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Sample records for skeletal muscle fibres

  1. Polymorphism of myofibrillar proteins of rabbit skeletal-muscle fibres. An electrophoretic study of single fibres.

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    Salviati, G; Betto, R; Danieli Betto, D

    1982-01-01

    Rabbit predominantly fast-twitch-fibre and predominantly slow-twitch-fibre skeletal muscles of the hind limbs, the psoas, the diaphragm and the masseter muscles were fibre-typed by one-dimensional polyacrylamide-gel electrophoresis of the myofibrillar proteins of chemically skinned single fibres. Investigation of the distribution of fast-twitch-fibre and slow-twitch-fibre isoforms of myosin light chains and the type of myosin heavy chains, based on peptide 'maps' published in Cleveland. Fisch...

  2. Purinergic receptors expressed in human skeletal muscle fibres

    DEFF Research Database (Denmark)

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

    2012-01-01

    distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.......Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content...... of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy...

  3. Human skeletal muscle: transition between fast and slow fibre types.

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    Neunhäuserer, Daniel; Zebedin, Michaela; Obermoser, Magdalena; Moser, Gerhard; Tauber, Mark; Niebauer, Josef; Resch, Herbert; Galler, Stefan

    2011-05-01

    Human skeletal muscles consist of different fibre types: slow fibres (slow twitch or type I) containing the myosin heavy chain isoform (MHC)-I and fast fibres (fast twitch or type II) containing MHC-IIa (type IIA) or MHC-IId (type IID). The following order of decreasing kinetics is known: type IID > type IIA > type I. This order is especially based on the kinetics of stretch activation, which is the most discriminative property among fibre types. In this study we tested if hybrid fibres containing both MHC-IIa and MHC-I (type C fibres) provide a transition in kinetics between fast (type IIA) and slow fibres (type I). Our data of stretch activation kinetics suggest that type C fibres, with different ratios of MHC-IIa and MHC-I, do not provide a continuous transition. Instead, a specialized group of slow fibres, which we called "transition fibres", seems to provide a transition. Apart of their kinetics of stretch activation, which is most close to that of type IIA, the transition fibres are characterized by large cross-sectional areas and low maximal tensions. The molecular cause for the mechanical properties of the transition fibres is unknown. It is possible that the transition fibres contain an unknown slow MHC isoform, which cannot be separated by biochemical methods. Alternatively, or in addition, isoforms of myofibrillar proteins, other than MHC, and posttranslational modifications of myofibrillar proteins could play a role regarding the characteristics of the transition fibres.

  4. 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...

  5. 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

  6. Inward rectifier potassium currents in mammalian skeletal muscle fibres

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    DiFranco, Marino; Yu, Carl; Quiñonez, Marbella; Vergara, Julio L

    2015-01-01

    Inward rectifying potassium (Kir) channels play a central role in maintaining the resting membrane potential of skeletal muscle fibres. Nevertheless their role has been poorly studied in mammalian muscles. Immunohistochemical and transgenic expression were used to assess the molecular identity and subcellular localization of Kir channel isoforms. We found that Kir2.1 and Kir2.2 channels were targeted to both the surface andthe transverse tubular system membrane (TTS) compartments and that both isoforms can be overexpressed up to 3-fold 2 weeks after transfection. Inward rectifying currents (IKir) had the canonical features of quasi-instantaneous activation, strong inward rectification, depended on the external [K+], and could be blocked by Ba2+ or Rb+. In addition, IKir records show notable decays during large 100 ms hyperpolarizing pulses. Most of these properties were recapitulated by model simulations of the electrical properties of the muscle fibre as long as Kir channels were assumed to be present in the TTS. The model also simultaneously predicted the characteristics of membrane potential changes of the TTS, as reported optically by a fluorescent potentiometric dye. The activation of IKir by large hyperpolarizations resulted in significant attenuation of the optical signals with respect to the expectation for equal magnitude depolarizations; blocking IKir with Ba2+ (or Rb+) eliminated this attenuation. The experimental data, including the kinetic properties of IKir and TTS voltage records, and the voltage dependence of peak IKir, while measured at widely dissimilar bulk [K+] (96 and 24 mm), were closely predicted by assuming Kir permeability (PKir) values of ∼5.5 × 10−6 cm s−1 and equal distribution of Kir channels at the surface and TTS membranes. The decay of IKir records and the simultaneous increase in TTS voltage changes were mostly explained by K+ depletion from the TTS lumen. Most importantly, aside from allowing an accurate estimation of

  7. Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism

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    Lee, Kevin Y.; Singh, Manvendra K.; Ussar, Siegfried; Wetzel, Petra; Hirshman, Michael F.; Goodyear, Laurie J.; Kispert, Andreas; Kahn, C. Ronald

    2015-01-01

    Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism. PMID:26299309

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus...... lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n = 8) not involved...

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

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

    2015-10-13

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

  10. Glucose intolerance in the West African Diaspora: a skeletal muscle fibre type distribution hypothesis.

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    Nielsen, J; Christensen, D L

    2011-08-01

    In the United States, Black Americans are largely descendants of West African slaves; they have a higher relative proportion of obesity and experience a higher prevalence of diabetes than White Americans. However, obesity rates alone cannot explain the higher prevalence of type 2 diabetes. Type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. We hypothesize that the higher prevalence of type 2 diabetes in African Americans (as compared to White Americans) is facilitated by an inherited higher percentage of skeletal muscle fibre type II and a lower percentage of skeletal muscle fibre type I. Skeletal muscle fibre type II is less oxidative and more glycolytic than skeletal muscle fibre type I. Lower oxidative capacity is associated with lower fat oxidation and a higher disposal of lipids, which are stored as muscular adipose tissue in higher amounts in Black compared to White Americans. In physically active individuals, the influence of muscle fibre composition will not be as detrimental as in physically inactive individuals. This discrepancy is caused by the plasticity in the skeletal muscle fibre characteristics towards a higher activity of oxidative enzymes as a consequence of physical activity. We suggest that a higher percentage of skeletal muscle fibre type II combined with physical inactivity has an impact on insulin sensitivity and high prevalence of type 2 diabetes in Blacks of West African ancestry. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  11. Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration.

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    Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

    2004-07-15

    Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca(2+)- and Sr(2+)-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had approximately 10% of the maximal force producing capacity (P(o)) of control (uninjured) fibres, and an altered sensitivity to Ca(2+) and Sr(2+) at 7 days post-injury. Increased force production and a shift in Ca(2+) sensitivity consistent with fibre maturation were observed during regeneration such that P(o) was restored to 36-45% of that in control fibres by 21 days, and sensitivity to Ca(2+) and Sr(2+) was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

  12. The expression of NFATc1 in adult rat skeletal muscle fibres.

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    Mutungi, Gabriel

    2008-03-01

    Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

  13. Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

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    Hanft, Laurin M; McDonald, Kerry S

    2010-08-01

    According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length

  14. Myosin heavy-chain isoform distribution, fibre-type composition and fibre size in skeletal muscle of patients on haemodialysis

    DEFF Research Database (Denmark)

    Molsted, Stig; Eidemak, Inge; Sorensen, Helle Tauby

    2007-01-01

    of age-, gender- and BMI-matched untrained control subjects. The aerobic work capacity of the patients was also determined. Results. The MHC composition for I, IIA and IIX isoforms was found to be 35.3%±18.2%, 35.9%±7.1% and 28.9%±15.6%, respectively, findings supported by the ATPase histochemically...... determined fibre-type composition of the vastus lateralis muscle. The mean fibre area of type 1 and 2 fibres was 3283±873 and 3594±1483 µm2, respectively. The MHC composition and the size of the type 1 fibres of the patients on HD were significantly different from those of the control subjects. Conclusions....... The data demonstrate relatively fewer type 1 and consequently more type 2x fibres, with a corresponding change in MHC isoforms (MHC I and MHC IIX) in the skeletal muscle of patiens on HD. Several patients on HD were found to have type 1 (or relative percentage of MHC I) fibres. Such a low percentage...

  15. McArdle disease does not affect skeletal muscle fibre type profiles in humans

    Directory of Open Access Journals (Sweden)

    Tertius Abraham Kohn

    2014-11-01

    Full Text Available Patients suffering from glycogen storage disease V (McArdle disease were shown to have higher surface electrical activity in their skeletal muscles when exercising at the same intensity as their healthy counterparts, indicating more muscle fibre recruitment. To explain this phenomenon, this study investigated whether muscle fibre type is shifted towards a predominance in type I fibres as a consequence of the disease. Muscle biopsies from the Biceps brachii (BB (n = 9 or Vastus lateralis (VL (n = 8 were collected over a 13-year period from male and female patients diagnosed with McArdle disease, analysed for myosin heavy chain (MHC isoform content using SDS-PAGE, and compared to healthy controls (BB: n = 3; VL: n = 10. All three isoforms were expressed and no difference in isoform expression in VL was found between the McArdle patients and healthy controls (MHC I: 33±19% vs. 43±7%; MHC IIa: 52±9% vs. 40±7%; MHC IIx: 15±18% vs. 17±9%. Similarly, the BB isoform content was also not different between the two groups (MHC I: 33±14% vs. 30±11%; MHC IIa: 46±17% vs. 39±5%; MHC IIx: 21±13% vs. 31±14%. In conclusion, fibre type distribution does not seem to explain the higher surface EMG in McArdle patients. Future studies need to investigate muscle fibre size and contractility of McArdle patients.

  16. The effect of exercise on skeletal muscle fibre type distribution in obesity: From cellular levels to clinical application.

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    Pattanakuhar, Sintip; Pongchaidecha, Anchalee; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    Skeletal muscles play important roles in metabolism, energy expenditure, physical strength, and locomotive activity. Skeletal muscle fibre types in the body are heterogeneous. They can be classified as oxidative types and glycolytic types with oxidative-type are fatigue-resistant and use oxidative metabolism, while fibres with glycolytic-type are fatigue-sensitive and prefer glycolytic metabolism. Several studies demonstrated that an obese condition with abnormal metabolic parameters has been negatively correlated with the distribution of oxidative-type skeletal muscle fibres, but positively associated with that of glycolytic-type muscle fibres. However, some studies demonstrated otherwise. In addition, several studies demonstrated that an exercise training programme caused the redistribution of oxidative-type skeletal muscle fibres in obesity. In contrast, some studies showed inconsistent findings. Therefore, the present review comprehensively summarizes and discusses those consistent and inconsistent findings from clinical studies, regarding the association among the distribution of skeletal muscle fibre types, obese condition, and exercise training programmes. Furthermore, the possible underlying mechanisms and clinical application of the alterations in muscle fibre type following obesity are presented and discussed. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  17. Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

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    Hernández-Ochoa, Erick O.; Schneider, Martin F.

    2012-01-01

    Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

  18. Altered myoplasmic Ca(2+) handling in rat fast-twitch skeletal muscle fibres during disuse atrophy.

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    Weiss, Norbert; Andrianjafiniony, Tina; Dupré-Aucouturier, Sylvie; Pouvreau, Sandrine; Desplanches, Dominique; Jacquemond, Vincent

    2010-03-01

    Calcium-dependent signalling pathways are believed to play an important role in skeletal muscle atrophy, but whether intracellular Ca(2+) homeostasis is affected in that situation remains obscure. We show here that there is a 20% atrophy of the fast-type flexor digitorum brevis (FDB) muscle in rats hind limb unloaded (HU) for 2 weeks, with no change in fibre type distribution. In voltage-clamp experiments, the amplitude of the slow Ca(2+) current was found similar in fibres from control and HU animals. In fibres loaded with the Ca(2+) dye indo-1, the value for the rate of [Ca(2+)] decay after the end of 5-100-ms-long voltage-clamp depolarisations from -80 to +10 mV was found to be 30-50% lower in fibres from HU animals. This effect was consistent with a reduced contribution of both saturable and non-saturable components of myoplasmic Ca(2+) removal. However, there was no change in the relative amount of parvalbumin, and type 1 sarco-endoplasmic reticulum Ca(2+)-ATPase was increased by a factor of three in the atrophied muscles. Confocal imaging of mitochondrial membrane potential showed that atrophied FDB fibres had significantly depolarized mitochondria as compared to control fibres. Depolarization of mitochondria in control fibres with carbonyl cyanide-p-trifluoromethoxyphenylhydrazone induced a slowing of the decay of [Ca(2+)] transients accompanied by an increase in resting [Ca(2+)] and a reduction of the peak amplitude of the transients. Overall results provide the first functional evidence for severely altered intracellular Ca(2+) removal capabilities in atrophied fast-type muscle fibres and highlight the possible contribution of reduced mitochondrial polarisation.

  19. Different β-adrenergic receptor density in different rat skeletal muscle fibre types

    International Nuclear Information System (INIS)

    Jensen, J.; Dahl, H.A.; Broers, O.

    1995-01-01

    The effects of adrenaline on skeletal muscle differ between fibre types. The aim of the present study was to investigate the β-adrenoceptor density, affinity and subtype in rat skeletal muscles with different fibre type composition. β-Adrenoceptors were determined in cryostat sections to avoid methodological problems with variable recovery, using the non-selective βadrenoceptor ligand [ 3 H]CGP-12177 and β 1 - and β 2 -selective cold ligands CGP 20712A and ICI 118,551. In the presence of protease inhibitors [ 3 H]CGP-12177 binding was stable, saturable, reversible, and displaceable. Scatchard analysis of binding saturation data was compatible with a single class of specific binding sites. Binding site density (B max ) was higher (P -1 ) than in adult extensor digitorum longus (4.74±0.39 fmol x mg protein -1 ), whereas the dissociation constants (K d ), 0.37±0.05 and 0.31±0.04 nM for soleus and extensor digitorum longus, respectively, were not significantly different. For young rats (5-6 weeks), B max was 11.21±0.33 and 5.45±0.11 fmol x mg protein -1 (P d was 0.27±0.02 and 0.24±0.04 nM for soleus and epitrochlearis, respectively. These results correspond to a receptor density of 2 and 1 pmol x g w.wt. -1 in muscles containing mainly type I and type II fibres, respectively. Displacement studies with CGP 20712A and ICI 118,551 were compatible with mainly β 2 -adrenoceptors, but 7-10% β 1 -adrenoceptors were present in both types of muscle. In conclusion, the receptor density is twice as high in muscles containing mainly type I muscle fibres compared to muscles containing mainly type II fibres, and this may explain some of the different effects of adrenaline between the two muscle fibre types. (au)

  20. Human skeletal muscle glycogen utilization in exhaustive exercise: role of subcellular localization and fibre type

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    Nielsen, Joachim; Holmberg, Hans-Christer; Schrøder, Henrik D; Saltin, Bengt; Ørtenblad, Niels

    2011-01-01

    Abstract 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 that utilization of glycogen with different subcellular localizations during exhaustive arm and leg exercise differs and examined the influence of fibre type and carbohydrate availability on its subsequent resynthesis. When 10 elite endurance athletes (22 ± 1 years, = 68 ± 5 ml kg−1 min−1, mean ± SD) performed one hour of exhaustive arm and leg exercise, transmission electron microscopy revealed more pronounced depletion of intramyofibrillar than of intermyofibrillar and subsarcolemmal glycogen. This phenomenon was the same for type I and II fibres, although at rest prior to exercise, the former contained more intramyofibrillar and subsarcolemmal glycogen than the latter. In highly glycogen-depleted fibres, the remaining small intermyofibrillar and subsarcolemmal glycogen particles were often found to cluster in groupings. In the recovery period, when the athletes received either a carbohydrate-rich meal or only water the impaired resynthesis of glycogen with water alone was associated primarily with intramyofibrillar glycogen. In conclusion, after prolonged high-intensity exercise the depletion of glycogen is dependent on subcellular localization. In addition, the localization of glycogen appears 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. PMID:21486810

  1. Local depletion of glycogen with supramaximal exercise in human skeletal muscle fibres.

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    Gejl, Kasper D; Ørtenblad, Niels; Andersson, Erik; Plomgaard, Peter; Holmberg, Hans-Christer; Nielsen, Joachim

    2017-05-01

    Glycogen is stored in local spatially distinct compartments within skeletal muscle fibres and is the main energy source during supramaximal exercise. Using quantitative electron microscopy, we show that supramaximal exercise induces a differential depletion of glycogen from these compartments and also demonstrate how this varies with fibre types. Repeated exercise alters this compartmentalized glycogen depletion. The results obtained in the present study help us understand the muscle metabolic dynamics of whole body repeated supramaximal exercise, and suggest that the muscle has a compartmentalized local adaptation to repeated exercise, which affects glycogen depletion. Skeletal muscle glycogen is heterogeneously distributed in three separated compartments (intramyofibrillar, intermyofibrillar and subsarcolemmal). Although only constituting 3-13% of the total glycogen volume, the availability of intramyofibrillar glycogen is of particular importance to muscle function. The present study aimed to investigate the depletion of these three subcellular glycogen compartments during repeated supramaximal exercise in elite athletes. Ten elite cross-country skiers (aged 25 ± 4 years, V̇O2 max : 65 ± 4 ml kg -1  min -1 ; mean ± SD) performed four ∼4 min supramaximal sprint time trials (STT 1-4) with 45 min of recovery. The subcellular glycogen volumes in musculus triceps brachii were quantified from electron microscopy images before and after both STT 1 and 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type 1 fibres [-52%; (-89:-15%)] than type 2 fibres [-15% (-52:22%)] (P = 0.02), whereas the depletion of intermyofibrillar glycogen [main effect: -19% (-33:0%), P = 0.006] and subsarcolemmal glycogen [main effect: -35% (-66:0%), P = 0.03] was similar between fibre types. By contrast, only intermyofibrillar glycogen volume was significantly reduced during STT 4, in both fibre types [main effect: -31% (-50:-11%), P = 0

  2. GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Gaster, M; Vach, W; Beck-Nielsen, H

    2002-01-01

    In this study we examined the relationship between GLUT4 expression at the plasma membrane and muscle fibre size in fibre-typed human muscle fibres by immunocytochemistry and morphometry in order to gain further insight into the regulation of GLUT4 expression. At the site of the plasma membrane...

  3. Rigor force responses of permeabilized fibres from fast and slow skeletal muscles of aged rats.

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    Plant, D R; Lynch, G S

    2001-09-01

    1. Ageing is generally associated with a decline in skeletal muscle mass and strength and a slowing of muscle contraction, factors that impact upon the quality of life for the elderly. The mechanisms underlying this age-related muscle weakness have not been fully resolved. The purpose of the present study was to determine whether the decrease in muscle force as a consequence of age could be attributed partly to a decrease in the number of cross-bridges participating during contraction. 2. Given that the rigor force is proportional to the approximate total number of interacting sites between the actin and myosin filaments, we tested the null hypothesis that the rigor force of permeabilized muscle fibres from young and old rats would not be different. 3. Permeabilized fibres from the extensor digitorum longus (fast-twitch; EDL) and soleus (predominantly slow-twitch) muscles of young (6 months of age) and old (27 months of age) male F344 rats were activated in Ca2+-buffered solutions to determine force-pCa characteristics (where pCa = -log(10)[Ca2+]) and then in solutions lacking ATP and Ca2+ to determine rigor force levels. 4. The rigor forces for EDL and soleus muscle fibres were not different between young and old rats, indicating that the approximate total number of cross-bridges that can be formed between filaments did not decline with age. We conclude that the age-related decrease in force output is more likely attributed to a decrease in the force per cross-bridge and/or decreases in the efficiency of excitation-contraction coupling.

  4. Correlation between pennation angle and image quality of skeletal muscle fibre tractography using deterministic diffusion tensor imaging.

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    Okamoto, Yoshikazu; Okamoto, Toru; Yuka, Kujiraoka; Hirano, Yuji; Isobe, Tomonori; Minami, Manabu

    2012-12-01

    The aim of this study was to ascertain whether a correlation existed between muscle pennation angle and the ability to successfully perform tractography of the lower leg muscle fibres with deterministic diffusion tensor imaging (DTI) in normal volunteers. Fourteen volunteers aged 20-39 (mean 28.2 years old) were recruited. All volunteers were scanned using DTI, and six fibre tractographs were constructed from one lower leg of each volunteer, and the 'fibre density' was calculated in each of the tractographs. The pennation angle is the angle formed by the muscle fibre and the aponeurosis. The average pennation angle (AVPA) and standard deviation of the pennation angle (SDPA) were also measured for each muscle by ultrasonography in the same region as the MRI scan. For all 84 tractography images, the correlation coefficient between the fibre density and AVPA or SDPA was calculated. Fibre density and AVPA showed a moderate negative correlation (R = -0.72), and fibre density and SDPA showed a weak negative correlation (R = -0.47). With respect to comparisons within each muscle, AVPA and fibre density showed a moderate negative correlation in the gastrocnemius lateralis muscle (R = -0.57). Our data suggest that a larger, more variable pennation angle resulted in worse skeletal muscle tractography using deterministic DTI. © 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.

  5. Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture

    DEFF Research Database (Denmark)

    Higginson, James; Wackerhage, Henning; Woods, Niall

    2002-01-01

    A and mitogen-activated protein kinase kinase (MEK1/2) blockade with U0126 upon myosin heavy chain (MHC) isoform mRNA levels and activities of metabolic enzymes after 1 day, 3 days and 7 days of treatment in primary cultures of spontaneously twitching rat skeletal muscle. U0126 treatment significantly decreased......Activation of either the calcineurin or the extracellular signal-regulated kinase (ERK1/2) pathway increases the percentage of slow fibres in vivo suggesting that both pathways can regulate fibre phenotypes in skeletal muscle. We investigated the effect of calcineurin blockade with cyclosporin...

  6. Skeletal Muscle Fibre-Specific Knockout of p53 Does Not Reduce Mitochondrial Content or Enzyme Activity

    Directory of Open Access Journals (Sweden)

    Ben Stocks

    2017-12-01

    Full Text Available Tumour protein 53 (p53 has been implicated in the regulation of mitochondrial biogenesis in skeletal muscle, with whole-body p53 knockout mice displaying impairments in basal mitochondrial content, respiratory capacity, and enzyme activity. This study aimed to determine the effect of skeletal muscle-specific loss of p53 on mitochondrial content and enzyme activity. Mitochondrial protein content, enzyme activity and mRNA profiles were assessed in skeletal muscle of 8-week-old male muscle fibre-specific p53 knockout mice (p53 mKO and floxed littermate controls (WT under basal conditions. p53 mKO and WT mice displayed similar content of electron transport chain proteins I-V and citrate synthase enzyme activity in skeletal muscle. In addition, the content of proteins regulating mitochondrial morphology (MFN2, mitofillin, OPA1, DRP1, FIS1, fatty acid metabolism (β-HAD, ACADM, ACADL, ACADVL, carbohydrate metabolism (HKII, PDH, energy sensing (AMPKα2, AMPKβ2, and gene transcription (NRF1, PGC-1α, and TFAM were comparable in p53 mKO and WT mice (p > 0.05. Furthermore, p53 mKO mice exhibited normal mRNA profiles of targeted mitochondrial, metabolic and transcriptional proteins (p > 0.05. Thus, it appears that p53 expression in skeletal muscle fibres is not required to develop or maintain mitochondrial protein content or enzyme function in skeletal muscle under basal conditions.

  7. Exploring the Role of PGC-1α in Defining Nuclear Organisation in Skeletal Muscle Fibres.

    Science.gov (United States)

    Ross, Jacob A; Pearson, Adam; Levy, Yotam; Cardel, Bettina; Handschin, Christoph; Ochala, Julien

    2017-06-01

    Muscle fibres are multinucleated cells, with each nucleus controlling the protein synthesis in a finite volume of cytoplasm termed the myonuclear domain (MND). What determines MND size remains unclear. In the present study, we aimed to test the hypothesis that the level of expression of the transcriptional coactivator PGC-1α and subsequent activation of the mitochondrial biogenesis are major contributors. Hence, we used two transgenic mouse models with varying expression of PGC-1α in skeletal muscles. We isolated myofibres from the fast twitch extensor digitorum longus (EDL) and slow twitch diaphragm muscles. We then membrane-permeabilised them and analysed the 3D spatial arrangements of myonuclei. In EDL muscles, when PGC-1α is over-expressed, MND volume decreases; whereas, when PGC-1α is lacking, no change occurs. In the diaphragm, no clear difference was noted. This indicates that PGC-1α and the related mitochondrial biogenesis programme are determinants of MND size. PGC-1α may facilitate the addition of new myonuclei in order to reach MND volumes that can support an increased mitochondrial density. J. Cell. Physiol. 232: 1270-1274, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Gene gun bombardment-mediated expression and translocation of EGFP-tagged GLUT4 in skeletal muscle fibres in vivo

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M M; Reynet, Christine; Schjerling, Peter

    2002-01-01

    the enhanced green fluorescent protein (EGFP) labelling technique with physical transfection methods in vivo: intramuscular plasmid injection or gene gun bombardment. During optimisation experiments with plasmid coding for the EGFP reporter alone EGFP-positive muscle fibres were counted after collagenase...... treatment of in vivo transfected flexor digitorum brevis (FDB) muscles. In contrast to gene gun bombardment, intramuscular injection produced EGFP expression in only a few fibres. Regardless of the transfection technique, EGFP expression was higher in muscles from 2-week-old rats than in those from 6-week......Cellular protein trafficking has been studied to date only in vitro or with techniques that are invasive and have a low time resolution. To establish a gentle method for analysis of glucose transporter-4 (GLUT4) trafficking in vivo in fully differentiated rat skeletal muscle fibres we combined...

  9. Upper motor neurone modulation of the structure of the terminal cisternae in rat skeletal muscle fibres.

    Science.gov (United States)

    Dulhunty, A F; Gage, P W; Valois, A A

    1981-12-23

    There are fewer indentations on the flat surfaces of terminal cisternae in soleus (slow-twitch) than in extensor digitorum longus (EDL, fast-twitch) muscle fibres of rats. Following mid-thoracic spinal cord transection, there is an increase in the number of indentations in soleus fibres but no change in EDL fibres. The increase in the numbers of indentations after spinal cord transections is correlated with changes in the contractile and charge movement properties of the soleus fibres so that they resemble normal EDL fibres. The indentations appear to have an important role in excitation-contraction coupling.

  10. Effect of ascorbic acid on fatigue of skeletal muscle fibres in long term cold exposed sprague dawley rats

    International Nuclear Information System (INIS)

    Rashid, A.; Ayub, M.

    2011-01-01

    On exposure to prolonged cold temperature, the body responds for effective heat production both by shivering and non-shivering thermo genesis. Cold exposure increases the production of reactive oxygen species which influence the sarcoplasmic reticulum Ca/sup ++/ release from the skeletal muscles and affect their contractile properties. The role of ascorbic acid supplementation on force of contraction during fatigue of cold exposed skeletal muscles was evaluated in this study. Method: Ninety healthy, male Sprague Dawley rats were randomly divided into three groups of control, cold exposed, and cold exposed with ascorbic acid 500 mg/L supplementation mixed in drinking water. Group II and III were given cold exposure by keeping their cages in ice-filled tubs for 1 hr/day for one month. After one month, the extensor digitorum longus muscle was dissected out and force of contraction during fatigue in the skeletal muscle fibres was analysed on a computerised data acquisition system. Results: The cold exposed group showed a significant delay in the force of contraction during fatigue of skeletal muscle fibres compared to control group. Group III showed easy fatigability and a better force of contraction than the cold exposed group. Conclusions: Ascorbic acid increases the force of contraction and decreases resistance to fatigue in the muscles exposed to chronic cold. (author)

  11. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

    Science.gov (United States)

    Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

    2014-01-01

    Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

  12. Power output of skinned skeletal muscle fibres from the cheetah (Acinonyx jubatus)

    Science.gov (United States)

    West, T.G.; Toepfer, Christopher N.; Woledge, Roger C.; Curtin, N.A.; Rowlerson, Anthea; Kalakoutis, Michaeljohn; Hudson, Penny; Wilson, Alan M.

    2015-01-01

    SUMMARY Muscle samples were taken from the gluteus, semitendinosus and longissimus muscles of a captive cheetah immediately after euthanasia. Fibres were “skinned” to remove all membranes leaving the contractile filament array intact and functional. Segments of skinned fibres from these cheetah muscles and from rabbit psoas muscle were activated at 20°C by a temperature jump protocol. Step and ramp length changes were imposed after active stress had developed. The stiffness of the non-contractile ends of the fibres (series elastic component) was measured at two different stress values in each fibre; stiffness was strongly dependent on stress. Using these stiffness values, the speed of shortening of the contractile component was evaluated, and hence the power it was producing. Fibres were analysed for myosin heavy chain content using gel electrophoresis, and identified as either slow (Type I) or fast (Type II). The power output of cheetah Type II fibre segments was 92.5 ± 4.3 W kg−1 (mean ±s.e., 14 fibres) during shortening at relative stress 0.15 (=stress during shortening/isometric stress). For rabbit psoas fibre segments (presumably Type IIX) the corresponding value was significantly higher (Pcheetah was less than that of rabbit when maximally activated at 20°C, and does not account for the superior locomotor performance of the cheetah. PMID:23580727

  13. Power output of skinned skeletal muscle fibres from the cheetah (Acinonyx jubatus).

    Science.gov (United States)

    West, Timothy G; Toepfer, Christopher N; Woledge, Roger C; Curtin, Nancy A; Rowlerson, Anthea; Kalakoutis, Michaeljohn; Hudson, Penny; Wilson, Alan M

    2013-08-01

    Muscle samples were taken from the gluteus, semitendinosus and longissimus muscles of a captive cheetah immediately after euthanasia. Fibres were 'skinned' to remove all membranes, leaving the contractile filament array intact and functional. Segments of skinned fibres from these cheetah muscles and from rabbit psoas muscle were activated at 20°C by a temperature-jump protocol. Step and ramp length changes were imposed after active stress had developed. The stiffness of the non-contractile ends of the fibres (series elastic component) was measured at two different stress values in each fibre; stiffness was strongly dependent on stress. Using these stiffness values, the speed of shortening of the contractile component was evaluated, and hence the power it was producing. Fibres were analysed for myosin heavy chain content using gel electrophoresis, and identified as either slow (type I) or fast (type II). The power output of cheetah type II fibre segments was 92.5±4.3 W kg(-1) (mean ± s.e., 14 fibres) during shortening at relative stress 0.15 (the stress during shortening/isometric stress). For rabbit psoas fibre segments (presumably type IIX) the corresponding value was significantly higher (Pcheetah was less than that of rabbit when maximally activated at 20°C, and does not account for the superior locomotor performance of the cheetah.

  14. Mitochondrial oxidative enzyme activity in individual fibre types in hypo- and hyperthyroid rat skeletal muscles.

    Science.gov (United States)

    Johnson, M A; Turnbull, D M

    1984-04-01

    Quantitative cytochemical and biochemical techniques have been used in combination to study the response of mitochondrial oxidative enzymes in individual muscle fibre types to hypo- and hyperthyroidism. Hypothyroidism resulted in decreased activity of succinate dehydrogenase (SDH), L-glycerol-3-phosphate dehydrogenase (L-GPDH), and D-3-hydroxybutyrate dehydrogenase (D-HBDH) in all fibre types of both slow-twitch soleus and fast-twitch extensor digitorum longus (e.d.l.) muscles. In hyperthyroidism, only L-GPDH activity increased in e.d.l. but more marked increases were seen in soleus muscles, which also showed increased SDH activity. In addition to these alterations in the enzyme activity in individual fibre types the metabolic profile of the muscle is further modified by the hormone-induced interconversion of slow- to fast-twitch fibres and vice versa.

  15. A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

    Science.gov (United States)

    Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

    2013-10-15

    Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

  16. A role for Insulin-like growth factor 2 in specification of the fast skeletal muscle fibre

    Directory of Open Access Journals (Sweden)

    Ting Tao

    2007-06-01

    Full Text Available Abstract Background Fibre type specification is a poorly understood process beginning in embryogenesis in which skeletal muscle myotubes switch myosin-type to establish fast, slow and mixed fibre muscle groups with distinct function. Growth factors are required to establish slow fibres; it is unknown how fast twitch fibres are specified. Igf-2 is an embryonically expressed growth factor with established in vitro roles in skeletal muscle. Its localisation and role in embryonic muscle differentiation had not been established. Results Between E11.5 and E15.5 fast Myosin (FMyHC localises to secondary myotubes evenly distributed throughout the embryonic musculature and gradually increasing in number so that by E15.5 around half contain FMyHC. The Igf-2 pattern closely correlates with FMyHC from E13.5 and peaks at E15.5 when over 90% of FMyHC+ myotubes also contain Igf-2. Igf-2 lags FMyHC and it is absent from muscle myotubes until E13.5. Igf-2 strongly down-regulates by E17.5. A striking feature of the FMyHC pattern is its increased heterogeneity and attenuation in many fibres from E15.5 to day one after birth (P1. Transgenic mice (MIG which express Igf-2 in all of their myotubes, have increased FMyHC staining, a higher proportion of FMyHC+ myotubes and loose their FMyHC staining heterogeneity. In Igf-2 deficient mice (MatDi FMyHC+ myotubes are reduced to 60% of WT by E15.5. In vitro, MIG induces a 50% excess of FMyHC+ and a 30% reduction of SMHyC+ myotubes in C2 cells which can be reversed by Igf-2-targeted ShRNA resulting in 50% reduction of FMyHC. Total number of myotubes was not affected. Conclusion In WT embryos the appearance of Igf-2 in embryonic myotubes lags FMyHC, but by E15.5 around 45% of secondary myotubes contain both proteins. Forced expression of Igf-2 into all myotubes causes an excess, and absence of Igf-2 suppresses, the FMyHC+ myotube component in both embryonic muscle and differentiated myoblasts. Igf-2 is thus required, not for

  17. Immunolabelling, histochemistry and in situ hybridisation in human skeletal muscle fibres to detect myosin heavy chain expression at the protein and mRNA level

    Science.gov (United States)

    SERRANO, A. L.; PÉREZ, MARGARITA; LUCÍA, A.; CHICHARRO, J. L.; QUIROZ-ROTHE, E.; RIVERO, J. L. L.

