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Sample records for denervated skeletal muscles

  1. Glucose metabolism in rats submitted to skeletal muscle denervation

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    Wilton Marlindo Santana Nunes

    2005-07-01

    Full Text Available This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the control. There was increased glucose uptake in the same paw 28 days after denervation. The rate of glucose removal in response to exogenous insulin after 28 days of denervation was significantly higher than in control animals and those observed after 3 and 7 days of denervation. These results suggest that immobilization by denervation interfered not only in glucose metabolism in the skeletal muscle involved but also in other tissues.O estudo analisou os efeitos locais e sistêmicos da imobilização por desnervação do músculo esquelético sobre o metabolismo glicidico. Ratos foram submetidos à secção do nervo ciático da pata direita. Observou-se redução da captação de glicose pelo músculo sóleo isolado da pata desnervada após 3 e 7 mas não após 28 dias em relação a animais controle. Não houve diferença após 3 e 7 dias na captação de glicose pelo músculo sóleo da pata contralateral intacta em relação ao controle. Houve aumento da captação de glicose nesta mesma pata 28 dias após a desnervação. A taxa de remoção da glicose em resposta à insulina exógena após 28 dias de desnervação foi significantemente superior à do controle e àquelas observadas após 3 e 7 dias da desnervação. Esses resultados sugerem que a imobilização por desnervação interfere não só no metabolismo da glicose no músculo esquelético envolvido como também em outros tecidos.

  2. Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation

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    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.

  3. Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle

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    Wei, Jih-Hua [Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan (China); Chang, Nen-Chung [Division of Cardiology, Department of Internal Medicine, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chen, Sy-Ping [Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China); Geraldine, Pitchairaj [Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu (India); Jayakumar, Thanasekaran, E-mail: tjaya_2002@yahoo.co.in [Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Fong, Tsorng-Harn, E-mail: thfong@tmu.edu.tw [Department of Anatomy and Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2015-10-09

    The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P < 0.05) decreased, about 24.6% and 40.2% in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin/MHC, nebulin/actin, and nebulin/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres. - Highlights: • We successfully

  4. Atypical expression of circadian clock genes in denervated mouse skeletal muscle.

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    Nakao, Reiko; Yamamoto, Saori; Horikawa, Kazumasa; Yasumoto, Yuki; Nikawa, Takeshi; Mukai, Chiaki; Oishi, Katsutaka

    2015-05-01

    The central circadian clock in the suprachiasmatic nucleus of the hypothalamus synchronizes peripheral clocks through neural and humoral signals in most mammalian tissues. Here, we analyzed the effects of unilateral sciatic denervation on the expression of circadian clock- and clock-controlled genes in the gastrocnemius muscles of mice twice per day on days 0, 3, 7, 9, 11 and 14 after denervation and six times on each of days 7 and 28 after denervation to assess the regulation mechanism of the circadian clock in skeletal muscle. Sciatic denervation did not affect systemic circadian rhythms since core body temperature (Day 7), corticosterone secretion (Days 7 and 28), and hepatic clock gene expression remained intact (Days 7 and 28). Expression levels of most circadian clock-related genes such as Arntl, Per1, Rora, Nr1d1 and Dbp were reduced in accordance with the extent of muscle atrophy, although circadian Per2 expression was significantly augmented (Day 28). Cosinor analysis revealed that the circadian expression of Arntl (Days 7 and 28) and Dbp (Day 28) was phase advanced in denervated muscle. The mRNA expression of Clock was significantly increased in denervated muscle on Day 3 when the severe atrophy was absent, and it was not affected by atrophic progression for 28 days. Sciatic denervation did not affect the expression of these genes in the contralateral muscle (Days 7 and 28), suggesting that humoral changes were not involved in denervation-induced muscle clock disruption. We then analyzed genome-wide gene expression using microarrays to determine the effects of disrupting the molecular clock in muscle on circadian rhythms at Day 7. Among 478 circadian genes, 313 lost rhythmicity in the denervated muscles. These denervation-sensitive genes included the lipid metabolism-related genes, Nrip1, Bbs1, Ptgis, Acot1, Scd2, Hpgd, Insig1, Dhcr24, Ldlr and Mboat1. Our findings revealed that sciatic denervation disrupts the circadian expression of clock and clock

  5. Dynamic changes in the mouse skeletal muscle proteome during denervation-induced atrophy

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    Lang, Franziska; Aravamudhan, Sriram; Nolte, Hendrik; Türk, Clara; Hölper, Soraya; Müller, Stefan; Günther, Stefan; Blaauw, Bert; Braun, Thomas

    2017-01-01

    ABSTRACT Loss of neuronal stimulation enhances protein breakdown and reduces protein synthesis, causing rapid loss of muscle mass. To elucidate the pathophysiological adaptations that occur in atrophying muscles, we used stable isotope labelling and mass spectrometry to quantify protein expression changes accurately during denervation-induced atrophy after sciatic nerve section in the mouse gastrocnemius muscle. Additionally, mice were fed a stable isotope labelling of amino acids in cell culture (SILAC) diet containing 13C6-lysine for 4, 7 or 11 days to calculate relative levels of protein synthesis in denervated and control muscles. Ubiquitin remnant peptides (K-ε-GG) were profiled by immunoaffinity enrichment to identify potential substrates of the ubiquitin-proteasomal pathway. Of the 4279 skeletal muscle proteins quantified, 850 were differentially expressed significantly within 2 weeks after denervation compared with control muscles. Moreover, pulse labelling identified Lys6 incorporation in 4786 proteins, of which 43 had differential Lys6 incorporation between control and denervated muscle. Enrichment of diglycine remnants identified 2100 endogenous ubiquitination sites and revealed a metabolic and myofibrillar protein diglycine signature, including myosin heavy chains, myomesins and titin, during denervation. Comparative analysis of these proteomic data sets with known atrogenes using a random forest approach identified 92 proteins subject to atrogene-like regulation that have not previously been associated directly with denervation-induced atrophy. Comparison of protein synthesis and proteomic data indicated that upregulation of specific proteins in response to denervation is mainly achieved by protein stabilization. This study provides the first integrated analysis of protein expression, synthesis and ubiquitin signatures during muscular atrophy in a living animal. PMID:28546288

  6. Dynamic changes in the mouse skeletal muscle proteome during denervation-induced atrophy

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    Franziska Lang

    2017-07-01

    Full Text Available Loss of neuronal stimulation enhances protein breakdown and reduces protein synthesis, causing rapid loss of muscle mass. To elucidate the pathophysiological adaptations that occur in atrophying muscles, we used stable isotope labelling and mass spectrometry to quantify protein expression changes accurately during denervation-induced atrophy after sciatic nerve section in the mouse gastrocnemius muscle. Additionally, mice were fed a stable isotope labelling of amino acids in cell culture (SILAC diet containing 13C6-lysine for 4, 7 or 11 days to calculate relative levels of protein synthesis in denervated and control muscles. Ubiquitin remnant peptides (K-ε-GG were profiled by immunoaffinity enrichment to identify potential substrates of the ubiquitin-proteasomal pathway. Of the 4279 skeletal muscle proteins quantified, 850 were differentially expressed significantly within 2 weeks after denervation compared with control muscles. Moreover, pulse labelling identified Lys6 incorporation in 4786 proteins, of which 43 had differential Lys6 incorporation between control and denervated muscle. Enrichment of diglycine remnants identified 2100 endogenous ubiquitination sites and revealed a metabolic and myofibrillar protein diglycine signature, including myosin heavy chains, myomesins and titin, during denervation. Comparative analysis of these proteomic data sets with known atrogenes using a random forest approach identified 92 proteins subject to atrogene-like regulation that have not previously been associated directly with denervation-induced atrophy. Comparison of protein synthesis and proteomic data indicated that upregulation of specific proteins in response to denervation is mainly achieved by protein stabilization. This study provides the first integrated analysis of protein expression, synthesis and ubiquitin signatures during muscular atrophy in a living animal.

  7. Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

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    Fabio Francini

    2010-09-01

    Full Text Available Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury or disease. Thus, the etiology of atrophy can be different. Atrophy in denervated muscle is a consequence of two factors: 1 the complete lack of motoneuron activity inducing the deficiency of neurotransmitter release and 2 the muscles disuse. The balance of the muscular functions depends on extra- and intra-muscular signals. In the balance are involved the excitation-contraction coupling (ECC, local growth factors, Ca2+-dependent and independent intracellular signals, mechano-sensitivity and mechano-transduction that activate Ca2+-dependent signaling proteins and cytoskeleton- nucleus pathways to the nucleus, that regulate the gene expression. Moreover, retrograde signal from intracellular compartments and cytoskeleton to the sarcolemma are additional factors that regulate the muscle function. Proteolytic systems that operate in atrophic muscles progressively reduce the muscle protein content and so the sarcolemma, ECC and the force generation. In this review we will focus on the more relevant changes of the sarcolemma, excitation-contraction coupling, ECC and mechano-transduction evaluated by electrophysiological methods and observed from early- to long-term denervated skeletal muscles. This review put in particular evidence that long-term denervated muscle maintain a sub-population of fibers with ECC and contractile machinery able to be activated, albeit in lesser amounts, by electrical and mechanical stimulation. Accordingly, this provides a potential molecular explanation of the muscle recovery that occurs in response to rehabilitation strategy as transcutaneous electrical stimulation and passive stretching of denervated muscles, which wre developed as a result of empirical clinical observations.

  8. Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation.

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    Lin, David C; Hershey, John D; Mattoon, John S; Robbins, Charles T

    2012-06-15

    Hibernating bears retain most of their skeletal muscle strength despite drastically reduced weight-bearing activity. Regular neural activation of muscles is a potential mechanism by which muscle atrophy could be limited. However, both mechanical loading and neural activity are usually necessary to maintain muscle size. An alternative mechanism is that the signaling pathways related to the regulation of muscle size could be altered so that neither mechanical nor neural inputs are needed for retaining strength. More specifically, we hypothesized that muscles in hibernating bears are resistant to a severe reduction in neural activation. To test this hypothesis, we unilaterally transected the common peroneal nerve, which innervates ankle flexor muscles, in hibernating and summer-active brown bears (Ursus arctos). In hibernating bears, the long digital extensor (LDE) and cranial tibial (CT) musculotendon masses on the denervated side decreased after 11 weeks post-surgery by 18 ± 11 and 25 ± 10%, respectively, compared with those in the intact side. In contrast, decreases in musculotendon masses of summer-active bears after denervation were 61 ± 4 and 58 ± 5% in the LDE and CT, respectively, and significantly different from those of hibernating bears. The decrease due to denervation in summer-active bears was comparable to that occurring in other mammals. Whole-muscle cross-sectional areas (CSAs) measured from ultrasound images and myofiber CSAs measured from biopsies decreased similarly to musculotendon mass. Thus, hibernating bears alter skeletal muscle catabolic pathways regulated by neural activity, and exploration of these pathways may offer potential solutions for disuse atrophy of muscles.

  9. Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy

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    Sepulveda, Patricio V.; Lamon, Séverine; Hagg, Adam; Thomson, Rachel E.; Winbanks, Catherine E.; Qian, Hongwei; Bruce, Clinton R.; Russell, Aaron P.; Gregorevic, Paul

    2015-01-01

    Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting. In this study, the delivery of a recombinant adeno-associated viral vector expressing follistatin (rAAV:Fst) to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles. However, administration of rAAV:Fst to muscles at the time of denervation or tenotomy did not prevent subsequent muscle wasting. Administration of rAAV:Fst to innervated or denervated muscles increased protein synthesis, but markedly reduced protein degradation only in innervated muscles. Phosphorylation of the signalling proteins mTOR and S6RP, which are associated with protein synthesis, was increased in innervated muscles administered rAAV:Fst, but not in treated denervated muscles. These results demonstrate that the anabolic effects of follistatin are influenced by the interaction between muscle fibres and motor nerves. These findings have important implications for understanding the potential efficacy of follistatin-based therapies for non-degenerative muscle wasting. PMID:26657343

  10. Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy.

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    Sepulveda, Patricio V; Lamon, Séverine; Hagg, Adam; Thomson, Rachel E; Winbanks, Catherine E; Qian, Hongwei; Bruce, Clinton R; Russell, Aaron P; Gregorevic, Paul

    2015-12-11

    Follistatin is an inhibitor of TGF-β superfamily ligands that repress skeletal muscle growth and promote muscle wasting. Accordingly, follistatin has emerged as a potential therapeutic to ameliorate the deleterious effects of muscle atrophy. However, it remains unclear whether the anabolic effects of follistatin are conserved across different modes of non-degenerative muscle wasting. In this study, the delivery of a recombinant adeno-associated viral vector expressing follistatin (rAAV:Fst) to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles. However, administration of rAAV:Fst to muscles at the time of denervation or tenotomy did not prevent subsequent muscle wasting. Administration of rAAV:Fst to innervated or denervated muscles increased protein synthesis, but markedly reduced protein degradation only in innervated muscles. Phosphorylation of the signalling proteins mTOR and S6RP, which are associated with protein synthesis, was increased in innervated muscles administered rAAV:Fst, but not in treated denervated muscles. These results demonstrate that the anabolic effects of follistatin are influenced by the interaction between muscle fibres and motor nerves. These findings have important implications for understanding the potential efficacy of follistatin-based therapies for non-degenerative muscle wasting.

  11. Permanent LMN denervation of human skeletal muscle and recovery by h-b FES: management and monitoring

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    Helmut Kern

    2010-09-01

    Full Text Available Denervation of a defined skeletal muscle is due to lower motor neuron (LMN or peripheral nerve lesions that have major consequences on the muscle tissue. After early atrophy, the mid- and late-phases presents two very contrasting myofibers populations: beside those severely atrophic with internalized groups of myonuclei, large fast-type muscle fibers continue to be present 4 to 6 years after Spinal Cord Injury (SCI. Recent results of rat experiments provides the rational basis for understanding the residual functional characteristics of the long-term denervated muscle and the molecular explanation of its ability to respond to home-base functional electrical stimulation (h-b FES using custom-designed electrodes and stimulators. Further outcomes of the Vienna-Padova ten-year collaboration are: 1. a world-unique Myo- Bank of muscle biopsies and 2. improved imaging procedures (Color Computer Tomography (CT scan and Functional Echomyography, all demonstrating that h-b FES induces improvements in muscle contractility, tissue composition and mass, despite permanent LMN denervation. The benefits of h-b FES could be extended from patents suffering with complete Conus-Cauda Syndrome to the numerous patients with incomplete LMN denervation of skeletal muscles to determine whether h-b FES reduces secondary complications related to disuse and impaired blood perfusion (reduction in bone density, risk of bone fracture, decubitus ulcers, and pulmonary thromboembolism. We are confident that translation of the results of a clinical experiment, the EU Project RISE, to the larger cohort of incomplete LMN denervated muscles will provide the wanted results.

  12. Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

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    Libelius, R.; Lundquist, I.; Templeton, W.; Thesleff, S.

    1978-01-01

    Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules [ 3 H] α-neurotoxin, [ 3 H]inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a [ 3 H]monoacetylated α-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of [ 3 H] inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of [ 3 H]inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of [ 3 H]inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of [ 3 H]inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized [ 3 H]inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of [ 3 H]inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified [ 3 H]inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as [ 3 H]inulin. Additional radioactivity consisted of lower molecular weight compounds. These degradation products of [ 3 H]inulin were only present in the muscle homogenate and were not detected in the incubation solution. The results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur. (author)

  13. ALS-Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology.

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    Jesse, C M; Bushuven, E; Tripathi, P; Chandrasekar, A; Simon, C M; Drepper, C; Yamoah, A; Dreser, A; Katona, I; Johann, S; Beyer, C; Wagner, S; Grond, M; Nikolin, S; Anink, J; Troost, D; Sendtner, M; Goswami, A; Weis, J

    2017-11-01

    Alpha-motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd 2J mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A-SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB-immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha-motoneurons. Thus, ER pathology could contribute to the selective build-up of degenerative changes in the neuromuscular axis in MNDs. © 2016 International Society of Neuropathology.

  14. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

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    Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

    2017-10-24

    Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

  15. MRI appearance of muscle denervation

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    Kamath, S. [University Hospital of Wales, Department of Radiology, Cardiff (United Kingdom); Venkatanarasimha, N.; Walsh, M.A.; Hughes, P.M. [Derriford Hospital, Department of Radiology, Plymouth (United Kingdom)

    2008-05-15

    Muscle denervation results from a variety of causes including trauma, neoplasia, neuropathies, infections, autoimmune processes and vasculitis. Traditionally, the diagnosis of muscle denervation was based on clinical examination and electromyography. Magnetic resonance imaging (MRI) offers a distinct advantage over electromyography, not only in diagnosing muscle denervation, but also in determining its aetiology. MRI demonstrates characteristic signal intensity patterns depending on the stage of muscle denervation. The acute and subacutely denervated muscle shows a high signal intensity pattern on fluid sensitive sequences and normal signal intensity on T1-weighted MRI images. In chronic denervation, muscle atrophy and fatty infiltration demonstrate high signal changes on T1-weighted sequences in association with volume loss. The purpose of this review is to summarise the MRI appearance of denervated muscle, with special emphasis on the signal intensity patterns in acute and subacute muscle denervation. (orig.)

  16. Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

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    Kouki Nakagawa

    2017-01-01

    Full Text Available The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON, denervation (DN, and denervation with direct ES (DN + ES. Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA, and capillary-to-fiber (C/F ratio of the tibialis anterior (TA muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs.

  17. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

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    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2018-01-01

    changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  18. Electrical Stimulation of Denervated Rat Skeletal Muscle Ameliorates Bone Fragility and Muscle Loss in Early-Stage Disuse Musculoskeletal Atrophy.

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    Tamaki, Hiroyuki; Yotani, Kengo; Ogita, Futoshi; Hayao, Keishi; Nakagawa, Kouki; Sugawara, Kazuhiro; Kirimoto, Hikari; Onishi, Hideaki; Kasuga, Norikatsu; Yamamoto, Noriaki

    2017-04-01

    We tested whether daily muscle electrical stimulation (ES) can ameliorate the decrease in cortical bone strength as well as muscle and bone geometric and material properties in the early stages of disuse musculoskeletal atrophy. 7-week-old male F344 rats were randomly divided into three groups: age-matched control group (Cont); a sciatic denervation group (DN); and a DN + direct electrical stimulation group (DN + ES). Denervated tibialis anterior (TA) muscle in the DN + ES group received ES with 16 mA at 10 Hz for 30 min/day, 6 days/week. Micro CT, the three-point bending test, and immunohistochemistry were used to characterize cortical bone mechanical, structural, and material properties of tibiae. TA muscle in the DN + ES group showed significant improvement in muscle mass and myofiber cross-sectional area relative to the DN group. Maximal load and stiffness of tibiae, bone mineral density estimated by micro CT, and immunoreactivity of DMP1 in the cortical bone tissue were also significantly greater in the DN + ES group than in the DN group. These results suggest that daily ES-induced muscle contraction treatment reduced the decrease in muscle mass and cortical bone strength in early-stage disuse musculoskeletal atrophy and is associated with a beneficial effect on material properties such as mineralization of cortical bone tissue.

  19. Pyrroloquinoline Quinone Resists Denervation-Induced Skeletal Muscle Atrophy by Activating PGC-1α and Integrating Mitochondrial Electron Transport Chain Complexes.

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    Yung-Ting Kuo

    Full Text Available Denervation-mediated skeletal muscle atrophy results from the loss of electric stimulation and leads to protein degradation, which is critically regulated by the well-confirmed transcriptional co-activator peroxisome proliferator co-activator 1 alpha (PGC-1α. No adequate treatments of muscle wasting are available. Pyrroloquinoline quinone (PQQ, a naturally occurring antioxidant component with multiple functions including mitochondrial modulation, demonstrates the ability to protect against muscle dysfunction. However, it remains unclear whether PQQ enhances PGC-1α activation and resists skeletal muscle atrophy in mice subjected to a denervation operation. This work investigates the expression of PGC-1α and mitochondrial function in the skeletal muscle of denervated mice administered PQQ. The C57BL6/J mouse was subjected to a hindlimb sciatic axotomy. A PQQ-containing ALZET® osmotic pump (equivalent to 4.5 mg/day/kg b.w. was implanted subcutaneously into the right lower abdomen of the mouse. In the time course study, the mouse was sacrificed and the gastrocnemius muscle was prepared for further myopathological staining, energy metabolism analysis, western blotting, and real-time quantitative PCR studies. We observed that PQQ administration abolished the denervation-induced decrease in muscle mass and reduced mitochondrial activities, as evidenced by the reduced fiber size and the decreased expression of cytochrome c oxidase and NADH-tetrazolium reductase. Bioenergetic analysis demonstrated that PQQ reprogrammed the denervation-induced increase in the mitochondrial oxygen consumption rate (OCR and led to an increase in the extracellular acidification rate (ECAR, a measurement of the glycolytic metabolism. The protein levels of PGC-1α and the electron transport chain (ETC complexes were also increased by treatment with PQQ. Furthermore, PQQ administration highly enhanced the expression of oxidative fibers and maintained the type II glycolytic

  20. Denervation and high-fat diet reduce insulin signaling in T-tubules in skeletal muscle of living mice

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    Lauritzen, Hans P M; Ploug, Thorkil; Ai, Hua

    2008-01-01

    OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during these co......OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during...... receptors. RESULTS: Denervation and high-fat diet reduced insulin-mediated glucose transport. In denervated muscle, insulin-stimulated phosphatidylinositol 3,4,5 P(3) (PIP3) production was abolished in T-tubules, while PIP3 production at sarcolemma was increased 2.6-fold. Correspondingly, GLUT4-GFP...

  1. Effect of salbutamol on innervated and denervated rat soleus muscle

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    ?oic-Vranic T.

    2005-01-01

    Full Text Available The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a ß2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10, treated with salbutamol (N = 30, denervated (N = 30, and treated with salbutamol after denervation (N = 30. Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21% in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other ß2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.

  2. ULTRASTRUCTURAL STUDIES ON MUSCULAR ATROPHY IN MAREK'S DISEASE : I. DENERVATION ATROPHY IN CHICKEN SKELETAL MUSCLE A LIGHT AND ELECTRON MICROSCOPIC STUDY

    OpenAIRE

    MADARAME, Hiroo; FUJIMOTO, Yutaka; MORIGUCHI, Ryozo

    1986-01-01

    When denervation was performed by nerve-cutting and nerve-crushing in chickens, three phases could be observed morphologically. The first phase was characterized by foregoing degenerative changes of the neuro-muscular junctions (axon terminals), followed by atrophic changes of the muscle fibers. The second phase was characterized by irregular arrangement of the myofilaments in atrophic muscle fibers and appearance of regenerative muscular changes by 20 days after denervation. By this time, no...

  3. Sarco(endo)plasmic reticulum Ca2+ pump and metabolic enzyme expression in rabbit fast-type and slow-type denervated skeletal muscles. A time course study.

    Science.gov (United States)

    Nozais, M; Lompré, A M; Janmot, C; D'Albis, A

    1996-06-15

    Recent reports by d'Albis et al. have shown that denervation of 8-day-old rabbit fast-twitch muscle (gastrocnemius) leads to the transformation of the muscle towards a slow phenotype but the changes towards slow-type myosin isoforms and contractile properties of the muscle were temporally uncoordinated. We analyzed the time course of the effects of denervation of the gastrocnemius on the expression of the sarcoplasmic reticulum calcium pump isoforms (SERCA) and on the metabolic state of the muscle. Northern-blot analysis showed a rapid loss of the fast Ca2+ pump isoform (SERCA 1) mRNA from the denervated gastrocnemius which became of the oxidative type. The changes observed were complete as early as 35 days post-natal, i.e at the time when changes in contractile properties were previously observed. Denervation of the slow-twitch soleus led to a 50% decrease in the level of the slow Ca2+ pump isoform (SERCA 2) mRNA and was without effect on the metabolic state of the muscle. These findings extend previous results suggesting that in rabbit, continuous innervation is required for differentiation of fast-twitch muscles but is not an absolute requirement for differentiation of the slow-twitch muscle.

  4. Electrical stimulation attenuates denervation and age-related atrophy in extensor digitorum longus muscles of old rats.

    Science.gov (United States)

    Dow, Douglas E; Dennis, Robert G; Faulkner, John A

    2005-04-01

    Skeletal muscles of old rats and elderly humans lose muscle mass and maximum force. Denervation is a major cause of age-related muscle atrophy and weakness, because denervated fibers do not contract, and undergo atrophy. At any age, surgical denervation causes even more dramatic muscle atrophy and loss in force than aging does. Electrical stimulation that generates tetanic contractions of denervated muscles reduces the denervation-induced declines. We investigated whether a stimulation protocol that maintains mass and force of denervated extensor digitorum longus muscles of adult rats would also maintain these properties in denervated muscles of old rats during a 2-month period of age-induced declines in these properties. Contractile activity generated by the electrical stimulation eliminated age-related losses in muscle mass and reduced the deficit in force by 50%. These data provide support for the hypothesis that during aging, lack of contractile activity in fibers contributes to muscle atrophy and weakness.

  5. Denervation of rabbit gastrocnemius and soleus muscles: effect on muscle-specific enolase.

    Science.gov (United States)

    Nozais, M; Merkulova, T; Keller, A; Janmot, C; Lompré, A M; D'Albis, A; Lucas, M

    1999-07-01

    We report here, for the first time, the expression of the muscle-specific isoform of the glycolytic enzyme, enolase (EC 4.2.1. 11) (beta enolase), in rabbit skeletal muscles. We have analysed the fast-twitch gastrocnemius and the slow-twitch soleus muscles during normal postnatal development and following denervation. We show that, in rabbit, as already described in rodents, beta enolase gene expression behaves as a good marker of the fast-twitch fibers. In soleus muscle, the beta enolase transcript level is 10-20% of that found in gastrocnemius. Denervation, performed at 8 postnatal days, induces an important drop of beta enolase transcript levels in both developing soleus and gastrocnemius muscles, with a 80% decrease observed 1 week after denervation in the operated muscles, as compared to the corresponding contralateral muscles. Thereafter, the beta enolase transcript level continues to decrease in the fast-twitch muscle, with the beta enolase subunit being detectable only in the atrophic fast-twitch fibers. In contrast, the beta transcript level tends to increase in the denervated slow-twitch muscle, reaching about 50% of that in contralateral soleus, at 7 weeks after surgery. The level of beta enolase transcripts still expressed after denervation seems to stabilize at the same low level in both types of inactive muscles. This suggests that the small fraction of beta enolase expression which is not controlled by the nerve, or by the contractile activity imposed by it, is independent of the muscle phenotype.

  6. Denervated muscle fibers induce mitochondrial peroxide generation in neighboring innervated fibers: Role in muscle aging.

    Science.gov (United States)

    Pollock, Natalie; Staunton, Caroline A; Vasilaki, Aphrodite; McArdle, Anne; Jackson, Malcolm J

    2017-11-01

    Disruption of neuromuscular junctions and denervation of some muscle fibers occurs in ageing skeletal muscle and contribute to loss of muscle mass and function. Aging is associated with mitochondrial dysfunction and loss of redox homeostasis potentially occurs through increased mitochondrial generation of reactive oxygen species (ROS). No specific link between increased mitochondrial ROS generation and denervation has been defined in muscle ageing. To address this, we have examined the effect of experimental denervation of all fibers, or only a proportion of the fibers, in the mouse tibialis anterior (TA) muscle on muscle mitochondrial peroxide generation. Transection of the peroneal nerve of mice caused loss of pre-synaptic axons within 1-3 days with no significant morphological changes in post-synaptic structures up to 10 days post-surgery when decreased TA mass and fiber size were apparent. Mitochondria in the denervated muscle showed increased peroxide generation by 3 days post-transection. Use of electron transport chain (ETC) substrates and inhibitors of specific pathways indicated that the ETC was unlikely to contribute to increased ROS generation, but monoamine oxidase B, NADPH oxidase and phospholipase enzymes were implicated. Transection of one of the 3 branches of the peroneal nerve caused denervation of some TA muscle fibers while others retained innervation, but increased mitochondrial peroxide generation occurred in both denervated and innervated fibers. Thus the presence of recently denervated fibers leads to increased ROS generation by mitochondria in neighboring innervated fibers providing a novel explanation for the increased mitochondrial oxidative stress and damage seen with aging in skeletal muscles. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle

    Science.gov (United States)

    Henriksen, Erik J.; Rodnick, Kenneth J.; Mondon, Carl E.; James, David E.; Holloszy, John O.

    1991-01-01

    The study is intended to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). Results obtained indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. It is concluded that muscle activity is an important factor in the regulation of the GLUT-4 expression in skeletal muscle.

  8. Impact of denervation-induced muscle atrophy on housekeeping gene expression in mice.

    Science.gov (United States)

    Nakao, Reiko; Yamamoto, Saori; Yasumoto, Yuki; Kadota, Koji; Oishi, Katsutaka

    2015-02-01

    Immobilization induced by experimental denervation leads to rapid and progressive alterations in structural and biochemical properties of skeletal muscle. Real-time reverse transcription-polymerase chain reaction (RT-PCR) is a popular method of elucidating the molecular mechanisms involved in muscle atrophy. Identification of suitable reference genes that are not affected by experimental conditions is a critical step in accurate normalization of real-time RT-PCR. We investigated the impact of denervation-induced muscle atrophy for 2 weeks on the expression of common housekeeping genes. Denervation differentially affected the expression levels of these genes. RefFinder software identified TATA box binding protein (Tbp) as the most stable gene and showed that the stability of glyceraldehyde-3-phosphate dehydrogenase (Gapdh) and hypoxanthine guanine phosphoribosyl transferase (Hprt) genes was low, even though they are widely used for normalization. The appropriate reference gene for normalization of genes of interest in denervated muscle is Tbp. © 2014 Wiley Periodicals, Inc.

  9. Clenbuterol, a beta(2)-agonist, retards atrophy in denervated muscles

    Science.gov (United States)

    Zeman, Richard J.; Ludemann, Robert; Etlinger, Joseph D.

    1987-01-01

    The effects of a beta(2) agonist, clenbuterol, on the protein content as well as on the contractile strength and the muscle fiber cross-sectional area of various denervated muscles from rats were investigated. It was found that denervated soleus, anterior tibialis, and gastrocnemius muscles, but not the extensor digitorum longus, of rats treated for 2-3 weeks with clenbuterol contained 95-110 percent more protein than denervated controls. The twofold difference in the protein content of denervated solei was paralleled by similar changes in contractile strength and muscle fiber cross-sectional area.

  10. Denervation pseudohypertrophy of calf muscles associated with diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Kin Hoi Wong, MBBS, FRCR

    2017-12-01

    Full Text Available Denervation of muscle usually leads to muscle atrophy with fatty replacement but, uncommonly, also results in muscle hypertrophy or pseudohypertrophy with fatty replacement. We report the ultrasonographic and magnetic resonance imaging (MRI findings of a patient with diffuse fatty infiltration of calf muscles as a result of denervation pseudohypertrophy. The elevated fasting glucose, neurogenic electromyographic changes, and muscle atrophy with adipose tissue infiltration are consistent with diabetic neuropathy as the cause of denervation pseudohypertrophy. Lumbosacral radiculopathy and plexopathy were excluded by MRI. The imaging features reported in the literature are reviewed. The important differential diagnosis of infiltrating lipoma and denervation hypertrophy, as well as other causes of monomelic hypertrophy or swelling, is discussed. This case report demonstrates the importance of MRI, with clinical, biochemical, electrophysiological, and histologic correlation in the diagnosis of denervation pseudohypertrophy. Correct diagnosis of denervation pseudohypertrophy has an important role in guiding further investigations and treatment of the disease and the underlying cause.

  11. Denervation pseudohypertrophy of calf muscles associated with diabetic neuropathy.

    Science.gov (United States)

    Wong, Kin Hoi; Chow, Maria Bernadette Che Ying; Lui, Tun Hing; Cheong, Yue Kew; Tam, Kwok Fai

    2017-12-01

    Denervation of muscle usually leads to muscle atrophy with fatty replacement but, uncommonly, also results in muscle hypertrophy or pseudohypertrophy with fatty replacement. We report the ultrasonographic and magnetic resonance imaging (MRI) findings of a patient with diffuse fatty infiltration of calf muscles as a result of denervation pseudohypertrophy. The elevated fasting glucose, neurogenic electromyographic changes, and muscle atrophy with adipose tissue infiltration are consistent with diabetic neuropathy as the cause of denervation pseudohypertrophy. Lumbosacral radiculopathy and plexopathy were excluded by MRI. The imaging features reported in the literature are reviewed. The important differential diagnosis of infiltrating lipoma and denervation hypertrophy, as well as other causes of monomelic hypertrophy or swelling, is discussed. This case report demonstrates the importance of MRI, with clinical, biochemical, electrophysiological, and histologic correlation in the diagnosis of denervation pseudohypertrophy. Correct diagnosis of denervation pseudohypertrophy has an important role in guiding further investigations and treatment of the disease and the underlying cause.

