from either primary embrionic avain or neonatal rodent myoblasts.

  4. Hyperinsulinemia and skeletal muscle fatty acid trafficking

    OpenAIRE

    Kanaley, Jill A.; Shadid, Samyah; Sheehan, Michael T.; Guo, ZengKui; Jensen, Michael D

    2013-01-01

    We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-13C]palmitate (0400–0900 h) and [U-13C]oleate (0800–1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass−1·min−1) clamp (0800–1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-13C]palmitate in...

  5. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Nielsen, Søren; Scheele, Camilla; Yfanti, Christina;

    2010-01-01

    of all four myomiRs (P training expression levels 14 days after ceasing the training programme. Components of major pathways involved in endurance adaptation such as MAPK and TGF-ß were predicted to be targeted by the myomiRs examined. Tested......, but their role in regulating human skeletal muscle adaptation remains unknown.......Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus...

  6. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  7. Muscle atrophy in response to cytotoxic chemotherapy is dependent on intact glucocorticoid signaling in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Theodore P Braun

    Full Text Available Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia.

  8. The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Loeffler, Jean-Philippe; Picchiarelli, Gina; Dupuis, Luc; Gonzalez De Aguilar, Jose-Luis

    2016-03-01

    Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets.

  9. "Nutraceuticals" in relation to human skeletal muscle and exercise.

    Science.gov (United States)

    Deane, Colleen S; Wilkinson, Daniel J; Phillips, Bethan E; Smith, Kenneth; Etheridge, Timothy; Atherton, Philip J

    2017-04-01

    Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cachexia, COPD, and organ failure, via engendering favorable adaptations such as increased muscle mass and oxidative capacity. Therefore, it is important to consider the effects of established and novel effectors of muscle mass, function, and metabolism in relation to nutrition and exercise. To address this gap, in this review, we detail existing evidence surrounding the efficacy of a nonexhaustive list of macronutrient, micronutrient, and "nutraceutical" compounds alone and in combination with exercise in relation to skeletal muscle mass, metabolism (protein and fuel), and exercise performance (i.e., strength and endurance capacity). It has long been established that macronutrients have specific roles and impact upon protein metabolism and exercise performance, (i.e., protein positively influences muscle mass and protein metabolism), whereas carbohydrate and fat intakes can influence fuel metabolism and exercise performance. Regarding novel nutraceuticals, we show that the following ones in particular may have effects in relation to 1) muscle mass/protein metabolism: leucine, hydroxyl β-methylbutyrate, creatine, vitamin-D, ursolic acid, and phosphatidic acid; and 2) exercise performance: (i.e., strength or endurance capacity): hydroxyl β-methylbutyrate, carnitine, creatine, nitrates, and β-alanine. Copyright © 2017 the American Physiological Society.

  10. Modulation of nitric oxide synthase isoenzymes inreperfused skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the modulation of nitric oxide synthnse (NOS) isoenzymes in skeletal muscle during 3 h ischemia/reperfusion (I/R, 3 h ischemia followed by 3 h reperfusion). Methods: The extensor digitorum longuses (EDLs)from 20 adult rats were divided into 4 groups: the normal,the sham operation, the ischemia (3 h), and the ischemia/reperfusion group. One normal EDL from each rat was used as the non-operated control, and the opposite ones are distributed into the 3 remaining groups. All the samples were studied with Western blotting technique and immumohistochemistry staining. Results: Three sizes of protein bands verified with the proteins of relative molecule to be of 155 000, 140 000and 135 000, were detected in the EDL homogenate by Western blotting, which were comparable with the positive controls for nNOS, eNOS and iNOS, respectively. Immunostaining demonstrated that nNOS was present in the muscle fiber, with a similar location of the muscle stria, eNOS was found apparently in microvascular endothelia,but not found in muscle fibers, and iNOS was found in the leukocytes around the muscle fiber and some endothelia cells. Immunostaining paralleled the Western blotting results. Conclusions: It suggests that the constitutive nNOS and eNOS protein can be regulated by I/R, and I/R results in a down regulation of nNOS and up-regulation of eNOS and iNOS in reperfused skeletal muscle. The fact that nNOS is present around stria suggests that nNOS may have a close relationship with muscle function. The localization of eNOS in endothelial cell indicates its role in regulating blood supply of the muscle. Based on these findings, it is possible that NO produced by distinct NOS may play a different role in I/R injury.

  11. A novel potassium channel in skeletal muscle mitochondria.

    Science.gov (United States)

    Skalska, Jolanta; Piwońska, Marta; Wyroba, Elzbieta; Surmacz, Liliana; Wieczorek, Rafal; Koszela-Piotrowska, Izabela; Zielińska, Joanna; Bednarczyk, Piotr; Dołowy, Krzysztof; Wilczynski, Grzegorz M; Szewczyk, Adam; Kunz, Wolfram S

    2008-01-01

    In this work we provide evidence for the potential presence of a potassium channel in skeletal muscle mitochondria. In isolated rat skeletal muscle mitochondria, Ca(2+) was able to depolarize the mitochondrial inner membrane and stimulate respiration in a strictly potassium-dependent manner. These potassium-specific effects of Ca(2+) were completely abolished by 200 nM charybdotoxin or 50 nM iberiotoxin, which are well-known inhibitors of large conductance, calcium-activated potassium channels (BK(Ca) channel). Furthermore, NS1619, a BK(Ca)-channel opener, mimicked the potassium-specific effects of calcium on respiration and mitochondrial membrane potential. In agreement with these functional data, light and electron microscopy, planar lipid bilayer reconstruction and immunological studies identified the BK(Ca) channel to be preferentially located in the inner mitochondrial membrane of rat skeletal muscle fibers. We propose that activation of mitochondrial K(+) transport by opening of the BK(Ca) channel may be important for myoprotection since the channel opener NS1619 protected the myoblast cell line C2C12 against oxidative injury.

  12. Comparing Simplification Strategies for the Skeletal Muscle Proteome

    Directory of Open Access Journals (Sweden)

    Bethany Geary

    2016-03-01

    Full Text Available Skeletal muscle is a complex tissue that is dominated by the presence of a few abundant proteins. This wide dynamic range can mask the presence of lower abundance proteins, which can be a confounding factor in large-scale proteomic experiments. In this study, we have investigated a number of pre-fractionation methods, at both the protein and peptide level, for the characterization of the skeletal muscle proteome. The analyses revealed that the use of OFFGEL isoelectric focusing yielded the largest number of protein identifications (>750 compared to alternative gel-based and protein equalization strategies. Further, OFFGEL led to a substantial enrichment of a different sub-population of the proteome. Filter-aided sample preparation (FASP, coupled to peptide-level OFFGEL provided more confidence in the results due to a substantial increase in the number of peptides assigned to each protein. The findings presented here support the use of a multiplexed approach to proteome characterization of skeletal muscle, which has a recognized imbalance in the dynamic range of its protein complement.

  13. Signalling and the control of skeletal muscle size

    Energy Technology Data Exchange (ETDEWEB)

    Otto, Anthony [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom); Patel, Ketan, E-mail: ketan.patel@reading.ac.uk [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom)

    2010-11-01

    Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

  14. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

    Science.gov (United States)

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F

    2015-10-13

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  15. Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Yuji Miyamoto

    Full Text Available Skeletal muscle depletion (sarcopenia is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC.We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS or overall survival (OS associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5% after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009. Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194-3.619; p = 0.010 was independently associated with OS.Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC.

  16. Metastases of esophageal carcinoma to skeletal muscle:Single center experience

    Institute of Scientific and Technical Information of China (English)

    Jan Cincibuch; Miroslav Myslive(c)ek; Bohuslav Melichar; (C)estmír Neoral; Iva Metelková; Michaela Zezulová; Hana Procházková-(S)tudentová

    2012-01-01

    Metastases of esophageal carcinoma to the skeletal muscle are rare,but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT).A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases.Four patients had skeletal muscle metastases of esophageal carcinoma,including two patients with squamous cell carcinoma.In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases,muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma.In all cases,skeletal muscle metastases were the first manifestation of systemic disease.In three patients palliation was obtained with the combination of external beam radiation therapy,systemic chemotherapy or surgical resection.Skeletal muscle metastases are a rare complication of esophageal carcinoma.

  17. In Vivo Molecular Responses of Fast and Slow Muscle Fibers to Lipopolysaccharide in a Teleost Fish, the Rainbow Trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Leonardo J. Magnoni

    2015-02-01

    Full Text Available The physiological consequences of the activation of the immune system in skeletal muscle in fish are not completely understood. To study the consequences of the activation of the immune system by bacterial pathogens on skeletal muscle function, we administered lipopolysaccharide (LPS, an active component of Gram-negative bacteria, in rainbow trout and performed transcriptomic and proteomic analyses in skeletal muscle. We examined changes in gene expression in fast and slow skeletal muscle in rainbow trout at 24 and 72 h after LPS treatment (8 mg/kg by microarray analysis. At the transcriptional level, we observed important changes in metabolic, mitochondrial and structural genes in fast and slow skeletal muscle. In slow skeletal muscle, LPS caused marked changes in the expression of genes related to oxidative phosphorylation, while in fast skeletal muscle LPS administration caused major changes in the expression of genes coding for glycolytic enzymes. We also evaluated the effects of LPS administration on the fast skeletal muscle proteome and identified 14 proteins that were differentially induced in LPS-treated trout, primarily corresponding to glycolytic enzymes. Our results evidence a robust and tissue-specific response of skeletal muscle to an acute inflammatory challenge, affecting energy utilization and possibly growth in rainbow trout.

  18. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  19. Energy conservation attenuates the loss of skeletal muscle excitability during intense contractions

    DEFF Research Database (Denmark)

    Macdonald, W A; Ørtenblad, N; Nielsen, Ole Bækgaard

    2007-01-01

    High-frequency stimulation of skeletal muscle has long been associated with ionic perturbations, resulting in the loss of membrane excitability, which may prevent action potential propagation and result in skeletal muscle fatigue. Associated with intense skeletal muscle contractions are large...... conservation on skeletal muscle excitability. Muscle ATP utilization was reduced using a combination of the cross-bridge cycling blocker N-benzyl-p-toluene sulfonamide (BTS) and the SR Ca2+ release channel blocker Na-dantrolene, which reduce activity of the myosin ATPase and SR Ca2+-ATPase. Compared...

  20. Human skeletal muscle fibroblasts stimulate in vitro myogenesis and in vivo muscle regeneration.

    Science.gov (United States)

    Mackey, Abigail L; Magnan, Mélanie; Chazaud, Bénédicte; Kjaer, Michael

    2017-08-01

    Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. The extent of cross-talk between fibroblasts, as the source of matrix protein, and satellite cells in humans is unknown. We studied this in human muscle biopsies and cell-culture studies. We observed a strong stimulation of myogenesis by human fibroblasts in cell culture. In biopsies collected 30 days after a muscle injury protocol, fibroblast number increased to four times control levels, where fibroblasts were found to be preferentially located immediately surrounding regenerating muscle fibres. These novel findings indicate an important role for fibroblasts in supporting the regeneration of muscle fibres, potentially through direct stimulation of satellite cell differentiation and fusion, and contribute to understanding of cell-cell cross-talk during physiological and pathological muscle remodelling. Accumulation of skeletal muscle extracellular matrix is an unfavourable characteristic of many muscle diseases, muscle injury and sarcopenia. In addition to the indispensable role satellite cells play in muscle regeneration, there is emerging evidence in rodents for a regulatory influence on fibroblast activity. However, the influence of fibroblasts on satellite cells and muscle regeneration in humans is unknown. The purpose of this study was to investigate this in vitro and during in vivo regeneration in humans. Following a muscle injury protocol in young healthy men (n = 7), the number of fibroblasts (TCF7L2+), satellite cells (Pax7+), differentiating myogenic cells (myogenin+) and regenerating fibres (neonatal/embryonic myosin+) was determined from biopsy cross-sections. Fibroblasts and myogenic precursor cells (MPCs) were also isolated from human skeletal muscle (n = 4) and co-cultured using different cell ratios, with the two cell populations either in direct contact with each other or separated by a permeable

  1. The role of hyperplasia on the increase of skeletal muscle

    Directory of Open Access Journals (Sweden)

    Victor Hugo Maciel Meloni

    2005-06-01

    Full Text Available Skeletal muscle hypertrophy is resulted from the individual increase of the fiber cross-sectional area. This adaptative phenomenon is normally observed in the muscle tissue submitted to a regimen of physical exercises, like strength training. The degree of muscular hypertrophy is directly related to the type of exercise and its intensity. Strength training normally produces a hypertrophy of greater magnitude when compared to other types of physical exercise. However, it is possible that there is another adaptive mechanism contributing for increasing skeletal muscle size. This mechanism is called hyperplasia, and can be defined as an increase in the cells, or fibers, number in the muscle. This brief review aims to verify the role of hyperplasia in the increase of skeletal muscle size. RESUMO A hipertrofia do músculo esquelético é resultado do aumento individual da área transversal da fibra. Este fenômeno adaptativo é comumente observado no tecido muscular submetido à um regime de exercícios físicos, como o treinamento de força. O grau de hipertrofia muscular está diretamente relacionado ao tipo de exercício e sua intensidade. O treinamento de força normalmente produz uma hipertrofia de maior magnitude, quando comparada aos outros tipos de exercício físico. Todavia, é provável que haja outro mecanismo adaptativo contribuindo para a hipertrofia do músculo esquelético. Este mecanismo chama-se hiperplasia, e pode ser traduzida por um aumento no número de células, ou fibras musculares em relação ao número original. Este breve resumo tem por objetivo verificar qual é o papel da hiperplasia na hipertrofia do músculo esquelético.