    2001-01-01

    The distribution of muscle fibres classified on the basis of their content of different myosin heavy chain (MHC) isoforms was analysed in vastus lateralis muscle biopsies of 15 young men (with an average age of 22 y) by correlating immunohistochemistry with specific anti-MHC monoclonal antibodies, myofibrillar ATPase (mATPase) histochemistry and in situ hybridisation with probes specific for MHC β-slow, MHC-IIA and MHC-IIX. The characterisation of a large number of individual fibres was compared and correlated on a fibre-to-fibre basis. The panel of monoclonal antibodies used in the study allowed classification of human skeletal muscle fibres into 5 categories according to the MHC isoform they express at the protein level, types I, I+IIA, IIA, IIAX and IIX. Hybrid fibres coexpressing two isoforms represented a considerable proportion of the fibre composition (about 14%) and were clearly underestimated by mATPase histochemistry. For a very high percentage of fibres there was a precise correspondence between the MHC protein isoforms and mRNA transcripts. The integrated methods used demonstrate a high degree of precision of the immunohistochemical procedure used for the identification and quantification of human skeletal muscle fibre types. The monoclonal antibody S5-8H2 is particularly useful for identifying hybrid IIAX fibres. This protocol offers new prospects for muscle fibre classification in human experimental studies. PMID:11554510

  18. The influence of stress on substrate utilization in skeletal muscle fibres of reindeer (Rangifer tarandus L

    Directory of Open Access Journals (Sweden)

    B. Essén-Gustavsson

    1984-05-01

    Full Text Available Moderate stress in connection with handling, sampling and herding of reindeer caused a very pronounced depletion of glycogen in mainly type IIA and IIB fibres. Also intramuscular triglyceride levels decreased but mainly in type I fibres. Muscle lactate levéls increased in all animals but not to the levels found in pigs exposed to stress or exertion. Reindeer muscles appeared to have a great capacity to oxidize both carbohydrates and lipids. All animals showed increased Cortisol, urea and AS AT values. A marked depletion of glycogen and lipids in many of the fibres may be a factor involved in the development of skeletal muscle degeneration in connection with mental stress and exertion as there seems to be a correlation between high ASAT values and substrate depleted musclefibres. A connection may therefore exist between high instramuscular substrate stores and the ability of a muscle to tolerate stress.Av stress påverkat substratutnyttjande i skelettmuskelfibrer hos renAbstract in Swedish / Sammanfattning: Måttlig stress betingad av hantering, provtagning och drivning av ren orsakade en mycket kraftig minskning av muskelglykogen i fråmst typ IIA och typ IIB fibrer. Aven triglycerider minskade framfor allt i typ I fibrer. Muskellaktatnivåerna okade i samtliga undersokta djur, men inte till nivåer som ses hos gris utsatta for stress eller fysisk anstrångning.Renens muskler uppvisade en mycket hog kapacitet att oxidera, forbranna, både kolhydrat och fett. Alla djur uppvisade forhojda Cortisol, urea och ASAT varden. Den mycket kraftiga tomningen av kolhydrat och fett i många muskelfibrer kan vara en faktor medverkande till muskeldegeneration i samband med mental stress och anstrangning då hoga ASAT-vården synes vara korrelerade till uttomda muskelfibrer. Ett samband mellan hog instramuskulår substratupplagring och formåga att tåla stress kan således foreligga.Stressin vaikuttaneen poron substraattihyvåk-sikåytto luurangon lihaksiston

  19. A comparative study of charge movement in rat and frog skeletal muscle fibres.

    Science.gov (United States)

    Hollingworth, S; Marshall, M W

    1981-12-01

    1. The middle of the fibre voltage--clamp technique (Adrian & Marshall, 1977), modified where necessary for electrically short muscle fibres, has been used to measure non-linear charge movements in mammalian fast twitch (rat extensor digitorum longus), mammalian slow twitch (rat soleus) and frog (sartorius) muscles. 2. The maximum amount of charge moved in mammalian fast twitch muscle at 2 degrees C in hypertonic solution, was 3--5 times greater than in slow twitch muscle. The voltage distribution of fast twitch charge was 10--15 mV more positive when compared to slow twitch. 3. In both mammalian muscle types hypertonic Ringer solution negatively shifted the voltage distribution of charge some 6 mV. The steepness of charge moved around mechanical threshold was unaffected by hypertonicity. 4. The amount of charge in frog sartorius fibres at 2 degrees C in hypertonic solution was about half of that in rat fast twitch muscle; the voltage distribution of the frog charge was similar to rat soleus muscle. 5. Warming between 2 and 15 degrees C had no effect on either the amount of steady-state distribution of charge in mammalian or frog muscles. 6. At 2 degrees C, the kinetics of charge movement in fast and slow twitch mammalian muscles were similar and 2--3 times faster than frog muscle at the same temperature. In fast and slow mammalian fibres at 2 degrees C similar times were taken to shift the same fractions of the total amount of charge. The Q10 of charge movement kinetics was between 1.2 and 2.0 in the three muscles studied.

  20. Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high-intensity exercise training.

    Science.gov (United States)

    Wyckelsma, Victoria L; Levinger, Itamar; McKenna, Michael J; Formosa, Luke E; Ryan, Michael T; Petersen, Aaron C; Anderson, Mitchell J; Murphy, Robyn M

    2017-06-01

    Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) in human skeletal muscle with the increased abundance of Mfn2 being exclusive to type II muscle fibres. These changes occur despite a similar content of mitochondria, as measured by COXIV, NDUFA9 and complexes in their native states (Blue Native PAGE). Following 12 weeks of high-intensity training (HIT), older adults exhibit a robust increase in mitochondria content, while there is a decline in Mfn2 in type II fibres. We propose that the upregulation of Mfn2 and MiD49 with age may be a protective mechanism to protect against mitochondrial dysfunction, in particularly in type II skeletal muscle fibres, and that exercise may have a unique protective effect negating the need for an increased turnover of mitochondria. Mitochondrial dynamics proteins are critical for mitochondrial turnover and maintenance of mitochondrial health. High-intensity interval training (HIT) is a potent training modality shown to upregulate mitochondrial content in young adults but little is known about the effects of HIT on mitochondrial dynamics proteins in older adults. This study investigated the abundance of protein markers for mitochondrial dynamics and mitochondrial content in older adults compared to young adults. It also investigated the adaptability of mitochondria to 12 weeks of HIT in older adults. Both older and younger adults showed a higher abundance of mitochondrial respiratory chain subunits COXIV and NDUFA9 in type I compared with type II fibres, with no difference between the older adults and young groups. In whole muscle homogenates, older adults had higher mitofusin-2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) contents compared to the young group. Also, older adults had higher levels of Mfn2 in type II fibres compared with young adults. Following HIT in older adults, MiD49 and Mfn2 levels were not different in whole

  1. Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres.

    Science.gov (United States)

    Wendowski, Oskar; Redshaw, Zoe; Mutungi, Gabriel

    2017-02-01

    Sarcopenia, the progressive decline in skeletal muscle mass and function with age, is a debilitating condition. It leads to inactivity, falls, and loss of independence. Despite this, its cause(s) and the underlying mechanism(s) are still poorly understood. In this study, small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast-twitch muscle) and the soleus (a slow-twitch muscle) of adult mice of different ages (range 100-900 days old) were used to investigate the effects of ageing and dihydrotestosterone (DHT) treatment on protein synthesis as well as the expression and function of two amino acid transporters; the sodium-coupled neutral amino acid transporter (SNAT) 2, and the sodium-independent L-type amino-acid transporter (LAT) 2. At all ages investigated, protein synthesis was always higher in the slow-twitch than in the fast-twitch muscle fibres and decreased with age in both fibre types. However, the decline was greater in the fast-twitch than in the slow-twitch fibres and was accompanied by a reduction in the expression of SNAT2 and LAT2 at the protein level. Again, the decrease in the expression of the amino acid transporters was greater in the fast-twitch than in the slow-twitch fibres. In contrast, ageing had no effect on SNAT2 and LAT2 expressions at the mRNA level. Treating the muscle fibre bundles with physiological concentrations (~2 nM) of DHT for 1 h completely reversed the effects of ageing on protein synthesis and the expression of SNAT2 and LAT2 protein in both fibre types. From the observations that ageing is accompanied by a reduction in protein synthesis and transporter expression and that these effects are reversed by DHT treatment, we conclude that sarcopenia arises from an age-dependent reduction in protein synthesis caused, in part, by the lack of or by the low bioavailability of the male sex steroid, DHT.

  2. The effects of tetracaine on charge movement in fast twitch rat skeletal muscle fibres.

    Science.gov (United States)

    Hollingworth, S; Marshall, M W; Robson, E

    1990-02-01

    1. The effects of tetracaine, a local anaesthetic that inhibits muscle contraction, on membrane potential and intramembrane charge movements were investigated in fast twitch rat muscle fibres (extensor digitorum longus). 2. The resting membrane potentials of surface fibres from muscles bathed in isotonic Ringer solution containing 2 mM-tetracaine were well maintained, but higher concentrations of tetracaine caused a time-dependent fall of potential. Muscle fibres bathed in hypertonic solutions containing 2 mM-tetracaine were rapidly depolarized. In both isotonic and hypertonic solutions, the depolarizing effect of tetracaine could not be reversed. 3. Charge movement measurements were made using the middle-of-the-fibre voltage clamp technique. The voltage dependence of charge movements measured in cold isotonic solutions was well fitted by a Boltzmann distribution (Q(V) = Qmax/(1 + exp(-(V-V)/k] where Qmax = 37.3 +/- 2.8 nC muF-1, V = -17.9 +/- 1.2 mV and k = 12.6 +/- 0.8 mV (n = 6, 2 degrees C; means +/- S.E. of means). Similar values were obtained when 2 mM-tetracaine was added to the isotonic bathing fluid (Qmax = 40.6 +/- 2.3 nC microF-1, V = -14.1 +/- 1.3 mV, k = 15.3 +/- 0.8 mV; n = 8, 2 degrees C). 4. Charge movements measured around mechanical threshold in muscle fibres bathed in hypertonic solutions were reduced when 2 mM-tetracaine was added to the bathing fluid. The tetracaine-sensitive component of charge was well fitted with an unconstrained Boltzmann distribution which gave: Qmax = 7.5 nC microF-1, V = -46.5 mV, k = 5.5 mV. The e-fold rise of the foot of the curve was 9.3 mV.

  3. Muscle Fibre Types, Ubiquinone Content and Exercise Capacity in Hypertension and Effort Angina

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Folkers, Karl

    1991-01-01

    Farmakologi, hypertension, IHD, skeletal muscle fibre composition, muscle coenzyme Q10, ischaemic heart disease, effort angina, muscle fibre lesion, muscle ubiquinone......Farmakologi, hypertension, IHD, skeletal muscle fibre composition, muscle coenzyme Q10, ischaemic heart disease, effort angina, muscle fibre lesion, muscle ubiquinone...

  4. Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres.

    Science.gov (United States)

    Hamdi, M M; Mutungi, G

    2010-02-01

    It is generally believed that steroid hormones have both genomic and non-genomic (rapid) actions. Although the latter form an important component of the physiological response of these hormones, little is known about the cellular signalling pathway(s) mediating these effects and their physiological functions in adult mammalian skeletal muscle fibres. Therefore, the primary aim of this study was to investigate the non-genomic actions of dihydrotestosterone (DHT) and their physiological role in isolated intact mammalian skeletal muscle fibre bundles. Our results show that treating the fibre bundles with physiological concentrations of DHT increases both twitch and tetanic contractions in fast twitch fibres. However, it decreases them in slow twitch fibres. These changes in force are accompanied by an increase in the phosphorylation of MAPK/ERK1/2 in both fibre types and that of regulatory myosin light chains in fast twitch fibres. Both effects were insensitive to inhibitors of Src kinase, androgen receptor, insulin-like growth factor 1 receptor and platelet-derived growth factor receptor. However, they were abolished by the MAPK/ERK1/2 kinase inhibitor PD98059 and the epidermal growth factor (EGF) receptor inhibitor tyrphostin AG 1478. In contrast, testosterone had no effect on force and increased the phosphorylation of ERK1/2 in slow twitch fibres only. From these results we conclude that sex steroids have non-genomic actions in isolated intact mammalian skeletal muscle fibres. These are mediated through the EGF receptor and one of their main physiological functions is the enhancement of force production in fast twitch skeletal muscle fibres.

  5. Effects of hypothyroidism on myosin heavy chain composition and fibre types of fast skeletal muscles in a small marsupial, Antechinus flavipes.

    Science.gov (United States)

    Zhong, Wendy W H; Withers, Kerry W; Hoh, Joseph F Y

    2010-04-01

    Effects of drug-induced hypothyroidism on myosin heavy chain (MyHC) content and fibre types of fast skeletal muscles were studied in a small marsupial, Antechinus flavipes. SDS-PAGE of MyHCs from the tibialis anterior and gastrocnemius revealed four isoforms, 2B, 2X, 2A and slow, in that order of decreasing abundance. After 5 weeks treatment with methimazole, the functionally fastest 2B MyHC significantly decreased, while 2X, 2A and slow MyHCs increased. Immunohistochemistry using monospecific antibodies to each of the four MyHCs revealed decreased 2b and 2x fibres, and increased 2a and hybrid fibres co-expressing two or three MyHCs. In the normally homogeneously fast superficial regions of these muscles, evenly distributed slow-staining fibres appeared, resembling the distribution of slow primary myotubes in fast muscles during development. Hybrid fibres containing 2A and slow MyHCs were virtually absent. These results are more detailed but broadly similar to the earlier studies on eutherians. We hypothesize that hypothyroidism essentially reverses the effects of thyroid hormone on MyHC gene expression of muscle fibres during myogenesis, which differ according to the developmental origin of the fibre: it induces slow MyHC expression in 2b fibres derived from fast primary myotubes, and shifts fast MyHC expression in fibres of secondary origin towards 2A, but not slow, MyHC.

  6. Twitchin can regulate the ATPase cycle of actomyosin in a phosphorylation-dependent manner in skinned mammalian skeletal muscle fibres.

    Science.gov (United States)

    Avrova, Stanislava V; Rysev, Nikita A; Matusovsky, Oleg S; Shelud'ko, Nikolay S; Borovikov, Yurii S

    2012-05-01

    The effect of twitchin, a thick filament protein of molluscan muscles, on the actin-myosin interaction at several mimicked sequential steps of the ATPase cycle was investigated using the polarized fluorescence of 1.5-IAEDANS bound to myosin heads, FITC-phalloidin attached to actin and acrylodan bound to twitchin in the glycerol-skinned skeletal muscle fibres of mammalian. The phosphorylation-dependent multi-step changes in mobility and spatial arrangement of myosin SH1 helix, actin subunit and twitchin during the ATPase cycle have been revealed. It was shown that nonphosphorylated twitchin inhibited the movements of SH1 helix of the myosin heads and actin subunits and decreased the affinity of myosin to actin by freezing the position and mobility of twitchin in the muscle fibres. The phosphorylation of twitchin reverses this effect by changing the spatial arrangement and mobility of the actin-binding portions of twitchin. In this case, enhanced movements of SH1 helix of the myosin heads and actin subunits are observed. The data imply a novel property of twitchin incorporated into organized contractile system: its ability to regulate the ATPase cycle in a phosphorylation-dependent fashion by changing the affinity and spatial arrangement of the actin-binding portions of twitchin. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Local depletion of glycogen with supra-maximal exercise in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Gejl, Kasper Degn; Ørtenblad, Niels; Andersson, Erik

    2017-01-01

    importance to muscle function. The present study was designed to investigate the depletion of these three sub-cellular glycogen compartments during repeated supra-maximal exercise in elite athletes. Ten elite cross-country skiers (age: 25 ± 4 yrs., VO2 max : 65 ± 4 ml kg(-1) min(-1) , mean ± SD) performed...... four ∼4-minute supra-maximal sprint time trials (STT 1-4) with 45 min recovery. The sub-cellular glycogen volumes in m. triceps brachii were quantified from electron microscopy images before and after both STT 1 and STT 4. During STT 1, the depletion of intramyofibrillar glycogen was higher in type I...... fibres (-52% [-89:-15%]) than type 2 fibres (-15% [-52:22%]) (P = 0.02), while the depletion of intermyofibrillar glycogen (main effect: -19% [-33:0], P = 0.006) and subsarcolemmal glycogen (main effect: -35% [-66:0%], P = 0.03) was similar between fibre types. In contrast, only intermyofibrillar...

  8. Properties of Ca2+ release induced by clofibric acid from the sarcoplasmic reticulum of mouse skeletal muscle fibres

    Science.gov (United States)

    Ikemoto, Takaaki; Endo, Makoto

    2001-01-01

    To characterize the effect of clofibric acid (Clof) on the Ca2+ release mechanism in the sarcoplasmic reticulum (SR) of skeletal muscle, we analysed the properties of Clof-induced Ca2+ release under various conditions using chemically skinned skeletal muscle fibres of the mouse.Clof (>0.5 mM) released Ca2+ from the SR under Ca2+-free conditions buffered with 10 mM EGTA (pCa >8).Co-application of ryanodine and Clof at pCa >8 but not ryanodine alone reduced the Ca2+ uptake capacity of the SR. Thus, Ca2+ release induced by Clof at pCa >8 must be a result of the activation of the ryanodine receptor (RyR).At pCa >8, (i) Clof-induced Ca2+ release was inhibited by adenosine monophosphate (AMP), (ii) the inhibitory effect of Mg2+ on the Clof-induced Ca2+ release was saturated at about 1 mM, and (iii) Clof-induced Ca2+ release was not inhibited by procaine (10 mM). These results indicate that Clof may activate the RyR-Ca2+ release channels in a manner different from Ca2+-induced Ca2+ release (CICR).In addition to this unique mode of opening, Clof also enhanced the CICR mode of opening of RyR-Ca2+ release channels.Apart from CICR, a high concentration of Ca2+ might also enhance the unique mode of opening by Clof.These results suggest that some features of Ca2+ release activated by Clof are similar to those of physiological Ca2+ release (PCR) in living muscle cells and raise the possibility that Clof may be useful in elucidating the mechanism of PCR in skeletal muscle. PMID:11606311

  9. The role of Six1 in muscle progenitor cells and the establishment of fast-twitch muscle fibres

    OpenAIRE

    Nord, Hanna

    2014-01-01

    Myogenesis is the process of skeletal muscle tissue formation where committed muscle progenitor cells differentiate into skeletal muscle fibres. Depending on the instructive cues the muscle progenitor cells receive they will differentiate into specific fibre types with different properties. The skeletal muscle fibres can be broadly classified as fast-twitch fibres or slow-twitch fibres, based on their contractile speed. However, subgroups of fast- and slow-twitch fibres with different metabol...

  10. 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...

  11. Hydrogen peroxide increases depolarization-induced contraction of mechanically skinned slow twitch fibres from rat skeletal muscles.

    Science.gov (United States)

    Plant, David R; Lynch, Gordon S; Williams, David A

    2002-03-15

    The effect of exogenous hydrogen peroxide (H(2)O(2)) on excitation-contraction (E-C) coupling and sarcoplasmic reticulum (SR) function was compared in mechanically skinned slow twitch fibres (prepared from the soleus muscles) and fast twitch fibres (prepared from the extensor digitorum longus; EDL muscles) of adult rats. Equilibration (5 min) with 1 mM H(2)O(2) diminished the ability of the Ca(2+)-depleted SR to reload Ca(2+) in both slow (P fast twitch fibres (P fast twitch fibres by 24 +/- 5 % (P slow twitch fibres. Treatment with 1 mM H(2)O(2) also increased the peak force of low [caffeine] contracture by approximately 45% in both fibre types compared to control (P slow twitch fibres, compared to control (no H(2)O(2); P fast twitch fibres was not altered by 1 mM H(2)O(2) treatment. Equilibration with 5 mM H(2)O(2) induced a spontaneous force response in both slow and fast twitch fibres, which could be partly reversed by 2 min treatment with 10 mM DTT. Peak DICR was also increased approximately 40% by 5 mM H(2)O(2) in slow twitch fibres compared to control (no H(2)O(2); P slow but not fast twitch fibres. The increase in depolarization-induced contraction in slow twitch fibres might be mediated by an increased SR Ca(2+) release during contraction and/or an increase in Ca(2+) sensitivity.

  12. Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice.

    Science.gov (United States)

    Bruton, Joseph D; Place, Nicolas; Yamada, Takashi; Silva, José P; Andrade, Francisco H; Dahlstedt, Anders J; Zhang, Shi-Jin; Katz, Abram; Larsson, Nils-Göran; Westerblad, Håkan

    2008-01-01

    Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.

  13. Sensitivity of different types of fibres in rabbit skeletal muscle to pneumatic compression by tourniquet and to ischaemia.

    Science.gov (United States)

    Fridén, J; Pedowitz, R A; Thornell, L E

    1994-06-01

    Morphometric properties (distribution of types of fibre and fibre areas) in the non-necrotic regions of four different rabbit muscles (superficial portions of semimembranosus, biceps femoris, tibialis anterior, and soleus muscles) were measured 48 hours after a tourniquet had been applied around the thigh for two hours at either 125 or 350 mmHg. There was an considerable increase of the relative numbers of both large and small fibres as well as changes in the proportions of the types of fibre. The most dramatic percentage change in type of fibre was in the semimembranosus when compressed at 350 mmHg, which showed an increase of the relative frequency of fibres with type 2AB staining characteristics from 10.2% to 18.0% (p < 0.001). Extreme changes in fibre area were found exclusively in semimembranosus and biceps femoris. Most fibres of abnormal size were of type 2, type 2B fibre areas being the most affected. This study shows that morphometry is a valuable tool in the assessment of the more subtle indications of injury. Compression and ischaemia together have a more dramatic effect on muscle morphology and morphometric properties in the non-necrotic regions than ischaemia alone. These data also show that muscles are differentially sensitive to compression and ischaemia. This information may be useful into the understanding of more complex functional deficits observed after the use of tourniquet.

  14. Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism

    Science.gov (United States)

    Hamdi, M M; Mutungi, G

    2011-01-01

    Abstract Dihydrotestosterone (DHT) has acute/non-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acute/non-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and α-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acute/non-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression. PMID:21606113

  15. Contractile properties and sarcoplasmic reticulum calcium content in type I and type II skeletal muscle fibres in active aged humans.

    Science.gov (United States)

    Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D

    2015-06-01

    Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca(2+) content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca(2+) sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf ) markedly increased Ca(2+) sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca(2+) content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca(2+) by a combined caffeine and low Mg(2+) stimulus, whereas in fibres of Old the amount of non-releasable Ca(2+) was significantly increased (by > 12% of endogenous Ca(2+) content). Western

  16. Effects of dantrolene and its derivatives on Ca2+ release from the sarcoplasmic reticulum of mouse skeletal muscle fibres

    Science.gov (United States)

    Ikemoto, Takaaki; Hosoya, Takamitsu; Aoyama, Hiroshi; Kihara, Yasutaka; Suzuki, Masaaki; Endo, Makoto

    2001-01-01

    We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca2+ release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle.In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185.In skinned fibres, Dan inhibited Ca2+-induced Ca2+ release (CICR) under Mg2+-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions.Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185.GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca2+ release, as did Dan.Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca2+ release.The magnitudes of inhibition of Clof-induced Ca2+ release by all Dan derivatives were well correlated with those of twitch inhibition. This supports the notion that the mode of Clof-induced opening of the RyR-Ca2+ release channel may be similar to that of physiological Ca2+ release (PCR).These results indicate that the difference in opening modes of the RyR-Ca2+ release channel is recognized by certain Dan derivatives. PMID:11606312

  17. Hydrogen peroxide modulates Ca2+-activation of single permeabilized fibres from fast- and slow-twitch skeletal muscles of rats.

    Science.gov (United States)

    Plant, D R; Lynch, G S; Williams, D A

    2000-01-01

    We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H2O2. The effects of H2O2 on maximum Ca2+-activated force were dose-dependent with 30 min exposure to 5 mM H2O2 causing a progressive decrease by 22+/-3 and 13+/-2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H2O2 (100 microM and 1 mM) had no effect on maximum Ca2+-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H2O2-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca2+-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca2+ (pCa50) was not altered by exposure to any concentration of exogenous H2O2. However, all concentrations of H2O2 diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca2+ binding to troponin is altered. H2O2 (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H2O2 may reduce the maximum Ca2+ activated force production in skinned muscle fibres by decreasing the force per crossbridge.

  18. Effects of in vivo-like activation frequency on the length-dependent force generation of skeletal muscle fibre bundles

    NARCIS (Netherlands)

    Zuurbier, C. J.; Lee-de Groot, M. B.; van der Laarse, W. J.; Huijing, P. A.

    1998-01-01

    It is known that a range of firing frequencies can be observed during in vivo muscle activity, yet information is lacking as to how different in vivo-like frequencies may affect force generation of skeletal muscle. This study examined the effects of constant (CSF, constant within one contraction)

  19. Drastic increase of myosin light chain MLC-2 in senescent skeletal muscle indicates fast-to-slow fibre transition in sarcopenia of old age.

    Science.gov (United States)

    Gannon, Joan; Doran, Philip; Kirwan, Anne; Ohlendieck, Kay

    2009-11-01

    The age-dependent decline in skeletal muscle mass and function is believed to be due to a multi-factorial pathology and represents a major factor that blocks healthy aging by increasing physical disability, frailty and loss of independence in the elderly. This study has focused on the comparative proteomic analysis of contractile elements and revealed that the most striking age-related changes seem to occur in the protein family representing myosin light chains (MLCs). Comparative screening of total muscle extracts suggests a fast-to-slow transition in the aged MLC population. The mass spectrometric analysis of the myofibril-enriched fraction identified the MLC2 isoform of the slow-type MLC as the contractile protein with the most drastically changed expression during aging. Immunoblotting confirmed an increased abundance of slow MLC2, concomitant with a switch in fast versus slow myosin heavy chains. Staining of two-dimensional gels of crude extracts with the phospho-specific fluorescent dye ProQ-Diamond identified the increased MLC2 spot as a muscle protein with a drastically enhanced phosphorylation level in aged fibres. Comparative immunofluorescence microscopy, using antibodies to fast and slow myosin isoforms, confirmed a fast-to-slow transformation process during muscle aging. Interestingly, the dramatic increase in slow MLC2 expression was restricted to individual senescent fibres. These findings agree with the idea that aged skeletal muscles undergo a shift to more aerobic-oxidative metabolism in a slower-twitching fibre population and suggest the slow MLC2 isoform as a potential biomarker for fibre type shifting in sarcopenia of old age.

  20. Effects of rapid shortening on rate of force regeneration and myoplasmic [Ca2+] in intact frog skeletal muscle fibres

    Science.gov (United States)

    Vandenboom, R; Claflin, D R; Julian, F J

    1998-01-01

    The effect of rapid shortening on rate of force regeneration (dF/dtR) was examined in single, intact frog (Rana temporaria) skeletal muscle fibres (3·0 °C). Step releases leading to unloaded shortening were applied after 500 ms of stimulation, during the plateau of an isometric tetanus. Initial mean sarcomere length ranged from 2·05 to 2·35 μm; force regeneration after shortening was at 2·00 μm.Values for dF/dtR following a 25 nm half-sarcomere−1 release were 3·17 ± 0·17 (mean ± s.e.m., n= 8) times greater than the initial rate of rise of force before release (dF/dtI). As release size was increased from 25 to 175 nm half-sarcomere−1, the relationship between release size and dF/dtR decreased sharply before attaining a plateau value that was 1·34 ± 0·09 times greater than dF/dtI. Despite wide variations in dF/dtR, the velocity of unloaded shortening remained constant (2·92 ± 0·08 μm half-sarcomere−1 s−1; n= 8) for the different release amplitudes used in this study.To investigate its role in the attenuation of dF/dtR with increased shortening, the effects of rapid ramp (constant velocity) shortening on intracellular free Ca2+ concentration ([Ca2+]i) were monitored using the Ca2+-sensitive fluorescent dye furaptra. Compared with an isometric contraction, rapid fibre shortening was associated with a transient increase in [Ca2+]i while force regeneration after shortening was associated with a transient reduction in [Ca2+]i. The greatest reductions in [Ca2+]i were associated with the largest amplitude ramps.Cross-bridge-mediated modifications of the Ca2+ affinity of troponin C (TnC) may explain the fluctuations in [Ca2+]i observed during and after ramps. Associated fluctuations in TnC Ca2+ occupancy could play a role in the reduction of dF/dtR with increasing release size. PMID:9679172

  1. 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...... 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......, which is expected to represent the number of membrane transporter molecules. Km is unaffected by most treatments and appears to be independent of fibre type....

  2. Tetanic Ca2+ transient differences between slow- and fast-twitch mouse skeletal muscle fibres: a comprehensive experimental approach.

    Science.gov (United States)

    Calderón, Juan C; Bolaños, Pura; Caputo, Carlo

    2014-12-01

    One hundred and eighty six enzymatically dissociated murine muscle fibres were loaded with Mag-Fluo-4 AM, and adhered to laminin, to evaluate the effect of modulating cytosolic Ca(2+) buffers and sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), mitochondria, and Na(+)/Ca(2+) exchanger (NCX) on the differential tetanic Ca(2+) transient kinetics found in different fibre types. Tetanic Ca(2+) transients were classified as morphology type I (MT-I) or type II (MT-II) according to their shape. The first peak of the MT-I (n = 25) and MT-II (n = 23) tetanic Ca(2+) transients had an amplitude (∆F/F) of 0.41 ± 0.03 and 0.83 ± 0.05 and a rise time (ms) of 1.35 and 0.98, respectively. MT-I signals had a time constant of decay (τ1, ms) of 75.9 ± 4.2 while MT-II transients showed a double exponential decay with time constants of decay (τ1 and τ2, ms) of 18.3 ± 1.4 and 742.2 ± 130.3. Sarcoendoplasmic reticulum Ca(2+) ATPase inhibition demonstrated that the decay phase of the tetanic transients mostly rely on SERCA function. Adding Ca(2+) chelators in the AM form to MT-I fibres changed the morphology of the initial five peaks to a MT-II one, modifying the decay phase of the signal in a dose-dependent manner. Mitochondria and NCX function have a minor role in explaining differences in tetanic Ca(2+) transients among fibre types but still help in removing Ca(2+) from the cytosol in both MT-I and MT-II fibres. Cytoplasmic Ca(2+) buffering capacity and SERCA function explain most of the different kinetics found in tetanic Ca(2+) transients from different fibre types, but mitochondria and NCX have a measurable role in shaping tetanic Ca(2+) responses in both slow and fast-twitch muscle fibre types. We provided experimental evidence on the mechanisms that help understand the kinetics of tetanic Ca(2+) transients themselves and explain kinetic differences found among fibre types.

  3. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

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

  4. A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Skov, Vibe; Petersson, Stine Juhl

    2014-01-01

    Insulin resistance in obesity and type 2 diabetes is related to abnormalities in mitochondrial oxidative phosphorylation (OxPhos) in skeletal muscle. We tested the hypothesis that mitochondrial oxidative metabolism is impaired in muscle of patients with inherited insulin resistance and defective...

  5. GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fibre type-specific pattern

    DEFF Research Database (Denmark)

    Gaster, M; Handberg, A; Schürmann, A

    2004-01-01

    or amyotrophic lateral sclerosis (ALS) were studied. GLUT8 and 12 immunoreactivity was below detection level in both developing and adult muscle fibres. GLUT11 immunoreactivity, however, was present in slow-twitch muscle fibres, but not in fast twitch fibres. Since, in contrast, GLUT4 was expressed in all...... exclusively in slow-twitch muscle fibres and is unaffected by physiological and pathophysiological conditions except in primary myopathy. GLUT8 and GLUT12 do not appear to be of importance in human muscle under physiological and pathophysiological conditions....... to induce GLUT8 or -12 expression. Likewise, the fibre type-dependent pattern of GLUT11 immunoreactivity was unaltered. However, some slow muscle fibres lose their GLUT11 immunoreactivity under regeneration. Our results indicate that GLUT11 immunoreactivity, in contrast to that of GLUT4, is expressed...

  6. Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue.

    Science.gov (United States)

    Knuth, S T; Dave, H; Peters, J R; Fitts, R H

    2006-09-15

    Historically, an increase in intracellular H(+) (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H(+) as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15 degrees C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded shortening velocity (V(0)), force-velocity, and force-power relationships determined. Consistent with previous observations, low pH depressed the P(0) of both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V(0) was unaltered by temperature, while for peak power the inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the force-velocity relationship was temperature sensitive, and showed a higher a/P(0) ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow- and fast-twitch fibres at near-in vivo temperatures (30 degrees C) is greater than would be predicted based on changes in P(0), and that the

  7. Regenerating human muscle fibres express GLUT3 protein

    DEFF Research Database (Denmark)

    Gaster, M; Beck-Nielsen, H; Schrøder, H D

    2002-01-01

    The presence of the GLUT3 glucose transporter protein in human muscle cells is a matter of debate. The present study was designed to establish whether GLUT3 is expressed in mature human skeletal muscle fibres and, if so, whether its expression changes under different conditions, such as metabolic...... muscle fibres, nor did metabolic stress, training or de- and re-innervation induce GLUT3 expression, while a few GLUT3 expressing fibres were seen in some cases of polymyositis. In contrast, GLUT4 was expressed in all investigated muscle fibres. GLUT3 immunoreactivity was found in perineural...... and endoneural cells, indicating that GLUT3 is important for glucose transport into nerves through the perineurium. Taken together, these data suggest that GLUT3 expression is restricted to regenerating muscle fibres and nerves in adult human muscle. Although the significance of GLUT3 in adult human muscle...

  8. 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...... myosin heavy chain I and IIA, αB-crystallin, HSP27, HSP60 and HSP70. RESULTS: In ACT and RES, but not in END, a fibre type specific expression with higher staining intensity in type I than type II fibres was seen for αB-crystallin. The opposite (II>I) was found for HSP27 in subjects from ACT (6 of 12...... 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...

  9. in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Espen E. Spangenburg

    2011-01-01

    Full Text Available Triglyceride storage is altered across various chronic health conditions necessitating various techniques to visualize and quantify lipid droplets (LDs. Here, we describe the utilization of the BODIPY (493/503 dye in skeletal muscle as a means to analyze LDs. We found that the dye was a convenient and simple approach to visualize LDs in both sectioned skeletal muscle and cultured adult single fibers. Furthermore, the dye was effective in both fixed and nonfixed cells, and the staining seemed unaffected by permeabilization. We believe that the use of the BODIPY (493/503 dye is an acceptable alternative and, under certain conditions, a simpler method for visualizing LDs stored within skeletal muscle.

  10. Cryopreservation of human skeletal muscle impairs mitochondrial function

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  11. Lipolysis in Skeletal Muscle

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck

    chemical structure of DAG. We took advantage of the fact that insulin sensitivity is increased after exercise, and that mice knocked out (KO) of HSL accumulate DAG after exercise, and measured insulin stimulated glucose uptake after treadmill running in skeletal muscle from HSL KO mice and wildtype control...

  12. 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.

  13. Nox4 Is Dispensable for Exercise Induced Muscle Fibre Switch.

    Directory of Open Access Journals (Sweden)

    Juri Vogel

    Full Text Available By producing H2O2, the NADPH oxidase Nox4 is involved in differentiation of mesenchymal cells. Exercise alters the composition of slow and fast twitch fibres in skeletal. Here we hypothesized that Nox4 contributes to exercise-induced adaptation such as changes in muscle metabolism or muscle fibre specification and studied this in wildtype and Nox4-/- mice.Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill induced a switch from fast twitch to intermediate fibres. However the induced muscle fibre switch was similar between Nox4-/- and wildtype mice. The same held true for exercise-induced expression of PGC1α or AMPK activation. Both are increased in response to exercise, but with no difference was observed between wildtype and Nox4-/- mice.Thus, exercise-induced muscle fibre switch is Nox4-independent.

  14. 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

    fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1alpha mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies...... from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1......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...

  15. Swimming-induced exercise promotes hypertrophy and vascularization of fast skeletal muscle fibres and activation of myogenic and angiogenic transcriptional programs in adult zebrafish

    NARCIS (Netherlands)

    Palstra, A.P.; Rovira, M.; Rizo-Roca, D.; Torrella, J.R.; Spaink, H.P.; Planas, J.V.