  12. Expression of TGF-β1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice.

    Science.gov (United States)

    Liu, Fei; Tang, Weifang; Chen, Donghui; Li, Meng; Gao, Yinna; Zheng, Hongliang; Chen, Shicai

    2016-01-01

    Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

  13. Distinct signal transductions in fast- and slow- twitch muscles upon denervation.

    Science.gov (United States)

    Gao, Hongbo; Li, Yi-Fan

    2018-02-01

    Denervation induces skeletal muscle atrophy, which primarily impairs oxidative slow twitch fibers. The underlying mechanism of this phenomenon, however, remains to be addressed. We hypothesize that denervation-induced fiber-specific atrophy may result from the distinct activities of different signaling pathways that are involved in protein synthesis and degradation in fast- and slow-twitch fibers. In this study, 1-month-old male mice were subjected to unilateral sciatic denervation for 4 days. Fast-twitch muscle extensor digitorum longus (EDL) and slow-twitch muscle soleus were collected from the denervated side and the control side of hind limbs. Total and phosphorylated protein levels of key factors of major signaling pathways in these tissues were determined using western blot assay. Our data showed that total AKT and FoxO3 protein levels were upregulated in denervated muscles as compared with control sides. Phosphorylation of AKT and FoxO3 were proportionally enhanced in denervated EDL but not soleus, indicating AKT activation drives phosphorylation of FoxO3 in EDL but not in soleus upon denervation. As a result, FoxO3-targeted atrogenes MurF1 and Atrogin1 protein abundances were reduced in denervated EDL but not altered in soleus. In consistent with this change, polyubiquitination were significantly increased in denervated soleus, but only a slight increase in ubiquitination was found in denervated EDL. Autophagy marker LC3 protein level was significantly increased in both muscle types, but in greater extent in EDL after denervation. IRS1 protein level and active ERK were reduced in both muscles upon denervation, which might contribute to the upregulation of total AKT protein level and FoxO3 abundance in EDL and soleus. Total and phosphorylated AMPK protein levels were increased in denervated soleus but not in EDL. Overall, these data reveal that the key signaling pathways that regulate protein synthesis and degradation are more sensitive in soleus than EDL

  14. Diffusion-weighted MRI of denervated muscle: a clinical and experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Holl, Nathalie; Bierry, Guillaume; Moser, Thomas; Dietemann, Jean-Louis; Kremer, Stephane [Hopitaux Universitaires de Strasbourg, Service de Radiologie 2, Strasbourg (France); Echaniz-Laguna, Andoni [Hopitaux Universitaires de Strasbourg, Departement de Neurologie, BP 426, Strasbourg (France); Mohr, Michel [Hopitaux Universitaires de Strasbourg, Departement d' Anatomie Pathologique, Strasbourg (France); Loeffler, Jean-Philippe [INSERM U692, Laboratoire de Signalisations Moleculaires et Neurodegenerescence, Faculte de Medecine, Strasbourg (France)

    2008-12-15

    The aim of this study was to investigate skeletal muscle denervation using diffusion-weighted magnetic resonance imaging (DWMRI). Sciatic nerve axotomy was performed in a group of nine New Zealand White rabbits, and electromyographic (EMG), pathological, and DWMRI studies were conducted on ipsilateral hamstring muscles 1 and 8 days after axotomy. In addition, DWMRI studies were carried out on leg muscles of ten patients with acute and subacute lumbosacral radiculopathy. High intensity signals on short tau inversion recovery (STIR) magnetic resonance imaging and an increased apparent diffusion coefficient (ADC) were observed in denervated muscles of the animals 1 and 8 days after axotomy as well as in denervated muscles of the patients with radiculopathy. In the clinical study, ADC was 1.26{+-}0.18 x 10{sup -9} m{sup 2}/s in normal muscle and increased to 1.56{+-}0.23 x 10{sup -9} m{sup 2}/s in denervated muscles (p =0.0016). In animals, EMG and muscle pathological studies were normal 1 day after axotomy, and the muscles demonstrated spontaneous activity on EMG and neurogenic atrophy on histological studies 7 days later. This DWMRI study demonstrates that enlargement of extracellular fluid space in muscle denervation is an early phenomenon occurring several days before the appearance of EMG and histological abnormalities. (orig.)

  15. Diffusion-weighted MRI of denervated muscle: a clinical and experimental study

    International Nuclear Information System (INIS)

    Holl, Nathalie; Bierry, Guillaume; Moser, Thomas; Dietemann, Jean-Louis; Kremer, Stephane; Echaniz-Laguna, Andoni; Mohr, Michel; Loeffler, Jean-Philippe

    2008-01-01

    The aim of this study was to investigate skeletal muscle denervation using diffusion-weighted magnetic resonance imaging (DWMRI). Sciatic nerve axotomy was performed in a group of nine New Zealand White rabbits, and electromyographic (EMG), pathological, and DWMRI studies were conducted on ipsilateral hamstring muscles 1 and 8 days after axotomy. In addition, DWMRI studies were carried out on leg muscles of ten patients with acute and subacute lumbosacral radiculopathy. High intensity signals on short tau inversion recovery (STIR) magnetic resonance imaging and an increased apparent diffusion coefficient (ADC) were observed in denervated muscles of the animals 1 and 8 days after axotomy as well as in denervated muscles of the patients with radiculopathy. In the clinical study, ADC was 1.26±0.18 x 10 -9 m 2 /s in normal muscle and increased to 1.56±0.23 x 10 -9 m 2 /s in denervated muscles (p =0.0016). In animals, EMG and muscle pathological studies were normal 1 day after axotomy, and the muscles demonstrated spontaneous activity on EMG and neurogenic atrophy on histological studies 7 days later. This DWMRI study demonstrates that enlargement of extracellular fluid space in muscle denervation is an early phenomenon occurring several days before the appearance of EMG and histological abnormalities. (orig.)

  16. mTORC1 promotes denervation-induced muscle atrophy through a mechanism involving the activation of FoxO and E3 ubiquitin ligases.

    Science.gov (United States)

    Tang, Huibin; Inoki, Ken; Lee, Myung; Wright, Erika; Khuong, Andy; Khuong, Amanda; Sugiarto, Sista; Garner, Matthew; Paik, Jihye; DePinho, Ronald A; Goldman, Daniel; Guan, Kun-Liang; Shrager, Joseph B

    2014-02-25

    Skeletal muscle mass and function are regulated by motor innervation, and denervation results in muscle atrophy. The activity of mammalian target of rapamycin complex 1 (mTORC1) is substantially increased in denervated muscle, but its regulatory role in denervation-induced atrophy remains unclear. At early stages after denervation of skeletal muscle, a pathway involving class II histone deacetylases and the transcription factor myogenin mediates denervation-induced muscle atrophy. We found that at later stages after denervation of fast-twitch muscle, activation of mTORC1 contributed to atrophy and that denervation-induced atrophy was mitigated by inhibition of mTORC1 with rapamycin. Activation of mTORC1 through genetic deletion of its inhibitor TSC1 (tuberous sclerosis complex 1) sensitized mice to denervation-induced muscle atrophy and suppressed the kinase activity of Akt, leading to activation of FoxO transcription factors and increasing the expression of genes encoding E3 ubiquitin ligases atrogin [also known as MAFbx (muscle atrophy F-box protein)] and MuRF1 (muscle-specific ring finger 1). Rapamycin treatment of mice restored Akt activity, suggesting that the denervation-induced increase in mTORC1 activity was producing feedback inhibition of Akt. Genetic deletion of the three FoxO isoforms in skeletal muscle induced muscle hypertrophy and abolished the late-stage induction of E3 ubiquitin ligases after denervation, thereby preventing denervation-induced atrophy. These data revealed that mTORC1, which is generally considered to be an important component of anabolism, is central to muscle catabolism and atrophy after denervation. This mTORC1-FoxO axis represents a potential therapeutic target in neurogenic muscle atrophy.

  17. Denervated muscle fibers explain the deficit in specific force following reinnervation of the rat extensor digitorum longus muscle.

    Science.gov (United States)

    van der Meulen, Jack H; Urbanchek, Melanie G; Cederna, Paul S; Eguchi, Tomoaki; Kuzon, William M

    2003-10-01

    The authors tested the hypothesis that, after denervation and reinnervation of skeletal muscle, observed deficits in specific force can be completely attributed to the presence of denervated muscle fibers. The peroneal nerve innervating the extensor digitorum longus muscle in rats was sectioned and the distal stump was coapted to the proximal stump, allowing either a large number of motor axons (nonreduced, n = 12) or a drastically reduced number of axons access to the distal nerve stump (drastically reduced, n = 18). A control group of rats underwent exposure of the peroneal nerve, without transection, followed by wound closure (control, n = 9). Four months after the operation, the maximum tetanic isometric force (Fo) of the extensor digitorum longus muscle was measured in situ and the specific force (sFo) was calculated. Cross-sections of the muscles were labeled for neural cell adhesion molecule (NCAM) protein to distinguish between innervated and denervated muscle fibers. Compared with extensor digitorum longus muscles from rats in the control (295 +/- 11 kN/m2) and nonreduced (276 +/- 12 kN/m2) groups, sFo of the extensor digitorum longus muscles from animals in the drastically reduced group was decreased (227 +/- 15 kN/m2, p extensor digitorum longus muscles from animals in the drastically reduced group (18 +/- 3 percent) was significantly higher than in the control (3 +/- 1 percent) group, but not compared with the nonreduced (9 +/- 2 percent) group. After exclusion of the denervated fibers, sFo did not differ between extensor digitorum longus muscles from animals in the drastically reduced (270 +/- 20 kN/m2), nonreduced (301 +/- 13 kN/m2), or control (303 +/- 10 kN/m2) groups. The authors conclude that, under circumstances of denervation and rapid reinnervation, the decrease in sFo of muscle can be attributed to the presence of denervated muscle fibers.

  18. Functional Echomyography of the human denervated muscle: first results

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato

    2011-03-01

    Full Text Available In this study we followed with ultrasound three patients with permanent denervation to evaluate changes in morphology, thickness, contraction and vascularisation of muscles undergoing the home-based electrical stimulation program of the Rise2-Italy project. During a period of 1 year for the first subject, 6 months for the second subject and 3 months for the third subject we studied with ultrasound the denervated muscle comparing it (if possible to the contralateral normal muscle. We evaluated: 1. Changes in morphology and sonographic structure of the pathologic muscle; 2. Muscular thickness in response to the electrical stimulation therapy; 3. Short-term modifications in muscle perfusion and arterial flow patterns after stimulation; 4. Contraction-relaxation kinetic induced by volitional activity or electrical stimulation. Morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete muscular atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third than in the proximal and distal third of the denervated muscle, reaching in the last measurements of the first subject approximately the same thickness as the contralateral normal muscle. In all the measurements done within this study, arterial flow of the denervated muscle showed at rest a low-resistance pattern with Doppler Ultra Sound (US, and a pulsed pattern after electrical stimulation. The stimulation- induced pattern is similar to the trifasic high-resistance pattern of the normal muscle. Contraction- relaxation kinetic, measured by recording the muscular movements during electrical stimulation, showed an abnormal behaviour of the denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle (880 msec in the denervated muscle vs 240 msec in the contralateral normal one

  19. Persistent muscle fiber regeneration in long term denervation. Past, present, future

    Directory of Open Access Journals (Sweden)

    Ugo Carraro

    2015-03-01

    Full Text Available Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES. Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb. Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest

  20. 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 m...

  1. Intermittent stretching induces fibrosis in denervated rat muscle.

    Science.gov (United States)

    Faturi, Fernanda M; Franco, Rúbia C; Gigo-Benato, Davilene; Turi, Andriette C; Silva-Couto, Marcela A; Messa, Sabrina P; Russo, Thiago L

    2016-01-01

    Stretching (St) has been used for treating denervated muscles. However, its effectiveness and safety claims require further study. Rats were divided into: (1) those with denervated (D) muscles, evaluated 7 or 15 days after sciatic nerve crush injury; (2) those with D muscles submitted to St during 7 or 15 days; and (3) those with normal muscles. Muscle fiber cross-sectional area, serial sarcomere number, sarcomere length, and connective tissue density were measured. MMP-2, MMP-9, TIMP-1, TGF-β1, and myostatin mRNAs were determined by real-time polymerase chain reaction. MMP-2 and MMP-9 activity was evaluated by zymography. Collagen I was localized using immunofluorescence. St did not prevent muscle atrophy due to denervation, but it increased fibrosis and collagen I deposition at day 15. St also upregulated MMP-9 and TGF-β1 gene expressions at day 7, and myostatin at day 15. Stretching denervated muscle does not prevent atrophy, but it increases fibrosis via temporal modulation of TGF-β1/myostatin and MMP-9 cascades. © 2015 Wiley Periodicals, Inc.

  2. Engineering Skeletal Muscle Repair

    OpenAIRE

    Juhas, Mark; Bursac, Nenad

    2013-01-01

    Healthy skeletal muscle has a remarkable capacity for regeneration. Even at a mature age, muscle tissue can undergo a robust rebuilding process that involves the formation of new muscle cells and extracellular matrix and the re-establishment of vascular and neural networks. Understanding and reverse-engineering components of this process is essential for our ability to restore loss of muscle mass and function in cases where the natural ability of muscle for self-repair is exhausted or impaire...

  3. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy*

    OpenAIRE

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko

    2016-01-01

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice ex...

  4. Lipolysis in Skeletal Muscle

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck

    of AMPK in regulation of lipid handling and lipolysis in the basal non-contracting state and during muscle contractions in skeletal muscle. To evaluate the role of AMPK, we measured protein expression and phosphorylation as well as gene expression of proteins important for regulation of lipid handling...... and lipolysis in skeletal muscle from wildtype mice and mice overexpressing a kinase dead AMPKα2 construct (AMPKα2 KD) in the basal non-contracting state and during in situ stimulated muscle contractions. We found, that IMTG levels were ~50% lower in AMPKα2 KD in the basal resting state, explained by a lower....... IMTG was in wildtype mice reduced with ~50% after muscle contractions with no effect of contractions in AMPKα2 KD mice. Concomitantly, ATGL was phosphorylated at ser406 and HSL on ser565 with muscle contractions in an AMPK dependent manner, suggesting that these sites actives lipolysis during muscle...

  5. Effects of electrical stimulation and stretching on the adaptation of denervated skeletal muscle: implications for physical therapy Efeitos da eletroestimulação e do alongamento muscular sobre a adaptação do músculo desnervado: implicações para a fisioterapia

    Directory of Open Access Journals (Sweden)

    Tania F. Salvini

    2012-06-01

    Full Text Available BACKGROUND: This review will describe the main cellular mechanisms involved in the reduction and increase of myoproteins synthesis commonly associated with muscle atrophy and hypertrophy, respectively. OBJECTIVE: We analyzed the effects of electrical stimulation (ES and stretching exercise on the molecular pathways involved in muscle atrophy and hypertrophy. We also described the main effects and limits of these resources in the skeletal muscle, particularly on the denervated muscle. DISCUSSION: Recently, our studies showed that the ES applied in a similar manner as performed in clinical practice is able to attenuate the increase of genes expression involved in muscle atrophy. However, ES was not effective to prevent the loss of muscle mass caused by denervation. Regarding to stretching exercises, their mechanisms of action on the denervated muscle are not fully understood and studies on this area are scarce. Studies from our laboratory have found that stretching exercise increased the extracellular matrix remodeling and decreased genes expression related to atrophy in denervated muscle. Nevertheless, it was not enough to prevent muscle atrophy after denervation. CONCLUSIONS: In spite of the use of stretching exercise and ES in clinical practice in order to minimize the atrophy of denervated muscle, there is still lack of scientific evidence to justify the effectiveness of these resources to prevent muscle atrophy in denervated muscle.CONTEXTUALIZAÇÃO: Esta revisão abordará os principais mecanismos celulares envolvidos na redução e aumento da síntese de mioproteínas comumente associadas às situações de atrofia e hipertrofia muscular, respectivamente. OBJETIVO: Analisaremos os efeitos da estimulação elétrica (EE e do exercício de alongamento sobre as vias moleculares envolvidas na atrofia e hipertrofia muscular. Serão descritos os principais efeitos e os limites desses recursos no músculo esquelético, particularmente sobre o m

  6. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  7. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  8. Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

    Energy Technology Data Exchange (ETDEWEB)

    Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Feinberg, Joseph H. [Physical Medicine and Rehabilitation, Hospital for Special Surgery, New York, NY (United States); Amber, Ian [MedStar Georgetown University Hospital, Department of Radiology, DC, Washington (United States)

    2017-12-15

    Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

  9. Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

    International Nuclear Information System (INIS)

    Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P.; Feinberg, Joseph H.; Amber, Ian

    2017-01-01

    Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

  10. Mechanisms regulating skeletal muscle growth and atrophy.

    Science.gov (United States)

    Schiaffino, Stefano; Dyar, Kenneth A; Ciciliot, Stefano; Blaauw, Bert; Sandri, Marco

    2013-09-01

    Skeletal muscle mass increases during postnatal development through a process of hypertrophy, i.e. enlargement of individual muscle fibers, and a similar process may be induced in adult skeletal muscle in response to contractile activity, such as strength exercise, and specific hormones, such as androgens and β-adrenergic agonists. Muscle hypertrophy occurs when the overall rates of protein synthesis exceed the rates of protein degradation. Two major signaling pathways control protein synthesis, the IGF1-Akt-mTOR pathway, acting as a positive regulator, and the myostatin-Smad2/3 pathway, acting as a negative regulator, and additional pathways have recently been identified. Proliferation and fusion of satellite cells, leading to an increase in the number of myonuclei, may also contribute to muscle growth during early but not late stages of postnatal development and in some forms of muscle hypertrophy in the adult. Muscle atrophy occurs when protein degradation rates exceed protein synthesis, and may be induced in adult skeletal muscle in a variety of conditions, including starvation, denervation, cancer cachexia, heart failure and aging. Two major protein degradation pathways, the proteasomal and the autophagic-lysosomal pathways, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These pathways involve a variety of atrophy-related genes or atrogenes, which are controlled by specific transcription factors, such as FoxO3, which is negatively regulated by Akt, and NF-κB, which is activated by inflammatory cytokines. © 2013 The Authors Journal compilation © 2013 FEBS.

  11. Improved neurological outcome by intramuscular injection of human amniotic fluid derived stem cells in a muscle denervation model.

    Directory of Open Access Journals (Sweden)

    Chun-Jung Chen

    Full Text Available The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model.Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups.NT-3 (Neurotrophin 3, BDNF (Brain derived neurotrophic factor, CNTF (Ciliary neurotrophic factor, and GDNF (Glia cell line derived neurotrophic factor were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology.Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve

  12. Homer 2 antagonizes protein degradation in slow-twitch skeletal muscles.

    Science.gov (United States)

    Bortoloso, Elena; Megighian, Aram; Furlan, Sandra; Gorza, Luisa; Volpe, Pompeo

    2013-01-01

    Homer represents a new and diversified family of proteins made up of several isoforms. The presence of Homer isoforms, referable to 1b/c and 2a/b, was investigated in fast- and slow-twitch skeletal muscles from both rat and mouse. Homer 1b/c was identical irrespective of the muscle, and Homer 2a/b was instead characteristic of the slow-twitch phenotype. Transition in Homer isoform composition was studied in two established experimental models of atrophy, i.e., denervation and disuse of slow-twitch skeletal muscles of the rat. No change of Homer 1b/c was observed up to 14 days after denervation, whereas Homer 2a/b was found to be significantly decreased at 7 and 14 days after denervation by 70 and 90%, respectively, and in parallel to reduction of muscle mass; 3 days after denervation, relative mRNA was reduced by 90% and remained low thereafter. Seven-day hindlimb suspension decreased Homer 2a/b protein by 70%. Reconstitution of Homer 2 complement by in vivo transfection of denervated soleus allowed partial rescue of the atrophic phenotype, as far as muscle mass, muscle fiber size, and ubiquitinazion are concerned. The counteracting effects of exogenous Homer 2 were mediated by downregulation of MuRF1, Atrogin, and Myogenin, i.e., all genes known to be upregulated at the onset of atrophy. On the other hand, slow-to-fast transition of denervated soleus, another landmark of denervation atrophy, was not rescued by Homer 2 replacement. The present data show that 1) downregulation of Homer 2 is an early event of atrophy, and 2) Homer 2 participates in the control of ubiquitinization and ensuing proteolysis via transcriptional downregulation of MuRF1, Atrogin, and Myogenin. Homers are key players of skeletal muscle plasticity, and Homer 2 is required for trophic homeostasis of slow-twitch skeletal muscles.

  13. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy*

    Science.gov (United States)

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko; Tomita, Masaru; Matsumoto, Morio; Nakamura, Masaya; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-01-01

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes. PMID:27129272

  14. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.

    Science.gov (United States)

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko; Tomita, Masaru; Matsumoto, Morio; Nakamura, Masaya; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-06-03

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. 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.

  16. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle

    OpenAIRE

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; dos Santos, Thais Caroline Pereira; Dias, Daniel Ventura; Dar?, Let?cia Rossi; Rosa, Geraldo Marco

    2017-01-01

    ABSTRACT Objective To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Methods Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the ani...

  17. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle

    OpenAIRE

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto Junior, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; Santos, Thais Caroline Pereira dos; Dias, Daniel Ventura; Daré, Letícia Rossi; Rosa Junior, Geraldo Marco

    2017-01-01

    ABSTRACT Objective To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Methods Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the...

  18. Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration.

    Science.gov (United States)

    Liu, Wenxuan; Klose, Alanna; Forman, Sophie; Paris, Nicole D; Wei-LaPierre, Lan; Cortés-Lopéz, Mariela; Tan, Aidi; Flaherty, Morgan; Miura, Pedro; Dirksen, Robert T; Chakkalakal, Joe V

    2017-06-06

    Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss of skeletal muscle integrity. Previously, we showed that muscle stem cells activate and contribute to mouse neuromuscular junction regeneration in response to denervation (Liu et al., 2015). Here, we examined gene expression profiles and neuromuscular junction integrity in aged mouse muscles, and unexpectedly found limited denervation despite a high level of degenerated neuromuscular junctions. Instead, degenerated neuromuscular junctions were associated with reduced contribution from muscle stem cells. Indeed, muscle stem cell depletion was sufficient to induce neuromuscular junction degeneration at a younger age. Conversely, prevention of muscle stem cell and derived myonuclei loss was associated with attenuation of age-related neuromuscular junction degeneration, muscle atrophy, and the promotion of aged muscle force generation. Our observations demonstrate that deficiencies in muscle stem cell fate and post-synaptic myogenesis provide a cellular basis for age-related neuromuscular junction degeneration and associated skeletal muscle decline.

  19. Mitochondrial Involvement and Impact in Aging Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Russell T. Hepple

    2014-09-01

    Full Text Available Atrophy is a defining feature of aging skeletal muscle that contributes to progressive weakness and an increased risk of mobility impairment, falls, and physical frailty in very advanced age. Amongst the most frequently implicated mechanisms of aging muscle atrophy is mitochondrial dysfunction. Recent studies employing methods that are well-suited to interrogating intrinsic mitochondrial function find that mitochondrial respiration and reactive oxygen species emission changes are inconsistent between aging rat muscles undergoing atrophy and appear normal in human skeletal muscle from septuagenarian physically active subjects. On the other hand, a sensitization to permeability transition seems to be a general property of atrophying muscle with aging and this effect is even seen in atrophying muscle from physically active septuagenarian subjects. In addition to this intrinsic alteration in mitochondrial function, factors extrinsic to the mitochondria may also modulate mitochondrial function in aging muscle. In particular, recent evidence implicates oxidative stress in the aging milieu as a factor that depresses respiratory function in vivo (an effect not present ex vivo. Furthermore, in very advanced age not only does muscle atrophy become more severe and clinically relevant in terms of its impact, but also there is evidence that this is driven by an accumulation of severely atrophied denervated myofibers. As denervation can itself modulate mitochondrial function and recruit mitochondrial-mediated atrophy pathways, future investigations need to address the degree to which skeletal muscle mitochondrial alterations in very advanced age are a consequence of denervation, rather than a primary organelle defect, to refine our understanding of the relevance of mitochondria as a therapeutic target at this more advanced age.

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

    Science.gov (United States)

    Porporato, Paolo E; Filigheddu, Nicoletta; Reano, Simone; Ferrara, Michele; Angelino, Elia; Gnocchi, Viola F; Prodam, Flavia; Ronchi, Giulia; Fagoonee, Sharmila; Fornaro, Michele; Chianale, Federica; Baldanzi, Gianluca; Surico, Nicola; Sinigaglia, Fabiola; Perroteau, Isabelle; Smith, Roy G; Sun, Yuxiang; Geuna, Stefano; Graziani, Andrea

    2013-02-01

    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. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.

  1. 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...... 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...... in this thesis that alpha-ketoglutarate, a tricarboxylic acid cycle metabolite, has the potential to control the metabolism of this particular tissue. Finally, a new microscopic method is introduced which allows the study of thermal denaturation of fibrillar collagen and myofibers in real time without any label...

  2. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

    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......  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...

  3. Diagnostic signs of motor neuropathy in MR neurography: nerve lesions and muscle denervation.

    Science.gov (United States)

    Schwarz, Daniel; Weiler, Markus; Pham, Mirko; Heiland, Sabine; Bendszus, Martin; Bäumer, Philipp

    2015-05-01

    To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. • In peripheral neuropathy, T2-w nerve lesions are more frequent than muscle denervation. • Muscle denervation almost never occurs without detectable lesions in corresponding nerves. • MRN-aided diagnosis of peripheral motor neuropathy should focus primarily on nerve lesions. • Increased muscular T2-w signal intensity without concomitant nerve lesions indicates other aetiology.

  4. Diagnostic signs of motor neuropathy in MR neurography: Nerve lesions and muscle denervation

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Daniel; Pham, Mirko; Bendszus, Martin; Baeumer, Philipp [Heidelberg University Hospital, Department of Neuroradiology, Heidelberg (Germany); Weiler, Markus [Heidelberg University Hospital, Department of Neurology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neurooncology, Heidelberg (Germany); Heiland, Sabine [Heidelberg University Hospital, Section of Experimental Radiology, Department of Neuroradiology, Heidelberg (Germany)

    2015-05-01

    To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. (orig.)

  5. Metabolismo glicídico em ratos submetidos a desnervação do músculo esquelético e ao exercício de natação Glicidic metabolism in rats submitted to denervation of skeletal muscle and swimming exercise

    Directory of Open Access Journals (Sweden)

    Wilton Marlindo Santana Nunes

    2009-02-01

    . Além disso, o exercício melhorou o aporte e a utilização da glicose no músculo desnervado.Denervation of the skeletal muscle involves well known alterations of the glucose metabolism; however, little is known about the influence of these alterations on the peripheral sensitivity to insulin of the animal as a whole. This study aimed to analyze the glucose metabolism in the soleus muscle of rats submitted to denervation as well as their response to exogenous insulin and to exercise. Wistar rats aged from 3 to 5 months were submitted to section of the sciatic nerve in the right paw. After 48 hours, half of them started a swimming program of 1 hour/day, 5 days/week. Intact animals, either submitted to exercise or not, were used as control. The rats were submitted to the insulin tolerance test after 28 days for evaluating the response to insulin. The results were analyzed by determination of the blood glucose removal rate (Kitt. In another batch of animals, slices of the denerved soleus muscle and the counterlateral intact paw were incubated in the presence of glucose (5.5mM, containing [³H]2-deoxyglucose (0.5µCi/mL and [U14C] glucose (0.25µCi/mL and insulin (100U/mL, for analysis of glucose uptake, oxidation and glycogen synthesis. Denerved rats submitted to exercise presented KiTT (%/min higher (7.22 ± 0.49 than the sedentary animals (5.31 ± 0.22, and the sedentary control animals (4.53 ± 0.27. Glucose uptake (3.55 ± 0.21 µmol/g.h by the denerved muscle was lower than those of the opposite muscle in the sedentary rats (5.12 ± 0.38 µmol/g.h. Chronic exercise raised glucose uptake and oxidation in the counterlateral muscle (uptake: 6.53 ± 0.37, oxidation: 20.39 ± 1.91 and in the denerved muscle (uptake: 5.70 ± 0.41, oxidation: 20.54 ± 1.97. The same situation occurred with the exercised control group. These results suggest that restricted alterations of the muscular glucose metabolism influenced the response to insulin of the animals as a whole

  6. 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

  7. Skeletal muscle performance and ageing.

    Science.gov (United States)

    Tieland, Michael; Trouwborst, Inez; Clark, Brian C

    2018-02-01

    The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co-morbidity, and premature death. An important cause of physical limitations is the age-related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation-contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  8. 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)....

  9. Morphological differences in skeletal muscle atrophy of rats with motor nerve and/or sensory nerve injury★

    OpenAIRE

    Zhao, Lei; Lv, Guangming; Jiang, Shengyang; Yan, Zhiqiang; Sun, Junming; Wang, Ling; Jiang, Donglin

    2012-01-01

    Skeletal muscle atrophy occurs after denervation. The present study dissected the rat left ventral root and dorsal root at L4-6 or the sciatic nerve to establish a model of simple motor nerve injury, sensory nerve injury or mixed nerve injury. Results showed that with prolonged denervation time, rats with simple motor nerve injury, sensory nerve injury or mixed nerve injury exhibited abnormal behavior, reduced wet weight of the left gastrocnemius muscle, decreased diameter and cross-sectional...

  10. MRI diagnosis of muscle denervation from herpes zoster with discordant distribution of the skin rash

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Amit; Sundaram, Murali [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Winalski, Carl S. [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Cleveland Clinic, Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States)

    2014-10-15

    Herpes zoster is a common disorder characterized by a painful rash along a dermatome caused by reactivation of the varicella zoster virus (VZV). Muscle denervation injury from motor involvement is an uncommon phenomenon. Discordant distribution of the skin rash and motor nerve involvement, presenting as a skin rash in one body part and muscle weakness or pain from nerve involvement in another body part is an even more uncommonly reported finding. We present an unusual case of muscle denervation injury resulting from motor involvement of a peripheral nerve by VZV diagnosed by magnetic resonance imaging with cutaneous manifestations in a different dermatomal distribution. To the best of our knowledge, there has been no similar case reported in the English radiology literature. We suggest that whenever a radiologist notices MRI findings suggesting denervation injury and a cause not readily identified, VZV-related denervation injury should be included in the differential diagnosis, especially in an older immunocompromised patient. (orig.)

  11. 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

  12. Immunology Guides Skeletal Muscle Regeneration

    OpenAIRE

    F. Andrea Sass; Michael Fuchs; Matthias Pumberger; Sven Geissler; Georg N. Duda; Carsten Perka; Katharina Schmidt-Bleek

    2018-01-01

    Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is d...

  13. Functional Echomyography: thickness, ecogenicity, contraction and perfusion of the LMN denervated human muscle before and during h-bFES

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato

    2010-03-01

    Full Text Available Permanent denervated muscles were evaluated by ultrasound to monitor changes in morphology, thickness, contraction-relaxation kinetics and perfusion due to the electrical stimulation program of the Rise2-Italy project. In a case of monolateral lesion, morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete denervation-induced muscle atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third of the denervated muscle, reaching the same value as the contralateral innervated muscle. Contraction-relaxation kinetics, measured by recording the muscle movements during electrical stimulation, showed an abnormal behavior of the chronically denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle. The long-term denervated muscles analyzed with Echo Doppler showed at rest a low resistance arterial flow that became pulsed during and after electrical stimulation. As expected, the ultra sound measured electrical stimulation-induced hyperemia lasted longer than the stimulation period. The higher than normal energy of the delivered electrical stimuli of the Vienna home-based Functional Electrical Stimulation strategy (h-b FES demonstrate that the explored muscles were still almost completely denervated during the one-year of training. In conclusion, this pilot study confirms the usefulness of Functional Echomyography in the follow-up and the positive effects of h-b FES of denervated muscles.

  14. Unorthodox angiogenesis in skeletal muscle.

    Science.gov (United States)

    Egginton, S; Zhou, A L; Brown, M D; Hudlická, O

    2001-02-16

    The morphological pattern of angiogenesis occurring in mature, differentiated skeletal muscle in response to chronically increased muscle blood flow, muscle stretch or repetitious muscle contractions was examined to determine (a) whether capillary neoformation follows the generally accepted temporal paradigm, and (b) how the growth pattern is influenced by mechanical stimuli. Adult rats were treated for a maximum of 14 days either with the vasodilator prazosin, to elevate skeletal muscle blood flow, or underwent surgical removal of one ankle flexor, to induce compensatory overload in the remaining muscles, or had muscles chronically stimulated by implanted electrodes. Extensor digitorum longus and/or extensor hallucis proprius muscles were removed at intervals and processed for electron microscopy. A systematic examination of capillaries and their ultrastructure characterised the sequence of morphological changes indicative of angiogenesis, i.e., basement membrane disruption, endothelial cell (EC) sprouting and proliferation [immunogold labelling after bromodeoxyuridine (BrdU) incorporation]. Capillary growth in response to increased blood flow occurred by luminal division without sprouting or basement membrane (BM) breakage. In stretched muscles, EC proliferation and abluminal sprouting gave rise to new capillaries, with BM loss only at sprout tips. These distinct mechanisms appear to be additive as in chronically stimulated muscles (increased blood flow with repetitive stretch and shortening during muscle contractions) both forms of capillary growth occurred. Endothelial cell numbers per capillary profile, mitotic EC nuclei, and BrdU labelling confirmed cell proliferation prior to overt angiogenesis. Physiological angiogenesis within adult skeletal muscle progresses by mechanisms that do not readily conform to the consensus view of capillary growth, derived mainly from observations made during development, pathological vessel growth, or from in vitro systems. The

  15. The response of denervated muscle to long-term stimulation (1985, revisited here in 2014

    Directory of Open Access Journals (Sweden)

    Terje Lomo

    2014-03-01

    Full Text Available In 1985, at a meeting in Abano, I presented results showing that direct stimulation of skeletal muscles with appropriate stimulus patterns prevents the effects of denervation on non-junctional properties of muscle fibers. Hence, it appeared unnecessary to postulate that unknown nerve-derived trophic factors control such properties, as posited by the (anterograde neurotrophic hypothesis. Here I discuss this conclusion in the light of what we know today, particularly with respect to the many lines of evidence that were then taken to support the trophic hypothesis, but which today have alternative interpretations consistent with control by evoked impulse activity. Despite much effort, no one has yet identified any nerve-derived factor consistent with the neurotrophic hypothesis. Reports favoring the existence of neurotrophic factors were numerous before 2000. Now they have essentially disappeared from the literature, including original research papers, textbooks and handbooks, suggesting that the hypothesis is no longer arguable. Thus, the results that I presented in our paper in 1985 seem to have held up rather well.

  16. 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...