  2. Comprehensive analysis of tropomyosin isoforms in skeletal muscles by top-down proteomics.

    Science.gov (United States)

    Jin, Yutong; Peng, Ying; Lin, Ziqing; Chen, Yi-Chen; Wei, Liming; Hacker, Timothy A; Larsson, Lars; Ge, Ying

    2016-04-01

    Mammalian skeletal muscles are heterogeneous in nature and are capable of performing various functions. Tropomyosin (Tpm) is a major component of the thin filament in skeletal muscles and plays an important role in controlling muscle contraction and relaxation. Tpm is known to consist of multiple isoforms resulting from different encoding genes and alternative splicing, along with post-translational modifications. However, a systematic characterization of Tpm isoforms in skeletal muscles is still lacking. Therefore, we employed top-down mass spectrometry (MS) to identify and characterize Tpm isoforms present in different skeletal muscles from multiple species, including swine, rat, and human. Our study revealed that Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. Tandem MS was utilized to identify the sequences of the major Tpm isoforms. Furthermore, quantitative analysis revealed muscle-type specific differences in the abundance of un-modified and modified Tpm isoforms in rat and human skeletal muscles. This study represents the first systematic investigation of Tpm isoforms in skeletal muscles, which not only demonstrates the capabilities of top-down MS for the comprehensive characterization of skeletal myofilament proteins but also provides the basis for further studies on these Tpm isoforms in muscle-related diseases.

  3. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard;

    2013-01-01

    of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...

  4. Optical reflectance in fibrous tissues and skeletal muscles

    Science.gov (United States)

    Ranasinghesagara, Janaka C.

    We studied two biological tissues with optically anisotropic structures: high moisture soy protein extrudates and skeletal muscles. High moisture extrusion has been used to produce vegetable meat analogs that resemble real animal meat and have significant health benefits. Since visual and textural properties are key factors for consumer acceptance, assessing fiber formation in the extruded soy protein product is important for quality control purpose. A non-destructive method based on photon migration was developed to measure fiber formation in extruded soy proteins. The measured fiber formation index in intact samples showed good agreement with that obtained from image analysis on peeled samples. By implementing this new method in a fast laser scanning system, we have acquired two dimensional mappings of fiber formation and orientation in the entire sample in real time. In addition to fibrous structures, skeletal muscles have a unique periodic sarcomere structure which produces strong light diffractions. However, inconsistent experimental results have been reported in single fiber diffraction studies. By applying the three-dimensional coupled wave theory in a physical sarcomere model, we found that a variety of experimental observations can be explained if inhomogeneous muscle morphological profiles are considered. We also discovered that the sarcomere structure produced a unique optical reflectance pattern in whole muscle. None of the existing light propagation theories are able to describe this pattern. We developed a Monte Carlo model incorporating the sarcomere diffraction effect. The simulated results quantitatively resemble the unique patterns observed in experiments. We used a set of parameters to quantify the optical reflectance profiles produced by a point incident light in whole muscle. Two parameters, q and B, were obtained by numerically fitting the equi-intensity contours of the reflectance pattern. Two spatial gradients were calculated along the

  5. MicroRNA transcriptome profiles during swine skeletal muscle development

    Directory of Open Access Journals (Sweden)

    Sonstegard Tad S

    2009-02-01

    Full Text Available Abstract Background MicroRNA (miR are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells, three stages of fetal growth, day-old neonate, and the adult. Results Twelve potential novel miR were detected that did not match previously reported sequences. In addition, a number of miR previously reported to be expressed in mammalian muscle were detected, having a variety of abundance patterns through muscle development. Muscle-specific miR-206 was nearly absent in proliferating satellite cells in culture, but was the highest abundant miR at other time points evaluated. In addition, miR-1 was moderately abundant throughout developmental stages with highest abundance in the adult. In contrast, miR-133 was moderately abundant in adult muscle and either not detectable or lowly abundant throughout fetal and neonate development. Changes in abundance of ubiquitously expressed miR were also observed. MiR-432 abundance was highest at the earliest stage of fetal development tested (60 day-old fetus and decreased throughout development to the adult. Conversely, miR-24 and miR-27 exhibited greatest abundance in proliferating satellite cells and the adult, while abundance of miR-368, miR-376, and miR-423-5p was greatest in the neonate. Conclusion These data present a complete set of transcriptome profiles to evaluate miR abundance at specific stages of skeletal muscle growth in swine. Identification of these miR provides an initial group of miR that may play a vital role in muscle development and growth.

  6. Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Mounier, Rémi; Pedersen, Bente Klarlund; Plomgaard, Peter

    2010-01-01

    from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1...... a significantly higher VEGF protein content than vastus lateralis and triceps muscle. In conclusion, we have shown that there are muscle-specific differences in HIF-1alpha and VEGF expression within human skeletal muscle at rest in normoxic conditions. Recent results, when combined with the findings described...

  7. Alpha-adrenergic receptors in rat skeletal muscle

    DEFF Research Database (Denmark)

    Rattigan, S; Appleby, G J; Edwards, S J;

    1986-01-01

    Sarcolemma-enriched preparations from muscles rich in slow oxidative red fibres contained specific binding sites for the alpha 1 antagonist, prazosin (e.g. soleus Kd 0.13 nM, Bmax 29 fmol/mg protein). Binding sites for prazosin were almost absent from white muscle. Displacement of prazosin bindin...... adrenergic receptors are present on the sarcolemma of slow oxidative red fibres of rat skeletal muscle. The presence provides the mechanistic basis for apparent alpha-adrenergic effects to increase glucose and oxygen uptake in perfused rat hindquarter.......Sarcolemma-enriched preparations from muscles rich in slow oxidative red fibres contained specific binding sites for the alpha 1 antagonist, prazosin (e.g. soleus Kd 0.13 nM, Bmax 29 fmol/mg protein). Binding sites for prazosin were almost absent from white muscle. Displacement of prazosin binding...... from sarcolemma of soleus muscle (phentolamine greater than phenylephrine greater than idazoxan greater than yohimbine) suggested that the receptors were alpha 1. Binding sites for dihydroalprenolol (beta antagonist) were also more concentrated on red than white muscle and outnumbered prazosin sites...

  8. Fetal stem cells and skeletal muscle regeneration: a therapeutic approach

    Directory of Open Access Journals (Sweden)

    Michela ePozzobon

    2014-08-01

    Full Text Available More than 40% of the body mass is represented by muscle tissue, which possesses the innate ability to regenerate after damage through the activation of muscle specific stem cell, namely satellite cells. Muscle diseases, in particular chronic degenerative state of skeletal muscle such as dystrophies, lead to a perturbation of the regenerative process, which causes the premature exhaustion of satellite cell reservoir due to continue cycles of degeneration/regeneration. Nowadays, the research is focused on different therapeutic approaches, ranging from gene and cell to pharmacological therapy, but still there is not a definitive cure in particular for genetic muscle disease. Taking this in mind, in this article we will give special consideration to muscle diseases and the use of fetal derived stem cells as new approach for therapy. Cells of fetal origin, from cord blood to placenta and amniotic fluid, can be easily obtained without ethical concern, expanded and differentiated in culture, and possess immunemodulatory properties. The in vivo approach in animal models can be helpful to study the mechanism underneath the operating principle of the stem cell reservoir, namely the niche, which holds great potential to understand the onset of muscle pathologies.

  9. Adipophilin distribution and colocalization with lipid droplets in skeletal muscle.

    LENUS (Irish Health Repository)

    Shaw, Christopher S

    2009-05-01

    Intramyocellular lipids (IMCL) are stored as discrete lipid droplets which are associated with a number of proteins. The lipid droplet-associated protein adipophilin (the human orthologue of adipose differentiation-related protein) is ubiquitously expressed and is one of the predominant lipid droplet-proteins in skeletal muscle. The aim of this study was to investigate the subcellular distribution of adipophilin in human muscle fibres and to measure the colocalization of adipophilin with IMCL. Muscle biopsies from six lean male cyclists (BMI 23.4 +\\/- 0.4, aged 31 +\\/- 2 years, W (max) 346 +\\/- 8) were stained for myosin heavy chain type 1, IMCL, adipophilin and mitochondria using immunofluorescence and viewed with widefield and confocal fluorescence microscopy. The present study shows that like IMCL, the adipophilin content is ~twofold greater in type I skeletal muscle fibres and is situated in the areas between the mitochondrial network. Colocalization analysis demonstrated that 61 +\\/- 2% of IMCL contain adipophilin. Although the majority of adipophilin is contained within IMCL, 36 +\\/- 4% of adipophilin is not associated with IMCL. In conclusion, this study indicates that the IMCL pool is heterogeneous, as the majority but not all IMCL contain adipophilin.

  10. Erythropoietin treatment enhances mitochondrial function in human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ulla ePlenge

    2012-03-01

    Full Text Available Abstract Erythropoietin (Epo treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over eight weeks with oral iron (100 mg supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92±5 to 113±7 pmol.sec-1.mg-1 and ETS (107±4 to 143±14 pmol.sec-1.mg-1, P<0.05, demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

  11. Quercetin protects rat skeletal muscle from ischemia reperfusion injury.

    Science.gov (United States)

    Ekinci Akdemir, Fazile Nur; Gülçin, İlhami; Karagöz, Berna; Soslu, Recep

    2016-01-01

    In this study, we investigated the potential beneficial effects of quercetin on skeletal muscle ischemia reperfusion injury. Twenty-four Sprague-Dawley type rats were randomly divided into four groups. In the sham group, only gastrocnemius muscle were removed and given no quercetin. In ischemia group, all the femoral artery, vein and collaterals were occluded in the left hindlimb by applying tourniquate under general anaesthesia for three hours but reperfusion was not done. In the Quercetin + Ischemia reperfusion group, quercetin (200 mg kg(-1) dose orally) was given during one-week reoperation and later ischemia reperfusion model was done. Finally, gastrocnemius muscle samples were removed to measure biochemical parameters. The biomarkers, MDA levels, SOD, CAT and GPx activities, were evaluated related to skeletal muscle ischemia reperfusion injury. MDA levels reduced and SOD, CAT and GPx activities increased significantly in Quercetin + Ischemia reperfusion group. Results clearly showed that Quercetin have a protective role against oxidative damage induced by ischemia reperfusion in rats.

  12. Defective Homocysteine Metabolism: Potential Implications for Skeletal Muscle Malfunction

    Directory of Open Access Journals (Sweden)

    Suresh C. Tyagi

    2013-07-01

    Full Text Available Hyperhomocysteinemia (HHcy is a systemic medical condition and has been attributed to multi-organ pathologies. Genetic, nutritional, hormonal, age and gender differences are involved in abnormal homocysteine (Hcy metabolism that produces HHcy. Homocysteine is an intermediate for many key processes such as cellular methylation and cellular antioxidant potential and imbalances in Hcy production and/or catabolism impacts gene expression and cell signaling including GPCR signaling. Furthermore, HHcy might damage the vagus nerve and superior cervical ganglion and affects various GPCR functions; therefore it can impair both the parasympathetic and sympathetic regulation in the blood vessels of skeletal muscle and affect long-term muscle function. Understanding cellular targets of Hcy during HHcy in different contexts and its role either as a primary risk factor or as an aggravator of certain disease conditions would provide better interventions. In this review we have provided recent Hcy mediated mechanistic insights into different diseases and presented potential implications in the context of reduced muscle function and integrity. Overall, the impact of HHcy in various skeletal muscle malfunctions is underappreciated; future studies in this area will provide deeper insights and improve our understanding of the association between HHcy and diminished physical function.