    2014-01-01

    Background The adult skeletal muscle is a plastic tissue with a remarkable ability to adapt to different levels of activity by altering its excitability, its contractile and metabolic phenotype and its mass. We previously reported on the potential of adult zebrafish as a tractable experimental model

  16. 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...

  17. Skeletal Muscle Na+ Channel Disorders

    Directory of Open Access Journals (Sweden)

    Dina eSimkin

    2011-10-01

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

  18. 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.

  19. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

    Science.gov (United States)

    Lin, Jiandie; Wu, Hai; Tarr, Paul T; Zhang, Chen-Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F; Puigserver, Pere; Isotani, Eiji; Olson, Eric N; Lowell, Bradford B; Bassel-Duby, Rhonda; Spiegelman, Bruce M

    2002-08-15

    The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination.

  20. 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)....

  1. Cardiac troponin T and fast skeletal muscle denervation in ageing.

    Science.gov (United States)

    Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

    2017-10-01

    Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii

  2. 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. ....... that utilization of glycogen with different subcellular localizations during exhaustive arm and leg exercise differs and examined the influence of fibre type and carbohydrate availability on its subsequent resynthesis. When 10 elite endurance athletes (22 ± 1 years, VO2 max = 68 ± 5 ml kg-1 min-1, mean ± SD...

  3. Matching of sarcoplasmic reticulum and contractile properties in rat fast- and slow-twitch muscle fibres.

    Science.gov (United States)

    Trinh, Huong H; Lamb, Graham D

    2006-07-01

    1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle fibres are determined not only by the contractile apparatus properties of the fibre, but also by the time-course of Ca2+ release and re-uptake by the sarcoplasmic reticulum (SR). The present study examined, in individual fibres from non-transforming muscle of the rat, whether particular SR properties are matched to the contractile apparatus properties of the fibre, in particular in the case of fibres with fast-twitch contractile apparatus located in a slow-twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus longus and soleus muscles. Using repeated cycles in which the SR was emptied of all releasable Ca2+ and then reloaded, it was possible to determine the relative amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or mixed (fibres examined) and thereby identify the likely troponin C and myosin heavy chain types present. 3. There was no significant difference in SR properties between the groups of FT fibres obtained from the four different muscles, including soleus. Despite some overlap in the SR properties of individual fibres between the FT and ST groups, the properties of the FT fibres in all four muscles studied were significantly different from those of the ST and mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the endogenous Ca2+ content was a relatively lower percentage of maximum compared with ST fibres. Importantly, in terms of their SR properties, FT fibres from soleus muscle more closely resembled FT fibres from other muscles than they did ST fibres from soleus muscle.

  4. Capillary network in slow and fast muscles and in oxidative and glycolytic muscle fibres

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

    Roč. 24, March (2005), s. 51-58 ISSN 1580-3139 Grant - others:SI-CZ(CZ) KONTAKT 19/2005 Institutional research plan: CEZ:AV0Z50110509 Keywords : capillaries * skeletal muscle fibre s-oxidative and glycolytic * stereology Subject RIV: EA - Cell Biology

  5. Alpha-adrenergic receptors in rat skeletal muscle

    DEFF Research Database (Denmark)

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

    1986-01-01

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

  6. Skeletal muscle lymphoma: observations at MR imaging

    International Nuclear Information System (INIS)

    Eustace, S.; Winalski, C.S.; McGowen, A.; Lan, H.; Dorfman, D.

    1996-01-01

    We present the MR appearances of three patients with biopsy-proven primary lymphoma of skeletal muscle. In each case lymphoma resulted in bulky expansion of the involved muscle, homogeneously isointense to skeletal muscle on T1-weighted images, homogeneously hyperintense to skeletal muscle on T2-weighted images and diffusely enhancing following intravenous administration of gadopentate dimeglumine. (orig.)

  7. Relationships between myonuclear domain size and fibre properties in the muscles of Thoroughbred horses.

    Science.gov (United States)

    Kawai, M; Kuwano, A; Hiraga, A; Miyata, H

    2010-11-01

    The myonuclear domain (MND) is the region of cytoplasm governed by a single myonucleus. Myonuclear domain size is an important factor for muscle fibre plasticity because each myonucleus has limitations in the capacity of protein synthesis. Previous studies have demonstrated that differences in MND size exist in different fibre types in several species, including horses. To understand the basic mechanism of muscle plasticity, the relationships between MND size, muscle fibre type population and metabolic properties of skeletal muscles throughout the whole body in Thoroughbred horses were examined. Post mortem samples were taken from 20 muscles in 3 Thoroughbred horses aged 3-5 years of age. Fibre type population was determined on serial cross sections of each muscle sample, stained for monoclonal antibodies to each myosin heavy chain isoform. Oxidative (succinic dehydrogenase; SDH) and glycolytic (phosphofructokinase; PFK) enzyme activities were determined spectrophotometrically in each muscle sample. Furthermore, 30 single fibres were isolated from each muscle under stereomicroscopy and then fibre volume and myonuclear number for a given length analysed under confocal microscopy. The MND size of each single fibre was measured after normalisation of sarcomere length to 2.8 µm by staining with membrane-specific dye. Immunohistochemical staining indicated that soleus, vastus lateralis and gluteus medius muscles had the highest percentage of type I, IIa and IIx muscle fibre, respectively. Biochemical analysis indicated highest activities of SDH and PFK in diaphragm and longissimus lumborum muscles, respectively. MNDs were largest in the splenius muscle and smallest in the soleus and masseter muscles. Myonuclear domain size is significantly related to type I muscle fibre population, but not to SDH activities of the muscles. The MND size of muscle fibre depends on fibre type population rather than mitochondrial enzyme activities. © 2010 EVJ Ltd.

  8. Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia

    Directory of Open Access Journals (Sweden)

    Luciana Hagström

    2010-01-01

    Full Text Available Erythropoietin (Epo and vascular growth factor (VEGF are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh. Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1 but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency.

  9. 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

    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. ABSTRACT: 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...

  10. 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.

  11. 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...

  12. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

    in the structure of fibrous collagen and myofibers at high-resolution. The results demonstrate that the collagen composition in the extra cellular matrix of Gadus morhua fish muscle is much more complex than previously anticipated, as it contains type III, IV, V  and VI collagen in addition to type I. The vascular....... Consequently, functional structures, ensuring "tissue maintenance" must form a major role of connective tissue, in addition that is to the force transmitting structures one typically finds in muscle. Vascular structures have also been shown to change their mechanical properties with age and it has been shown...

  13. 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.

  14. Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older men.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; Joanisse, Sophie; Leenders, Marika; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2017-04-01

    Adequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown. Twenty-two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary-to-fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry. Overall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm 2 , P muscle fibre, P muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm 2 , P muscle fibre, P muscle fibre capillarization were observed in response to 12 and 24 weeks of resistance exercise training in both the LOW and HIGH group. Type II muscle fibre capillarization at baseline may be a critical factor for allowing muscle fibre hypertrophy to occur during prolonged resistance exercise training in older men. © 2016 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.

  15. Functional characterization of muscle fibres from patients with chronic fatigue syndrome: case-control study.

    Science.gov (United States)

    Pietrangelo, T; Toniolo, L; Paoli, A; Fulle, S; Puglielli, C; Fanò, G; Reggiani, C

    2009-01-01

    Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Although immunological and psychological aspects are present, symptoms related to skeletal muscles, such as muscle soreness, fatigability and increased lactate accumulation, are prominent in CFS patients. In this case-control study, the phenotype of the same biopsy samples was analyzed by determining i) fibre-type proportion using myosin isoforms as fibre type molecular marker and gel electrophoresis as a tool to separate and quantify myosin isoforms, and ii) contractile properties of manually dissected, chemically made permeable and calcium-activated single muscle fibres. The results showed that fibre-type proportion was significantly altered in CSF samples, which showed a shift from the slow- to the fast-twitch phenotype. Cross sectional area, force, maximum shortening velocity and calcium sensitivity were not significantly changed in single muscle fibres from CSF samples. Thus, the contractile properties of muscle fibres were preserved but their proportion was changed, with an increase in the more fatigue-prone, energetically expensive fast fibre type. Taken together, these results support the view that muscle tissue is directly involved in the pathogenesis of CSF and it might contribute to the early onset of fatigue typical of the skeletal muscles of CFS patients.

  16. Capillarity, oxidative capacity and fibre composition of the soleus and gastrocnemius muscles of rats in hypothyroidism.

    Science.gov (United States)

    Sillau, A H

    1985-01-01

    Muscle capillarity, mean and maximal diffusion distances and muscle fibre composition were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the gastrocnemius medial head (gastrocnemius) of rats made hypothyroid by the injection of propylthiouracil (PTU) (50 mg kg-1) every day for 21 or 42 days. Oxygen consumption in the presence of excess ADP and Pi with pyruvate plus malate as substrates and the activity of cytochrome c oxidase were measured in muscle homogenates. Treatment with PTU decreased body oxygen consumption and the concentration of triiodothyronine in plasma. The capacity of the soleus and gastrocnemius muscles' homogenates to oxidize pyruvate plus malate and their cytochrome c oxidase activity were reduced after 21 or 42 days of treatment with PTU. Fibre composition in the soleus muscle was changed by treatment with PTU. There was a decrease in the proportion of type IIa or fast glycolytic oxidative fibres and an increase in type I or slow oxidative fibres. After 21 days of PTU administration there was also an increase in the proportion of fibres classified as IIc. The changes in fibre composition are believed to be the result of changes in the types of myosin synthesized by the fibres. Therefore, the fibres classified as IIc are, most probably, IIa fibres in the process of changing their myosin to that of the type I fibres. No changes in fibre composition were evident in the white area of the gastrocnemius medial head, an area made up of IIb or fast glycolytic fibres. The indices of capillarity: capillary density and capillary to fibre ratio, as well as mean and maximal diffusion distances from the capillaries, were not changed by the treatment with PTU in the muscles studied. The lack of changes in capillarity in spite of significant changes in oxidative capacity indicates that in skeletal muscle capillarity is not necessarily related to the oxidative capacity of the fibres. PMID:3989729

  17. 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

  18. 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…

  19. 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

  20. AMPK in skeletal muscle function and metabolism

    DEFF Research Database (Denmark)

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

    2018-01-01

    Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK's role as an energy sensor is particularly critical in tissues displaying...... 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...

  1. The exercised skeletal muscle: a review

    Directory of Open Access Journals (Sweden)

    Marina Marini

    2010-09-01

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

  2. Radiation injury to skeletal muscle

    International Nuclear Information System (INIS)

    Persons, C.C.M.; Wondergem, J.; Leer, J.W.H.

    1997-01-01

    Radiotherapy of neoplasia has increased the mean life expectancy of cancer patients. On the other hand, more reports are published on morbidity of the treatment with regard to normal tissue. Studies on skeletal muscle injury specifically are scarce, but many clinical long term follow-up studies make note of side effects as muscle atrophy, fibrosis and limited function. Furthermore it is suggested that skeletal muscles of children are more prone to radiation injury than those of adult subjects. Effects of radiation on skeletal muscle were studied in rats. On hind limb of young (100 g) and adult (350 g) rats was irradiated with single doses (15-30 Gy), while the other served as control. Follow-up was up to 12 months post treatment. Muscular function in young rats was decreased significantly at 6 months post irradiation, but did not further decrease in the following 6 months. The amount of collagen, on the other hand, was not increased at 6 months, but became highly elevated at 12 months past treatment. This suggests that at 6 months, impaired muscular function may not be explained by increased fibrotic tissues. This is an agreement with results obtained in adult rats, where function was also impaired, without concomitant increase in collagen. In an earlier study, mitochondrial oxygen consumption was dose dependently decreased after irradiation, at 12 months, but not at 6 months post treatment. Furthermore, myosin-actin interaction was measured in skinned fibers. The first results of this study indicate changes in the interaction of contraction proteins, as early as 6 months post treatment. (authors)

  3. 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.

  4. Coupling between skeletal muscle fiber size and capillarization is maintained during healthy aging.

    Science.gov (United States)

    Barnouin, Yoann; McPhee, Jamie S; Butler-Browne, Gillian; Bosutti, Alessandra; De Vito, Giuseppe; Jones, David A; Narici, Marco; Behin, Anthony; Hogrel, Jean-Yves; Degens, Hans

    2017-08-01

    As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres. Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity. There was no significant age-related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people. The similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age-related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during 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.

  5. 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.

  6. Skeletal Muscle Regeneration, Repair and Remodelling in Aging: The Importance of Muscle Stem Cells and Vascularization.

    Science.gov (United States)

    Joanisse, Sophie; Nederveen, Joshua P; Snijders, Tim; McKay, Bryon R; Parise, Gianni

    2017-01-01

    Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults. © 2016 S. Karger AG, Basel.

  7. Skeletal muscle and fetal alcohol spectrum disorder.

    Science.gov (United States)

    Myrie, Semone B; Pinder, Mark A

    2018-04-01

    Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ("prenatal alcohol exposure"; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.

  8. 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

  9. Postnatal changes in electromyographic signals during piglet growth, and in relation to muscle fibre types

    DEFF Research Database (Denmark)

    Andersen, Ninette Kieme; Ravn, L.S.; Guy, J.H.

    2008-01-01

    This study uses non-invasive evoked surface electromyography (SEMG) to investigate postnatal muscle development in pigs, and to assess any correlation between recorded signal parameters and muscle fibre types in two different skeletal muscles. Four litters (n=43) of Large White x Landrace pigs were...... used. Evoked SEMG mesurements were taken on days 2, 5, 14, 26, 60 and 151 post partum from m. Longissimus dorsi (LD) and on days 14, 26, 60 and 151 post partum from m. Biceps femoris (BF). A third of each litter was slaughtered at days 27, 61 and 153 post partum. Biopsy samples for LD and BF were taken...... to categorize day 5 post partum, whilst for BF significant increases occurred from days 14 to 26 post partum. Fibre type development in both muscles showed a significant decrease in type IIA fibre number (Ptype IIB fibre number (P

  10.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  11. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  12. Response of skeletal muscle mitochondria to hypoxia.

    Science.gov (United States)

    Hoppeler, Hans; Vogt, Michael; Weibel, Ewald R; Flück, Martin

    2003-01-01

    This review explores the current concepts relating the structural and functional modifications of skeletal muscle mitochondria to the molecular mechanisms activated when organisms are exposed to a hypoxic environment. In contrast to earlier assumptions it is now established that permanent or long-term exposure to severe environmental hypoxia decreases the mitochondrial content of muscle fibres. Oxidative muscle metabolism is shifted towards a higher reliance on carbohydrates as a fuel, and intramyocellular lipid substrate stores are reduced. Moreover, in muscle cells of mountaineers returning from the Himalayas, we find accumulations of lipofuscin, believed to be a mitochondrial degradation product. Low mitochondrial contents are also observed in high-altitude natives such as Sherpas. In these subjects high-altitude performance seems to be improved by better coupling between ATP demand and supply pathways as well as better metabolite homeostasis. The hypoxia-inducible factor 1 (HIF-1) has been identified as a master regulator for the expression of genes involved in the hypoxia response, such as genes coding for glucose transporters, glycolytic enzymes and vascular endothelial growth factor (VEGF). HIF-1 achieves this by binding to hypoxia response elements in the promoter regions of these genes, whereby the increase of HIF-1 in hypoxia is the consequence of a reduced degradation of its dominant subunit HIF-1a. A further mechanism that seems implicated in the hypoxia response of muscle mitochondria is related to the formation of reactive oxygen species (ROS) in mitochondria during oxidative phosphorylation. How exactly ROS interfere with HIF-1a as well as MAP kinase and other signalling pathways is debated. The current evidence suggests that mitochondria themselves could be important players in oxygen sensing.

  13. Muscle fibre type composition of a number of limb muscles in different types of horse.

    Science.gov (United States)

    Snow, D H; Guy, P S

    1980-03-01

    Skeletal muscle of the equine was differentiated into three fibre types according to myosin ATPase (pH 9.4) and succinic dehydrogenase activity. The percentage of these types was determined in the musculus deltoideus, m triceps brachii caput longum, m gluteus medius, m semitendinosis, m biceps femoris and m vastus lateralis of the thoroughbred, Shetland pony, pony, heavy hunter and donkey. In addition the m gluteus medius was examined in the arab and American racing quarterhorse. High myosin ATPase activity fibres varied from a mean of 93.2 per cent in the m gluteus medius of the quarterhorse to 58.2 per cent in the m vastus lateralis of the donkey. In the m gluteus medius it was found that the percentage of high mycosin ATPase (pH 9.4) fibres varied significantly among breeds and these differences were related to the sprinting speed of the breed.

  14. New Insights into Muscle Fibre Types in Casertana Pig

    OpenAIRE

    Salvatore Velotto; Claudia Vitale; Tommaso Stasi; Antonio Crasto

    2010-01-01

    Little is known about the Casertana pig. The aim of this study was to evaluate the effect of sex on histochemical and morphometrical characteristics of muscle fibres (myocytes) in this pure breed and to verify the presence of giant fibres as well as vascularity of the muscle. Finally, maximum shortening velocity and isometric tension were measured in single muscle fibres. Sixteen Casertana pigs (8 males, 8 females) from a farm in Campania (Italy) were slaughtered at one year of age. Muscle ti...

  15. [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.

  16. Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex.

    NARCIS (Netherlands)

    Postel, R.; Vakeel, P.; Topczewski, J.; Knoll, R.; Bakkers, J.

    2008-01-01

    Mechanical instability of skeletal muscle cells is the major cause of congenital muscular dystrophy. Here we show that the zebrafish lost-contact mutant, that lacks a functional integrin-linked kinase (ilk) gene, suffers from mechanical instability of skeletal muscle fibres. With genetic and

  17. Skeletal muscle and hormonal adaptation to physical training in the rat

    DEFF Research Database (Denmark)

    Henriksson, J; Svedenhag, J; Richter, Erik

    1985-01-01

    The main purpose of the present study was to test the hypothesis that adrenergic stimulation of muscle fibres during exercise is a major stimulus for the training-induced enhancement of skeletal muscle respiratory capacity. Therefore, Sprague-Dawley rats either underwent bilateral surgical ablati...

  18. Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging

    OpenAIRE

    Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian

    2014-01-01

    Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres...

  19. Human skeletal muscle type 1 fibre distribution and response of stress-sensing proteins along the titin molecule after submaximal exhaustive exercise.

    Science.gov (United States)

    Koskinen, Satu O A; Kyröläinen, Heikki; Flink, Riina; Selänne, Harri P; Gagnon, Sheila S; Ahtiainen, Juha P; Nindl, Bradley C; Lehti, Maarit

    2017-11-01

    Early responses of stress-sensing proteins, muscle LIM protein (MLP), ankyrin repeat proteins (Ankrd1/CARP and Ankrd2/Arpp) and muscle-specific RING finger proteins (MuRF1 and MuRF2), along the titin molecule were investigated in the present experiment after submaximal exhaustive exercise. Ten healthy men performed continuous drop jumping unilaterally on a sledge apparatus with a submaximal height until complete exhaustion. Five stress-sensing proteins were analysed by mRNA measurements from biopsies obtained immediately and 3 h after the exercise from exercised vastus lateralis muscle while control biopsies were obtained from non-exercised legs before the exercise. Decreased maximal jump height and increased serum creatine kinase activities as indirect markers for muscle damage and HSP27 immunostainings on muscle biopsies as a direct marker for muscle damage indicated that the current exercised protocol caused muscle damage. mRNA levels for four (MLP, Ankrd1/CARP, MuRF1 and MuRF2) out of the five studied stress sensors significantly (p exercise. The magnitude of MLP and Ankrd2 responses was related to the proportion of type 1 myofibres. Our data showed that the submaximal exhaustive exercise with subject's own physical fitness level activates titin-based stretch-sensing proteins. These results suggest that both degenerative and regenerative pathways are activated in very early phase after the exercise or probably already during the exercise. Activation of these proteins represents an initial step forward adaptive remodelling of the exercised muscle and may also be involved in the initiation of myofibre repair.

  20. 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.

  1. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

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

    2014-01-01

    , skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), prespiration rates were normalized by CS (respiration...... per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, Complex I state 2 normalized for CS activity, an index of non-phosphorylating respiration per mitochondrial content, increased progressively from cardiac, skeletal...

  2. New Insights into Muscle Fibre Types in Casertana Pig

    Directory of Open Access Journals (Sweden)

    Salvatore Velotto

    2010-01-01

    Full Text Available Little is known about the Casertana pig. The aim of this study was to evaluate the effect of sex on histochemical and morphometrical characteristics of muscle fibres (myocytes in this pure breed and to verify the presence of giant fibres as well as vascularity of the muscle. Finally, maximum shortening velocity and isometric tension were measured in single muscle fibres. Sixteen Casertana pigs (8 males, 8 females from a farm in Campania (Italy were slaughtered at one year of age. Muscle tissues were obtained from psoas minor, rhomboideus and longissimus dorsi. Myofibres were stained for myosin adenosine triphosphatase, succinic dehydrogenase, and α-amylase-periodic acid schiff. For all fibre types, the area and perimeter were measured. Slowtwitch oxidative fibres, fast-twitch glycolytic fibres and fast-twitch oxidative-glycolytic fibres were histochemically differentiated; an image-analyzing system was used. The results showed significant differences between the sexes in the size of all three fibre types. The psoas minor muscle had a high percentage of slow-twitch oxidative fibres and contained more capillaries per fibre and per mm2 than rhomboideus and longissimus dorsi, in which fast-twitch glycolytic fibres dominated. The cross-sectional area of all fibre types was larger in longissimus dorsi than in rhomboideus and psoas minor muscles; the giant fibres were present in the longissimus dorsi muscle only. Besides, isometric tension values were higher in fast-twitch glycolytic fibres than in the other ones. Variations in fibre type composition may contribute to meat quality.

  3. Exercise Promotes Healthy Aging of Skeletal Muscle.

    Science.gov (United States)

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

    2016-06-14

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice.

    Science.gov (United States)

    Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

    2012-06-01

    Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  5. 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.

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

    Science.gov (United States)

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

    2018-06-01

    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.

  7. 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.

  8. 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...

  9. 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

  10. Skeletal muscle weakness in osteogenesis imperfecta mice.

    Science.gov (United States)

    Gentry, Bettina A; Ferreira, J Andries; McCambridge, Amanda J; Brown, Marybeth; Phillips, Charlotte L

    2010-09-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (P(o), P(o)/mg and P(o)/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased P(o) and an inability to sustain P(o) for the 300-ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

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

  12. Muscle architecture and fibre characteristics of rat gastrocnemius and semimembranosus muscles during isometric contractions.

    Science.gov (United States)

    Huijing, P A; van Lookeren Campagne, A A; Koper, J F

    1989-01-01

    Rat gastrocnemius medialis (GM) and semimembranosus (SM) muscles have a very different morphology. GM is a very pennate muscle, combining relatively short muscle fibre length with sizable fibre angles and long muscle and aponeurosis lengths. SM is a more parallel-fibred muscle, combining a relatively long fibre length with a small fibre angle and short aponeurosis length. The mechanisms of fibre shortening as well as angle increase are operational in GM as well as SM. However, as a consequence of isometric contraction, changes of fibre length and angle are greater for GM than for SM at any relative muscle length. These differences are particularly notable at short muscle lengths: at 80% of optimum muscle length, fibre length changes of approximately 30% are coupled to fibre angle changes of 15 degrees in GM, while for SM these changes are 4% and 0.6 degrees, respectively. A considerable difference was found for normalized active slack muscle length (GM approximately 80 and SM approximately 45%). This is explained by differences of degree of pennation as well as factors related to differences found for estimated fibre length-force characteristics. Estimated normalized active fibre slack length was considerably smaller for SM than for GM (approximately 40 and 60%, respectively). The most likely explanation of these findings are differences of distribution of optimum fibre lengths, possibly in combination with differences of myofilament lengths and/or fibre length distributions.

  13. A physiologically based, multi-scale model of skeletal muscle structure and function

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    Oliver eRöhrle

    2012-09-01

    Full Text Available Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle's response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modelling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle's response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modelling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibres and their grouping. Together with a well-established model of motor unit recruitment, the electro-physiological behaviour of single muscle fibres within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenisation. The effect of homogenisation has been investigated by varying the number of embedded skeletal muscle fibres and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the Tibialis Anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modelling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behaviour ranging from motor unit recruitment to force generation and fatigue.

  14. A neuro-mechanical model of a single leg joint highlighting the basic physiological role of fast and slow muscle fibres of an insect muscle system.

    Directory of Open Access Journals (Sweden)

    Tibor Istvan Toth

    Full Text Available In legged animals, the muscle system has a dual function: to produce forces and torques necessary to move the limbs in a systematic way, and to maintain the body in a static position. These two functions are performed by the contribution of specialized motor units, i.e. motoneurons driving sets of specialized muscle fibres. With reference to their overall contraction and metabolic properties they are called fast and slow muscle fibres and can be found ubiquitously in skeletal muscles. Both fibre types are active during stepping, but only the slow ones maintain the posture of the body. From these findings, the general hypothesis on a functional segregation between both fibre types and their neuronal control has arisen. Earlier muscle models did not fully take this aspect into account. They either focused on certain aspects of muscular function or were developed to describe specific behaviours only. By contrast, our neuro-mechanical model is more general as it allows functionally to differentiate between static and dynamic aspects of movement control. It does so by including both muscle fibre types and separate motoneuron drives. Our model helps to gain a deeper insight into how the nervous system might combine neuronal control of locomotion and posture. It predicts that (1 positioning the leg at a specific retraction angle in steady state is most likely due to the extent of recruitment of slow muscle fibres and not to the force developed in the individual fibres of the antagonistic muscles; (2 the fast muscle fibres of antagonistic muscles contract alternately during stepping, while co-contraction of the slow muscle fibres takes place during steady state; (3 there are several possible ways of transition between movement and steady state of the leg achieved by varying the time course of recruitment of the fibres in the participating muscles.

  15. Histochemical and functional fibre typing of the rabbit masseter muscle

    NARCIS (Netherlands)

    Bredman, J. J.; Weijs, W. A.; Moorman, A. F.; Brugman, P.

    1990-01-01

    The fibre-type distribution of the masseter muscle of the rabbit was studied by means of the myosin-ATPase and succinate dehydrogenase reactions. Six different fibre types were found and these were unequally distributed between and within the anatomical compartments of the muscle. Most of the

  16. 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.

  17. 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 b...

  18. The Human Skeletal Muscle Proteome Project

    DEFF Research Database (Denmark)

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

    2017-01-01

    Skeletal muscle is a large organ that accounts for up to half the total mass of the human body. A progressive decline in muscle mass and strength occurs with ageing and in some individuals configures the syndrome of ‘sarcopenia’, a condition that impairs mobility, challenges autonomy, and is a ri...

  19. 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.

  20. Leucine stimulation of skeletal muscle protein synthesis

    International Nuclear Information System (INIS)

    Layman, D.K.; Grogan, C.K.

    1986-01-01

    Previous work in this laboratory has demonstrated a stimulatory effect of leucine on skeletal muscle protein synthesis measured in vitro during catabolic conditions. Studies in other laboratories have consistently found this effect in diaphragm muscle, however, studies examining effects on nitrogen balance or with in vivo protein synthesis in skeletal muscle are equivocal. This experiment was designed to determine the potential of leucine to stimulate skeletal muscle protein synthesis in vivo. Male Sprague-Dawley rats weighing 200 g were fasted for 12 hrs, anesthetized, a jugular cannula inserted, and protein synthesis measured using a primed continuous infusion of 14 C-tyrosine. A plateau in specific activity was reached after 30 to 60 min and maintained for 3 hrs. The leucine dose consisted of a 240 umole priming dose followed by a continuous infusion of 160 umoles/hr. Leucine infusion stimulated protein synthesis in the soleus muscle (28%) and in the red (28%) and white portions (12%) of the gastrocnemius muscle compared with controls infused with only tyrosine. The increased rates of protein synthesis were due to increased incorporation of tyrosine into protein and to decreased specific activity of the free tyrosine pool. These data indicate that infusion of leucine has the potential to stimulate in vivo protein synthesis in skeletal muscles

  1. Two functionally different muscle fibre types in some salps?

    Directory of Open Access Journals (Sweden)

    Q. Bone

    1998-12-01

    Full Text Available This paper describes the structure and operation of the fibres in the locomotor muscle bands of several salp species. In many species, for example Thalia democratica or Pegea confoederata, all the muscle fibres of the locomotor muscle bands are similar in width and structure. In others, for example Salpa fusiformis and S. maxima, although fibre structure is similar, the marginal fibres edging the bands may be some 3-4 times the width of those in the centre of the band. In Ihlea punctata, not only is there a more striking difference in width between the marginal and central fibres of the bands, but also the two differ in structure. The marginal fibres are up to 10 times the width of the central fibres and the two differ in myofibrillar and mitochondrial content. Intracellular recordings from the fibres show that the normally compound spike potentials do not overshoot resting potentials (up to -70 mV, and are decremental. The two types of fibre may be separately activated. It is suggested that in Ihlea punctata, the wide marginal fibres may be involved in slow swimming, the central narrow fibres in `escape´ swimming.

  2. Eccentric Contraction-Induced Muscle Fibre Adaptation

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    Arabadzhiev T. I.

    2009-12-01

    Full Text Available Hard-strength training induces strength increasing and muscle damage, especially after eccentric contractions. Eccentric contractions also lead to muscle adaptation. Symptoms of damage after repeated bout of the same or similar eccentrically biased exercises are markedly reduced. The mechanism of this repeated bout effect is unknown. Since electromyographic (EMG power spectra scale to lower frequencies, the adaptation is related to neural adaptation of the central nervous system (CNS presuming activation of slow-non-fatigable motor units or synchronization of motor unit firing. However, the repeated bout effect is also observed under repeated stimulation, i.e. without participation of the CNS. The aim of this study was to compare the possible effects of changes in intracellular action potential shape and in synchronization of motor units firing on EMG power spectra. To estimate possible degree of the effects of central and peripheral changes, interferent EMG was simulated under different intracellular action potential shapes and different degrees of synchronization of motor unit firing. It was shown that the effect of changes in intracellular action potential shape and muscle fibre propagation velocity (i.e. peripheral factors on spectral characteristics of EMG signals could be stronger than the effect of synchronization of firing of different motor units (i.e. central factors.

  3. 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.

  4. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

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

  5. Differential response of early and late phases of skeletal muscle regeneration to exogenous supply of testosterone and insulin

    International Nuclear Information System (INIS)

    Qazi, I.; Riaz, S.

    2005-01-01

    Effect of insulin and testosterone, separately and in combination on the regeneration of skeletal fibres within intact extensor digitorum longus (EDL) muscle grafts was studied in mice. It was found that intraperitoneal supply of 2 mg/100 g body weight/day of testosterone accelerated skeletal muscle regeneration within ten days of grafting. The regenerated muscle fibres in such grafts attained significantly higher % recovery of average cross-sectional area (ACSA) than in the controls grafts. Later on, provision of the hormone did not further promote growth of the regenerated muscle fibres. In the insulin-supplemented animals (2 units/100 g body weight/day) the grafts showed hyperplasia and atrophy of the regenerating muscle fibres during the first and the last study periods, respectively. Histological and morphometric analysis of 20-day old EDL muscle regenerates that were supplied with either insulin or testosterone during the first 10-days of transplantation followed by hormone administration in reverse sequence revealed valuable differences. Supply of testosterone and then insulin escalated the process of regeneration and growth so that the ACSA of the regenerated muscle fibres in such grafts turned out to be significantly higher that in the corresponding stages of control, or when only insulin and only testosterone were administered. Reverse sequence of the administration of the hormones exerted negative effects and the regenerated muscle fibres showed various levels of atrophy. These results indicate the importance of identification of particular phases of the process of skeletal muscle regeneration that may be more responsive to anabolic agents. Proper sequence of administration of the hormones to promote the regeneration of skeletal muscle fibres in whole EDL muscle autotransplants is also explained. (author)

  6. 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

  7. A mini-overview of single muscle fibre mechanics: the effects of age, inactivity and exercise in animals and humans.

    Science.gov (United States)

    Jee, Hyunseok; Kim, Jong-Hee

    2017-09-05

    Many basic movements of living organisms are dependent on muscle function. Muscle function allows for the coordination and harmonious integrity of movement that is necessary for various biological processes. Gross and fine motor skills are both regulated at the micro-level (single muscle fibre level), controlled by neuronal regulation, and it is therefore important to understand muscle function at both micro- and macro-levels to understand the overall movement of living organisms. Single muscle mechanics and the cellular environment of muscles fundamentally allow for the harmonious movement of our bodies. Indeed, a clear understanding of the functionality of muscle at the micro-level is indispensable for explaining muscular function at the macro-(whole gross muscle) level. By investigating single muscle fibre mechanics, we can also learn how other factors such Ca2+ kinetics, enzyme activity and contractile proteins can contribute to muscle mechanics at the micro- and macro-levels. Further, we can also describe how aging affects the capacity of skeletal muscle cells, as well as how exercise can prevent aging-based sarcopenia and frailty. The purpose of this review is to introduce and summarise the current knowledge of single muscle fibre mechanics in light of aging and inactivity. We then describe how exercise mitigates negative muscle adaptations that occur under those circumstances. In addition, single muscle fibre mechanics in both animal and human models are discussed.

  8. 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.

  9. 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

  10. Redox responses are preserved across muscle fibres with differential susceptibility to aging.

    Science.gov (United States)

    Smith, Neil T; Soriano-Arroquia, Ana; Goljanek-Whysall, Katarzyna; Jackson, Malcolm J; McDonagh, Brian

    2018-04-15

    Age-related loss of muscle mass and function is associated with increased frailty and loss of independence. The mechanisms underlying the susceptibility of different muscle types to age-related atrophy are not fully understood. Reactive oxygen species (ROS) are recognised as important signalling molecules in healthy muscle and redox sensitive proteins can respond to intracellular changes in ROS concentrations modifying reactive thiol groups on Cysteine (Cys) residues. Conserved Cys residues tend to occur in functionally important locations and can have a direct impact on protein function through modifications at the active site or determining protein conformation. The aim of this work was to determine age-related changes in the redox proteome of two metabolically distinct murine skeletal muscles, the quadriceps a predominantly glycolytic muscle and the soleus which contains a higher proportion of mitochondria. To examine the effects of aging on the global proteome and the oxidation state of individual redox sensitive Cys residues, we employed a label free proteomics approach including a differential labelling of reduced and reversibly oxidised Cys residues. Our results indicate the proteomic response to aging is dependent on muscle type but redox changes that occur primarily in metabolic and cytoskeletal proteins are generally preserved between metabolically distinct tissues. Skeletal muscle containing fast twitch glycolytic fibres are more susceptible to age related atrophy compared to muscles with higher proportions of oxidative slow twitch fibres. Contracting skeletal muscle generates reactive oxygen species that are required for correct signalling and adaptation to exercise and it is also known that the intracellular redox environment changes with age. To identify potential mechanisms for the distinct response to age, this article combines a global proteomic approach and a differential labelling of reduced and reversibly oxidised Cysteine residues in two

  11. Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse.