  17. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

  18. AMPK in skeletal muscle function and metabolism

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Hingst, Janne Rasmuss; Fentz, Joachim

    2018-01-01

    highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation......, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives...

  19. Immunology Guides Skeletal Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    F. Andrea Sass

    2018-03-01

    Full Text Available Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

  20. Immunology Guides Skeletal Muscle Regeneration.

    Science.gov (United States)

    Sass, F Andrea; Fuchs, Michael; Pumberger, Matthias; Geissler, Sven; Duda, Georg N; Perka, Carsten; Schmidt-Bleek, Katharina

    2018-03-13

    Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

  1. Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury.

    Science.gov (United States)

    Nikolaou, Sia; Peterson, Elizabeth; Kim, Annie; Wylie, Christopher; Cornwall, Roger

    2011-03-02

    The etiology of shoulder and elbow contractures following neonatal brachial plexus injury is incompletely understood. With use of a mouse model, the current study tests the novel hypothesis that reduced growth of denervated muscle contributes to contractures following neonatal brachial plexus injury. Unilateral brachial plexus injuries were created in neonatal mice by supraclavicular C5-C6 nerve root excision. Shoulder and elbow range of motion was measured four weeks after injury. Fibrosis, cross-sectional area, and functional length of the biceps, brachialis, and subscapularis muscles were measured over four weeks following injury. Muscle satellite cells were cultured from denervated and control biceps muscles to assess myogenic capability. In a comparison group, shoulder motion and subscapularis length were assessed following surgical excision of external rotator muscles. Shoulder internal rotation and elbow flexion contractures developed on the involved side within four weeks following brachial plexus injury. Excision of the biceps and brachialis muscles relieved the elbow flexion contractures. The biceps muscles were histologically fibrotic, whereas fatty infiltration predominated in the brachialis and rotator cuff muscles. The biceps and brachialis muscles displayed reduced cross-sectional and longitudinal growth compared with the contralateral muscles. The upper subscapularis muscle similarly displayed reduced longitudinal growth, with the subscapularis shortening correlating with internal rotation contracture. However, excision of the external rotators without brachial plexus injury caused no contractures or subscapularis shortening. Myogenically capable satellite cells were present in denervated biceps muscles despite impaired muscle growth in vivo. Injury of the upper trunk of the brachial plexus leads to impaired growth of the biceps and brachialis muscles, which are responsible for elbow flexion contractures, and impaired growth of the subscapularis

  2. The Skeletal Muscle Satellite Cell

    Science.gov (United States)

    2011-01-01

    The skeletal muscle satellite cell was first described and named based on its anatomic location between the myofiber plasma and basement membranes. In 1961, two independent studies by Alexander Mauro and Bernard Katz provided the first electron microscopic descriptions of satellite cells in frog and rat muscles. These cells were soon detected in other vertebrates and acquired candidacy as the source of myogenic cells needed for myofiber growth and repair throughout life. Cultures of isolated myofibers and, subsequently, transplantation of single myofibers demonstrated that satellite cells were myogenic progenitors. More recently, satellite cells were redefined as myogenic stem cells given their ability to self-renew in addition to producing differentiated progeny. Identification of distinctively expressed molecular markers, in particular Pax7, has facilitated detection of satellite cells using light microscopy. Notwithstanding the remarkable progress made since the discovery of satellite cells, researchers have looked for alternative cells with myogenic capacity that can potentially be used for whole body cell-based therapy of skeletal muscle. Yet, new studies show that inducible ablation of satellite cells in adult muscle impairs myofiber regeneration. Thus, on the 50th anniversary since its discovery, the satellite cell’s indispensable role in muscle repair has been reaffirmed. PMID:22147605

  3. 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…

  4. Mechanical modeling of skeletal muscle functioning

    NARCIS (Netherlands)

    van der Linden, B.J.J.J.

    1998-01-01

    For movement of body or body segments is combined effort needed of the central nervous system and the muscular-skeletal system. This thesis deals with the mechanical functioning of skeletal muscle. That muscles come in a large variety of geometries, suggest the existence of a relation between muscle

  5. Ultra structure of the denervated vocal muscle mechanically in hogs (sus scrofa domestica

    Directory of Open Access Journals (Sweden)

    Leão, Henrique Zaquia

    2010-03-01

    Full Text Available Introduction: The literature is not clear in the ultra-structural manifestations of the vocal wrinkles after neural wound. Objective: To verify the alterations that occur in a vocal fold mechanically denervated. Method: In this prospective study, it were utilized 15 hogs of commercial race (Sus scrofa domesticates, with age of 4 to 12 weeks. The animals were distributed in three groups, chosen at random. Everybody was submitted to the denervation of the right vocal fold, with surgical removal of a segment with three centimeters of the recurring right laryngeal nerve. After 45, 90 and 180 days of the operations, it was proceeded the biopsy of the vocal muscles, it was prosecuted the samples for transmission electron microscopy and, for the ultra-structural study, utilized the transmission electron microscopy Philips, model EM208S. Results: The biopsied groups with 45 and 90 days after operation of mechanical denervation, presented disorganization miofibrilar, only vestigial lines Z in many samples, as well like altered mithochondrions presenting limited sizes, and matrix mithocondrial rarefied with rare mithocondrial cristae present. The biopsied group with 180 days after operation of denervation, presented regular sarcomeres, mithocondrions with sizes and regular number with correct positioning between the sarcomerical units. Conclusion: The finds in the ultra-structure of the vocal muscles suggest to re enervation of the muscle being that the muscular mithochondrions were the most sensible structures to the denervated condition, successions by the cytoarchiteture of the miofibrilas; the finds in the ultra-structure of the vocal muscles suggests to reinervation of the muscle in the period of approximately six months.

  6. Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy.

    Science.gov (United States)

    Bentzinger, C Florian; Lin, Shuo; Romanino, Klaas; Castets, Perrine; Guridi, Maitea; Summermatter, Serge; Handschin, Christoph; Tintignac, Lionel A; Hall, Michael N; Rüegg, Markus A

    2013-03-06

    Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1α, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by ablation of synergistic muscles or by denervation . Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy response of muscles was based on the suppressed phosphorylation

  7. Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy

    Science.gov (United States)

    2013-01-01

    Background Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1α, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. Method Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by ablation of synergistic muscles or by denervation . Results Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy response of muscles was based on the

  8. Exercise Promotes Healthy Aging of Skeletal Muscle

    Science.gov (United States)

    Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

    2016-01-01

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes 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. PMID:27304505

  9. Sex hormones and skeletal muscle weakness

    DEFF Research Database (Denmark)

    Sipilä, Sarianna; Narici, Marco; Kjaer, Michael

    2013-01-01

    in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical...... properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal...

  10. Redox Control of Skeletal Muscle Regeneration.

    Science.gov (United States)

    Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

    2017-08-10

    Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

  11. 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.

  12. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

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

    2014-01-01

    in cardiac, skeletal, and smooth muscle suggest all mitochondria are created equal, the contrasting RCR and non-phosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation...

  13. Signaling pathways controlling skeletal muscle mass

    Science.gov (United States)

    Egerman, Marc A.

    2014-01-01

    The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed “atrophy”, is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle. PMID:24237131

  14. 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....

  15. Aging of Skeletal Muscle Fibers

    Science.gov (United States)

    Miljkovic, Natasa; Lim, Jae-Young; Miljkovic, Iva

    2015-01-01

    Aging has become an important topic for scientific research because life expectancy and the number of men and women in older age groups have increased dramatically in the last century. This is true in most countries of the world including the Republic of Korea and the United States. From a rehabilitation perspective, the most important associated issue is a progressive decline in functional capacity and independence. Sarcopenia is partly responsible for this decline. Many changes underlying the loss of muscle mass and force-generating capacity of skeletal muscle can be understood at the cellular and molecular levels. Muscle size and architecture are both altered with advanced adult age. Further, changes in myofibers include impairments in several physiological domains including muscle fiber activation, excitation-contraction coupling, actin-myosin cross-bridge interaction, energy production, and repair and regeneration. A thorough understanding of these alterations can lead to the design of improved preventative and rehabilitative interventions, such as personalized exercise training programs. PMID:25932410

  16. Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity

    DEFF Research Database (Denmark)

    Juel; Pilegaard

    1998-01-01

    and hypothyroidism was due to a decrease in Vmax. The denervation-induced decline in lactate/H+ transport capacity resulted from both an increased Km and a reduced Vmax. The present data show that muscle type differences and most changes in the lactate/H+ transport capacity are mediated by modifications in Vmax......Lactate/H+ transport kinetics were determined by means of the pH-sensitive probe BCECF in sarcolemmal giant vesicles, obtained from rat skeletal muscle, and related to variations in lactate/H+ transport capacity. Vesicle preparations were made from red and white muscles, mixed muscles, denervated...... muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H+ transport capacity of red muscles was greater than that of white muscles, and this difference...

  17. Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity

    DEFF Research Database (Denmark)

    Juel; Pilegaard

    1998-01-01

    muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H+ transport capacity of red muscles was greater than that of white muscles, and this difference......Lactate/H+ transport kinetics were determined by means of the pH-sensitive probe BCECF in sarcolemmal giant vesicles, obtained from rat skeletal muscle, and related to variations in lactate/H+ transport capacity. Vesicle preparations were made from red and white muscles, mixed muscles, denervated...... and hypothyroidism was due to a decrease in Vmax. The denervation-induced decline in lactate/H+ transport capacity resulted from both an increased Km and a reduced Vmax. The present data show that muscle type differences and most changes in the lactate/H+ transport capacity are mediated by modifications in Vmax...

  18. 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.

  19. The effects of heat stress on morphological properties and intracellular signaling of denervated and intact soleus muscles in rats.

    Science.gov (United States)

    Ohira, Takashi; Higashibata, Akira; Seki, Masaya; Kurata, Yoichi; Kimura, Yayoi; Hirano, Hisashi; Kusakari, Yoichiro; Minamisawa, Susumu; Kudo, Takashi; Takahashi, Satoru; Ohira, Yoshinobu; Furukawa, Satoshi

    2017-08-01

    The effects of heat stress on the morphological properties and intracellular signaling of innervated and denervated soleus muscles were investigated. Heat stress was applied to rats by immersing their hindlimbs in a warm water bath (42°C, 30 min/day, every other day following unilateral denervation) under anesthesia. During 14 days of experimental period, heat stress for a total of seven times promoted growth-related hypertrophy in sham-operated muscles and attenuated atrophy in denervated muscles. In denervated muscles, the transcription of ubiquitin ligase, atrogin-1/muscle atrophy F-box ( Atrogin-1 ), and muscle RING-finger protein-1 ( MuRF-1 ), genes was upregulated and ubiquitination of proteins was also increased. Intermittent heat stress inhibited the upregulation of Atrogin-1 , but not MuRF-1 transcription. And the denervation-caused reduction in phosphorylated protein kinase B (Akt), 70-kDa heat-shock protein (HSP70), and peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1 α ), which are negative regulators of Atrogin-1 and MuRF-1 transcription, was mitigated. In sham-operated muscles, repeated application of heat stress did not affect Atrogin-1 and MuRF-1 transcription, but increased the level of phosphorylated Akt and HSP70, but not PGC-1 α Furthermore, the phosphorylation of Akt and ribosomal protein S6, which is known to stimulate protein synthesis, was increased immediately after a single heat stress particularly in the sham-operated muscles. The effect of a heat stress was suppressed in denervated muscles. These results indicated that the beneficial effects of heat stress on the morphological properties of muscles were brought regardless of innervation. However, the responses of intracellular signaling to heat stress were distinct between the innervated and denervated muscles. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological

  20. Magnesium for skeletal muscle cramps.

    Science.gov (United States)

    Garrison, Scott R; Allan, G Michael; Sekhon, Ravneet K; Musini, Vijaya M; Khan, Karim M

    2012-09-12

    Skeletal muscle cramps are common and often presented to physicians in association with pregnancy, advanced age, exercise or disorders of the motor neuron (such as amyotrophic lateral sclerosis). Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this indication has never been evaluated by systematic review. To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps.   We searched the Cochrane Neuromuscular Disease Group Specialized Register (11 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 3), MEDLINE (January 1966 to September 2011), EMBASE (January 1980 to September 2011), LILACS (January 1982 to September 2011), CINAHL Plus (January 1937 to September 2011), AMED (January 1985 to October 2011) and SPORTDiscus (January 1975 to September 2011). Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy. Two authors independently selected trials for inclusion and extracted data. Two authors assessed risk of bias. We attempted to contact all study authors and obtained patient level data for three of the included trials, one of which was unpublished. All data on adverse effects were collected from the included RCTs. We identified seven trials (five parallel, two cross-over) enrolling a total of 406 individuals amongst whom 118 cross-over participants additionally served as their own controls. Three trials enrolled women with pregnancy-associated leg cramps (N = 202) and four trials enrolled idiopathic cramp sufferers (N = 322 including cross-over controls). Magnesium was compared to placebo in six trials and to no treatment in one trial.For idiopathic cramps (largely older

  1. Muscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts.

    Science.gov (United States)

    Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva-Cepas, Fernando; Ruz-Caracuel, Ignacio; Peña, José

    2016-12-01

    This study was conducted to determine the effects of extracts obtained from both normal and denervated muscles on different muscle types. Wistar rats were used and were divided into a control group and four experimental groups. Each experimental group was treated intraperitoneally during 10 consecutive days with a different extract. These extracts were obtained from normal soleus muscle, denervated soleus, normal extensor digitorum longus, and denervated extensor digitorum longus. Following treatment, the soleus and extensor digitorum longus muscles were obtained for study under optic and transmission electron microscope; morphometric parameters and myogenic responses were also analyzed. The results demonstrated that the treatment with normal soleus muscle and denervated soleus muscle extracts provoked hypertrophy and increased myogenic activity. In contrast, treatment with extracts from the normal and denervated EDL had a different effect depending on the muscle analyzed. In the soleus muscle it provoked hypertrophy of type I fibers and increased myogenic activity, while in the extensor digitorum longus atrophy of the type II fibers was observed without changes in myogenic activity. This suggests that the muscular responses of atrophy and hypertrophy may depend on different factors related to the muscle type which could be related to innervation.

  2. 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.

  3. [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.

  4. Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.

    Science.gov (United States)

    Willand, Michael P; Holmes, Michael; Bain, James R; de Bruin, Hubert; Fahnestock, Margaret

    2014-11-01

    Long-term muscle denervation leads to severe and irreversible atrophy coupled with loss of force and motor function. These factors contribute to poor functional recovery following delayed reinnervation. The authors' previous work demonstrated that temporarily suturing a sensory nerve to the distal motor stump (called sensory protection) significantly reduces muscle atrophy and improves function following reinnervation. The authors have also shown that 1 month of electrical stimulation of denervated muscle significantly improves function and reduces atrophy. In this study, the authors tested whether a combination of sensory protection and electrical stimulation would enhance functional recovery more than either treatment alone. Rat gastrocnemius muscles were denervated by cutting the tibial nerve. The peroneal nerve was then sutured to the distal tibial stump following 3 months of treatment (i.e., electrical stimulation, sensory protection, or both). Three months after peroneal repair, functional and histologic measurements were taken. All treatment groups had significantly higher muscle weight (pstimulation or sensory protection alone. The combined treatment also produced motor unit counts significantly greater than sensory protection alone (p<0.05). The combination treatment synergistically reduces atrophy and improves reinnervation and functional measures following delayed nerve repair, suggesting that these approaches work through different mechanisms. The authors' research supports the clinical use of both modalities together following peripheral nerve injury.

  5. Expression of mouse agrin in normal, denervated and dystrophic muscle.

    Science.gov (United States)

    Eusebio, Alexander; Oliveri, Filippo; Barzaghi, Patrizia; Ruegg, Markus A

    2003-06-01

    Agrin is a heparan sulfate proteoglycan that is required for the development of postsynaptic specializations at the neuromuscular junction. An alternatively spliced isoform of agrin that lacks this activity is found in basement membranes of several tissues including embryonic muscle. Overexpression of a miniaturized form of this agrin isoform ameliorates the severe muscle dystrophy of laminin alpha2-deficient mice, a mouse model for merosin-deficient congenital muscle dystrophy. Several lines of evidence indicate that this amelioration is based on the high-affinity binding of the mini-agrin to the laminins and to alpha-dystroglycan. Here, we used antibodies raised against mouse agrin to evaluate protein expression in adult muscle of normal and dystrophic mice. We find that expression of agrin in non-synaptic region varies greatly between different muscles in wild-type mice and that its levels are altered in dystrophic muscle.

  6. Cytoskeleton, L-type Ca2+ and stretch activated channels in injured skeletal muscle

    Directory of Open Access Journals (Sweden)

    Fabio Francini

    2013-07-01

    Full Text Available The extra-sarcomeric cytoskeleton (actin microfilaments and anchoring proteins is involved in maintaining the sarco-membrane stiffness and integrity and in turn the mechanical stability and function of the intra- and sub-sarcoplasmic proteins. Accordingly, it regulates Ca2+ entry through the L-type Ca2+ channels and the mechano-sensitivity of the stretch activated channels (SACs. Moreover, being intra-sarcomeric cytoskeleton bound to costameric proteins and other proteins of the sarcoplasma by intermediate filaments, as desmin, it integrates the properties of the sarcolemma with the skeletal muscle fibres contraction. The aim of this research was to compare the cytoskeleton, SACs and the ECC alterations in two different types of injured skeletal muscle fibres: by muscle denervation and mechanical overload (eccentric contraction. Experiments on denervation were made in isolated Soleus muscle of male Wistar rats; forced eccentric-contraction (EC injury was achieved in Extensor Digitorum Longus muscles of Swiss mice. The method employed conventional intracellular recording with microelectrodes inserted in a single fibre of an isolated skeletal muscle bundle. The state of cytoskeleton was evaluated by recording SAC currents and by evaluating the resting membrane potential (RMP value determined in current-clamp mode. The results demonstrated that in both injured skeletal muscle conditions the functionality of L-type Ca2+ current, ICa, was affected. In parallel, muscle fibres showed an increase of the resting membrane permeability and of the SAC current. These issues, together with a more depolarized RMP are an index of altered cytoskeleton. In conclusion, we found a symilar alteration of ICa, SAC and cytoskeleton in both injured skeletal muscle conditions.

  7. 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.

  8. The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

    Science.gov (United States)

    Chen, Justin L.; Qian, Hongwei; Liu, Yingying; Bernardo, Bianca C.; Beyer, Claudia; Watt, Kevin I.; Thomson, Rachel E.; Connor, Timothy; Turner, Bradley J.; McMullen, Julie R.; Larsson, Lars; McGee, Sean L.; Harrison, Craig A.

    2013-01-01

    Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders. PMID:24145169

  9. 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.

  10. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    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...

  11. The influence of passive stretch on the growth and protein turnover of the denervated extensor digitorum longus muscle

    Science.gov (United States)

    Goldspink, David F.

    1978-01-01

    At 7 days after cutting the sciatic nerve, the extensor digitorum longus muscle was smaller and contained less protein than its innervated control. Correlating with these changes was the finding of elevated rates of protein degradation (measured in vitro) in the denervated tissue. However, at this time, rates of protein synthesis (measured in vitro) and nucleic acid concentrations were also higher in the denervated tissue, changes more usually associated with an active muscle rather than a disused one. These anabolic trends have, at least in part, been explained by the possible greater exposure of the denervated extensor digitorum longus to passive stretch. When immobilized under a maintained influence of stretch the denervated muscle grew to a greater extent. Although this stretch-induced growth appeared to occur predominantly through a stimulation of protein synthesis, it was opposed by smaller increases in degradative rates. Nucleic acids increased at a similar rate to the increase in muscle mass when a continuous influence of stretch was imposed on the denervated tissue. In contrast, immobilization of the denervated extensor digitorum longus in a shortened unstretched state reversed most of the stretch-induced changes; that is, the muscle became even smaller, with protein synthesis decreasing to a greater extent than breakdown after the removal of passive stretch. The present investigation suggests that stretch will promote protein synthesis and hence growth of the extensor digitorum longus even in the absence of an intact nerve supply. However, some factor(s), in addition to passive stretch, must contribute to the anabolic trends in this denervated muscle. PMID:708412

  12. Skeletal muscle regeneration is modulated by inflammation

    Directory of Open Access Journals (Sweden)

    Wenjun Yang

    2018-04-01

    Full Text Available Skeletal muscle regeneration is a complex process orchestrated by multiple steps. Recent findings indicate that inflammatory responses could play central roles in bridging initial muscle injury responses and timely muscle injury reparation. The various types of immune cells and cytokines have crucial roles in muscle regeneration process. In this review, we briefly summarise the functions of acute inflammation in muscle regeneration. The translational potential of this article: Immune system is closely relevant to the muscle regeneration. Understanding the mechanisms of inflammation in muscle regeneration is therefore critical for the development of effective regenerative, and therapeutic strategies in muscular disorders. This review provides information for muscle regeneration research regarding the effects of inflammation on muscle regeneration. Keywords: Chronic muscle disorders, Cytokines, Immune cells, Inflammation, Muscle regeneration, Muscle stem cells

  13. Sumoylated α-skeletal muscle actin in the skeletal muscle of adult rats.

    Science.gov (United States)

    Uda, Munehiro; Kawasaki, Hiroaki; Iizumi, Kyoichi; Shigenaga, Ayako; Baba, Takeshi; Naito, Hisashi; Yoshioka, Toshitada; Yamakura, Fumiyuki

    2015-11-01

    Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.

  14. Deletion of Pofut1 in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes in cis and in trans

    Science.gov (United States)

    Zygmunt, Deborah A.; Singhal, Neha; Kim, Mi-Lyang; Cramer, Megan L.; Crowe, Kelly E.; Xu, Rui; Jia, Ying; Adair, Jessica; Martinez-Pena y Valenzuela, Isabel; Akaaboune, Mohammed; White, Peter; Janssen, Paulus M.

    2017-01-01

    ABSTRACT Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the protein O-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction. Changed phenotypes include reduced skeletal muscle size and strength, decreased myofiber size, increased slow fiber (type 1) density, increased muscle degeneration and regeneration in aged muscles, decreased satellite cell self-renewal and regenerative potential, and increased neuromuscular fragmentation and occasional denervation. Pofut1 deletion in skeletal myofibers reduced NotchR signaling in young adult muscles, but this effect was lost with age. Increasing muscle NotchR signaling also reduced muscle size. Gene expression studies point to regulation of cell cycle genes, muscle myosins, NotchR and Wnt pathway genes, and connective tissue growth factor by Pofut1 in skeletal muscle, with additional effects on α dystroglycan glycosylation. PMID:28265002

  15. 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.

  16. The skeletal muscle circadian clock: current insights

    Directory of Open Access Journals (Sweden)

    Nakao R

    2017-11-01

    Full Text Available Reiko Nakao,1 Takeshi Nikawa,2 Katsutaka Oishi1,3,4 1Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST, Tsukuba, 2Department of Nutritional Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 3Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, 4Department of Computational and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Japan Abstract: Skeletal muscle functions in locomotion, postural support, and energy metabolism. The loss of skeletal muscle mass and function leads to diseases such as sarcopenia and metabolic disorders. Inactivity (lack of exercise and an imbalanced diet (increased fat or decreased protein intake are thought to be involved in the prevalence of such pathologies. On the other hand, recent epidemiological studies of humans have suggested that circadian disruption caused by shift work, jet lag, and sleep disorders is associated with obesity and metabolic syndrome. Experimental studies of mice deficient in clock genes have also identified skeletal muscle defects, suggesting a molecular link between circadian clock machinery and skeletal muscle physiology. Furthermore, accumulating evidence about chronotherapy, including chronopharmacology, chrononutrition, and chronoexercise, has indicated that timing is important to optimize medical intervention for various diseases. The present review addresses current understanding of the functional roles of the molecular clock with respect to skeletal muscle and the potential of chronotherapy for diseases associated with skeletal muscle. Keywords: biological rhythm, metabolic syndrome, physical activity, neural signal, chronotherapy

  17. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

    PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue...... 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...... with its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...

  18. Motor neuron targeting of IGF-1 attenuates age-related external Ca2+-dependent skeletal muscle contraction in senescent mice

    Science.gov (United States)

    Payne, Anthony M.; Messi, María Laura; Zheng, Zhenlin; Delbono, Osvaldo

    2007-01-01

    A population of fast muscle fibers from aging mice is dependent on external Ca2+ to maintain tetanic force during repeated contractions. We hypothesized that age-related denervation in muscle fibers plays a role in initiating this contractile deficit, and that prevention of denervation by IGF-1 overexpression would prevent external Ca2+-dependent contraction in aging mice. IGF-1 overexpression in skeletal muscle prevents age-related denervation, and prevented external Ca2+-dependent contraction in this work. To determine if the effects of IGF-1 overexpression are on muscle or nerve, aging mice were injected with a tetanus toxin fragment-C (TTC) fusion protein that targets IGF-1 to spinal cord motor neurons. This treatment prevented external Ca2+-dependent contraction. We also show evidence that injections of the IGF-1-TTC fusion protein prevent age-related alterations to the nerve terminals at the neuromuscular junctions. We conclude that the slow age-related denervation of fast muscle fibers underlies dependence on external Ca2+ to maintain tetanic force in a population of muscle fibers from senescent mice. PMID:17174053

  19. 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.

  20. Interleukin-6 myokine signaling in skeletal muscle

    DEFF Research Database (Denmark)

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

    2013-01-01

    Interleukin (IL)-6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL-6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL-6 signaling has...

  1. The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury.

    Science.gov (United States)

    Weekley, Holly; Nikolaou, Sia; Hu, Liangjun; Eismann, Emily; Wylie, Christopher; Cornwall, Roger

    2012-08-01

    The pathophysiology of paradoxical elbow flexion contractures following neonatal brachial plexus injury (NBPI) is incompletely understood. The current study tests the hypothesis that this contracture occurs by denervation-induced impairment of elbow flexor muscle growth. Unilateral forelimb paralysis was created in mice in four neonatal (5-day-old) BPI groups (C5-6 excision, C5-6 neurotomy, C5-6 neurotomy/repair, and C5-T1 global excision), one non-neonatal BPI group (28-day-old C5-6 excision), and two neonatal muscle imbalance groups (triceps tenotomy ± C5-6 excision). Four weeks post-operatively, motor function, elbow range of motion, and biceps/brachialis functional lengths were assessed. Musculocutaneous nerve (MCN) denervation and reinnervation were assessed immunohistochemically. Elbow flexion motor recovery and elbow flexion contractures varied inversely among the neonatal BPI groups. Contracture severity correlated with biceps/brachialis shortening and MCN denervation (relative axon loss), with no contractures occurring in mice with MCN reinnervation (presence of growth cones). No contractures or biceps/brachialis shortening occurred following non-neonatal BPI, regardless of denervation or reinnervation. Neonatal triceps tenotomy did not cause contractures or biceps/brachialis shortening, nor did it worsen those following neonatal C5-6 excision. Denervation-induced functional shortening of elbow flexor muscles leads to variable elbow flexion contractures depending on the degree, permanence, and timing of denervation, independent of muscle imbalance. Copyright © 2012 Orthopaedic Research Society.

  2. Heat stress inhibits skeletal muscle hypertrophy

    OpenAIRE

    Frier, Bruce C.; Locke, Marius

    2007-01-01

    Heat shock proteins (Hsps) are molecular chaperones that aid in protein synthesis and trafficking and have been shown to protect cells/tissues from various protein damaging stressors. To determine the extent to which a single heat stress and the concurrent accumulation of Hsps influences the early events of skeletal muscle hypertrophy, Sprague-Dawley rats were heat stressed (42°C, 15 minutes) 24 hours prior to overloading 1 plantaris muscle by surgical removal of the gastrocnemius muscle. The...

  3. Role of microRNAs in skeletal muscle hypertrophy

    OpenAIRE

    Hitachi, Keisuke; Tsuchida, Kunihiro

    2014-01-01

    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 n...

  4. Omega-3 Fatty Acids and Skeletal Muscle Health

    OpenAIRE

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

    2015-01-01

    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 muscl...

  5. cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

    Science.gov (United States)

    Stewart, Randi

    2012-01-01

    Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets. PMID:22354781

  6. cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration.

    Science.gov (United States)

    Berdeaux, Rebecca; Stewart, Randi

    2012-07-01

    Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3',5'-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets.

  7. Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

    Science.gov (United States)

    Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2016-10-01

    Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. 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.

  9. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G.

    1990-01-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  10. Insulin binding to individual rat skeletal muscles

    Energy Technology Data Exchange (ETDEWEB)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G. (Univ. of Washington, Seattle (USA))

    1990-10-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white (extensor digitorum longus (EDL), gastrocnemius) muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding.

  11. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle.

    Science.gov (United States)

    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; Santos, Thais Caroline Pereira Dos; Dias, Daniel Ventura; Daré, Letícia Rossi; Rosa, Geraldo Marco

    2017-01-01

    To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the animals were euthanized and histological and morphometric analyses were performed. Data were submitted to statistical analysis with a significance level of pprotocolo de corrente russa aplicada três vezes por semanas, durante 45 dias. Ao final, os animais foram eutanasiados e, em seguida, foram realizadas as análises histológica e morfométrica. Os dados foram submetidos à análise estatística, com nível de significância de p<0,05. Os Grupos Experimental Desnervado e o Grupo Experimental Desnervado Tratado apresentaram área de secção transversal da fibra menor quando comparados ao Grupo Controle Final. Entretanto, constatou-se diferença significativa entre o Grupo Experimental Desnervado e o Grupo Experimental Desnervado Tratado, mostrando que a estimulação elétrica minimizou atrofia muscular. Ainda, observou-se que o Grupo Experimental Desnervado Tratado apresentou resultados semelhantes ao Grupo Controle Inicial. A estimulação elétrica por meio da corrente russa foi favorável na manutenção da morfologia do músculo tibial cranial desnervado experimentalmente, minimizando a atrofia muscular.

  12. Satellite cells in human skeletal muscle plasticity

    Directory of Open Access Journals (Sweden)

    Tim eSnijders

    2015-10-01

    Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. 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/remodelling 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/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  13. 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

  14. 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.

  15. Cellular Players in Skeletal Muscle Regeneration

    OpenAIRE

    Ceafalan, Laura Cristina; Popescu, Bogdan Ovidiu; Hinescu, Mihail Eugen

    2014-01-01

    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 ther...

  16. 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.

  17. Redox characterization of functioning skeletal muscle

    Directory of Open Access Journals (Sweden)

    Li eZuo

    2015-11-01

    Full Text Available Skeletal muscle physiology is influenced by the presence of chemically reactive molecules such as reactive oxygen species (ROS. These molecules regulate multiple redox-sensitive signaling pathways that play a critical role in cellular processes including gene expression and protein modification. While ROS have gained much attention for their harmful effects in muscle fatigue and dysfunction, research has also shown ROS to facilitate muscle adaptation after stressors such as physical exercise. This manuscript aims to provide a comprehensive review of the current understanding of redox signaling in skeletal muscle. ROS-induced oxidative stress and its role in the aging process are discussed. Mitochondria have been shown to generate large amounts of ROS during muscular contractions, and thus are susceptible to oxidative stress. ROS can modify proteins located in the mitochondrial membrane leading to cell death and osmotic swelling. ROS also contribute to the necrosis and inflammation of muscle fibers that is associated with muscular diseases including Duchenne muscular dystrophy (DMD. It is imperative that future research continues to investigate the exact role of ROS in normal skeletal muscle function as well as muscular dysfunction and disease.

  18. Human skeletal muscle biochemical diversity.

    Science.gov (United States)

    Tirrell, Timothy F; Cook, Mark S; Carr, J Austin; Lin, Evie; Ward, Samuel R; Lieber, Richard L

    2012-08-01

    The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy - titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to 'tune' the protein's mechanotransduction capability.

  19. Vasodilatory mechanisms in contracting skeletal muscle

    DEFF Research Database (Denmark)

    Clifford, Philip S.; Hellsten, Ylva

    2004-01-01

    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...

  20. 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...

  1. Signalling role of skeletal muscle during exercise

    NARCIS (Netherlands)

    Catoire, M.

    2014-01-01

    Abstract Upon  acute exercise skeletal muscle is immediately and heavily recruited, while other organs appear to play only a minor role during exercise. These other organs show significant changes and improvements in function, although they are not directly targeted by

  2. Signalling role of skeletal muscle during exercise

    NARCIS (Netherlands)

    Catoire, M.

    2014-01-01

    Abstract

    Upon acute exercise skeletal muscle is immediately and heavily recruited, while other organs appear to play only a minor role during exercise. These other organs show significant changes and improvements in function, although they are not directly targeted by

  3. Calcium model for mammalian skeletal muscle

    NARCIS (Netherlands)

    Wallinga, W.; Boom, H.B.K.; Heijink, R.J.; van der Vliet, G.H.

    1981-01-01

    A model is presented describing quantitatively the events between excitation and force development in skeletal muscle. It consists of a calcium mediated activation model (c.m.a.m.) in series with a force generator model (f.g.m.). The c.m.a.m. was based on intracellular processes such as cisternal

  4. 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.

  5. Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator-cuff muscle.

    Science.gov (United States)

    Gigliotti, Deanna; Leiter, Jeff R S; Macek, Bryce; Davidson, Michael J; MacDonald, Peter B; Anderson, Judy E

    2015-09-15

    The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)-based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alpha-bungarotoxin staining, and the γ:ε subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU+ (activated) Pax7+ satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher γ:ε subunit ratio than deltoid (P = 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO-donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome. Copyright © 2015 the American Physiological Society.

  6. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    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-body...... was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The Prazosin treatment did not affect...

  7. Insulin Increases Ceramide Synthesis in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    M. E. Hansen

    2014-01-01

    Full Text Available Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.