  13. Age- and stroke-related skeletal muscle changes: a review for the geriatric clinician.

    Science.gov (United States)

    Sions, Jaclyn Megan; Tyrell, Christine M; Knarr, Brian A; Jancosko, Angela; Binder-Macleod, Stuart A

    2012-01-01

    Independently, aging and stroke each have a significant negative impact on skeletal muscle, but the potential cumulative effects of aging and stroke have not been explored. Optimal interventions for individuals post stroke may include those that specifically target skeletal muscle. Addressing changes in muscles may minimize activity limitations and enhance participation post stroke. This article reviews the impact of aging and stroke on muscle morphology and composition, including fiber atrophy, reductions in muscle cross-sectional area, changes in muscle fiber distributions, and increases in intramuscular fat. Relationships between changes in muscle structure, muscle function, and physical mobility are reviewed. Clinical recommendations that preserve and enhance skeletal muscle in the aging adult and individuals post stroke are discussed. Future research directions that include systematic comparison of the differences in skeletal muscle between younger and older adults who have sustained a stroke are suggested.

  14. AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity

    DEFF Research Database (Denmark)

    Lantier, Louise; Fentz, Joachim; Mounier, Rémi

    2014-01-01

    AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a central role in skeletal muscle metabolism. We used skeletal muscle-specific AMPKα1α2 double-knockout (mdKO) mice to provide direct genetic evidence of the physiological importance of AMPK in regulating muscle ...

  15. The Molecular Basis for Load-Induced Skeletal Muscle Hypertrophy

    Science.gov (United States)

    Marcotte, George R.; West, Daniel W.D.; Baar, Keith

    2016-01-01

    In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Lastly, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

  16. The molecular basis for load-induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Marcotte, George R; West, Daniel W D; Baar, Keith

    2015-03-01

    In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Last, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise.

  17. A simple and rapid method to characterize lipid fate in skeletal muscle.

    Science.gov (United States)

    Massart, Julie; Zierath, Juleen R; Chibalin, Alexander V

    2014-06-24

    Elevated fatty acids contribute to the development of type 2 diabetes and affect skeletal muscle insulin sensitivity. Since elevated intramuscular lipids and insulin resistance is strongly correlated, aberrant lipid storage or lipid intermediates may be involved in diabetes pathogenesis. The aim of this study was to develop a method to determine the dynamic metabolic fate of lipids in primary human skeletal muscle cells and in intact mouse skeletal muscle. We report a simple and fast method to characterize lipid profiles in skeletal muscle using thin layer chromatography. The described method was specifically developed to assess lipid utilization in cultured and intact skeletal muscle. We determined the effect of a pan-diacylglycerol kinase (DGK) class I inhibitor (R59949) on lipid metabolism to validate the method. In human skeletal muscle cells, DGK inhibition impaired diacylglycerol (DAG) conversion to phosphatidic acid and increased triglyceride synthesis. In intact glycolytic mouse skeletal muscle, DGK inhibition triggered the accumulation of DAG species. Conversely, the DGK inhibitor did not affect DAG content in oxidative muscle. This simple assay detects rapid changes in the lipid species composition of skeletal muscle with high sensitivity and specificity. Determination of lipid metabolism in skeletal muscle may further elucidate the mechanisms contributing to the pathogenesis of insulin resistance in type 2 diabetes or obesity.

  18. Skeletal muscle adaptation in response to exercise(Ⅱ)

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Zhen Yan

    2004-01-01

    @@ MITOCHONDRIAL BIOGENESIS AND SLOW MUSCLE GENE EXPRESSION Recent findings in proxisome proliferators-activated recep tor γ (PPARγ) coactivator-1α (PGC-1α) gene regulation and function have led to the consideration of PGC-1α as a key regulator in regulating important features of skeletal muscle adaptation.PGC-1α is a transcriptional coactivator cloned originally by a yeast-two-hybrid screen from a differentiated brown fat cell line using PPARγ as bait[80]. PGC-1α mRNA and protein are highly expressed in slow,oxidative fibers compared to the fast, glycolytic fibers[81-82],consistent with the function of a gene involved in fiber type specialization. The functional importance of PGC-1α in striated muscles has been suggested by several different models [83-84].

  19. Fasting- and Exercise-Induced PDH Regulation in Skeletal Muscle

    DEFF Research Database (Denmark)

    Gudiksen, Anders

    state. Fasting-induced down-regulation of PDHa activity in skeletal muscle of control mice was associated with increased phosphorylation of all four known sites in PDH-E1α as well as with increased PDK4 and SIRT3 protein without changes in total acetylation of PDH-E1α. Lack of muscle PGC-1α reduced PDH......-E1α, PDK1, 2, 4, PDP1, and SIRT3 protein content as well as increased total lysine PDH-E1α acetylation in the fed state. Knockout of muscle PGC-1α did not influence the fasting-induced increase in PDH-E1α phosphorylation, but prevented the fasting-induced increase in SIRT3 protein. Study IV...

  20. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  1. Norepinephrine spillover from skeletal muscle during exercise in humans

    DEFF Research Database (Denmark)

    Savard, G K; Richter, Erik; Strange, S

    1989-01-01

    The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one...... in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising...... legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise...

  2. Hyperinsulinemia and skeletal muscle fatty acid trafficking.

    Science.gov (United States)

    Kanaley, Jill A; Shadid, Samyah; Sheehan, Michael T; Guo, ZengKui; Jensen, Michael D

    2013-08-15

    We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-¹³C]palmitate (0400-0900 h) and [U-¹³C]oleate (0800-1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass⁻¹·min⁻¹) clamp (0800-1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-¹³C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ~1/10th of that observed in the previous saline control studies (P women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin.

  3. Skeletal muscle vasodilation during systemic hypoxia in humans.

    Science.gov (United States)

    Dinenno, Frank A

    2016-01-15

    In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response.

  4. Hypohydration does not impair skeletal muscle glycogen resynthesis after exercise.

    Science.gov (United States)

    Neufer, P D; Sawka, M N; Young, A J; Quigley, M D; Latzka, W A; Levine, L

    1991-04-01

    The purpose of this investigation was to examine the effects of moderate hypohydration (HY) on skeletal muscle glycogen resynthesis after exhaustive exercise. On two occasions, eight males completed 2 h of intermittent cycle ergometer exercise (4 bouts of 17 min at 60% and 3 min at 80% of maximal O2 consumption/10 min rest) to reduce muscle glycogen concentrations (control values 711 +/- 41 mumol/g dry wt). During one trial, cycle exercise was followed by several hours of light upper body exercise in the heat without fluid replacement to induce HY (-5% body wt); in the second trial, sufficient water was ingested during the upper body exercise and heat exposure to maintain euhydration (EU). In both trials, 400 g of carbohydrate were ingested at the completion of exercise and followed by 15 h of rest while the desired hydration level was maintained. Muscle biopsy samples were obtained from the vastus lateralis immediately after intermittent cycle exercise (T1) and after 15 h of rest (T2). During the HY trial, the muscle water content was lower (P less than 0.05) at T1 and T2 (288 +/- 9 and 265 +/- 5 ml/100 g dry wt, respectively; NS) than during EU (313 +/- 8 and 301 +/- 4 ml/100 g dry wt, respectively; NS). Muscle glycogen concentration was not significantly different during EU and HY at T1 (200 +/- 35 vs. 251 +/- 50 mumol/g dry wt) or T2 (452 +/- 34 vs. 491 +/- 35 mumol/g dry wt). These data indicate that, despite reduced water content during the first 15 h after heavy exercise, skeletal muscle glycogen resynthesis is not impaired.

  5. Studies on physiological and intracellular effects of moxonidine in human skeletal muscle cells

    OpenAIRE

    Rønning, Camilla

    2006-01-01

    The sympatholytic antihypertensive agent moxonidine, a centrally-acting I1-imidazoline receptor agonist, has in clinical studies shown a beneficial effect on insulin resistance in hypertensive patients. Since skeletal muscle is the major organ involved in glucose disposal, experiments were performed to investigate whether moxonidine have direct effects on skeletal muscle cells in vitro. Satellite cells from skeletal muscle biopsies (musculus vastus lateralis and musculus transversus abdo...

  6. A simple and rapid method to characterize lipid fate in skeletal muscle

    OpenAIRE

    Massart, Julie; Juleen R Zierath; Chibalin, Alexander V.

    2014-01-01

    Background Elevated fatty acids contribute to the development of type 2 diabetes and affect skeletal muscle insulin sensitivity. Since elevated intramuscular lipids and insulin resistance is strongly correlated, aberrant lipid storage or lipid intermediates may be involved in diabetes pathogenesis. The aim of this study was to develop a method to determine the dynamic metabolic fate of lipids in primary human skeletal muscle cells and in intact mouse skeletal muscle. We report a simple and fa...

  7. A simple and rapid method to characterize lipid fate in skeletal muscle

    OpenAIRE

    Massart, Julie; Zierath, Juleen R.; Chibalin, Alexander V.

    2014-01-01

    Background Elevated fatty acids contribute to the development of type 2 diabetes and affect skeletal muscle insulin sensitivity. Since elevated intramuscular lipids and insulin resistance is strongly correlated, aberrant lipid storage or lipid intermediates may be involved in diabetes pathogenesis. The aim of this study was to develop a method to determine the dynamic metabolic fate of lipids in primary human skeletal muscle cells and in intact mouse skeletal muscle. We report a simple and fa...

  8. Expression of dystrophin-glycoprotein complex at the skeletal muscle sarcolemma in Duchenne muscular dystrophy

    OpenAIRE

    Zhao, Lei; Chao-ping HU; Wang, Yi; Shui-zhen ZHOU; Shi, Yi-Yun; Xi-hua LI

    2015-01-01

    Background  Eccentric exercise or high tension exercise could cause damage to skeletal muscle structure, resulting in deficiency of dystrophin and secondary loss of dystrophin-glycoprotein complex (DGC) from the sarcolemma, which indicated that down-regulation of dystrophin was one of the key points of skeletal muscle injury from eccentric exercise. Duchenne muscular dystrophy (DMD) is caused by mutations of DMD gene, resulting in the absence of dystrophin, which means that skeletal muscles o...

  9. Hyperinsulinemia and skeletal muscle fatty acid trafficking

    Science.gov (United States)

    Kanaley, Jill A.; Shadid, Samyah; Sheehan, Michael T.; Guo, ZengKui

    2013-01-01

    We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-13C]palmitate (0400–0900 h) and [U-13C]oleate (0800–1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass−1·min−1) clamp (0800–1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-13C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ∼1/10th of that observed in the previous saline control studies (P < 0.001). At the time of the second biopsy, the enrichment in oleoylcarnitine was <25% of that in imTG-oleate and was not correlated with imTG-oleate enrichment. The intramyocellular nonesterified fatty acid-palmitate-to-imTG-palmitate enrichment ratio was greater (P < 0.05) in women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin. PMID:23820622

  10. Skeletal muscle CT of lower extremities in myotonic dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirofumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya

    1988-02-01

    We evaluated the leg and thigh muscles of 4 control subjects and 10 patients with myotonic dystrophy using computed tomography. Taking previous reports about the skeletal muscle CT of myotonic dystrophy into account, we concluded that the following 5 features are characteristic of myotonic dystrophy: 1. The main change is the appearance of low-density areas in muscles; these areas reflect fat tissue. In addition, the muscle mass decreases in size. 2. The leg is more severely affected than the thigh. 3. In the thigh, although the m. quadriceps femoris, especially the vastus muscles, tends to be affected, the m. adductor longus and magnus tend to be preserved. 4. In the leg, although the m. tibialis anterior and m. triceps surae tend to be affected, the m. peroneus longus, brevis, and m. tibialis posterior tend to be preserved. 5. Compensatory hypertrophy is often observed in the m. rectus femoris, m. adductor longus, m. adductor magnus, m. peroneus longus, and m. peroneus brevis, accompanied by the involvement of their agonist muscles.

  11. Short-range mechanical properties of skeletal and cardiac muscles.

    Science.gov (United States)

    Campbell, Kenneth S

    2010-01-01

    Striated muscles are disproportionately stiff for small movements. This facet of their behavior can be demonstrated by measuring the force produced when the muscle is stretched more than about 1% of its initial length. When this is done, it can be seen that force rises rapidly during the initial phases of the movement and much less rapidly during the latter stages of the stretch. Experiments performed using chemically permeabilized skeletal and cardiac muscles show that the initial stiffness of the preparations increases in proportion with isometric force as the free Ca²(+) concentration in the bathing solution is raised from a minimal to a saturating value. This is strong evidence that the short-range mechanical properties of activated muscle result from stretching myosin cross-bridges that are attached between the thick and thin filaments. Relaxed intact muscles also exhibit short-range mechanical properties but the molecular mechanisms underlying this behavior are less clear. This chapter summarizes some of the interesting features of short-range mechanical properties in different types of muscle preparation, describes some of the likely underlying mechanisms and discusses the potential physiological significance of the behavior.