    Science.gov (United States)

    Rooney, Mary F; Porter, Richard K; Katz, Lisa M; Hill, Emmeline W

    2017-01-01

    Variation in the myostatin (MSTN) gene has been reported to be associated with race distance, body composition and skeletal muscle fibre composition in the horse. The aim of the present study was to test the hypothesis that MSTN variation influences mitochondrial phenotypes in equine skeletal muscle. Mitochondrial abundance and skeletal muscle fibre types were measured in whole muscle biopsies from the gluteus medius of n = 82 untrained (21 ± 3 months) Thoroughbred horses. Skeletal muscle fibre type proportions were significantly (p T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of mitochondrial complex activities indicated higher combined mitochondrial complex I+III and II+III activities in the presence of the C-allele / I allele (p ≤ 0.05). The restoration of complex I+III and complex II+III activities following addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme Q in these animals. In addition, decreased gene expression in two coenzyme Q (CoQ) biosynthesis pathway genes (COQ4, p ≤ 0.05; ADCK3, p ≤ 0.01) in the TT/NN horses was observed. This study has identified several mitochondrial phenotypes associated with MSTN genotype in untrained Thoroughbred horses and in addition, our findings suggest that nutritional supplementation with CoQ may aid to restore coenzyme Q activity in TT/NN horses.

  12. Ultrasound of skeletal muscle injury.

    Science.gov (United States)

    Koh, Eamon Su Chun; McNally, Eugene G

    2007-06-01

    The professional and recreational demands of modern society make the treatment of muscle injury an increasingly important clinical problem, particularly in the athletic population. In the elite athlete, significant financial and professional pressures may also exist that emphasize the need for accurate diagnosis and treatment. With new advances in ultrasound technology, images of exquisite detail allow diagnosis of muscle injury that matches the accuracy of magnetic resonance imaging (MRI). Furthermore, the benefits of real-time and Doppler imaging, ability to perform interventional procedures, and relative cost benefits compared with MRI place ultrasound at the forefront for investigation for these injuries in many circumstances. Muscle injury may be divided into acute and chronic pathology, with muscle strain injury the most common clinical problem presenting to sports physicians. This article reviews the spectrum of acute and chronic muscle injuries, with particular attention to clinical features and some common or important muscle strain injuries.

  13. Analysis of myofibrillar proteins and transcripts in adult skeletal muscles of the American lobster Homarus americanus: variable expression of myosins, actin and troponins in fast, slow-twitch and slow-tonic fibres.

    Science.gov (United States)

    Medler, Scott; Mykles, Donald L

    2003-10-01

    Skeletal muscles are diverse in their contractile properties, with many of these differences being directly related to the assemblages of myofibrillar isoforms characteristic of different fibers. Crustacean muscles are similar to other muscles in this respect, although the majority of information about differences in muscle organization comes from vertebrate species. In the present study, we examined the correlation between myofibrillar protein isoforms and the patterns of myofibrillar gene expression in fast, slow-phasic (S(1)) and slow-tonic (S(2)) fibers of the American lobster Homarus americanus. SDS-PAGE and western blotting were used to identify isoform assemblages of myosin heavy chain (MHC), P75, troponin T (TnT) and troponin I (TnI). RT-PCR was used to monitor expression of fast and slow (S(1)) MHC, P75 and actin in different fiber types, and the MHC and actin levels were quantified by real-time PCR. Fast and slow fibers from the claw closers predominantly expressed fast and S(1) MHC, respectively, but also lower levels of the alternate MHC. By contrast, fast fibers from the deep abdominal muscle expressed fast MHC exclusively. In addition, slow muscles expressed significantly higher levels of actin than fast fibers. A distal bundle of fibers in the cutter claw closer muscle was found to be composed of a mixture of S(1) and S(2) fibers, many of which possessed a mixture of S(1) and S(2) MHC isoforms. This pattern supports the idea that S(1) and S(2) fibers represent extremes in a continuum of slow muscle phenotype. Overall, these patterns demonstrate that crustacean skeletal muscles cannot be strictly categorized into discrete fiber types, but a muscle's properties probably represent a point on a continuum of fiber types. This trend may result from differences in innervation pattern, as each muscle is controlled by a unique combination of phasic, tonic or both phasic and tonic motor nerves. In this respect, future studies examining how muscle phenotype

  14. Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle.

    Science.gov (United States)

    Fusi, L; Brunello, E; Yan, Z; Irving, M

    2016-10-31

    Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.

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

    Science.gov (United States)

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

    2017-08-01

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

  16. Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

    Science.gov (United States)

    Lee, Peter H U; Vandenburgh, Herman H

    2013-10-01

    Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

  17. Myonuclear domain size and myosin isoform expression in muscle fibres from mammals representing a 100,000-fold difference in body size.

    Science.gov (United States)

    Liu, Jing-Xia; Höglund, Anna-Stina; Karlsson, Patrick; Lindblad, Joakim; Qaisar, Rizwan; Aare, Sudhakar; Bengtsson, Ewert; Larsson, Lars

    2009-01-01

    This comparative study of myonuclear domain (MND) size in mammalian species representing a 100,000-fold difference in body mass, ranging from 25 g to 2500 kg, was undertaken to improve our understanding of myonuclear organization in skeletal muscle fibres. Myonuclear domain size was calculated from three-dimensional reconstructions in a total of 235 single muscle fibre segments at a fixed sarcomere length. Irrespective of species, the largest MND size was observed in muscle fibres expressing fast myosin heavy chain (MyHC) isoforms, but in the two smallest mammalian species studied (mouse and rat), MND size was not larger in the fast-twitch fibres expressing the IIA MyHC isofom than in the slow-twitch type I fibres. In the larger mammals, the type I fibres always had the smallest average MND size, but contrary to mouse and rat muscles, type IIA fibres had lower mitochondrial enzyme activities than type I fibres. Myonuclear domain size was highly dependent on body mass in the two muscle fibre types expressed in all species, i.e. types I and IIA. Myonuclear domain size increased in muscle fibres expressing both the beta/slow (type I; r = 0.84, P fast IIA MyHC isoform (r = 0.90; P muscle fibre type, independent of species. However, myosin isoform expression is not the sole protein determining MND size, and other protein systems, such as mitochondrial proteins, may be equally or more important determinants of MND size.

  18. Muscle fibre types of fishes : structural and functional specialization

    NARCIS (Netherlands)

    Akster, H.A.

    1984-01-01

    Muscles of fishes are active in a variety of movements that differ in velocity, duration and excursion length. To investigate how muscles meet the, often conflicting, demands imposed upon them by these movements, the fibre type composition of several muscles was determined. The ultrastructural and

  19. 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.

  20. The essence of biophysical cues in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Langelaan, M.L.P.

    2010-01-01

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications. Evidently, tissue engineered skeletal muscle can be used in the field of regenerative medicine to repair muscular defects or dystrophies. Engineered skeletal muscle constructs can also be used as a

  1. 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

  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. Training induced adaptation in horse skeletal muscle

    NARCIS (Netherlands)

    Dam, K.G. van

    2006-01-01

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

  4. A re-examination of the biphasic theory of skeletal muscle growth.

    Science.gov (United States)

    Levine, A S; Hegarty, P V

    1977-01-01

    Because of the importance of fibre diameter measurements it was decided to re-evaluate the biphasic theory of skeletal muscle growth and development. This theory proposes an initial memophasic distribution of muscle fibres which changes to a biphasic distribution during development. The theory is based on observations made on certain muscles in mice, where two distinct populations of fibre diameters (20 and 40 micronm) contribute to the biphasic distribution. In the present investigation corss sections of frozen biceps brachii of mice in rigor mortis were examined. The rigor state was used to avoid complications produced by thaw-rigor contraction. The diameters of the outermost and innermost fibres were found to be significantly different. However, if the outer and inner fibres were combined to form one group, no significant difference between this group and other random groups was found. The distributions of all groups were monophasic. The diameters of isolated fibres from mice and rats also displayed a monophasic distribution. This evidence leads to the conclusion that the biphasic theory of muscle growth is untenable. Some of the variables which may occur in fibre size and shape are discussed. Images Fig. 1 PMID:858691

  5. Adaptive functional specialisation of architectural design and fibre type characteristics in agonist shoulder flexor muscles of the llama, Lama glama.

    Science.gov (United States)

    Graziotti, Guillermo H; Chamizo, Verónica E; Ríos, Clara; Acevedo, Luz M; Rodríguez-Menéndez, J M; Victorica, C; Rivero, José-Luis L

    2012-08-01

    Like other camelids, llamas (Lama glama) have the natural ability to pace (moving ipsilateral limbs in near synchronicity). But unlike the Old World camelids (bactrian and dromedary camels), they are well adapted for pacing at slower or moderate speeds in high-altitude habitats, having been described as good climbers and used as pack animals for centuries. In order to gain insight into skeletal muscle design and to ascertain its relationship with the llama's characteristic locomotor behaviour, this study examined the correspondence between architecture and fibre types in two agonist muscles involved in shoulder flexion (M. teres major - TM and M. deltoideus, pars scapularis - DS and pars acromialis - DA). Architectural properties were found to be correlated with fibre-type characteristics both in DS (long fibres, low pinnation angle, fast-glycolytic fibre phenotype with abundant IIB fibres, small fibre size, reduced number of capillaries per fibre and low oxidative capacity) and in DA (short fibres, high pinnation angle, slow-oxidative fibre phenotype with numerous type I fibres, very sparse IIB fibres, and larger fibre size, abundant capillaries and high oxidative capacity). This correlation suggests a clear division of labour within the M. deltoideus of the llama, DS being involved in rapid flexion of the shoulder joint during the swing phase of the gait, and DA in joint stabilisation during the stance phase. However, the architectural design of the TM muscle (longer fibres and lower fibre pinnation angle) was not strictly matched with its fibre-type characteristics (very similar to those of the postural DA muscle). This unusual design suggests a dual function of the TM muscle both in active flexion of the shoulder and in passive support of the limb during the stance phase, pulling the forelimb to the trunk. This functional specialisation seems to be well suited to a quadruped species that needs to increase ipsilateral stability of the limb during the support

  6. Adaptive functional specialisation of architectural design and fibre type characteristics in agonist shoulder flexor muscles of the llama, Lama glama

    Science.gov (United States)

    Graziotti, Guillermo H; Chamizo, Verónica E; Ríos, Clara; Acevedo, Luz M; Rodríguez-Menéndez, J M; Victorica, C; Rivero, José-Luis L

    2012-01-01

    Like other camelids, llamas (Lama glama) have the natural ability to pace (moving ipsilateral limbs in near synchronicity). But unlike the Old World camelids (bactrian and dromedary camels), they are well adapted for pacing at slower or moderate speeds in high-altitude habitats, having been described as good climbers and used as pack animals for centuries. In order to gain insight into skeletal muscle design and to ascertain its relationship with the llama’s characteristic locomotor behaviour, this study examined the correspondence between architecture and fibre types in two agonist muscles involved in shoulder flexion (M. teres major – TM and M. deltoideus, pars scapularis – DS and pars acromialis – DA). Architectural properties were found to be correlated with fibre-type characteristics both in DS (long fibres, low pinnation angle, fast-glycolytic fibre phenotype with abundant IIB fibres, small fibre size, reduced number of capillaries per fibre and low oxidative capacity) and in DA (short fibres, high pinnation angle, slow-oxidative fibre phenotype with numerous type I fibres, very sparse IIB fibres, and larger fibre size, abundant capillaries and high oxidative capacity). This correlation suggests a clear division of labour within the M. deltoideus of the llama, DS being involved in rapid flexion of the shoulder joint during the swing phase of the gait, and DA in joint stabilisation during the stance phase. However, the architectural design of the TM muscle (longer fibres and lower fibre pinnation angle) was not strictly matched with its fibre-type characteristics (very similar to those of the postural DA muscle). This unusual design suggests a dual function of the TM muscle both in active flexion of the shoulder and in passive support of the limb during the stance phase, pulling the forelimb to the trunk. This functional specialisation seems to be well suited to a quadruped species that needs to increase ipsilateral stability of the limb during the

  7. Effect of the bendiocarb on the ultrastructure of rabbit skeletal muscle

    Directory of Open Access Journals (Sweden)

    Katarína Holovská

    2017-01-01

    Full Text Available Bendiocarb belongs to the group of carbamate insecticides that inhibit acetylcholinesterase. In agriculture, it is used to control a variety of insects, therefore it is important to examine every potential aspect of its toxicology. The aim of this study was to observe the effect of bendiocarb on the ultrastructure of the skeletal muscle in rabbits. Rabbits in all experimental groups received capsules of bendiocarb (96% Bendiocarb, Bayer, Germany per os daily at a dose of 5 mg/kg body weight. Samples of skeletal muscles were collected on days 10 and 20. On day 10 of the experiment, muscle fibres were not affected consistently. The observed changes were moderate and focal. Electron microscopy revealed dilatation of sarcoplasmic reticulum, and myofilament disorganization. On day 20 of the experiment, the ultrastructural changes in muscle fibres were more intense and more frequent. The most important alteration was the disruption of the sarcomeres due to the lysis of both thick and thin myofilaments. However, in the unchanged regions of muscle fibres a prominent mitochondrial swelling was observed. Many mitochondria lacked cristae and thus appeared as large membrane-bound cytoplasmic vesicles. The results presented in this study indicate that bendiocarb affects the ultrastructure of skeletal muscles. The intensity of damage (dissolution of myofilaments and disruption of sarcomeres was related to the duration of administration of bendiocarb.

  8. Photothermal imaging of skeletal muscle mitochondria.

    Science.gov (United States)

    Tomimatsu, Toru; Miyazaki, Jun; Kano, Yutaka; Kobayashi, Takayoshi

    2017-06-01

    The morphology and topology of mitochondria provide useful information about the physiological function of skeletal muscle. Previous studies of skeletal muscle mitochondria are based on observation with transmission, scanning electron microscopy or fluorescence microscopy. In contrast, photothermal (PT) microscopy has advantages over the above commonly used microscopic techniques because of no requirement for complex sample preparation by fixation or fluorescent-dye staining. Here, we employed the PT technique using a simple diode laser to visualize skeletal muscle mitochondria in unstained and stained tissues. The fine mitochondrial network structures in muscle fibers could be imaged with the PT imaging system, even in unstained tissues. PT imaging of tissues stained with toluidine blue revealed the structures of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria and the swelling behavior of mitochondria in damaged muscle fibers with sufficient image quality. PT image analyses based on fast Fourier transform (FFT) and Grey-level co-occurrence matrix (GLCM) were performed to derive the characteristic size of mitochondria and to discriminate the image patterns of normal and damaged fibers.

  9. 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.

  10. Magnetic resonance findings in skeletal muscle tears

    International Nuclear Information System (INIS)

    De Smet, A.A.

    1993-01-01

    Magnetic resonance (MR) images of skeletal muscle tears can clearly delineate the severity of muscle injury. Although MR imaging is seldom necessary in patients with acute musle trauma, it can be helpful in deciding on clinical management. The two major MR findings in acute muscle tears are deformity of the muscle and the presence of abnormal signal reflecting hemorrhage and edema. In acute tears, methemoglobin within the extravascular blood causes high-signal areas on both T1- and T2-weighted images. With partial tears, the blood may dissect in a distinctive linear pattern along the muscle bundles and fibers. As healing begins, the muscle signal diminishes, first on the T1-weighted images and then on the T2-weighted images. When there is residual abnormal signal on images obtained more than several months after the injury, it is presumed to represent hemorrhage from recurrent tears. In patients with a questionable history of a remote injury, the clinical presentation may be that of persistent pain or a soft tissue mass. In these cases MR imaging may identify the cause of the pain and can exclude a neoplasm by proving that the mass is a hypertrophied or retracted musle. Thus, MR imaging has a limited, but occasionally important role in selected patients with skeletal muscle tears. (orig.)

  11. Characterisation of L-Type Amino Acid Transporter 1 (LAT1 Expression in Human Skeletal Muscle by Immunofluorescent Microscopy

    Directory of Open Access Journals (Sweden)

    Nathan Hodson

    2017-12-01

    Full Text Available The branch chain amino acid leucine is a potent stimulator of protein synthesis in skeletal muscle. Leucine rapidly enters the cell via the L-Type Amino Acid Transporter 1 (LAT1; however, little is known regarding the localisation and distribution of this transporter in human skeletal muscle. Therefore, we applied immunofluorescence staining approaches to visualise LAT1 in wild type (WT and LAT1 muscle-specific knockout (mKO mice, in addition to basal human skeletal muscle samples. LAT1 positive staining was visually greater in WT muscles compared to mKO muscle. In human skeletal muscle, positive LAT1 staining was noted close to the sarcolemmal membrane (dystrophin positive staining, with a greater staining intensity for LAT1 observed in the sarcoplasmic regions of type II fibres (those not stained positively for myosin heavy-chain 1, Type II—25.07 ± 5.93, Type I—13.71 ± 1.98, p < 0.01, suggesting a greater abundance of this protein in these fibres. Finally, we observed association with LAT1 and endothelial nitric oxide synthase (eNOS, suggesting LAT1 association close to the microvasculature. This is the first study to visualise the distribution and localisation of LAT1 in human skeletal muscle. As such, this approach provides a validated experimental platform to study the role and regulation of LAT1 in human skeletal muscle in response to various physiological and pathophysiological models.

  12. Orthogonal muscle fibres have different instructive roles in planarian regeneration.

    Science.gov (United States)

    Scimone, M Lucila; Cote, Lauren E; Reddien, Peter W

    2017-11-30

    The ability to regenerate missing body parts exists throughout the animal kingdom. Positional information is crucial for regeneration, but how it is harboured and used by differentiated tissues is poorly understood. In planarians, positional information has been identified from study of phenotypes caused by RNA interference in which the wrong tissues are regenerated. For example, inhibition of the Wnt signalling pathway leads to regeneration of heads in place of tails. Characterization of these phenotypes has led to the identification of position control genes (PCGs)-genes that are expressed in a constitutive and regional manner and are associated with patterning. Most PCGs are expressed within planarian muscle; however, how muscle is specified and how different muscle subsets affect regeneration is unknown. Here we show that different muscle fibres have distinct regulatory roles during regeneration in the planarian Schmidtea mediterranea. myoD is required for formation of a specific muscle cell subset: the longitudinal fibres, oriented along the anterior-posterior axis. Loss of longitudinal fibres led to complete regeneration failure because of defects in regeneration initiation. A different transcription factor-encoding gene, nkx1-1, is required for the formation of circular fibres, oriented along the medial-lateral axis. Loss of circular fibres led to a bifurcated anterior-posterior axis with fused heads forming in single anterior blastemas. Whereas muscle is often viewed as a strictly contractile tissue, these findings reveal that different muscle types have distinct and specific regulatory roles in wound signalling and patterning to enable regeneration.

  13. 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.

  14. IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.

    Science.gov (United States)

    Lynch, G S; Cuffe, S A; Plant, D R; Gregorevic, P

    2001-04-01

    Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering from muscle wasting conditions, few studies have investigated the functional properties of dystrophic skeletal muscle following IGF-I treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a deficiency in the structural protein, laminin, and exhibit severe muscle wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment ( approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously) would increase the mass and force producing capacity of skeletal muscles from dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively, compared with untreated dystrophic mice (administered saline-vehicle only). Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was increased by 23% in the EDL muscles of treated compared with untreated mice, but in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decreased the proportion of type I fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic mice, IGF-I treatment increased the proportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus muscles of treated compared with untreated mice. We conclude that IGF-I treatment ameliorates muscle wasting and improves the functional properties of skeletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the muscular dystrophies.

  15. A new approach for the validation of skeletal muscle modelling using MRI data

    Science.gov (United States)

    Böl, Markus; Sturmat, Maike; Weichert, Christine; Kober, Cornelia

    2011-05-01

    Active and passive experiments on skeletal muscles are in general arranged on isolated muscles or by consideration of the whole muscle packages, such as the arm or the leg. Both methods exhibit advantages and disadvantages. By applying experiments on isolated muscles it turns out that no information about the surrounding tissues are considered what leads to insufficient specifications of the isolated muscle. Especially, the muscle shape and the fibre directions of an embedded muscle are completely different to that of the same isolated muscle. An explicit advantage, in contrast, is the possibility to study the mechanical characteristics in an unique, isolated way. On the other hand, by applying experiments on muscle packages the aforementioned pros and cons reverse. In such situation, the whole surrounding tissue is considered in the mechanical characteristics of the muscle which are much more difficult to identify. However, an embedded muscle reflects a much more realistic situation as in isolated condition. Thus, in the proposed work to our knowledge, we, for the first time, suggest a technique that allows to study characteristics of single skeletal muscles inside a muscle package without any computation of the tissue around the muscle of interest. In doing so, we use magnetic resonance imaging data of an upper arm during contraction. By applying a three-dimensional continuum constitutive muscle model we are able to study the biceps brachii inside the upper arm and validate the modelling approach by optical experiments.

  16. 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.

  17. Effect of statins on skeletal muscle function.

    Science.gov (United States)

    Parker, Beth A; Capizzi, Jeffrey A; Grimaldi, Adam S; Clarkson, Priscilla M; Cole, Stephanie M; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S; Simpson, Kathleen; White, C Michael; Thompson, Paul D

    2013-01-01

    Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (Pmuscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

  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. Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

    Science.gov (United States)

    Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

    2015-05-28

    Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

  20. Skeletal Muscle Angiogenesis and Its Relation to Insulin Sensitivity

    DEFF Research Database (Denmark)

    Lindqvist, Anna Maria Charlotte K

    mediator of angiogenesis) are reduced in insulin resistant individuals. Exercise training can improve skeletal muscle capillarization and the angiogenic potential and physical activity has also been proven to enhance muscle insulin sensitivity. Increased skeletal muscle capillarization is associated......) or by overexpression of VEGF-A in the tibialis anterior muscle (transfection; study II) and the effect of the increased muscle capillarization on muscle insulin sensitivity was examined. In study I skeletal muscle specific angiogenesis was induced by administering an α1-adrenergic antagonist (prazosin) to healthy...

  1. Inward flux of lactate⁻ through monocarboxylate transporters contributes to regulatory volume increase in mouse muscle fibres.

    Directory of Open Access Journals (Sweden)

    Michael I Lindinger

    Full Text Available Mouse and rat skeletal muscles are capable of a regulatory volume increase (RVI after they shrink (volume loss resultant from exposure to solutions of increased osmolarity and that this RVI occurs mainly by a Na-K-Cl-Cotransporter (NKCC-dependent mechanism. With high-intensity exercise, increased extracellular osmolarity is accompanied by large increases in extracellular [lactate⁻]. We hypothesized that large increases in [lactate⁻] and osmolarity augment the NKCC-dependent RVI response observed with a NaCl (or sucrose-induced increase in osmolarity alone; a response that is dependent on lactate⁻ influx through monocarboxylate transporters (MCTs. Single mouse muscle fibres were isolated and visualized under light microscopy under varying osmolar conditions. When solution osmolarity was increased by adding NaLac by 30 or 60 mM, fibres lost significantly less volume and regained volume sooner compared to when NaCl was used. Phloretin (MCT1 inhibitor accentuated the volume loss compared to both NaLac controls, supporting a role for MCT1 in the RVI response in the presence of elevated [lactate⁻]. Inhibition of MCT4 (with pCMBS resulted in a volume loss, intermediate to that seen with phloretin and NaLac controls. Bumetanide (NKCC inhibitor, in combination with pCMBS, reduced the magnitude of volume loss, but volume recovery was complete. While combined phloretin-bumetanide also reduced the magnitude of the volume loss, it also largely abolished the cell volume recovery. In conclusion, RVI in skeletal muscle exposed to raised tonicity and [lactate⁻] is facilitated by inward flux of solute by NKCC- and MCT1-dependent mechanisms. This work demonstrates evidence of a RVI response in skeletal muscle that is facilitated by inward flux of solute by MCT-dependent mechanisms. These findings further expand our understanding of the capacities for skeletal muscle to volume regulate, particularly in instances of raised tonicity and lactate

  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. Human skeletal muscle mitochondrial capacity.

    Science.gov (United States)

    Rasmussen, U F; Rasmussen, H N

    2000-04-01

    Under aerobic work, the oxygen consumption and major ATP production occur in the mitochondria and it is therefore a relevant question whether the in vivo rates can be accounted for by mitochondrial capacities measured in vitro. Mitochondria were isolated from human quadriceps muscle biopsies in yields of approximately 45%. The tissue content of total creatine, mitochondrial protein and different cytochromes was estimated. A number of activities were measured in functional assays of the mitochondria: pyruvate, ketoglutarate, glutamate and succinate dehydrogenases, palmitoyl-carnitine respiration, cytochrome oxidase, the respiratory chain and the ATP synthesis. The activities involved in carbohydrate oxidation could account for in vivo oxygen uptakes of 15-16 mmol O2 min-1 kg-1 or slightly above the value measured at maximal work rates in the knee-extensor model of Saltin and co-workers, i.e. without limitation from the cardiac output. This probably indicates that the maximal oxygen consumption of the muscle is limited by the mitochondrial capacities. The in vitro activities of fatty acid oxidation corresponded to only 39% of those of carbohydrate oxidation. The maximal rate of free energy production from aerobic metabolism of glycogen was calculated from the mitochondrial activities and estimates of the DeltaG or ATP hydrolysis and the efficiency of the actin-myosin reaction. The resultant value was 20 W kg-1 or approximately 70% of the maximal in vivo work rates of which 10-20% probably are sustained by the anaerobic ATP production. The lack of aerobic in vitro ATP synthesis might reflect termination of some critical interplay between cytoplasm and mitochondria.

  4. Stem Cells for Skeletal Muscle Tissue Engineering.

    Science.gov (United States)

    Pantelic, Molly N; Larkin, Lisa M

    2018-04-19

    Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

  5. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels

    2014-01-01

    In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator...... of sarcoplasmic reticulum Ca(2+) release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca(2+) ([Ca(2+)]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz...... in tetanic [Ca(2+)]i, and hence force, is accompanied by major reductions in inter- and intramyofibrillar glycogen. The stronger correlation between decreased tetanic [Ca(2+)]i and reduced intramyofibrillar glycogen implies that sarcoplasmic reticulum Ca(2+) release critically depends on energy supply from...

  6. Type grouping in skeletal muscles after experimental reinnervation: another explanation

    NARCIS (Netherlands)

    Vleggeert-lankamp, C.L.A.M.; de Ruiter, G.C.W.; Wolfs, J.F.C.; Pêgo, A.P.; Feirabend, H.K.P.; Lakke, E.A.J.F.; Malessy, M.J.A.

    2005-01-01

    Type grouping signifies clustering of muscle fibres of the same metabolic type, and is a frequent finding in reinnervated muscles. To elucidate the mechanism behind it, the rat sciatic nerve was either autografted or grafted with hollow synthetic nerve grafts. Twelve weeks later the number and fibre

  7. Phosphorylation of human skeletal muscle myosin

    International Nuclear Information System (INIS)

    Houston, M.E.; Lingley, M.D.; Stuart, D.S.; Hoffman-Goetz, L.

    1986-01-01

    Phosphorylation of the P-light chains (phosphorylatable light chains) in human skeletal muscle myosin was studied in vitro and in vivo under resting an d contracted conditions. biopsy samples from rested vastus lateralis muscle of male and female subjects were incubated in oxygenated physiological solution at 30 0 C. Samples frozen following a quiescent period showed the presence of only unphosphorylated P-light chains designated LC2f (light chain two of fast myosin) CL2s and LC2s'(light chains two of slow myosin). Treatment with caffeine (10 mM) or direct electrical stimulation resulted in the appearance of three additional bands which were identified as the phosphorylated forms of the P-light chains i.e. LC2f-P, LC2s-P and LC2s'-P. The presence of phosphate was confirmed by prior incubation with ( 30 P) orthophosphate. Muscle samples rapidly frozen from resting vastus lateralis muscle revealed the presence of unphosphorylated and phosphorylated P-light chains in approximately equal ratios. Muscle samples rapidly frozen following a maximal 10 second isometric contraction showed virtually only phosphorylated fast and slow P-light chains. These results reveal that the P-light chains in human fast and slow myosin may be rapidly phosphorylated, but the basal level of phosphorylation in rested human muscle considerably exceeds that observed in animal muscles studied in vitro or in situ

  8. 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...

  9. CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability.

    Science.gov (United States)

    Meng, Jinhong; Muntoni, Francesco; Morgan, Jennifer

    2018-05-12

    Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the missing dystrophin protein, thus improving muscle function. CD133+ cells derived from normal human skeletal muscle contribute to regenerated muscle fibres and form muscle stem cells after their intra-muscular transplantation into an immunodeficient mouse model. But it is not known whether CD133+ cells derived from DMD patient muscles have compromised muscle regenerative function. To test this, we compared CD133+ cells derived from DMD and normal human muscles. DMD CD133+ cells had a reduced capacity to undergo myogenic differentiation in vitro compared with CD133+ cells derived from normal muscle. In contrast to CD133+ cells derived from normal human muscle, those derived from DMD muscle formed no satellite cells and gave rise to significantly fewer muscle fibres of donor origin, after their intra-muscular transplantation into an immunodeficient, non-dystrophic, mouse muscle. DMD CD133+ cells gave rise to more clones of smaller size and more clones that were less myogenic than did CD133+ cells derived from normal muscle. The heterogeneity of the progeny of CD133+ cells, combined with the reduced proliferation and myogenicity of DMD compared to normal CD133+ cells, may explain the reduced regenerative capacity of DMD CD133+ cells. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension.

    Science.gov (United States)

    Malenfant, Simon; Potus, François; Fournier, Frédéric; Breuils-Bonnet, Sandra; Pflieger, Aude; Bourassa, Sylvie; Tremblay, Ève; Nehmé, Benjamin; Droit, Arnaud; Bonnet, Sébastien; Provencher, Steeve

    2015-05-01

    Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles.

  11. Sex hormones and skeletal muscle weakness

    DEFF Research Database (Denmark)

    Sipilä, Sarianna; Narici, Marco; Kjaer, Michael

    2013-01-01

    Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia...... and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss...... 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...

  12. Development of a porcine skeletal muscle cDNA microarray: analysis of differential transcript expression in phenotypically distinct muscles

    Directory of Open Access Journals (Sweden)

    Stear Michael

    2003-03-01

    Full Text Available Abstract Background Microarray profiling has the potential to illuminate the molecular processes that govern the phenotypic characteristics of porcine skeletal muscles, such as hypertrophy or atrophy, and the expression of specific fibre types. This information is not only important for understanding basic muscle biology but also provides underpinning knowledge for enhancing the efficiency of livestock production. Results We report on the de novo development of a composite skeletal muscle cDNA microarray, comprising 5500 clones from two developmentally distinct cDNA libraries (longissimus dorsi of a 50-day porcine foetus and the gastrocnemius of a 3-day-old pig. Clones selected for the microarray assembly were of low to moderate abundance, as indicated by colony hybridisation. We profiled the differential expression of genes between the psoas (red muscle and the longissimus dorsi (white muscle, by co-hybridisation of Cy3 and Cy5 labelled cDNA derived from these two muscles. Results from seven microarray slides (replicates correctly identified genes that were expected to be differentially expressed, as well as a number of novel candidate regulatory genes. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray. Conclusion We have developed a porcine skeletal muscle cDNA microarray and have identified a number of candidate genes that could be involved in muscle phenotype determination, including several members of the casein kinase 2 signalling pathway.

  13. Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

    Directory of Open Access Journals (Sweden)

    Lisa Vu, MD

    2014-01-01

    Full Text Available Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus.

  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. 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...

  17. HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy

    Science.gov (United States)

    Smeets, Cleo J. L. M.; Franklin, Sophie A.; Bondulich, Marie K.; Jolinon, Nelly; Muller, Thomas; Ahmed, Mhoriam; Dick, James R. T.; Piotrowska, Izabela; Greensmith, Linda; Smolenski, Ryszard T.; Bates, Gillian P.

    2015-01-01

    Skeletal muscle remodelling and contractile dysfunction occur through both acute and chronic disease processes. These include the accumulation of insoluble aggregates of misfolded amyloid proteins that is a pathological feature of Huntington’s disease (HD). While HD has been described primarily as a neurological disease, HD patients’ exhibit pronounced skeletal muscle atrophy. Given that huntingtin is a ubiquitously expressed protein, skeletal muscle fibres may be at risk of a cell autonomous HD-related dysfunction. However the mechanism leading to skeletal muscle abnormalities in the clinical and pre-clinical HD settings remains unknown. To unravel this mechanism, we employed the R6/2 transgenic and HdhQ150 knock-in mouse models of HD. We found that symptomatic animals developed a progressive impairment of the contractile characteristics of the hind limb muscles tibialis anterior (TA) and extensor digitorum longus (EDL), accompanied by a significant loss of motor units in the EDL. In symptomatic animals, these pronounced functional changes were accompanied by an aberrant deregulation of contractile protein transcripts and their up-stream transcriptional regulators. In addition, HD mouse models develop a significant reduction in muscle force, possibly as a result of a deterioration in energy metabolism and decreased oxidation that is accompanied by the re-expression of the HDAC4-DACH2-myogenin axis. These results show that muscle dysfunction is a key pathological feature of HD. PMID:25748626

  18. Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from mdx mice.

    Science.gov (United States)

    Divet, Alexandra; Huchet-Cadiou, Corinne

    2002-08-01

    The aim of the present study was to establish whether alterations in sarcoplasmic reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic reticulum and contractile proteins of fast- and slow-twitch muscles were therefore investigated in chemically skinned fibres isolated from the extensor digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4 and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by the Ca(2+) release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca(2+) quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of the contractile apparatus was not significantly different. These results indicate that mdx hindlimb muscles are affected differently by the disease process and suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca(2+) homeostasis.

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

    Directory of Open Access Journals (Sweden)

    Einar Eftestøl

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

  20. Muscle fibre type composition and body composition in hammer throwers.

    Science.gov (United States)

    Terzis, Gerasimos; Spengos, Konstantinos; Kavouras, Stavros; Manta, Panagiota; Georgiadis, Giorgos

    2010-01-01

    Aim of the present study was to describe the muscle fibre type composition and body composition of well-trained hammer throwers. Six experienced hammer throwers underwent the following measurements: one repetition maximum in squat, snatch, and clean, standing broad jump, backward overhead shot throw and the hammer throw. Dual x-ray absorptiometry was used for body composition analysis. Fibre type composition and cross sectional area was determined in muscle biopsy samples of the right vastus lateralis. Eight physical education students served as a control group. One repetition maximum in squat, snatch and clean for the hammer throwers was 245 ± 21, 132 ± 13 and 165 ± 12kg, respectively. Lean body mass was higher in hammer throwers (85.9 ± 3. 9kg vs. 62.7 ± 5.1kg (p hammer throwers and 51 ± 8% in the control group (p Hammer throwers had significantly larger type IIA fibres (7703 ± 1171 vs. 5676 ± 1270μm(2), p Hammer throwing performance correlated significantly with lean body mass (r = 0.81, p hammer throwers have larger lean body mass and larger muscular areas occupied by type II fibres, compared with relatively untrained subjects. Moreover, it seems that the enlarged muscle mass of the hammer throwers contributes significantly to the hammer throwing performance. Key pointsWell-trained hammer throwers had increased lean body mass, higher type IIA muscle fibres cross sectional areas, as well as higher bone mineral density, compared to controls.Increased lean body mass was closely related with hammer throwing performance.The relative high percentage of type IIX muscle fibres in vastus lateralis in hammer throwers warrants further investigation.