  8. Factors related to skeletal muscle mass in the frail elderly.

    Science.gov (United States)

    Sagawa, Keiichiro; Kikutani, Takeshi; Tamura, Fumiyo; Yoshida, Mitsuyoshi

    2017-01-01

    It is important for the elderly to maintain their skeletal muscle mass, which in turn helps to maintain physical functions. This study aimed to clarify factors related to skeletal muscle mass maintenance. Home-bound elderly (94 men and 216 women), at least 75 years of age, attending a day-care center in Tokyo, were enrolled in this study. Dentists specializing in dysphagia rehabilitation evaluated skeletal muscle mass, occlusal status and swallowing function. Physical function, cognitive function and nutritional status were also evaluated by interviewing caregivers. Correlations of skeletal muscle mass with various factors were determined in each gender group. Multiple regression analysis revealed that skeletal muscle mass was significantly related to nutritional status in both men and women. In men, there was a significant difference in skeletal muscle mass between those with and without occlusion of the natural teeth. Our results suggest that dental treatments and dentures would be useful for maintaining skeletal muscle mass, especially in men.

  9. 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; Khademhosseini, Ali

    2014-10-01

    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.

  10. 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

  11. 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.

  12. Skeletal muscle proteomics in livestock production.

    Science.gov (United States)

    Picard, Brigitte; Berri, Cécile; Lefaucheur, Louis; Molette, Caroline; Sayd, Thierry; Terlouw, Claudia

    2010-05-01

    Proteomics allows studying large numbers of proteins, including their post-translational modifications. Proteomics has been, and still are, used in numerous studies on skeletal muscle. In this article, we focus on its use in the study of livestock muscle development and meat quality. Changes in protein profiles during myogenesis are described in cattle, pigs and fowl using comparative analyses across different ontogenetic stages. This approach allows a better understanding of the key stages of myogenesis and helps identifying processes that are similar or divergent between species. Genetic variability of muscle properties analysed by the study of hypertrophied cattle and sheep are discussed. Biological markers of meat quality, particularly tenderness in cattle, pigs and fowl are presented, including protein modifications during meat ageing in cattle, protein markers of PSE meat in turkeys and of post-mortem muscle metabolism in pigs. Finally, we discuss the interest of proteomics as a tool to understand better biochemical mechanisms underlying the effects of stress during the pre-slaughter period on meat quality traits. In conclusion, the study of proteomics in skeletal muscles allows generating large amounts of scientific knowledge that helps to improve our understanding of myogenesis and muscle growth and to control better meat quality.

  13. 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...... of four separate and specific substrate titration protocols, the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (P = 0.003). The addition...... 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...

  14. Tissue Engineered Strategies for Skeletal Muscle Injury

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

    Full Text Available Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression, and elevation, nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells.

  15. The Human Skeletal Muscle Proteome Project

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...... of 5431 non-redundant muscle proteins identified by mass spectrometry-based proteomics from 38 peer-reviewed scientific publications from 2002 to November 2015 was created. We also developed a nosology system for the classification of muscle proteins based on localization and function. Such inventory...

  16. Skeletal muscle regeneration and impact of aging and nutrition.

    Science.gov (United States)

    Domingues-Faria, Carla; Vasson, Marie-Paule; Goncalves-Mendes, Nicolas; Boirie, Yves; Walrand, Stephane

    2016-03-01

    After skeletal muscle injury a regeneration process takes place to repair muscle. Skeletal muscle recovery is a highly coordinated process involving cross-talk between immune and muscle cells. It is well known that the physiological activities of both immune cells and muscle stem cells decline with advancing age, thereby blunting the capacity of skeletal muscle to regenerate. The age-related reduction in muscle repair efficiency contributes to the development of sarcopenia, one of the most important factors of disability in elderly people. Preserving muscle regeneration capacity may slow the development of this syndrome. In this context, nutrition has drawn much attention: studies have demonstrated that nutrients such as amino acids, n-3 polyunsaturated fatty acids, polyphenols and vitamin D can improve skeletal muscle regeneration by targeting key functions of immune cells, muscle cells or both. Here we review the process of skeletal muscle regeneration with a special focus on the cross-talk between immune and muscle cells. We address the effect of aging on immune and skeletal muscle cells involved in muscle regeneration. Finally, the mechanisms of nutrient action on muscle regeneration are described, showing that quality of nutrition may help to preserve the capacity for skeletal muscle regeneration with age. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Skeletal Muscle Mitochondria and Aging: A Review

    Directory of Open Access Journals (Sweden)

    Courtney M. Peterson

    2012-01-01

    Full Text Available Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline.

  18. Extrarenal potassium adaptation: role of skeletal muscle

    International Nuclear Information System (INIS)

    Blachley, J.D.; Crider, B.P.; Johnson, J.H.

    1986-01-01

    Following the ingestion of a high-potassium-content diet for only a few days, the plasma potassium of rats rises only modestly in response to a previously lethal dose of potassium salts. This acquired tolerance, termed potassium adaptation, is principally the result of increased capacity to excrete potassium into the urine. However, a substantial portion of the acute potassium dose is not immediately excreted and is apparently translocated into cells. Previous studies have failed to show an increase in the content of potassium of a variety of tissues from such animals. Using 86 Rb as a potassium analogue, we have shown that the skeletal muscle of potassium-adapted rats takes up significantly greater amounts of potassium in vivo in response to an acute challenge than does that of control animals. Furthermore, the same animals exhibit greater efflux of 86 Rb following the termination of the acute infusion. We have also shown that the Na+-K+-ATPase activity and ouabain-binding capacity of skeletal muscle microsomes are increased by the process of potassium adaptation. We conclude that skeletal muscle is an important participant in potassium adaptation and acts to temporarily buffer acute increases in the extracellular concentration of potassium

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

    OpenAIRE

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

    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 technic...

  20. Differences in histone modifications between slow- and fast-twitch muscle of adult rats and following overload, denervation, or valproic acid administration.

    Science.gov (United States)

    Kawano, Fuminori; Nimura, Keisuke; Ishino, Saki; Nakai, Naoya; Nakata, Ken; Ohira, Yoshinobu

    2015-11-15

    Numerous studies have reported alterations in skeletal muscle properties and phenotypes in response to various stimuli such as exercise, unloading, and gene mutation. However, a shift in muscle fiber phenotype from fast twitch to slow twitch is not completely induced by stimuli. This limitation is hypothesized to result from the epigenetic differences between muscle types. The main purpose of the present study was to identify the differences in histone modification for the plantaris (fast) and soleus (slow) muscles of adult rats. Genome-wide analysis by chromatin immunoprecipitation followed by DNA sequencing revealed that trimethylation at lysine 4 and acetylation of histone 3, which occurs at transcriptionally active gene loci, was less prevalent in the genes specific to the slow-twitch soleus muscle. Conversely, gene loci specific to the fast-twitch plantaris muscle were associated with the aforementioned histone modifications. We also found that upregulation of slow genes in the plantaris muscle, which are related to enhanced muscular activity, is not associated with activating histone modifications. Furthermore, silencing of muscle activity by denervation caused the displacement of acetylated histone and RNA polymerase II (Pol II) in 5' ends of genes in plantaris, but minor effects were observed in soleus. Increased recruitment of Pol II induced by forced acetylation of histone was also suppressed in valproic acid-treated soleus. Our present data indicate that the slow-twitch soleus muscle has a unique set of histone modifications, which may relate to the preservation of the genetic backbone against physiological stimuli. Copyright © 2015 the American Physiological Society.

  1. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    Science.gov (United States)

    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 muscle weakness can increase the duration of hospitalization, result in exercise limitation, and contribute to a poor quality of life. Importantly, skeletal muscle atrophy is also associated with increased morbidity and mortality of patients. Therefore, improving our understanding of the mechanism(s) responsible for skeletal muscle weakness and fatigue in patients is a required first step to develop clinical protocols to prevent these skeletal muscle problems. This review will highlight the consequences and potential mechanisms responsible for skeletal muscle atrophy and fatigue in patients suffering from acute critical illness, cancer, chronic inflammatory diseases, and neurological disorders. PMID:27128663

  2. Regulatory T cells and skeletal muscle regeneration.

    Science.gov (United States)

    Schiaffino, Stefano; Pereira, Marcelo G; Ciciliot, Stefano; Rovere-Querini, Patrizia

    2017-02-01

    Skeletal muscle regeneration results from the activation and differentiation of myogenic stem cells, called satellite cells, located beneath the basal lamina of the muscle fibers. Inflammatory and immune cells have a crucial role in the regeneration process. Acute muscle injury causes an immediate transient wave of neutrophils followed by a more persistent infiltration of M1 (proinflammatory) and M2 (anti-inflammatory/proregenerative) macrophages. New studies show that injured muscle is also infiltrated by a specialized population of regulatory T (Treg) cells, which control both the inflammatory response, by promoting the M1-to-M2 switch, and the activation of satellite cells. Treg cells accumulate in injured muscle in response to specific cytokines, such as IL-33, and promote muscle growth by releasing growth factors, such as amphiregulin. Muscle repair during aging is impaired due to reduced number of Treg cells and can be enhanced by IL-33 supplementation. Migration of Treg cells could also contribute to explain the effect of heterochronic parabiosis, whereby muscle regeneration of aged mice can be improved by a parabiotically linked young partners. In mdx dystrophin-deficient mice, a model of human Duchenne muscular dystrophy, muscle injury, and inflammation is mitigated by expansion of the Treg-cell population but exacerbated by Treg-cell depletion. These findings support the notion that immunological mechanisms are not only essential in the response to pathogenic microbes and tumor cells but also have a wider homeostatic role in tissue repair, and open new perspectives for boosting muscle growth in chronic muscle disease and during aging. © 2016 Federation of European Biochemical Societies.

  3. 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.

  4. PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Jian; Liang, Bing-Sheng [Department of Orthopedics, the Second Hospital, Shanxi Medical University, Taiyuan (China)

    2012-05-18

    Activated inhibitor of nuclear factor-κB kinase β (IKKβ) is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg{sup 2+}/Mn{sup 2+}-dependent protein phosphatase 1B (PPM1B) inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ) during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control), 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.

  5. PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

    Directory of Open Access Journals (Sweden)

    Jian Wei

    2012-08-01

    Full Text Available Activated inhibitor of nuclear factor-κB kinase β (IKKβ is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg2+/Mn2+-dependent protein phosphatase 1B (PPM1B inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control, 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.

  6. Skeletal muscle abnormalities in pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Ana Paula Breda

    Full Text Available Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH.The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls.PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO2 max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output.Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH.

  7. FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

    Directory of Open Access Journals (Sweden)

    Gerrard Dave

    2007-04-01

    Full Text Available Abstract Background Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs and their receptors are synthesized by, and intimately involved in, embryonic skeletal muscle growth and repair, their role maintaining adult muscle status has not been examined. Methods We examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice. Results We found skeletal muscle FGF4 and FGFR1 mRNA expression to be modified by hind limb suspension,. In addition, we found FGFR1 protein localized in muscle fibers within atrophying mouse muscle which appeared to be resistant to atrophy. Electroporation and ectopic expression of FGFR1 significantly inhibited the decrease in muscle fiber area within skeletal muscles of mice undergoing suspension induced muscle atrophy. Ectopic FGFR1 expression in muscle also significantly stimulated protein synthesis in muscle fibers, and increased protein degradation in weight bearing muscle fibers. Conclusion These results support the theory that FGF signaling can play a role in regulation of postnatal skeletal muscle maintenance, and could offer potentially novel and efficient therapeutic options for attenuating muscle atrophy during aging, illness and spaceflight.

  8. Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    David J. Gifondorwa

    2012-01-01

    Full Text Available A prominent clinical feature of ALS is muscle weakness due to dysfunction, denervation and degeneration of motoneurons (MNs. While MN degeneration is a late stage event in the ALS mouse model, muscle denervation occurs significantly earlier in the disease. Strategies to prevent this early denervation may improve quality of life by maintaining muscle control and slowing disease progression. The precise cause of MN dysfunction and denervation is not known, but several mechanisms have been proposed that involve potentially toxic intra- and extracellular changes. Many cells confront these changes by mounting a stress response that includes increased expression of heat shock protein 70 (Hsp70. MNs do not upregulate Hsp70, and this may result in a potentially increased vulnerability. We previously reported that recombinant human hsp70 (rhHsp70 injections delayed symptom onset and increased lifespan in SOD1G93A mice. The exogenous rhHsp70 was localized to the muscle and not to spinal cord or brain suggesting it modulates peripheral pathophysiology. In the current study, we focused on earlier administration of Hsp70 and its effect on initial muscle denervation. Injections of the protein appeared to arrest denervation with preserved large myelinated peripheral axons, and reduced glial activation.

  9. 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.

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

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    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......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...... 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...

  11. Myofibre damage in human skeletal muscle

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...... 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......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...

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

    DEFF Research Database (Denmark)

    Mackey, Abigail L.; Magnan, Mélanie; Chazaud, Bénédicte

    2017-01-01

    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...

  13. Inferring crossbridge properties from skeletal muscle energetics.

    Science.gov (United States)

    Barclay, C J; Woledge, R C; Curtin, N A

    2010-01-01

    Work is generated in muscle by myosin crossbridges during their interaction with the actin filament. The energy from which the work is produced is the free energy change of ATP hydrolysis and efficiency quantifies the fraction of the energy supplied that is converted into work. The purpose of this review is to compare the efficiency of frog skeletal muscle determined from measurements of work output and either heat production or chemical breakdown with the work produced per crossbridge cycle predicted on the basis of the mechanical responses of contracting muscle to rapid length perturbations. We review the literature to establish the likely maximum crossbridge efficiency for frog skeletal muscle (0.4) and, using this value, calculate the maximum work a crossbridge can perform in a single attachment to actin (33 x 10(-21) J). To see whether this amount of work is consistent with our understanding of crossbridge mechanics, we examine measurements of the force responses of frog muscle to fast length perturbations and, taking account of filament compliance, determine the crossbridge force-extension relationship and the velocity dependences of the fraction of crossbridges attached and average crossbridge strain. These data are used in combination with a Huxley-Simmons-type model of the thermodynamics of the attached crossbridge to determine whether this type of model can adequately account for the observed muscle efficiency. Although it is apparent that there are still deficiencies in our understanding of how to accurately model some aspects of ensemble crossbridge behaviour, this comparison shows that crossbridge energetics are consistent with known crossbridge properties.

  14. 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....

  15. Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation

    DEFF Research Database (Denmark)

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

    2010-01-01

    During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative...... 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...... of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188...

  16. 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...... 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...... of oxidative phosphorylation was significantly (P cryopreserved human skeletal muscle samples. Cryopreservation impaired respiration with substrates linked to Complex I more than for Complex II (P

  17. Woman skeletal muscle transcriptome with bed rest and countermeasures.

    Data.gov (United States)

    National Aeronautics and Space Administration — Microgravity has a dramatic impact on human physiology illustrated in particular with skeletal muscle impairment. A thorough understanding of the mechanisms leading...

  18. 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...... 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...... of oxidative phosphorylation was significantly (P skeletal muscle samples. Cryopreservation impaired respiration with substrates linked to Complex I more than for Complex II (P

  19. 3D Modelling and monitoring of denervated muscle under Functional Electrical Stimulation treatment and associated bone structural changes

    Directory of Open Access Journals (Sweden)

    Paolo Gargiulo

    2011-03-01

    Full Text Available A novel clinical rehabilitation method for patients who have permanent and non recoverable muscle denervation in the legs was developed in the frame of the European Project RISE. The technique is based on FES and the project results shows, in these severely disabled patients, restoration of muscle tissue and function. This study propose novel methods based on image processing technique and medical modelling to monitor growth in denervated muscle treated with FES. Geometrical and structural changes in muscle and bone are studied and modelled. Secondary effects on the bone mineral density produced by the stimulation treatment and due the elicited muscle contraction are also investigated. The restoration process in DDM is an important object of discussion since there isn’t yet a complete understanding of the mechanisms regulating growth in denervated muscle. This study approaches the problem from a macroscopic point of view, developing 3-dimensional models of the whole stimulated muscles and following changes in volume, geometry and density very accurately. The method is based on the acquisition of high resolution Spiral CT scans from patients who have long-term flaccid paraplegia and the use of special image processing tools allowing tissue discriminations and muscle segmentation. Three patients were measured at different points of time during 4 years of electrical stimulation treatment. In this study is quantitatively demonstrated the influences of FES treatment on the different quadriceps bellies. The rectus femoris muscle is positioned in the middle of the quadriceps and responds (in general better to stimulation. In a patient with abundant adipose tissue surrounding the quadriceps, rectus femoris almost doubled the volume during the FES treatment while in the other bellies the changes measured were minimal. The analysis of the density shows clearly a restoration of the muscular structure in the growing muscle. The remarkable increase of

  20. Insights into the role and regulation of TCTP in skeletal muscle.

    Science.gov (United States)

    Goodman, Craig A; Coenen, Allison M; Frey, John W; You, Jae-Sung; Barker, Robert G; Frankish, Barnaby P; Murphy, Robyn M; Hornberger, Troy A

    2017-03-21

    The translationally controlled tumor protein (TCTP) is upregulated in a range of cancer cell types, in part, by the activation of the mechanistic target of rapamycin (mTOR). Recently, TCTP has also been proposed to act as an indirect activator of mTOR. While it is known that mTOR plays a major role in the regulation of skeletal muscle mass, very little is known about the role and regulation of TCTP in this post-mitotic tissue. This study shows that muscle TCTP and mTOR signaling are upregulated in a range of mouse models (mdx mouse, mechanical load-induced hypertrophy, and denervation- and immobilization-induced atrophy). Furthermore, the increase in TCTP observed in the hypertrophic and atrophic conditions occurred, in part, via a rapamycin-sensitive mTOR-dependent mechanism. However, the overexpression of TCTP was not sufficient to activate mTOR signaling (or increase protein synthesis) and is thus unlikely to take part in a recently proposed positive feedback loop with mTOR. Nonetheless, TCTP overexpression was sufficient to induce muscle fiber hypertrophy. Finally, TCTP overexpression inhibited the promoter activity of the muscle-specific ubiquitin proteasome E3-ligase, MuRF1, suggesting that TCTP may play a role in inhibiting protein degradation. These findings provide novel data on the role and regulation of TCTP in skeletal muscle in vivo.

  1. 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.

  2. Connective tissue cells expressing fibro/adipogenic progenitor markers increase under chronic damage: relevance in fibroblast-myofibroblast differentiation and skeletal muscle fibrosis.

    Science.gov (United States)

    Contreras, Osvaldo; Rebolledo, Daniela L; Oyarzún, Juan Esteban; Olguín, Hugo C; Brandan, Enrique

    2016-06-01

    Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition.

  3. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers.

    Directory of Open Access Journals (Sweden)

    David Gonzalez

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα, Tcf4 and α-smooth muscle actin (α-SMA levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs, which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases.

  4. 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

  5. Effects of spaceflight on murine skeletal muscle gene expression

    Data.gov (United States)

    National Aeronautics and Space Administration — Spaceflight results in a number of adaptations to skeletal muscle including atrophy and shifts towards faster muscle fiber types. To identify changes in gene...

  6. How is AMPK activity regulated in skeletal muscles during exercise?

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    AMPK is a metabolic "master" controller activated in skeletal muscle by exercise in a time and intensity dependent manner, and has been implicated in regulating metabolic pathways in muscle during physical exercise. AMPK signaling in skeletal muscle is regulated by several systemic...... and intracellular factors and the regulation of skeletal muscle AMPK in response to exercise is the focus of this review. Specifically, the role of LKB1 and phosphatase PP2C in nucleotide-dependent activation of AMPK, and ionized calcium in CaMKK-dependent activation of AMPK in working muscle is discussed. We also...

  7. Somitogenesis: From somite to skeletal muscle.

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Coleman, Raymond; Szychlinska, Marta Anna; Salvatorelli, Lucia; Parenti, Rosalba; Magro, Gaetano; Imbesi, Rosa

    2015-01-01

    Myogenesis is controlled by an elaborate system of extrinsic and intrinsic regulatory mechanisms in all development stages. The aim of this review is to provide an overview of the different stages of myogenesis and muscle differentiation in mammals, starting from somitogenesis and analysis of the different portions that constitute the mature somite. Particular attention was paid to regulatory genes, in addition to mesodermal stem cells, which represent the earliest elements of myogenesis. Finally, the crucial role of growth factors, molecules of vital importance in contractile regulation, hormones and their function in skeletal muscle differentiation, growth and metabolism, and the role played by central nervous system, are discussed. Copyright © 2015 Elsevier GmbH. All rights reserved.

  8. Masseter muscle thickness in different skeletal morphology: An ultrasonographic study

    Directory of Open Access Journals (Sweden)

    Rani Sushma

    2010-01-01

    Full Text Available Background: The thickness of the masseter muscle during relaxation and contraction states was measured by ultrasonography. Subjects were classified according to their sagittal skeletal relationships. The association between muscle thickness and facial morphology was studied. Context: Masseter muscle thickness influences the skeletal patterns. Aim: To measure and compare the thickness of the masseter muscle in individuals with skeletal class I occlusion and skeletal class II malocclusions and to correlate its relationship with craniofacial morphology. Settings and Design: The study was conducted in a hospital setup and was designed to study the thickness of the masseter muscle in different skeletal morphologies. Materials and Methods: Seventy two individuals between the ages of 18 and 25 years were divided into Group I, Group IIA and Group IIB according to their skeletal relationships. Masseter muscle thickness was measured by ultrasonography. Eight linear and six angular cephalometric measurements were assessed. Statistical Analysis Used: Analysis of variance and Pearson′s correlation analysis. Results: There was a statistically significant difference in muscle thickness between subjects of different skeletal patterns. Significant positive correlation between masseter muscle thickness and posterior total face height, jarabak ratio, ramus height, mandibular length and significant negative correlations with mandibular plane angle, gonial angle and PP-MP angle were observed. Conclusion: This study indicates the strong association between the masseter muscle and skeletal morphology.

  9. Redox regulation in skeletal muscle during contractile activity and aging.

    Science.gov (United States)

    Palomero, J; Jackson, M J

    2010-04-01

    Skeletal muscle has the ability to adapt and remodel after functional, mechanical, and metabolic stresses by activation of different adaptation mechanisms that induce gene expression, biochemical changes, and structural remodeling. Skeletal muscle cells continuously generate reactive oxygen and nitrogen species (RONS), which can act as mediators in cellular signaling pathways that regulate the adaptation mechanisms. There is strong evidence that indicates that RONS are generated in skeletal muscle cells during contractile activity and this induces the activation of transcription factors which modulate gene expression of antioxidant and protective proteins. Thus, it has been proposed that RONS act as signals that modulate the adaptation mechanisms in skeletal muscle and other cells. Structural and functional changes occur in skeletal muscle during aging and are characterized by a reduction of muscle mass and force (sarcopenia). The causes are known, however, there is considerable support for an involvement of RONS in the process of aging and sarcopenia. Several studies indicate that adaptive responses of skeletal muscle that are activated and regulated by RONS are disrupted during aging. This reduction of skeletal muscle adaptation to contractile activity during aging might be responsible for the loss of muscle mass and function and the progressive deterioration of this organ. In summary, there is sufficient evidence that indicates that cellular redox regulation in skeletal muscle is crucial in the physiology and pathology of skeletal muscle. However, new methodologies and experimental models are required for understanding the complex biology of RONS in the cell. This will provide future interventions that mitigate pathologies and aging of skeletal muscle.

  10. Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis.

    Science.gov (United States)

    Nikolaou, Sia; Liangjun, Hu; Tuttle, Lori J; Weekley, Holly; Christopher, Wylie; Lieber, Richard L; Cornwall, Roger

    2014-03-01

    We investigated the contribution of muscle fibrosis to elbow flexion contractures in a murine model of neonatal brachial plexus injury (NBPI). Four weeks after NBPI, biceps and brachialis fibrosis were assessed histologically and compared with the timing of contracture development and the relative contribution of each muscle to contractures. Modulus of elasticity and hydroxyproline (collagen) content were measured and correlated with contracture severity. The effect of halofuginone antifibrotic therapy on fibrosis and contractures was investigated. Elbow contractures preceded muscle fibrosis development. The brachialis was less fibrotic than the biceps, yet contributed more to contractures. Modulus and hydroxyproline content increased in both elbow flexors, but neither correlated with contracture severity. Halofuginone reduced biceps fibrosis but did not reduce contracture severity. Contractures after NBPI cannot be explained solely by muscle fibrosis, arguing for investigation of alternate pathophysiologic targets for contracture prevention and treatment. Copyright © 2013 Wiley Periodicals, Inc.

  11. Satellite cell proliferation in adult skeletal muscle

    Science.gov (United States)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  12. Regulatory factors and cell populations involved in skeletal muscle regeneration.

    NARCIS (Netherlands)

    Broek, R.W. Ten; Grefte, S.; Hoff, J.W. Von den

    2010-01-01

    Skeletal muscle regeneration is a complex process, which is not yet completely understood. Satellite cells, the skeletal muscle stem cells, become activated after trauma, proliferate, and migrate to the site of injury. Depending on the severity of the myotrauma, activated satellite cells form new

  13. [The spectrum of hereditary skeletal-muscle channelopathies

    NARCIS (Netherlands)

    Trip, J.; Drost, G.; Ginjaar, H.B.; Engelen, B.G.M. van; Faber, C.G.

    2005-01-01

    Channelopathies are a heterogeneous group of genetic diseases in which a defective ion channel is responsible for the symptoms. They manifest as diseases of the heart, brain or skeletal muscle. Hereditary skeletal-muscle channelopathies are characterised by myotonia, periodic paralysis or a

  14. 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...

  15. 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

  16. 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

  17. Skeletal Muscle Angiogenesis and Its Relation to Insulin Sensitivity

    DEFF Research Database (Denmark)

    Lindqvist, Anna Maria Charlotte K

    with improved glucose tolerance and insulin sensitivity however a direct causal relationship has not previously been established. The main hypothesis of this thesis was that skeletal muscle capillarization is important for skeletal muscle glucose uptake and thereby whole-body insulin sensitivity...

  18. 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

  19. 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....

  20. Excitation-calcium release uncoupling in aged single human skeletal muscle fibers.

    Science.gov (United States)

    Delbono, O; O'Rourke, K S; Ettinger, W H

    1995-12-01

    The biological mechanisms underlying decline in muscle power and fatigue with age are not completely understood. The contribution of alterations in the excitation-calcium release coupling in single muscle fibers was explored in this work. Single muscle fibers were voltage-clamped using the double Vaseline gap technique. The samples were obtained by needle biopsy of the vastus lateralis (quadriceps) from 9 young (25-35 years; 25.9 +/- 9.1; 5 female and 4 male) and 11 old subjects (65-75 years; 70.5 +/- 2.3; 6 f, 5 m). Data were obtained from 36 and 39 fibers from young and old subjects, respectively. Subjects included in this study had similar physical activity. Denervated and slow-twitch muscle fibers were excluded from this study. A significant reduction of maximum charge movement (Qmax) and DHP-sensitive Ca current were recorded in muscle fibers from the 65-75 group. Qmax values were 7.6 +/- 0.9 and 3.2 +/- 0.3 nC/muF for young and old muscle fibers, respectively (P charge inactivation or interconversion (charge 1 to charge 2) were found. The peak Ca current was (-)4.7 +/- 0.08 and (-)2.15 +/- 0.11 muA/muF for young and old fibers, respectively (P muscle fibers, respectively. Caffeine (0.5 mM) induced potentiation of the peak calcium transient in both groups. The decrease in the voltage-/Ca-dependent Ca release ratio in old fibers (0.18 +/- 0.02) compared to young fibers (0.47 +/- 0.03) (P skeletal muscle and, the reduction of Ca release is due to DHPR-ryanodine receptor uncoupling in fast-twitch fibers. These alterations can account, at least partially for the skeletal muscle function impairment associated with aging.

  1. Computed tomography (CT) of skeletal muscle in neuromuscular disorders

    International Nuclear Information System (INIS)

    Nagao, Hideo; Morimoto, Takehiko; Takahashi, Mitsugi; Habara, Shinji; Nagai, Hironao; Matsuda, Hiroshi

    1987-01-01

    We investigated whether or not computerized tomography (CT) of skeletal muscle was of value for the diagnosis of neuromuscular disorders, through a comparison of CT findings in the skeletal muscle with histological findings in the muscle obtained by surgical biopsy. There were clear histological lesions even in cases in which low density areas were not seen on CT of the skeletal muscle. The muscle exhibiting remarkably low density areas showed high proliferation of the connective tissue and high accumulation of fat, but contained no muscle fibers. Therefore, the most suitable site for a biopsy was the muscle which exhibited mildly low density areas on CT. In floppy infants, the CT value was helpful for the diagnosis, even if low density areas did not appear because of remarkable muscle atrophy and monotonous lesions of the whole muscle. (author)

  2. 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.

  3. 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.

  4. Osteogenic sarcoma with skeletal muscle metastases

    International Nuclear Information System (INIS)

    Peh, W.C.G.; Shek, T.W.H.; Wang Shihchang; Wong, J.W.K.; Chien, E.P.

    1999-01-01

    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.)

  5. 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.

  6. Combined application of neutrophin-3 gene and neural stem cells is ameliorative to delay of denervated skeletal muscular atrophy after tibial nerve transection in rats.

    Science.gov (United States)

    Lin, Sen; Xu, Jianguang; Hu, Shaonan; Xu, Lei; Zhang, Changqing; Wang, Yang; Gu, Yudong

    2011-01-01

    Examination of the therapeutic efficacy of neural stem cells (NSCs) has recently become the focus of much investigation. In this study we present an insight of the effects of combined application with neurotrophin-3 (NT-3) and NSCs that derived from rat embryo spinal cord on delaying denervated skeletal muscular atrophy after tibial nerve was severed. NT-3 gene was amplified by PCR and subcloned into lentiviral vector pWPXL-MOD to construct a lentiviral expression vector pWPXL-MOD-NT-3. A positive clone expressing NT-3 (named NSCs-NT-3) was obtained and used for differentiation in vitro and transplantation. Sixty adult rats, whose tibial nerves were sectioned, were divided into two groups: one grafted with NSCs-NT-3 (experimental group, n = 30) and the other with NSCs transfected by pWPXL-MOD (control group, n = 30). The cell survival and differentiation, NT-3 gene expression, and effect of delaying denervated skeletal muscular atrophy were examined through immunohistostaining, RT-PCR, Western blot, electrophysiological analysis, and mean cross-sectional area (CSA) of gastrocnemius, respectively. The results show that the NT-3 gene, which is comprised of 777 bp, was cloned and significantly different expression were detected between NSCs and NSCs-NT-3 in vitro. Quantitative analysis of the choline acetyltransferase (ChAT) immunopositive cells revealed a significant increase in experimental group compared to the control group 4 weeks after implantation (p muscular atrophy is indicated in the EMG examination and mean CSA of gastrocnemius. These findings suggest that the neural stem cells expressing NT-3 endogenously would be a better graft candidate for the delay of denervated skeletal muscular atrophy.

  7. Tissue Triage and Freezing for Models of Skeletal Muscle Disease

    Science.gov (United States)

    Meng, Hui; Janssen, Paul M.L.; Grange, Robert W.; Yang, Lin; Beggs, Alan H.; Swanson, Lindsay C.; Cossette, Stacy A.; Frase, Alison; Childers, Martin K.; Granzier, Henk; Gussoni, Emanuela; Lawlor, Michael W.

    2014-01-01

    Skeletal muscle is a unique tissue because of its structure and function, which requires specific protocols for tissue collection to obtain optimal results from functional, cellular, molecular, and pathological evaluations. Due to the subtlety of some pathological abnormalities seen in congenital muscle disorders and the potential for fixation to interfere with the recognition of these features, pathological evaluation of frozen muscle is preferable to fixed muscle when evaluating skeletal muscle for congenital muscle disease. Additionally, the potential to produce severe freezing artifacts in muscle requires specific precautions when freezing skeletal muscle for histological examination that are not commonly used when freezing other tissues. This manuscript describes a protocol for rapid freezing of skeletal muscle using isopentane (2-methylbutane) cooled with liquid nitrogen to preserve optimal skeletal muscle morphology. This procedure is also effective for freezing tissue intended for genetic or protein expression studies. Furthermore, we have integrated our freezing protocol into a broader procedure that also describes preferred methods for the short term triage of tissue for (1) single fiber functional studies and (2) myoblast cell culture, with a focus on the minimum effort necessary to collect tissue and transport it to specialized research or reference labs to complete these studies. Overall, this manuscript provides an outline of how fresh tissue can be effectively distributed for a variety of phenotypic studies and thereby provides standard operating procedures (SOPs) for pathological studies related to congenital muscle disease. PMID:25078247

  8. Molecular Signals and Skeletal Muscle Adaptation to Exercise

    Directory of Open Access Journals (Sweden)

    Mark Wilson

    2013-08-01

    Full Text Available The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing. However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely

  9. 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’.

  10. How is AMPK activity regulated in skeletal muscles during exercise?

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    AMPK is a metabolic "master" controller activated in skeletal muscle by exercise in a time and intensity dependent manner, and has been implicated in regulating metabolic pathways in muscle during physical exercise. AMPK signaling in skeletal muscle is regulated by several systemic...... and intracellular factors and the regulation of skeletal muscle AMPK in response to exercise is the focus of this review. Specifically, the role of LKB1 and phosphatase PP2C in nucleotide-dependent activation of AMPK, and ionized calcium in CaMKK-dependent activation of AMPK in working muscle is discussed. We also...... discuss the influence of reactive oxygen species produced within the muscle as well as muscle glycogen and TAK1 in regulating AMPK during exercise. Currently, during intensive contraction, activation of alpha2-AMPK seems mainly to rely on AMP accumulating from ATP-hydrolysis whereas calcium signaling may...

  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. © 2015 Elsevier Inc. All rights reserved.

  12. 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.

  13. 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...

  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. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

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

    2000-01-01

    The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal amplifica......The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal...... 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...

  16. Diffuse metastatic infiltration of a carcinoma into skeletal muscle

    International Nuclear Information System (INIS)

    Hundt, W.; Braunschweig, R.; Reiser, M.