  12. Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

    Science.gov (United States)

    Max, Stephen R.; Konagaya, Masaaki; Konagaya, Yoko; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa

    1986-01-01

    The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

  13. Mitochondrial Ca(2+) uptake in skeletal muscle health and disease.

    Science.gov (United States)

    Zhou, Jingsong; Dhakal, Kamal; Yi, Jianxun

    2016-08-01

    Muscle uses Ca(2+) as a messenger to control contraction and relies on ATP to maintain the intracellular Ca(2+) homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca(2+) from their surroundings, a process called mitochondrial Ca(2+) uptake. Under physiological conditions, Ca(2+) uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca(2+) overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca(2+) uptake could shape spatio-temporal patterns of intracellular Ca(2+) signaling. Malfunction of mitochondrial Ca(2+) uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca(2+) levels. Besides the sudden elevation of Ca(2+) level induced by action potentials, Ca(2+) transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca(2+) uptake is fast and big enough to shape intracellular Ca(2+) signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca(2+) inside mitochondria. This review focuses on characterization of mitochondrial Ca(2+) uptake in skeletal muscle and its role in muscle physiology and diseases.

  14. Spectrum of Nondystrophic Skeletal Muscle Channelopathies in Children.

    Science.gov (United States)

    Al-Ghamdi, Fouad; Darras, Basil T; Ghosh, Partha S

    2017-05-01

    The nondystrophic skeletal muscle channelopathies are a group of disorders caused by mutations of various voltage-gated ion channel genes, including nondystrophic myotonia and periodic paralysis. We identified patients with a diagnosis of muscle channelopathy from our neuromuscular database in a tertiary care pediatric center from 2005 to 2015. We then performed a retrospective review of their medical records for demographic characteristics, clinical features, investigations, treatment, and follow-up. Thirty-three patients were identified. Seventeen had nondystrophic myotonia. Seven of them had chloride channelopathy (four Becker disease and three Thomsen disease). Warm-up phenomenon and muscle hypertrophy were common clinical manifestations in this subgroup. Ten patients had sodium channelopathy (four paramyotonia congenita and six other sodium channel myotonia). Stiffness of the facial muscles was an important presenting symptom, and eyelid myotonia was a common clinical finding in this subgroup. The majority of these patients had electrical myotonia. Mexiletine was effective in controlling the symptoms in patients who had received treatment. Sixteen children had periodic paralysis (four hyperkalemic periodic paralysis, eight hypokalemic periodic paralysis, and four Andersen-Tawil syndrome). Acetazolamide was commonly used to prevent paralytic attacks and was found to be effective. Nondystrophic muscle channelopathies present with diverse clinical manifestations (myotonia, muscle hypertrophy, proximal weakness, swallowing difficulties, and periodic paralysis). Cardiac arrhythmias are potentially life threatening in Andersen-Tawil syndrome. Timely identification of these disorders is helpful for effective symptomatic management and genetic counseling. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Viscoelasticity-based MR elastography of skeletal muscle

    Science.gov (United States)

    Klatt, Dieter; Papazoglou, Sebastian; Braun, Jürgen; Sack, Ingolf

    2010-11-01

    An in vivo multifrequency magnetic resonance elastography (MRE) protocol was developed for studying the viscoelastic properties of human skeletal muscle in different states of contraction. Low-frequency shear vibrations in the range of 25-62.5 Hz were synchronously induced into the femoral muscles of seven volunteers and measured in a cross-sectional view by encoding the fast-transverse shear wave component parallel to the muscle fibers. The so-called springpot model was used for deriving two viscoelastic constants, μ and α, from the dispersion functions of the complex shear modulus in relaxed and in loaded muscle. Representing the shear elasticity parallel to the muscle fibers, μ increased in all volunteers upon contraction from 2.68 ± 0.23 kPa to 3.87 ± 0.50 kPa. Also α varied with load, indicating a change in the geometry of the mechanical network of muscle from relaxation (α = 0.253 ± 0.009) to contraction (α = 0.270 ± 0.009). These results provide a reference for a future assessment of muscular dysfunction using rheological parameters.

  16. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.

    Science.gov (United States)

    Bullard, Steven A; Seo, Seongjin; Schilling, Birgit; Dyle, Michael C; Dierdorff, Jason M; Ebert, Scott M; DeLau, Austin D; Gibson, Bradford W; Adams, Christopher M

    2016-08-19

    Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Role of active contraction and tropomodulins in regulating actin filament length and sarcomere structure in developing zebrafish skeletal muscle

    Directory of Open Access Journals (Sweden)

    Lise eMazelet

    2016-03-01

    Full Text Available Whilst it is recognised that contraction plays an important part in maintaining the structure and function of mature skeletal muscle, its role during development remains undefined. In this study the role of movement in skeletal muscle maturation was investigated in intact zebrafish embryos using a combination of genetic and pharmacological approaches. An immotile mutant line (cacnb1ts25 which lacks functional voltage-gated calcium channels (dihydropyridine receptors in the muscle and pharmacological immobilisation of embryos with a reversible anaesthetic (Tricaine, allowed the study of paralysis (in mutants and anaesthetised fish and recovery of movement (reversal of anaesthetic treatment. The effect of paralysis in early embryos (aged between 17-24 hours post fertilisation, hpf on skeletal muscle structure at both myofibrillar and myofilament level was determined using both immunostaining with confocal microscopy and small angle X-ray diffraction. The consequences of paralysis and subsequent recovery on the localisation of the actin capping proteins Tropomodulin 1 &4 (Tmod in fish aged from 17hpf until 42hpf was also assessed. The functional consequences of early paralysis were investigated by examining the mechanical properties of the larval muscle. The length-force relationship, active and passive tension, was measured in immotile, recovered and control skeletal muscle at 5 and 7 day post fertilisation (dpf. Recovery of muscle function was also assessed by examining swimming patterns in recovered and control fish. Inhibition of the initial embryonic movements (up to 24 hpf resulted in an increase in myofibril length and a decrease in width followed by almost complete recovery in both moving and paralysed fish by 42hpf. In conclusion, myofibril organisation is regulated by a dual mechanism involving movement-dependent and movement-independent processes. The initial contractile event itself drives the localisation of Tmod1 to its sarcomeric

  18. Hedgehog can drive terminal differentiation of amniote slow skeletal muscle

    Directory of Open Access Journals (Sweden)

    Bildsoe Heidi

    2004-07-01

    Full Text Available Abstract Background Secreted Hedgehog (Hh signalling molecules have profound influences on many developing and regenerating tissues. Yet in most vertebrate tissues it is unclear which Hh-responses are the direct result of Hh action on a particular cell type because Hhs frequently elicit secondary signals. In developing skeletal muscle, Hhs promote slow myogenesis in zebrafish and are involved in specification of medial muscle cells in amniote somites. However, the extent to which non-myogenic cells, myoblasts or differentiating myocytes are direct or indirect targets of Hh signalling is not known. Results We show that Sonic hedgehog (Shh can act directly on cultured C2 myoblasts, driving Gli1 expression, myogenin up-regulation and terminal differentiation, even in the presence of growth factors that normally prevent differentiation. Distinct myoblasts respond differently to Shh: in some slow myosin expression is increased, whereas in others Shh simply enhances terminal differentiation. Exposure of chick wing bud cells to Shh in culture increases numbers of both muscle and non-muscle cells, yet simultaneously enhances differentiation of myoblasts. The small proportion of differentiated muscle cells expressing definitive slow myosin can be doubled by Shh. Shh over-expression in chick limb bud reduces muscle mass at early developmental stages while inducing ectopic slow muscle fibre formation. Abundant later-differentiating fibres, however, do not express extra slow myosin. Conversely, Hh loss of function in the limb bud, caused by implanting hybridoma cells expressing a functionally blocking anti-Hh antibody, reduces early slow muscle formation and differentiation, but does not prevent later slow myogenesis. Analysis of Hh knockout mice indicates that Shh promotes early somitic slow myogenesis. Conclusions Taken together, the data show that Hh can have direct pro-differentiative effects on myoblasts and that early-developing muscle requires Hh for

  19. Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae

    Directory of Open Access Journals (Sweden)

    Rodrigues Alexandre

    2012-02-01

    Full Text Available Abstract Background Mammals are not able to restore lost appendages, while many amphibians are. One important question about epimorphic regeneration is related to the origin of the new tissues and whether they come from mature cells via dedifferentiation and/or from stem cells. Several studies in urodele amphibians (salamanders indicate that, after limb or tail amputation, the multinucleated muscle fibres do dedifferentiate by fragmentation and proliferation, thereby contributing to the regenerate. In Xenopus laevis tadpoles, however, it was shown that muscle fibres do not contribute directly to the tail regenerate. We set out to study whether dedifferentiation was present during muscle regeneration of the tadpole limb and zebrafish larval tail, mainly by cell tracing and histological observations. Results Cell tracing and histological observations indicate that zebrafish tail muscle do not dedifferentiate during regeneration. Technical limitations did not allow us to trace tadpole limb cells, nevertheless we observed no signs of dedifferentiation histologically. However, ultrastructural and gene expression analysis of regenerating muscle in tadpole tail revealed an unexpected dedifferentiation phenotype. Further histological studies showed that dedifferentiating tail fibres did not enter the cell cycle and in vivo cell tracing revealed no evidences of muscle fibre fragmentation. In addition, our results indicate that this incomplete dedifferentiation was initiated by the retraction of muscle fibres. Conclusions Our results show that complete skeletal muscle dedifferentiation is less common than expected in lower vertebrates. In addition, the discovery of incomplete dedifferentiation in muscle fibres of the tadpole tail stresses the importance of coupling histological studies with in vivo cell tracing experiments to better understand the regenerative mechanisms.

  20. Skeletal muscle adaptation in response to mechanical stress in p130cas-/- mice.

    Science.gov (United States)

    Akimoto, Takayuki; Okuhira, Kanako; Aizawa, Katsuji; Wada, Shogo; Honda, Hiroaki; Fukubayashi, Toru; Ushida, Takashi

    2013-03-01

    Mammalian skeletal muscles undergo adaptation in response to changes in the functional demands upon them, involving mechanical-stress-induced cellular signaling called "mechanotransduction." We hypothesized that p130Cas, which is reported to act as a mechanosensor that transduces mechanical extension into cellular signaling, plays an important role in maintaining and promoting skeletal muscle adaptation in response to mechanical stress via the p38 MAPK signaling pathway. We demonstrate that muscle-specific p130Cas-/- mice express the contractile proteins normally in skeletal muscle. Furthermore, muscle-specific p130Cas-/- mice show normal mechanical-stress-induced muscle adaptation, including exercise-induced IIb-to-IIa muscle fiber type transformation and hypertrophy. Finally, we provide evidence that exercise-induced p38 MAPK signaling is not impaired by the muscle-specific deletion of p130Cas. We conclude that p130Cas plays a limited role in mechanical-stress-induced skeletal muscle adaptation.

  1. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Al-Khazraji, Baraa K; Mortensen, Stefan P

    2013-01-01

    During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However......, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were...... studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 µM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition...

  2. Ca2+-Dependent Regulations and Signaling in Skeletal Muscle: From Electro-Mechanical Coupling to Adaptation

    Directory of Open Access Journals (Sweden)

    Sebastian Gehlert

    2015-01-01

    Full Text Available Calcium (Ca2+ plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca2+ ions in adult muscle but also highlight recent findings of critical Ca2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance.

  3. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

    DEFF Research Database (Denmark)

    Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke

    2013-01-01

    Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin...... deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development...... of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy...

  4. Isochoric and isobaric freezing of fish muscle.

    Science.gov (United States)

    Năstase, Gabriel; Lyu, Chenang; Ukpai, Gideon; Șerban, Alexandru; Rubinsky, Boris

    2017-02-19

    We have recently shown that, a living organism, which succumbs to freezing to -4 °C in an isobaric thermodynamic system (constant atmospheric pressure), can survive freezing to -4 °C in an isochoric thermodynamic system (constant volume). It is known that the mechanism of cell damage in an isobaric system is the freezing caused increase in extracellular osmolality, and, the consequent cell dehydration. An explanation for the observed survival during isochoric freezing is the thermodynamic modeling supported hypothesis that, in the isochoric frozen solution the extracellular osmolality is comparable to the cell intracellular osmolality. Therefore, cells in the isochoric frozen organism do not dehydrate, and the tissue maintains its morphological integrity. Comparing the histology of: a) fresh fish white muscle, b) fresh muscle frozen to -5 °C in an isobaric system and c) fresh muscle frozen to -5 °C I in an isochoric system, we find convincing evidence of the mechanism of cell dehydration during isobaric freezing. In contrast, the muscle tissue frozen to -5 °C in an isochoric system appears morphologically identical to fresh tissue, with no evidence of dehydration. This is the first experimental evidence in support of the hypothesis that in isochoric freezing there is no cellular dehydration and therefore the morphology of the frozen tissue remains intact.