  1. Skeletal muscle contraction-induced vasodilation in the microcirculation.

    Science.gov (United States)

    Hong, Kwang-Seok; Kim, Kijeong

    2017-10-01

    Maximal whole body exercise leads skeletal muscle blood flow to markedly increase to match metabolic demands, a phenomenon termed exercise hyperaemia that is accomplished by increasing vasodilation. However, local vasodilatory mechanisms in response to skeletal muscle contraction remain uncertain. This review highlights metabolic vasodilators released from contracting skeletal muscle, endothelium, or blood cells. As a considerable skeletal muscle vasodilation potentially results in hypotension, sympathetic nerve activity needs to be augmented to elevate cardiac output and blood pressure during dynamic exercise. However, since the enhanced sympathetic vasoconstriction restrains skeletal muscle blood flow, intramuscular arteries have an indispensable ability to blunt sympathetic activity for exercise hyperaemia. In addition, we discuss that mechanical compression of the intramuscular vasculature contributes to causing the initial phase of increasing vasodilation following a single muscle contraction. We have also chosen to focus on conducted (or ascending) electrical signals that evoke vasodilation of proximal feed arteries to elevate blood flow in the microcirculation of skeletal muscle. Endothelial hyperpolarization originating within distal arterioles ascends into the proximal feed arteries, thereby increasing total blood flow in contracting skeletal muscle. This brief review summarizes molecular mechanisms underlying the regulation of skeletal muscle blood flow to a single or sustained muscle contraction.

  2. Osmoregulatory processes and skeletal muscle metabolism

    Science.gov (United States)

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

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

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

    Directory of Open Access Journals (Sweden)

    Alexander M Zöllner

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

  4. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  5. Glucose metabolism and metabolic flexibility in cultured skeletal muscle cells is related to exercise status in young male subjects

    DEFF Research Database (Denmark)

    Lund, Jenny; S Tangen, Daniel; Wiig, Håvard

    2018-01-01

    deoxyglucose accumulation and fractional glucose oxidation (glucose oxidation relative to glucose uptake), and were also more sensitive to the suppressive action of acutely added oleic acid to the cells. Despite lack of correlation of fibre types between skeletal muscle biopsies and cultured cells, myotubes...

  6. Extracellular adenosine initiates rapid arteriolar vasodilation induced by a single skeletal muscle contraction in hamster cremaster muscle.

    Science.gov (United States)

    Ross, G A; Mihok, M L; Murrant, C L

    2013-05-01

    Recent studies suggest that adenosine (ADO) can be produced extracellularly in response to skeletal muscle contraction. We tested the hypothesis that a single muscle contraction produces extracellular ADO rapidly enough and in physiologically relevant concentrations to be able to contribute to the rapid vasodilation that occurs at the onset of muscle contraction. We stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction (stimulus frequencies: 4, 20 and 60 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of non-specific ADO membrane receptor antagonists 8-phenyltheophylline (8-PT, 10(-6) M) or xanthine amine congener (XAC, 10(-6) M) or an inhibitor of an extracellular source of ADO, ecto-5'-nucleotidase inhibitor α,β-methylene adenosine 5'-diphosphate (AMPCP, 10(-5) M). We observed that the dilatory event at 4 s following a single contraction was significantly inhibited at all stimulus frequencies by an average of 63.9 ± 2.6% by 8-PT. The 20-s dilatory event that occurred at 20 and 60 Hz was significantly inhibited by 53.6 ± 2.6 and 73.8 ± 2.3% by 8-PT and XAC respectively. Further, both the 4- and 20-s dilatory events were significantly inhibited by AMPCP by 78.6 ± 6.6 and 67.1 ± 1.5%, respectively, at each stimulus frequency tested. Our data show that ADO is produced extracellularly during a single muscle contraction and that it is produced rapidly enough and in physiologically relevant concentrations to contribute to the rapid vasodilation in response to muscle contraction. © 2013 The Authors Acta Physiologica © 2013 Scandinavian Physiological Society.

  7. Wearing of complete dentures reduces slow fibre and enhances hybrid fibre fraction in masseter muscle

    Czech Academy of Sciences Publication Activity Database

    Cvetko, E.; Karen, Petr; Eržen, I.

    2012-01-01

    Roč. 39, č. 8 (2012), s. 608-614 ISSN 0305-182X R&D Projects: GA MŠk(CZ) MEB090910; GA MŠk(CZ) LC06063 Institutional research plan: CEZ:AV0Z50110509 Keywords : human masseter * MyHC isoforms * muscle fibre types Subject RIV: FH - Neurology Impact factor: 2.344, year: 2012

  8. 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...

  9. Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

    DEFF Research Database (Denmark)

    Hvid, L G; Gejl, Kasper Degn; Bech, R D

    2013-01-01

    Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...... recovery on the contractile function of single muscle fibres obtained from elite athletes....

  10. Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

    Science.gov (United States)

    Gao, Yingxin; Zhang, Chi

    2015-03-01

    A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

  11. Structure–function relationship of skeletal muscle provides inspiration for design of new artificial muscle

    International Nuclear Information System (INIS)

    Gao, Yingxin; Zhang, Chi

    2015-01-01

    A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure–function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure–function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure–function relationship of skeletal muscle into the design of artificial muscle. (topical review)

  12. 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.

  13. 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...

  14. 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

  15. Direct effects of doxorubicin on skeletal muscle contribute to fatigue

    NARCIS (Netherlands)

    Norren, van K.; Helvoort, van A.; Argiles, J.M.; Tuijl, van S.; Arts, K.; Gorselink, M.; Laviano, A.; Kegler, D.; Haagsman, H.P.; Beek, E.M.

    2009-01-01

    Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    The aim of this study was to test the hypotheses that 1) skeletal muscles of elderly subjects can adapt to a single endurance exercise bout and 2) endurance trained elderly subjects have higher expression/activity of oxidative and angiogenic proteins in skeletal muscle than untrained elderly peop...

  17. 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...

  18. 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.

  19. Performances in extreme environments: effects of hyper/hypobarism and hypogravity on skeletal muscle

    Directory of Open Access Journals (Sweden)

    Gerardo Bosco

    2010-09-01

    Full Text Available Many environmental factors may affect muscle plasticity but some have exclusive characteristics that allow them to play a key role to maintain the muscle capacity to generate force; these factors are: i the oxygen availability and ii the load applied to muscle fibres. Hyperbarism is a condition that occurs when a man is subjected to pressure increases. To keep the lungs from collapsing, the air is supplied to him under high pressure which exposes the blood in the lungs to high alveolar gas pressures. Under this condition, the PO2 become sufficiently increased, serious disorders may occur, such as modification of oxygen delivery and/or oxygen availability to permit regular muscle contraction. Also altitude hypobaric hypoxia induces modification of muscle capacity to generate work. Prolonged exposure to high altitude leads significant loss in body mass, thigh muscle mass, muscle fiber area and volume density of muscle mitochondria. Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and early muscle fatigue. Muscle atrophy is observed in a wide range of muscles, with the most extensive loss occurring in the legs, because astronauts are no longer needed to support the body's weight. This review will describe the background on these topics suggesting the strategies to correct the specific muscle changes in presence of environmental stresses, such as the alteration in oxygen-derived signaling pathways or the metabolic consequence of microgravity that may indicate rational interventions to maintain muscle mass and function.

  20. Histological Evaluation of Decellularized Skeletal Muscle Tissue Using Two Different Decellularization Agents

    Directory of Open Access Journals (Sweden)

    Hana Hrebíková

    2017-02-01

    Full Text Available The aim of the present study was to determine effect of two decellularized agents, sodium dodecyl sulphate (SDS and Triton X-100, to the skeletal muscle tissue. Final scaffold was evaluated by several histological techniques to analyse preservation of essential structures including collagen and elastic fibres, basement membranes, glycosaminoglycans and also to confirm elimination of nuclear and cytoplasmic components which are redundant in effectively prepared decellularized scaffolds. Comparison of tissue scaffolds processed with different detergents proved that SDS is superior to Triton X-100 as it can effectively decellularize muscle tissue.

  1. Skeletal Muscle Insulin Resistance in Endocrine Disease

    Directory of Open Access Journals (Sweden)

    Melpomeni Peppa

    2010-01-01

    Full Text Available We summarize the existing literature data concerning the involvement of skeletal muscle (SM in whole body glucose homeostasis and the contribution of SM insulin resistance (IR to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS, adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

  2. Volume regulation in mammalian skeletal muscle: the role of sodium-potassium-chloride cotransporters during exposure to hypertonic solutions.

    Science.gov (United States)

    Lindinger, Michael I; Leung, Matthew; Trajcevski, Karin E; Hawke, Thomas J

    2011-06-01

    Controversy exists as to whether mammalian skeletal muscle is capable of volume regulation in response to changes in extracellular osmolarity despite evidence that muscle fibres have the required ion transport mechanisms to transport solute and water in situ. We addressed this issue by studying the ability of skeletal muscle to regulate volume during periods of induced hyperosmotic stress using single, mouse extensor digitorum longus (EDL) muscle fibres and intact muscle (soleus and EDL). Fibres and intact muscles were loaded with the fluorophore, calcein, and the change in muscle fluorescence and width (single fibres only) used as a metric of volume change. We hypothesized that skeletal muscle exposed to increased extracellular osmolarity would elicit initial cellular shrinkage followed by a regulatory volume increase (RVI) with the RVI dependent on the sodium–potassium–chloride cotransporter (NKCC). We found that single fibres exposed to a 35% increase in extracellular osmolarity demonstrated a rapid, initial 27–32% decrease in cell volume followed by a RVI which took 10-20 min and returned cell volume to 90–110% of pre-stimulus values. Within intact muscle, exposure to increased extracellular osmolarity of varying degrees also induced a rapid, initial shrinkage followed by a gradual RVI, with a greater rate of initial cell shrinkage and a longer time for RVI to occur with increasing extracellular tonicities. Furthermore, RVI was significantly faster in slow-twitch soleus than fast-twitch EDL. Pre-treatment of muscle with bumetanide (NKCC inhibitor) or ouabain (Na+,K+-ATPase inhibitor), increased the initial volume loss and impaired the RVI response to increased extracellular osmolarity indicating that the NKCC is a primary contributor to volume regulation in skeletal muscle. It is concluded that mouse skeletal muscle initially loses volume then exhibits a RVI when exposed to increases in extracellular osmolarity. The rate of RVI is dependent on the

  3. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  4. Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats

    Science.gov (United States)

    Mendias, Christopher L; Lynch, Evan B; Gumucio, Jonathan P; Flood, Michael D; Rittman, Danielle S; Van Pelt, Douglas W; Roche, Stuart M; Davis, Carol S

    2015-01-01

    Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN+/+) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTNΔ/Δ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from that of myostatin-deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTNΔ/Δ rats demonstrated 20–33% increases in mass, 35–45% increases in fibre number, 20–57% increases in isometric force and no differences in specific force. The insulin-like growth factor-1 pathway was activated to a greater extent in MSTNΔ/Δ muscles, but no substantial differences in atrophy-related genes were observed. Tendons of MSTNΔ/Δ rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling. PMID:25640143

  5. Regional organization of fibre types in normal and reinnervated hindlimb muscles

    NARCIS (Netherlands)

    Wang, Liangchun

    2001-01-01

    The present thesis concerns the spatial distribution of the "slow" type I fibres within muscles of the hindlimb. It is known since long ago that some muscles may have strikingly heterogeneous distributions of type I and II fibres, but this phenomenon of "fibre type regionalization" has still not

  6. Hypertrophy of mature xenopus muscle fibres in culture induced by synergy of albumin and insulin

    NARCIS (Netherlands)

    Jaspers, R.T.; van Beek-Harmsen, B.J.; Blankenstein, M.A.; Goldspink, G.; Huijing, P.A.J.B.M.; van der Laarse, W.J.

    2008-01-01

    The aim of this study was to investigate effects of albumin and insulin separately as well as in combination on mature muscle fibres during long-term culture. Single muscle fibres were dissected from m. iliofibularis of Xenopus laevis and attached to a force transducer in a culture chamber. Fibres

  7. Molecular Signals and Skeletal Muscle Adaptation to Exercise

    Directory of Open Access Journals (Sweden)

    Mark Wilson

    2013-09-01

    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

  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. 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.)

  11. 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.

  12. Aging is associated with diminished muscle re-growth and myogenic precursor cell expansion in the early recovery phase after immobility-induced atrophy in human skeletal muscle

    DEFF Research Database (Denmark)

    Suetta, Charlotte Arneboe; Frandsen, Ulrik; Mackey, Abigail L

    2013-01-01

    Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and old human subjects subsequent to 2 weeks of immobility...... expression analysis of key growth and transcription factors associated with local skeletal muscle milieu were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of re-training. OM demonstrated no detectable gains in MFA (VL muscle) and no increases in number of Pax7......-induced muscle atrophy. Re-training consisted of 4 weeks of supervised resistive exercise in 9 older (OM: 67.3yrs, range 61-74) and 11 young (YM: 24.4yrs, range 21-30) males. Measures of myofiber area (MFA), Pax7-positive satellite cells (SC) associated with type I and type II muscle fibres, as well as gene...

  13. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

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

  14. Inositol 1,4,5-trisphosphate-sensitive Ca2+ release in rat fast- and slow-twitch skinned muscle fibres.

    Science.gov (United States)

    Talon, S; Huchet-Cadiou, C; Léoty, C

    1999-11-01

    Inositol 1,4,5-trisphosphate (InsP3), an intracellular messenger, induces Ca2+ release in various types of cells, particularly smooth muscle cells. Its role in skeletal muscle, however, is controversial. The present study shows that the application of InsP3 to rat slow- and fast-twitch saponin-skinned fibres induced contractile responses that were not related to an effect of InsP3 on the properties of the contractile proteins. The amplitude of the contractures was dependent upon the Ca(2+)-loading period, and was larger in slow- than in fast-twitch muscle. In both types of skeletal muscle, these responses, unlike caffeine contractures, were not inhibited by ryanodine (100 microM), but were abolished by heparin (20 micrograms.ml-1). In soleus muscle, the concentration of heparin required to inhibit the response by 50% (IC50) was 5.7 micrograms.ml-1, a similar value to that obtained previously in smooth muscle. Furthermore, the results show that in slow-twitch muscle, the InsP3 contractures have a "bell-shaped" dependency on the intracellular Ca2+ concentration. These results show that InsP3 receptors should be present in skeletal muscle. Thus, it is possible that InsP3 participates in the regulation of sarcoplasmic reticulum Ca2+ release in skeletal muscle, particularly in slow-twitch fibres.

  15. TAK1 regulates skeletal muscle mass and mitochondrial function

    Science.gov (United States)

    Hindi, Sajedah M.; Sato, Shuichi; Xiong, Guangyan; Bohnert, Kyle R.; Gibb, Andrew A.; Gallot, Yann S.; McMillan, Joseph D.; Hill, Bradford G.

    2018-01-01

    Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-β–activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. In addition, targeted inactivation of TAK1 leads to the accumulation of dysfunctional mitochondria and oxidative stress in skeletal muscle of adult mice. Inhibition of TAK1 does not attenuate denervation-induced muscle wasting in adult mice. Finally, TAK1 activity is highly upregulated during overload-induced skeletal muscle growth, and inactivation of TAK1 prevents myofiber hypertrophy in response to functional overload. Overall, our study demonstrates that TAK1 is a key regulator of skeletal muscle mass and oxidative metabolism. PMID:29415881

  16. 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.

  17. Lifting the nebula: novel insights into skeletal muscle contractility.

    Science.gov (United States)

    Ottenheijm, Coen A C; Granzier, Henk

    2010-10-01

    Nebulin is a giant protein and a constituent of the skeletal muscle sarcomere. The name of this protein refers to its unknown (i.e., nebulous) function. However, recent rapid advances reveal that nebulin plays important roles in the regulation of muscle contraction. When these functions of nebulin are compromised, muscle weakness ensues, as is the case in patients with nemaline myopathy.

  18. Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury.

    Science.gov (United States)

    Smith, H K; Plyley, M J; Rodgers, C D; McKee, N H

    1999-07-01

    The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10) g] were either assigned as non-exercised controls or subjected to 30 min of treadmill exercise (grade, -16 degrees; speed, 15 m x min(-1)), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n = 5-6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd+) were seldom detected in the TA. In the VI and S, higher proportions of MHCd+ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P < or = 0.01). In S, MHCd+ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd+ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd+ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd+ fibres were smaller (< 2500 microm2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd+ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.

  19. The expression of the skeletal muscle force-length relationship in vivo: a simulation study.

    Science.gov (United States)

    Winter, Samantha L; Challis, John H

    2010-02-21

    The force-length relationship is one of the most important mechanical characteristics of skeletal muscle in humans and animals. For a physiologically realistic joint range of motion and therefore range of muscle fibre lengths only part of the force-length curve may be used in vivo, i.e. only a section of the force-length curve is expressed. A generalised model of a mono-articular muscle-tendon complex was used to examine the effect of various muscle architecture parameters on the expressed section of the force-length relationship for a 90 degrees joint range of motion. The parameters investigated were: the ratio of tendon resting length to muscle fibre optimum length (L(TR):L(F.OPT)) (varied from 0.5 to 11.5), the ratio of muscle fibre optimum length to average moment arm (L(F.OPT):r) (varied from 0.5 to 5), the normalised tendon strain at maximum isometric force (c) (varied from 0 to 0.08), the muscle fibre pennation angle (theta) (varied from 0 degrees to 45 degrees) and the joint angle at which the optimum muscle fibre length occurred (phi). The range of values chosen for each parameter was based on values reported in the literature for five human mono-articular muscles with different functional roles. The ratios L(TR):L(F.OPT) and L(F.OPT):r were important in determining the amount of variability in the expressed section of the force-length relationship. The modelled muscle operated over only one limb at intermediate values of these two ratios (L(TR):L(F.OPT)=5; L(F.OPT):r=3), whether this was the ascending or descending limb was determined by the precise values of the other parameters. It was concluded that inter-individual variability in the expressed section of the force-length relationship is possible, particularly for muscles with intermediate values of L(TR):L(F.OPT) and L(F.OPT):r such as the brachialis and vastus lateralis. Understanding the potential for inter-individual variability in the expressed section is important when using muscle models to

  20. Effects of acute exercise on gene expression in exercising and non-exercising human skeletal muscle

    NARCIS (Netherlands)

    Catoire, Milene; Mensink, Marco; Boekschoten, Mark; Hangelbroek, Roland; Muller, Michael; Schrauwen, Patricht; Kersten, Sander

    2012-01-01

    Background: Exercising is know to have an effect on exercising skeletal muscle, but unkown is the effect on non-exercising skeletal muscle. Gene expression changes in the non-exercising skeletal muscle would point to a signalling role of skeletal muscle

  1. 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.

  2. 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.

  3. Dissemination of Walker 256 carcinoma cells to rat skeletal muscle

    International Nuclear Information System (INIS)

    Ueoka, H.; Hayashi, K.; Namba, T.; Grob, D.

    1986-01-01

    After injection of 10 6 Walker 256 carcinoma cells labelled with 125 I-5-iodo-2'-deoxyuridine into the tail vein, peak concentration in skeletal muscle was 46 cells/g at 60 minutes, which was lower than 169202, 1665, 555, 198 and 133 cells/g, respectively, at 30 or 60 minutes in lung, liver, spleen, kidney and heart. Because skeletal muscle constitutes 37.4% of body weight, the total number of tumor cells was 2323 cells, which was much greater than in spleen, kidney and heart with 238, 271, and 85 cells, respectively, and only less than in lung and liver, at 222857 and 11700 cells, respectively. The total number in skeletal muscle became greater than in liver at 4 hours and than in lung at 24 hours. Ten minutes after injection of 7.5 x 10 6 Walker 256 carcinoma cells into the abdominal aorta of rats, a mean of 31 colony-forming cells were recovered from the gastrocnemius, while 106 cells were recovered from the lung after injection into the tail vein. These results indicate that a large number of viable tumor cells can be arrested in skeletal muscle through circulation. The rare remote metastasis of malignancies into skeletal muscle despite constantly circulating tumor cells does not appear to be due to poor dissemination of tumor cells into muscle but due to unhospitable environment of skeletal muscle

  4. Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

    DEFF Research Database (Denmark)

    Hütter, Eveline; Skovbro, Mette; Lener, Barbara

    2007-01-01

    According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...... from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional...

  5. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells...... 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...

  6. Skeletal muscle architectural adaptations to marathon run training.

    Science.gov (United States)

    Murach, Kevin; Greever, Cory; Luden, Nicholas D

    2015-01-01

    We assessed lateral gastrocnemius (LG) and vastus lateralis (VL) architecture in 16 recreational runners before and after 12 weeks of marathon training. LG fascicle length decreased 10% while pennation angle increased 17% (p training can modify skeletal muscle architectural features.

  7. 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...... 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...... to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise...

  8. 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 t...... accumulation and attenuates peripheral insulin resistance in obese mice........ 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......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...

  9. Inducible satellite cell depletion attenuates skeletal muscle regrowth following a scald-burn injury.

    Science.gov (United States)

    Finnerty, Celeste C; McKenna, Colleen F; Cambias, Lauren A; Brightwell, Camille R; Prasai, Anesh; Wang, Ye; El Ayadi, Amina; Herndon, David N; Suman, Oscar E; Fry, Christopher S

    2017-11-01

    Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors. Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7 CreER -DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2'-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P satellite cells in the aetiology of lean

  10. Ossified skeletal muscle hemangioma: Radiologic and pathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Engelstad, B L; Gilula, L A [Mallinckrodt Inst. of Radiology, St. Louis, MO (USA); Kynakos, M [Washington Univ., St. Louis, MO (USA). Dept. of Surgical Pathology

    1980-01-01

    Skeletal muscle hemangiomas are relatively uncommon tumors in children and young adults. Although the operative management of these lesions may be affected by their vascularity, the correct preoperative diagnosis is often not made. Ossification of these lesions is rare. Two patients are described whose skeletal muscle hemangiomas contained abundant osseous tissue. This was radiologically reflected by the 'swiss cheese' appearance of the tumors. Such an appearance in an ossified soft tissue mass may allow the correct preoperative diagnosis of this condition.

  11. Phosphorylation and function of DGAT1 in skeletal muscle cells

    OpenAIRE

    Yu, Jinhai; Li, Yiran; Zou, Fei; Xu, Shimeng; Liu, Pingsheng

    2015-01-01

    Aberrant intramuscular triacylglycerol (TAG) storage in human skeletal muscle is closely related to insulin insensitivity. Excessive lipid storage can induce insulin resistance of skeletal muscle, and under severe conditions, lead to type 2 diabetes. The balance of interconversion between diacylglycerol and TAG greatly influences lipid storage and utilization. Diacylglycerol O-acyltransferase 1 (DGAT1) plays a key role in this process, but its activation and phosphorylation requires further d...

  12. Role of skeletal muscle in ear development.

    Science.gov (United States)

    Rot, Irena; Baguma-Nibasheka, Mark; Costain, Willard J; Hong, Paul; Tafra, Robert; Mardesic-Brakus, Snjezana; Mrduljas-Djujic, Natasa; Saraga-Babic, Mirna; Kablar, Boris

    2017-10-01

    The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants' cristae was further used here to identify a profile of genes specific to the lacking cell type. Microarrays followed by a detailed consultation of web-accessible mouse databases allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have associated inner ear abnormalities. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X-linked deafness in humans. Our current study suggests an epigenetic role that mechanical, and potentially other, stimuli originating from muscle, play in organogenesis, and offers an approach to finding novel genes responsible for altered inner ear phenotypes.

  13. Patient-specific fibre-based models of muscle wrapping

    Science.gov (United States)

    Kohout, J.; Clapworthy, G. J.; Zhao, Y.; Tao, Y.; Gonzalez-Garcia, G.; Dong, F.; Wei, H.; Kohoutová, E.

    2013-01-01

    In many biomechanical problems, the availability of a suitable model for the wrapping of muscles when undergoing movement is essential for the estimation of forces produced on and by the body during motion. This is an important factor in the Osteoporotic Virtual Physiological Human project which is investigating the likelihood of fracture for osteoporotic patients undertaking a variety of movements. The weakening of their skeletons makes them particularly vulnerable to bone fracture caused by excessive loading being placed on the bones, even in simple everyday tasks. This paper provides an overview of a novel volumetric model that describes muscle wrapping around bones and other muscles during movement, and which includes a consideration of how the orientations of the muscle fibres change during the motion. The method can calculate the form of wrapping of a muscle of medium size and visualize the outcome within tenths of seconds on commodity hardware, while conserving muscle volume. This makes the method suitable not only for educational biomedical software, but also for clinical applications used to identify weak muscles that should be strengthened during rehabilitation or to identify bone stresses in order to estimate the risk of fractures. PMID:24427519

  14. 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

  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. Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle.

    Science.gov (United States)

    Alsted, Thomas J; Ploug, Thorkil; Prats, Clara; Serup, Annette K; Høeg, Louise; Schjerling, Peter; Holm, Cecilia; Zimmermann, Robert; Fledelius, Christian; Galbo, Henrik; Kiens, Bente

    2013-10-15

    In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.

  17. Morphology of lesions in striated muscle fibres from the beige mouse

    DEFF Research Database (Denmark)

    Kirkeby, S

    1982-01-01

    Lesions in striated muscle fibres from the beige mouse are described at both the light- and electronmicroscopical levels. The muscles have two types of lesions, one is well defined cores in the fibres and the other is diffusely enlarged intermyofibrillar spaces (IMS). The cores can be filled...... with membrane-like structures or a fluffy unstructured material. In the areas with enlarged IMS comparatively few organelles are present and the muscle fibres seem to be fragmented....

  18. Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis.

    Science.gov (United States)

    Gosker, Harry R; Zeegers, Maurice P; Wouters, Emiel F M; Schols, Annemie M W J

    2007-11-01

    Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease (COPD) which is associated with intrinsic muscular abnormalities. One of the most consistently reported alterations is a shift from fibre type I to II in the vastus lateralis of these patients. Surprisingly, the relationship between this shift and the severity and phenotype of COPD remains unclear. A study was conducted to determine whether vastus lateralis muscle fibre type proportions are associated with COPD disease severity and to provide reference values for the proportions of fibre types in the vastus lateralis in COPD. A systematic review and a meta-analysis were conducted in which muscle fibre type data and markers of disease severity were collected from the literature. The forced expiratory volume in 1 s (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC) and body mass index were positively associated with the proportion of type I fibres in COPD. A proportion of 51% for vastus lateralis fibre type I and 13% for fibre type IIX were calculated from the combined data as normal values for patients with typical GOLD stage 3-4 COPD aged 60-70 years. Based on these reference values, a proportion of fibre type I 29% were defined as pathologically abnormal. This review sheds new light on the relationship between skeletal muscle abnormalities and important hallmarks of the disease in severe COPD, and identifies absence of data in GOLD stages 1-2. This review also provides reference values on fibre type composition for diagnostic purposes in COPD.

  19. Plasticity of human skeletal muscle: gene expression to in vivo function.

    Science.gov (United States)

    Harridge, Stephen D R

    2007-09-01

    Human skeletal muscle is a highly heterogeneous tissue, able to adapt to the different challenges that may be placed upon it. When overloaded, a muscle adapts by increasing its size and strength through satellite-cell-mediated mechanisms, whereby protein synthesis is increased and new nuclei are added to maintain the myonuclear domain. This process is regulated by an array of mechanical, hormonal and nutritional signals. Growth factors, such as insulin-like growth factor I (IGF-I) and testosterone, are potent anabolic agents, whilst myostatin acts as a negative regulator of muscle mass. Insulin-like growth factor I is unique in being able to stimulate both the proliferation and the differentiation of satellite cells and works as part of an important local repair and adaptive mechanism. Speed of movement, as characterized by maximal velocity of shortening (V(max)), is regulated primarily by the isoform of myosin heavy chain (MHC) contained within a muscle fibre. Human fibres can express three MHCs: MHC-I, -IIa and -IIx, in order of increasing V(max) and maximal power output. Training studies suggest that there is a subtle interplay between the MHC-IIa and -IIx isoforms, with the latter being downregulated by activity and upregulated by inactivity. However, switching between the two main isoforms appears to require significant challenges to a muscle. Upregulation of fast gene programs is caused by prolonged disuse, whilst upregulation of slow gene programs appears to require significant and prolonged activity. The potential mechanisms by which alterations in muscle composition are mediated are discussed. The implications in terms of contractile function of altering muscle phenotype are discussed from the single fibre to the whole muscle level.

  20. Bex1 knock out mice show altered skeletal muscle regeneration

    International Nuclear Information System (INIS)

    Koo, Jae Hyung; Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-01-01

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca 2+ /CaM may be involved in skeletal muscle regeneration

  1. The cell nuclei of skeletal muscle cells are transcriptionally active in hibernating edible dormice

    Directory of Open Access Journals (Sweden)

    Muller Sylviane

    2009-03-01

    Full Text Available Abstract Background Skeletal muscle is able to react in a rapid, dynamic way to metabolic and mechanical stimuli. In particular, exposure to either prolonged starvation or disuse results in muscle atrophy. At variance, in hibernating animals muscle atrophy may be scarce or absent after bouts of hibernation i.e., periods of prolonged (months inactivity and food deprivation, and muscle function is fully preserved at arousal. In this study, myocytes from the quadriceps muscle of euthermic and hibernating edible dormice were investigated by a combination of morphological, morphometrical and immunocytochemical analyses at the light and electron microscopy level. The focus was on cell nuclei and mitochondria, which are highly sensitive markers of changing metabolic rate. Results Findings presented herein demonstrate that: 1 the general histology of the muscle, inclusive of muscle fibre shape and size, and the ratio of fast and slow fibre types are not affected by hibernation; 2 the fine structure of cytoplasmic and nuclear constituents is similar in euthermia and hibernation but for lipid droplets, which accumulate during lethargy; 3 during hibernation, mitochondria are larger in size with longer cristae, and 4 myonuclei maintain the same amount and distribution of transcripts and transcription factors as in euthermia. Conclusion In this study we demonstrate that skeletal muscle cells of the hibernating edible dormouse maintain their structural and functional integrity in full, even after months in the nest. A twofold explanation for that is envisaged: 1 the maintenance, during hibernation, of low-rate nuclear and mitochondrial activity counterbalancing myofibre wasting, 2 the intensive muscle stimulation (shivering during periodic arousals in the nest, which would mimic physical exercise. These two factors would prevent muscle atrophy usually occurring in mammals after prolonged starvation and/or inactivity as a consequence of prevailing catabolism

  2. Heterogeneity among muscle precursor cells in adult skeletal muscles with differing regenerative capacities.

    Science.gov (United States)

    Pavlath, G K; Thaloor, D; Rando, T A; Cheong, M; English, A W; Zheng, B

    1998-08-01

    Skeletal muscle has a remarkable capacity to regenerate after injury, although studies of muscle regeneration have heretofore been limited almost exclusively to limb musculature. Muscle precursor cells in skeletal muscle are responsible for the repair of damaged muscle. Heterogeneity exists in the growth and differentiation properties of muscle precursor cell (myoblast) populations throughout limb development but whether the muscle precursor cells differ among adult skeletal muscles is unknown. Such heterogeneity among myoblasts in the adult may give rise to skeletal muscles with different regenerative capacities. Here we compare the regenerative response of a masticatory muscle, the masseter, to that of limb muscles. After exogenous trauma (freeze or crush injuries), masseter muscle regenerated much less effectively than limb muscle. In limb muscle, normal architecture was restored 12 days after injury, whereas in masseter muscle, minimal regeneration occurred during the same time period. Indeed, at late time points, masseter muscles exhibited increased fibrous connective tissue in the region of damage, evidence of ineffective muscle regeneration. Similarly, in response to endogenous muscle injury due to a muscular dystrophy, widespread evidence of impaired regeneration was present in masseter muscle but not in limb muscle. To explore the cellular basis of these different regenerative capacities, we analyzed the myoblast populations of limb and masseter muscles both in vivo and in vitro. From in vivo analyses, the number of myoblasts in regenerating muscle was less in masseter compared with limb muscle. Assessment of population growth in vitro indicated that masseter myoblasts grow more slowly than limb myoblasts under identical conditions. We conclude that the impaired regeneration in masseter muscles is due to differences in the intrinsic myoblast populations compared to limb muscles.

  3. 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.

  4. 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

  5. MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

    Directory of Open Access Journals (Sweden)

    Valentina Conti

    Full Text Available Rett syndrome (RTT is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

  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. Protein and amino acid metabolism in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guoyao.

    1989-01-01

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

  8. Molecular responses to moderate endurance exercise in skeletal muscle

    Science.gov (United States)

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

  9. 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....

  10. 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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  12. Quantitative analysis of single muscle fibre action potentials recorded at known distances

    NARCIS (Netherlands)

    Albers, B.A.; Put, J.H.M.; Wallinga, W.; Wirtz, P.

    1989-01-01

    In vivo records of single fibre action potentials (SFAPs) have always been obtained at unknown distance from the active muscle fibre. A new experimental method has been developed enabling the derivation of the recording distance in animal experiments. A single fibre is stimulated with an

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained...... in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known...... as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of approximately 50...

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

  16. Skeletal muscle inflammation and insulin resistance in obesity

    Science.gov (United States)

    Wu, Huaizhu; Ballantyne, Christie M.

    2017-01-01

    Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance. PMID:28045398

  17. Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle

    DEFF Research Database (Denmark)

    Boushel, R; Gnaiger, E; Schjerling, P

    2007-01-01

    AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes are associated with mitochondrial dysfunction. The aim of the present study was to test the hypothesis that oxidative phosphorylation and electron transport capacity are diminished in the skeletal muscle of type 2 diabetic subjects......, as a result of a reduction in the mitochondrial content. MATERIALS AND METHODS: The O(2) flux capacity of permeabilised muscle fibres from biopsies of the quadriceps in healthy subjects (n = 8; age 58 +/- 2 years [mean+/-SEM]; BMI 28 +/- 1 kg/m(2); fasting plasma glucose 5.4 +/- 0.2 mmol/l) and patients...... with type 2 diabetes (n = 11; age 62 +/- 2 years; BMI 32 +/- 2 kg/m(2); fasting plasma glucose 9.0 +/- 0.8 mmol/l) was measured by high-resolution respirometry. RESULTS: O(2) flux expressed per mg of muscle (fresh weight) during ADP-stimulated state 3 respiration was lower (p type 2...