    1999-01-01

    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.)

  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. Finite element modelling of contracting skeletal muscle.

    Science.gov (United States)

    Oomens, C W J; Maenhout, M; van Oijen, C H; Drost, M R; Baaijens, F P

    2003-09-29

    To describe the mechanical behaviour of biological tissues and transport processes in biological tissues, conservation laws such as conservation of mass, momentum and energy play a central role. Mathematically these are cast into the form of partial differential equations. Because of nonlinear material behaviour, inhomogeneous properties and usually a complex geometry, it is impossible to find closed-form analytical solutions for these sets of equations. The objective of the finite element method is to find approximate solutions for these problems. The concepts of the finite element method are explained on a finite element continuum model of skeletal muscle. In this case, the momentum equations have to be solved with an extra constraint, because the material behaves as nearly incompressible. The material behaviour consists of a highly nonlinear passive part and an active part. The latter is described with a two-state Huxley model. This means that an extra nonlinear partial differential equation has to be solved. The problems and solutions involved with this procedure are explained. The model is used to describe the mechanical behaviour of a tibialis anterior of a rat. The results have been compared with experimentally determined strains at the surface of the muscle. Qualitatively there is good agreement between measured and calculated strains, but the measured strains were higher.

  19. Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing

    Directory of Open Access Journals (Sweden)

    Elisa Giorgetti

    2016-09-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA, a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR. Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO, a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations.

  20. 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.

  1. 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...

  2. Skeletal muscle regeneration models for experimental stem cell therapy

    Czech Academy of Sciences Publication Activity Database

    Čížková, D.; Mokrý, J.; Soukup, Tomáš

    2006-01-01

    Roč. 8, č. S2 (2006), s. 64-65 ISSN 1465-3249. [International Conference "Strategies in Tissue Engineering" /2./. 31.05.2006-02.06.2006, Würzburg] Keywords : rat * skeletal muscle * stem cell s * muscle regeneration * muscle regeneration model Subject RIV: ED - Physiology

  3. Heparan sulfate in skeletal muscle development

    International Nuclear Information System (INIS)

    Noonan, D.M.

    1985-01-01

    In this study, chick breast skeletal muscle cells developing in vitro from myoblasts to myotubes were found to synthesize heparan sulfate (HS), chrondroitin-6-sulfate, chrondroitin-4-sulfate, dermatan sulfate, unsulfated chrondroitin and hyaluronic acid in both the substratum attached material (SAM) and the cellular fraction. SAM was found to contain predominantly chrondroitin-6-sulfate and relatively little HS whereas the cellular fraction contained relatively higher levels of HS and lower levels of chrondroitin-6-sulfate. Hyaluronic acid was also a major component in both fractions with the other glycosaminoglycan isomers present as minor components. Muscle derived fibroblast cultures had higher levels of dermatan sulfate in the cell layer and higher levels of HS in the SAM fraction than did muscle cultures. The structure of the proteoglycans were partially characterized in 35 SO 4 2- radio-labeled cultures which indicated an apparent increase in the hydrodynamic size of the cell fraction heparan sulfate proteoglycan (HS PG). Myotubes incorporated 35 SO 4 2- into HS PG at a rate 3 times higher than myoblasts. The turnover rate of HS in the cellular fraction was the same for myoblasts and myotubes, with a t/sub 1/2/ of approximately 5 hours. Fibroblasts in culture synthesized the smallest HS PG, and incorporated 35 SO 4 2- into HS PG at a rate lower than that of myotubes. Studies in which fusion was reversibly inhibited with decreased medium [Ca ++ ] closely linked the increased synthesis of cell fraction, but not SAM fraction, HS with myotube formation. However, decreasing medium calcium appeared to cause significant alterations in the metabolism of inorganic sulfate

  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. 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...

  7. 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 Hyperinsul...

  8. GRMD cardiac and skeletal muscle metabolism gene profiles are distinct

    OpenAIRE

    Markham, Larry W.; Brinkmeyer-Langford, Candice L.; Soslow, Jonathan H.; Gupte, Manisha; Sawyer, Douglas B.; Kornegay, Joe N.; Galindo, Cristi L.

    2017-01-01

    Background Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to skeletal muscle dysfunction. Methods To address this question, we analyzed cardiac and skeletal muscle tissue microarrays from golden retriever muscular dystrophy (GRMD) dogs, a gen...

  9. 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 poten...... no apparent effect on capillarization or muscle fiber hypertrophy.......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...

  10. 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.

  11. Effects of guandinoethane sulfonate on contraction of skeletal muscle.

    OpenAIRE

    Cuisinier, C; Gailly, Philippe; Francaux, Marc; Lebacq, Jean

    2000-01-01

    Guanidinoethane sulfonic acid (GES), a chemical and biological analog of taurine, decreases rat muscle taurine content when added to drinking water. Over the same period, GES appears in muscle. GES supplementation is often used to study the effect of taurine depletion on physiological mechanisms, without taking into account the possible actions of GES. The purpose of the present study was to investigate the specific actions of GES on contraction of skeletal muscle. In mice EDL muscle, the tim...

  12. Sarcolipin: a key thermogenic and metabolic regulator in skeletal muscle

    OpenAIRE

    Pant, Meghna; Bal, Naresh. C; Periasamy, Muthu

    2016-01-01

    Skeletal muscle constitutes ∼40 % of body mass and has the capacity to play a major role as thermogenic, metabolic and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis, heat production an...

  13. 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.

  14. The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat.

    OpenAIRE

    Cairns, S. P.; Dulhunty, A. F.

    1993-01-01

    1. The aim of the experiments was to examined the effects of beta-adrenoceptor activation on twitch and tetanic contractions in fast- and slow-twitch mammalian skeletal muscle fibres. Isometric force was recorded from bundles of intact fibres isolated from the normal and denervated slow-twitch soleus and normal fast-twitch sternomastoid muscles of the rat. 2. Terbutaline (10 microM), a beta 2-adrenoceptor agonist, induced an average 15% potentiation of peak twitch and peak tetanic force in no...

  15. Macrophage Plasticity in Skeletal Muscle Repair

    Directory of Open Access Journals (Sweden)

    Elena Rigamonti

    2014-01-01

    Full Text Available Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1 or an alternative anti-inflammatory (M2 phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.

  16. Quantitative studies of skeletal muscle lactate metabolism

    International Nuclear Information System (INIS)

    Pagliassotti, M.J.

    1988-01-01

    In Situ, single-pass perfusions were employed on three isolated rabbit skeletal muscle preparations of differing fiber type and oxidative capacity to investigate the influence of fiber type and oxidative capacity per se on net carbon, 14 C-lactate, and 3 H-glucose fluxes. Preparations were exposed to six lactate concentrations ranging from 1-11mM. At basal lactate concentrations all preparations displayed net lactate release, 14 C-lactate removal and 14 CO 2 release, all were linearly correlated with lactate concentration. By 4mM all preparations switched to net lactate uptake and 14 C-lactate removal always exceeded net lactate uptake. To quantify the fate of net carbon, 14 C-lactate, and 3 H-glucose removal preparations were perfused at either basal or elevated lactate. Under basal conditions net carbon influx from glucose and glycogen was removed primarily via net lactate release in the glycolytic and mixed preparations and oxidation and net lactate release in the oxidative preparation. At elevated lactate, net carbon influx from lactate, pyruvate and glucose was removed primarily by net glycogen synthesis in the glycolytic preparation and both alanine release and oxidation in the mixed and oxidative preparations

  17. Musculoskeletal growth in the upper arm in infants after obstetric brachial plexus lesions partial denervation and its relation with residual muscle function

    NARCIS (Netherlands)

    Ruoff, J.M.; van der Sluijs, J.A.; van Ouwerkerk, W.J.R.; Jaspers, R.T.

    2012-01-01

    Aim Denervation after obstetric brachial plexus lesion (OBPL) is associated with reduced musculoskeletal growth in the upper arm. The aim of this study was to investigate whether reduced growth of upper arm flexor and extensor muscles is related to active elbow function and humeral length. Method In

  18. Obestatin controls skeletal muscle fiber-type determination.

    Science.gov (United States)

    Santos-Zas, Icía; Cid-Díaz, Tania; González-Sánchez, Jessica; Gurriarán-Rodriguez, Uxía; Seoane-Mosteiro, Carlos; Porteiro, Begoña; Nogueiras, Rubén; Casabiell, Xesús; Luis Relova, José; Gallego, Rosalía; Mouly, Vincent; Pazos, Yolanda; Camiña, Jesus P

    2017-05-18

    Obestatin/GPR39 signaling stimulates skeletal muscle growth and repair by inducing both G-protein-dependent and -independent mechanisms linking the activated GPR39 receptor with distinct sets of accessory and effector proteins. In this work, we describe a new level of activity where obestatin signaling plays a role in the formation, contractile properties and metabolic profile of skeletal muscle through determination of oxidative fiber type. Our data indicate that obestatin regulates Mef2 activity and PGC-1α expression. Both mechanisms result in a shift in muscle metabolism and function. The increase in Mef2 and PGC-1α signaling activates oxidative capacity, whereas Akt/mTOR signaling positively regulates myofiber growth. Taken together, these data indicate that the obestatin signaling acts on muscle fiber-type program in skeletal muscle.

  19. Desmin-regulated lentiviral vectors for skeletal muscle gene transfer.

    Science.gov (United States)

    Talbot, Gillian E; Waddington, Simon N; Bales, Olivia; Tchen, Rose C; Antoniou, Michael N

    2010-03-01

    Lentiviral vectors (LVs) are highly attractive as a gene therapy agent as they are able to stably integrate their genomes in both dividing and nondividing cells and, in principle, provide long-term therapeutic benefit. However, their performance in skeletal muscle in adult animals has, to date, been disappointing. In order to gain clearer insight into their utility in this tissue type, we have conducted an extensive quantitative comparison of constitutive and muscle-specific promoter activities in skeletal muscle and nonmuscle systems following LV delivery in cell lines and neonatal mice. Our data show that LV delivery to hind leg skeletal muscle of neonatal mouse results in long-term transgene expression in adulthood. We find that the human desmin (DES) promoter/enhancer is the first muscle-specific control region to match the activity of the highly active constitutive human cytomegalovirus (hCMV) promoter/enhancer in skeletal muscle within a LV context both in vitro and in vivo. Furthermore, the DES promoter/enhancer provides six- to eightfold greater expression per viral copy than the muscle-specific human muscle creatine kinase (CKM) promoter/enhancer. DES also confers a more reproducible and tissue-specific transgene expression profile compared to CKM and is therefore a highly attractive regulatory element for use in muscle gene therapy vectors.

  20. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways.

    Science.gov (United States)

    Rodriguez, J; Vernus, B; Chelh, I; Cassar-Malek, I; Gabillard, J C; Hadj Sassi, A; Seiliez, I; Picard, B; Bonnieu, A

    2014-11-01

    Myostatin, a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth and is conserved in many species, from rodents to humans. Myostatin inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. As it represents a potential target for stimulating muscle growth and/or preventing muscle wasting, myostatin regulation and functions in the control of muscle mass have been extensively studied. A wealth of data strongly suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression. Moreover, myostatin plays a central role in integrating/mediating anabolic and catabolic responses. Myostatin negatively regulates the activity of the Akt pathway, which promotes protein synthesis, and increases the activity of the ubiquitin-proteasome system to induce atrophy. Several new studies have brought new information on how myostatin may affect both ribosomal biogenesis and translation efficiency of specific mRNA subclasses. In addition, although myostatin has been identified as a modulator of the major catabolic pathways, including the ubiquitin-proteasome and the autophagy-lysosome systems, the underlying mechanisms are only partially understood. The goal of this review is to highlight outstanding questions about myostatin-mediated regulation of the anabolic and catabolic signaling pathways in skeletal muscle. Particular emphasis has been placed on (1) the cross-regulation between myostatin, the growth-promoting pathways and the proteolytic systems; (2) how myostatin inhibition leads to muscle hypertrophy; and (3) the regulation of translation by myostatin.

  1. 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...

  2. 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....

  3. 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.

  4. Engineered matrices for skeletal muscle satellite cell engraftment and function.

    Science.gov (United States)

    Han, Woojin M; Jang, Young C; García, Andrés J

    2017-07-01

    Regeneration of traumatically injured skeletal muscles is severely limited. Moreover, the regenerative capacity of skeletal muscle declines with aging, further exacerbating the problem. Recent evidence supports that delivery of muscle satellite cells to the injured muscles enhances muscle regeneration and reverses features of aging, including reduction in muscle mass and regenerative capacity. However, direct delivery of satellite cells presents a challenge at a translational level due to inflammation and donor cell death, motivating the need to develop engineered matrices for muscle satellite cell delivery. This review will highlight important aspects of satellite cell and their niche biology in the context of muscle regeneration, and examine recent progresses in the development of engineered cell delivery matrices designed for skeletal muscle regeneration. Understanding the interactions of muscle satellite cells and their niche in both native and engineered systems is crucial to developing muscle pathology-specific cell- and biomaterial-based therapies. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  5. 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

    2015-01-01

    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. PMID:25762009

  6. 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

  7. Capillarization in skeletal muscle of rats with cardiac hypertrophy.

    NARCIS (Netherlands)

    Degens, H.; Anderson, R.K.; Alway, S.E.

    2002-01-01

    PURPOSE: Exercise intolerance during chronic heart failure (CHF) is localized mainly in skeletal muscle. A decreased capillarization may impair exchange of oxygen between capillaries and muscle tissue and in this way contribute to exercise intolerance. We assessed changes in capillary supply in

  8. Skeletal muscle perfusion measured by positron emission tomography during exercise

    NARCIS (Netherlands)

    Ament, W; Lubbers, J; Rakhorst, G; Vaalburg, W; Verkerke, GJ; Paans, AMJ; Willemsen, ATM

    1998-01-01

    The applicability of (H2O)-O-15-positron emission tomographic (PET) imaging for the assessment of skeletal muscle perfusion during exercise was investigated in five healthy subjects performing intermittent isometric contractions on a calf ergometer. The workload of the left calf muscles was kept

  9. 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 ...

  10. 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)

  11. Three-dimensional ultrasound strain imaging of skeletal muscles

    NARCIS (Netherlands)

    Gijsbertse, K.; Sprengers, A. M. J.; Nillesen, M. M.; Hansen, Hendrik H.G.; Lopata, R.G.P.; Verdonschot, N.; de Korte, C. L.

    2017-01-01

    In this study, a multi-dimensional strain estimation method is presented to assess local relative deformation in three orthogonal directions in 3D space of skeletal muscles during voluntary contractions. A rigid translation and compressive deformation of a block phantom, that mimics muscle

  12. 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....

  13. Role of pericytes in skeletal muscle regeneration and fat accumulation.

    Science.gov (United States)

    Birbrair, Alexander; Zhang, Tan; Wang, Zhong-Min; Messi, Maria Laura; Enikolopov, Grigori N; Mintz, Akiva; Delbono, Osvaldo

    2013-08-15

    Stem cells ensure tissue regeneration, while overgrowth of adipogenic cells may compromise organ recovery and impair function. In myopathies and muscle atrophy associated with aging, fat accumulation increases dysfunction, and after chronic injury, the process of fatty degeneration, in which muscle is replaced by white adipocytes, further compromises tissue function and environment. Some studies suggest that pericytes may contribute to muscle regeneration as well as fat formation. This work reports the presence of two pericyte subpopulations in the skeletal muscle and characterizes their specific roles. Skeletal muscle from Nestin-GFP/NG2-DsRed mice show two types of pericytes, Nestin-GFP-/NG2-DsRed+ (type-1) and Nestin-GFP+/NG2-DsRed+ (type-2), in close proximity to endothelial cells. We also found that both Nestin-GFP-/NG2-DsRed+ and Nestin-GFP+/NG2-DsRed+ cells colocalize with staining of two pericyte markers, PDGFRβ and CD146, but only type-1 pericyte express the adipogenic progenitor marker PDGFRα. Type-2 pericytes participate in muscle regeneration, while type-1 contribute to fat accumulation. Transplantation studies indicate that type-1 pericytes do not form muscle in vivo, but contribute to fat deposition in the skeletal muscle, while type-2 pericytes contribute only to the new muscle formation after injury, but not to the fat accumulation. Our results suggest that type-1 and type-2 pericytes contribute to successful muscle regeneration which results from a balance of myogenic and nonmyogenic cells activation.

  14. Overweight in elderly people induces impaired autophagy in skeletal muscle.

    Science.gov (United States)

    Potes, Yaiza; de Luxán-Delgado, Beatriz; Rodriguez-González, Susana; Guimarães, Marcela Rodrigues Moreira; Solano, Juan J; Fernández-Fernández, María; Bermúdez, Manuel; Boga, Jose A; Vega-Naredo, Ignacio; Coto-Montes, Ana

    2017-09-01

    Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers

    Directory of Open Access Journals (Sweden)

    Styliana Philippou

    2018-03-01

    Full Text Available Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show loss of therapeutic molecules to non-target tissues leading to lower target efficacy. Therefore, strategies that increase uptake efficiency would be particularly compelling. To address this need, we applied a cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment approach and identified a skeletal muscle-specific RNA aptamer. A01B RNA aptamer preferentially internalizes in skeletal muscle cells and exhibits decreased affinity for off-target cells. Moreover, this in vitro selected aptamer retained its functionality in vivo, suggesting a potential new approach for targeting skeletal muscles. Ultimately, this will aid in the development of targeted oligonucleotide therapies against muscular dystrophies.

  16. A method for preparing skeletal muscle fiber basal laminae

    International Nuclear Information System (INIS)

    Carlson, E.C.; Carlson, B.M.

    1991-01-01

    Previous attempts to prepare skeletal muscle basal laminae (BL) for ultrastructural analyses have been hampered by difficulties in successfully removing skeletal muscle proteins and cellular debris from BL tubes. In the present study the authors describe a two phase method which results in an acellular muscle preparation, the BL of which are examined by light, transmission electron, and scanning electron microscopy. In the first phase, excised rat extensor digitorum longus muscles are subjected to x-radiation and then soaked in Marcaine to inhibit muscle regeneration and to destroy peripheral muscle fibers. The muscles are then grafted back into their original sites and allowed to remain in place 7-14 days to allow for maximal removal of degenerating muscle tissue with minimal scar tissue formation. In the second phase, the muscle grafts are subjected sequentially to EDTA, triton X-100, DNAase, and sodium deoxycholate to remove phagocytizing cells and associated degenerating muscle tissue. These procedures result in translucent, acellular muscle grafts which show numerous empty tubes of BL backed by endomysial collagenous fibers. These preparations should be useful for morphological analyses of isolated muscle BL and for possible in vitro studies by which the biological activity of muscle BL can be examined

  17. A method for preparing skeletal muscle fiber basal laminae

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, E.C.; Carlson, B.M. (University of North Dakota, Grand Forks (USA))

    1991-07-01

    Previous attempts to prepare skeletal muscle basal laminae (BL) for ultrastructural analyses have been hampered by difficulties in successfully removing skeletal muscle proteins and cellular debris from BL tubes. In the present study the authors describe a two phase method which results in an acellular muscle preparation, the BL of which are examined by light, transmission electron, and scanning electron microscopy. In the first phase, excised rat extensor digitorum longus muscles are subjected to x-radiation and then soaked in Marcaine to inhibit muscle regeneration and to destroy peripheral muscle fibers. The muscles are then grafted back into their original sites and allowed to remain in place 7-14 days to allow for maximal removal of degenerating muscle tissue with minimal scar tissue formation. In the second phase, the muscle grafts are subjected sequentially to EDTA, triton X-100, DNAase, and sodium deoxycholate to remove phagocytizing cells and associated degenerating muscle tissue. These procedures result in translucent, acellular muscle grafts which show numerous empty tubes of BL backed by endomysial collagenous fibers. These preparations should be useful for morphological analyses of isolated muscle BL and for possible in vitro studies by which the biological activity of muscle BL can be examined.

  18. The role of subscapularis muscle denervation in the pathogenesis of shoulder internal rotation contracture after neonatal brachial plexus palsy: a study in a rat model.

    Science.gov (United States)

    Mascarenhas, Vasco V; Casaccia, Marcelo; Fernandez-Martin, Alejandra; Marotta, Mario; Fontecha, Cesar G; Haddad, Sleiman; Knörr, Jorge; Soldado, Francisco

    2014-12-01

    We assessed the role of subscapularis muscle denervation in the development of shoulder internal rotation contracture in neonatal brachial plexus injury. Seventeen newborn rats underwent selective denervation of the subscapular muscle. The rats were evaluated at weekly intervals to measure passive shoulder external rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness was measured using 7.2T MRI axial images. The subscapularis muscle was then studied grossly, and its mass was registered. The fiber area and the area of fibrosis were measured using collagen-I inmunostained muscle sections. Significant progressive decrease in passive shoulder external rotation was noted with a mean loss of 58° at four weeks. A significant decrease in thickness and mass of the subscapularis muscles in the involved shoulders was also found with a mean loss of 69%. Subscapularis muscle fiber size decreased significantly, while the area of fibrosis remained unchanged. Our study shows that subscapularis denervation, per se, could explain shoulder contracture after neonatal brachial plexus injury, though its relevance compared to other pathogenic factors needs further investigation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2012-07-01

    Full Text Available Skeletal muscles are the agent of motion and one of the most important tissues responsible for the control of metabolism. The maintenance of muscle homeostasis is finely regulated by the balance between catabolic and anabolic process. Macroautophagy (or autophagy is a catabolic process that provides the degradation of protein aggregation and damaged organelles through the fusion between autophagosomes and lysosomes. Proper regulation of the autophagy flux is fundamental for the homeostasis of skeletal muscles during physiological situations and in response to stress. Defective as well as excessive autophagy is harmful for muscle health and has a pathogenic role in several forms of muscle diseases. This review will focus on the role of autophagy in muscle homeostasis and diseases.

  20. High skeletal muscle adenylate cyclase in malignant hyperthermia.

    OpenAIRE

    Willner, J H; Cerri, C G; Wood, D S

    1981-01-01

    Malignant hyperthermia occurs in humans with several congenital myopathies, usually in response to general anesthesia. Commonly, individuals who develop this syndrome lack symptoms of muscle disease, and their muscle lacks specific pathological changes. A biochemical marker for this myopathy has not previously been available; we found activity of adenylate cyclase and content of cyclic AMP to be abnormally high in skeletal muscle. Secondary modification of protein phosphorylation could explai...

  1. 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.)

  2. Skeletal muscle pathology in Huntington’s Disease.

    Directory of Open Access Journals (Sweden)

    Daniel eZielonka

    2014-10-01

    Full Text Available Huntington’s disease (HD is a hereditary neurodegenerative disorder caused by the expansion of a polyglutamine stretch within the huntingtin protein (HTT. The neurological symptoms, that involve motor, cognitive and psychiatric disturbances, are caused by neurodegeneration that is particularly widespread in the basal ganglia and cereberal cortex. HTT is ubiquitously expressed and in recent years it has become apparent that HD patients experience a wide array of peripheral organ dysfunction including severe metabolic phenotype, weight loss, HD-related cardiomyopathy and skeletal muscle wasting, . Although skeletal muscles became a hallmark of HD, the mechanisms underlying muscular atrophy in this disorder are unknown. Skeletal muscles account for approximately 40% of body mass and are highly adaptive to physiological and pathological conditions that may result in muscle hypertrophy (due to increased mechanical load or atrophy (inactivity, chronic disease states. The atrophy is caused by degeneration of myofibers and their replacement by fibrotic tissue is the major pathological feature in many genetic muscle disorders. Under normal physiological conditions the muscle function is orchestrated by a network of intrinsic hypertrophic and atrophic signals linked to the functional properties of the motor units that are likely to be imbalanced in HD. In this article, we highlight the emerging field of research with particular focus on the recent studies of the skeletal muscle pathology and the identification of new disease-modifying treatments.

  3. 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.

  4. 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.

  5. eIF3f: a central regulator of the antagonism atrophy/hypertrophy in skeletal muscle.

    Science.gov (United States)

    Sanchez, Anthony M J; Csibi, Alfredo; Raibon, Audrey; Docquier, Aurélie; Lagirand-Cantaloube, Julie; Leibovitch, Marie-Pierre; Leibovitch, Serge A; Bernardi, Henri

    2013-10-01

    The eukaryotic initiation factor 3 subunit f (eIF3f) is one of the 13 subunits of the translation initiation factor complex eIF3 required for several steps in the initiation of mRNA translation. In skeletal muscle, recent studies have demonstrated that eIF3f plays a central role in skeletal muscle size maintenance. Accordingly, eIF3f overexpression results in hypertrophy through modulation of protein synthesis via the mTORC1 pathway. Importantly, eIF3f was described as a target of the E3 ubiquitin ligase MAFbx/atrogin-1 for proteasome-mediated breakdown under atrophic conditions. The biological importance of the MAFbx/atrogin-1-dependent targeting of eFI3f is highlighted by the finding that expression of an eIF3f mutant insensitive to MAFbx/atrogin-1 polyubiquitination is associated with enhanced protection against starvation-induced muscle atrophy. A better understanding of the precise role of this subunit should lead to the development of new therapeutic approaches to prevent or limit muscle wasting that prevails in numerous physiological and pathological states such as immobilization, aging, denervated conditions, neuromuscular diseases, AIDS, cancer, diabetes. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. Copyright © 2013 Elsevier Ltd. All rights reserved.

  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. FDG-PET/CT in Skeletal Muscle: Pitfalls and Pathologies.

    Science.gov (United States)

    Parida, Girish Kumar; Roy, Shambo Guha; Kumar, Rakesh

    2017-07-01

    FDG-PET/CT is an integral part of modern-day practice of medicine. By detecting increased cellular metabolism, FDG-PET/CT can help us detect infection, inflammatory disorders, or tumors, and also help us in prognostication of patients. However, one of the most important challenges is to correctly differentiate the abnormal uptake that is potentially pathologic from the physiological uptake. So while interpreting a PET/CT, one must be aware of normal biodistribution and different physiological variants of FDG uptake. Skeletal muscles constitute a large part of our body mass and one of the major users of glucose. Naturally, they are often the site of increased FDG uptake in a PET study. We as a nuclear medicine physician must be aware of all the pitfalls of increased skeletal muscle uptake to differentiate between physiological and pathologic causes. In this review, we have discussed the different causes and patterns of physiological FDG uptake in skeletal muscles. This knowledge of normal physiological variants of FDG uptake in the skeletal muscles is essential for differentiating pathologic uptake from the physiological ones. Also, we reviewed the role of FDG-PET/CT in various benign and malignant diseases involving skeletal muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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

  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

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → 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-related hormones such as leptin

  11. 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

  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 < 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.

  13. 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.

  14. Coffee consumption promotes skeletal muscle hypertrophy and myoblast differentiation.

    Science.gov (United States)

    Jang, Young Jin; Son, Hyo Jeong; Kim, Ji-Sun; Jung, Chang Hwa; Ahn, Jiyun; Hur, Jinyoung; Ha, Tae Youl

    2018-02-21

    Coffee is a widely consumed beverage worldwide and is believed to help prevent the occurrence of various chronic diseases. However, the effect of coffee on skeletal muscle hypertrophy, differentiation and the mechanisms of action responsible have remained unclear. To investigate the effect of coffee on skeletal muscle hypertrophy, mice were fed a normal diet or a normal diet supplemented with 0.3% coffee or 1% coffee. Coffee supplementation was observed to increase skeletal muscle hypertrophy, while simultaneously upregulating protein expression of total MHC, MHC2A, and MHC2B in quadricep muscle. Myostatin expression was also attenuated, and IGF1 was upregulated with subsequent phosphorylation of Akt and mTOR, while AMPK phosphorylation was attenuated. Coffee also increased the grip strength and PGC-1α protein expression, and decreased the expressions of TGF-β and myostatin in tricep muscle. Coffee activated the MKK3/6-p38 pathway and upregulated PGC-1α, which may play a role in promoting myogenic differentiation and myogenin expression in C2C12 cells. These results suggest that coffee increases skeletal muscle function and hypertrophy by regulating the TGF-β/myostatin - Akt - mTORC1.

  15. GRMD cardiac and skeletal muscle metabolism gene profiles are distinct.

    Science.gov (United States)

    Markham, Larry W; Brinkmeyer-Langford, Candice L; Soslow, Jonathan H; Gupte, Manisha; Sawyer, Douglas B; Kornegay, Joe N; Galindo, Cristi L

    2017-04-08

    Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to skeletal muscle dysfunction. To address this question, we analyzed cardiac and skeletal muscle tissue microarrays from golden retriever muscular dystrophy (GRMD) dogs, a genetically and clinically homologous model for DMD. A total of 15 dogs, 3 each GRMD and controls at 6 and 12 months plus 3 older (47-93 months) GRMD dogs, were assessed. GRMD dogs exhibited tissue- and age-specific transcriptional profiles and enriched functions in skeletal but not cardiac muscle, consistent with a "metabolic crisis" seen with DMD microarray studies. Most notably, dozens of energy production-associated molecules, including all of the TCA cycle enzymes and multiple electron transport components, were down regulated. Glycolytic and glycolysis shunt pathway-associated enzymes, such as those of the anabolic pentose phosphate pathway, were also altered, in keeping with gene expression in other forms of muscle atrophy. On the other hand, GRMD cardiac muscle genes were enriched in nucleotide metabolism and pathways that are critical for neuromuscular junction maintenance, synaptic function and conduction. These findings suggest differential metabolic dysfunction may contribute to distinct pathological phenotypes in skeletal and cardiac muscle.

  16. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

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

    2000-01-01

    The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal amplifica......The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal...... 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...

  17. 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...... in the sarcolemma as well as the cytoplasm of type I muscle fibres. NADPH diaphorase activity confirmed a higher level of NO synthase activity in the sarcolemma as well as the cytoplasm of type I muscle fibers. Histochemical staining for cytochrome oxidase showed a staining pattern similar to that observed for type...... 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...

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

    Science.gov (United States)

    Murphy, Sandra; Dowling, Paul; Ohlendieck, Kay

    2016-01-01

    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. PMID:28248237

  19. Regulation of Blood Flow in Contracting Skeletal Muscle in Aging

    DEFF Research Database (Denmark)

    Piil, Peter Bergmann

    Oxygen delivery to skeletal muscle is regulated precisely to match the oxygen demand; however, with aging the regulation of oxygen delivery during exercise is impaired. The present thesis investigated mechanisms underlying the age-related impairment in regulation of blood flow and oxygen delivery...... to contracting skeletal muscle. Two studies, one acute exercise study and one large 8-week training intervention study, were conducted in young (18-28 years) and older (65-80 years) healthy, male subjects. In both studies, pharmacologic potentiation of the formation of cyclic guanosine monophosphate (c...... that improving sympatholytic capacity by training may be a slower process in older than in young men. In conclusion, this thesis provides new important knowledge related to the regulation of skeletal muscle blood flow in aging. Specifically, it demonstrates that changes in cGMP signaling is an underlying cause...

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

    DEFF Research Database (Denmark)

    Olesen, Jesper; Kiilerich, Kristian; Pilegaard, Henriette

    2010-01-01

    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......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...... involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested...

  1. 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. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  2. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation......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...

  3. Changes in skeletal muscle gene expression following clenbuterol administration

    Science.gov (United States)

    Spurlock, Diane M; McDaneld, Tara G; McIntyre, Lauren M

    2006-01-01

    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 clenbuterol treatment. A total of 22,605 probesets were evaluated with 52 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signalling pathways, and genes involved in polyamine metabolism. 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

  4. 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.

  5. 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.

  6. Substrate kinetics in patients with disorders of skeletal muscle metabolism.

    Science.gov (United States)

    Ørngreen, Mette Cathrine

    2016-07-01

    The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before

  7. 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.

  8. Human skeletal muscle glycogen utilization in exhaustive exercise

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... 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. ....

  9. Functional heterogeneity of side population cells in skeletal muscle

    International Nuclear Information System (INIS)

    Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro; Ikemoto, Madoka; Masuda, Satoru; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2006-01-01

    Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31 - CD45 - SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31 - CD45 - SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31 - CD45 - SP cells participate in muscle regeneration

  10. Lactate and force production in skeletal muscle

    DEFF Research Database (Denmark)

    Kristensen, Michael; Albertsen, Janni; Rentsch, Maria

    2005-01-01

    Lactic acid accumulation is generally believed to be involved in muscle fatigue. However, one study reported that in rat soleus muscle (in vitro), with force depressed by high external K+ concentrations a subsequent incubation with lactic acid restores force and thereby protects against fatigue...... muscle. Three incubation solutions were used: 20 mm Na-lactate (which acidifies internal pH), 12 mm Na-lactate +8 mm lactic acid (which mimics the pH changes during muscle activity), and 20 mm lactic acid (which acidifies external pH more than internal pH). All three solutions improved force in K+-depressed...... development in repetitively stimulated muscle (Na-lactate had a negative effect). It is concluded that although lactate/lactic acid incubation regains force in K+-depressed resting muscle, a similar incubation has no or a negative effect on force development in active muscle. It is suggested...

  11. Wnt Signaling in Skeletal Muscle Development and Regeneration.

    Science.gov (United States)

    Girardi, Francesco; Le Grand, Fabien

    2018-01-01

    Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in target cells. Several studies, within the last decades, showed that several Wnt ligands are involved in myogenesis and both canonical and noncanonical Wnt pathways regulate muscle formation and the maintenance of adult tissue homeostasis. In this review, we provide a comprehensive overview of the roles of Wnt signaling during muscle development and an updated description of Wnt functions during muscle repair. Lastly, we discuss the crosstalk between Wnt and TGFβ signaling pathways in skeletal muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Regulation of exercise-induced lipid metabolism in skeletal muscle

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting; Kiens, Bente

    2014-01-01

    mice. In skeletal muscle, 98% of the lipase activity is accounted for by adipose triglyceride lipase and hormone-sensitive lipase. Give that inhibition or knockout of hormone-sensitive lipase does not impair lipolysis in muscle during contraction, the data point to an important role of adipose...... triglyceride lipase in regulation of muscle lipolysis. Although the molecular regulation of the lipases in muscle is not understood, it is speculated that intramuscular lipolysis may be regulated in part by the availability of the plasma concentration of long-chain fatty acids....