  5. Differentially expressed fibroblast growth factors regulate skeletal muscle development through autocrine and paracrine mechanisms

    OpenAIRE

    1996-01-01

    Several FGF family members are expressed in skeletal muscle; however, the roles of these factors in skeletal muscle development are unclear. We examined the RNA expression, protein levels, and biological activities of the FGF family in the MM14 mouse skeletal muscle cell line. Proliferating skeletal muscle cells express FGF-1, FGF-2, FGF-6, and FGF-7 mRNA. Differentiated myofibers express FGF-5, FGF-7, and reduced levels of FGF-6 mRNA. FGF-3, FGF-4, and FGF-8 were not detectable by RT-PCR in ...

  6. A 3D skeletal muscle model coupled with active contraction of muscle fibres and hyperelastic behaviour.

    Science.gov (United States)

    Tang, C Y; Zhang, G; Tsui, C P

    2009-05-11

    This paper presents a three-dimensional finite element model of skeletal muscle which was developed to simulate active and passive non-linear mechanical behaviours of the muscle during lengthening or shortening under either quasi-static or dynamic condition. Constitutive relation of the muscle was determined by using a strain energy approach, while active contraction behaviour of the muscle fibre was simulated by establishing a numerical algorithm based on the concept of the Hill's three-element muscle model. The proposed numerical algorithm could be used to predict concentric, eccentric, isometric and isotonic contraction behaviours of the muscle. The proposed numerical algorithm and constitutive model for the muscle were derived and implemented into a non-linear large deformation finite element programme ABAQUS by using user-defined material subroutines. A number of scenarios have been used to demonstrate capability of the model for simulating both quasi-static and dynamic response of the muscle. Validation of the proposed model has been performed by comparing the simulated results with the experimental ones of frog gastrocenemius muscle deformation. The effects of the fusiform muscle geometry and fibre orientation on the stress and fibre stretch distributions of frog muscle during isotonic contraction have also been investigated by using the proposed model. The predictability of the present model for dynamic response of the muscle has been demonstrated by simulating the extension of a squid tentacle during a strike to catch prey.

  7. Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting

    Science.gov (United States)

    Al-Sawaf, Othman; Fragoulis, Athanassios; Rosen, Christian; Kan, Yuet Wai; Sönmez, Tolga Taha; Pufe, Thomas; Wruck, Christoph Jan

    2014-01-01

    Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration.

  8. The Hippo signal transduction network in skeletal and cardiac muscle.

    Science.gov (United States)

    Wackerhage, Henning; Del Re, Dominic P; Judson, Robert N; Sudol, Marius; Sadoshima, Junichi

    2014-08-05

    The discovery of the Hippo pathway can be traced back to two areas of research. Genetic screens in fruit flies led to the identification of the Hippo pathway kinases and scaffolding proteins that function together to suppress cell proliferation and tumor growth. Independent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads. Additionally, many other signal transduction proteins crosstalk to members of the Hippo pathway forming a Hippo signal transduction network. We discuss evidence that the Hippo signal transduction network plays important roles in myogenesis, regeneration, muscular dystrophy, and rhabdomyosarcoma in skeletal muscle, as well as in myogenesis, organ size control, and regeneration of the heart. Understanding the role of Hippo kinases in skeletal and heart muscle physiology could have important implications for translational research. Copyright © 2014, American Association for the Advancement of Science.

  9. Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

    Directory of Open Access Journals (Sweden)

    Lisa Staunton

    2011-01-01

    Full Text Available Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration.

  10. Measuring parvalbumin levels in fish muscle tissue: relevance of muscle locations and storage conditions.

    Science.gov (United States)

    Lee, Poi-Wah; Nordlee, Julie A; Koppelman, Stef J; Baumert, Joseph L; Taylor, Steve L

    2012-11-15

    Fish is an allergenic food capable of provoking severe anaphylactic reactions. Parvalbumin is the major allergen identified in fish and frog muscles. Antibodies against fish and frog parvalbumin have been used to quantify parvalbumin levels from fish. However, these antibodies react variably with parvalbumin from different fish species. Several factors might be responsible for this variation including instability of parvalbumin in fish muscle as a result of frozen storage and differential parvalbumin expression in muscles from various locations within the whole fish. We aimed to investigate whether these factors contribute to the previously observed variable immunoreactivity of the anti-parvalbumin antibodies. Results showed the detection of parvalbumin by these antibodies was unaffected by frozen storage of muscles for 112 days. However, the parvalbumin content decreased in fish muscles from anterior to posterior positions. This factor may partially explain for the inconsistent reactivity of anti-parvalbumin antibodies to different fish species. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Muscle biopsy and cell cultures: potential diagnostic tools in hereditary skeletal muscle channelopathies

    Directory of Open Access Journals (Sweden)

    G Meola

    2009-06-01

    Full Text Available Hereditary muscle channelopathies are caused by dominant mutations in the genes encoding for subunits of muscle voltage- gated ion channels. Point mutations on the human skeletal muscle Na+ channel (Nav1.4 give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2. Point mutations on the human skeletal muscle Ca2+ channel give rise to hypokalemic periodic paralysis and malignant hyperthermia. Point mutations in the human skeletal chloride channel ClC-1 give rise to myotonia congenita. Point mutations in the inwardly rectifying K+ channel Kir2.1 give rise to a syndrome characterized by periodic paralysis, severe cardiac arrhythmias and skeletal alterations (Andersen’s syndrome. Involvement of the same ion channel can thus give rise to different phenotypes. In addition, the same mutation can lead to different phenotypes or similar phenotypes can be caused by different mutations on the same or on different channel subtypes. Bearing in mind, the complexity of this field, the growing number of potential channelopathies (such as the myotonic dystrophies, and the time and cost of the genetic procedures, before a biomolecular approach is addressed, it is mandatory to apply strict diagnostic protocols to screen the patients. In this study we propose a protocol to be applied in the diagnosis of the hereditary muscle channelopathies and we demonstrate that muscle biopsy studies and muscle cell cultures may significantly contribute towards the correct diagnosis of the channel involved. DNAbased diagnosis is now a reality for many of the channelopathies. This has obvious genetic counselling, prognostic and therapeutic implications.

  12. Genetic architecture of gene expression in ovine skeletal muscle

    Directory of Open Access Journals (Sweden)

    Kogelman Lisette JA

    2011-12-01

    Full Text Available Abstract Background In livestock populations the genetic contribution to muscling is intensively monitored in the progeny of industry sires and used as a tool in selective breeding programs. The genes and pathways conferring this genetic merit are largely undefined. Genetic variation within a population has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle. Results The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing and expressed as an Estimated Breeding Value by comparison with contemporary sires. Microarray gene expression data were obtained for longissimus lumborum samples taken from forty progeny of the six sires (4-8 progeny/sire. Initial unsupervised hierarchical clustering analysis revealed strong genetic architecture to the gene expression data, which also discriminated the sire-based Estimated Breeding Value for the trait. An integrated systems biology approach was then used to identify the major functional pathways contributing to the genetics of enhanced muscling by using both Estimated Breeding Value weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome, RNA processing, mitochondrial function and transcriptional regulation. Conclusions This study has revealed strong genetic structure in the gene expression program within

  13. Levels of glutathione and related enzymes in yellowtail fish muscle subjected to ice storage in a modified atmosphere.

    Science.gov (United States)

    Tanimoto, Shota; Song, Xing An; Sakaguchi, Morihiko; Sugawara, Tatsuya; Hirata, Takashi

    2011-09-01

    We investigated the effects of ice storage in a modified atmosphere on levels of glutathione (GSH) and its related enzyme activities, the metmyoglobin to total myoglobin ratio (metMb%), and the K value (a freshness index) of yellowtail fish muscle. GSH in ordinary muscle (fast skeletal muscle) as well as in dark muscle (slow skeletal muscle) stored in air decreased. GSH in those muscles was almost unchanged during storage when packaged with an oxygen absorber or with an oxygen absorber-CO(2) generator. Glutathione disulfide in each type of packaging remained at low concentrations during storage. The GSH peroxidase activities of ordinary muscle and of dark muscle after 7 d of storage in air were lower than when packaged with the oxygen absorber or with the oxygen absorber-CO(2) generator. The GSH reductase (GR) activities of ordinary muscle at the 4th and 7th day of storage when packaged with the oxygen absorber showed a tendency to be lower than when stored in air. The GR activity of dark muscle in each type of packaging method was unchanged during storage. The packaging method did not influence the K values of either the ordinary muscle or the dark muscle during storage. The metMb% of dark muscle when packaged with the oxygen absorber was lower than in the other types of packaging during storage. Therefore, packaging with the oxygen absorber is an effective method to prevent the loss of GSH in fish meat as well as to reduce the discoloration during storage. This study examined whether modified atmosphere packaging preserves the level of GSH, which is unstable to oxidative stress, in fish muscle. The use of an oxygen absorber for packaging can allow us to take in a sufficient amount of the bioactive compound from fish meat after storage as well as fresh fish. © 2011 Institute of Food Technologists®

  14. Preservation of rat skeletal muscle energy metabolism by illumination.

    Science.gov (United States)

    Lindgård, Ann; Lundberg, Jonas; Rakotonirainy, Olivier; Elander, Anna; Soussi, Bassam

    2003-04-25

    Skeletal muscle viability is crucially dependent on the tissue levels of its high energy phosphates. In this study we investigated the effect of the preservation medium Perfadex and illumination with Singlet Oxygen Energy (SOE). Singlet oxygen can be produced photochemically by energy transfer from an excited photosensitizer. The energy emitted from singlet oxygen upon relaxation to its triplet state is captured as photons at 634 nm and is here referred to as SOE. Rat hind limb rectus femoris muscles were preserved for five hours at 22 degrees C in Perfadex, saline, SOE illuminated Perfadex or SOE illuminated saline. Extracts of the muscles were analysed by 31P NMR. Data were analysed using two-way analysis of variance and are given as mean values micromol/g dry weight) +/- SEM. The ATP concentration was higher (p = 0.006) in saline groups (4.52) compared with Perfadex groups (2.82). There was no statistically significant difference in PCr between the saline groups (1.25) and Perfadex groups (0.82). However, there were higher (p = 0.003) ATP in the SOE illuminated groups (4.61) compared with the non-illuminated groups (2.73). The PCr was also higher (p < 0.0001) in the SOE illuminated groups (1.89) compared with the non-illuminated groups (0.18). In conclusion, Perfadex in this experimental model was incapable of preserving the high energy phosphates in skeletal muscle during 5 hours of ischemia. Illumination with SOE at 634 nm improved the preservation potential, in terms of a positive effect on the energy status of the muscle cell.

  15. MicroRNAs in skeletal muscle: their role and regulation in development, disease and function.

    Science.gov (United States)

    Güller, Isabelle; Russell, Aaron P

    2010-11-01

    Maintaining skeletal muscle function throughout the lifespan is a prerequisite for good health and independent living. For skeletal muscle to consistently function at optimal levels, the efficient activation of processes that regulate muscle development, growth, regeneration and metabolism is required. Numerous conditions including neuromuscular disorders, physical inactivity, chronic disease and ageing are associated with perturbations in skeletal muscle function. A loss or reduction in skeletal muscle function often leads to increased morbidity and mortality either directly, or indirectly, via the development of secondary diseases such as diabetes, obesity, cardiovascular and respiratory disease. Identifying mechanisms which influence the processes regulating skeletal muscle function is a key priority. The discovery of microRNAs (miRNAs) provides a new avenue that will extend our knowledge of factors controlling skeletal muscle function. miRNAs may also improve our understanding and application of current therapeutic approaches as well as enable the identification of new therapeutic strategies and targets aimed at maintaining and/or improving skeletal muscle health. This review brings together the latest developments in skeletal muscle miRNA biology and focuses on their role and regulation under physiological and patho-physiological conditions with an emphasis on: myogenesis, hypertrophy, atrophy and regeneration; exercise and nutrition; muscle disease, ageing, diabetes and obesity.

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  1. File list: InP.Myo.05.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: His.Myo.10.AllAg.Satellite_Cells,_Skeletal_Muscle [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. Skeletal muscle signature of a champion sprint runner.

    Science.gov (United States)

    Trappe, Scott; Luden, Nicholas; Minchev, Kiril; Raue, Ulrika; Jemiolo, Bozena; Trappe, Todd A

    2015-06-15

    We had the unique opportunity to study the skeletal muscle characteristics, at the single fiber level, of a world champion sprint runner who is the current indoor world record holder in the 60-m hurdles (7.30 s) and former world record holder in 110-m hurdles (12.91 s). Muscle biopsies were obtained from the vastus lateralis at rest and 4 h after a high-intensity exercise challenge (4 × 7 repetitions of resistance exercise). Single muscle fiber analyses were conducted for fiber type distribution (myosin heavy chain, MHC), fiber size, contractile function (strength, speed, and power) and mRNA expression (before and after the exercise bout). The world-class sprinter's leg muscle had a high abundance (24%) of the pure MHC IIx muscle fibers with a total fast-twitch fiber population of 71%. Power output of the MHC IIx fibers (35.1 ± 1.4 W/l) was 2-fold higher than MHC IIa fibers (17.1 ± 0.5 W/l) and 14-fold greater than MHC I fibers (2.5 ± 0.1 W/l). Additionally, the MHC IIx fibers were highly responsive to intense exercise at the transcriptional level for genes involved with muscle growth and remodeling (Fn14 and myostatin). To our knowledge, the abundance of pure MHC IIx muscle fibers is the highest observed in an elite sprinter. Further, the power output of the MHC IIa and MHC IIx muscle fibers was greater than any human values reported to date. These data provide a myocellular basis for the high level of sprinting success achieved by this individual.