  18. Proteomic profiling of non-obese type 2 diabetic skeletal muscle.

    Science.gov (United States)

    Mullen, Edel; Ohlendieck, Kay

    2010-03-01

    Abnormal glucose handling has emerged as a major clinical problem in millions of diabetic patients worldwide. Insulin resistance affects especially one of the main target organs of this hormone, the skeletal musculature, making impaired glucose metabolism in contractile fibres a major feature of type 2 diabetes. High levels of circulating free fatty acids, an increased intramyocellular lipid content, impaired insulin-mediated glucose uptake, diminished mitochondrial functioning and an overall weakened metabolic flexibility are pathobiochemical hallmarks of diabetic skeletal muscles. In order to increase our cellular understanding of the molecular mechanisms that underlie this complex diabetes-associated skeletal muscle pathology, we initiated herein a mass spectrometry-based proteomic analysis of skeletal muscle preparations from the non-obese Goto-Kakizaki rat model of type 2 diabetes. Following staining of high-resolution two-dimensional gels with colloidal Coomassie Blue, 929 protein spots were detected, whereby 21 proteins showed a moderate differential expression pattern. Decreased proteins included carbonic anhydrase, 3-hydroxyisobutyrate dehydrogenase and enolase. Increased proteins were identified as monoglyceride lipase, adenylate kinase, Cu/Zn superoxide dismutase, phosphoglucomutase, aldolase, isocitrate dehydrogenase, cytochrome c oxidase, small heat shock Hsp27/B1, actin and 3-mercaptopyruvate sulfurtransferase. These proteomic findings suggest that the diabetic phenotype is associated with a generally perturbed protein expression pattern, affecting especially glucose, fatty acid, nucleotide and amino acid metabolism, as well as the contractile apparatus, the cellular stress response, the anti-oxidant defense system and detoxification mechanisms. The altered expression levels of distinct skeletal muscle proteins, as documented in this study, might be helpful for the future establishment of a comprehensive biomarker signature of type 2 diabetes

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

    International Nuclear Information System (INIS)

    Surov, Alexey; Spielmann, Rolf Peter; Behrmann, Curd; Hainz, Michael; Holzhausen, Hans-Juergen; Arnold, Dirk; Katzer, Michaela; Schmidt, Joerg

    2010-01-01

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

  20. 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.)

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

    OpenAIRE

    Deane, Colleen Siobhan; Wilkinson, D.J.; Phillips, B.E.; Smith, K.; Etheridge, T.; Atherton, P.J.

    2017-01-01

    Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cach...

  2. Human skeletal muscle contains no detectable guanidinoacetic acid

    DEFF Research Database (Denmark)

    Ostojic, Sergej M; Ostojic, Jelena

    2018-01-01

    We analyzed data from previously completed trials to determine the effects of supplemental guanidinoacetic acid (GAA) on markers of muscle bioenergetics in healthy men using 1.5 T magnetic resonance spectroscopy. No detectable GAA (<0.1 μmol/L) was found in the vastus medialis muscle at baseline ...... nor at follow-up. This implies deficient GAA availability in the human skeletal muscle, suggesting absent or negligible potential for creatine synthesis from GAA inside this tissue, even after GAA loading....

  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. Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle

    Science.gov (United States)

    Yu, Ji-Guo; Bonnerud, Patrik; Eriksson, Anders; Stål, Per S.; Tegner, Yelverton; Malm, Christer

    2014-01-01

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained

  5. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    Science.gov (United States)

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

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

  6. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne

    2007-01-01

    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

  7. Primary non-Hodgkin lymphoma of skeletal muscle: imaging findings

    International Nuclear Information System (INIS)

    Zhou Liangping; Peng Weijun; Tang Feng; Mao Jian; Yang Wentao

    2006-01-01

    Objective: To analyze the imaging manifestations of primary non-Hodgkin lymphoma of skeletal muscle and improve the recognition of this rare disease. Methods: Five cases of primary non- Hodgkin lymphoma of skeletal muscle proved pathologically underwent imaging exam, including MRI and CT in 3 cases, only MRI in 1 case, only CT in 1 case, X-ray in 2 cases and bone scintigraphy in 2 cases. Results: Diffuse enlargements of involved muscle with presentation of overall configuration were observed in all five cases. All 4 cases manifested as homogeneous soft masses, which is isoattenuating to normal muscle on unenhanced CT images. After intravenous injection of contrast media, the masses enhanced homogeneously and slightly (2 cases) or moderately (1 case) on CT images. The lesions were homogenous and had isointense or slightly low signal intensity compared with that of uninvolved muscle on T 1 -weighted images and high signal intensity on T 2 -weighted images. After intravenous injection of contrast media, all 2 cases enhanced homogeneously and moderately with the enhanced signal intensity of involved muscle greatly higher than that of uninvolved muscle on MR images. Two cases of X-ray plain showed no destruction of bone and 2 cases of bone scintigraphy exams showed increased radiotracer uptake of involved muscle with no infiltration of bone marrow. Conclusion: There are several characteristics on the imaging of primary non-Hodgkin lymphoma of skeletal muscle. MRI is the optimal imaging method for the diagnosis of this disease. (authors)

  8. Selection, processing and clinical application of muscle-skeletal tissue

    International Nuclear Information System (INIS)

    Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G.

    2007-01-01

    Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

  9. 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.

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

    DEFF Research Database (Denmark)

    Kragstrup, T W; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging....... Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross...

  11. 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

  12. 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

  13. 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

  14. 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); others, and

    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

  15. A quantitative description of tubular system Ca2+ handling in fast‐ and slow‐twitch muscle fibres

    Science.gov (United States)

    Cully, Tanya R.; Edwards, Joshua N.; Murphy, Robyn M.

    2016-01-01

    Key points Current methods do not allow a quantitative description of Ca2+ movements across the tubular (t‐) system membrane without isolating the membranes from their native skeletal muscle fibre.Here we present a fluorescence‐based method that allows determination of the t‐system [Ca2+] transients and derivation of t‐system Ca2+ fluxes in mechanically skinned skeletal muscle fibres. Differences in t‐system Ca2+‐handling properties between fast‐ and slow‐twitch fibres from rat muscle are resolved for the first time using this new technique.The method can be used to study Ca2+ handling of the t‐system and allows direct comparisons of t‐system Ca2+ transients and Ca2+ fluxes between groups of fibres and fibres from different strains of animals. Abstract The tubular (t‐) system of skeletal muscle is an internalization of the plasma membrane that maintains a large Ca2+ gradient and exchanges Ca2+ between the extracellular and intracellular environments. Little is known of the Ca2+‐handling properties of the t‐system as the small Ca2+ fluxes conducted are difficult to resolve with conventional methods. To advance knowledge in this area we calibrated t‐system‐trapped rhod‐5N inside skinned fibres from rat and [Ca2+]t‐sys, allowing confocal measurements of Ca2+‐dependent changes in rhod‐5N fluorescence during rapid changes in the intracellular ionic environment to be converted to [Ca2+] transients in the t‐system ([Ca2+]t‐sys (t)). Furthermore, t‐system Ca2+‐buffering power was determined so that t‐system Ca2+ fluxes could be derived from [Ca2+]t‐sys (t). With this new approach, we show that rapid depletion of sarcoplasmic reticulum (SR) Ca2+ induced a robust store‐operated Ca2+ entry (SOCE) in fast‐ and slow‐twitch fibres, reducing [Ca2+]t‐sys to fibre types. Abruptly introducing internal solutions with 1 mm Mg2+ and [Ca2+]cyto (28 nm–1.3 μm) to Ca2+‐depleted fibres generated t‐system Ca2+ uptake rates

  16. A quantitative description of tubular system Ca(2+) handling in fast- and slow-twitch muscle fibres.

    Science.gov (United States)

    Cully, Tanya R; Edwards, Joshua N; Murphy, Robyn M; Launikonis, Bradley S

    2016-06-01

    Current methods do not allow a quantitative description of Ca(2+) movements across the tubular (t-) system membrane without isolating the membranes from their native skeletal muscle fibre. Here we present a fluorescence-based method that allows determination of the t-system [Ca(2+) ] transients and derivation of t-system Ca(2+) fluxes in mechanically skinned skeletal muscle fibres. Differences in t-system Ca(2+) -handling properties between fast- and slow-twitch fibres from rat muscle are resolved for the first time using this new technique. The method can be used to study Ca(2+) handling of the t-system and allows direct comparisons of t-system Ca(2+) transients and Ca(2+) fluxes between groups of fibres and fibres from different strains of animals. The tubular (t-) system of skeletal muscle is an internalization of the plasma membrane that maintains a large Ca(2+) gradient and exchanges Ca(2+) between the extracellular and intracellular environments. Little is known of the Ca(2+) -handling properties of the t-system as the small Ca(2+) fluxes conducted are difficult to resolve with conventional methods. To advance knowledge in this area we calibrated t-system-trapped rhod-5N inside skinned fibres from rat and [Ca(2+) ]t-sys , allowing confocal measurements of Ca(2+) -dependent changes in rhod-5N fluorescence during rapid changes in the intracellular ionic environment to be converted to [Ca(2+) ] transients in the t-system ([Ca(2+) ]t-sys (t)). Furthermore, t-system Ca(2+) -buffering power was determined so that t-system Ca(2+) fluxes could be derived from [Ca(2+) ]t-sys (t). With this new approach, we show that rapid depletion of sarcoplasmic reticulum (SR) Ca(2+) induced a robust store-operated Ca(2+) entry (SOCE) in fast- and slow-twitch fibres, reducing [Ca(2+) ]t-sys to fibre types. Abruptly introducing internal solutions with 1 mm Mg(2+) and [Ca(2+) ]cyto (28 nm-1.3 μm) to Ca(2+) -depleted fibres generated t-system Ca(2+) uptake rates dependent on [Ca(2

  17. Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans.

    Science.gov (United States)

    Krustrup, Peter; Secher, Niels H; Relu, Mihai U; Hellsten, Ylva; Söderlund, Karin; Bangsbo, Jens

    2008-12-15

    We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P fibres, whereas in CON, CP decreased (P fibres, respectively. From 127 s of exercise, muscle VO2 was higher (P muscle VO2 response was slower (P muscle homogenate CP was lowered (P muscle lactate production was similar in CUR and CON (37.8 +/- 4.1 versus 35.2 +/- 6.2 mmol). Estimated total muscle ATP turnover was 19% higher (P fibres are less efficient than ST fibres in vivo at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation.

  18. Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue.

    Science.gov (United States)

    Macdonald, W A; Stephenson, D G

    2006-05-15

    Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 microm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (-log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 microm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 microm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres.

  19. 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.

  20. Localization of 3H-diethylstilbestrol in skeletal muscle

    International Nuclear Information System (INIS)

    Gruber, B.; Cohen, L.

    1981-01-01

    The localization of diethylstilbestrol (DES) in skeletal muscle was studied in CF1 mice and perfused rat hindlimbs. There was a slow accumulation of 3H-DES in mouse muscle from 4 to 24 hours following i.p. injection even though plasma DES was decreasing. Twenty-four hours after injection of 50 microCi 3H-DES (714 pmole) mouse gastrocnemius contained 8.9 x 10(-17) mole unaltered 3H-DES per mg muscle. Extrapolating to the entire skeletal muscle mass of the animal, this represents 0.15% of the radioactivity injected. The radioactivity in muscle was completely extracted with 95% ethanol or ether: ethanol (3:1), and both unaltered DES and DES-metabolites were present in the extracts. The fraction of radioactivity due to unaltered DES 4 hours after injection was 0.51 +/- 0.09 in muscle and 0.30 +/- 0.11 in plasma. Significant extrahepatic metabolism of DES was demonstrated in perfused isolated rat hindlimbs by the presence of DES-metabolites in the perfusate. The radioactivity extracted from the perfused muscle itself was unaltered DES. These results indicate that skeletal muscle is an important site of DES localization in rodents

  1. How does tissue preparation affect skeletal muscle transverse isotropy?

    Science.gov (United States)

    Wheatley, Benjamin B.; Odegard, Gregory M.; Kaufman, Kenton R.; Haut Donahue, Tammy L.

    2016-01-01

    The passive tensile properties of skeletal muscle play a key role in its physiological function. Previous research has identified conflicting reports of muscle transverse isotropy, with some data suggesting the longitudinal direction is stiffest, while others show the transverse direction is stiffest. Accurate constitutive models of skeletal muscle must be employed to provide correct recommendations for and observations of clinical methods. The goal of this work was to identify transversely isotropic tensile muscle properties as a function of post mortem handling. Six pairs of tibialis anterior muscles were harvested from Giant Flemish rabbits and split into two groups: fresh testing (within four hours post mortem), and non-fresh testing (subject to delayed testing and a freeze/thaw cycle). Longitudinal and transverse samples were removed from each muscle and tested to identify tensile modulus and relaxation behavior. Longitudinal non-fresh samples exhibited a higher initial modulus value and faster relaxation than longitudinal fresh, transverse fresh, and transverse rigor samples (p<0.05), while longitudinal fresh samples were less stiff at lower strain levels than longitudinal non-fresh, transverse fresh, and transverse non-fresh samples (p<0.05), but exhibited more nonlinear behavior. While fresh skeletal muscle exhibits a higher transverse modulus than longitudinal modulus, discrepancies in previously published data may be the result of a number of differences in experimental protocol. Constitutive modeling of fresh muscle should reflect these data by identifying the material as truly transversely isotropic and not as an isotropic matrix reinforced with fibers. PMID:27425557

  2. Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression.

    Science.gov (United States)

    Goljanek-Whysall, Katarzyna; Iwanejko, Lesley A; Vasilaki, Aphrodite; Pekovic-Vaughan, Vanja; McDonagh, Brian

    2016-08-01

    Ageing is associated with a progressive loss of skeletal muscle mass, quality and function-sarcopenia, associated with reduced independence and quality of life in older generations. A better understanding of the mechanisms, both genetic and epigenetic, underlying this process would help develop therapeutic interventions to prevent, slow down or reverse muscle wasting associated with ageing. Currently, exercise is the only known effective intervention to delay the progression of sarcopenia. The cellular responses that occur in muscle fibres following exercise provide valuable clues to the molecular mechanisms regulating muscle homoeostasis and potentially the progression of sarcopenia. Redox signalling, as a result of endogenous generation of ROS/RNS in response to muscle contractions, has been identified as a crucial regulator for the adaptive responses to exercise, highlighting the redox environment as a potentially core therapeutic approach to maintain muscle homoeostasis during ageing. Further novel and attractive candidates include the manipulation of microRNA expression. MicroRNAs are potent gene regulators involved in the control of healthy and disease-associated biological processes and their therapeutic potential has been researched in the context of various disorders, including ageing-associated muscle wasting. Finally, we discuss the impact of the circadian clock on the regulation of gene expression in skeletal muscle and whether disruption of the peripheral muscle clock affects sarcopenia and altered responses to exercise. Interventions that include modifying altered redox signalling with age and incorporating genetic mechanisms such as circadian- and microRNA-based gene regulation, may offer potential effective treatments against age-associated sarcopenia.

  3. 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 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.

  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. 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......GMP) was used as intervention, and skeletal muscle blood flow, oxygen delivery, and functional sympatholysis was examined. The two studies included 53 healthy, habitually active, male subjects. All subjects participated in an experimental day in which femoral arterial blood flow and blood pressure were assessed...... 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...

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

    Science.gov (United States)

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

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

  7. 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...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... 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...

  8. The role of skeletal muscle in the pathophysiology and management of knee osteoarthritis.

    Science.gov (United States)

    Krishnasamy, Priathashini; Hall, Michelle; Robbins, Sarah R

    2018-05-01

    The role of skeletal muscle in the pathophysiology of knee OA is poorly understood. To date, the majority of literature has focused on the association of muscle strength with OA symptoms, disease onset and progression. However, deficits or improvements in skeletal muscle strength do not fully explain the mechanisms behind outcome measures in knee OA, such as pain, function and structural disease. This review aims to summarize components of skeletal muscle, providing a holistic view of skeletal muscle mechanisms that includes muscle function, quality and composition and their interactions. Similarly, the role of skeletal muscle in the management of knee OA will be discussed.

  9. Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

    Science.gov (United States)

    Guderley, Helga; Joanisse, Denis R; Mokas, Sophie; Bilodeau, Geneviève M; Garland, Theodore

    2008-03-01

    Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

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

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

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

  11. Neuromuscular organization of avian flight muscle: architecture of single muscle fibres in muscle units of the pectoralis (pars thoracicus) of pigeon (Columba livia)

    Science.gov (United States)

    Sokoloff, A. J.

    1999-01-01

    The M. pectoralis (pars thoracicus) of pigeons (Columba livia) is comprised of short muscle fibres that do not extend from muscle origin to insertion but overlap 'in-series'. Individual pectoralis motor units are limited in territory to a portion of muscle length and are comprised of either fast twitch, oxidative and glycolytic fibres (FOG) or fast twitch and glycolytic fibres (FG). FOG fibres make up 88 to 90% of the total muscle population and have a mean diameter one-half of that of the relatively large FG fibres. Here we report on the organization of individual fibres identified in six muscle units depleted of glycogen, three comprised of FOG fibres and three comprised of FG fibres. For each motor unit, fibre counts revealed unequal numbers of depleted fibres in different unit cross-sections. We traced individual fibres in one unit comprised of FOG fibres and a second comprised of FG fibres. Six fibres from a FOG unit (total length 15.45 mm) ranged from 10.11 to 11.82 mm in length and averaged (± s.d.) 10.74 ± 0.79 mm. All originated bluntly (en mass) from a fascicle near the proximal end of the muscle unit and all terminated intramuscularly. Five of these ended in a taper and one ended bluntly. Fibres coursed on average for 70% of the muscle unit length. Six fibres from a FG unit (total length 34.76 mm) ranged from 8.97 to 18.38 mm in length and averaged 15.32 ± 3.75 mm. All originated bluntly and terminated intramuscularly; one of these ended in a taper and five ended bluntly. Fibres coursed on average for 44% of the muscle unit length. Because fibres of individual muscle units do not extend the whole muscle unit territory, the effective cross-sectional area changes along the motor unit length. These non-uniformities in the distribution of fibres within a muscle unit emphasize that the functional interactions within and between motor units are complex.

  12. 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

  13. Specific fibre composition and metabolism of the rectus abdominis muscle of bovine Charolais cattle

    Science.gov (United States)

    2010-01-01

    Background An important variability of contractile and metabolic properties between muscles has been highlighted. In the literature, the majority of studies on beef sensorial quality concerns M. longissimus thoracis. M. rectus abdominis (RA) is easy to sample without huge carcass depreciation and may appear as an alternative to M. longissimus thoracis for fast and routine physicochemical analysis. It was considered interesting to assess the muscle fibres of M. rectus abdominis in comparison with M. longissimus thoracis (LT) and M. triceps brachii (TB) on the basis of metabolic and contractile properties, area and myosin heavy chain isoforms (MyHC) proportions. Immuno-histochemical, histochemical, histological and enzymological techniques were used. This research concerned two populations of Charolais cattle: RA was compared to TB in a population of 19 steers while RA was compared to LT in a population of 153 heifers. Results RA muscle had higher mean fibre areas (3350 μm2 vs 2142 to 2639 μm2) than the two other muscles. In RA muscle, the slow-oxidative fibres were the largest (3957 μm2) and the fast-glycolytic the smallest (2868 μm2). The reverse was observed in TB muscle (1725 and 2436 μm2 respectively). In RA muscle, the distinction between fast-oxidative-glycolytic and fast-glycolytic fibres appeared difficult or impossible to establish, unlike in the other muscles. Consequently the classification based on ATPase and SDH activities seemed inappropriate, since the FOG fibres presented rather low SDH activity in this muscle in comparison to the other muscles of the carcass. RA muscle had a higher proportion of I fibres than TB and LT muscles, balanced by a lower proportion either of IIX fibres (in comparison to TB muscle) or of IIA fibres (in comparison to LT muscle). However, both oxidative and glycolytic enzyme activities were lower in RA than in TB muscle, although the LDH/ICDH ratio was higher in RA muscle (522 vs 340). Oxidative enzyme activities were

  14. Cannabinoid signalling inhibits sarcoplasmic Ca2+ release and regulates excitation–contraction coupling in mammalian skeletal muscle

    Science.gov (United States)

    Oláh, Tamás; Bodnár, Dóra; Tóth, Adrienn; Vincze, János; Fodor, János; Reischl, Barbara; Kovács, Adrienn; Ruzsnavszky, Olga; Dienes, Beatrix; Szentesi, Péter; Friedrich, Oliver

    2016-01-01

    Key points Marijuana was found to cause muscle weakness, although the exact regulatory role of its receptors (CB1 cannabinoid receptor; CB1R) in the excitation–contraction coupling (ECC) of mammalian skeletal muscle remains unknown.We found that CB1R activation or its knockout did not affect muscle force directly, whereas its activation decreased the Ca2+‐sensitivity of the contractile apparatus and made the muscle fibres more prone to fatigue.We demonstrate that CB1Rs are not connected to the inositol 1,4,5‐trisphosphate pathway either in myotubes or in adult muscle fibres.By contrast, CB1Rs constitutively inhibit sarcoplasmic Ca2+ release and sarcoplasmic reticulum Ca2+ ATPase during ECC in a Gi/o protein‐mediated way in adult skeletal muscle fibres but not in myotubes.These results help with our understanding of the physiological effects and pathological consequences of CB1R activation in skeletal muscle and may be useful in the development of new cannabinoid drugs. Abstract Marijuana was found to cause muscle weakness, although it is unknown whether it affects the muscles directly or modulates only the motor control of the central nervous system. Although the presence of CB1 cannabinoid receptors (CB1R), which are responsible for the psychoactive effects of the drug in the brain, have recently been demonstrated in skeletal muscle, it is unclear how CB1R‐mediated signalling affects the contraction and Ca²⁺ homeostasis of mammalian skeletal muscle. In the present study, we demonstrate that in vitro CB1R activation increased muscle fatigability and decreased the Ca2+‐sensitivity of the contractile apparatus, whereas it did not alter the amplitude of single twitch contractions. In myotubes, CB1R agonists neither evoked, nor influenced inositol 1,4,5‐trisphosphate (IP3)‐mediated Ca2+ transients, nor did they alter excitation–contraction coupling. By contrast, in isolated muscle fibres of wild‐type mice, although CB1R agonists did not evoke IP3

  15. Cannabinoid signalling inhibits sarcoplasmic Ca2+ release and regulates excitation-contraction coupling in mammalian skeletal muscle.

    Science.gov (United States)

    Oláh, Tamás; Bodnár, Dóra; Tóth, Adrienn; Vincze, János; Fodor, János; Reischl, Barbara; Kovács, Adrienn; Ruzsnavszky, Olga; Dienes, Beatrix; Szentesi, Péter; Friedrich, Oliver; Csernoch, László

    2016-12-15

    Marijuana was found to cause muscle weakness, although the exact regulatory role of its receptors (CB1 cannabinoid receptor; CB1R) in the excitation-contraction coupling (ECC) of mammalian skeletal muscle remains unknown. We found that CB1R activation or its knockout did not affect muscle force directly, whereas its activation decreased the Ca 2+ -sensitivity of the contractile apparatus and made the muscle fibres more prone to fatigue. We demonstrate that CB1Rs are not connected to the inositol 1,4,5-trisphosphate pathway either in myotubes or in adult muscle fibres. By contrast, CB1Rs constitutively inhibit sarcoplasmic Ca 2+ release and sarcoplasmic reticulum Ca 2+ ATPase during ECC in a G i/o protein-mediated way in adult skeletal muscle fibres but not in myotubes. These results help with our understanding of the physiological effects and pathological consequences of CB1R activation in skeletal muscle and may be useful in the development of new cannabinoid drugs. Marijuana was found to cause muscle weakness, although it is unknown whether it affects the muscles directly or modulates only the motor control of the central nervous system. Although the presence of CB1 cannabinoid receptors (CB1R), which are responsible for the psychoactive effects of the drug in the brain, have recently been demonstrated in skeletal muscle, it is unclear how CB1R-mediated signalling affects the contraction and Ca²⁺ homeostasis of mammalian skeletal muscle. In the present study, we demonstrate that in vitro CB1R activation increased muscle fatigability and decreased the Ca 2+ -sensitivity of the contractile apparatus, whereas it did not alter the amplitude of single twitch contractions. In myotubes, CB1R agonists neither evoked, nor influenced inositol 1,4,5-trisphosphate (IP 3 )-mediated Ca 2+ transients, nor did they alter excitation-contraction coupling. By contrast, in isolated muscle fibres of wild-type mice, although CB1R agonists did not evoke IP 3 -mediated Ca 2

  16. Culturing muscle fibres in hanging drop: a novel approach to solve an old problem.

    Science.gov (United States)

    Archacka, Karolina; Pozzobon, Michela; Repele, Andrea; Rossi, Carlo Alberto; Campanella, Michelangelo; De Coppi, Paolo

    2014-02-01

    The satellite cells (SCs) associated with muscle fibres play a key role in postnatal growth and regeneration of skeletal muscle. Commonly used methods of isolation and in vitro culture of SCs lead to the mixture of their subpopulations that exist within muscle. To solve this problem, we used the well established technique, the hanging drop system, to culture SCs in a three-dimensional environment and thus, to monitor them in their original niche. Using hanging drop technique, we were able to culture SCs associated with the fibre at least for 9 days with one transfer of fibres to the fresh drops. In comparison, in the classical method of myofibres culture, that is, on the dishes coated with Matrigel, SCs leave the fibres within 3 days after the isolation. Cells cultured in both systems differed in expression of Pax7 and MyoD. While almost all cells cultured in adhesion system expressed MyoD before the fifth day of the culture, the majority of SCs cultured in hanging drop still maintained expression of Pax7 and were not characterised by the presence of MyoD. Among the cells cultured with single myofibre for up to 9 days, we identified two different subclones of SCs: low proliferative clone and high proliferative clone, which differed in proliferation rate and membrane potential. The hanging drop enables the myofibres to be kept in suspension for at least 9 days, and thus, allows SCs and their niche to interact each other for prolonged time. In a consequence, SCs cultured in hanging drop maintain expression of Pax7 while those cultured in a traditional adhesion culture, that is, devoid of signals from the original niche, activate and preferentially undergo differentiation as manifested by expression of MyoD. Thus, the innovative method of SCs culturing in the hanging drop system may serve as a useful tool to study the fate of different subpopulations of these cells in their anatomical location and to determine reciprocal interactions between them and their niche.

  17. 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

  18. Skeletal Muscle Laminopathies: A Review of Clinical and Molecular Features

    Directory of Open Access Journals (Sweden)

    Lorenzo Maggi

    2016-08-01

    Full Text Available LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases.

  19. 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.

  20. 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.

  1. Ionic currents and charge movements in organ-cultured rat skeletal muscle.

    Science.gov (United States)

    Hollingworth, S; Marshall, M W; Robson, E

    1984-12-01

    The middle of the fibre voltage-clamp technique was used to measure ionic currents and non-linear charge movements in intact, organ-cultured (in vitro denervated) mammalian fast-twitch (rat extensor digitorum longus) muscle fibres. Muscle fibres organ cultured for 4 days can be used as electrophysiological and morphological models for muscles in vivo denervated for the same length of time. Sodium currents in organ-cultured muscle fibres are similar to innervated fibres except that in the temperature range 0-20 degrees C (a) in the steady state, the voltage distribution of inactivation in cultured fibres is shifted negatively some 20 mV; (b) at the same temperature and membrane potential, the time constant of inactivation in cultured fibres is about twice that of innervated fibres. Potassium currents in innervated and cultured fibres at 15 degrees C can be fitted with the Hodgkin-Huxley n variable raised to the second power. Despite the large range we would estimate that the maximum value of the steady-state potassium conductance of cultured fibres is about one-half that of innervated fibres. The estimated maximum amount of charge moved in cultured fibre is about one-third that in innervated fibres. Compared to innervated fibres, culturing doubles the kinetics of the decay phase of charge movement. The possibility of a negative shift of the voltage distribution of charge movements in cultured fibres is discussed.

  2. Skeletal muscle plasticity with marathon training in novice runners.

    Science.gov (United States)

    Luden, N; Hayes, E; Minchev, K; Louis, E; Raue, U; Conley, T; Trappe, S

    2012-10-01

    The purpose of this study was to investigate leg muscle adaptation in runners preparing for their first marathon. Soleus and vastus lateralis (VL) biopsies were obtained from six recreational runners (23 ± 1 years, 61 ± 3 kg) before (T1), after 13 weeks of run training (T2), and after 3 weeks of taper and marathon (T3). Single muscle fiber size, contractile function (strength, speed, and power) and oxidative enzyme activity [citrate synthase (CS)] were measured at all three time points, and fiber type distribution was determined before and after the 16-week intervention. Training increased VO(2max) ∼9% (Pmarathon training elicits very specific skeletal muscle adaptations that likely support the ability to perform 42.2 km of continuous running - further strengthening the existing body of evidence for skeletal muscle specificity. © 2011 John Wiley & Sons A/S.

  3. 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.

  4. Effects of 45Ca on murine skeletal muscle. 3

    International Nuclear Information System (INIS)

    Malhotra, R.K.; Asotra, K.; Katoch, S.S.; Krishan, K.

    1983-01-01

    Swiss albino mice were injected intraperitoneally with 3.7x10 4 Bq and 7.4x10 4 Bq 45 Ca/g body weight. Mice of both dose groups were autopsied on days 1, 3, 5, 7, 14 and 28 and activities of alanine aminotransferase and aspartate aminotransferase bioassayed in diaphragm and gastrocnemius in 45 Ca-treated and normal mice. Alanine aminotransferase activity in the two muscles increased in response to 45 Ca administration suggesting a stepped up utilization of alanine in glucose generation. Aspartate aminotransferase levels, on the other hand, diminished in both the 45 Ca-treated muscles and are maintained at low values throughout the 28 day period of study. The results suggest an innate ability of skeletal muscle to selectively utilize either of the two glucogenic amino acids during radiation stress. The data are discussed in light of previous findings on glycogen accumulation in irradiated skeletal muscle. (author)

  5. EFFECT OF REARING SYSTEM ON THE MUSCLE FIBRE CHARACTERISTICS OF CHICKEN BREEDS WITH DIFFERENT GROWTH SPEED

    Directory of Open Access Journals (Sweden)

    P. Avellini

    2009-06-01

    Full Text Available The study was conducted to evaluate the influence of the rearing system on the muscle fibre characteristics of two meat chicken breeds such as the Ross and the Livorno characterized by extremely fast and extremely slow growth speed respectively. No differences between the breeds were found in the conventional rearing system except for muscle fibre area. On the other hand, in the free range rearing system, differences in muscle fibre composition were evidenced between the breeds especially in the Ileotibialis lateralis muscle with the Livorno having a greater percentage of αR fibres (57,71 vs 36,65. A higher percentage of αR fibres (57,71 vs 46,90 was found in the Ileotibialis lateralis of the free range reared Livorno chickens compared to the conventionally reared ones.

  6. 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....

  7. Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

    OpenAIRE

    Korzeniewski, Bernard; Zoladz, Jerzy A

    2003-01-01

    Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial protein...

  8. Pixel-based meshfree modelling of skeletal muscles

    OpenAIRE

    Chen, Jiun-Shyan; Basava, Ramya Rao; Zhang, Yantao; Csapo, Robert; Malis, Vadim; Sinha, Usha; Hodgson, John; Sinha, Shantanu

    2015-01-01

    This paper introduces the meshfree Reproducing Kernel Particle Method (RKPM) for 3D image-based modeling of skeletal muscles. This approach allows for construction of simulation model based on pixel data obtained from medical images. The material properties and muscle fiber direction obtained from Diffusion Tensor Imaging (DTI) are input at each pixel point. The reproducing kernel (RK) approximation allows a representation of material heterogeneity with smooth transition. A ...

  9. 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.

  10. Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery

    Science.gov (United States)

    Py, G; Ramonatxo, C; Sirvent, P; Sanchez, A M J; Philippe, A G; Douillard, A; Galbès, O; Lionne, C; Bonnieu, A; Chopard, A; Cazorla, O; Lacampagne, A; Candau, R B

    2015-01-01

    Clenbuterol is a β2-adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg−1 day−1) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P fast rate constant of relaxation in soleus muscle (P fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (−19%, P < 0.01) and 21 days (−25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca2+ release during contraction could partially explain these deleterious effects. PMID:25656230

  11. Regenerated rat skeletal muscle after periodic contusions

    Directory of Open Access Journals (Sweden)

    V.B. Minamoto

    2001-11-01

    Full Text Available In the present study we evaluated the morphological aspect and changes in the area and incidence of muscle fiber types of long-term regenerated rat tibialis anterior (TA muscle previously submitted to periodic contusions. Animals received eight consecutive traumas: one trauma per week, for eight weeks, and were evaluated one (N = 8 and four (N = 9 months after the last contusion. Serial cross-sections were evaluated by toluidine blue staining, acid phosphatase and myosin ATPase reactions. The weight of injured muscles was decreased compared to the contralateral intact one (one month: 0.77 ± 0.15 vs 0.91 ± 0.09 g, P = 0.03; four months: 0.79 ± 0.14 vs 1.02 ± 0.07 g, P = 0.0007, respectively and showed abundant presence of split fibers and fibers with centralized nuclei, mainly in the deep portion. Damaged muscles presented a higher incidence of undifferentiated fibers when compared to the intact one (one month: 3.4 ± 2.1 vs 0.5 ± 0.3%, P = 0.006; four months: 2.3 ± 1.6 vs 0.3 ± 0.3%, P = 0.007, respectively. Injured TA evaluated one month later showed a decreased area of muscle fibers when compared to the intact one (P = 0.003. Thus, we conclude that: a muscle fibers were damaged mainly in the deep portion, probably because they were compressed against the tibia; b periodic contusions in the TA muscle did not change the percentage of type I and II muscle fibers; c periodically injured TA muscles took four months to reach a muscle fiber area similar to that of the intact muscle.

  12. Energetic aspects of skeletal muscle contraction: implications of fiber types.

    Science.gov (United States)

    Rall, J A

    1985-01-01

    In this chapter fundamental energetic properties of skeletal muscles as elucidated from isolated muscle preparations are described. Implications of these intrinsic properties for the energetic characterization of different fiber types and for the understanding of locomotion have been considered. Emphasis was placed on the myriad of physical and chemical techniques that can be employed to understand muscle energetics and on the interrelationship of results from different techniques. The anaerobic initial processes which liberate energy during contraction and relaxation are discussed in detail. The high-energy phosphate (approximately P) utilized during contraction and relaxation can be distributed between actomyosin ATPase or cross-bridge cycling (70%) and the Ca2+ ATPase of the sacroplasmic reticulum (30%). Muscle shortening increases the rate of approximately P hydrolysis, and stretching a muscle during contraction suppresses the rate of approximately P hydrolysis. The economy of an isometric contraction is defined as the ratio of isometric mechanical response to energetic cost and is shown to be a fundamental intrinsic parameter describing muscle energetics. Economy of contraction varies across the animal kingdom by over three orders of magnitude and is different in different mammalian fiber types. In mammalian skeletal muscles differences in economy of contraction can be attributed mainly to differences in the specific actomyosin and Ca2+ ATPase of muscles. Furthermore, there is an inverse relationship between economy of contraction and maximum velocity of muscle shortening (Vmax) and maximum power output. This is a fundamental relationship. Muscles cannot be economical at developing and maintaining force and also exhibit rapid shortening. Interestingly, there appears to be a subtle system of unknown nature that modulates the Vmax and economy of contraction. Efficiency of a work-producing contraction is defined and contrasted to the economy of contraction

  13. Impact of placental insufficiency on fetal skeletal muscle growth

    Science.gov (United States)

    Hay, William W.

    2016-01-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

  14. 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...