  13. Therapeutic approaches to skeletal muscle repair and healing.

    Science.gov (United States)

    Danna, Natalie R; Beutel, Bryan G; Campbell, Kirk A; Bosco, Joseph A

    2014-07-01

    Skeletal muscle is comprised of a highly organized network of cells, neurovascular structures, and connective tissue. Muscle injury is typically followed by a well-orchestrated healing response that consists of the following phases: inflammation, regeneration, and fibrosis. This review presents the mechanisms of action and evidence supporting the effectiveness of various traditional and novel therapies at each phase of the skeletal muscle healing process. Relevant published articles were identified using MEDLINE (1978-2013). Clinical review. Level 3. To facilitate muscle healing, surgical techniques involving direct suture repair, as well as the implantation of innovative biologic scaffolds, have been developed. Nonsteroidal anti-inflammatory drugs may be potentially supplanted by nitric oxide and curcumin in modulating the inflammatory pathway. Studies in muscle regeneration have identified stem cells, myogenic factors, and β-agonists capable of enhancing the regenerative capabilities of injured tissue. Furthermore, transforming growth factor-β1 (TGF-β1) and, more recently, myostatin and the rennin-angiotensin system have been implicated in fibrous tissue formation; several antifibrotic agents have demonstrated the ability to disrupt these systems. Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention. For full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis. B.

  14. 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

  15. Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

    Directory of Open Access Journals (Sweden)

    Ninghao Zhu

    2017-06-01

    Full Text Available Reconstitution of tissue morphology with inherent left–right (LR asymmetry is essential for tissue/organ functions. For skeletal muscle, the largest tissue in mammalian organisms, successful myogenesis requires the regulation of the LR asymmetry to form the appropriate muscle alignment. However, the key factor for reproducing the LR asymmetry of skeletal tissues in a controllable, engineering context remains largely unknown. Recent reports indicate that cell chirality may underlie the LR development in tissue morphogenesis. Here, we report that a rigid substrate is required for the chirality of skeletal muscle cells. By using alternating micropatterned cell-adherent and cell-repellent stripes on a rigid substrate, we found that C2C12 skeletal muscle myoblasts exhibited a unidirectional tilted orientation with respect to the stripe boundary. Importantly, such chiral orientation was reduced when soft substrates were used instead. In addition, we demonstrated the key role of actin stress fibers in the formation of the chiral orientation. This study reveals that a rigid substrate is required for the chiral pattern of myoblasts, paving the way for reconstructing damaged muscle tissue with inherent LR asymmetry in the future.

  16. 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.

  17. Insights into skeletal muscle development and applications in regenerative medicine.

    Science.gov (United States)

    Tran, T; Andersen, R; Sherman, S P; Pyle, A D

    2013-01-01

    Embryonic and postnatal development of skeletal muscle entails highly regulated processes whose complexity continues to be deconstructed. One key stage of development is the satellite cell, whose niche is composed of multiple cell types that eventually contribute to terminally differentiated myotubes. Understanding these developmental processes will ultimately facilitate treatments of myopathies such as Duchenne muscular dystrophy (DMD), a disease characterized by compromised cell membrane structure, resulting in severe muscle wasting. One theoretical approach is to use pluripotent stem cells in a therapeutic setting to help replace degenerated muscle tissue. This chapter discusses key myogenic developmental stages and their regulatory pathways; artificial myogenic induction in pluripotent stem cells; advantages and disadvantages of DMD animal models; and therapeutic approaches targeting DMD. Furthermore, skeletal muscle serves as an excellent paradigm for understanding general cell fate decisions throughout development. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 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....

  19. 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.

  20. Effects of overtraining on skeletal muscle growth and gene expression.

    Science.gov (United States)

    Xiao, W; Chen, P; Dong, J

    2012-10-01

    The aim of this study was to investigate the effects of overtraining on skeletal muscle growth and growth-related gene expression. The rats of overtraining group (OT) and overtraining recovery group (OTR) were subject to 11 experimental weeks of overtraining protocol. It was found that the absolute gastrocnemius muscle wet weight of the OT group was significantly lower than that of the sedentary group (23.6%, Povertraining. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Cell death, clearance and immunity in the skeletal muscle

    OpenAIRE

    Sciorati, C; Rigamonti, E; Manfredi, A A; Rovere-Querini, P

    2016-01-01

    The skeletal muscle is an immunologically unique tissue. Leukocytes, virtually absent in physiological conditions, are quickly recruited into the tissue upon injury and persist during regeneration. Apoptosis, necrosis and autophagy coexist in the injured/regenerating muscles, including those of patients with neuromuscular disorders, such as inflammatory myopathies, dystrophies, metabolic and mitochondrial myopathies and drug-induced myopathies. Macrophages are able to alter their function in ...

  2. Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

    OpenAIRE

    Murray, IR; Baily, JE; Chen, WCW; Dar, A; Gonzalez, ZN; Jensen, AR; Petrigliano, FA; Deb, A; Henderson, NC

    2017-01-01

    Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. I...

  3. 3D Visualization and Measurement of Capillaries Supplying Metabolically Different Fiber Types in the Rat Extensor Digitorum Longus Muscle During Denervation and Reinnervation

    Czech Academy of Sciences Publication Activity Database

    Janáček, Jiří; Čebašek, V.; Kubínová, Lucie; Ribarič, S.; Eržen, I.

    2009-01-01

    Roč. 57, č. 5 (2009), s. 437-447 ISSN 0022-1554 R&D Projects: GA MŠk(CZ) LC06063; GA MŠk(CZ) MEB090606; GA AV ČR(CZ) IAA100110502 Institutional research plan: CEZ:AV0Z50110509 Keywords : capillaries * denervation * muscle fiber types Subject RIV: ED - Physiology Impact factor: 2.372, year: 2009

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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

  6. Skeletal muscle injury and repair in marathon runners after competition.

    Science.gov (United States)

    Warhol, M J; Siegel, A J; Evans, W J; Silverman, L M

    1985-02-01

    Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competition may arise from injury to skeletal muscle, myocardium, or a combined tissue source. Normal radionuclide myocardial scintigraphy and the selective increase in skeletal muscle CK-MB reported in such runners strongly suggest a peripheral source. To understand this biochemical finding, the authors examined gastrocnemius muscles by electron microscopy from 40 male marathon runners at intervals after competition and from 12 male nonrunners. Muscle from runners showed post-race ultrastructural changes of focal fiber injury and repair: intra- and extracellular edema with endothelial injury; myofibrillar lysis, dilation and disruption of the T-tubule system, and focal mitochondrial degeneration without inflammatory infiltrate (1-3 days). The mitochondrial and myofibrillar damage showed progressive repair by 3-4 weeks. Late biopsies showed central nuclei and satellite cells characteristic of the regenerative response (8-12 weeks). Muscle from veteran runners showed intercellular collagen deposition suggestive of a fibrotic response to repetitive injury. Control tissue from nonrunners showed none of these findings. The sequential morphologic changes in runners suggest that the increase in skeletal muscle CK-MB is a marker of cellular regeneration.

  7. Potential of laryngeal muscle regeneration using induced pluripotent stem cell-derived skeletal muscle cells.

    Science.gov (United States)

    Dirja, Bayu Tirta; Yoshie, Susumu; Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Nakamura, Ryosuke; Otsuki, Koshi; Nomoto, Yukio; Wada, Ikuo; Hazama, Akihiro; Omori, Koichi

    2016-01-01

    Conclusion Induced pluripotent stem (iPS) cells may be a new potential cell source for laryngeal muscle regeneration in the treatment of vocal fold atrophy after recurrent laryngeal nerve paralysis. Objectives Unilateral vocal fold paralysis can lead to degeneration, atrophy, and loss of force of the thyroarytenoid muscle. At present, there are some treatments such as thyroplasty, arytenoid adduction, and vocal fold injection. However, such treatments cannot restore reduced mass of the thyroarytenoid muscle. iPS cells have been recognized as supplying a potential resource for cell transplantation. The aim of this study was to assess the effectiveness of the use of iPS cells for the regeneration of laryngeal muscle through the evaluation of both in vitro and in vivo experiments. Methods Skeletal muscle cells were generated from tdTomato-labeled iPS cells using embryoid body formation. Differentiation into skeletal muscle cells was analyzed by gene expression and immunocytochemistry. The tdTomato-labeled iPS cell-derived skeletal muscle cells were transplanted into the left atrophied thyroarytenoid muscle. To evaluate the engraftment of these cells after transplantation, immunohistochemistry was performed. Results The tdTomato-labeled iPS cells were successfully differentiated into skeletal muscle cells through an in vitro experiment. These cells survived in the atrophied thyroarytenoid muscle after transplantation.

  8. 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...

  9. 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.

  10. 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...

  11. 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…

  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. Physical injuries, contractures and rigidity of skeletal muscle

    International Nuclear Information System (INIS)

    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

  14. 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...

  15. 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...

  16. Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina; O'Neill, Hayley M; Kleinert, Maximilian

    2015-01-01

    INTRODUCTION: Members of the interleukin-6 (IL-6) family, IL-6 and ciliary neurotrophic factor (CNTF) have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well...

  17. The impact of low skeletal muscle mass in abdominal surgery

    NARCIS (Netherlands)

    J.L.A. van Vugt (Jeroen)

    2017-01-01

    textabstractAlthough perioperative outcome in transplant and surgical oncology patients has greatly improved during the last decades, preoperative risk assessment remains of utmost importance to further improve outcomes and adapt patient-tailored treatment strategies. Low skeletal muscle mass is

  18. 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.

  19. 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...

  20. Advancements in stem cells treatment of skeletal muscle wasting

    Directory of Open Access Journals (Sweden)

    mirella emeregalli

    2014-02-01

    Full Text Available Muscular dystrophies (MDs are a heterogeneous group of inherited disorders, in which progressive muscle wasting and weakness is often associated with exhaustion of muscle regeneration potential. Although physiological properties of skeletal muscle tissue are now well known, no treatments are effective for these diseases. Muscle regeneration was attempted by means transplantation of myogenic cells (from myoblast to embryonic stem cells and also by interfering with the malignant processes that originate in pathological tissues, such as uncontrolled fibrosis and inflammation. Taking into account the advances in the isolation of new subpopulation of stem cells and in the creation of artificial stem cell niches, we discuss how these emerging technologies offer great promises for therapeutic approaches to muscle diseases and muscle wasting associated with aging.

  1. Genetic architecture of gene expression in ovine skeletal muscle

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... 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...

  2. Exercise-induced Protein Arginine Methyltransferase Expression in Skeletal Muscle.

    Science.gov (United States)

    Vanlieshout, Tiffany L; Stouth, Derek W; Tajik, Tania; Ljubicic, Vladimir

    2018-03-01

    This study aimed to determine protein arginine methyltransferase 1 (PRMT1), -4 (also known as coactivator-associated arginine methyltransferase 1 [CARM1]), and -5 expression and function during acute, exercise-induced skeletal muscle remodeling in vivo. C57BL/6 mice were assigned to one of three experimental groups: sedentary, acute bout of exercise, or acute exercise followed by 3 h of recovery. Mice in the exercise groups performed a single bout of treadmill running at 15 m·min for 90 min. Hindlimb muscles were collected, and quantitative real-time polymerase chain reaction and Western blotting were used to examine exercise-induced gene expression. The PRMT gene expression and global enzyme activity were muscle-specific, generally being higher (P < 0.05) in slow, oxidative muscle, as compared with faster, more glycolytic tissue. Despite the significant activation of canonical exercise-induced signaling involving AMP-activated protein kinase and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), PRMT expression and activity at the whole muscle level were unchanged. However, subcellular analyses revealed a significant exercise-evoked myonuclear translocation of PRMT1 before the nuclear accumulation of PGC-1α. Acute physical activity also augmented (P < 0.05) the targeted methyltransferase activities of the PRMT in the myonuclear compartment, suggesting that PRMT-mediated histone arginine methylation is part of the early signals that drive muscle plasticity. Finally, basal PGC-1α asymmetric dimethylarginine status, as well as constitutive interactions between PGC-1α and PRMT1 or CARM1 may contribute to the exercise-induced muscle remodeling process. The present study provides the first evidence that PRMT activity is selectively augmented during the initial activation of exercise-induced skeletal muscle remodeling in vivo. These data support the emergence of PRMTs as important players in the regulation of skeletal muscle plasticity.

  3. Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

    OpenAIRE

    Park, Song-Young; Gifford, Jayson R.; Andtbacka, Robert H. I.; Trinity, Joel D.; Hyngstrom, John R.; Garten, Ryan S.; Diakos, Nikolaos A.; Ives, Stephen J.; Dela, Flemming; Larsen, Steen; Drakos, Stavros; Richardson, Russell S.

    2014-01-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index...

  4. 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...... 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...

  5. Skeletal muscle substrate metabolism during exercise: methodological considerations

    DEFF Research Database (Denmark)

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

    1999-01-01

    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...... substrates. There are several methodological concerns to be aware of when studying the metabolic response to exercise in human subjects. These concerns include: (1) the muscle mass involved in the exercise is largely unknown (bicycle or treadmill). Moreover, whether the muscle sample obtained from a limb...

  6. Skeletal muscle responses to lower limb suspension in humans

    Science.gov (United States)

    Hather, Bruce M.; Adams, Gregory R.; Tesch, Per A.; Dudley, Gary A.

    1992-01-01

    The morphological responses of human skeletal muscle to unweighting were assessed by analyzing multiple transaxial magnetic resonance (MR) images of both lower limbs and skeletal muscle biopsies of the unweighted lower limb before and after six weeks of unilaterial (left) lower limb suspension (ULLS). Results indicated that, as a results of 6 weeks of unweighting (by the subjects walking on crutches using only one limb), the cross sectional area (CSA) of the thigh muscle of the unweighted left limb decreased 12 percent, while the CSA of the right thigh muscle did not change. The decrease was due to a twofold greater response of the knee extensors than the knee flexors. The pre- and post-ULLS biopsies of the left vastus lateralis showed a 14 percent decrease in average fiber CSA due to unweighting. The number of capillaries surrounding the different fiber types was unchanged after ULLS. Results showed that the adaptive responses of human skeletal muscle to unweighting are qualitatively, but not quantitatively, similar to those of lower mammals and not necessarily dependent on the fiber-type composition.

  7. Protein Availability and Satellite Cell Dynamics in Skeletal Muscle.

    Science.gov (United States)

    Shamim, Baubak; Hawley, John A; Camera, Donny M

    2018-03-20

    Human skeletal muscle satellite cells are activated in response to both resistance and endurance exercise. It was initially proposed that satellite cell proliferation and differentiation were only required to support resistance exercise-induced hypertrophy. However, satellite cells may also play a role in muscle fibre remodelling after endurance-based exercise and extracellular matrix regulation. Given the importance of dietary protein, particularly branched chain amino acids, in supporting myofibrillar and mitochondrial adaptations to both resistance and endurance-based training, a greater understanding of how protein intake impacts satellite cell activity would provide further insight into the mechanisms governing skeletal muscle remodelling with exercise. While many studies have investigated the capacity for protein ingestion to increase post-exercise rates of muscle protein synthesis, few investigations have examined the role for protein ingestion to modulate satellite cell activity. Here we review the molecular mechanisms controlling the activation of satellite cells in response to mechanical stress and protein intake in both in vitro and in vivo models. We provide a mechanistic framework that describes how protein ingestion may enhance satellite activity and promote exercise adaptations in human skeletal muscle.

  8. Skeletal muscle mechanics: questions, problems and possible solutions.

    Science.gov (United States)

    Herzog, Walter

    2017-09-16

    Skeletal muscle mechanics have been studied ever since people have shown an interest in human movement. However, our understanding of muscle contraction and muscle mechanical properties has changed fundamentally with the discovery of the sliding filament theory in 1954 and associated cross-bridge theory in 1957. Nevertheless, experimental evidence suggests that our knowledge of the mechanisms of contraction is far from complete, and muscle properties and muscle function in human movement remain largely unknown.In this manuscript, I am trying to identify some of the crucial challenges we are faced with in muscle mechanics, offer possible solutions to questions, and identify problems that might be worthwhile exploring in the future. Since it is impossible to tackle all (worthwhile) problems in a single manuscript, I identified three problems that are controversial, important, and close to my heart. They may be identified as follows: (i) mechanisms of muscle contraction, (ii) in vivo whole muscle mechanics and properties, and (iii) force-sharing among synergistic muscles. These topics are fundamental to our understanding of human movement and movement control, and they contain a series of unknowns and challenges to be explored in the future.It is my hope that this paper may serve as an inspiration for some, may challenge current beliefs in selected areas, tackle important problems in the area of muscle mechanics, physiology and movement control, and may guide and focus some of the thinking of future muscle mechanics research.

  9. Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

    Science.gov (United States)

    Staunton, Lisa; O'Connell, Kathleen; Ohlendieck, Kay

    2011-01-01

    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. PMID:21437005

  10. 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.

  11. 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......The ability to sustain a given absolute submaximal workload declines with advancing age likely due to a lower level of blood flow and O2 delivery to the exercising muscles. Given that physical inactivity mimics many of the physiological changes associated with ageing, separating the physiological...... the O2 demand of the active skeletal muscle of aged individuals during conditions where systemic blood flow is not limited by cardiac output seems to a large extent to be related to the level of physical activity. This article is protected by copyright. All rights reserved....

  12. Compartmentalization of NO signaling cascade in skeletal muscles

    International Nuclear Information System (INIS)

    Buchwalow, Igor B.; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim; Punkt, Karla

    2005-01-01

    Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma

  13. Neonatal epicardial-derived progenitors aquire myogenic traits in skeletal muscle, but not cardiac muscle

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Jensen, Charlotte H; Skovrind, Ida

    2016-01-01

    heart missing regenerative signals essential for directed differentiation of EPDCs. Herein, we aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal mouse myocardium, as well as in skeletal muscle. The two latter tissues have an intrinsic capability to develop and regenerate......, in contrast to the adult heart. METHODS: Highly purified mouse EPDCs were transplanted into damaged neonatal and adult myocardium as well as regenerating skeletal muscle. Co-cultures with skeletal myoblasts were used to distinguish fusion independent myogenic conversion. RESULTS: No donor EPDC......-derived cardiomyocytes were observed in hearts. In contrast, a remarkable contribution of EPDCs to skeletal muscle myofiber formation was evident in vivo. Furthermore, co-cultures of EPDCs with myoblasts showed that EPDCs became part of multinucleated fibers and appeared to acquire myogenic traits independent...

  14. Neuropeptide Y and neurovascular control in skeletal muscle and skin

    Science.gov (United States)

    Hodges, Gary J.; Jackson, Dwayne N.; Mattar, Louis; Johnson, John M.; Shoemaker, J. Kevin

    2009-01-01

    Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y1-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the α1-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y1-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y1-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered. PMID:19571208

  15. Muscle size explains low passive skeletal muscle force in heart failure patients.

    Science.gov (United States)

    Panizzolo, Fausto Antonio; Maiorana, Andrew J; Naylor, Louise H; Dembo, Lawrence G; Lloyd, David G; Green, Daniel J; Rubenson, Jonas

    2016-01-01

    Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. We found reduced passive SOL forces (∼30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening.

  16. Atomoxetine prevents dexamethasone-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

    Jesinkey, Sean R; Korrapati, Midhun C; Rasbach, Kyle A; Beeson, Craig C; Schnellmann, Rick G

    2014-12-01

    Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1-Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. U.S. Government work not protected by U

  17. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

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

    2014-01-01

    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....... 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......B transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma...

  18. Biphasic regulation of development of the high-affinity saxitoxin receptor by innervation in rat skeletal muscle

    International Nuclear Information System (INIS)

    Sherman, S.J.; Catterall, W.A.

    1982-01-01

    Specific binding of 3 H-saxitoxin (STX) was used to quantitate the density of voltage-sensitive sodium channels in developing rat skeletal muscle. In adult triceps surae, a single class of sites with a KD . 2.9 nM and a density of 21 fmol/mg wet wt was detected. The density of these high-affinity sites increased from 2.0 fmol/mg wet wt to the adult value in linear fashion during days 2-25 after birth. Denervation of the triceps surae at day 11 or 17 reduced final saxitoxin receptor site density to 10.4 or 9.2 fmol/mg wet wt, respectively, without changing KD. Denervation of the triceps surae at day 5 did not alter the subsequent development of saxitoxin receptor sites during days 5-9 and accelerated the increase of saxitoxin receptor sites during days 9-13. After day 13, saxitoxin receptor development abruptly ceased and the density of saxitoxin receptor sites declined to 11 fmol/wg wet wt. These results show that the regulation of high-affinity saxitoxin receptor site density by innervation is biphasic. During the first phase, which is independent of continuing innervation, the saxitoxin receptor density increases to 47-57% of the adult level. After day 11, the second phase of development, which is dependent on continuing innervation, gives rise to the adult density of saxitoxin receptors

  19. Increased Plin2 Expression in Human Skeletal Muscle Is Associated with Sarcopenia and Muscle Weakness

    NARCIS (Netherlands)

    Conte, Maria; Vasuri, Francesco; Trisolino, Giovanni; Bellavista, Elena; Santoro, Aurelia; Degiovanni, Alessio; Martucci, Ermanno; D'Errico-Grigioni, Antonia; Caporossi, Daniela; Capri, Miriam; Maier, Andrea B.; Seynnes, Olivier; Barberi, Laura; Musarò, Antonio; Narici, Marco V.; Franceschi, Claudio; Salvioli, Stefano

    2013-01-01

    Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in

  20. FIRST SOUND EVIDENCE OF MUSCLE REGENERATION IN RECOVERY OF FUNCTION OF HUMAN PERMANENT DENERVATED MUSCLES BY A LONG-LASTING FUNCTIONAL ELECTRICAL STIMULATION (FES TRAINING: BIOPSY FINDINGS

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2004-12-01

    Full Text Available Contrary to general believe, in one case of 18month cauda equina lesion four-month electrical stimulation of thigh muscles (impulse energy 1.92 Joule increased stimulation frequency from 2 to 20 Hz, i. e., up to tetanic contractions. After 2 years of treatment, CT-cross sectional area of quadriceps improved 58.3% (right and 44.4% (left with increased muscle density. Mean myofiber size was 37.2 ± 24.8 µm (right and 40.5 ±  24.9 µm (left. Improvement of stimulated knee torque, from zero to 12.0 Nm and 10.5 Nm, respectively, enabled to stand up trials. Surviving myofibers undergo re-growth (they show the chess board appearance of normal muscle, and dying myofibers continuously regenerate (up to 3% are embryonic myosin positive 3-year post-FES. Regeneration events are essential components of the FES rehabilitation protocol due to superior excitability of regenerated myofibers in comparison to long-term denervated, degenerated myofibers, which were almost not excitable before FES training.

  1. Pathology of skeletal muscle in fibromyalgia

    DEFF Research Database (Denmark)

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

    1993-01-01

    of muscle disease. Nevertheless, we subjected biopsies from nine of the patients and five other controls for further ultrastructural evaluations and demonstrated pathologic findings e.g. empty sleeves of basement membrane, many lipofuschin bodies and other degenerative changes. We conclude......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...

  2. 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 ...

  3. Lack of CFTR in skeletal muscle predisposes to muscle wasting and diaphragm muscle pump failure in cystic fibrosis mice.

    Directory of Open Access Journals (Sweden)

    Maziar Divangahi

    2009-07-01

    Full Text Available Cystic fibrosis (CF patients often have reduced mass and strength of skeletal muscles, including the diaphragm, the primary muscle of respiration. Here we show that lack of the CF transmembrane conductance regulator (CFTR plays an intrinsic role in skeletal muscle atrophy and dysfunction. In normal murine and human skeletal muscle, CFTR is expressed and co-localized with sarcoplasmic reticulum-associated proteins. CFTR-deficient myotubes exhibit augmented levels of intracellular calcium after KCl-induced depolarization, and exposure to an inflammatory milieu induces excessive NF-kB translocation and cytokine/chemokine gene upregulation. To determine the effects of an inflammatory environment in vivo, sustained pulmonary infection with Pseudomonas aeruginosa was produced, and under these conditions diaphragmatic force-generating capacity is selectively reduced in Cftr(-/- mice. This is associated with exaggerated pro-inflammatory cytokine expression as well as upregulation of the E3 ubiquitin ligases (MuRF1 and atrogin-1 involved in muscle atrophy. We conclude that an intrinsic alteration of function is linked to the absence of CFTR from skeletal muscle, leading to dysregulated calcium homeostasis, augmented inflammatory/atrophic gene expression signatures, and increased diaphragmatic weakness during pulmonary infection. These findings reveal a previously unrecognized role for CFTR in skeletal muscle function that may have major implications for the pathogenesis of cachexia and respiratory muscle pump failure in CF patients.

  4. Long-lasting effect of obesity on skeletal muscle transcriptome.

    Science.gov (United States)

    Messaoudi, Ilhem; Handu, Mithila; Rais, Maham; Sureshchandra, Suhas; Park, Byung S; Fei, Suzanne S; Wright, Hollis; White, Ashley E; Jain, Ruhee; Cameron, Judy L; Winters-Stone, Kerri M; Varlamov, Oleg

    2017-05-25

    Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. Six male rhesus macaques of 12-13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitivity, the majority of WSD-induced (n = 457) and WSD-suppressed (n = 47) genes remained significantly dysregulated after caloric restriction (FDR ≤0.05). The Metacore TM pathway analysis reveals that western-style diet induced the sustained activation of the transforming growth factor-β gene network, associated with extracellular matrix remodeling, and the downregulation of genes involved in muscle structure development and nutritional processes. Western-style diet, in the absence of exercise, induced skeletal muscle transcriptional programing, which persisted even after insulin resistance and glucose intolerance were completely reversed with caloric restriction.

  5. Secretome profiling of primary human skeletal muscle cells.

    Science.gov (United States)

    Hartwig, Sonja; Raschke, Silja; Knebel, Birgit; Scheler, Mika; Irmler, Martin; Passlack, Waltraud; Muller, Stefan; Hanisch, Franz-Georg; Franz, Thomas; Li, Xinping; Dicken, Hans-Dieter; Eckardt, Kristin; Beckers, Johannes; de Angelis, Martin Hrabe; Weigert, Cora; Häring, Hans-Ulrich; Al-Hasani, Hadi; Ouwens, D Margriet; Eckel, Jürgen; Kotzka, Jorg; Lehr, Stefan

    2014-05-01

    The skeletal muscle is a metabolically active tissue that secretes various proteins. These so-called myokines have been proposed to affect muscle physiology and to exert systemic effects on other tissues and organs. Yet, changes in the secretory profile may participate in the pathophysiology of metabolic diseases. The present study aimed at characterizing the secretome of differentiated primary human skeletal muscle cells (hSkMC) derived from healthy, adult donors combining three different mass spectrometry based non-targeted approaches as well as one antibody based method. This led to the identification of 548 non-redundant proteins in conditioned media from hSkmc. For 501 proteins, significant mRNA expression could be demonstrated. Applying stringent consecutive filtering using SignalP, SecretomeP and ER_retention signal databases, 305 proteins were assigned as potential myokines of which 12 proteins containing a secretory signal peptide were not previously described. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and may contribute to our understanding of the role of myokines in multiple biological processes. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013.

  6. Skeletal muscle abnormalities and genetic factors related to vertical talus.

    Science.gov (United States)

    Merrill, Laura J; Gurnett, Christina A; Connolly, Anne M; Pestronk, Alan; Dobbs, Matthew B

    2011-04-01

    Congenital vertical talus is a fixed dorsal dislocation of the talonavicular joint and fixed equinus contracture of the hindfoot, causing a rigid deformity recognizable at birth. The etiology and epidemiology of this condition are largely unknown, but some evidence suggests it relates to aberrations of skeletal muscle. Identifying the tissue abnormalities and genetic causes responsible for vertical talus has the potential to lead to improved treatment and preventive strategies. We therefore (1) determined whether skeletal muscle abnormalities are present in patients with vertical talus and (2) identified associated congenital anomalies and genetic abnormalities in these patients. We identified associated congenital anomalies and genetic abnormalities present in 61 patients affected with vertical talus. We obtained abductor hallucis muscle biopsy specimens from the affected limbs of 11 of the 61 patients and compared the histopathologic characteristics with those of age-matched control subjects. All muscle biopsy specimens (n = 11) had abnormalities compared with those from control subjects including combinations of abnormal variation in muscle fiber size (n = 7), type I muscle fiber smallness (n = 6), and abnormal fiber type predominance (n = 5). Isolated vertical talus occurred in 23 of the 61 patients (38%), whereas the remaining 38 patients had associated nervous system, musculoskeletal system, and/or genetic and genomic abnormalities. Ten of the 61 patients (16%) had vertical talus in one foot and clubfoot in the other. Chromosomal abnormalities, all complete or partial trisomies, were identified in three patients with vertical talus who had additional congenital abnormalities. Vertical talus is a heterogeneous birth defect resulting from many diverse etiologies. Abnormal skeletal muscle biopsies are common in patients with vertical talus although it is unclear whether this is primary or secondary to the joint deformity. Associated anomalies are present in 62

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Margaret N. Deane

    2014-08-01

    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.

  9. 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.

  10. 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.

  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. Skeletal, cardiac, and smooth muscle failure in Duchenne muscular dystrophy.

    Science.gov (United States)

    Boland, B J; Silbert, P L; Groover, R V; Wollan, P C; Silverstein, M D

    1996-01-01

    The goals of this study were to describe the clinical course of skeletal, cardiac, and gastrointestinal muscle manifestations and trends in age at diagnosis and survival of Duchenne muscular dystrophy (DMD) patients. A retrospective cohort of 33 male patients with DMD, born between 1953 and 1983 and followed at the Mayo Clinic during their second decade of life, was studied. The mean age at DMD diagnosis was 4.6 years. Skeletal muscle weakness present in all patients at diagnosis progressed to wheelchair dependency in 32 patients (97%) by the age of 13 years (median age 10 years). Cardiac muscle failure developed in 5 patients (15%) (median age 21.5 years). Smooth muscle manifestations related to the digestive and urinary tracts occurred in 7 (21%) and 2 (6%) patients (median age 15 years), respectively. The gastrointestinal dilatations were primary in 2 patients or secondary to surgery or acute respiratory illness in 5 patients. By the end of the study period, 17 deaths had occurred (median age 17 years). Over time, there was a decrease in the time to DMD diagnosis (P = .05) but no significant change in survival (P = .44). Cardiac and smooth muscle manifestations occur late in the course of DMD. Clinical gastrointestinal symptoms related to smooth muscle function most often were secondary to surgery or a respiratory illness. In recent years, the diagnosis of DMD has been made at a younger age, but survival has not changed.

  13. Implementation of skeletal muscle model with advanced activation control

    Directory of Open Access Journals (Sweden)

    Kocková H.

    2009-12-01

    Full Text Available The paper summarizes main principles of an advanced skeletal muscle model. The proposed mathematical model is suitable for a 3D muscle representation. It respects the microstructure of the muscle which is represented by three basic components: active fibers, passive fibers and a matrix. For purposes of presented work the existing material models suitable for the matrix and passive fibers are used and a new active fiber model is proposed. The active fiber model is based on the sliding cross-bridge theory of contraction. This theory is often used in modeling of skeletal and cardiac muscle contractions. In this work, a certain simplification of the cross-bridge distribution function is proposed, so that the 3D computer implementation becomes feasible. The new active fiber model is implemented into our research finite element code. A simple 3D muscle bundle-like model is created and the implemented composite model (involving the matrix, passive and active fibers is used to perform the isometric, concentric and excentric muscle contraction simulations.

  14. Skeletal muscle aging: influence of oxidative stress and physical exercise.

    Science.gov (United States)

    Gomes, Mariana Janini; Martinez, Paula Felippe; Pagan, Luana Urbano; Damatto, Ricardo Luiz; Cezar, Marcelo Diacardia Mariano; Lima, Aline Regina Ruiz; Okoshi, Katashi; Okoshi, Marina Politi

    2017-03-21

    Skeletal muscle abnormalities are responsible for significant disability in the elderly. Sarcopenia is the main alteration occurring during senescence and a key public health issue as it predicts frailty, poor quality of life, and mortality. Several factors such as reduced physical activity, hormonal changes, insulin resistance, genetic susceptibility, appetite loss, and nutritional deficiencies are involved in the physiopathology of muscle changes. Sarcopenia is characterized by structural, biochemical, molecular and functional muscle changes. An imbalance between anabolic and catabolic intracellular signaling pathways and an increase in oxidative stress both play important roles in muscle abnormalities. Currently, despite the discovery of new targets and development of new drugs, nonpharmacological therapies such as physical exercise and nutritional support are considered the basis for prevention and treatment of age-associated muscle abnormalities. There has been an increase in information on signaling pathways beneficially modulated by exercise; nonetheless, studies are needed to establish the best type, intensity, and frequency of exercise to prevent or treat age-induced skeletal muscle alterations.

  15. Identification of new dystroglycan complexes in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available The dystroglycan complex contains the transmembrane protein β-dystroglycan and its interacting extracellular mucin-like protein α-dystroglycan. In skeletal muscle fibers, the dystroglycan complex plays an important structural role by linking the cytoskeletal protein dystrophin to laminin in the extracellular matrix. Mutations that affect any of the proteins involved in this structural axis lead to myofiber degeneration and are associated with muscular dystrophies and congenital myopathies. Because loss of dystrophin in Duchenne muscular dystrophy (DMD leads to an almost complete loss of dystroglycan complexes at the myofiber membrane, it is generally assumed that the vast majority of dystroglycan complexes within skeletal muscle fibers interact with dystrophin. The residual dystroglycan present in dystrophin-deficient muscle is thought to be preserved by utrophin, a structural homolog of dystrophin that is up-regulated in dystrophic muscles. However, we found that dystroglycan complexes are still present at the myofiber membrane in the absence of both dystrophin and utrophin. Our data show that only a minority of dystroglycan complexes associate with dystrophin in wild type muscle. Furthermore, we provide evidence for at least three separate pools of dystroglycan complexes within myofibers that differ in composition and are differentially affected by loss of dystrophin. Our findings indicate a more complex role of dystroglycan in muscle than currently recognized and may help explain differences in disease pathology and severity among myopathies linked to mutations in DAPC members.