  5. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Somik [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yin, Hongshan [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei (China); Nam, Deokhwa [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Li, Yong [Department of Pediatric Surgery, Center for Stem Cell Research and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Ma, Ke, E-mail: kma@houstonmethodist.org [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States)

    2015-02-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

  6. Effects of calcium phosphate bioceramics on skeletal muscle cells.

    Science.gov (United States)

    Sun, J S; Tsuang, Y H; Yao, C H; Liu, H C; Lin, F H; Hang, Y S

    1997-02-01

    With advances in ceramics technology, calcium phosphate bioceramics have been applied as bone substitutes. The effects of implants on bony tissue have been investigated. The effects upon adjacent skeletal muscles have not been determined. The focus of this work is to elucidate the biological effects of various calcium phosphate bioceramics on skeletal muscles. Four different kinds of powder of calcium phosphate biomaterials including beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA), beta-dicalcium pyrophosphate (beta-DCP) and sintered beta-dicalcium pyrophosphate (SDCP), were tested by myoblast cell cultures. The results were analyzed by cell count, cell morphology and concentration of transforming growth factor beta 1 (TGF-beta 1) in culture medium. The cell population and TGF-beta 1 concentration of the control sample increased persistently as the time of culture increased. The changes in cell population and TGF-beta 1 concentration in culture medium of the beta-TCP and HA were quite low in the first 3 days of culture, then increased gradually toward the seventh day. The changes in cell population and TGF-beta 1 concentration in culture medium of the silica, beta-DCP, and SDCP were quite similar. They were lower during the first day of culture but increased and reached that of the control medium after 7 days' culture. Most cells on B-TCP and HA diminished in size with radially spread, long pseudopods. We conclude that HA and beta-TCP are thought to have an inhibitory effect on growth of the myoblasts. The HA and beta-TCP may interfere with the repair and regeneration of injured skeletal muscle after orthopedic surgery.

  7. Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

    Science.gov (United States)

    Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

    2014-04-01

    Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

  8. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  9. Reduced blood flow to contracting skeletal muscle in ageing humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Hellsten, Ylva

    2016-01-01

    consequences of ageing and physical inactivity can be challenging; yet, observations from cross-sectional and longitudinal studies on the effects of physical activity have provided some insight. Physical activity has the potential to offset the age-related decline in blood flow to contracting skeletal muscle...... and the ability for functional sympatholysis; an attenuation of the vasoconstrictor effect of sympathetic nervous activity. These vascular adaptations with physical activity are likely to be an effect of improved nitric oxide and ATP signaling. Collectively, precise matching of blood flow and O2 delivery to meet...

  10. Modeling cellular lysis in skeletal muscle due to electric shock.

    Science.gov (United States)

    Cela, Carlos J; Lee, Raphael C; Lazzi, Gianluca

    2011-05-01

    High-voltage electrical trauma frequently results in injury patterns that cannot be completely attributed to Joule heating. An electrical-injury model describing cellular lysis damage caused by supraphysiological electric fields is introduced, and used to evaluate the effects of high-voltage electric shock on the skeletal muscle of a human upper limb in a configuration that simulates hand-to-hand contact. A novel multiresolution admittance method, capable of efficiently handling large computational models while maintaining excellent accuracy, was used to perform the numerical computations. Values for the computed current through the arm and the upper limb impedance are reported.

  11. Mechanism of latency relaxation in frog skeletal muscle.

    Science.gov (United States)

    Yagi, N

    2011-05-01

    The latency relaxation is a small drop of tension before skeletal muscle begins to develop active tension. This phenomenon was found nearly one century ago but its origin has not been clarified. In this review, the hypotheses for its mechanism are discussed in terms of the recent experimental results using X-ray diffraction. The latency relaxation takes place almost simultaneously as the structural change of the regulatory protein troponin, an unspecified structural change of the thick filament, and increase in stiffness. It seems difficult to associate all of these with the latency relaxation by assuming a simple mechanism. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Prednisolone-induced changes in dystrophic skeletal muscle.

    Science.gov (United States)

    Fisher, Ivan; Abraham, David; Bouri, Khaled; Hoffmann, Eric P; Hoffman, Eric P; Muntoni, Francesco; Morgan, Jennifer

    2005-05-01

    Although glucocorticoids delay the progression of Duchenne muscular dystrophy (DMD) their mechanism of action is unknown. Skeletal muscle gene expression profiles of mdx mice, an animal model of DMD, treated with prednisolone were compared with control mice at 1 and 6 wk. Of the 89 early differentially regulated genes and ESTs, delta-sarcoglycan, myosin Va, FK506-binding protein 51 (FKBP51), the potassium channel regulator potassium inwardly-rectifying channel Isk-like (IRK2) and ADAM 10 were overexpressed, whereas growth hormone-releasing hormone receptor (GHRHR) and Homer-2 were underexpressed. The 58 late differentially overexpressed genes included kallikreins (13, 16, and 26), FKBP51, PI3K alpha regulatory subunit, and IGFBP6, while underexpressed genes included NeuroD and nicotinic cholinergic receptor gamma. At both time points, overexpression of a cohort of genes relating to metabolism and proteolysis was apparent, alongside the differential expression of genes relating to calcium metabolism. Treatment did not increase muscle regeneration, reduce the number of infiltrating macrophages, or alter utrophin expression or localization. However, in the treated mdx soleus muscle, the percentage of slow fibers was significantly lower compared with untreated controls after 6 wk of treatment. These results show that glucocorticoids confer their benefit to dystrophic muscle in a complex fashion, culminating in a switch to a more normal muscle fiber type.

  13. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    Science.gov (United States)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  14. Skeletal muscle to pancreatic β-cell cross-talk

    DEFF Research Database (Denmark)

    Christensen, Camilla S; P. Christensen, Dan; Lundh, Morten

    2015-01-01

    CONTEXT: Mechanisms explaining exercise-induced β-cell health are unknown. OBJECTIVE: To define the role of muscle contraction and acute exercise-derived soluble humoral mediators on β-cell health. DESIGN: In vitro models. SETTING: University. PARTICIPANTS: Healthy subjects. INTERVENTION(S): Cond......CONTEXT: Mechanisms explaining exercise-induced β-cell health are unknown. OBJECTIVE: To define the role of muscle contraction and acute exercise-derived soluble humoral mediators on β-cell health. DESIGN: In vitro models. SETTING: University. PARTICIPANTS: Healthy subjects. INTERVENTION......(S): Conditioned media (CM) were collected from human skeletal muscle (HSkM) cells treated with or without electrical pulse stimulation (EPS). Antecubital and femoral venous blood serum were collected before and after an exercise bout. CM and sera with or without IL-6 neutralization were used to incubate insulin...... and exercise increased circulating IL-6 levels in antecubital and femoral serum. IL-6 neutralization demonstrated that muscle-derived IL-6 prevents INS-1 and islet apoptosis in the absence of IL-1β+IFN-γ, but augments apoptosis under proinflammatory conditions, and that muscle-derived IL-6 supports islet...

  15. Angiotensin II infusion induces marked diaphragmatic skeletal muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Bashir M Rezk

    Full Text Available Advanced congestive heart failure (CHF and chronic kidney disease (CKD are characterized by increased angiotensin II (Ang II levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1 and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase and of the satellite cell marker M-cadherin (59.2±22.2% increase. Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase, those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD.

  16. Procedures for rat in situ skeletal muscle contractile properties.

    Science.gov (United States)

    MacIntosh, Brian R; Esau, Shane P; Holash, R John; Fletcher, Jared R

    2011-10-15

    There are many circumstances where it is desirable to obtain the contractile response of skeletal muscle under physiological circumstances: normal circulation, intact whole muscle, at body temperature. This includes the study of contractile responses like posttetanic potentiation, staircase and fatigue. Furthermore, the consequences of disease, disuse, injury, training and drug treatment can be of interest. This video demonstrates appropriate procedures to set up and use this valuable muscle preparation. To set up this preparation, the animal must be anesthetized, and the medial gastrocnemius muscle is surgically isolated, with the origin intact. Care must be taken to maintain the blood and nerve supplies. A long section of the sciatic nerve is cleared of connective tissue, and severed proximally. All branches of the distal stump that do not innervate the medial gastrocnemius muscle are severed. The distal nerve stump is inserted into a cuff lined with stainless steel stimulating wires. The calcaneus is severed, leaving a small piece of bone still attached to the Achilles tendon. Sonometric crystals and/or electrodes for electromyography can be inserted. Immobilization by metal probes in the femur and tibia prevents movement of the muscle origin. The Achilles tendon is attached to the force transducer and the loosened skin is pulled up at the sides to form a container that is filled with warmed paraffin oil. The oil distributes heat evenly and minimizes evaporative heat loss. A heat lamp is directed on the muscle, and the muscle and rat are allowed to warm up to 37°C. While it is warming, maximal voltage and optimal length can be determined. These are important initial conditions for any experiment on intact whole muscle. The experiment may include determination of standard contractile properties, like the force-frequency relationship, force-length relationship, and force-velocity relationship. With care in surgical isolation, immobilization of the origin of the

  17. Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle.

    Science.gov (United States)

    Khayrullin, Andrew; Smith, Lauren; Mistry, Dhwani; Dukes, Amy; Pan, Y Albert; Hamrick, Mark W

    2016-10-21

    Muscle wasting is estimated to affect 40-60% of alcoholics, and is more common than cirrhosis among chronic alcohol abusers. The molecular and cellular mechanisms underlying alcohol-related musculoskeletal dysfunction are, however, poorly understood. Muscle-specific microRNAs (miRNAs) referred to as myoMirs are now known to play a key role in both myogenesis and muscle atrophy. Yet, no studies have investigated a role for myoMirs in alcohol-related skeletal muscle damage. We developed a zebrafish model of chronic ethanol exposure to better define the mechanisms mediating alcohol-induced muscle atrophy. Adult fish maintained at 0.5% ethanol for eight weeks demonstrated significantly reduced muscle fiber cross-sectional area (∼12%, P < 0.05) compared to fish housed in normal water. Zebrafish miRNA microarray revealed marked changes in several miRNAs with ethanol treatment. Importantly, miR-140, a miRNA that shows 100% sequence homology with miR-140 from both mouse and human, is decreased 10-fold in ethanol treated fish. miR-140 targets several members of the Notch signaling pathway such as DNER, JAG1, and Hey1, and PCR data show that both Hey1 and Notch 1 are significantly up-related (3-fold) in muscle of ethanol treated fish. In addition, miR-146a, which targets the Notch antagonist Numb, is elevated in muscle from ethanol-treated fish. Upregulation of Notch signaling suppresses myogenesis and maintains muscle satellite cell quiescence. These data suggest that miRNAs targeting Notch are likely to play important roles in alcohol-related myopathy. Furthermore, zebrafish may serve as a useful model for better understanding the role of microRNAs in alcohol-related tissue damage.

  18. Overexpression of IGF-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

    OpenAIRE

    Ye, Fan; Mathur, Sunita; Liu, Min; Stephen E Borst; Walter, Glenn A; Sweeney, H. Lee; Vandenborne, Krista

    2013-01-01

    Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Since insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of viral mediated overexpression of IGF-1...

  19. The STARS signaling pathway: a key regulator of skeletal muscle function.

    Science.gov (United States)

    Lamon, Séverine; Wallace, Marita A; Russell, Aaron P

    2014-09-01

    During the last decade, the striated muscle activator of Rho signaling (STARS), a muscle-specific protein, has been proposed to play an increasingly important role in skeletal muscle growth, metabolism, regeneration and stress adaptation. STARS influences actin dynamics and, as a consequence, regulates the myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) transcriptional program, a well-known pathway controlling skeletal muscle development and function. Muscle-specific stress conditions, such as exercise, positively regulates, while disuse and degenerative muscle diseases are associated with a downregulation of STARS and its downstream partners, suggesting a pivotal role for STARS in skeletal muscle health. This review provides a comprehensive overview of the known role and regulation of STARS and the members of its signaling pathway, RhoA, MRTF-A and SRF, in skeletal muscle.

  20. Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy?