  15. HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses.

    Science.gov (United States)

    Pigna, Eva; Renzini, Alessandra; Greco, Emanuela; Simonazzi, Elena; Fulle, Stefania; Mancinelli, Rosa; Moresi, Viviana; Adamo, Sergio

    2018-02-24

    Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitin-proteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

  16. 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...... in contracting muscle by increasing the phosphorylase a activity via increased cyclic AMP production. The availability of blood-borne substrates may also influence muscle glycogenolysis and, therefore, exercise performance......., increases in the AMP and IMP levels may increase phosphorylase activity. The rate of muscle-glycogen breakdown during exercise depends on the pre-exercise glycogen concentration and is also influenced by hormones. Insulin may inhibit glycogen breakdown, whereas epinephrine enhances the rate of glycogen use...

  17. Slow and fast fatigable frog muscle fibres: electrophysiological and histochemical characteristics.

    Science.gov (United States)

    Vydevska-Chichova, M; Mileva, K; Todorova, R; Dimitrova, M; Radicheva, N

    2005-12-01

    Continuous activity of isolated frog gastrocnemius muscle fibres provoked by repetitive stimulation of 5 Hz was used as an experimental model for fatigue development in different fibre types. Parameter changes of the elicited intracellular action potentials and mechanical twitches during the period of uninterrupted activity were used as criteria for fatigue evaluation. Slow fatigable muscle fibre (SMF) and fast fatigable muscle fibre (FMF) types were distinguished depending on the duration of their uninterrupted activity, which was significantly longer in SMFs than in FMFs. The normalized changes of action potential amplitude and duration were significantly smaller in FMFs than in SMFs. The average twitch force and velocity of contraction and relaxation were significantly higher in FMFs than in SMFs. Myosin ATPase (mATPase) and succinate dehydrogenase activity were studied by histochemical assessment in order to validate the fibre type classification based on their electrophysiological characteristics. Based on the relative mATPase reactivity, the fibres of the studied muscle were classified as one of five different types (1-2, 2, 2-3, 3 and tonic). Smaller sized fibres (tonic and type 3) expressed higher succinate dehydrogenase activity than larger sized fibres (type 1-2, 2), which is related to the fatigue resistance. The differences between fatigue development in SMFs and FMFs during continuous activity were associated with fibre-type specific mATPase and succinate dehydrogenase activity.

  18. 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...

  19. 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...

  20. 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.

  1. 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.

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

    International Nuclear Information System (INIS)

    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

  3. Dynamic imaging of skeletal muscle contraction in three orthogonal directions

    NARCIS (Netherlands)

    Lopata, R.G.; van Dijk, J.P; Pillen, S.; Nillisen, M.M.; Maas, H.; Thijssen, J.M.; Stegeman, D.F.; Korte, C.L.

    2010-01-01

    In this study, a multidimensional strain estimation method using biplane ultrasound is presented to assess local relative deformation (i.e., local strain) in three orthogonal directions in skeletal muscles during induced and voluntary contractions. The method was tested in the musculus biceps

  4. Dynamic imaging of skeletal muscle contraction in three orthogonal directions.

    NARCIS (Netherlands)

    Lopata, R.G.P.; Dijk, J.P. van; Pillen, S.; Nillesen, M.M.; Maas, H.; Thijssen, J.M.; Stegeman, D.F.; Korte, C.L. de

    2010-01-01

    In this study, a multidimensional strain estimation method using biplane ultrasound is presented to assess local relative deformation (i.e., local strain) in three orthogonal directions in skeletal muscles during induced and voluntary contractions. The method was tested in the musculus biceps

  5. Skeletal muscle mitochondrial respiration in AMPKa2 kinase dead mice

    DEFF Research Database (Denmark)

    Larsen, Steen; Kristensen, Jonas Møller; Stride, Nis

    2012-01-01

    AIM: To study if the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKa2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2...

  6. 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...

  7. 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.

  8. 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

  9. Factors regulating fat oxidation in human skeletal muscle

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  10. Acute exercise remodels promoter methylation in human skeletal muscle

    DEFF Research Database (Denmark)

    Barrès, Romain; Yan, Jie; Egan, Brendan

    2012-01-01

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

  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. Meet the new meat: tissue engineered skeletal muscle

    NARCIS (Netherlands)

    Langelaan, M.L.P.; Boonen, K.J.M.; Polak, R.B.; Baaijens, F.P.T.; Post, M.J.; Schaft, van der D.W.J.

    2010-01-01

    Contemporary large-scale farming and transportation of livestock brings along a high risk of infectious animal diseases and environmental burden through greenhouse gas emission. A new approach to produce meat and thereby reducing these risks is found in tissue engineering of skeletal muscle. This

  13. Redox regulation of calcium release in skeletal and cardiac muscle

    Directory of Open Access Journals (Sweden)

    CECILIA HIDALGO

    2002-01-01

    Full Text Available In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist and Mg2+ (endogenous inhibitor on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 µM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 µM [Ca2+]. In 10 µM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] ­ 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 µM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed

  14. In vivo generation of a mature and functional artificial skeletal muscle.

    Science.gov (United States)

    Fuoco, Claudia; Rizzi, Roberto; Biondo, Antonella; Longa, Emanuela; Mascaro, Anna; Shapira-Schweitzer, Keren; Kossovar, Olga; Benedetti, Sara; Salvatori, Maria L; Santoleri, Sabrina; Testa, Stefano; Bernardini, Sergio; Bottinelli, Roberto; Bearzi, Claudia; Cannata, Stefano M; Seliktar, Dror; Cossu, Giulio; Gargioli, Cesare

    2015-04-01

    Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for a large number of pathological conditions involving muscle tissue wasting. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  15. 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.

  16. Skeletal muscle substrate metabolism during exercise: methodological considerations

    DEFF Research Database (Denmark)

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

    1999-01-01

    and the respiratory exchange ratio. However, if the aim is to quantify limb or muscle metabolism, invasive measurements have to be carried out, such as the determination of blood flow, arterio-venous (a-v) difference measurements for O2 and relevant substrates, and biopsies of the active muscle. As many substrates...... 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......; (3) the use of net limb glycerol release to estimate lipolysis is probably not valid (triacylglycerol utilization by muscle), since glycerol can be metabolized in skeletal muscle; (4) the precision of blood-borne substrate concentrations during exercise measured by a-v difference is hampered since...

  17. Plasticity of the transverse tubules following denervation and subsequent reinnervation in rat slow and fast muscle fibres.

    Science.gov (United States)

    Takekura, Hiroaki; Tamaki, Hiroyuki; Nishizawa, Tomie; Kasuga, Norikatsu

    2003-01-01

    We have studied the effects of short term denervation followed by reinnervation on the ultrastructure of the membrane systems and on the content of and distribution of key proteins involved in calcium regulation of fast-twitch (FT) extensor digitorum longus (EDL) and slow-twitch (ST) soleus (SOL) muscle fibres. Ischiadic nerve freezing resulted in total lack of neuromuscular transmission for 3 days followed by a slow recovery, but no decline in twitch force elicited by direct stimulation. The latter measurements indicate no significant atrophy within this time frame. The membrane systems of skeletal muscle fibres were visualized using Ca92+)-K3Fe(CN)6-OsO4 techniques and observed using a high voltage electron microscope. [3H]nitrendipine binding was used to detect levels of dihydropyridine receptor (DHPR) expression. The Ca2+ pumping free sarcoplasmic reticulum domains were not affected by the denervation, but the Ca2+ release domains were dramatically increased, particularly in the FT-EDL muscle fibres. The increase is evidenced by a doubling up of the areas of contacts between SR and transverse (t-) tubules, so that in place of the normal triadic arrangement, pentadic and heptadic junctions, formed by multiple interacting layers of ST and t-tubules are seen. Frequency of pentads and heptads increases and declines in parallel to the denervation and reinnervation but with a delay. Immunofluorecence and electron microscopy observations show presence of DHPR and ryanodine receptor clusters at pentads and heptads junctions. A significant (P muscle fibres indicating that overexpression of DHPRs accompanies the build up extra junctional contacts. The results indicate that denervation reversibly affects the domains of the membrane systems involved in excitation-contraction coupling.

  18. Effect of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle.

    Science.gov (United States)

    Carter, W J; Van Der Weijden Benjamin, W S; Faas, F H

    1980-10-01

    Since experimental hyperthyroidism reduces skeletal muscle mass while simultaneously increasing cardiac muscle mass, the effect of hyperthyroidism on muscle protein degradation was compared in skeletal and cardiac muscle. Pulse-labeling studies using (3H) leucine and (14C) carboxyl labeled aspartate and glutamate were carried out. Hyperthyroidism caused a 25%-29% increase in protein breakdown in both sarcoplasmic and myofibrillar fractions of skeletal muscle. Increased muscle protein degradation may be a major factor in the development of skeletal muscle wasting and weakness in hyperthyroidism. In contrast, protein breakdown appeared to be reduced 22% in the sarcoplasmic fraction of hyperthyroid heart muscle and was unchanged in the myofibrillar fraction. Possible reasons for the contrasting effects of hyperthyroidism on skeletal and cardiac muscle include increased sensitivity of the hyperthyroid heart to catecholamines, increased cardiac work caused by the hemodynamic effects of hyperthyroidism, and a different direct effect of thyroid hormone at the nuclear level in cardiac as opposed to skeletal muscle.

  19. Androgens regulate gene expression in avian skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Matthew J Fuxjager

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

  20. Tomographic elastography of contracting skeletal muscles from their natural vibrations

    Science.gov (United States)

    Sabra, Karim G.; Archer, Akibi

    2009-11-01

    Conventional elastography techniques require an external mechanical or radiation excitation to measure noninvasively the viscoelastic properties of skeletal muscles and thus monitor human motor functions. We developed instead a passive elastography technique using only an array of skin-mounted accelerometers to record the low-frequency vibrations of the biceps brachii muscle naturally generated during voluntary contractions and to determine their two-dimensional directionality. Cross-correlating these recordings provided travel-times measurements of these muscle vibrations between multiple sensor pairs. Travel-time tomographic inversions yielded spatial variations of their propagation velocity during isometric elbow flexions which indicated a nonuniform longitudinal stiffening of the biceps.

  1. Passive in vivo elastography from skeletal muscle noise

    International Nuclear Information System (INIS)

    Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A.

    2007-01-01

    Measuring the in vivo elastic properties of muscles (e.g., stiffness) provides a means for diagnosing and monitoring muscular activity. The authors demonstrated a passive in vivo elastography technique without an active external radiation source. This technique instead uses cross correlations of contracting skeletal muscle noise recorded with skin-mounted sensors. Each passive sensor becomes a virtual in vivo shear wave source. The results point to a low-cost, noninvasive technique for monitoring biomechanical in vivo muscle properties. The efficacy of the passive elastography technique originates from the high density of cross paths between all sensor pairs, potentially achieving the same sensitivity obtained from active elastography methods

  2. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

    2016-01-01

    Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...... at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals....

  3. Pixel-based meshfree modelling of skeletal muscles.

    Science.gov (United States)

    Chen, Jiun-Shyan; Basava, Ramya Rao; Zhang, Yantao; Csapo, Robert; Malis, Vadim; Sinha, Usha; Hodgson, John; Sinha, Shantanu

    2016-01-01

    This paper introduces the meshfree Reproducing Kernel Particle Method (RKPM) for 3D image-based modeling of skeletal muscles. This approach allows for construction of simulation model based on pixel data obtained from medical images. The material properties and muscle fiber direction obtained from Diffusion Tensor Imaging (DTI) are input at each pixel point. The reproducing kernel (RK) approximation allows a representation of material heterogeneity with smooth transition. A multiphase multichannel level set based segmentation framework is adopted for individual muscle segmentation using Magnetic Resonance Images (MRI) and DTI. The application of the proposed methods for modeling the human lower leg is demonstrated.

  4. Could a functional artificial skeletal muscle be useful in muscle wasting?

    Science.gov (United States)

    Fuoco, Claudia; Cannata, Stefano; Gargioli, Cesare

    2016-05-01

    Regardless of the underlying cause, skeletal muscle wasting is detrimental for a person's life quality, leading to impaired strength, locomotion, and physiological activity. Here, we propose a series of studies presenting tissue engineering-based approaches to reconstruct artificial muscle in vitro and in vivo. Skeletal muscle tissue engineering is attracting more and more attention from scientists, clinicians, patients, and media, thanks to the promising results obtained in the last decade with animal models of muscle wasting. The use of novel and refined biomimetic scaffolds mimicking three-dimensional muscle environment, thus supporting cell survival and differentiation, in combination with well characterized myogenic stem/progenitor cells, revealed the noteworthy potential of these technologies for creating artificial skeletal muscle tissue. In vitro, the production of three-dimensional muscle structures offer the possibility to generate a drug-screening platform for patient-specific pharmacological treatment, opening new frontiers in the development of new compounds with specific therapeutic actions. In vivo, three-dimensional artificial muscle biomimetic constructs offer the possibility to replace, in part or entirely, wasted muscle by means of straight reconstruction and/or by enhancing endogenous regeneration. Reports of tissue engineering approaches for artificial muscle building appeared in large numbers in the specialized press lately, advocating the suitability of this technology for human application upon scaling up and a near future applicability for medical care of muscle wasting. http://links.lww.com/COCN/A9

  5. Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Kristensen, Michael; Juel, Carsten

    2004-01-01

    AIM: Sodium/bicarbonate co-transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. METHODS AND RESULTS: Western blotting of muscle homogenates...... the T-tubules. The two NBCs localized in muscle have distinct fibre type distributions. CONCLUSIONS: Skeletal muscle possesses two variants of the sodium/bicarbonate co-transporter (NBC) isoforms, which have been called NBCe1 and NBCe2....... and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate...

  6. 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.

  7. Exercise-induced phospho-proteins in skeletal muscle

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  8. Vasodilator interactions in skeletal muscle blood flow regulation

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Nyberg, Michael Permin; Jensen, Lasse Gliemann

    2012-01-01

    During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or the extraluminal side of the blood vessels. A number...... vasodilators are both stimulated by several compounds, eg. adenosine, ATP, acetylcholine, bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other...... is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperemic response remains unexplained. It is plausible...

  9. Reduced blood flow to contracting skeletal muscle in ageing humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Hellsten, Ylva

    2016-01-01

    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...... 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 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....

  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. 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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose......-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKCδKO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCδ...... in the regulation of mitochondrial mass at older age. These data indicate an important role of PKCδ in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging....

  13. A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse

    Directory of Open Access Journals (Sweden)

    Craig Robert Wright

    2017-01-01

    Full Text Available Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD. There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S (Seps1 are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion (mdx:Seps1−/+ were generated. The mdx:Seps1−/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL muscles, mRNA expression of monocyte chemoattractant protein 1 (Mcp-1 (P=0.034, macrophage marker F4/80 (P=0.030, and transforming growth factor-β1 (Tgf-β1 (P=0.056 were increased in mdx:Seps1−/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.

  14. A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse.

    Science.gov (United States)

    Wright, Craig Robert; Allsopp, Giselle Larissa; Addinsall, Alex Bernard; McRae, Natasha Lee; Andrikopoulos, Sofianos; Stupka, Nicole

    2017-01-01

    Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD). There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S ( Seps1 ) are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion ( mdx : Seps1 -/+ ) were generated. The mdx:Seps1 -/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL) muscles, mRNA expression of monocyte chemoattractant protein 1 ( Mcp-1 ) ( P = 0.034), macrophage marker F4/80 ( P = 0.030), and transforming growth factor-β1 ( Tgf-β1 ) ( P = 0.056) were increased in mdx:Seps1 -/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.

  15. Skeletal muscle wasting with disuse atrophy is multi-dimensional: the response and interaction of myonuclei, satellite cells and signaling pathways

    Directory of Open Access Journals (Sweden)

    Naomi Elisabeth Brooks

    2014-03-01

    Full Text Available Maintenance of skeletal muscle is essential for health and survival. There are marked losses of skeletal muscle mass as well as strength and physiological function under conditions of low mechanical load, such as space flight, as well as ground based models such as bed rest, immobilisation, disuse and various animal models. Disuse atrophy is caused by mechanical unloading of muscle and this leads to reduced muscle mass without fibre attrition. Skeletal muscle stem cells (satellite cells and myonuclei are integrally involved in skeletal muscle responses to environmental changes that induce atrophy. Myonuclear domain size is influenced differently in fast and slow twitch muscle, but also by different models of muscle wasting, a factor that is not yet understood. Although the myonuclear domain is 3-dimensional this is rarely considered. Apoptosis as a mechanism for myonuclear loss with atrophy is controversial, whereas cell death of satellite cells has not been considered. Molecular signals such as myostatin/SMAD pathway, MAFbx and MuRF1 E3 ligases of the ubiquitin proteasome pathway and IGF1-AKT-mTOR pathway are 3 distinctly different contributors to skeletal muscle protein adaptation to disuse. Molecular signalling pathways activated in muscle fibres by disuse are rarely considered within satellite cells themselves despite similar exposure to unloading or low mechanical load. These molecular pathways interact with each other during atrophy and also when various interventions are applied that could alleviate atrophy. Re-applying mechanical load is an obvious method to restore muscle mass, however how nutrient supplementation (e.g. amino acids may further enhance recovery (or reduce atrophy despite unloading or ageing is currently of great interest. Satellite cells are particularly responsive to myostatin and to growth factors. Recently, the hibernating squirrel has been identified as an innovative model to study resistance to atrophy.

  16. Association between statin-associated myopathy and skeletal muscle damage.

    Science.gov (United States)

    Mohaupt, Markus G; Karas, Richard H; Babiychuk, Eduard B; Sanchez-Freire, Verónica; Monastyrskaya, Katia; Iyer, Lakshmanan; Hoppeler, Hans; Breil, Fabio; Draeger, Annette

    2009-07-07

    Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10x the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.

  17. Are skeletal muscles independent actuators? Force transmission from soleus muscle in the cat

    NARCIS (Netherlands)

    Maas, H.; Sandercock, T.G.

    2008-01-01

    It is unclear if skeletal muscles act mechanically as independent actuators. The purpose of the present study was to investigate force transmission from soleus (SO) muscle for physiological lengths as well as relative positions in the intact cat hindlimb. We hypothesized that force transmission from

  18. 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.

    2014-01-01

    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. PMID:25292181

  19. The effects of ramp stretches on active contractions in intact mammalian fast and slow muscle fibres.

    Science.gov (United States)

    Mutungi, G; Ranatunga, K W

    2001-01-01

    The effects of a ramp stretch (amplitude muscle fibre length (L0), speed twitch tension and twitch tension re-development were examined in intact mammalian (rat) fast and slow muscle fibre bundles. The experiments were done in vitro at 20 degrees C and at an initial sarcomere length of 2.68 microm. In both fibre types, a stretch applied during the rising phase of the twitch response (including the time of stimulation) increased the re-developed twitch tension (15-35%). A stretch applied before the stimulus had little or no effect on the twitch myogram in fast muscle fibres, but it increased the twitch tension (approximately 5%) in slow muscle fibres. A similar stretch had little or no effect on tetanic tension in either muscle fibre type. In general, the results indicate that the contractile-activation mechanism may be stretch sensitive and this is particularly pronounced in slow muscle fibres. Recorded at a high sampling rate and examined at an appropriate time scale, the transitory tension response to a stretch rose in at least two phases; an initial rapid tension rise to a break (break point tension, P1a) followed by a slower tension rise (apparent P2a) to a peak reached at the end of the stretch. Plotted against stretch velocity, P1a tension increased in direct proportion to stretch velocity (viscous-like) whereas, P2a tension (calculated as peak tension minus P1a tension) increased with stretch velocity to a plateau (visco-elastic). Examined at the peak of a twitch, P1a tension had a slope (viscosity coefficient) of 1.8 kN m(-2) per L0 s(-1) in fast fibres and 4.7 kN m(-2) per L0 s(-1) in slow muscle fibres. In the same preparations, P2a tension had a relaxation time of 8 ms in the fast muscle fibres and 25 ms in the slow muscle fibres. The amplitudes of both tension components scaled with the instantaneous twitch tension in qualitatively the same way as the instantaneous fibre stiffness. These fast/slow fibre type differences probably reflect differences in

  20. Modulation effects of cordycepin on the skeletal muscle contraction of toad gastrocnemius muscle.

    Science.gov (United States)

    Yao, Li-Hua; Meng, Wei; Song, Rong-Feng; Xiong, Qiu-Ping; Sun, Wei; Luo, Zhi-Qiang; Yan, Wen-Wen; Li, Yu-Ping; Li, Xin-Ping; Li, Hai-Hang; Xiao, Peng

    2014-03-05

    Isolated toad gastrocnemius muscle is a typical skeletal muscle tissue that is frequently used to study the motor system because it is an important component of the motor system. This study investigates the effects of cordycepin on the skeletal muscle contractile function of isolated toad gastrocnemius muscles by electrical field stimulation. Results showed that cordycepin (20 mg/l to 100 mg/l) significantly decreased the contractile responses in a concentration-dependent manner. Cordycepin (50 mg/l) also produced a rightward shift of the contractile amplitude-stimulation intensity relationship, as indicated by the increases in the threshold stimulation intensity and the saturation stimulation intensity. However, the most notable result was that the maximum amplitude of the muscle contractile force was significantly increased under cordycepin application (122±3.4% of control). This result suggests that the skeletal muscle contractile function and muscle physical fitness to the external stimulation were improved by the decreased response sensitivity in the presence of cordycepin. Moreover, cordycepin also prevented the repetitive stimulation-induced decrease in muscle contractile force and increased the recovery amplitude and recovery ratio of muscle contraction. However, these anti-fatigue effects of cordycepin on muscle contraction during long-lasting muscle activity were absent in Ca2+-free medium or in the presence of all Ca2+ channels blocker (0.4 mM CdCl2). These results suggest that cordycepin can positively affect muscle performance and provide ergogenic and prophylactic benefits in decreasing skeletal muscle fatigue. The mechanisms involving excitation-coupled Ca2+ influxes are strongly recommended.

  1. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway.

    Science.gov (United States)

    Feng, Xiaoli; Luo, Zhidan; Ma, Liqun; Ma, Shuangtao; Yang, Dachun; Zhao, Zhigang; Yan, Zhencheng; He, Hongbo; Cao, Tingbing; Liu, Daoyan; Zhu, Zhiming

    2011-07-01

    Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  2. Some factors determining the PCr recovery overshoot in skeletal muscle.

    Science.gov (United States)

    Korzeniewski, Bernard; Zoladz, Jerzy A

    2005-07-01

    It has been proposed recently that the phosphocreatine (PCr) overshoot (increase above the resting level) during muscle recovery after exercise is caused by a slow decay during this recovery of the direct activation of oxidative phosphorylation taking place during muscle work. In the present article the factors determining the appearance and size of the PCr overshoot are studied using the computer model of oxidative phosphorylation in intact skeletal muscle developed previously. It is demonstrated that the appearance and duration of this overshoot is positively correlated with the value of the characteristic decay time of the direct activation of oxidative phosphorylation. It is also shown that the size of PCr overshoot is increased by low resting PCr/Cr ratio (what is confirmed by our unpublished experimental data), by high intensity of the direct activation of oxidative phosphorylation, by high muscle work intensity and by low rate of the return of cytosolic pH to the resting value during muscle recovery.

  3. 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

    in the sarcoplasmic reticulum. In addition, a multitude of Ca(2+)-binding proteins is present in muscle tissue including parvalbumin, calmodulin, S100 proteins, annexins, sorcin, myosin light chains, beta-actinin, calcineurin, and calpain. These Ca(2+)-binding proteins may either exert an important role in Ca(2......Mammalian skeletal muscle shows an enormous variability in its functional features such as rate of force production, resistance to fatigue, and energy metabolism, with a wide spectrum from slow aerobic to fast anaerobic physiology. In addition, skeletal muscle exhibits high plasticity that is based...... on the potential of the muscle fibers to undergo changes of their cytoarchitecture and composition of specific muscle protein isoforms. Adaptive changes of the muscle fibers occur in response to a variety of stimuli such as, e.g., growth and differentition factors, hormones, nerve signals, or exercise...

  4. Proteomic and carbonylation profile analysis of rat skeletal muscles following acute swimming exercise.

    Directory of Open Access Journals (Sweden)

    Francesca Magherini

    Full Text Available Previous studies by us and other groups characterized protein expression variation following long-term moderate training, whereas the effects of single bursts of exercise are less known. Making use of a proteomic approach, we investigated the effects of acute swimming exercise (ASE on protein expression and carbonylation patterns in two hind limb muscles: the Extensor Digitorum Longus (EDL and the Soleus, mostly composed of fast-twitch and slow-twitch fibres, respectively. Carbonylation is one of the most common oxidative modifications of proteins and a marker of oxidative stress. In fact, several studies suggest that physical activity and the consequent increase in oxygen consumption can lead to increase in reactive oxygen and nitrogen species (RONS production, hence the interest in examining the impact of RONS on skeletal muscle proteins following ASE. Results indicate that protein expression is unaffected by ASE in both muscle types. Unexpectedly, the protein carbonylation level was reduced following ASE. In particular, the analysis found 31 and 5 spots, in Soleus and EDL muscles respectively, whose carbonylation is reduced after ASE. Lipid peroxidation levels in Soleus were markedly reduced as well. Most of the decarbonylated proteins are involved either in the regulation of muscle contractions or in the regulation of energy metabolism. A number of hypotheses may be advanced to account for such results, which will be addressed in future studies.

  5. Pathology of skeletal muscle in fibromyalgia

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  6. Effect of controlled exercise on middle gluteal muscle fibre composition in Thoroughbred foals.

    Science.gov (United States)

    Eto, D; Yamano, S; Kasashima, Y; Sugiura, T; Nasu, T; Tokuriki, M; Miyata, H

    2003-11-01

    Most racehorses are trained regularly from about age 18 months; therefore, little information is available on the effect of training in Thoroughbred foals. Well-controlled exercise could improve muscle potential ability for endurance running. Thoroughbred foals at age 2 months were separated into control and training (treadmill exercise) groups and samples obtained from the middle gluteal muscle at 2 and 12 months post partum. Muscle fibre compositions were determined by histochemical and electrophoretical techniques and succinic dehydrogenase (SDH) activity was analysed in each fibre type. All fibre types were hypertrophied with growth and type I and IIA fibres were significantly larger in the training than the control group at age 12 months. A significant increase of SDH activity was found in type IIX muscle fibres in the training group. Training in young Thoroughbred horses can facilitate muscle fibre hypertrophy and increase the oxidative capacity of type IIX fibres, which could potentially enhance stamina at high speeds. To apply this result to practical training, further studies are needed to determine more effective and safe intensities of controlled exercise.

  7. Expression of Pannexin 1 and Pannexin 3 during skeletal muscle development, regeneration, and Duchenne muscular dystrophy.

    Science.gov (United States)

    Pham, Tammy L; St-Pierre, Marie-Eve; Ravel-Chapuis, Aymeric; Parks, Tara E C; Langlois, Stéphanie; Penuela, Silvia; Jasmin, Bernard J; Cowan, Kyle N

    2018-05-10

    Pannexin 1 (Panx1) and Pannexin 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well as myoblast proliferation and differentiation in vitro. However, their expression patterns during skeletal muscle development and regeneration had yet to be investigated. Here, we show that Panx1 levels increase during skeletal muscle development becoming highly expressed together with Panx3 in adult skeletal muscle. In adult mice, Panx1 and Panx3 were differentially expressed in fast- and slow-twitch muscles. We also report that Panx1/PANX1 and Panx3/PANX3 are co-expressed in mouse and human satellite cells, which play crucial roles in skeletal muscle regeneration. Interestingly, Panx1 and Panx3 levels were modulated in muscle degeneration/regeneration, similar to the pattern seen during skeletal muscle development. As Duchenne muscular dystrophy is characterized by skeletal muscle degeneration and impaired regeneration, we next used mild and severe mouse models of this disease and found a significant dysregulation of Panx1 and Panx3 levels in dystrophic skeletal muscles. Together, our results are the first demonstration that Panx1 and Panx3 are differentially expressed amongst skeletal muscle types with their levels being highly modulated during skeletal muscle development, regeneration, and dystrophy. These findings suggest that Panx1 and Panx3 channels may play important and distinct roles in healthy and diseased skeletal muscles. © 2018 Wiley Periodicals, Inc.

  8. 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.

  9. Response of macrophages in rat skeletal muscle after eccentric exercise.

    Science.gov (United States)

    Zuo, Qun; Wang, Shu-Chen; Yu, Xin-Kai; Chao, Wei-Wei

    2018-04-01

    Macrophages are known to be important for healing numerous injured tissues depending on their functional phenotypes in response to different stimuli. The objective of this study was to reveal macrophage phenotypic changes involved in exercise-induced skeletal muscle injury and regeneration. Adult male Sprague-Dawley rats experienced one session of downhill running (16° decline, 16 m/min) for 90 min. After exercise the blood and soleus muscles were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 3 d, 1 w and 2 w after exercise, separately. It was showed that CD68 + M1 macrophages mainly infiltrated into muscle necrotic sites at 1-3 d, while CD163 + M2 macrophages were present in muscles from 0 h to 2 weeks after exercise. Using transmission electron microscopy, we observed activated satellite cells 1 d after exercise. Th1-associated transcripts of iNOS and Ccl2 were inhibited post exercise, while COX-2 mRNA was dramatically increased 12 h after running (p < 0.01). M2 phenotype marker Arg-1 increased 12 h and 3 d (p < 0.05, p < 0.01) after exercise, and Clec10a and Mrc2 were up-regulated in muscles 12 h following exercise (p < 0.05, p < 0.05). The data demonstrate the dynamic patterns of macrophage phenotype in skeletal muscle upon eccentric exercise stimuli, and M1 and M2 phenotypes perform different functions during exercise-induced skeletal muscle injury and recovery. Copyright © 2018 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  10. Diaphragmatic lymphatic vessel behavior during local skeletal muscle contraction.

    Science.gov (United States)

    Moriondo, Andrea; Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela

    2015-02-01

    The mechanism through which the stresses developed in the diaphragmatic tissue during skeletal muscle contraction sustain local lymphatic function was studied in 10 deeply anesthetized, tracheotomized adult Wistar rats whose diaphragm was exposed after thoracotomy. To evaluate the direct effect of skeletal muscle contraction on the hydraulic intraluminal lymphatic pressures (Plymph) and lymphatic vessel geometry, the maximal contraction of diaphragmatic fibers adjacent to a lymphatic vessel was elicited by injection of 9.2 nl of 1 M KCl solution among diaphragmatic fibers while Plymph was recorded through micropuncture and vessel geometry via stereomicroscopy video recording. In lymphatics oriented perpendicularly to the longitudinal axis of muscle fibers and located at skeletal muscle contraction (Dmc) decreased to 61.3 ± 1.4% of the precontraction value [resting diameter (Drest)]; however, if injection was at >900 μm from the vessel, Dmc enlarged to 131.1 ± 2.3% of Drest. In vessels parallel to muscle fibers, Dmc increased to 122.8 ± 2.9% of Drest. During contraction, Plymph decreased as much as 22.5 ± 2.6 cmH2O in all submesothelial superficial vessels, whereas it increased by 10.7 ± 5.1 cmH2O in deeper vessels running perpendicular to contracting muscle fibers. Hence, the three-dimensional arrangement of the diaphragmatic lymphatic network seems to be finalized to efficiently exploit the stresses exerted by muscle fibers during the contracting inspiratory phase to promote lymph formation in superficial submesothelial lymphatics and its further propulsion in deeper intramuscular vessels. Copyright © 2015 the American Physiological Society.

  11. 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.

  12. 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.

  13. Skeletal muscle expresses the extracellular cyclic AMP–adenosine pathway

    Science.gov (United States)

    Chiavegatti, T; Costa, V L; Araújo, M S; Godinho, R O

    2007-01-01

    Background and purpose: cAMP is a key intracellular signalling molecule that regulates multiple processes of the vertebrate skeletal muscle. We have shown that cAMP can be actively pumped out from the skeletal muscle cell. Since in other tissues, cAMP efflux had been associated with extracellular generation of adenosine, in the present study we have assessed the fate of interstitial cAMP and the existence of an extracellular cAMP-adenosine signalling pathway in skeletal muscle. Experimental approach: cAMP efflux and/or its extracellular degradation were analysed by incubating rat cultured skeletal muscle with exogenous cAMP, forskolin or isoprenaline. cAMP and its metabolites were quantified by radioassay or HPLC, respectively. Key results: Incubation of cells with exogenous cAMP was followed by interstitial accumulation of 5′-AMP and adenosine, a phenomenon inhibited by selective inhibitors of ecto-phosphodiesterase (DPSPX) and ecto-nucleotidase (AMPCP). Activation of adenylyl cyclase (AC) in cultured cells with forskolin or isoprenaline increased cAMP efflux and extracellular generation of 5′-AMP and adenosine. Extracellular cAMP-adenosine pathway was also observed after direct and receptor-dependent stimulation of AC in rat extensor muscle ex vivo. These events were attenuated by probenecid, an inhibitor of ATP binding cassette family transporters. Conclusions and implications: Our results show the existence of an extracellular biochemical cascade that converts cAMP into adenosine. The functional relevance of this extracellular signalling system may involve a feedback modulation of cellular response initiated by several G protein-coupled receptor ligands, amplifying cAMP influence to a paracrine mode, through its metabolite, adenosine. PMID:18157164

  14. Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging.

    Science.gov (United States)

    Jayasinghe, Isuru D; Munro, Michelle; Baddeley, David; Launikonis, Bradley S; Soeller, Christian

    2014-10-06

    Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  15. Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans

    DEFF Research Database (Denmark)

    Krustrup, Peter; Secher, Niels; Relu, Mihai U.

    2008-01-01

    We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W...... without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P fibres, whereas in CON, CP decreased (P ... at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation....

  16. 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.

  17. Skeletal muscle repair in a mouse model of nemaline myopathy.

    Science.gov (United States)

    Sanoudou, Despina; Corbett, Mark A; Han, Mei; Ghoddusi, Majid; Nguyen, Mai-Anh T; Vlahovich, Nicole; Hardeman, Edna C; Beggs, Alan H

    2006-09-01

    Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is a variably severe neuromuscular disorder for which no effective treatment is available. Although a number of genes have been identified in which mutations can cause NM, the pathogenetic mechanisms leading to the phenotypes are poorly understood. To address this question, we examined gene expression patterns in an NM mouse model carrying the human Met9Arg mutation of alpha-tropomyosin slow (Tpm3). We assessed five different skeletal muscles from affected mice, which are representative of muscles with differing fiber-type compositions, different physiological specializations and variable degrees of pathology. Although these same muscles in non-affected mice showed marked variation in patterns of gene expression, with diaphragm being the most dissimilar, the presence of the mutant protein in nemaline muscles resulted in a more similar pattern of gene expression among the muscles. This result suggests a common process or mechanism operating in nemaline muscles independent of the variable degrees of pathology. Transcriptional and protein expression data indicate the presence of a repair process and possibly delayed maturation in nemaline muscles. Markers indicative of satellite cell number, activated satellite cells and immature fibers including M-Cadherin, MyoD, desmin, Pax7 and Myf6 were elevated by western-blot analysis or immunohistochemistry. Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles.