  16. 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.

  17. The effect of pneumatic tourniquets on skeletal muscle physiology.

    Science.gov (United States)

    Patterson, S; Klenerman, L; Biswas, M; Rhodes, A

    1981-01-01

    The effect of 3- and 5-hour pneumatic tourniquets on skeletal muscle physiology was investigated. Maximum isometric tension development, contraction and half relaxation times were measured in the muscles lying immediately under and distal to the tourniquet. On release of the tourniquet no consistent difference between control and experimental muscles was observed with respect to contraction and half relaxation times; however, there was a marked reduction in maximum isometric tension development. On the sixth day after release of a 5-hour tourniquet, isometric tension was reduced to 2--20 per cent of the control value in the distal muscle and to 40--60 per cent of the control value in the compressed muscle. Six days after a 3-hour tourniquet the compressed muscle tension was reduced to approximately 80 per cent of the control value whilst in the distal muscle, tension development varied from normal to 64 per cent of the control value. Thus it is shown that the effect on muscle contraction after a 3-hour tourniquet is not immediately reversed by the restoration of the blood supply. A reduction in muscle strength follows which may take a week or more to recover.

  18. Sodium nitrate ingestion increases skeletal muscle nitrate content in humans.

    Science.gov (United States)

    Nyakayiru, Jean; Kouw, Imre W K; Cermak, Naomi M; Senden, Joan M; van Loon, Luc J C; Verdijk, Lex B

    2017-09-01

    Nitrate ([Formula: see text]) ingestion has been shown to have vasoactive and ergogenic effects that have been attributed to increased nitric oxide (NO) production. Recent observations in rodents suggest that skeletal muscle tissue serves as an endogenous [Formula: see text] "reservoir." The present study determined [Formula: see text] contents in human skeletal muscle tissue in a postabsorptive state and following ingestion of a sodium nitrate bolus (NaNO 3 ). Seventeen male, type 2 diabetes patients (age 72 ± 1 yr; body mass index 26.5 ± 0.5 kg/m 2 ; means ± SE) were randomized to ingest a dose of NaNO 3 (NIT; 9.3 mg [Formula: see text]/kg body wt) or placebo (PLA; 8.8 mg NaCl/kg body wt). Blood and muscle biopsy samples were taken before and up to 7 h following [Formula: see text] or placebo ingestion to assess [Formula: see text] [and plasma nitrite ([Formula: see text])] concentrations. Additionally, basal plasma and muscle [Formula: see text] concentrations were assessed in 10 healthy young (CON-Y; age 21 ± 1 yr) and 10 healthy older (CON-O; age 75 ± 1 yr) control subjects. In all groups, baseline [Formula: see text] concentrations were higher in muscle (NIT, 57 ± 7; PLA, 61 ± 7; CON-Y, 80 ± 10; CON-O, 54 ± 6 µmol/l) than in plasma (NIT, 35 ± 3; PLA, 32 ± 3; CON-Y, 38 ± 3; CON-O, 33 ± 3 µmol/l; P ≤ 0.011). Ingestion of NaNO 3 resulted in a sustained increase in plasma [Formula: see text], plasma [Formula: see text], and muscle [Formula: see text] concentrations (up to 185 ± 25 µmol/l) in the NIT group (time effect P nitrate ingestion is usually limited to the changes observed in plasma nitrate and nitrite concentrations. The present investigation assessed the skeletal muscle nitrate content in humans during the postabsorptive state, as well as following dietary nitrate ingestion. We show that basal nitrate content is higher in skeletal muscle tissue than in plasma and that ingestion of a dietary nitrate bolus strongly increases both plasma

  19. 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

    Skeletal muscle is well known to exhibit a high degree of plasticity depending on environmental changes, such as various oxygen concentrations. Studies of the oxygen-sensitive subunit alpha of hypoxia-inducible factor-1 (HIF-1) are difficult owing to the large variety of functionally diverse muscle......alpha protein level. Interestingly, none of the HIF-1alpha target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented...... here, support a key role for HIF-1alpha for maintaining muscle homeostasis in non-hypoxic conditions....

  20. Optical NIR monitoring of skeletal muscle contraction

    Science.gov (United States)

    Lago, Paolo; Gelmetti, Andrea; Pavesi, Roberta; Zambarbieri, Daniela

    1996-12-01

    NIR spectroscopy allows monitoring of muscle oxygenation and perfusion during contraction. The knowledge of modifications of blood characteristics in body tissues has relevant clinical interest. A compact and reliable device, which makes use of two laser diodes at 750 and 810 nm coupled with the skin surface through optical fibers, was tested. NIR and surface EMG signals during isometric contractions both in normal and ischaemic conditions were analyzed. A set of parameters from the 750/810 spectroscopic curve was analyzed. Two different categories depending on the recovery rate from maximal voluntary contraction to basal oxygenation conditions were found. This behavior can give information about metabolic modifications during muscle fatigue. Interesting results in testing isokinetic rehabilitation training were also obtained.

  1. Proteomic Analysis of Chicken Skeletal Muscle during Embryonic Development

    Directory of Open Access Journals (Sweden)

    Hongjia Ouyang

    2017-05-01

    Full Text Available Embryonic growth and development of skeletal muscle is a major determinant of muscle mass, and has a significant effect on meat production in chicken. To assess the protein expression profiles during embryonic skeletal muscle development, we performed a proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ in leg muscle tissues of female Xinghua chicken at embryonic age (E 11, E16, and 1-day post hatch (D1. We identified 3,240 proteins in chicken embryonic muscle and 491 of them were differentially expressed (fold change ≥ 1.5 or ≤ 0.666 and p < 0.05. There were 19 up- and 32 down-regulated proteins in E11 vs. E16 group, 238 up- and 227 down-regulated proteins in E11 vs. D1 group, and 13 up- and 5 down-regulated proteins in E16 vs. D1 group. Protein interaction network analyses indicated that these differentially expressed proteins were mainly involved in the pathway of protein synthesis, muscle contraction, and oxidative phosphorylation. Integrative analysis of proteome and our previous transcriptome data found 189 differentially expressed proteins that correlated with their mRNA level. The interactions between these proteins were also involved in muscle contraction and oxidative phosphorylation pathways. The lncRNA-protein interaction network found four proteins DMD, MYL3, TNNI2, and TNNT3 that are all involved in muscle contraction and may be lncRNA regulated. These results provide several candidate genes for further investigation into the molecular mechanisms of chicken embryonic muscle development, and enable us to better understanding their regulation networks and biochemical pathways.

  2. Cylindrical spirals in human skeletal muscle.

    Science.gov (United States)

    Carpenter, S; Karpati, G; Robitaille, Y; Melmed, C

    1979-01-01

    Muscle biopsies from two patients revealed that numerous type 2 fibers contained large abnormal areas filled with cylindrical spirals. The cytochemical profile of these cylindrical spirals was sufficiently characteristic that they could be distinguished from tubular aggregates. Their electron microscopic appearance was unmistakable. Their origin and significance are uncertain. The diverse nature of the patients' conditions (cramps and malignancy, and an unusual form of spinocerebellar degeneration) indicate that these abnormal structures are not disease specific.

  3. Adaptations of mouse skeletal muscle to low intensity vibration training

    Science.gov (United States)

    McKeehen, James N.; Novotny, Susan A.; Baltgalvis, Kristen A.; Call, Jarrod A.; Nuckley, David J.; Lowe, Dawn A.

    2013-01-01

    Purpose We tested the hypothesis that low intensity vibration training in mice improves contractile function of hindlimb skeletal muscles and promotes exercise-related cellular adaptations. Methods We subjected C57BL/6J mice to 6 wk, 5 d·wk−1, 15 min·d−1 of sham or low intensity vibration (45 Hz, 1.0 g) while housed in traditional cages (Sham-Active, n=8; Vibrated-Active, n=10) or in small cages to restrict physical activity (Sham-Restricted, n=8; Vibrated-Restricted, n=8). Contractile function and resistance to fatigue were tested in vivo (anterior and posterior crural muscles) and ex vivo on the soleus muscle. Tibialis anterior and soleus muscles were evaluated histologically for alterations in oxidative metabolism, capillarity, and fiber types. Epididymal fat pad and hindlimb muscle masses were measured. Two-way ANOVAs were used to determine effects of vibration and physical inactivity. Results Vibration training resulted in a 10% increase in maximal isometric torque (P=0.038) and 16% faster maximal rate of relaxation (P=0.030) of the anterior crural muscles. Posterior crural muscles were unaffected by vibration, with the exception of greater rates of contraction in Vibrated-Restricted mice compared to Vibrated-Active and Sham-Restricted mice (P=0.022). Soleus muscle maximal isometric tetanic force tended to be greater (P=0.057) and maximal relaxation was 20% faster (P=0.005) in Vibrated compared to Sham mice. Restriction of physical activity induced muscle weakness but was not required for vibration to be effective in improving strength or relaxation. Vibration training did not impact muscle fatigability or any indicator of cellular adaptation investigated (P≥0.431). Fat pad but not hindlimb muscle masses were affected by vibration training. Conclusion Vibration training in mice improved muscle contractility, specifically strength and relaxation rates, with no indication of adverse effects to muscle function or cellular adaptations. PMID:23274599

  4. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

    OpenAIRE

    Yoon, Mee-Sup

    2017-01-01

    Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrop...

  5. Skeletal Muscle Responses to Negative Energy Balance: Effects of Dietary Protein12

    OpenAIRE

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

    2012-01-01

    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 ...

  6. Thermal unfolding of Acanthamoeba myosin II and skeletal muscle myosin.

    Science.gov (United States)

    Zolkiewski, M; Redowicz, M J; Korn, E D; Ginsburg, A

    1996-04-16

    Studies on the thermal unfolding of monomeric Acanthamoeba myosin II and other myosins, in particular skeletal muscle myosin, using differential scanning calorimetry (DSC) are reviewed. The unfolding transitions for intact myosin or its head fragment are irreversible, whereas those of the rod part and its fragments are completely reversible. Acanthamoeba myosin II unfolds with a high degree of cooperativity from ca. 40-45 degrees C at pH 7.5 in 0.6 M KCl, producing a single, sharp endotherm in DSC. In contrast, thermal transitions of rabbit skeletal muscle myosin occur over a broader temperature range (ca. 40-60 degrees C) under the same conditions. The DSC studies on the unfolding of the myosin rod and its fragments allow identification of cooperative domains, each of which unfolds according to a two-state mechanism. Also, DSC data show the effect of the nucleotide-induced conformational changes in the myosin head on the protein stability.

  7. 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....

  8. 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.

  9. Training increases the concentration of [3H]ouabain-binding sites in rat skeletal muscle

    DEFF Research Database (Denmark)

    Kjeldsen, K; Richter, Erik; Galbo, H

    1986-01-01

    ]ouabain-binding-site concentration in the diaphragm, but in the heart ventricles, the K+-dependent 3-O-methylfluorescein phosphatase activity increased by 20% (P less than 0.001). Muscle inactivity induced by denervation, plaster immobilisation or tenotomy reduced the [3H]ouabain-binding-site concentration by 20-30% (P less than 0...

  10. 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 control leg, together with venous blood samples, were obtained prior to exercise and at 45 min, 24, 48 and 96 h after exercise. The time courses of xanthine oxidase immunoreactivity and indicators of muscle damage and inflammation were examined. 2. The number of xanthine oxidase structures observed...... by immunohistological methods in the exercised muscle was up to eightfold higher than control from day 1 to day 4 after exercise (P

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

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content......, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase......, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene...

  12. Purinergic receptors expressed in human skeletal muscle fibres

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... 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...... and sarcolemma. P2Y(4) receptors were present in sarcolemma. P2Y(11) receptors were abundantly and diffusely expressed intracellularly and were more explicitly expressed in type I than in type II fibres, whereas P2X(1) and P2Y(4) showed no fibre-type specificity. Both diabetic patients and healthy controls...

  13. 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 control leg, together with venous blood samples, were obtained prior to exercise and at 45 min, 24, 48 and 96 h after exercise. The time courses of xanthine oxidase immunoreactivity and indicators of muscle damage and inflammation were examined. 2. The number of xanthine oxidase structures observed...... by immunohistological methods in the exercised muscle was up to eightfold higher than control from day 1 to day 4 after exercise (P xanthine oxidase in microvascular endothelial cells and an invasion of leucocytes containing xanthine oxidase. 3...

  14. Oxidation of urate in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

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

    1997-01-01

    the level was more than twofold higher and remained elevated throughout recovery (p exercise, probably due to generation of free radicals. Furthermore, the findings support the suggested importance of urate......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...... cycling exercise. Muscle samples were obtained from m. v. lateralis before and during the first few minutes after the exercise. Venous blood samples were obtained before and up to 45 min after the exercise. The concentration of urate in muscle decreased from a resting level of 0.26 +/- 0.023 to 0...

  15. 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.

  16. 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...

  17. 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....... The use of ultrasonography was helpful in selecting a suitable area for the biopsy and vascular structures could be avoided. The procedure was well tolerated and easy to perform, and no complications were recorded....

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

    Science.gov (United States)

    Wibberley, Anna; Staunton, Caroline A; Feetham, Claire H; Vereninov, Alexey A; Barrett-Jolley, Richard

    2015-01-01

    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.

  19. 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.

  20. 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.

  1. Computed tomography of skeletal muscles in neuromuscular disease

    International Nuclear Information System (INIS)

    Rodiek, S.O.; Kuether, G.; Muenchen Univ.

    1985-01-01

    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. (orig.) [de

  2. 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...... methylation of PGC-1a, PDK4, and PPAR-d was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene...

  3. Skeletal muscle: energy metabolism, fiber types, fatigue and adaptability.

    Science.gov (United States)

    Westerblad, Håkan; Bruton, Joseph D; Katz, Abram

    2010-11-01

    Skeletal muscles cope with a large range of activities, from being able to support the body weight during long periods of upright standing to perform explosive movements in response to an unexpected threat. This requires systems for energy metabolism that can provide energy during long periods of moderately increased energy consumption as well as being able to rapidly increasing the rate of energy production more than 100-fold in response to explosive contractions. In this short review we discuss how muscles can deal with these divergent demands. We first outline the major energy metabolism pathways in skeletal muscle. Next we describe metabolic differences between different muscle fiber types. Contractile performance declines during intense activation, i.e. fatigue develops, and we discuss likely underlying mechanisms. Finally, we discuss the ability of muscle fibers to adapt to altered demands, and mechanisms behind these adaptations. The accumulated experimental evidence forces us to conclude that most aspects of energy metabolism involve multiple and overlapping signaling pathways, which indicates that the control of energy metabolism is too important to depend on one single molecule or mechanism. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. Prioritization of skeletal muscle growth for emergence from hibernation.

    Science.gov (United States)

    Hindle, Allyson G; Otis, Jessica P; Epperson, L Elaine; Hornberger, Troy A; Goodman, Craig A; Carey, Hannah V; Martin, Sandra L

    2015-01-15

    Mammalian hibernators provide an extreme example of naturally occurring challenges to muscle homeostasis. The annual hibernation cycle is characterized by shifts between summer euthermy with tissue anabolism and accumulation of body fat reserves, and winter heterothermy with fasting and tissue catabolism. The circannual patterns of skeletal muscle remodelling must accommodate extended inactivity during winter torpor, the motor requirements of transient winter active periods, and sustained activity following spring emergence. Muscle volume in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) calculated from MRI upper hindlimb images (n=6 squirrels, n=10 serial scans) declined from hibernation onset, reaching a nadir in early February. Paradoxically, mean muscle volume rose sharply after February despite ongoing hibernation, and continued total body mass decline until April. Correspondingly, the ratio of muscle volume to body mass was steady during winter atrophy (October-February) but increased (+70%) from February to May, which significantly outpaced changes in liver or kidney examined by the same method. Generally stable myocyte cross-sectional area and density indicated that muscle remodelling is well regulated in this hibernator, despite vastly altered seasonal fuel and activity levels. Body composition analysis by echo MRI showed lean tissue preservation throughout hibernation amid declining fat mass by the end of winter. Muscle protein synthesis was 66% depressed in early but not late winter compared with a summer fasted baseline, while no significant changes were observed in the heart, liver or intestine, providing evidence that could support a transition in skeletal muscle regulation between early and late winter, prior to spring emergence and re-feeding. © 2015. Published by The Company of Biologists Ltd.

  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. 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.

  9. Skeletal Muscle Channelopathies: Rare Disorders with Common Pediatric Symptoms.

    Science.gov (United States)

    Matthews, Emma; Silwal, Arpana; Sud, Richa; Hanna, Michael G; Manzur, Adnan Y; Muntoni, Francesco; Munot, Pinki

    2017-09-01

    To ascertain the presenting symptoms of children with skeletal muscle channelopathies to promote early diagnosis and treatment. Retrospective case review of 38 children with a skeletal muscle channelopathy attending the specialist pediatric neuromuscular service at Great Ormond Street Hospital over a 15-year period. Gait disorder and leg cramps are a frequent presentation of myotonic disorders (19 of 29). Strabismus or extraocular myotonia (9 of 19) and respiratory and/or bulbar symptoms (11 of 19) are common among those with sodium channelopathy. Neonatal hypotonia was observed in periodic paralysis. Scoliosis and/or contractures were demonstrated in 6 of 38 children. School attendance or ability to engage fully in all activities was often limited (25 of 38). Children with skeletal muscle channelopathies frequently display symptoms that are uncommon in adult disease. Any child presenting with abnormal gait, leg cramps, or strabismus, especially if intermittent, should prompt examination for myotonia. Those with sodium channel disease should be monitored for respiratory or bulbar complications. Neonatal hypotonia can herald periodic paralysis. Early diagnosis is essential for children to reach their full educational potential. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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.

  11. Low intensity exercise training improves skeletal muscle regeneration potential

    Directory of Open Access Journals (Sweden)

    Tiziana ePietrangelo

    2015-12-01

    Full Text Available Purpose: The aim of this study was to determine whether 12 days of low-to-moderate exercise training at low altitude (598 m a.s.l. improves skeletal muscle regeneration in sedentary adult women.Methods: Satellite cells were obtained from the vastus lateralis skeletal muscle of seven women before and after this exercise training at low altitude. They were investigated for differentiation aspects, superoxide anion production, antioxidant enzymes, mitochondrial potential variation after a depolarizing insult, intracellular Ca2+ concentrations, and micro (miRNA expression (miR-1, miR-133, miR-206.Results: In these myogenic populations of adult stem cells, those obtained after exercise training, showed increased Fusion Index and intracellular Ca2+ concentrations. This exercise training also generally reduced superoxide anion production in cells (by 12% to 67%, although not in two women, where there was an increase of ~15% along with a reduced superoxide dismutase activity. miRNA expression showed an exercise-induced epigenetic transcription profile that was specific according to the reduced or increased superoxide anion production of the cells. Conclusions: The present study shows that low-to-moderate exercise training at low altitude improves the regenerative capacity of skeletal muscle in adult women. The differentiation of cells was favored by increased intracellular calcium concentration and increased the fusion index. This low-to-moderate training at low altitude also depicted the epigenetic signature of cells.

  12. CT-guided injection of botulinic toxin for percutaneous therapy of piriformis muscle syndrome with preliminary MRI results about denervative process

    Energy Technology Data Exchange (ETDEWEB)

    Fanucci, E.; Masala, S.; Sodani, G.; Varrucciu, V.; Romagnoli, A.; Squillaci, E.; Simonetti, G. [Dept. of Radiology, Univ. of Rome (Italy)

    2001-12-01

    Piriformis muscle syndrome (PMS) is a cause of sciatica, leg or buttock pain and disability. The pain is usually increased by muscular contraction, palpation or prolonged sitting. The aim of our paper was to evaluate the feasibility of CT-guided percutaneous botulinic toxin (BTX) injection for the purpose of PMS treatment. Thirty patients suffering from PMS, suspected with clinical and electrophysiological criteria, after imaging examinations excluding other causes of sciatic pain, resulted positive at the lidocaine test and were treated by intramuscular injection of BTX type A under CT guidance. The follow-up (12 months) was performed with clinical examination in all cases and with MR 3 months after the procedure in 9 patients to evaluate the denervative process entity of the treated muscle. In 26 cases relief of symptoms was obtained after 5-7 days. In 4 patients an insufficient relief of pain justified a second percutaneous treatment which was clinically successful. No complications or side effects were recorded after BTX injection. The MR examination showed a signal intensity change of the treated muscle in 7 patients due to the denervative process of PM, whereas in the remaining 2 cases only an atrophy of the treated muscle was detected. Larger series are necessary to confirm these MRI preliminary results. The CT-guided BTX injection in the PMS is an emergent and feasible technique that obtains an excellent local therapeutic effect without risk of imprecise inoculation. (orig.)

  13. Denervation of the infraspinatus and release of the posterior deltoid muscles in the management of dyskinetic external shoulder rotation in cerebral palsy.

    Science.gov (United States)

    Blaszczyk, Izabela; Granström, Anna Cecilia; Wiberg, Mikael

    2015-04-01

    The dyskinetic subtype of cerebral palsy is difficult to manage, and there is no established gold standard for treatment. External rotation of the shoulder(s) is often managed nonsurgically using injections of botulinum toxin A into the external rotator muscles. This article reports a new surgical technique for managing external rotation when botulinum toxin A treatment is not sufficient or possible. Six patients with dyskinetic cerebral palsy underwent denervation of the infraspinatus muscle and release of the posterior part of the deltoid muscle. Postoperative questionnaires were given to the patients/caregivers, and video recordings were made both pre- and postoperatively. Preoperative and postoperative Assisting Hand Assessment was possible in only 1 case. Five patients were very satisfied with their outcome. Four patients' video recordings showed improvement in their condition. One patient developed postoperative complications. The results indicate that denervation of the infraspinatus muscle and posterior deltoid release can be an option for patients with dyskinetic cerebral palsy to manage external rotation of the shoulder when other treatment alternatives are insufficient.

  14. Adaptation of muscle fibre types and capillary network to acute denervation and shortlasting reinnervation

    Czech Academy of Sciences Publication Activity Database

    Čebašek, V.; Kubínová, Lucie; Janáček, Jiří; Ribarič, S.; Eržen, I.

    2007-01-01

    Roč. 330, č. 2 (2007), s. 279-289 ISSN 0302-766X R&D Projects: GA MŠk(CZ) LC06063 Grant - others:KONTAKT(SI) 9-06-6 Institutional research plan: CEZ:AV0Z50110509 Keywords : capillaries * rat extensor digitorum longus muscle * stereology Subject RIV: EA - Cell Biology Impact factor: 2.613, year: 2007

  15. Regulation of PGC-1α and exercise training-induced metabolic adaptations in skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina

    and intracellular signalling in human skeletal muscle depend on adrenaline levels or metabolic stress. 2) PGC-1α mediated exercise and exercise training-induced adaptive metabolic responses in mouse skeletal muscle depend on exercise intensity. 3) β-adrenergic signalling contributes to exercise training......-induced metabolic adaptations in mouse skeletal muscle through PGC-1α . Paper I demonstrated that di erences in plasma adrenaline and muscle metabolic stress during exercise do not reinforce exercise-induced PGC-1 α mRNA response in human skeletal muscle. In addition, di erences in exercise-induced AMPK and p38......-adrenergic signaling mediates exercise-induced PGC-1α mRNA responses with most potent stimulation of the alternative promoter of the PGC-1α gene in mouse skeletal muscle but, neither elevated plasma adrenaline nor metabolic stress augment exercise-induced PGC-1α mRNA response in human skeletal muscle. While...

  16. Renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

    2015-01-01

    PURPOSE OF REVIEW: Renal denervation (RDN) has, within recent years, been suggested as a novel treatment option for patients with resistant hypertension. This review summarizes the current knowledge on this procedure as well as limitations and questions that remain to be answered. RECENT FINDINGS...

  17. Home-based Functional Electrical Stimulation for long-term denervated human muscle: History, basics, results and perspectives of the Vienna Rehabilitation Strategy

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2014-03-01

    Full Text Available We will here discuss the following points related to Home-based Functional Electrical Stimulation (h-b FES as treatment for patients with permanently denervated muscles in their legs: 1. Upper (UMN and lower motor neuron (LMN damage to the lower spinal cord; 2. Muscle atrophy/hypertrophy versus processes of degeneration, regeneration, and recovery; 3. Recovery of twitch- and tetanic-contractility by h-b FES; 4. Clinical effects of h-b FES using the protocol of the “Vienna School”; 5. Limitations and perspectives. Arguments in favor of using the Vienna protocol include: 1. Increased muscle size in both legs; 2. Improved tetanic force production after 3-5 months of percutaneous stimulation using long stimulus pulses (> 100 msec of high amplitude (> 80 mAmp, tolerated only in patients with no pain sensibility; 3. Histological and electron microscopic evidence that two years of h-b FES return muscle fibers to a state typical of two weeks denervated muscles with respect to atrophy, disrupted myofibrillar structure, and disorganized Excitation-Contraction Coupling (E-CC structures; 4. The excitability never recovers to that typical of normal or reinnervated muscles where pulses less than 1 msec in duration and 25 mAmp in intensity excite axons and thereby muscle fibres. It is important to motivate these patients for chronic stimulation throughout life, preferably standing up against the load of the body weight rather than sitting. Only younger and low weight patients can expect to be able to stand-up and do some steps more or less independently. Some patients like to maintain the h-b FES training for decades. Limitations of the procedure are obvious, in part related to the use of multiple, large surface electrodes and the amount of time patients are willing to use for such muscle training.

  18. Home-Based Functional Electrical Stimulation for Long-Term Denervated Human Muscle: History, Basics, Results and Perspectives of the Vienna Rehabilitation Strategy.

    Science.gov (United States)

    Kern, Helmut; Carraro, Ugo

    2014-03-31

    We will here discuss the following points related to Home-based Functional Electrical Stimulation (h-b FES) as treatment for patients with permanently denervated muscles in their legs: 1. Upper (UMN) and lower motor neuron (LMN) damage to the lower spinal cord; 2. Muscle atrophy/hypertrophy versus processes of degeneration, regeneration, and recovery; 3. Recovery of twitch- and tetanic-contractility by h-b FES; 4. Clinical effects of h-b FES using the protocol of the "Vienna School"; 5. Limitations and perspectives. Arguments in favor of using the Vienna protocol include: 1. Increased muscle size in both legs; 2. Improved tetanic force production after 3-5 months of percutaneous stimulation using long stimulus pulses (> 100 msec) of high amplitude (> 80 mAmp), tolerated only in patients with no pain sensibility; 3. Histological and electron microscopic evidence that two years of h-b FES return muscle fibers to a state typical of two weeks denervated muscles with respect to atrophy, disrupted myofibrillar structure, and disorganized Excitation-Contraction Coupling (E-CC) structures; 4. The excitability never recovers to that typical of normal or reinnervated muscles where pulses less than 1 msec in duration and 25 mAmp in intensity excite axons and thereby muscle fibres. It is important to motivate these patients for chronic stimulation throughout life, preferably standing up against the load of the body weight rather than sitting. Only younger and low weight patients can expect to be able to stand-up and do some steps more or less independently. Some patients like to maintain the h-b FES training for decades. Limitations of the procedure are obvious, in part related to the use of multiple, large surface electrodes and the amount of time patients are willing to use for such muscle training.

  19. Muscle-specific GSK-3β ablation accelerates regeneration of disuse-atrophied skeletal muscle.

    Science.gov (United States)

    Pansters, Nicholas A M; Schols, Annemie M W J; Verhees, Koen J P; de Theije, Chiel C; Snepvangers, Frank J; Kelders, Marco C J M; Ubags, Niki D J; Haegens, Astrid; Langen, Ramon C J

    2015-03-01

    Muscle wasting impairs physical performance, increases mortality and reduces medical intervention efficacy in chronic diseases and cancer. Developing proficient intervention strategies requires improved understanding of the molecular mechanisms governing muscle mass wasting and recovery. Involvement of muscle protein- and myonuclear turnover during recovery from muscle atrophy has received limited attention. The insulin-like growth factor (IGF)-I signaling pathway has been implicated in muscle mass regulation. As glycogen synthase kinase 3 (GSK-3) is inhibited by IGF-I signaling, we hypothesized that muscle-specific GSK-3β deletion facilitates the recovery of disuse-atrophied skeletal muscle. Wild-type mice and mice lacking muscle GSK-3β (MGSK-3β KO) were subjected to a hindlimb suspension model of reversible disuse-induced muscle atrophy and followed during recovery. Indices of muscle mass, protein synthesis and proteolysis, and post-natal myogenesis which contribute to myonuclear accretion, were monitored during the reloading of atrophied muscle. Early muscle mass recovery occurred more rapidly in MGSK-3β KO muscle. Reloading-associated changes in muscle protein turnover were not affected by GSK-3β ablation. However, coherent effects were observed in the extent and kinetics of satellite cell activation, proliferation and myogenic differentiation observed during reloading, suggestive of increased myonuclear accretion in regenerating skeletal muscle lacking GSK-3β. This study demonstrates that muscle mass recovery and post-natal myogenesis from disuse-atrophy are accelerated in the absence of GSK-3β. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. 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.

  1. 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

  2. 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

  3. Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity

    DEFF Research Database (Denmark)

    Skovbro, M; Baranowski, M; Skov-Jensen, C

    2008-01-01

    : The middle-aged male participants (n=33) were matched for lean body mass and divided into four groups: type 2 diabetes (T2D, n=8), impaired glucose tolerance (IGT, n=9), healthy controls (CON, n=8) and endurance-trained (TR, n=8). A two step (28 and 80 mU m(-2) min(-1)) sequential euglycaemic......AIMS/HYPOTHESIS: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. This study investigated total skeletal muscle ceramide fatty acid content in participants exhibiting a wide range of insulin sensitivities. METHODS...

  4. 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...

  5. Diversity effect of capsaicin on different types of skeletal muscle.

    Science.gov (United States)

    Zhou, Gan; Wang, Lina; Xu, Yaqiong; Yang, Kelin; Luo, Lv; Wang, Leshan; Li, Yongxiang; Wang, Jiawen; Shu, Gang; Wang, Songbo; Gao, Ping; Zhu, Xiaotong; Xi, Qianyun; Sun, Jiajie; Zhang, Yongliang; Jiang, Qingyan

    2017-11-20

    Capsaicin is a major pungent content in green and red peppers which are widely used as spice, and capsaicin may activate different receptors. To determine whether capsaicin has different effects on different types of skeletal muscle, we applied different concentrations (0, 0.01, and 0.02%) of capsaicin in the normal diet and conducted a four-week experiment on Sprague-Dawley rats. The fiber type composition, glucose metabolism enzyme activity, and different signaling molecules' expressions of receptors were detected. Our results suggested that capsaicin reduced the body fat deposition, while promoting the slow muscle-related gene expression and increasing the enzyme activity in the gastrocnemius and soleus muscles. However, fatty acid metabolism was significantly increased only in the soleus muscle. The study of intracellular signaling suggested that the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid receptors in the soleus muscle were more sensitive to capsaicin. In conclusion, the distribution of TRPV1 and cannabinoid receptors differs in different types of muscle, and the different roles of capsaicin in different types of muscle may be related to the different degrees of activation of receptors.

  6. 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.

  7. Reprimed charge movement in skeletal muscle fibres.

    Science.gov (United States)

    Rakowski, R F

    1978-08-01

    1. The three intracellular micro-electrode voltage-clamp technique was used to study the recovery of membrane charge movement in semitendinosus muscles of Rana pipiens. Muscles were placed in a hypertonic depolarizing solution to inactivate voltage dependent charge movement. Tetrodotoxin and tetraethylammonium ions (TEA+) were present to block voltage dependent ionic conductances. Rb+ and SO4(2-) were present to reduce inward rectification and leakage conductance. 2. The recovery ('repriming') of membrane charge movement was studied following hyperpolarizing pulses from a holding potential of -20 mV to membrane potentials from -30 to -140 mV for durations of 2--100 sec. The reprimed charge movement measured as the difference in membrane current required for identical voltage steps before and after long duration hyperpolarizing pulses was a linear function of membrane potential and symmetrical in shape. Reprimed charge is, therefore, simply the result of an increase in the linear capacitance of the fibre. 3. The mean value of the percent increase in capacitance for repriming at -100 mV was 12.3 +/- 1.7% (S.E. of mean) for 25 sec duration pulses and 27.8 +/- 2.9% for 100 sec duration pulses. If these data are corrected to the steady state and the surface contribution subtracted, the mean increase in 'volume' capacity is 40.3 +/- 3.6% (n = 21) for fibres with a mean diameter of 51 +/- 4 micron. 4. The increase in capacity can arise either by an increase in the transverse tubular length constant (lambdaT) or by gaining electrical access to additional linear capacitance within the fibre volume. If the capacitance arises solely from the transverse tubular system, the value of lambdaT before repriming can be no larger than 20 micron in order to explain the observed increase in volume capacity. A value of lambdaT as small as this seems unlikely. 5. The observation that reprimed charge is simply the result of an increase in linear capacitance is not consistent with the

  8. 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.