    Science.gov (United States)

    Schoenfeld, Brad J

    2012-05-01

    Exercise-induced muscle damage (EIMD) occurs primarily from the performance of unaccustomed exercise, and its severity is modulated by the type, intensity, and duration of training. Although concentric and isometric actions contribute to EIMD, the greatest damage to muscle tissue is seen with eccentric exercise, where muscles are forcibly lengthened. Damage can be specific to just a few macromolecules of tissue or result in large tears in the sarcolemma, basal lamina, and supportive connective tissue, and inducing injury to contractile elements and the cytoskeleton. Although EIMD can have detrimental short-term effects on markers of performance and pain, it has been hypothesized that the associated skeletal muscle inflammation and increased protein turnover are necessary for long-term hypertrophic adaptations. A theoretical basis for this belief has been proposed, whereby the structural changes associated with EIMD influence gene expression, resulting in a strengthening of the tissue and thus protection of the muscle against further injury. Other researchers, however, have questioned this hypothesis, noting that hypertrophy can occur in the relative absence of muscle damage. Therefore, the purpose of this article will be twofold: (a) to extensively review the literature and attempt to determine what, if any, role EIMD plays in promoting skeletal muscle hypertrophy and (b) to make applicable recommendations for resistance training program design.

  1. New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass

    OpenAIRE

    Goodman, Craig A.; Hornberger, Troy A.

    2014-01-01

    Skeletal muscle is essential for normal bodily function and the loss of skeletal muscle (i.e. muscle atrophy/wasting) can have a major impact on mobility, whole-body metabolism, disease resistance, and quality of life. Thus, there is a clear need for the development of therapies that can prevent the loss, or increase, of skeletal muscle mass. However, in order to develop such therapies, we will first have to develop a thorough understanding of the molecular mechanisms that regulate muscle mas...

  2. Autocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle

    Science.gov (United States)

    Adams, Gregory R.

    2002-01-01

    Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.

  3. New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass

    OpenAIRE

    Goodman, Craig A.; Hornberger, Troy A.

    2014-01-01

    Skeletal muscle is essential for normal bodily function and the loss of skeletal muscle (i.e. muscle atrophy/wasting) can have a major impact on mobility, whole-body metabolism, disease resistance, and quality of life. Thus, there is a clear need for the development of therapies that can prevent the loss, or increase, of skeletal muscle mass. However, in order to develop such therapies, we will first have to develop a thorough understanding of the molecular mechanisms that regulate muscle mas...

  4. Autocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle

    Science.gov (United States)

    Adams, Gregory R.

    2002-01-01

    Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.

  5. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

    Science.gov (United States)

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

    2016-10-14

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2(fl/fl)) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2(fl/fl) mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2(fl/fl) mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Extracellular matrix adaptation of tendon and skeletal muscle to exercise

    DEFF Research Database (Denmark)

    Kjaer, Michael; Magnusson, Peter; Krogsgaard, Michael

    2006-01-01

    The extracellular matrix (ECM) of connective tissues enables linking to other tissues, and plays a key role in force transmission and tissue structure maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by physical activity, and both collagen synthesis and metalloprotease......-beta and IL-6 is enhanced following exercise. For tendons, metabolic activity (e.g. detected by positron emission tomography scanning), circulatory responses (e.g. as measured by near-infrared spectroscopy and dye dilution) and collagen turnover are markedly increased after exercise. Tendon blood flow...... is supported by findings of gender-related differences in the activation of collagen synthesis with exercise. These findings may provide the basis for understanding tissue overloading and injury in both tendons and skeletal muscle....

  7. Structural dynamics of troponin during activation of skeletal muscle

    Science.gov (United States)

    Fusi, Luca; Brunello, Elisabetta; Sevrieva, Ivanka R.; Sun, Yin-Biao; Irving, Malcolm

    2014-01-01

    Time-resolved changes in the conformation of troponin in the thin filaments of skeletal muscle were followed during activation in situ by photolysis of caged calcium using bifunctional fluorescent probes in the regulatory and the coiled-coil (IT arm) domains of troponin. Three sequential steps in the activation mechanism were identified. The fastest step (1,100 s−1) matches the rate of Ca2+ binding to the regulatory domain but also dominates the motion of the IT arm. The second step (120 s−1) coincides with the azimuthal motion of tropomyosin around the thin filament. The third step (15 s−1) was shown by three independent approaches to track myosin head binding to the thin filament, but is absent in the regulatory head. The results lead to a four-state structural kinetic model that describes the molecular mechanism of muscle activation in the thin filament–myosin head complex under physiological conditions. PMID:24616505

  8. Skeletal muscle mitochondrial respiration in AMPKa2 kinase dead mice

    DEFF Research Database (Denmark)

    Larsen, Steen; Kristensen, Jonas Møller; Stride, Nis

    2012-01-01

    ) was studied. METHODS: In tibialis anterior (almost exclusively type 2 fibers) muscle from young (12-17 weeks, n = 7) and mature (25-27 weeks, n = 12) KD and wild type (WT) (12-17 weeks, n = 9; 25-27 weeks, n = 11) littermates JO(2) was quantified in permeabilized fibers ex vivo by respirometry, using......AIM: To study if the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKa2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2...... was highest in young WT animals, and lower in KD animals compared with age-matched WT. JO(2) per mg tissue was lower (P...

  9. Skeletal Muscle Mitochondrial Function in Polycystic Ovarian Syndrome

    DEFF Research Database (Denmark)

    Rabøl, Rasmus; Svendsen, Pernille Maj; Skovbro, Mette

    2011-01-01

    Objective Polycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance, which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry. Methods...... Hyperinsulinemic euglycemic clamps (40 mU/min/m2) and muscle biopsies were performed on 23 women with PCOS (9 lean (body mass index (BMI) 25 kg/m2)) and 17 age- and weight-matched controls (6 lean and 11 obese). Western blotting and high-resolution respirometry was used to determine mitochondrial function. Results...... Insulin sensitivity decreased with PCOS and increasing body weight. Mitochondrial respiration with substrates for complex I and complex I+II were similar in all groups, and PCOS was not associated with a decrease in mitochondrial content as measured by mtDNA/genomicDNA. We found no correlation between...

  10. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation

    DEFF Research Database (Denmark)

    Dzamko, Nicolas; Schertzer, Jonathan D.; Ryall, James G.

    2008-01-01

    , malonyl-CoA levels were reduced and rates of fatty acid oxidation were comparable between genotypes. During treadmill exercise both KD and WT mice had similar values of respiratory exchange ratio. These studies suggested the presence of an alternative ACC2 kinase(s). Using a phosphoproteomics......The activation of AMP-activated protein kinase (AMPK) and phosphorylation/inhibition of acetyl-CoA carboxylase 2 (ACC2) is believed to be the principal pathway regulating fatty acid oxidation. However, during exercise AMPK activity and ACC Ser-221 phosphorylation does not always correlate...... with rates of fatty acid oxidation. To address this issue we have investigated the requirement for skeletal muscle AMPK in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) and contraction-stimulated fatty acid oxidation utilizing transgenic mice expressing a muscle-specific kinase...

  11. Computer-aided mechanogenesis of skeletal muscle organs from single cells in vitro

    Science.gov (United States)

    Vanderburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

    1991-01-01

    Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

  12. Computer aided mechanogenesis of skeletal muscle organs from single cells in vitro

    Science.gov (United States)

    Vandenburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

    1990-01-01

    Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

  13. The application of 2H2O to measure skeletal muscle protein synthesis

    Directory of Open Access Journals (Sweden)

    Fluckey James D

    2010-04-01

    Full Text Available Abstract Skeletal muscle protein synthesis has generally been determined by the precursor:product labeling approach using labeled amino acids (e.g., [13C]leucine or [13C]-, [15N]-, or [2H]phenylalanine as the tracers. Although reliable for determining rates of protein synthesis, this methodological approach requires experiments to be conducted in a controlled environment, and as a result, has limited our understanding of muscle protein renewal under free-living conditions over extended periods of time (i.e., integrative/cumulative assessments. An alternative tracer, 2H2O, has been successfully used to measure rates of muscle protein synthesis in mice, rats, fish and humans. Moreover, perturbations such as feeding and exercise have been included in these measurements without exclusion of common environmental and biological factors. In this review, we discuss the principle behind using 2H2O to measure muscle protein synthesis and highlight recent investigations that have examined the effects of feeding and exercise. The framework provided in this review should assist muscle biologists in designing experiments that advance our understanding of conditions in which anabolism is altered (e.g., exercise, feeding, growth, debilitating and metabolic pathologies.

  14. Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation

    Science.gov (United States)

    Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

    1984-02-01

    Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

  15. Module-based multiscale simulation of angiogenesis in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Mac Gabhann Feilim

    2011-04-01

    Full Text Available Abstract Background Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem. Results We present an object-oriented module-based computational integration strategy to build a multiscale model of angiogenesis that links currently available models. As an example case, we use this approach to integrate modules representing microvascular blood flow, oxygen transport, vascular endothelial growth factor transport and endothelial cell behavior (sensing, migration and proliferation. Modeling methodologies in these modules include algebraic equations, partial differential equations and agent-based models with complex logical rules. We apply this integrated model to simulate exercise-induced angiogenesis in skeletal muscle. The simulation results compare capillary growth patterns between different exercise conditions for a single bout of exercise. Results demonstrate how the computational infrastructure can effectively integrate multiple modules by coordinating their connectivity and data exchange. Model parameterization offers simulation flexibility and a platform for performing sensitivity analysis. Conclusions This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions.

  16. Phenotypic variability in childhood of skeletal muscle sodium channelopathies.

    Science.gov (United States)

    Yoshinaga, Harumi; Sakoda, Shunichi; Shibata, Takashi; Akiyama, Tomoyuki; Oka, Makio; Yuan, Jun-Hui; Takashima, Hiroshi; Takahashi, Masanori P; Kitamura, Tetsuro; Murakami, Nagako; Kobayashi, Katsuhiro

    2015-05-01

    Mutations of the SCN4A gene cause several skeletal muscle channelopathies and overlapping forms of these disorders. However, the variability of the clinical presentation in childhood is confusing and not fully understood among pediatric neurologists. We found three different mutations (p.V445M, p.I693L, and a novel mutation, p.V1149L) in SCN4A but not in the CLCN1 gene. The patient with p.V445M showed the clinical phenotype of sodium channel myotonia, but her clear symptoms did not appear until 11 years of age. Her younger sister and mother, who have the same mutation, displayed marked intrafamilial phenotypic heterogeneity from mild to severe painful myotonia with persistent weakness. The patient with p.I693L exhibited various symptoms that evolved with age, including apneic episodes, tonic muscular contractions during sleep, fluctuating severe episodic myotonia, and finally episodic paralyses. The patient with the novel p.V1149L mutation exhibited episodic paralyses starting at 3 years of age, and myotonic discharges were detected at 11 years of age for the first time. The present cohort reveals the complexity, variability, and overlapping nature of the clinical features of skeletal muscle sodium channelopathies. These are basically treatable disorders, so it is essential to consider genetic testing before the full development of a patient's condition. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. A simplified immunohistochemical classification of skeletal muscle fibres in mouse

    Directory of Open Access Journals (Sweden)

    M. Kammoun

    2014-06-01

    Full Text Available The classification of muscle fibres is of particular interest for the study of the skeletal muscle properties in a wide range of scientific fields, especially animal phenotyping. It is therefore important to define a reliable method for classifying fibre types. The aim of this study was to establish a simplified method for the immunohistochemical classification of fibres in mouse. To carry it out, we first tested a combination of several anti myosin heavy chain (MyHC antibodies in order to choose a minimum number of antibodies to implement a semi-automatic classification. Then, we compared the classification of fibres to the MyHC electrophoretic pattern on the same samples. Only two anti MyHC antibodies on serial sections with the fluorescent labeling of the Laminin were necessary to classify properly fibre types in Tibialis Anterior and Soleus mouse muscles in normal physiological conditions. This classification was virtually identical to the classification realized by the electrophoretic separation of MyHC. This immunohistochemical classification can be applied to the total area of Tibialis Anterior and Soleus mouse muscles. Thus, we provide here a useful, simple and time-efficient method for immunohistochemical classification of fibres, applicable for research in mouse

  18. Multistability inspired by the oblique, pennate architectures of skeletal muscle

    Science.gov (United States)

    Kidambi, Narayanan; Harne, Ryan L.; Wang, K. W.