  18. Fragility fracture risk and skeletal muscle function.

    Science.gov (United States)

    Pérez-López, F R; Ara, I

    2016-01-01

    Low-intensity fractures are closely related with age-related musculoskeletal disorders, including osteoporosis, muscle dysfunction and sarcopenia, age-related chronic diseases, and pharmacological treatments. During the last years, a huge amount of information and recommendations has been released in relation to bone metabolism and mineral content. Muscle dysfunction and sarcopenia are highly prevalent during the second half of life, especially in older subjects. The development of sarcopenia may be slowed through healthy lifestyle changes, which include adequate dietary protein, vitamin D and mineral intakes, and regular physical activity. Prevention of falls should be integral, including correction in major involved factors in order to reduce fragility fracture, improve quality of life and appropriately focus clinical and economic resources. Therefore, to obtain better results a global approach is needed to prevent age-related fractures in frail patients that is not only centered on bone metabolism and antiresorptive drugs.

  19. 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.

  20. Insulin action in denervated skeletal muscle

    International Nuclear Information System (INIS)

    Smith, R.L.

    1987-01-01

    The goal of this study was to determine the mechanisms responsible for reduced insulin response in denervated muscle. Denervation for 3 days of rat muscles consisting of very different compositions of fiber types decreased insulin stimulated [U- 14 C]glucose incorporation into glycogen by 80%. Associated with the reduction in glycogen synthesis was a decreased activation of glycogen synthase. Denervation of hemidiaphragms for 1 day decreased both the basal and insulin stimulated activity ratios of glycogen synthase and the rate of insulin stimulated [U- 14 C[glucose incorporation into glycogen by 50%. Insulin stimulation of 2-deoxy[ 3 H]glucose uptake was not decreased until 3 days after denervation. Consistent with the effects on glucose transport,insulin did not increase the intracellular concentration of glucose-6-P in muscles 3 days after denervation. Furthermore, since the Ka for glucose-6-P activation of glycogen synthase was not decreased by insulin in denervated hemidiaphragms, the effects of denervation on glycogen synthase and glucose transport were synergistic resulting in the 80% decrease in glycogen synthesis rates

  1. Fibre composition and enzyme activities in six muscles of the Swedish reindeer (Rangifer tarandus tarandus

    Directory of Open Access Journals (Sweden)

    K-H. Kiessling

    1983-05-01

    Full Text Available Six skeletal muscles have been studied as regards fibre properties and enzyme activities. The muscles are cranial part of M. gluteobiceps, M. semitendinosus, M. semimembranosus, M. longissimus dorsi, M. brachiocephalicus and M. sternocephalicus. Two histochemical methods were used for fibre identification, one based on myosin ATPase activities after preincubation at pH 4.3 and 4.6 and the other on oxidative capacity measured as NADH dehydrogenase activity. The two methods gave slightly differing results but allowed the general conclusion that of the three fibre types (I, II A and II B the type II B fibres, which are fast-twitch, glycolytic, make up some 40 - 60 % (mean 50 % of the muscles. Type I fibres, which are slow-twitch, oxidative, account for 30% of the total muscle volume in the two neck muscles but for only 20% or less in the rest. The third type, II A, which is fast-twitch, oxidative, glycolytic, accounts for only 20% of the volume in the neck muscles but as much as 40% in M. longissimus dorsi. Oxidative capacity is high throughout. This is valid also to the capacity to oxidize fatty acids, though reaching only half the activity previously found in the Svalbard reindeer (Kiessling and Kiessling, 1983. Lactate dehydrogenase activity is comparatively low in all muscles. The high respiratory chain activity and fatty acid oxidation and the low lactate dehydrogenase activities do not fit at all well with the high content of type II B fibres in the muscles. This high II B content is also unexpected when considering the activity pattern of the reindeer. An altogether different role for the type II B fibres, besides the traditional one, is therefore discussed.Fibersammansåttning och enzymaktiviteter i sex muskler från svensk tamren (Rangifer tarandus tarandus.Abstract in Swedish / Sammandrag: Sex skelettmuskler har undersokts med avseende på fiberegenskaper och enzymaktiviteter. De sex musklerna år kranial del av M. gluteobiceps. M

  2. 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.

  3. 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......Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase...

  4. 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......Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase...

  5. 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....

  6. Skeletal Muscle Metastasis from a Cecal Mucinous Adenocarcinoma: A Case Report

    International Nuclear Information System (INIS)

    Lee, Dong Hyun; Lee, Young Hwan; Jung, Kyung Jae; Park, Young Chan; Kim, Ho Kyun; Cho, Seung Hyun

    2008-01-01

    Skeletal muscle metastasis is a relatively rare finding in the setting of mucinous adenocarcinoma of the colon, and it typically exhibits nonspecific imaging findings. We report a case of a skeletal muscle metastasis originating from mucinous adenocarcinoma of the cecum. The skeletal lesion closely resembled intramuscular myxoma with regard to imaging findings, due to abundant mucin and internal calcification

  7. 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...

  8. 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...

  9. 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.

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

    DEFF Research Database (Denmark)

    Nielsen, Søren; Scheele, Camilla; Yfanti, Christina

    2010-01-01

    Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus...... lateralis of healthy young males (n = 10) in relation to a hyperinsulinaemic–euglycaemic clamp as well as acute endurance exercise before and after 12 weeks of endurance training. The subjects increased their endurance capacity, VO2max (l min-1) by 17.4% (P improved insulin sensitivity by 19......, but their role in regulating human skeletal muscle adaptation remains unknown....

  11. Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

    Science.gov (United States)

    Korzeniewski, Bernard; Zoladz, Jerzy A

    2003-08-15

    Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial proteins and by an intensification of the parallel activation of ATP usage and ATP supply (increase in direct stimulation of oxidative phosphorylation complexes accompanying stimulation of ATP consumption) during exercise.

  12. Value of radioimmunologic myoglobin determination in skeletal muscle disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, W.R.; Beckmann, R.

    1981-12-01

    Using a sensitive radioimmunoassay (RIA) serum myoglobin (Mb) was measured in healthy controls, patients with skeletal muscle disorders (polymyositis, different types of progressive muscular dystrophy, hypokalemic myopathy and myopathy due to cortisone treatment) and as well in definite as possible carriers of Duchenne muscular dystrophy, DMD. The results indicate that Mb is a useful parameter in the assessment of muscle cell damage. Moreover, definite DMD-carriers had hypermyoglobine in 70% and in two of twenty possible DMD-carriers (all had normal CK activities) Mb was found to be markedly increased. The usefulness of an additional Mb determination in the detection of DMD-carriers is discussed.

  13. Skeletal muscle metabolism in hypokinetic rats

    Science.gov (United States)

    Tischler, Marc E.

    1993-01-01

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

  14. 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

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

  18. The Effect of Statins on Skeletal Muscle Function

    Science.gov (United States)

    Parker, Beth A.; Capizzi, Jeffrey A.; Grimaldi, Adam S.; Clarkson, Priscilla M.; Cole, Stephanie M.; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S.; Simpson, Kathleen; White, C. Michael; Thompson, Paul D.

    2015-01-01

    Background Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials and the effect of statins on muscle performance has not been carefully studied. Methods and Results The Effect of STatins On Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase (CK), exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo were administered for 6 months to 420 healthy, statin-naive subjects. No individual CK value exceeded 10 times normal, but average CK increased 20.8 ± 141.1 U/L (pmuscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 vs 10; p = 0.05). Myalgic subjects on atorvastatin or placebo decreased muscle strength in 5 of 14 and 4 of 14 variables respectively (p = 0.69). Conclusions These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average CK suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in CK should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. Clinical Trial Registration Information: www.clinicaltrials.gov; Identifier: NCT00609063. PMID:23183941

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

    Science.gov (United States)

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

    2017-04-01

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

  20. 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.

  1. Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.

    Science.gov (United States)

    Tilignac, Thomas; Temparis, Sandrine; Combaret, Lydie; Taillandier, Daniel; Pouch, Marie-Noëlle; Cervek, Matjaz; Cardenas, Diana M; Le Bricon, Thierry; Debiton, Eric; Samuels, Susan E; Madelmont, Jean-Claude; Attaix, Didier

    2002-05-15

    Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting.

  2. 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

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......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...... 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...

  3. Signalling and the control of skeletal muscle size

    International Nuclear Information System (INIS)

    Otto, Anthony; Patel, Ketan

    2010-01-01

    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.

  4. 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.

  5. 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.

  6. Voluntary resistance running wheel activity pattern and skeletal muscle growth in rats.

    Science.gov (United States)

    Legerlotz, Kirsten; Elliott, Bradley; Guillemin, Bernard; Smith, Heather K

    2008-06-01

    The aims of this study were to characterize the pattern of voluntary activity of young rats in response to resistance loading on running wheels and to determine the effects of the activity on the growth of six limb skeletal muscles. Male Sprague-Dawley rats (4 weeks old) were housed individually with a resistance running wheel (R-RUN, n = 7) or a conventional free-spinning running wheel (F-RUN, n = 6) or without a wheel, as non-running control animals (CON, n = 6). The torque required to move the wheel in the R-RUN group was progressively increased, and the activity (velocity, distance and duration of each bout) of the two running wheel groups was recorded continuously for 45 days. The R-RUN group performed many more, shorter and faster bouts of running than the F-RUN group, yet the mean daily distance was not different between the F-RUN (1.3 +/- 0.2 km) and R-RUN group (1.4 +/- 0.6 km). Only the R-RUN resulted in a significantly (P RUN and R-RUN led to a significantly greater wet mass relative to increase in body mass and muscle fibre cross-sectional area in the soleus muscle compared with CON. We conclude that the pattern of voluntary activity on a resistance running wheel differs from that on a free-spinning running wheel and provides a suitable model to induce physiological muscle hypertrophy in rats.

  7. IL-1β-Induced Accumulation of Amyloid: Macroautophagy in Skeletal Muscle Depends on ERK

    Directory of Open Access Journals (Sweden)

    Karsten Schmidt

    2017-01-01

    Full Text Available The pathology of inclusion body myositis (IBM involves an inflammatory response and β-amyloid deposits in muscle fibres. It is believed that MAP kinases such as the ERK signalling pathway mediate the inflammatory signalling in cells. Further, there is evidence that autophagic activity plays a crucial role in the pathogenesis of IBM. Using a well established in vitro model of IBM, the autophagic pathway, MAP kinases, and accumulation of β-amyloid were examined. We demonstrate that stimulation of muscle cells with IL-1β and IFN-γ led to an increased phosphorylation of ERK. The ERK inhibitor PD98059 diminished the expression of proinflammatory markers as well as the accumulation of β-amyloid. In addition, IL-1β and IFN-γ led to an increase of autophagic activity, upregulation of APP, and subsequent accumulation of β-sheet aggregates. Taken together, the data demonstrate that the ERK pathway contributes to formation of β-amyloid and regulation of autophagic activity in muscle cells exposed to proinflammatory cell stress. This suggests that ERK serves as an important mediator between inflammatory mechanisms and protein deposition in skeletal muscle and is a crucial element of the pathology of IBM.

  8. A nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle.

    Science.gov (United States)

    van Bolhuis, A I; Holsheimer, J; Savelberg, H H

    2001-05-30

    Electrical stimulation of peripheral nerve results in a motor-unit recruitment order opposite to that attained by natural neural control, i.e. from large, fast-fatiguing to progressively smaller, fatigue-resistant motor-units. Yet animal studies involving physiological exercise protocols of low intensity and long duration require minimal fatigue. The present study sought to apply a nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle. Two pulse generators were used, independently supplying short supramaximal cathodal stimulating pulses (0.5 ms) and long subthreshold cathodal inactivating pulses (1.5 s) to the sciatic nerve. Propagation of action potentials was selectively blocked in nerve fibres of different diameter by adjusting the strength of the inactivating current. A tensile-testing machine was used to gauge isometric muscle force of the plantaris and both heads of the gastrocnemius muscle. The order of motor-unit recruitment was estimated from twitch characteristics, i.e. peak force and relaxation time. The results showed prolonged relaxation at lower twitch peak forces as the intensity of the inactivating current increased, indicating a reduction of the number of large motor-units to force production. It is shown that the nerve stimulation method described is effective in mimicking physiological muscle control.

  9. 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.

  10. Heart size and mean muscle fibre cross-sectional area related to birth weight in pigs

    Directory of Open Access Journals (Sweden)

    M. RUUSUNEN

    2008-12-01

    Full Text Available One of the aims in domestic pig breeding has been to increase the size of litters resulting in variation in birth weight of piglets. Pig breeding has also resulted in increased body muscle mass. Muscles with the same size can consist either of large number of thin muscle fibres or small number of thick muscle fibres. Larger body muscle content means that in living animal the heart must pump blood to larger muscle mass than earlier. Our interest in this study was to investigate the relationship between the pig’s birth weight and (i growth performance and carcass composition, (ii the size of organs, and (iii the mean muscle fibre cross-sectional area at slaughter. The study consisted of twenty pigs slaughtered at the age of 165±2 days. The day after the slaughter, the carcass composition was determined by dissecting the chilled carcass into lean, fat, bones, and skin and organs were weighed. The average cross sectional area of muscle fibres was determined from three fast-twitch muscles longissimus dorsi, semimembranosus, gluteus superficialis, and two slow-twitch muscles infraspinatus and masseter. The birth weight of pigs ranged from 0.9 to 2.2 kg. We found no clear relationships between the birth weight and the pig’s growth performance from birth to slaughter. When the birth weight increased the heart weight at slaughter increased as well (P < 0.01. The heart weight was higher in those pigs with high carcass weight (P < 0.05 and with the high weight of total muscle mass in the carcass (P < 0.001. The cross sectional area of muscle fibres in M. longissimus dorsi (P < 0.05, M. semimembranosus (P < 0.10, and M. gluteus superficialis (P < 0.05 was larger in those pigs with low birth weight compared to those found in pigs with high birth weight.;

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

    Science.gov (United States)

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

    2016-04-01

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

  12. ATP and phosphocreatine utilization in single human muscle fibres during the development of maximal power output at elevated muscle temperatures.

    Science.gov (United States)

    Gray, Stuart R; Söderlund, Karin; Ferguson, Richard A

    2008-05-01

    In this study, we examined the effect of muscle temperature (Tm) on adenosine triphosphate (ATP) and phosphocreatine utilization in single muscle fibres during the development of maximal power output in humans. Six male participants performed a 6-s maximal sprint on a friction-braked cycle ergometer under both normal (Tm = 34.3 degrees C, s = 0.6) and elevated (T(m) = 37.3 degrees C, s = 0.2) muscle temperature conditions. During the elevated condition, muscle temperature of the legs was raised, passively, by hot water immersion followed by wrapping in electrically heated blankets. Muscle biopsies were taken from the vastus lateralis before and immediately after exercise. Freeze-dried single fibres were dissected, characterized according to myosin heavy chain composition, and analysed for ATP and phosphocreatine content. Single fibres were classified as: type I, IIA, IIAX25 (1 - 25% IIX isoform), IIAX50 (26 - 50% IIX), IIAX75 (51 - 75% IIX), or IIAX100 (76 - 100% IIX). Maximal power output and pedal rate were both greater (P < 0.05) during the elevated condition by 258 W (s = 110) and 22 rev . min(-1) (s = 6), respectively. In both conditions, phosphocreatine content decreased significantly in all fibre types, with a greater decrease during the elevated condition in type IIA fibres (P < 0.01). Adenosine triphosphate content was also reduced to a greater (P < 0.01) extent in type IIA fibres during the elevated condition. The results of the present study indicate that after passive elevation of muscle temperature, there was a greater decrease in ATP and phosphocreatine content in type IIA fibres than in the normal trial, which contributed to the higher maximal power output.

  13. Automated image segmentation of haematoxylin and eosin stained skeletal muscle cross-sections

    DEFF Research Database (Denmark)

    Liu, F; Mackey, AL; Srikuea, R

    2013-01-01

    of two major steps: (1) A learning-based seed detection method to find the geometric centres of the muscle fibres, and (2) a colour gradient repulsive balloon snake deformable model that adopts colour gradient in Luv colour space. Automatic quantification of muscle fibre cross-sectional areas using...

  14. MicroRNA transcriptome profiles during swine skeletal muscle development

    Directory of Open Access Journals (Sweden)

    Sonstegard Tad S

    2009-02-01

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

  15. Impact of oxidative stress on exercising skeletal muscle.

    Science.gov (United States)

    Steinbacher, Peter; Eckl, Peter

    2015-04-10

    It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

  16. 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.

  17. Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles.

    Science.gov (United States)

    Wernig, A; Zweyer, M; Irintchev, A

    2000-01-15

    1. Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, culture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric contractile properties of the muscles were studied in vitro, and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe. 2. Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by about 18 %). Injection of 106 myoblasts abolished these deficiencies and innervation appeared normal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient as indicated by weak nerve-evoked contractions and elevated ACh sensitivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance of the new muscle.

  18. Effect of ionizing radiation on human skeletal muscle precursor cells

    International Nuclear Information System (INIS)

    Jurdana, Mihaela; Cemazar, Maja; Pegan, Katarina; Mars, Tomaz

    2013-01-01

    Long term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures. Human skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin – 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death. Compared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70). Our results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions

  19. Endurance training increases the efficiency of rat skeletal muscle mitochondria.

    Science.gov (United States)

    Zoladz, Jerzy A; Koziel, Agnieszka; Woyda-Ploszczyca, Andrzej; Celichowski, Jan; Jarmuszkiewicz, Wieslawa

    2016-10-01

    Endurance training enhances mitochondrial oxidative capacity, but its effect on mitochondria functioning is poorly understood. In the present study, the influence of an 8-week endurance training on the bioenergetic functioning of rat skeletal muscle mitochondria under different assay temperatures (25, 35, and 42 °C) was investigated. The study was performed on 24 adult 4-month-old male Wistar rats, which were randomly assigned to either a treadmill training group (n = 12) or a sedentary control group (n = 12). In skeletal muscles, endurance training stimulated mitochondrial biogenesis and oxidative capacity. In isolated mitochondria, endurance training increased the phosphorylation rate and elevated levels of coenzyme Q. Moreover, a decrease in mitochondrial uncoupling, including uncoupling protein-mediated proton leak, was observed after training, which could explain the increased reactive oxygen species production (in nonphosphorylating mitochondria) and enhanced oxidative phosphorylation efficiency. At all studied temperatures, endurance training significantly augmented H2O2 production (and coenzyme Q reduction level) in nonphosphorylating mitochondria and decreased H2O2 production (and coenzyme Q reduction level) in phosphorylating mitochondria. Endurance training magnified the hyperthermia-induced increase in oxidative capacity and attenuated the hyperthermia-induced decline in oxidative phosphorylation efficiency and reactive oxygen species formation of nonphosphorylating mitochondria via proton leak enhancement. Thus, endurance training induces both quantitative and qualitative changes in muscle mitochondria that are important for cell signaling as well as for maintaining muscle energy homeostasis, especially at high temperatures.

  20. Effects of 45Ca on murine skeletal muscle. 2

    International Nuclear Information System (INIS)

    Asotra, K.; Katoch, S.S.; Krishan, K.; Malhotra, R.K.

    1983-01-01

    Swiss albino mice were injected intraperitoneally with 3.7x10 4 Bq and 7.4x10 4 Bq 45 Ca/g body weight. 45 Ca-treated mice were sacrificed on days 1, 3, 5, 7, 14 and 28 and activities of acid phosphatase, alkaline phosphatase and glucose 6-phosphatase bioassayed in diaphragm and gastrocnemius. Activities of acid and alkaline phosphatases decreased after the 1st day of 45 Ca treatment in both the muscles compared with the normal controls. These two enzymes apparently do not contribute to myofiber necrosis in irradiated skeletal muscle. Glucose 6-phosphatase levels increased in the two irradiated muscles and with 7.4x10 4 Bq 45 Ca dose as much as 20-fold and 7-fold elevations are recorded in diaphragm and gastrocnemius, respectively, indicating a radiation-induced stimulation of inhibition of glucose 6-phosphatase channelization for energy generation. The possible role of elevated glucose 6-phosphatase levels in glycogen accumulation on account of radiations in skeletal muscle has been discussed. (author)

  1. Membrane glycoproteins of differentiating skeletal muscle cells

    International Nuclear Information System (INIS)

    Miller, K.R.; Remy, C.N.; Smith, P.B.

    1987-01-01

    The composition of N-linked glycoprotein oligosaccharides was studied in myoblasts and myotubes of the C2 muscle cell line. Oligosaccharides were radioactively labelled for 15 hr with [ 3 H] mannose and plasma membranes isolated. Ten glycopeptides were detected by SDS-PAGE and fluorography. The extent of labelling was 4-6 fold greater in myoblasts vs myotubes. A glycopeptide of Mr > 100,000 was found exclusively in myoblast membranes. Lectin chromatography revealed that the proportion of tri-, tetranntenary, biantennary and high mannose chains was similar throughout differentiation. The high mannose chain fraction was devoid of hybrid chains. The major high mannose chain contained nine mannose residues. The higher level of glycopeptide labelling in myoblasts vs myotubes corresponded to a 5-fold greater rate of protein synthesis. Pulse-chase experiments were used to follow the synthesis of the Dol-oligosaccharides. Myoblasts and myotubes labelled equivalently the glucosylated tetradecasaccharide but myoblasts labelled the smaller intermediates 3-4 greater than myotubes. Myoblasts also exhibited a 2-3 fold higher Dol-P dependent glycosyl transferase activity for chain elongation and Dol-sugar synthesis. Together these results show that the degree of protein synthesis and level of Dol-P are contributing factors in the higher capacity of myoblasts to produce N-glycoproteins compared to myotubes

  2. 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

  3. Oxygen Generating Biomaterials Preserve Skeletal Muscle Homeostasis under Hypoxic and Ischemic Conditions

    Science.gov (United States)

    2013-08-26

    injection” protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up...Oxygen Generating Biomaterials Preserve Skeletal Muscle Homeostasis under Hypoxic and Ischemic Conditions Catherine L. Ward, Benjamin T. Corona...investigation was to determine if sodium percarbonate (SPO), an oxygen generating biomaterial, is capable of maintaining resting skeletal muscle

  4. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Kiens, Bente

    2014-01-01

    higher insulin sensitivity of female skeletal muscle can be related to gender-specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism...

  5. 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.

  6. What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and Function.

    Science.gov (United States)

    Glass, David J

    2017-08-01

    In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Determination of mouse skeletal muscle architecture using three dimensional diffusion tensor imaging

    NARCIS (Netherlands)

    Heemskerk, A.M.; Strijkers, G.J.; Vilanova, A.; Drost, M.R.; Nicolaij, K.

    2005-01-01

    Muscle architecture is the main determinant of the mechanical behavior of skeletal muscles. This study explored the feasibility of diffusion tensor imaging (DTI) and fiber tracking to noninvasively determine the in vivo three-dimensional (3D) architecture of skeletal muscle in mouse hind leg. In six

  8. Determination of mouse skeletal muscle architecture using three-dimensional diffusion tensor imaging

    NARCIS (Netherlands)

    Heemskerk, Anneriet M.; Strijkers, Gustav J.; Vilanova, Anna; Drost, Maarten R.; Nicolay, Klaas

    2005-01-01

    Muscle architecture is the main determinant of the mechanical behavior of skeletal muscles. This study explored the feasibility of diffusion tensor imaging (DTI) and fiber tracking to noninvasively determine the in vivo three-dimensional (3D) architecture of skeletal muscle in mouse hind leg. In six

  9. 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....

  10. Increased mitochondrial energy efficiency in skeletal muscle after long-term fasting: its relevance to animal performance.

    Science.gov (United States)

    Bourguignon, Aurore; Rameau, Anaïs; Toullec, Gaëlle; Romestaing, Caroline; Roussel, Damien

    2017-07-01

    In the final stage of fasting, skeletal muscle mass and protein content drastically decrease when the maintenance of efficient locomotor activity becomes crucial for animals to reactivate feeding behaviour and survive a very long period of starvation. As mitochondrial metabolism represents the main physiological link between the endogenous energy store and animal performance, the aim of this study was to determine how a very long, natural period of fasting affected skeletal muscle mitochondrial bioenergetics in king penguin ( Aptenodytes patagonicus ) chicks. Rates of mitochondrial oxidative phosphorylation were measured in pectoralis permeabilized fibres and isolated mitochondria. Mitochondrial ATP synthesis efficiency and the activities of respiratory chain complexes were measured in mitochondria isolated from pectoralis muscle. Results from long-term (4-5 months) naturally fasted chicks were compared with those from short-term (10 day) fasted birds. The respiratory activities of muscle fibres and isolated mitochondria were reduced by 60% and 45%, respectively, on average in long-term fasted chicks compared with short-term fasted birds. Oxidative capacity and mitochondrial content of pectoralis muscle were lowered by long-term fasting. Bioenergetic analysis of pectoralis muscle also revealed that mitochondria were, on average, 25% more energy efficient in the final stage of fasting (4-5 months) than after 10 days of fasting (short-term fasted birds). These results suggest that the strong reduction in respiratory capacity of pectoralis muscle was partly alleviated by increased mitochondrial ATP synthesis efficiency. Such oxidative phosphorylation optimization can impact animal performance, e.g. the metabolic cost of locomotion or the foraging efficiency. © 2017. Published by The Company of Biologists Ltd.

  11. Quantification of fibre type regionalisation : an analysis of lower hindlimb muscles in the rat

    NARCIS (Netherlands)

    Wang, LC; Kernell, D

    Newly developed concepts and methods for the quantification of fibre type regionalisation were used for comparison between all muscles traversing the ankle of the rat lower hindlimb (n = 13). For each muscle, cross-sections from the proximodistal midlevel were stained for myofibrillar ATPase and

  12. Proximo-distal organization and fibre type regionalization in rat hindlimb muscles

    NARCIS (Netherlands)

    Wang, LC; Kernell, D

    Five muscles of the rat's lower hindlimb were compared with regard to their histochemical fibre type distribution at seven different proximo-distal levels. The muscles were: extensor digitorum longus (ED), flexor digitorum and hallucis longus (FD), gastrocnemius medialis (GM), peroneus longus (PE)

  13. Primary skeletal muscle cells cultured on gelatin bead microcarriers develop structural and biochemical features characteristic of adult skeletal muscle.

    Science.gov (United States)

    Kubis, Hans-Peter; Scheibe, Renate J; Decker, Brigitte; Hufendiek, Karsten; Hanke, Nina; Gros, Gerolf; Meissner, Joachim D

    2016-04-01

    A primary skeletal muscle cell culture, in which myoblasts derived from newborn rabbit hindlimb muscles grow on gelatin bead microcarriers in suspension and differentiate into myotubes, has been established previously. In the course of differentiation and beginning spontaneous contractions, these multinucleated myotubes do not detach from their support. Here, we describe the development of the primary myotubes with respect to their ultrastructural differentiation. Scanning electron microscopy reveals that myotubes not only grow around the surface of one carrier bead but also attach themselves to neighboring carriers, forming bridges between carriers. Transmission electron microscopy demonstrates highly ordered myofibrils, T-tubules, and sarcoplasmic reticulum. The functionality of the contractile apparatus is evidenced by contractile activity that occurs spontaneously or can be elicited by electrostimulation. Creatine kinase activity increases steadily until day 20 of culture. Regarding the expression of isoforms of myosin heavy chains (MHC), we could demonstrate that from day 16 on, no non-adult MHC isoform mRNAs are present. Instead, on day 28 the myotubes express predominantly adult fast MHCIId/x mRNA and protein. This MHC pattern resembles that of fast muscles of adult rabbits. In contrast, primary myotubes grown on matrigel-covered culture dishes express substantial amounts of non-adult MHC protein even on day 21. To conclude, primary myotubes grown on microcarriers in their later stages exhibit many features of adult skeletal muscle and characteristics of fast type II fibers. Thus, the culture represents an excellent model of adult fast skeletal muscle, for example, when investigating molecular mechanisms of fast-to-slow fiber-type transformation. © 2015 International Federation for Cell Biology.

  14. Imaging characteristics of malignant and benign lesions of skeletal muscle

    International Nuclear Information System (INIS)

    Leonard, L.; Meyer, H.J.; Surov, A.

    2017-01-01

    There are many different tumors and tumor-like lesions with variable biological behavior that may affect the skeletal musculature. The aim of this study was to review the different intramuscular lesions and to provide a classification based on their radiological patterns. Intramuscular lesions can present as solid, liquid, semiliquid or fat equivalent manifestations and also as diffuse muscle enlargement and muscle calcification. Additionally, lesions with mixed patterns of the aforementioned alterations can also occur. Benign and malignant muscle lesions can often manifest with identical radiological patterns, which is why a certain differentiation is often difficult. A systematic radiological description and when possible assignment with respect to etiology and dignity depending on the patient history is necessary in order to recommend a subsequent histological confirmation or to avoid unnecessary confirmation. (orig.) [de

  15. Norepinephrine spillover from skeletal muscle during exercise in humans

    DEFF Research Database (Denmark)

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

    1989-01-01

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

  16. MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

    OpenAIRE

    Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

    2012-01-01

    Muscle repair is regulated by satellite cells, adult skeletal muscle stem cells that control muscle regeneration by proliferating and fusing with injured myofibers. MyoD is required for muscle regeneration; however, the mechanisms regulating MyoD expression in satellite cells are unclear. In this study, Olson and colleagues have demonstrated that deletion of MASTR and MRTF-A, two members of the Myocardin family of transcription factors, leads to skeletal muscle regeneration defects and down-r...

  17. Skeletal Muscle-derived Hematopoietic Stem Cells: Muscular Dystrophy Therapy by Bone Marrow Transplantation

    OpenAIRE

    Asakura, Atsushi

    2012-01-01

    For postnatal growth and regeneration of skeletal muscle, satellite cells, a self-renewing pool of muscle stem cells, give rise to daughter myogenic precursor cells that contribute to the formation of new muscle fibers. In addition to this key myogenic cell class, adult skeletal muscle also contains hematopoietic stem cell and progenitor cell populations which can be purified as a side population (SP) fraction or as a hematopoietic marker CD45-positive cell population. These muscle-derived he...

  18. 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...

  19. Beta?hydroxy?beta?methylbutyrate supplementation and skeletal muscle in healthy and muscle?wasting conditions

    OpenAIRE

    Hole?ek, Milan

    2017-01-01

    Abstract Beta?hydroxy?beta?methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate ...

  20. An in vivo model for studying the dynamics of intracellular free calcium changes in slow- and fast-twitch muscle fibres.

    Science.gov (United States)

    Bátkai, S; Rácz, I B; Ivanics, T; Tóth, A; Hamar, J; Slaaf, D W; Reneman, R S; Ligeti, L

    1999-10-01

    The understanding of the regulation of the free cytosolic [Ca2+] ([Ca2+]i) in skeletal muscle is hampered by the lack of techniques for quantifying free [Ca2+]i in muscle fibres in situ. We describe a model for studying the dynamics of free [Ca2+]i in the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus (SOL) muscles of the rat in vivo using caffeine superfusion to induce changes in free [Ca2+]i. We assumed that differences in sensitivity between the two muscle types for this substance reflect differences in intracellular Ca2+ handling in the fibres of which these muscles consist. The Indo-1 ratiometric method, using intravital microscopy with incident light, was adapted to measure free [Ca2+]i in vivo. Fluorescence images were collected by means of a digital camera. Caffeine superfusion at 37 degrees C for 2 min, at concentrations of 1, 2, 5, 10 or 20 mmol/l, induced a concentration-dependent increase in free [Ca2+]i and revealed differences in caffeine sensitivity between the muscle types, with the SOL being more sensitive. In a separate set of experiments the contracture threshold, as assessed by topical application of caffeine, was determined in both muscle types. EDL had a higher threshold for developing contracture than SOL. These finding are in agreement with previous in vitro studies. We may conclude that the dynamics of free [Ca2+]i can be assessed reliably in intact mammalian muscle in vivo.

  1. the tnfluence of breed, castration and age on muscle fibre type and ...

    African Journals Online (AJOL)

    For histochemical demonstration of succinic de- hydrogenase situated in the ..... centage coefficient of variation elucidates the matter. At. 34/' in the case of the .... metabolic and functional properties of skeletal muscle in relation to meat quality,.

  2. 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.

  3. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase....... 3. Addition of microvascular endothelial cells to the cultured skeletal muscle cells enhanced the contraction-induced accumulation of extracellular adenosine (P Skeletal muscle cells were...... in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P contracted, but not in the moderately contracted muscle cells...

  4. Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille

    2003-01-01

    individuals. The IL-6 immunostainings of skeletal muscle cells were homogeneous and without difference between muscle fiber types. The IL-6 mRNA peaked immediately after the exercise, and, in accordance, the IL-6 protein expression within muscle cells was most pronounced around 3 h post-exercise. However......, the finding that plasma IL-6 concentration peaked in the end of exercise indicates a high turnover of muscle-derived IL-6. In conclusion, the finding of marked IL-6 protein expression exclusively within skeletal muscle fibers following exercise demonstrates that skeletal muscle fibers of all types...

  5. Skeletal muscle CT of lower extremities in myotonic dystrophy

    International Nuclear Information System (INIS)

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

    1988-01-01

    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. (author)

  6. 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.

  7. Viscoelasticity-based MR elastography of skeletal muscle

    Science.gov (United States)

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

    2010-11-01

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

  8. 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.

  9. Leucine incorporation into mixed skeletal muscle protein in humans

    International Nuclear Information System (INIS)

    Nair, K.S.; Halliday, D.; Griggs, R.C.

    1988-01-01

    Fractional mixed skeletal muscle protein synthesis (FMPS) was estimated in 10 postabsorptive healthy men by determining the increment in the abundance of [ 13 C]-leucine in quadriceps muscle protein during an intravenous infusion of L-[1- 13 C]leucine. Whole-body muscle protein synthesis (MPS) was calculated based on the estimation of muscle mass from creatinine excretion and compared with whole-body protein synthesis (WBPS) calculated from the nonoxidative portion of leucine flux. A significant correlation was found between MPS. The contribution of MPS to WBPS was 27 ± 1%, which is comparable to the reports in other species. Morphometric analyses of adjacent muscle samples in eight subjects demonstrated that the biopsy specimens consisted of 86.5 ± 2% muscular as opposed to other tissues. Because fiber type composition varies between biopsies, the authors examined the relationship between proportions of each fiber type and FMPS. Variation in the composition of biopsies and in fiber-type proportion did not affect the estimation of muscle protein synthesis rate. They conclude that stable isotope techniques using serial needle biopsies permit the direct measurement of FMPS in humans and that this estimation is correlated with an indirect estimation of WBPS

  10. MicroRNA in Skeletal Muscle: Its Crucial Roles in Signal Proteins, Mus cle Fiber Type, and Muscle Protein Synthesis.

    Science.gov (United States)

    Zhang, Jing; Liu, Yu Lan

    2017-01-01

    Pork is one of the most economical sources of animal protein for human consumption. Meat quality is an important economic trait for the swine industry, which is primarily determined by prenatal muscle development and postnatal growth. Identification of the molecular mechanisms underlying skeletal muscle development is a key priority. MicroRNAs (miRNAs) are a class of small noncoding RNAs that have emerged as key regulators of skeletal muscle