  9. Skeletal muscle mass and composition during mammalian hibernation.

    Science.gov (United States)

    Cotton, Clark J

    2016-01-01

    Hibernation is characterized by prolonged periods of inactivity with concomitantly low nutrient intake, conditions that would typically result in muscle atrophy combined with a loss of oxidative fibers. Yet, hibernators consistently emerge from winter with very little atrophy, frequently accompanied by a slight shift in fiber ratios to more oxidative fiber types. Preservation of muscle morphology is combined with down-regulation of glycolytic pathways and increased reliance on lipid metabolism instead. Furthermore, while rates of protein synthesis are reduced during hibernation, balance is maintained by correspondingly low rates of protein degradation. Proposed mechanisms include a number of signaling pathways and transcription factors that lead to increased oxidative fiber expression, enhanced protein synthesis and reduced protein degradation, ultimately resulting in minimal loss of skeletal muscle protein and oxidative capacity. The functional significance of these outcomes is maintenance of skeletal muscle strength and fatigue resistance, which enables hibernating animals to resume active behaviors such as predator avoidance, foraging and mating immediately following terminal arousal in the spring. © 2016. Published by The Company of Biologists Ltd.

  10. On the Behaviour of Porcine Adipose and Skeletal Muscle Tissues under Shock Compression

    Science.gov (United States)

    2012-09-01

    regarding the dynamic tensile behaviour of skeletal muscle, Morrow et al. [6] per- formed low-rate (0.05 % s−1) tensile tests upon extensor digitorum ... longus muscles from New Zealand White rabbits. This study into the ‘passive’ properties of skeletal muscle provided data for the ultimate tensile strength

  11. 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 ...... integrity....

  12. Charge movement and depolarization-contraction coupling in arthropod vs. vertebrate skeletal muscle.

    OpenAIRE

    Scheuer, T; Gilly, W F

    1986-01-01

    Voltage-dependent charge movement has been characterized in arthropod skeletal muscle. Charge movement in scorpion (Centuroides sculpturatus) muscle is distinguishable from that in vertebrate skeletal muscle by criteria of kinetics, voltage dependence, and pharmacology. The function of scorpion charge movement is gating of calcium channels in the sarcolemma, and depolarization-contraction coupling relies on calcium influx through these channels.

  13. Charge movement and depolarization-contraction coupling in arthropod vs. vertebrate skeletal muscle.

    Science.gov (United States)

    Scheuer, T; Gilly, W F

    1986-11-01

    Voltage-dependent charge movement has been characterized in arthropod skeletal muscle. Charge movement in scorpion (Centuroides sculpturatus) muscle is distinguishable from that in vertebrate skeletal muscle by criteria of kinetics, voltage dependence, and pharmacology. The function of scorpion charge movement is gating of calcium channels in the sarcolemma, and depolarization-contraction coupling relies on calcium influx through these channels.

  14. Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Christensen, Anders E; Nellemann, Birgitte

    2017-01-01

    In skeletal muscle, an accumulation of lipid droplets (LDs) in the subsarcolemmal space is associated with insulin resistance, but the underlying mechanism is not clear. We aimed to investigate how the size, number and location of LDs are associated with insulin sensitivity and muscle fiber types...... are associated with insulin resistance in skeletal 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. Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition

    Science.gov (United States)

    MacDonald, Elizabeth M.; Andres-Mateos, Eva; Mejias, Rebeca; Simmers, Jessica L.; Mi, Ruifa; Park, Jae-Sung; Ying, Stephanie; Hoke, Ahmet; Lee, Se-Jin; Cohn, Ronald D.

    2014-01-01

    The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization) and denervation (sciatic nerve resection) atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK) rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy. PMID:24504412

  18. Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition.

    Science.gov (United States)

    MacDonald, Elizabeth M; Andres-Mateos, Eva; Mejias, Rebeca; Simmers, Jessica L; Mi, Ruifa; Park, Jae-Sung; Ying, Stephanie; Hoke, Ahmet; Lee, Se-Jin; Cohn, Ronald D

    2014-04-01

    The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization) and denervation (sciatic nerve resection) atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK) rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.

  19. Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition

    Directory of Open Access Journals (Sweden)

    Elizabeth M. MacDonald

    2014-04-01

    Full Text Available The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization and denervation (sciatic nerve resection atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.

  20. Alpha-adrenergic receptors in rat skeletal muscle

    DEFF Research Database (Denmark)

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

    1986-01-01

    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...... by approx. 10:1. Binding sites for idazoxan (alpha 2 antagonist) were undetectable. Contamination of sarcolemma-enriched preparations by endothelial tissue indicated by the activity of angiotensin converting enzyme did not correlate with prazosin binding. It is concluded that post-synaptic alpha 1...... 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....

  1. Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function.

    Directory of Open Access Journals (Sweden)

    Brian Lin

    Full Text Available Myosin binding protein-C (MyBP-C exists in three major isoforms: slow skeletal, fast skeletal, and cardiac. While cardiac MyBP-C (cMyBP-C expression is restricted to the heart in the adult, it is transiently expressed in neonatal stages of some skeletal muscles. However, it is unclear whether this expression is necessary for the proper development and function of skeletal muscle. Our aim was to determine whether the absence of cMyBP-C alters the structure, function, or MyBP-C isoform expression in adult skeletal muscle using a cMyBP-C null mouse model (cMyBP-C((t/t. Slow MyBP-C was expressed in both slow and fast skeletal muscles, whereas fast MyBP-C was mostly restricted to fast skeletal muscles. Expression of these isoforms was unaffected in skeletal muscle from cMyBP-C((t/t mice. Slow and fast skeletal muscles in cMyBP-C((t/t mice showed no histological or ultrastructural changes in comparison to the wild-type control. In addition, slow muscle twitch, tetanus tension, and susceptibility to injury were all similar to the wild-type controls. Interestingly, fMyBP-C expression was significantly increased in the cMyBP-C((t/t hearts undergoing severe dilated cardiomyopathy, though this does not seem to prevent dysfunction. Additionally, expression of both slow and fast isoforms was increased in myopathic skeletal muscles. Our data demonstrate that i MyBP-C isoforms are differentially regulated in both cardiac and skeletal muscles, ii cMyBP-C is dispensable for the development of skeletal muscle with no functional or structural consequences in the adult myocyte, and iii skeletal isoforms can transcomplement in the heart in the absence of cMyBP-C.

  2. Three-dimensional optical coherence micro-elastography of skeletal muscle tissue

    OpenAIRE

    Chin, Lixin; Kennedy, Brendan F.; Kennedy, Kelsey M.; Wijesinghe, Philip; Pinniger, Gavin J.; Terrill, Jessica R.; McLaughlin, Robert A.; Sampson, David D.

    2014-01-01

    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 t...

  3. Muscle size explains low passive skeletal muscle force in heart failure patients

    Directory of Open Access Journals (Sweden)

    Fausto Antonio Panizzolo

    2016-09-01

    Full Text Available Background Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF. However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL, both in CHF patients and age- and physical activity-matched control participants. Methods Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging with a musculoskeletal model. Results We found reduced passive SOL forces (∼30% (at the same relative levels of muscle stretch in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. Discussion These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening.

  4. Site-dependent pathological differences in smooth muscles and skeletal muscles of the adult mdx mouse.

    Science.gov (United States)

    Boland, B; Himpens, B; Denef, J F; Gillis, J M

    1995-06-01

    This study presents a survey of the morphometric characteristics, the regeneration rate, and the extent of muscle dystrophy in several smooth and skeletal muscles from adult mdx mice, an animal model of the Duchenne muscular dystrophy (DMD). Smooth muscles from adult mdx mice showed neither cell necrosis nor fibrosis. As compared to control C57 mice, the thickness of the mdx smooth muscle was normal in the vascular and urogenital layers but significantly reduced in the digestive layers, a finding relevant to clinical reports of gastrointestinal dilatation in DMD patients, and suggesting that gastrointestinal dysfunctions should be systemically searched for in DMD patients. Adult mdx skeletal muscles, however, presented different patterns of muscle suffering: either absent (esophagus); very mild (trunk and limb muscles); or severe (diaphragm). In these three conditions we studied the fiber diameters, the nuclei locations, and the regeneration rate. From this comparative study, it seems that severe dystrophy occurs in muscle tissues showing large fiber diameter and peripheral location of the nuclei. We showed that this combination occurs in the mouse diaphragm which is thus a realistic model for human DMD muscles.

  5. Slow charge movement in mammalian skeletal muscle.

    Science.gov (United States)

    Simon, B J; Beam, K G

    1985-01-01

    Voltage-dependent charge movements were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Contraction was abolished with hypertonic sucrose. The standard (ON-OFF) protocol for eliciting charge movements was to depolarize the fiber from -90 mV to a variable test potential (V) and then repolarize the fiber to -90 mV. The quantity of charge moved saturated at test potentials of approximately 0 mV. The steady state dependence of the amount of charge that moves as a function of test potential could be well fitted by the Boltzmann relation: Q = Qmax/(1 + exp[-(V - V)/k]), where Qmax is the maximum charge that can be moved, V is the potential at which half the charge moves, and k is a constant. At 15 degrees C, these values were Qmax = 28.5 nC/microF, V = -34.2 mV, and k = 8.7 mV. Qmax, k, and V exhibited little temperature dependence over the range 7-25 degrees C. "Stepped OFF" charge movements were elicited by depolarizing the fiber from -90 mV to a fixed conditioning level that moved nearly all the mobile charge (0 mV), and then repolarizing the fiber to varying test potentials. The sum of the charge that moved when the fiber was depolarized directly from -90 mV to a given test potential and the stepped OFF charge that moved when the fiber was repolarized to the same test potential had at all test potentials a value close to Qmax for that fiber. In nearly all cases, the decay phase of ON, OFF, and stepped OFF charge movements could be well fitted with a single exponential. The time constant, tau decay, for an ON charge movement at a given test potential was comparable to tau decay for a stepped OFF charge movement at the same test potential. Tau decay had a bell-shaped dependence on membrane potential: it was slowest at a potential near V (the midpoint of the steady state charge distribution) and became symmetrically faster on either side of this potential. Raising the temperature from 7 to 15 degrees C caused tau decay to

  6. The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-09-01

    Conclusions: Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity.

  7. Delta-like 1 homolog (dlk1): a marker for rhabdomyosarcomas implicated in skeletal muscle regeneration

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Sellathurai, Jeeva; Davis, Erica E

    2013-01-01

    primitive childhood tumors to date. Here, we investigate the possible roles of Dlk1 in skeletal muscle tumor formation. We analyzed tumors of different mesenchymal origin for expression of Dlk1 and various myogenic markers and found that Dlk1 was present consistently in myogenic tumors. The coincident...... that Dlk1 is a candidate marker for skeletal muscle tumors and might be involved directly in skeletal muscle tumor formation through a modulatory effect on the myogenic programme....

  8. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans

    DEFF Research Database (Denmark)

    Karamouzis, M; Langberg, Henning; Skovgaard, D

    2001-01-01

    Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis...... amounts of prostaglandins and thromboxanes in the interstitial space of skeletal muscle. Furthermore, the concentration of prostaglandin E2 is unchanged during static calf exercise and increased markedly with dynamic thigh muscle exercise, which together with an exercise induced increase in muscle blood...... flow indicate, that prostaglandin E2 is released from skeletal muscle during exercise in humans....

  9. 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.

  10. 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.

  11. Viscoelasticity-based MR elastography of skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Klatt, Dieter; Papazoglou, Sebastian; Sack, Ingolf [Department of Radiology, Charite-Universitaetsmedizin, Berlin (Germany); Braun, Juergen, E-mail: ingolf.sack@charite.d [Institute of Medical Informatics, Charite-Universitaetsmedizin, Berlin (Germany)

    2010-11-07

    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, {mu} and {alpha}, from the dispersion functions of the complex shear modulus in relaxed and in loaded muscle. Representing the shear elasticity parallel to the muscle fibers, {mu} increased in all volunteers upon contraction from 2.68 {+-} 0.23 kPa to 3.87 {+-} 0.50 kPa. Also {alpha} varied with load, indicating a change in the geometry of the mechanical network of muscle from relaxation ({alpha} = 0.253 {+-} 0.009) to contraction ({alpha} = 0.270 {+-} 0.009). These results provide a reference for a future assessment of muscular dysfunction using rheological parameters.

  12. Viscoelasticity-based MR elastography of skeletal muscle

    International Nuclear Information System (INIS)

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

    2010-01-01

    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.

  13. 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.

  14. Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae.

    Science.gov (United States)

    Rodrigues, Alexandre Miguel Cavaco; Christen, Bea; Martí, Mercé; Izpisúa Belmonte, Juan Carlos

    2012-02-27

    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. 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. 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.

  15. Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae

    Science.gov (United States)

    2012-01-01

    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. PMID:22369050

  16. Identification of telocytes in skeletal muscle interstitium: implication for muscle regeneration.

    Science.gov (United States)

    Popescu, L M; Manole, Emilia; Serboiu, Crenguţa S; Manole, C G; Suciu, Laura C; Gherghiceanu, Mihaela; Popescu, B O

    2011-06-01

    Skeletal muscle interstitium is crucial for regulation of blood flow, passage of substances from capillaries to myocytes and muscle regeneration. We show here, probably, for the first time, the presence of telocytes (TCs), a peculiar type of interstitial (stromal) cells, in rat, mouse and human skeletal muscle. TC features include (as already described in other tissues) a small cell body and very long and thin cell prolongations-telopodes (Tps) with moniliform appearance, dichotomous branching and 3D-network distribution. Transmission electron microscopy (TEM) revealed close vicinity of Tps with nerve endings, capillaries, satellite cells and myocytes, suggesting a TC role in intercellular signalling (via shed vesicles or exosomes). In situ immunolabelling showed that skeletal muscle TCs express c-kit, caveolin-1 and secrete VEGF. The same phenotypic profile was demonstrated in cell cultures. These markers and TEM data differentiate TCs from both satellite cells (e.g. TCs are Pax7 negative) and fibroblasts (which are c-kit negative). We also described non-satellite (resident) progenitor cell niche. In culture, TCs (but not satellite cells) emerge from muscle explants and form networks suggesting a key role in muscle regeneration and repair, at least after trauma. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  17. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Birk, Jesper Bratz

    2015-01-01

    The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα md.......01), indicating a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPKα mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 (cluster of differentiation 36...... to sarcolemma, respectively. AMPKα is thus required for normal FA metabolism during exercise and muscle contraction.-Fentz, J., Kjøbsted, R., Birk, J. B., Jordy, A. B., Jeppesen, J., Thorsen, K., Schjerling, P., Kiens, B., Jessen, N., Viollet, B., Wojtaszewski, J. F. P. AMPKα is critical for enhancing skeletal...

  18. Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance

    Directory of Open Access Journals (Sweden)

    Sheila R. Costford

    2018-01-01

    Conclusions: Our studies have unveiled a fascinating interaction between elevated NAMPT activity in skeletal muscle and voluntary exercise that was manifest as a striking improvement in exercise endurance.

  19. Human skeletal muscle aging and the oxidative system: cellular events.

    Science.gov (United States)

    Rossi, Paola; Marzani, Barbara; Giardina, Silvana; Negro, Massimo; Marzatico, Fulvio

    2008-12-01

    As we age, the aerobic and functional capacities of our major physiological systems progressively decline. In the case of the neuromuscular system, reductions in strength and mobility cause a deterioration in motor performance and in turn a greater tendency to fall (with increased risk of fractures), impaired mobility, disability and loss of independence in the elderly. Given the increase in our life expectancy and the consequent growth in the elderly population, these conditions will have an increasing impact on modern healthcare systems, and their prevention and attenuation needs to be addressed. Several intervention strategies have been used to improve motor performance among the aging. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS) generated by the addition of a single electron to the oxygen molecule As the level of oxidative stress in skeletal muscle increases with age, the production of some antioxidant enzymes increases adaptively to compensate in part. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fiber composition, muscle type and function).

  20. Coexistence of potentiation and fatigue in skeletal muscle

    Directory of Open Access Journals (Sweden)

    D.E. Rassier

    2000-05-01

    Full Text Available Twitch potentiation and fatigue in skeletal muscle are two conditions in which force production is affected by the stimulation history. Twitch potentiation is the increase in the twitch active force observed after a tetanic contraction or during and following low-frequency stimulation. There is evidence that the mechanism responsible for potentiation is phosphorylation of the regulatory light chains of myosin, a Ca2+-dependent process. Fatigue is the force decrease observed after a period of repeated muscle stimulation. Fatigue has also been associated with a Ca2+-related mechanism: decreased peak Ca2+ concentration in the myoplasm is observed during fatigue. This decrease is probably due to an inhibition of Ca2+ release from the sarcoplasmic reticulum. Although potentiation and fatigue have opposing effects on force production in skeletal muscle, these two presumed mechanisms can coexist. When peak myoplasmic Ca2+ concentration is depressed, but myosin light chains are relatively phosphorylated, the force response can be attenuated, not different, or enhanced, relative to previous values. In circumstances where there is interaction between potentiation and fatigue, care must be taken in interpreting the contractile responses.

  1. 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.

  2. Therapeutic interventions against reperfusion injury in skeletal muscle.

    Science.gov (United States)

    Wang, Wei Z; Baynosa, Richard C; Zamboni, William A

    2011-11-01

    Ischemia/reperfusion (I/R) injury in the skeletal muscle is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive and transplantation surgeries. Although skeletal muscle has a higher tolerance to ischemia than other organs, prolonged ischemia can still result in significant complications, including muscle necrosis and apoptosis. One of the major goals in the treatment of ischemia is early restoration of blood flow (reperfusion) to the area at risk. However, reperfusion has led to a new pathophysiologic condition called "reperfusion injury," a phenomenon which actually provokes a distinct degree of tissue injury. The purpose of this review is to examine the current state of understanding of I/R injury as well as to highlight recent developments on I/R interventions including our own experience in this particular field. We expect, as our acquired experience and the increased knowledge of underlying mechanisms of I/R injury, more effective interventions aimed to reduce I/R injury will be developed to interfere with or modulate this particular pathophysiologic processes. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Cell death induced by gamma irradiation of developing skeletal muscle

    International Nuclear Information System (INIS)

    Olive, M.; Blanco, R.; Rivera, R.; Cinos, C.; Ferrer, I.

    1995-01-01

    Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 μg/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle. (author)

  4. Multiple skeletal muscle metastases revealing a cardiac intimal sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Crombe, Amandine [Institut Bergonie, Department of Radiology, Bordeaux (France); Lintingre, Pierre-Francois; Dallaudiere, Benjamin [Clinique du Sport de Bordeaux-Merignac, Department of Musculoskeletal Radiology, Merignac (France); Le Loarer, Francois [Institut Bergonie, Department of Pathology, Bordeaux (France); Lachatre, Denis [Dupuytren University Hospital, Department of Radiology, Limoges (France)

    2018-01-15

    We report the case of a 59-year-old female with progressive bilateral painful swelling of the thighs. MRI revealed multiple intramuscular necrotic masses with similar morphologic patterns. Whole-body CT and 18-FDG PET-CT scans demonstrated additional hypermetabolic muscular masses and a lobulated lesion within the left atrial cavity. As biopsy of a muscular mass was compatible with a poorly differentiated sarcoma with MDM2 oncogene amplification, two diagnoses were discussed: a dedifferentiated liposarcoma with muscle and heart metastases or a primary cardiac sarcoma, mainly a cardiac intimal sarcoma, with muscular metastases, which was finally confirmed by array-comparative genomic hybridization (aCGH) in a sarcoma reference center. This case emphasizes the potential for intimal sarcoma to disseminate in skeletal muscle prior to any other organ and the need for a genomic approach in addition to classical radiopathologic analyses to distinguish primary from secondary locations facing simultaneous tumors of the heart and skeletal muscles with MDM2 amplification. (orig.)

  5. Genetic architecture of gene expression in ovine skeletal muscle.

    Science.gov (United States)

    Kogelman, Lisette J A; Byrne, Keren; Vuocolo, Tony; Watson-Haigh, Nathan S; Kadarmideen, Haja N; Kijas, James W; Oddy, Hutton V; Gardner, Graham E; Gondro, Cedric; Tellam, Ross L

    2011-12-15

    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. 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. This study has revealed strong genetic structure in the gene expression program within ovine longissimus lumborum muscle. The balance between

  6. 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.

  7. Resistance exercise reverses aging in human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Simon Melov

    2007-05-01

    Full Text Available Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia. Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25 and younger (N = 26 adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001 such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training.

  8. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    International Nuclear Information System (INIS)

    Chatterjee, Somik; Yin, Hongshan; Nam, Deokhwa; Li, Yong; Ma, Ke

    2015-01-01

    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 −/− 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

  9. 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.

  10. 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.

  11. 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.

  12. Strength Training for Skeletal Muscle Endurance after Stroke.

    Science.gov (United States)

    Ivey, Frederick M; Prior, Steven J; Hafer-Macko, Charlene E; Katzel, Leslie I; Macko, Richard F; Ryan, Alice S

    2017-04-01

    Initial studies support the use of strength training (ST) as a safe and effective intervention after stroke. Our previous work shows that relatively aggressive, higher intensity ST translates into large effect sizes for paretic and non-paretic leg muscle volume, myostatin expression, and maximum strength post-stroke. An unanswered question pertains to how our unique ST model for stroke impacts skeletal muscle endurance (SME). Thus, we now report on ST-induced adaptation in the ability to sustain isotonic muscle contraction. Following screening and baseline testing, hemiparetic stroke participants were randomized to either ST or an attention-matched stretch control group (SC). Those in the ST group trained each leg individually to muscle failure (20 repetition sets, 3× per week for 3 months) on each of three pneumatic resistance machines (leg press, leg extension, and leg curl). Our primary outcome measure was SME, quantified as the number of submaximal weight leg press repetitions possible at a specified cadence. The secondary measures included one-repetition maximum strength, 6-minute walk distance (6MWD), 10-meter walk speeds, and peak aerobic capacity (VO 2 peak). ST participants (N = 14) had significantly greater SME gains compared with SC participants (N = 16) in both the paretic (178% versus 12%, P muscle contraction, a metric that may carry more practical significance for stroke than the often reported measures of maximum strength. Published by Elsevier Inc.

  13. TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah Nicklas

    Full Text Available Limb girdle muscular dystrophy type 2H (LGMD2H is an inherited autosomal recessive disease of skeletal muscle caused by a mutation in the TRIM32 gene. Currently its pathogenesis is entirely unclear. Typically the regeneration process of adult skeletal muscle during growth or following injury is controlled by a tissue specific stem cell population termed satellite cells. Given that TRIM32 regulates the fate of mammalian neural progenitor cells through controlling their differentiation, we asked whether TRIM32 could also be essential for the regulation of myogenic stem cells. Here we demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, we show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly we show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. Our studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H.

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

    Directory of Open Access Journals (Sweden)

    Ligen Lin

    Full Text Available 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 establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3. Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER, indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.

  15. Significance of insulin for glucose metabolism in skeletal muscle during contractions

    DEFF Research Database (Denmark)

    Hespel, P; Vergauwen, Lieven; Vandenberghe, K

    1996-01-01

    Glucose uptake rate in active skeletal muscles is markedly increased during exercise. This increase reflects a multifactorial process involving both local and systemic mechanisms that cooperate to stimulate glucose extraction and glucose delivery to the muscle cells. Increased glucose extraction ...

  16. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Richter, Erik; Wojtaszewski, Jørgen

    2006-01-01

    The 5'-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism...... during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We...... in relation to adaptation of skeletal muscle to exercise training....

  17. 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 β 2 -adrenergic receptor (β 2 AR) 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 β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. 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.

    2016-01-01

    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:GRK2fl/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:GRK2fl/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:GRK2fl/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. PMID:27566547

  19. 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 regulated by cyclooxygenase-2 (COX-2)-mediated pathways, and glucose uptake is regulated by specific pathways in tendons that differ from those in skeletal muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as to some degree of net collagen synthesis...

  20. 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): 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......-producing INS-1 cells and rat islets for 24 h in the presence or absence of proinflammatory cytokines (IL-1β+IFN-γ). MAIN OUTCOME MEASURE(S): INS-1 and islet apoptosis and accumulated insulin secretion. RESULTS: IL-1β+IFN-γ increased INS-1 and islet apoptosis and decreased insulin secretion. EPS-treated HSk...

  1. Skeletal muscle as a gene regulatory endocrine organ

    DEFF Research Database (Denmark)

    Karstoft, Kristian; Pedersen, Bente K.

    2016-01-01

    Purpose of review Skeletal muscle is gaining increased attention as an endocrine organ. Recently, novel myokines and new effects of already established myokines have been identified. The objective of this review is to give an update on the recent advances in the field. Recent findings Several...... hundred putative myokines have been described, some of which are induced by contraction and differentially regulated between healthy and metabolically diseased individuals. Interleukin-6 (IL-6) is the prototype myokine, which was identified as a muscle-derived cytokine 15 years ago. Recently, IL-6 has...... is an endocrine organ which, by the release of myokines, may influence metabolism in virtually all organs in the body. This knowledge may potentially open up for the possibility of designing new drugs that mimic the effects of myokine signaling....

  2. PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells.

    Science.gov (United States)

    Ho, Tsung-Chuan; Chiang, Yi-Pin; Chuang, Chih-Kuang; Chen, Show-Li; Hsieh, Jui-Wen; Lan, Yu-Wen; Tsao, Yeou-Ping

    2015-08-01

    In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser(93)-Leu(112)) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2'-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration. Copyright © 2015 the American Physiological Society.

  3. Nitrate supplementation enhances the contractile properties of human skeletal muscle.

    Science.gov (United States)

    Haider, Georg; Folland, Jonathan P

    2014-12-01

    Dietary nitrate supplementation positively affects cardiovascular function at rest and energy metabolism during exercise in humans and has recently also been reported to markedly enhance the in vitro contractile properties of mouse fast-twitch muscle. The aim of this study was to investigate the effects of short-term nitrate supplementation on the in vivo contractile properties of the skeletal muscle and voluntary muscle function of humans. In a double-blind, randomized, crossover design, 19 healthy untrained men (21 ± 3 yr) ingested a nitrate-rich concentrated beetroot juice (NIT; nitrate dosage, approximately 9.7 mmol·d) and a placebo (PLA) for seven consecutive days. After the last supplementation dose, force was recorded while participants completed a series of voluntary and involuntary (electrically evoked) unilateral isometric contractions of the knee extensors. NIT enhanced the peak force response to low-frequency electrical stimulation, as follows: maximal twitch (NIT, 149 ± 41 N, vs PLA, 138 ± 37 N; P = 0.008; effect size, r (ES) = 0.56) and submaximal 1- to 20-Hz contractions (5%-10%, ES = 0.53-0.63). Whereas explosive (rising phase) force production during the first 50 ms of evoked maximal twitch and octet contractions (eight electrical impulses at 300 Hz) was also 3%-15% greater after NIT compared with that after PLA (P = 0.023-0.048, ES = 0.52-0.59), explosive voluntary force remained similar (P = 0.510, ES = 0.16). Maximum voluntary force was also unchanged after NIT (P = 0.539, ES = 0.15). These results indicate that 7 d of dietary nitrate supplementation enhanced the in vivo contractile properties of the human skeletal muscle. Specifically, nitrate supplementation improved excitation-contraction coupling at low frequencies of stimulation and enhanced evoked explosive force production but did not affect maximum or explosive voluntary force production in untrained individuals.

  4. Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

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    Crist, Colin

    2017-01-01

    Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. Evidence for the contribution of muscle stem cells to nonhypertrophic skeletal muscle remodeling in humans

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    Joanisse, Sophie; Gillen, Jenna B.; Bellamy, Leeann M.; McKay, Bryon R.; Tarnopolsky, Mark A.; Gibala, Martin. J.; Parise, Gianni

    2013-01-01

    The purpose of this study was to explore the possible role of muscle stem cells, also referred to as satellite cells (SCs), in adaptation and remodeling following a nonhypertrophic stimulus in humans. Muscle biopsies were obtained from the vastus lateralis of previously untrained women (n=15; age: 27±8 yr, BMI: 29±6 kg/m2) before and after 6 wk of aerobic interval training. The fiber type-specific SC response to training was analyzed using immunofluorescent microscopy of muscle cross sections. Following training, the number of SCs associated with fibers expressing myosin heavy-chain type I and II isoforms (hybrid fibers) increased (pre: 0.062±0.035 SC/hybrid fiber; post: 0.38±0.063 SC/hybrid fiber; PTarnopolsky, M. A., Gibala, M. J., Parise, G. Evidence for the contribution of muscle stem cells to nonhypertrophic skeletal muscle remodeling in humans. PMID:23928822

  6. 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.

  7. Lysophosphatidic acid mediates pleiotropic responses in skeletal muscle cells

    International Nuclear Information System (INIS)

    Jean-Baptiste, Gael; Yang Zhao; Khoury, Chamel; Greenwood, Michael T.

    2005-01-01

    Lysophosphatidic acid (LPA) is a potent modulator of growth, cell survival, and apoptosis. Although all four LPA receptors are expressed in skeletal muscle, very little is known regarding the role they play in this tissue. We used RT-PCR to demonstrate that cultured skeletal muscle C2C12 cells endogenously express multiple LPA receptor subtypes. The demonstration that LPA mediates the activation of ERK1/2 MAP kinase and Akt/PKB in C2C12 cells is consistent with the widely observed mitogenic properties of LPA. In spite of these observations, LPA did not induce proliferation in C2C12 cells. Paradoxically, we found that prolonged treatment of C2C12 cells with LPA led to caspase 3 and PARP cleavage as well as the activation of stress-associated MAP kinases JNK and p38. In spite of these typically pro-apoptotic responses, LPA did not induce cell death. Blocking ERK1/2 and Akt/PKB activation with specific pharmacological inhibitors, nevertheless, stimulated LPA-mediated apoptosis. Taken together, these results suggest that both mitogenic and apoptotic responses serve to counterbalance the effects of LPA in cultured C2C12 cells

  8. 3D visualization and measurement of capillaries supplying metabolically different fiber types in the rat extensor digitorum longus muscle during denervation and reinnervation.

    Science.gov (United States)

    Janácek, Jirí; Cebasek, Vita; Kubínová, Lucie; Ribaric, Samo; Erzen, Ida

    2009-05-01

    The aim of this study was to determine whether capillarity in the denervated and reinnervated rat extensor digitorum longus muscle (EDL) is scaled by muscle fiber oxidative potential. We visualized capillaries adjacent to a metabolically defined fiber type and estimated capillarity of fibers with very high oxidative potential (O) vs fibers with very low oxidative potential (G). Capillaries and muscle fiber types were shown by a combined triple immunofluorescent technique and the histochemical method for NADH-tetrazolium reductase. Stacks of images were captured by a confocal microscope. Applying the Ellipse program, fibers were outlined, and the diameter, perimeter, cross-sectional area, length, surface area, and volume within the stack were calculated for both fiber types. Using the Tracer plug-in module, capillaries were traced within the three-dimensional (3D) volume, the length of capillaries adjacent to individual muscle fibers was measured, and the capillary length per fiber length (Lcap/Lfib), surface area (Lcap/Sfib), and volume (Lcap/Vfib) were calculated. Furthermore, capillaries and fibers of both types were visualized in 3D. In all experimental groups, O and G fibers significantly differed in girth, Lcap/Sfib, and Lcap/Vfib, but not in Lcap/Lfib. We conclude that capillarity in the EDL is scaled by muscle fiber size and not by muscle fiber oxidative potential.

  9. Imaging of denervation in the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093 Lisboa (Portugal)], E-mail: borgalexandra@gmail.com

    2010-05-15

    Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

  10. 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

  11. 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.

  12. The Role of Lumbar Sympathetic Nerves in Regulation of Blood Flow to Skeletal Muscle during Anaphylactic Hypotension in Anesthetized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Song

    Full Text Available During hypovolemic shock, skeletal muscle blood flow could be redistributed to vital organs via vasoconstriction in part evoked by activation of the innervating sympathetic nerve activity. However, it is not well known whether this mechanism operates during anaphylactic shock. We determined the femoral artery blood flow (FBF and lumbar sympathetic nerve activity (LSNA mainly regulating the hindquater muscle blood flow during anaphylactic hypotension in anesthetized rats. Anesthetized Sprague-Dawley rats were randomly allocated to the following groups (n = 7/group: (1 non-sensitized, (2 anaphylaxis, (3 anaphylaxis-lumbar sympathectomy (LS and (4 anaphylaxis-sinoaortic denervation (SAD groups. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen to the sensitized rats. The systemic arterial pressure (SAP, heart rate (HR, central venous pressure (CVP, FBF and LSNA were continuously measured. In the anaphylaxis group, LSNA and HR increased, while SAP and FBF decreased after antigen injection. In the anaphylaxis-SAD group, LSNA did not significantly change during the early phase, but the responses of SAP and FBF were similar to those in the anaphylaxis group. In the anaphylaxis-LS group, both FBF and SAP decreased similarly to the anaphylaxis group during anaphylactic hypotension. These results indicated that LSNA increased via baroreceptor reflex, but this sympathoexcitation or LS did not affect antigen-induced decreases in FBF or SAP. Lumbar sympathetic nerves are not involved in regulation of the blood flow to the hindlimb or systemic blood pressure during anaphylactic hypotension in anesthetized rats.

  13. Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.

    Science.gov (United States)

    Mendias, Christopher L; Schwartz, Andrew J; Grekin, Jeremy A; Gumucio, Jonathan P; Sugg, Kristoffer B

    2017-03-01

    Skeletal muscle can adapt to increased mechanical loads by undergoing hypertrophy. Transient reductions in whole muscle force production have been reported during the onset of hypertrophy, but contractile changes in individual muscle fibers have not been previously studied. Additionally, the extracellular matrix (ECM) stores and transmits forces from muscle fibers to tendons and bones, and determining how the ECM changes during hypertrophy is important in understanding the adaptation of muscle tissue to mechanical loading. Using the synergist ablation model, we sought to measure changes in muscle fiber contractility, collagen content, and cross-linking, and in the expression of several genes and activation of signaling proteins that regulate critical components of myogenesis and ECM synthesis and remodeling during muscle hypertrophy. Tissues were harvested 3, 7