    2017-04-01

    Skeletal muscle mechanics exhibit a range of noteworthy characteristics, providing great inspiration for the development of advanced structural and material systems. These characteristics arise from the synergies demonstrated between muscle's constituents across the various length scales. From the macroscale oblique orientation of muscle fibers to the microscale lattice spacing of sarcomeres, muscle takes advantage of geometries and multidimensionality for force generation or length change along a desired axis. Inspired by these behaviors, this research investigates how the incorporation of multidimensionality afforded by oblique, pennate architectures can uncover novel mechanics in structures exhibiting multistability. Experimental investigation of these mechanics is undertaken using specimens of molded silicone rubber with patterned voids, and results reveal tailorable mono-, bi-, and multi-stability under axial displacements by modulation of transverse confinement. If the specimen is considered as an architected material, these results show its ability to generate intriguing, non-monotonic shear stresses. The outcomes would foster the development of novel, advanced mechanical metamaterials that exploit pennation and multidimensionality.

  19. GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.

    Science.gov (United States)

    Egerman, Marc A; Cadena, Samuel M; Gilbert, Jason A; Meyer, Angelika; Nelson, Hallie N; Swalley, Susanne E; Mallozzi, Carolyn; Jacobi, Carsten; Jennings, Lori L; Clay, Ieuan; Laurent, Gaëlle; Ma, Shenglin; Brachat, Sophie; Lach-Trifilieff, Estelle; Shavlakadze, Tea; Trendelenburg, Anne-Ulrike; Brack, Andrew S; Glass, David J

    2015-07-07

    Age-related frailty may be due to decreased skeletal muscle regeneration. The role of TGF-β molecules myostatin and GDF11 in regeneration is unclear. Recent studies showed an age-related decrease in GDF11 and that GDF11 treatment improves muscle regeneration, which were contrary to prior studies. We now show that these recent claims are not reproducible and the reagents previously used to detect GDF11 are not GDF11 specific. We develop a GDF11-specific immunoassay and show a trend toward increased GDF11 levels in sera of aged rats and humans. GDF11 mRNA increases in rat muscle with age. Mechanistically, GDF11 and myostatin both induce SMAD2/3 phosphorylation, inhibit myoblast differentiation, and regulate identical downstream signaling. GDF11 significantly inhibited muscle regeneration and decreased satellite cell expansion in mice. Given early data in humans showing a trend for an age-related increase, GDF11 could be a target for pharmacologic blockade to treat age-related sarcopenia.

  20. Evidence for facilitated lactate uptake in lizard skeletal muscle.

    Science.gov (United States)

    Donovan, E R; Gleeson, T T

    2001-12-01

    To understand more fully lactate metabolism in reptilian muscle, lactate uptake in lizard skeletal muscle was measured and its similarities to the monocarboxylate transport system found in mammals were examined. At 2 min, uptake rates of 15 mmol l(-1) lactate into red iliofibularis (rIF) were 2.4- and 2.2-fold greater than white iliofibularis (wIF) and mouse soleus, respectively. alpha-Cyano-4-hydroxycinnamate (15 mmol l(-1)) caused little inhibition of uptake in wIF but caused a 42-54 % reduction in the uptake rate of lactate into rIF, suggesting that much of the lactate uptake by rIF is via protein-mediated transport. N-ethymaleimide (ETH) (10 mmol l(-1)) also caused a reduction in the rate of uptake, but measurements of adenylate and phosphocreatine concentrations show that ETH had serious effects on rIF and wIF and may not be appropriate for transport inhibition studies in reptiles. The higher net uptake rate by rIF than by wIF agrees with the fact that rIF shows much higher rates of lactate utilization and incorporation into glycogen than wIF. This study also suggests that lactate uptake by reptilian muscle is similar to that by mammalian muscle and that, evolutionarily, this transport system may be relatively conserved even in animals with very different patterns of lactate metabolism.

  1. Primary skeletal muscle lymphoma presenting as refractory cellulitis.

    Science.gov (United States)

    Baddour, L M; Haden, K H; Allen, J W

    2001-09-01

    The right torso of a 55-year-old woman showed diffuse skin and soft-tissue changes suggestive of cellulitis. However, several clinical and radiologic features, including the subacute and non-toxic nature of the illness and the patient's lack of response to antibiotic therapy, indicated a noninfectious etiology. Malignancy was suggested by striking changes seen on computed tomographic scanning--including extensive infiltration and enlargement of the musculature of the right shoulder girdle, the intercostal musculature, the latissimus dorsi, and the rhomboids; focal enlargement of the right paraspinal muscles; and enlargement of the psoas and the iliacus muscles and of the musculature around the hip joint. The mediastinal, hilar, and paraaortic regions showed no adenopathy. A large hypodense lesion of approximately 4.5 cm, which was seen in the caudate lobe of the liver, raised the concern of a metastatic focus of malignancy. Because of these findings, an immediate muscle biopsy was performed. Results showed a non-Hodgkin's lymphoma with a B-cell phenotype. Although primary skeletal muscle lymphoma is very uncommon in patients without human immunodeficiency virus infection, clinical presentation of refractory cellulitis, as seen in the current case, is extremely rare.

  2. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  3. Responses of mouse skeletal muscle to endurance exercise. Functional, metabolic, and genomic adaptations

    NARCIS (Netherlands)

    de Snoo, M.W.

    2009-01-01

    Endurance exercise is commonly known to improve skeletal muscle performance with respect to fatigue resistance. The exact mechanisms, however, as to how skeletal muscle adapts to increased physical demand are still largely unknown, despite extensive research. These processes were originally studied

  4. Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity

    Directory of Open Access Journals (Sweden)

    Mark Nixon

    2016-01-01

    Conclusions: SIK1 is dispensable for glycemic control on chow diet. SIK1 promotes insulin resistance on high fat diet by a cell-autonomous mechanism in skeletal muscle. Our study establishes SIK1 as a promising therapeutic target to improve skeletal muscle insulin sensitivity in obese individuals without deleterious effects on hepatic glucose production.

  5. Exercise and Type 2 Diabetes: Molecular Mechanisms Regulating Glucose Uptake in Skeletal Muscle

    Science.gov (United States)

    Stanford, Kristin I.; Goodyear, Laurie J.

    2014-01-01

    Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial…

  6. Regulation of pH in human skeletal muscle: adaptations to physical activity

    DEFF Research Database (Denmark)

    Juel, C

    2008-01-01

    Regulation of pH in skeletal muscle is the sum of mechanisms involved in maintaining intracellular pH within the normal range. Aspects of pH regulation in human skeletal muscle have been studied with various techniques from analysis of membrane proteins, microdialysis, and the nuclear magnetic...

  7. Correction to: Direct effects of doxorubicin on skeletal muscle contribute to fatigue

    NARCIS (Netherlands)

    Norren, van K.; Helvoort, van A.; Agriles, J.M.; Tuijl, van S.; Arts, K.; Gorselink, M.; Laviano, A.; Kegler, D.; Haagsman, H.P.; Beek, van der E.M.

    2009-01-01

    Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation fol

  8. Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men

    DEFF Research Database (Denmark)

    Rose, Adam John; Broholm, Christa; Kiillerich, Kristian;

    2005-01-01

    Protein synthesis in skeletal muscle is known to decrease during contractions but the underlying regulatory mechanisms are unknown. Here, the effect of exercise on skeletal muscle eukaryotic elongation factor 2 (eEF2) phosphorylation, a key component in protein translation machinery, was examined...

  9. Lower physical activity is associated with fat infiltration within skeletal muscle in young girls

    Science.gov (United States)

    Fat infiltration within skeletal muscle is strongly associated with obesity, type 2 diabetes mellitus, and metabolic syndrome. Lower physical activity may be a risk factor for greater fat infiltration within skeletal muscle, although whether lower physical activity is associated with fat infiltrati...

  10. Structure of skeletal muscles after hypokinesia and physical loading of middle aerobic power

    Directory of Open Access Journals (Sweden)

    Serg Popel’

    2014-11-01

    Full Text Available In the article is shown that determined degree of destructive changes in skeletal muscles is in direct dependence on the term of hypokinesiа limitation. Application of kinesiotherapy intensifies the repair processes and substantially reduces the terms of renewal of structurally-functional properties of skeletal muscles after hypokinesiа.

  11. Bio-impedance analysis for appendicular skeletal muscle mass assessment in (pre-) frail elderly people

    NARCIS (Netherlands)

    Baar, van H.; Hulshof, P.J.M.; Tieland, C.A.B.; Groot, de C.P.G.M.

    2015-01-01

    Background & aims Screening populations for skeletal muscle mass (SMM) is important for early detection of sarcopenia. Our aim was to develop an age specific bio-impedance (BI) prediction equation for the assessment of appendicular skeletal muscle mass (ASMM) in (pre-) frail elderly people aged

  12. Exercise and Type 2 Diabetes: Molecular Mechanisms Regulating Glucose Uptake in Skeletal Muscle

    Science.gov (United States)

    Stanford, Kristin I.; Goodyear, Laurie J.

    2014-01-01

    Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial…

  13. Long-term skeletal muscle mitochondrial dysfunction is associated with hypermetabolism in severely burned children

    Science.gov (United States)

    The long-term impact of burn trauma on skeletal muscle bioenergetics remains unknown. Here, we determined respiratory capacity and function of skeletal muscle mitochondria in healthy individuals and in burn victims for up to two years post-injury. Biopsies were collected from the m. vastus lateralis...

  14. Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

    DEFF Research Database (Denmark)

    Bertholdt, Lærke; Gudiksen, Anders; Schwartz, Camilla Lindgren

    2017-01-01

    The liver is essential in maintaining and regulating glucose homeostasis during prolonged exercise. IL-6 has been shown to be secreted from skeletal muscle during exercise and has been suggested to signal to the liver. Therefore, the aim of this study was to investigate the role of skeletal muscl...

  15. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, A.; Konings, E.; Goossens, G.H.; Bouwman, F.G.; Moors, C.C.; Boekschoten, M.V.; Afman, L.A.; Muller, M.R.; Mariman, E.C.; Blaak, E.E.

    2012-01-01

    Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial

  16. Three-dimensional optical coherence micro-elastography of skeletal muscle tissue.

    Science.gov (United States)

    Chin, Lixin; Kennedy, Brendan F; Kennedy, Kelsey M; Wijesinghe, Philip; Pinniger, Gavin J; Terrill, Jessica R; McLaughlin, Robert A; Sampson, David D

    2014-09-01

    In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue. We show that this technique can resolve features of muscle tissue including fibers, fascicles and tendon, and can also detect necrotic lesions in skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy. In many instances, OCME provides better or additional contrast complementary to that provided by OCT. These results suggest that OCME could provide new understanding and opportunity for assessment of skeletal muscle pathologies.

  17. Time course of gene expression during mouse skeletal muscle hypertrophy

    Science.gov (United States)

    Lee, Jonah D.; England, Jonathan H.; Esser, Karyn A.; McCarthy, John J.

    2013-01-01

    The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy. PMID:23869057

  18. Time course of gene expression during mouse skeletal muscle hypertrophy.

    Science.gov (United States)

    Chaillou, Thomas; Lee, Jonah D; England, Jonathan H; Esser, Karyn A; McCarthy, John J

    2013-10-01

    The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ≥2-fold increase or ≥50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy.

  19. Sphingosine 1-phosphate axis: a new leader actor in skeletal muscle biology

    Directory of Open Access Journals (Sweden)

    Chiara eDonati

    2013-11-01

    Full Text Available Sphingosine 1-phosphate (S1P is a bioactive lipid involved in the regulation of biological processes such as proliferation, differentiation, motility and survival. Here we review the role of S1P in the biology and homeostasis of skeletal muscle. S1P derives from the catabolism of sphingomyelin and is produced by sphingosine phosphorylation catalyzed by sphingosine kinase. S1P can act either intracellularly or extracellularly through specific ligation to its five G protein-coupled receptors named S1P receptors (S1PR. Many experimental findings obtained in the last 15 years demonstrate that S1P and its metabolism play a multifaceted role in the regulation of skeletal muscle regeneration. Indeed, this lipid is known to activate muscle-resident satellite cells, regulating their proliferation and differentiation, as well as mesenchymal progenitors such as mesoangioblasts that originate outside skeletal muscle, both involved in tissue repair following an injury or disease. The molecular mechanism of action of S1P in skeletal muscle cell precursors is highly complex, especially because S1P axis is under the control of a number of growth factors and cytokines, canonical regulators of skeletal muscle biology. Moreover, this lipid is crucially involved in the regulation of skeletal muscle contractile properties, responsiveness to insulin, fatigue resistance and trophism. Overall, on the basis of these findings S1P signalling appears to be an appealing pharmacological target for improving skeletal muscle repair. Nevertheless further understanding is required on the regulation of S1P downstream signalling pathways and the expression of S1PR. This article will resume our current knowledge on S1P signalling in skeletal muscle, hopefully stimulating further investigation in the field, aimed at individuating novel molecular targets for ameliorating skeletal muscle regeneration and reducing fibrosis of the tissue after a trauma or due to skeletal muscle diseases.

  20. Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

    Science.gov (United States)

    Sharples, Adam P; Stewart, Claire E; Seaborne, Robert A

    2016-08-01

    Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging.