Science.gov

Sample records for skeletal muscle perfusion

  1. Regulation of skeletal muscle perfusion during exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Laughlin, M. H.

    1998-01-01

    For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.

  2. Regulation of skeletal muscle perfusion during exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.; Laughlin, M. H.

    1998-01-01

    For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.

  3. Maximal perfusion of skeletal muscle in man.

    PubMed Central

    Andersen, P; Saltin, B

    1985-01-01

    Five subjects exercised with the knee extensor of one limb at work loads ranging from 10 to 60 W. Measurements of pulmonary oxygen uptake, heart rate, leg blood flow, blood pressure and femoral arterial-venous differences for oxygen and lactate were made between 5 and 10 min of the exercise. Flow in the femoral vein was measured using constant infusion of saline near 0 degrees C. Since a cuff was inflated just below the knee during the measurements and because the hamstrings were inactive, the measured flow represented primarily the perfusion of the knee extensors. Blood flow increased linearly with work load right up to an average value of 5.7 l min-1. Mean arterial pressure was unchanged up to a work load of 30 W, but increased thereafter from 100 to 130 mmHg. The femoral arterial-venous oxygen difference at maximum work averaged 14.6% (v/v), resulting in an oxygen uptake of 0.80 l min-1. With a mean estimated weight of the knee extensors of 2.30 kg the perfusion of maximally exercising skeletal muscle of man is thus in the order of 2.5 l kg-1 min-1, and the oxygen uptake 0.35 l kg-1 min-1. Limitations in the methods used previously to determine flow and/or the characteristics of the exercise model used may explain why earlier studies in man have failed to demonstrate the high perfusion of muscle reported here. It is concluded that muscle blood flow is closely related to the oxygen demand of the exercising muscles. The hyperaemia at low work intensities is due to vasodilatation, and an elevated mean arterial blood pressure only contributes to the linear increase in flow at high work rates. The magnitude of perfusion observed during intense exercise indicates that the vascular bed of skeletal muscle is not a limiting factor for oxygen transport. PMID:4057091

  4. Estimation of pyruvate decarboxylation in perfused rat skeletal muscle.

    PubMed

    Schadewaldt, P; Münch, U; Prengel, M; Staib, W

    1983-10-31

    By the determination of pyruvate dehydrogenase activity in tissue homogenates only limited information is gained on the actual metabolic flux. We therefore determined pyruvate decarboxylation in isolated rat hindlimbs non recirculating perfused with physiological (1-14C)pyruvate levels. On the basis of perfusate pyruvate specific activity a 14CO2 production of 15.8 +/- 0.5 nmol/min per g muscle was measured. However, by this method the actual pyruvate flux through the enzyme complex is underestimated by a factor of 7 due to the intracellular dilution of label.

  5. Hindlimb perfusion induces GLUT-1 and immediate early gene expression in skeletal muscle.

    PubMed

    Neufer, P D; Devente, J E; Tapscott, E B; Dohm, G L

    1995-05-01

    The purpose of the present study was to test the suitability of the rat hindlimb perfusion technique for studying the acute regulation of the GLUT-1 and GLUT-4 glucose transporter genes in adult skeletal muscle. To further examine the stability of the technique, we also monitored the transcription rate and mRNA content of selected immediate early genes. Nuclei and total RNA were isolated from red and white hindlimb muscle from perfused (2 h) and nonperfused control animals. Although GLUT-4 transcription and mRNA content remained stable, perfusion elicited a marked 3.5-fold increase in GLUT-1 mRNA in red and 2.2-fold increase in white skeletal muscle in the absence of any detectable change in transcription. In contrast to both GLUT-1 and GLUT-4, transcription originating from the c-fos and c-myc immediate early genes increased from 2.0- to 2.7-fold with perfusion in both red and white skeletal muscle, whereas transcription of the beta-actin gene decreased by 40-60%. Both c-fos and c-myc mRNA levels also increased with perfusion, whereas beta-actin mRNA remained unchanged. These findings clearly demonstrate that the current method of performing the hindlimb perfusion technique rapidly and dramatically alters the regulation of selected genes in skeletal muscle.

  6. Image-based calculation of perfusion and oxyhemoglobin saturation in skeletal muscle during submaximal isometric contractions.

    PubMed

    Elder, Christopher P; Cook, Ryan N; Chance, Marti A; Copenhaver, Elizabeth A; Damon, Bruce M

    2010-09-01

    The relative oxygen saturation of hemoglobin and the rate of perfusion are important physiological quantities, particularly in organs such as skeletal muscle, in which oxygen delivery and use are tightly coupled. The purpose of this study was to demonstrate the image-based calculation of the relative oxygen saturation of hemoglobin and quantification of perfusion in skeletal muscle during isometric contractions. This was accomplished by establishing an empirical relationship between the rate of radiofrequency-reversible dephasing and near-infrared spectroscopy-observed oxyhemoglobin saturation (relative oxygen saturation of hemoglobin) under conditions of arterial occlusion and constant blood volume. A calibration curve was generated and used to calculate the relative oxygen saturation of hemoglobin from radiofrequency-reversible dephasing changes measured during contraction. Twelve young healthy subjects underwent 300 s of arterial occlusion and performed isometric contractions of the dorsiflexors at 30% of maximal contraction for 120 s. Muscle perfusion was quantified during contraction by arterial spin labeling and measures of muscle T(1). Comparisons between the relative oxygen saturation of hemoglobin values predicted from radiofrequency-reversible dephasing and that measured by near-infrared spectroscopy revealed no differences between methods (P = 0.760). Muscle perfusion reached a value of 34.7 mL 100 g(-1) min(-1) during contraction. These measurements hold future promise in measuring muscle oxygen consumption in healthy and diseased skeletal muscle. 2010 Wiley-Liss, Inc.

  7. Image Based Calculation of Perfusion and Oxyhemoglobin Saturation in Skeletal Muscle during Submaximal Isometric Contractions

    PubMed Central

    Elder, Christopher P.; Cook, Ryan N.; Chance, Marti A.; Copenhaver, Elizabeth A.; Damon, Bruce M.

    2015-01-01

    The relative oxygen saturation of hemoglobin (%HbO2) and the rate of perfusion (θ̇) are important physiological quantities, particularly in organs such as skeletal muscle in which oxygen delivery and use are tightly coupled. The purpose of this study was to demonstrate the image-based calculation of %HbO2 and quantification of perfusion in skeletal muscle during isometric contractions. This was accomplished by establishing an empirical relationship between the rate of RF-reversible dephasing (R2′) and near infrared spectroscopy (NIRS)-observed oxyhemoglobin saturation (%HbO2) under conditions of arterial occlusion and constant blood volume. A calibration curve was generated and used to calculate %HbO2 from R2′ changes measured during contraction. Twelve young healthy subjects underwent 300 seconds of arterial occlusion and performed isometric contractions of the dorsiflexors at 30% of maximal contraction for 120s. Muscle perfusion was quantified during contraction by arterial spin labeling and measures of muscle T1. Comparisons between the %HbO2 values predicted from R2′ and that measured by NIRS revealed no differences between methods (p = 0.760). Muscle perfusion reached a value of 34.7 mL 100g−1 min−1 during contraction. These measurements hold future promise in measuring muscle oxygen consumption in healthy and diseased skeletal muscle. PMID:20806379

  8. Assessment of Skeletal Muscle Perfusion using Contrast-Enhanced Ultrasonography: Technical Note

    PubMed Central

    Qureshi, Adnan I.; Saleem, Muhammad A.; Aytac, Emrah; Wallery, Shawn S.

    2017-01-01

    Background Intravenous contrast-enhanced ultrasonography is a recently developed technique for assessment of tissue perfusion, but has not been used for assessment of skeletal muscle perfusion. Methods We studied a 42-year-old woman in whom myonecrosis was suspected due to systemic vasculitis and ischemia. The biceps brachii (right) and quadriceps femoris (vastus medialis) on right-hand side and subsequently left-hand side were imaged. Intravenous bolus of activated perflutren lipid microspheres was injected and B-Flow color mode (brown color) was used within a selected region of interest to image the passage of contrast through muscle parenchyma throughout three cardiac cycles. Results Visual interpretation of muscle perfusion was performed based on the maximal intensity of contrast in the muscle, and the speed of contrast replenishment. No deficits were noted in the perfusion pattern. The arterial phase demonstrated stellate vascularity, centrifugal filling, and homogeneous hypervascularity at peak enhancement. Conclusions The bolus of contrast resulted in good signal persistence and satisfactory imaging for multiple muscle groups. PMID:28243350

  9. The role of perfusion in the oxygen extraction capability of skin and skeletal muscle.

    PubMed

    Thorn, Clare E; Shore, Angela C

    2016-05-15

    Oxygen extraction (OE) by all cells is dependent on an adequate supply of oxygen in proximal blood vessels and the cell's need and ability to uptake that oxygen. Here the role of blood flow in regulating OE in skin and skeletal muscle was investigated in lean and obese men. OE was derived by two optical reflectance spectroscopy techniques: 1) from the rate of fall in mean blood saturation during a 4 min below knee arterial occlusion, and thus no blood flow, in calf skin and skeletal muscle and 2) in perfused, unperturbed skin, using the spontaneous falls in mean blood saturation induced by vasomotion in calf and forearm skin of 24 subjects, 12 lean and 12 obese. OE in perfused skin was significantly higher in lean compared with obese subjects in forearm (Mann-Whitney, P < 0.004) and calf (P < 0.001) and did not correlate with OE in unperfused skin (ρ = -0.01, P = 0.48). With arterial occlusion and thus no blood flow, skin OE in lean and obese subjects no longer differed (P = 0.23, not significant). In contrast in skeletal muscle with arterial occlusion and no blood flow, the difference in OE between lean and obese subjects occurred, with obese subjects exhibiting significantly higher OE (P < 0.012). The classic model of metabolic blood flow regulation to support oxygen extraction is evident in perfused skin; OE is perturbed without blood flow and reduced in obesity. In resting skeletal muscle other mechanism(s), independent of blood flow, are implicated in oxygen extraction. Copyright © 2016 the American Physiological Society.

  10. Control of skeletal muscle perfusion at the onset of dynamic exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.

    1999-01-01

    At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

  11. Control of skeletal muscle perfusion at the onset of dynamic exercise

    NASA Technical Reports Server (NTRS)

    Delp, M. D.

    1999-01-01

    At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

  12. DIVERGENCE BETWEEN ARTERIAL PERFUSION AND FATIGUE RESISTANCE IN SKELETAL MUSCLE IN THE METABOLIC SYNDROME

    PubMed Central

    Frisbee, Jefferson C.; Goodwill, Adam G.; Butcher, Joshua T.; Olfert, I. Mark

    2010-01-01

    The metabolic syndrome is associated with elevated peripheral vascular disease risk, characterized by mismatched blood flow delivery/distribution and local metabolism. The obese Zucker rat (OZR) model of the metabolic syndrome exhibits myriad vascular impairments, although their integrated impact on functional hyperemia remains unclear. In this study, arterial pressor responses and skeletal muscle perfusion were assessed in lean Zucker rats (LZR) and OZR during adrenergic stimulation (phenylephrine), challenge with thromboxane (U46619) and endothelium-dependent dilation (methacholine). OZR were hypertensive versus LZR, but this was abolished by adrenoreceptor blockade (phentolamine); pressor responses to U46619 were similar between strains and were abolished by blockade with the PGH2/TxA2 receptor antagonist, SQ-29548. Depressor reactivity to methacholine was impaired in OZR, but was improved by antioxidant treatment (TEMPOL). Across levels of metabolic demand, blood flow to in situ gastrocnemius muscle was restrained by adrenergic constriction in OZR, although this diminished with increased demand. O2 extraction, reduced in OZR vs. LZR across levels of metabolic demand, was improved by TEMPOL or SQ-29548; treatment with phentolamine did not impact extraction and neither TEMPOL nor SQ-29548 improved muscle blood flow in OZR. While VO2 and muscle performance were consistently reduced in OZR vs. LZR, treatment with all three agents improved outcomes, while treatment with individual agents was less effective. These results suggest that contributions of vascular dysfunction to perfusion, VO2 and muscle performance are spatially distinct, with adrenergic constriction impacting proximal resistance and endothelial dysfunction impacting distal microvessel-tissue exchange. Further, these data suggest that increasing skeletal muscle blood flow in OZR is not sufficient to improve performance, unless distal perfusion inhomogeneities are rectified. PMID:21123363

  13. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P < 0.05) over a 13-d period. Total protein synthesis rates could be determined accurately in the bioreactors for up to 30 h and total protein degradation rates could be measured for up to 3 wk. Special fixation and storage conditions necessary for space flight studies were validated as part of the studies. For example, the anabolic autocrine/paracrine skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  14. Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

    1998-01-01

    Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P < 0.05) over a 13-d period. Total protein synthesis rates could be determined accurately in the bioreactors for up to 30 h and total protein degradation rates could be measured for up to 3 wk. Special fixation and storage conditions necessary for space flight studies were validated as part of the studies. For example, the anabolic autocrine/paracrine skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

  15. Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation.

    PubMed

    Frisbee, Jefferson C; Butcher, Joshua T; Frisbee, Stephanie J; Olfert, I Mark; Chantler, Paul D; Tabone, Lawrence E; d'Audiffret, Alexandre C; Shrader, Carl D; Goodwill, Adam G; Stapleton, Phoebe A; Brooks, Steven D; Brock, Robert W; Lombard, Julian H

    2016-02-15

    To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning "healthy" to "high PVD risk" and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk.

  16. Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

    PubMed Central

    Butcher, Joshua T.; Frisbee, Stephanie J.; Olfert, I. Mark; Chantler, Paul D.; Tabone, Lawrence E.; d'Audiffret, Alexandre C.; Shrader, Carl D.; Goodwill, Adam G.; Stapleton, Phoebe A.; Brooks, Steven D.; Brock, Robert W.; Lombard, Julian H.

    2015-01-01

    To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. PMID:26702145

  17. Reducing body fat with altitude hypoxia training in swimmers: role of blood perfusion to skeletal muscles.

    PubMed

    Chia, Michael; Liao, Chin-An; Huang, Chih-Yang; Lee, Wen-Chih; Hou, Chien-Wen; Yu, Szu-Hsien; Harris, M Brennan; Hsu, Tung-Shiung; Lee, Shin-Da; Kuo, Chia-Hua

    2013-02-28

    Swimmers tend to have greater body fat than athletes from other sports. The purpose of the study was to examine changes in body composition after altitude hypoxia exposure and the role of blood distribution to the skeletal muscle in swimmers. With a constant training volume of 12.3 km/day, young male swimmers (N = 10, 14.8 ± 0.5 years) moved from sea-level to a higher altitude of 2,300 meters. Body composition was measured before and after translocation to altitude using dual-energy X-ray absorptiometry (DXA) along with 8 control male subjects who resided at sea level for the same period of time. To determine the effects of hypoxia on muscle blood perfusion, total hemoglobin concentration (THC) was traced by near-infrared spectroscopy (NIRS) in the triceps and quadriceps muscles under glucose-ingested and insulin-secreted conditions during hypoxia exposure (16% O2) after training. While no change in body composition was found in the control group, subjects who trained at altitude had unequivocally decreased fat mass (-1.7 ± 0.3 kg, -11.4%) with increased lean mass (+0.8 ± 0.2 kg, +1.5%). Arterial oxygen saturation significantly decreased with increased plasma lactate during hypoxia recovery mimicking 2,300 meters at altitude (~93% versus ~97%). Intriguingly, hypoxia resulted in elevated muscle THC, and sympathetic nervous activities occurred in parallel with greater-percent oxygen saturation in both muscle groups. In conclusion, the present study provides evidence that increased blood distribution to the skeletal muscle under postprandial condition may contribute to the reciprocally increased muscle mass and decreased body mass after a 3-week altitude exposure in swimmers.

  18. Hydrostatic Isolated Limb Perfusion with Adeno-associated Virus Vectors Enhances Correction of Skeletal Muscle in Pompe Disease

    PubMed Central

    Sun, Baodong; Li, Songtao; Bird, Andrew; Koeberl, Dwight D.

    2010-01-01

    Glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) stems from the inherited deficiency of acid-α-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle specific promoter could achieve relatively higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO) mice, in comparison with intravenous (IV) administration. ILP adminstration of AAV2/8 vectors encoding alkaline phosphatase or human GAA transduced skeletal muscles of the hindlimb widely, despite the relatively low number of vector particles administered (1×1011), and IV administration of an equivalent vector dose failed to transduce skeletal muscle detectably. Similarly, ILP administration of fewer vector particles of the AAV2/9 vector encoding human GAA (3×1010) transduced skeletal muscles of the hindlimb widely and significantly reduced glycogen content to, in comparison with IV administration. The only advantage for IV administration was moderately high level transduction of cardiac muscle, which demonstrated compellingly that ILP administration sequestered vector particles within the perfused limb. Reduction of glycogen storage in the extensor digitorum longus demonstrated the potential advantage of ILP-mediated delivery of AAV vectors in Pompe disease, because type II myofibers are resistant to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of multiple skeletal muscles while reducing the required dosages in terms of vector particle numbers. PMID:20686508

  19. Epoxyeicosatrienoic acids mediate insulin-mediated augmentation in skeletal muscle perfusion and blood volume

    PubMed Central

    Shim, Chi Young; Kim, Sajeevani; Chadderdon, Scott; Wu, Melinda; Qi, Yue; Xie, Aris; Alkayed, Nabil J.; Davidson, Brian P.

    2014-01-01

    Skeletal muscle microvascular blood flow (MBF) increases in response to physiological hyperinsulinemia. This vascular action of insulin may facilitate glucose uptake. We hypothesized that epoxyeicosatrienoic acids (EETs), a family of arachadonic, acid-derived, endothelium-derived hyperpolarizing factors, are mediators of insulin's microvascular effects. Contrast-enhanced ultrasound (CEU) was performed to quantify skeletal muscle capillary blood volume (CBV) and MBF in wild-type and obese insulin-resistant (db/db) mice after administration of vehicle or trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (t-AUCB), an inhibitor of soluble epoxide hydrolase that converts EETs to less active dihydroxyeicosatrienoic acids. Similar studies were performed in rats pretreated with l-NAME. CEU was also performed in rats undergoing a euglycemic hyperinsulinemic clamp, half of which were pretreated with the epoxygenase inhibitor MS-PPOH to inhibit EET synthesis. In both wild-type and db/db mice, intravenous t-AUCB produced an increase in CBV (65–100% increase at 30 min, P < 0.05) and in MBF. In db/db mice, t-AUCB also reduced plasma glucose by ∼15%. In rats pretreated with l-NAME, t-AUCB after produced a significant ≈20% increase in CBV, indicating a component of vascular response independent of nitric oxide (NO) production. Hyperinsulinemic clamp produced a time-dependent increase in MBF (19 ± 36 and 76 ± 49% at 90 min, P = 0.026) that was mediated in part by an increase in CBV. Insulin-mediated changes in both CBV and MBF during the clamp were blocked entirely by MS-PPOH. We conclude that EETs are a mediator of insulin-mediated augmentation in skeletal muscle perfusion and are involved in regulating changes in CBV during hyperinsulinemia. PMID:25336524

  20. Erythrocytes as controllers of perfusion distribution in the microvasculature of skeletal muscle.

    PubMed

    Sprague, R S; Bowles, E A; Achilleus, D; Ellsworth, M L

    2011-07-01

    In 1929, August Krogh identified the matching of oxygen (O(2)) supply with demand in skeletal muscle as a fundamental physiological process. In the intervening decades, much research has been focused on elucidating the mechanisms by which this important process occurs. For any control system to be effective, there must be a means by which the need is determined and a mechanism by which that information is coupled to an appropriate response. The focus of this review was to highlight current research in support of the hypothesis that the mobile erythrocyte, when exposed to reduced O(2) tension, releases ATP in a controlled manner. This ATP interacts with purinergic receptors on the endothelium producing both local and conducted vasodilation enabling the erythrocyte to distribute perfusion to precisely match O(2) delivery with need in skeletal muscle. If this is an important mechanism for normal physiological control of microvascular perfusion, defects in this process would be anticipated to have pathophysiological consequences. Individuals with either type 2 diabetes (DM2) or pre-diabetes have microvascular dysfunction that contributes to morbidity and mortality. DM2 erythrocytes and erythrocytes incubated with insulin at levels similar to those seen in pre-diabetes fail to release ATP in response to reduced O(2) tension. Knowledge of the components of the signal transduction pathway for low O(2) -induced ATP release suggest novel therapeutic approaches to ameliorating this defect. Although the erythrocyte may be but one component of the complex O(2) delivery process, it appears to play an important role in distributing oxygen within the microvasculature. © 2010 The Authors. Acta Physiologica © 2010 Scandinavian Physiological Society.

  1. Skeletal myofiber VEGF regulates contraction-induced perfusion and exercise capacity but not muscle capillarity in adult mice.

    PubMed

    Knapp, Amy E; Goldberg, Daniel; Delavar, Hamid; Trisko, Breanna M; Tang, Kechun; Hogan, Michael C; Wagner, Peter D; Breen, Ellen C

    2016-07-01

    A single bout of exhaustive exercise signals expression of vascular endothelial growth factor (VEGF) in the exercising muscle. Previous studies have reported that mice with life-long deletion of skeletal myofiber VEGF have fewer capillaries and a severe reduction in endurance exercise. However, in adult mice, VEGF gene deletion conditionally targeted to skeletal myofibers limits exercise capacity without evidence of capillary regression. To explain this, we hypothesized that adult skeletal myofiber VEGF acutely regulates skeletal muscle perfusion during muscle contraction. A tamoxifen-inducible skeletal myofiber-specific VEGF gene deletion mouse (skmVEGF-/-) was used to reduce skeletal muscle VEGF protein by 90% in adult mice. Three weeks after inducing deletion of the skeletal myofiber VEGF gene, skmVEGF-/- mice exhibited diminished maximum running speed (-10%, P < 0.05) and endurance capacity (-47%; P < 0.05), which did not persist after 8 wk. In skmVEGF-/- mice, gastrocnemius complex time to fatigue measured in situ was 71% lower than control mice. Contraction-induced perfusion measured by optical imaging during a period of electrically stimulated muscle contraction was 85% lower in skmVEGF-/- than control mice. No evidence of capillary rarefication was detected in the soleus, gastrocnemius, and extensor digitorum longus (EDL) up to 8 wk after tamoxifen-induced VEGF ablation, and contractility and fatigue resistance of the soleus measured ex vivo were also unchanged. The force-frequency of the EDL showed a small right shift, but fatigue resistance did not differ between EDL from control and skmVEGF-/- mice. These data suggest myofiber VEGF is required for regulating perfusion during periods of contraction and may in this manner affect endurance capacity. Copyright © 2016 the American Physiological Society.

  2. Skeletal muscle

    USDA-ARS?s Scientific Manuscript database

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

  3. Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease.

    PubMed

    Sun, B; Li, S; Bird, A; Koeberl, D D

    2010-12-01

    Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the inherited deficiency of acid-α-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle-specific promoter could achieve relatively higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO) mice, in comparison with intravenous (IV) administration. ILP administration of AAV2/8 vectors encoding alkaline phosphatase or human GAA-transduced skeletal muscles of the hindlimb widely, despite the relatively low number of vector particles administered (1 × 10¹¹), and IV administration of an equivalent vector dose failed to transduce skeletal muscle detectably. Similarly, ILP administration of fewer vector particles of the AAV2/9 vector encoding human GAA (3 × 10¹⁰) transduced skeletal muscles of the hindlimb widely and significantly reduced glycogen content to, in comparison with IV administration. The only advantage for IV administration was moderately high-level transduction of cardiac muscle, which demonstrated compellingly that ILP administration sequestered vector particles within the perfused limb. Reduction of glycogen storage in the extensor digitorum longus demonstrated the potential advantage of ILP-mediated delivery of AAV vectors in Pompe disease, because type II myofibers are resistant to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of multiple skeletal muscles while reducing the required dosages in terms of vector particle numbers.

  4. Is skeletal muscle luxury perfusion the main hemodynamic effect of high-dose insulin in cardiac surgery?

    PubMed

    Lindholm, L; Nilsson, B; Kirnö, K; Sellgren, J; Nilsson, F; Jeppsson, A

    2000-08-01

    Insulin, in combination with glucose and potassium (GIK), can be used in heart surgery to improve hemodynamic performance. This study evaluates the role of skeletal muscle vasodilation in hemodynamic effects of high-dose GIK therapy early after coronary surgery. Thirty-three male patients undergoing coronary artery bypass grafting were included in a prospective, randomized and controlled study. Eleven patients received infusions of mixed amino acids (11.4 g) and insulin solution (225 IU insulin, glucose with the glucose clamp technique, and potassium), 11 patients received infusions of mixed amino acids (11.4 g) and 11 patients served as control subjects. During combined insulin and amino acid infusion, cardiac output increased by 13+/-3% (+0.6+/-0.2 L x min(-1)) and systemic vascular resistance decreased by 24+/-3% (-320+/-46 dyn x s x cm(-5)). The changes differed from those in the control group (CO: -0.2+/-0.1 L x min(-1), p < 0.05; SVR: +136+/-42 dyn x s x cm(-5), p < 0.05). Changes in skeletal muscle perfusion and leg vascular resistance did not differ significantly among the groups. At most, changes in leg blood flow could explain 40% of the changes in cardiac output. Skeletal muscle luxury perfusion is not the main hemodynamic effect of high-dose insulin in the early postoperative period after coronary surgery.

  5. Quantitative, dynamic and noninvasive determination of skeletal muscle perfusion in mouse leg by NMR arterial spin-labeled imaging.

    PubMed

    Bertoldi, Didier; Loureiro de Sousa, Paulo; Fromes, Yves; Wary, Claire; Carlier, Pierre G

    2008-11-01

    Because mouse may relatively easily be genetically tailored to develop equivalent of human muscular diseases or to present controlled alterations of mechanisms involved in vasoregulation, it has become the prevalent species to explore such questions. However, the very small size of the animals represents a serious limitation when evaluating the functional consequences of these genetic manipulations. In this context, the recourse to arterial spin labeling (ASL) nuclear magnetic resonance (NMR) methods in which arterial water spins act as an endogenous and freely diffusible tracer of perfusion is tempting but challenging. This article shows that despite the small size of the animal, mouse muscle perfusion may be measured, at rest and in conditions of reactive hyperemia, using saturation inversion recovery sequence, a pulsed ASL variant, combined with NMR imaging. Baseline perfusion values in the mouse leg were 17+/-11 ml.min(-1).100 g(-1) (n=11) and were comparable to microsphere data from the literature. Under ischemia, leg perfusion was 1.2+/-9.3 ml.min(-1).100 g(-1) (n=11). The difference observed between basal and ischemic measurements was statistically different (P=.0001). The temporal pattern of hyperemia in mouse muscle was coherent with previously published measurements in humans and in rats. The mean peak perfusion was 62+/-24 ml.min(-1).100 g(-1) (n=6) occurring 48+/-27 s after the end of occlusion. In conclusion, this study demonstrated the ability of ASL combined to NMR imaging to quantify skeletal muscle perfusion in mice legs, both at rest and dynamically.

  6. Changes in skeletal muscle perfusion and spasticity in patients with poststroke hemiparesis treated by robotic assistance (Gloreha) of the hand

    PubMed Central

    Bissolotti, Luciano; Villafañe, Jorge Hugo; Gaffurini, Paolo; Orizio, Claudio; Valdes, Kristin; Negrini, Stefano

    2016-01-01

    [Purpose] The purpose of this case series was to determine the effects of robot-assisted hand rehabilitation with a Gloreha device on skeletal muscle perfusion, spasticity, and motor function in subjects with poststroke hemiparesis. [Subjects and Methods] Seven patients, 2 women and 5 men (mean ± SD age: 60.5 ±6.3 years), with hemiparesis (>6 months poststroke), received passive mobilization of the hand with a Gloreha (Idrogenet, Italy), device (30 min per day; 3 sessions a week for 3 weeks). The outcome measures were the total hemoglobin profiles and tissue oxygenation index (TOI) in the muscle tissue evaluated through near-infrared spectroscopy. The Motricity Index and modified Ashworth Scale for upper limb muscles were used to assess mobility of the upper extremity. [Results] Robotic assistance reduced spasticity after the intervention by 68.6% in the upper limb. The Motricity Index was unchanged in these patients after treatment. Regarding changes in muscle perfusion, significant improvements were found in total hemoglobin. There were significant differences between the pre- and posttreatment modified Ashworth scale. [Conclusion] The present work provides novel evidence that robotic assistance of the hand induced changes in local muscle blood flow and oxygen supply, diminished spasticity, and decreased subject-reported symptoms of heaviness and stiffness in subjects with post-stroke hemiparesis. PMID:27134356

  7. Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg

    PubMed Central

    2013-01-01

    Background The function of the peripheral microvascular may be interrogated by measuring perfusion, tissue oxygen concentration, or venous oxygen saturation (SvO2) recovery dynamics following induced ischemia. The purpose of this work is to develop and evaluate a magnetic resonance (MR) technique for simultaneous measurement of perfusion, SvO2, and skeletal muscle T2*. Methods Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT) is comprised of interleaved pulsed arterial spin labeling (PASL) and multi-echo gradient-recalled echo (GRE) sequences. During the PASL post-labeling delay, images are acquired with a multi-echo GRE to quantify SvO2 and T2* at a downstream slice location. Thus time-courses of perfusion, SvO2, and T2* are quantified simultaneously within a single scan. The new sequence was compared to separately measured PASL or multi-echo GRE data during reactive hyperemia in five young healthy subjects. To explore the impairment present in peripheral artery disease patients, five patients were evaluated with PIVOT. Results Comparison of PIVOT-derived data to the standard techniques shows that there was no significant bias in any of the time-course-derived metrics. Preliminary data show that PAD patients exhibited alterations in perfusion, SvO2, and T2* time-courses compared to young healthy subjects. Conclusion Simultaneous quantification of perfusion, SvO2, and T2* is possible with PIVOT. Kinetics of perfusion, SvO2, and T2* during reactive hyperemia may help to provide insight into the function of the peripheral microvasculature in patients with PAD. PMID:23958293

  8. Skeletal muscle perfusion and stem cell delivery in muscle disorders using intra-femoral artery canulation in mice.

    PubMed

    Matthias, Nadine; Hunt, Samuel D; Wu, Jianbo; Darabi, Radbod

    2015-11-15

    Muscular dystrophies are among major inherited muscle disorders characterized by progressive muscle damage and fibrosis with no definitive cure. Recently, gene or cell based therapies have been developed to restore the missing gene expression or replace the damaged tissues. In order to test the efficiency of these therapies in mice models of muscular dystrophies, the arterial route of delivery is very advantageous as it provides uniform muscle exposure to the therapeutic agents or cells. Although there are few reports of arterial delivery of the therapeutic agents or cells in mice, there is no in-depth description and evaluation of its efficacy in perfusion of downstream muscles. This study is aimed to develop a practical method for intra-femoral artery perfusion in mice and to evaluate perfusion efficiency using near-infrared-fluorescence (NIRF) imaging as well as histology following stem cell delivery. Our results provide a practical guide to perform this delicate method in mice. By using a sensitive fluorescent dye, different muscle groups of the hindlimb have been evaluated for proper perfusion. As the final step, we have validated the efficiency of arterial cell delivery into muscles using human iPS-derived myogenic cells in an immunodeficient mouse model for Duchenne muscular dystrophy (NSG-mdx(4cv)).

  9. Kinetic control of oxygen consumption during contractions in self-perfused skeletal muscle

    PubMed Central

    Wüst, Rob C I; Grassi, Bruno; Hogan, Michael C; Howlett, Richard A; Gladden, L Bruce; Rossiter, Harry B

    2011-01-01

    Abstract Fast kinetics of muscle oxygen consumption () is characteristic of effective physiological systems integration. The mechanism of kinetic control in vivo is equivocal as measurements are complicated by the twin difficulties of making high-frequency direct measurements of and intramuscular metabolites, and in attaining high [ADP]; complexities that can be overcome utilising highly aerobic canine muscle for the investigation of the transition from rest to contractions at maximal . Isometric tetanic contractions of the gastrocnemius complex of six anaesthetised, ventilated dogs were elicited via sciatic nerve stimulation (50 Hz; 200 ms duration; 1 contraction s−1). Muscle and lactate efflux were determined from direct Fick measurements. Muscle biopsies were taken at rest and every ∼10 s during the transient and analysed for [phosphates], [lactate] and pH. The temporal vs.[PCr] and [ADP] relationships were not well fitted by linear or classical hyperbolic models (respectively), due to the high sensitivity of to metabolic perturbations early in the transient. The time course of this apparent sensitisation was closely aligned to that of ATP turnover, which was lower in the first ∼25 s of contractions compared to the steady state. These findings provide the first direct measurements of skeletal muscle and [PCr] in the non-steady state, and suggest that simple phosphate feedback models (which are adequate for steady-state observations in vitro) are not sufficient to explain the dynamic control of in situ. Rather an allosteric or ‘parallel activation’ mechanism of energy consuming and producing processes is required to explain the kinetic control of in mammalian skeletal muscle. PMID:21690197

  10. Fast perfusion measurements in rat skeletal muscle at rest and during exercise with single-voxel FAIR (flow-sensitive alternating inversion recovery).

    PubMed

    Pohmann, Rolf; Künnecke, Basil; Fingerle, Jürgen; von Kienlin, Markus

    2006-01-01

    Non-invasive measurement of perfusion in skeletal muscle by in vivo magnetic resonance remains a challenge due to its low level and the correspondingly low signal-to-noise ratio. To enable accurate, quantitative, and time-resolved perfusion measurements in the leg muscle, a technique with a high sensitivity is required. By combining a flow-sensitive alternating inversion recovery (FAIR)-sequence with a single-voxel readout, we have developed a new technique to measure the perfusion in the rat gastrocnemius muscle at rest, yielding an average value of 19.4 +/- 4.8 mL/100 g/min (n = 22). In additional experiments, perfusion changes were elicited by acute ischemia and reperfusion or by exercise induced by electrical, noninvasive muscle stimulation with varying duration and intensity. The perfusion time courses during these manipulations were measured with a temporal resolution of 2.2 min, showing increases in perfusion of a factor of up to 2.5. In a direct comparison, the results agreed closely with values found with microsphere measurements in the same animals. The quantitative and noninvasive method can significantly facilitate the investigation of atherosclerotic diseases and the examination of drug efficacy.

  11. Determination of skeletal muscle perfusion using arterial spin labeling NMRI: validation by comparison with venous occlusion plethysmography.

    PubMed

    Raynaud, J S; Duteil, S; Vaughan, J T; Hennel, F; Wary, C; Leroy-Willig, A; Carlier, P G

    2001-08-01

    T(1)-based determination of perfusion was performed with the high temporal and spatial resolution that monitoring of exercise physiology requires. As no data were available on the validation of this approach in human muscles, T(1)-based NMRI of perfusion was compared to standard strain-gauge venous occlusion plethysmography performed simultaneously within a 4 T magnet. Two different situations were investigated in 21 healthy young volunteers: 1) a 5-min ischemia of the leg, or 2) a 2-3 min ischemic exercise consisting of a plantar flexion on an amagnetic ergometer. Leg perfusion was monitored over 5-15 min of the recovery phase, after the air-cuff arterial occlusion had been released. The interesting features of the sequence were the use of a saturation-recovery module for the introduction of a T(1) modulation and of single-shot spin echo for imaging. Spatial resolution was 1.7 x 2.0 mm and temporal resolution was 2 s. For data analysis, ROIs were traced on different muscles and perfusion was calculated from the differences in muscle signal intensity in successive images. To allow comparison with the global measurement of perfusion by plethysmography, the T(1)-based NMR measurements in exercising muscles were rescaled to the leg cross-section. The perfusion measurements obtained by plethysmography and NMRI were in close agreement with a correlation coefficient between 0.87 and 0.92. This indicates that pulsed arterial techniques provide determination of muscle perfusion not only with superior spatial and temporal resolution but also with exactitude.

  12. Near-infrared monitoring of perfusion and oxygen availability in abdominal organs and skeletal muscle during hypoxia

    NASA Astrophysics Data System (ADS)

    Maarek, Jean-Michel I.; Vari, Sandor G.; Marcu, Laura; Papaioannou, Thanassis; Pergadia, Vani R.; Snyder, Wendy J.; Grundfest, Warren S.

    1994-05-01

    Near-IR spectroscopy was used to quantify blood content and oxygenation dynamics in abdominal organs and skeletal muscle of 18 anesthetized rabbits during hypoxic hypoxia. Liver, kidney, and hindlimb muscle were exposed surgically. Laser diode pulses transmitted across the tissues were detected by means of a photomultiplier. The amount and redox level of tissue hemoglobin were estimated from the near-IR signals and monitored during 5- min-long hypoxic challenges and subsequent recovery periods. In the kidney, exposure to 10% FiO2 resulted in rapid and symmetrical changes in oxygenated and reduced hemoglobin with 50% of the variations occurring within 1 min and a plateau after 3 min. Total hemoglobin did not change and hemoglobin oxygenation returned to baseline within 1 min of hypoxia cessation. Exposure to 6% FiO2 doubled the decrease in oxygenated hemoglobin and induced a sustained vasoconstriction which decreased total hemoglobin content 2 min after initiation of hypoxia. Comparable patterns were observed in the liver and skeletal muscle with the following exceptions: local vasoconstriction was generally not observed at 6% FiO2, return to baseline oxygen availability was much slower in skeletal muscle than in the other organs.

  13. Insulin-induced changes in skeletal muscle microvascular perfusion are dependent upon perivascular adipose tissue in women.

    PubMed

    Meijer, Rick I; Serné, Erik H; Korkmaz, H Ibrahim; van der Peet, Donald L; de Boer, Michiel P; Niessen, Hans W M; van Hinsbergh, Victor W M; Yudkin, John S; Smulders, Yvo M; Eringa, Etto C

    2015-08-01

    Obesity increases the risk of cardiovascular disease and type 2 diabetes, partly through reduced insulin-induced microvascular vasodilation, which causes impairment of glucose delivery and uptake. We studied whether perivascular adipose tissue (PVAT) controls insulin-induced vasodilation in human muscle, and whether altered properties of PVAT relate to reduced insulin-induced vasodilation in obesity. Insulin-induced microvascular recruitment was measured using contrast enhanced ultrasound (CEU), before and during a hyperinsulinaemic-euglycaemic clamp in 15 lean and 18 obese healthy women (18-55 years). Surgical skeletal muscle biopsies were taken on a separate day to study perivascular adipocyte size in histological slices, as well as to study ex vivo insulin-induced vasoreactivity in microvessels in the absence and presence of PVAT in the pressure myograph. Statistical mediation of the relation between BMI and microvascular recruitment by PVAT was studied in a mediation model. Obese women showed impaired insulin-induced microvascular recruitment and lower metabolic insulin sensitivity compared with lean women. Microvascular recruitment was a mediator in the association between obesity and insulin sensitivity. Perivascular adipocyte size, determined in skeletal muscle biopsies, was larger in obese than in lean women, and statistically explained the difference in microvascular recruitment between obese and lean women. PVAT from lean women enhanced insulin-induced vasodilation in isolated skeletal muscle resistance arteries, while PVAT from obese women revealed insulin-induced vasoconstriction. PVAT from lean women enhances insulin-induced vasodilation and microvascular recruitment whereas PVAT from obese women does not. PVAT adipocyte size partly explains the difference in insulin-induced microvascular recruitment between lean and obese women.

  14. Supplementing essential amino acids with the nitric oxide precursor, l-arginine, enhances skeletal muscle perfusion without impacting anabolism in older men.

    PubMed

    Mitchell, W Kyle; Phillips, Bethan E; Wilkinson, Daniel J; Williams, John P; Rankin, Debbie; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J

    2016-10-06

    Postprandial limb blood flow and skeletal muscle microvascular perfusion reduce with aging. Here we tested the impact of providing bolus essential amino acids (EAA) in the presence and absence of the nitric oxide precursor, l-Arginine (ARG), upon skeletal muscle blood flow and anabolism in older men. Healthy young (YOUNG: 19.7 ± 0.5 y, N = 8) and older men (OLD, 70 ± 0.8 y, N = 8) received 15 g EAA or (older only) 15 g EAA +3 g ARG (OLD-ARG, 69.2 ± 1.2 y, N = 8). We quantified responses in muscle protein synthesis (MPS; incorporation of (13)C phenylalanine into myofibrillar proteins), leg and muscle microvascular blood flow (Doppler/contrast enhanced ultrasound (CEUS)) and insulin/EAA in response to EEA ± ARG. Plasma EAA increased similarly across groups but argininemia was evident solely in OLD-ARG (∼320 mmol, 65 min post feed); increases in plasma insulin (to ∼13 IU ml(-1)) were similar across groups. Increases in femoral flow were evident in YOUNG >2 h after feeding; these effects were blunted in OLD and OLD-ARG. Increases in microvascular blood volume (MBV) occurred only in YOUNG and these effects were isolated to the early postprandial phase (+45% at ∼45 min after feeding) coinciding with detectable arterio-venous differences in EAA reflecting net uptake by muscle. Increases in microvascular flow velocity (MFV) and tissue perfusion (MBV × MFV) occurred (∼2 h) in YOUNG and OLD-ARG, but not OLD. Postprandial protein accretion was greater in YOUNG than OLD or OLD-ARG; the latter two groups being indistinguishable. Therefore, ARG rescues aspects of muscle perfusion in OLD without impacting anabolic blunting, perhaps due to the "rescue" being beyond the period of active EAA-uptake.

  15. Continuous read-out of cytochrome b, flavin and pyridine nucleotide oxido-reduction processes in the perfused frog heart and contracting skeletal muscle.

    PubMed

    Rossini, L; Rossini, P; Chance, B

    1991-05-01

    The time-sharing instrument for continuous read-out of the fluorescence levels of NAD(P)H and oxidized-flavoproteins, which also makes simultaneous dual beam differential absorption measurements of cytochrome b, has been applied to the study of the metabolic control of the frog heart, perfused in vitro with normal and variously modified Ringer solutions, and to the frog skeletal muscle in situ. In the ionically depolarized resting heart, the long term kinetic analysis of the redox processes during oxygen/anoxia transitions has proved to be an adequate method for identifying and following three fundamental intracellular redox compartments: (1) the respiratory system, (2) the microsomal system, and (3) the glycolytic system. The provision of substrates and/or suitable inhibitors has allowed the description of functional interrelationships within the mitochondrial and the cytoplasmic spaces. The ouabain major site of response has been located on the cytosolic pyridine nucleotides, with a very small response in the mitochondrial space. The switching on and off of substantial fractions of the NAD(P)+/NAD(P)H and Fpoxidized/Fpreduced pools has been observed, which helps to clarify the large phase shift between the overall pyridine nucleotide and flavin oxidation-reduction processes, during the cycle of the spontaneously beating heart and during skeletal muscle contraction and recovery, here originally prompted out.

  16. Myoglobin Function in Exercising Skeletal Muscle

    NASA Astrophysics Data System (ADS)

    Cole, Randolph P.

    1982-04-01

    Short-term perfusion of the isolated dog gastrocnemius-plantaris muscle with hydrogen peroxide resulted in a decrease in steady-state muscle oxygen consumption and isometric tension generation. Hydrogen peroxide converted intracellular myoglobin to products incapable of combination with oxygen, but had no deleterious effect on neuromuscular transmission or on mitochondrial oxidative phosphorylation. It is concluded that functional intracellular myoglobin is important in maintaining oxygen consumption and tension generation in exercising skeletal muscle.

  17. Space travel directly induces skeletal muscle atrophy

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  18. Space travel directly induces skeletal muscle atrophy.

    PubMed

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

    1999-06-01

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

  19. Space travel directly induces skeletal muscle atrophy

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  20. Imaging of skeletal muscle.

    PubMed

    Goodwin, Douglas W

    2011-05-01

    Various diagnostic imaging techniques such as sonography, computed tomography, scintigraphy, radiography, and magnetic resonance imaging (MRI) have made possible the noninvasive evaluation of skeletal muscle injury and disease. Although these different modalities have roles to play, MRI is especially sensitive in the diagnosis of muscle disorders and injury and has proved to be useful in determining the extent of disease, in directing interventions, and in monitoring the response to therapies. This article describes how magnetic resonance images are formed and how the signal intensities in T1- and T2-weighted images may be used for diagnosis of the above-mentioned conditions and injuries. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Mechanotransduction in skeletal muscle

    PubMed Central

    Burkholder, Thomas J.

    2007-01-01

    Mechanical signals are critical to the development and maintenance of skeletal muscle, but the mechanisms that convert these shape changes to biochemical signals is not known. When a deformation is imposed on a muscle, changes in cellular and molecular conformations link the mechanical forces with biochemical signals, and the close integration of mechanical signals with electrical, metabolic, and hormonal signaling may disguise the aspect of the response that is specific to the mechanical forces. The mechanically induced conformational change may directly activate downstream signaling and may trigger messenger systems to activate signaling indirectly. Major effectors of mechanotransduction include the ubiquitous mitogen activated protein kinase (MAP) and phosphatidylinositol-3’ kinase (PI-3K), which have well described receptor dependent cascades, but the chain of events leading from mechanical stimulation to biochemical cascade is not clear. This review will discuss the mechanics of biological deformation, loading of cellular and molecular structures, and some of the principal signaling mechanisms associated with mechanotransduction. PMID:17127292

  2. Multiparametric assessment of vascular function in peripheral artery disease: dynamic measurement of skeletal muscle perfusion, blood-oxygen-level dependent signal, and venous oxygen saturation.

    PubMed

    Englund, Erin K; Langham, Michael C; Ratcliffe, Sarah J; Fanning, Molly J; Wehrli, Felix W; Mohler, Emile R; Floyd, Thomas F

    2015-04-01

    Endothelial dysfunction present in patients with peripheral artery disease may be better understood by measuring the temporal dynamics of blood flow and oxygen saturation during reactive hyperemia than by conventional static measurements. Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT), a recently developed MRI technique, was used to measure the response to an ischemia-reperfusion paradigm in 96 patients with peripheral artery disease of varying severity and 10 healthy controls. Perfusion, venous oxygen saturation SvO2, and T2* were each quantified in the calf at 2-s temporal resolution, yielding a dynamic time course for each variable. Compared with healthy controls, patients had a blunted and delayed hyperemic response. Moreover, patients with lower ankle-brachial index had (1) a more delayed reactive hyperemia response time, manifesting as an increase in time to peak perfusion in the gastrocnemius, soleus, and peroneus muscles, and in the anterior compartment, (2) an increase in the time to peak T2* measured in the soleus muscle, and (3) a prolongation of the posterior tibial vein SvO2 washout time. Intrasession and intersession repeatability were also assessed. Results indicated that time to peak perfusion and time to peak T2* were the most reliable extracted time course metrics. Perfusion, dynamic SvO2, and T2* response times after induced ischemia are highly correlated with peripheral artery disease severity. Combined imaging of peripheral microvascular blood flow and dynamics of oxygen saturation with Perfusion, intravascular SvO2, and T2* may be a useful tool to investigate the pathophysiology of peripheral artery disease. © 2015 American Heart Association, Inc.

  3. Multi-Parametric Assessment of Vascular Function in Peripheral Artery Disease: Dynamic Measurement of Skeletal Muscle Perfusion, BOLD Signal, and Venous Oxygen Saturation

    PubMed Central

    Englund, Erin K.; Langham, Michael C.; Ratcliffe, Sarah J.; Fanning, Molly; Wehrli, Felix W.; Mohler, Emile R.; Floyd, Thomas F.

    2015-01-01

    Background Endothelial dysfunction present in patients with peripheral artery disease (PAD) may be better understood by measuring the temporal dynamics of blood flow and oxygen saturation during reactive hyperemia than by conventional static measurements. Methods and Results Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT), a recently developed MRI technique, was used to measure the response to an ischemia-reperfusion paradigm in ninety-six patients with PAD of varying severity, and ten healthy controls. Perfusion, venous oxygen saturation (SvO2), and T2* were each quantified in the calf at two second temporal resolution, yielding a dynamic time course for each variable. Compared to healthy controls, patients had a blunted and delayed hyperemic response. Moreover, patients with lower ankle-brachial index had: 1) a more delayed reactive hyperemia response time, manifesting as an increase in time to peak perfusion in the gastrocnemius, soleus, and peroneus muscles, and in the anterior compartment; 2) an increase in the time to peak T2* measured in the soleus muscle; and 3) a prolongation of the posterior tibial vein SvO2 washout time. Intra- and inter-session repeatability was also assessed. Results indicated that time to peak perfusion and time to peak T2* were the most reliable extracted time course metrics. Conclusions Perfusion, dynamic SvO2, and T2* response times following induced ischemia are highly correlated with PAD disease severity. Combined imaging of peripheral microvascular blood flow and dynamics of oxygen saturation with PIVOT may be a useful tool to investigate the pathophysiology of PAD. PMID:25873722

  4. Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle.

    PubMed

    Hindel, Stefan; Sauerbrey, Anika; Maaß, Marc; Maderwald, Stefan; Schlamann, Marc; Lüdemann, Lutz

    2015-01-01

    The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the

  5. Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle

    PubMed Central

    Hindel, Stefan; Sauerbrey, Anika; Maaß, Marc; Maderwald, Stefan; Schlamann, Marc; Lüdemann, Lutz

    2015-01-01

    The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the

  6. Diffusion-weighted magnetic resonance imaging reveals the effects of different cooling temperatures on the diffusion of water molecules and perfusion within human skeletal muscle.

    PubMed

    Yanagisawa, O; Fukubayashi, T

    2010-11-01

    To evaluate the effect of local cooling on the diffusion of water molecules and perfusion within muscle at different cooling temperatures. Magnetic resonance diffusion-weighted (DW) images of the leg (seven males) were obtained before and after 30 min cooling (0, 10, and 20°C), and after a 30 min recovery period. Two types of apparent diffusion coefficient (ADC; ADC1, reflecting both water diffusion and perfusion within muscle, and ADC2, approximating the true water diffusion coefficient) of the ankle dorsiflexors were calculated from DW images. T2-weighted images were also obtained to calculate T2 values of the ankle dorsiflexors. The skin temperature was measured before, during, and after cooling. Both ADC values significantly decreased after cooling under all cooling conditions; the rate of decrease depended on the cooling temperature used (ADC1: -36% at 0°C, -27.8% at 10°C, and -22.6% at 20°C; ADC2: -26% at 0°C, -21.1% at 10°C, and -14.6% at 20°C). These significant decreases were maintained during the recovery period. Conversely, the T2 value showed no significant changes. Under all cooling conditions, skin temperature significantly decreased during cooling; the rate of decrease depended on the cooling temperature used (-74.8% at 0°C, -51.1% at 10°C, and -26.8% at 20°C). Decreased skin temperatures were not restored to pre-cooling values during the recovery period under any cooling conditions. Local cooling decreased the water diffusion and perfusion within muscle with decreased skin temperature; the rates of decrease depended on the cooling temperature used. These decreases were maintained for 30 min after cooling. Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  7. Localization of 3H-diethylstilbestrol in skeletal muscle

    SciTech Connect

    Gruber, B.; Cohen, L.

    1981-11-01

    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.

  8. Paraplegia increases skeletal muscle autophagy.

    PubMed

    Fry, Christopher S; Drummond, Micah J; Lujan, Heidi L; DiCarlo, Stephen E; Rasmussen, Blake B

    2012-11-01

    Paraplegia results in significant skeletal muscle atrophy through increases in skeletal muscle protein breakdown. Recent work has identified a novel SIRT1-p53 pathway that is capable of regulating autophagy and protein breakdown. Soleus muscle was collected from 6 male Sprague-Dawley rats 10 weeks after complete T4-5 spinal cord transection (paraplegia group) and 6 male sham-operated rats (control group). We utilized immunoblotting methods to measure intracellular proteins and quantitative real-time polymerase chain reaction to measure the expression of skeletal muscle microRNAs. SIRT1 protein expression was 37% lower, and p53 acetylation (LYS379) was increased in the paraplegic rats (P < 0.05). Atg7 and Beclin-1, markers of autophagy induction, were elevated in the paraplegia group compared with controls (P < 0.05). Severe muscle atrophy resulting from chronic paraplegia appears to increase skeletal muscle autophagy independent of SIRT1 signaling. We conclude that chronic paraplegia may cause an increase in autophagic cell death and negatively impact skeletal muscle protein balance. Copyright © 2012 Wiley Periodicals, Inc.

  9. Paraplegia increases skeletal muscle autophagy

    PubMed Central

    Fry, Christopher S.; Drummond, Micah J.; Lujan, Heidi L.; DiCarlo, Stephen E.; Rasmussen, Blake B.

    2012-01-01

    INTRODUCTION Paraplegia results in significant skeletal muscle atrophy through increases in skeletal muscle protein breakdown. Recent work has identified a novel SIRT1-p53 pathway that is capable of regulating autophagy and protein breakdown. METHODS Soleus muscle was collected from 6 male Sprague-Dawley rats 10 weeks following complete T(4)-T(5) spinal-cord transection (paraplegia) and 6 male sham-operated rats (control). We utilized immunoblotting methods to measure intracellular proteins and qRT-PCR to measure the expression of skeletal muscle microRNAs. RESULTS SIRT1 protein expression was 37% lower, and p53 acetylation (LYS379) was increased in the paraplegia rats (P<0.05). Atg7 and Beclin-1, markers of autophagy induction, were elevated in paraplegia compared to controls (P<0.05). DISCUSSION Severe muscle atrophy resulting from chronic paraplegia appears to increase skeletal muscle autophagy independent of SIRT1 signaling. We conclude that chronic paraplegia may cause an increase in autophagic cell-death and negatively impact skeletal muscle protein balance. PMID:23055316

  10. Skeletal Muscle Hypertrophy after Aerobic Exercise Training

    PubMed Central

    Konopka, Adam R.; Harber, Matthew P.

    2014-01-01

    Current dogma suggests aerobic exercise training has minimal effect on skeletal muscle size. We and others have demonstrated that aerobic exercise acutely and chronically alters protein metabolism and induces skeletal muscle hypertrophy. These findings promote an antithesis to the status quo by providing novel perspective on skeletal muscle mass regulation and insight into exercise-countermeasures for populations prone to muscle loss. PMID:24508740

  11. Skeletal muscle hypertrophy after aerobic exercise training.

    PubMed

    Konopka, Adam R; Harber, Matthew P

    2014-04-01

    Current dogma suggests that aerobic exercise training has minimal effects on skeletal muscle size. We and others have demonstrated that aerobic exercise acutely and chronically alters protein metabolism and induces skeletal muscle hypertrophy. These findings promote an antithesis to the status quo by providing novel perspective on skeletal muscle mass regulation and insight into exercise countermeasures for populations prone to muscle loss.

  12. Osmoregulatory processes and skeletal muscle metabolism

    NASA Astrophysics Data System (ADS)

    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

  13. Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells

    PubMed Central

    Tedesco, Francesco Saverio; Dellavalle, Arianna; Diaz-Manera, Jordi; Messina, Graziella; Cossu, Giulio

    2010-01-01

    Skeletal muscle damaged by injury or by degenerative diseases such as muscular dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends upon satellite cells, myogenic progenitors localized between the basal lamina and the muscle fiber membrane. However, other cell types outside the basal lamina, such as pericytes, also have myogenic potency. Here, we discuss the main properties of satellite cells and other myogenic progenitors as well as recent efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored cell therapy. Clinical trials utilizing these cells to treat muscular dystrophies, heart failure, and stress urinary incontinence are also briefly outlined. PMID:20051632

  14. Mechanisms modulating skeletal muscle phenotype.

    PubMed

    Blaauw, Bert; Schiaffino, Stefano; Reggiani, Carlo

    2013-10-01

    Mammalian skeletal muscles are composed of a variety of highly specialized fibers whose selective recruitment allows muscles to fulfill their diverse functional tasks. In addition, skeletal muscle fibers can change their structural and functional properties to perform new tasks or respond to new conditions. The adaptive changes of muscle fibers can occur in response to variations in the pattern of neural stimulation, loading conditions, availability of substrates, and hormonal signals. The new conditions can be detected by multiple sensors, from membrane receptors for hormones and cytokines, to metabolic sensors, which detect high-energy phosphate concentration, oxygen and oxygen free radicals, to calcium binding proteins, which sense variations in intracellular calcium induced by nerve activity, to load sensors located in the sarcomeric and sarcolemmal cytoskeleton. These sensors trigger cascades of signaling pathways which may ultimately lead to changes in fiber size and fiber type. Changes in fiber size reflect an imbalance in protein turnover with either protein accumulation, leading to muscle hypertrophy, or protein loss, with consequent muscle atrophy. Changes in fiber type reflect a reprogramming of gene transcription leading to a remodeling of fiber contractile properties (slow-fast transitions) or metabolic profile (glycolytic-oxidative transitions). While myonuclei are in postmitotic state, satellite cells represent a reserve of new nuclei and can be involved in the adaptive response. © 2013 American Physiological Society. Compr Physiol 3:1645-1687, 2013.

  15. Skeletal muscle satellite cells

    NASA Technical Reports Server (NTRS)

    Schultz, E.; McCormick, K. M.

    1994-01-01

    Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form

  16. Aging of skeletal muscle fibers.

    PubMed

    Miljkovic, Natasa; Lim, Jae-Young; Miljkovic, Iva; Frontera, Walter R

    2015-04-01

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

  17. The Skeletal Muscle Satellite Cell

    PubMed Central

    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. Taurine and skeletal muscle disorders.

    PubMed

    Conte Camerino, Diana; Tricarico, Domenico; Pierno, Sabata; Desaphy, Jean-François; Liantonio, Antonella; Pusch, Michael; Burdi, Rosa; Camerino, Claudia; Fraysse, Bodvael; De Luca, Annamaria

    2004-01-01

    Taurine is abundantly present in skeletal muscle. We give evidence that this amino acid exerts both short-term and long-term actions in the control of ion channel function and calcium homeostasis in striated fibers. Short-term actions can be estimated as the ability of this amino acid to acutely modulate both ion channel gating and the function of the structures involved in calcium handling. Long-term effects can be disclosed in situations of tissue taurine depletion and are likely related to the ability of the intracellular taurine to control transducing pathways as well as homeostatic and osmotic equilibrium in the tissue. The two activities are strictly linked because the intracellular level of taurine modulates the sensitivity of skeletal muscle to the exogenous application of taurine. Myopathies in which ion channels are directly or indirectly involved, as well as inherited or acquired pathologies characterized by metabolic alterations and change in calcium homeostasis, are often correlated with change in muscle taurine concentration and consequently with an enhanced therapeutic activity of this amino acid. We discuss both in vivo and in vitro evidence that taurine, through its ability to control sarcolemmal excitability and muscle contractility, can prove beneficial effects in many muscle dysfunctions.

  19. Effects of aestivation on skeletal muscle performance.

    PubMed

    James, Rob S

    2010-01-01

    Fitness, ecology, and behaviour of vertebrates are dependent upon locomotor performance. Locomotor performance can be constrained by underlying intrinsic skeletal muscle properties. Skeletal muscle is a highly plastic tissue undergoing phenotypic change in response to alteration in environment. Clinical and experimental models of muscle disuse cause decreases in skeletal muscle size and mechanical performance. However, in natural models of skeletal muscle disuse, both atrophy and changes in mechanical properties are more limited. Aestivation in frogs can cause decreases in muscle cross-sectional area and changes in some enzyme activities, with effects varying among muscles. However, long-term aestivation causes limited changes in muscle mechanics during simulated sprint or endurance type activities. Therefore, at least in frogs, there is maintenance of skeletal muscle performance during prolonged periods of aestivation, allowing avoidance of harsh environmental conditions without compromising the locomotor capacity to perform fitness-related activities when favourable environmental conditions return.

  20. Calf muscle perfusion as measured with magnetic resonance imaging to assess peripheral arterial disease.

    PubMed

    Brunner, Gerd; Bismuth, Jean; Nambi, Vijay; Ballantyne, Christie M; Taylor, Addison A; Lumsden, Alan B; Morrisett, Joel D; Shah, Dipan J

    2016-11-01

    We hypothesized that skeletal muscle perfusion is impaired in peripheral arterial disease (PAD) patients compared to healthy controls and that perfusion patterns exhibit marked differences across five leg muscle compartments including the anterior muscle group (AM), lateral muscle group (LM), deep posterior muscle group (DM), soleus (SM), and the gastrocnemius muscle (GM). A total of 40 individuals (26 PAD patients and 14 healthy controls) underwent contrast-enhanced magnetic resonance imaging (CE-MRI) utilizing a reactive hyperemia protocol. Muscle perfusion maps were developed for AM, LM, DM, SM, and GM. Perfusion maps were analyzed over the course of 2 min, starting at local pre-contrast arrival, to study early-to-intermediate gadolinium enhancement. PAD patients had a higher fraction of hypointense voxels at pre-contrast arrival for all five muscle compartments compared with healthy controls (p < 0.0005). Among PAD patients, the fraction of hypointense voxels of the AM, LM, and GM were inversely correlated with the estimated glomerular filtration rate (eGFR; r = -0.509, p = 0.008; r = -0.441, p = 0.024; and r = -0.431, p = 0.028, respectively). CE-MRI-based skeletal leg muscle perfusion is markedly reduced in PAD patients compared with healthy controls and shows heterogeneous patterns across calf muscle compartments.

  1. Muscle Bioenergetic Considerations for Intrinsic Laryngeal Skeletal Muscle Physiology

    ERIC Educational Resources Information Center

    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…

  2. Amino Acid Sensing in Skeletal Muscle.

    PubMed

    Moro, Tatiana; Ebert, Scott M; Adams, Christopher M; Rasmussen, Blake B

    2016-11-01

    Aging impairs skeletal muscle protein synthesis, leading to muscle weakness and atrophy. However, the underlying molecular mechanisms remain poorly understood. Here, we review evidence that mammalian/mechanistic target of rapamycin complex 1 (mTORC1)-mediated and activating transcription factor 4 (ATF4)-mediated amino acid (AA) sensing pathways, triggered by impaired AA delivery to aged skeletal muscle, may play important roles in skeletal muscle aging. Interventions that alleviate age-related impairments in muscle protein synthesis, strength, and/or muscle mass appear to do so by reversing age-related changes in skeletal muscle AA delivery, mTORC1 activity, and/or ATF4 activity. An improved understanding of the mechanisms and roles of AA sensing pathways in skeletal muscle may lead to evidence-based strategies to attenuate sarcopenia.

  3. Satellite cells: the architects of skeletal muscle.

    PubMed

    Chang, Natasha C; Rudnicki, Michael A

    2014-01-01

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

  4. Exercise Promotes Healthy Aging of Skeletal Muscle

    PubMed Central

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

    2016-01-01

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

  5. [Regeneration capacity of skeletal muscle].

    PubMed

    Wernig, A

    2003-07-01

    The organotypic stem cell of skeletal muscle has previously been known as satellite cell. They allow muscle fiber growth during ontogenesis, enable fiber hypertrophy and are responsible for the very efficient repair of muscle fibers. This efficient apparatus is to some degree counterbalanced by an enormous use of the satellite cell pool: fiber atrophy probably is accompanied by loss of myonuclei such that every reversal of atrophy is bound to use new myonuclei i.e. satellite cells. How often in life does this occur? Hard to say. Moreover, the potent repair capacity is challenged by an unexpected vulnerability of skeletal muscle fibers: Passive stretching of contracted muscles may cause multiple "microdamage," disruption of contractile elements or tiny areas of true necrosis (focal necrosis). How often does this happen? Well, for many of us at least once per year when we go up and down mountains during vacation time, followed by sour muscles. Others may decide to change his/her (locomotor) behaviour by severe onset of jogging; it may happen that they suffer kidney failure on Monday due to muscle microdamage and the transfer of myoproteins into the serum over weekend. Also 20 minutes of stepping up and down something like a chair will do: There is a remarkable increase in kreatin kinase and other muscle derived proteins which lasts for days and is bound to reflect some muscle damage. How about sportsmen and worker who repeatedly use their muscles in such a way? We don't have answers yet to most of these questions, but considerable amount of information has been collected over the last years both in animal and--less--in human. What is common in all cases of growth and repair is the proliferation of the satellite cells and their consequent incorporation and fusion with the parent fiber. This way focal damage is repaired often without visible reminders. We would run out of satellite cells were they not stem cells: After division one daughter remains a satellite cell

  6. Redox Control of Skeletal Muscle Regeneration.

    PubMed

    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.

  7. Signaling pathways controlling skeletal muscle mass.

    PubMed

    Egerman, Marc A; Glass, David J

    2014-01-01

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

  8. Signaling pathways controlling skeletal muscle mass

    PubMed Central

    Egerman, Marc A.

    2014-01-01

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

  9. Sympathetic actions on the skeletal muscle.

    PubMed

    Roatta, Silvestro; Farina, Dario

    2010-01-01

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

  10. Proteomic profiling of skeletal muscle plasticity.

    PubMed

    Ohlendieck, Kay

    2011-10-01

    One of the most striking physiological features of skeletal muscle tissues are their enormous capacity to adapt to changed functional demands. Muscle plasticity has been extensively studied by histological, biochemical, physiological and genetic methods over the last few decades. With the recent emergence of high-throughput and large-scale proteomic techniques, mass spectrometry-based surveys have also been applied to the global analysis of the skeletal muscle protein complement during physiological modifications and pathophysiological alterations. This review outlines and discusses the impact of recent proteomic profiling studies of skeletal muscle transitions, including the effects of chronic electro-stimulation, physical exercise, denervation, disuse atrophy, hypoxia, myotonia, motor neuron disease and age-related fibre type shifting. This includes studies on the human skeletal muscle proteome, animal models of muscle plasticity and major neuromuscular pathologies. The biomedical importance of establishing reliable biomarker signatures for the various molecular and cellular transition phases involved in muscle transformation is critically examined.

  11. REGULATION OF NADPH OXIDASES IN SKELETAL MUSCLE

    PubMed Central

    Ferreira, Leonardo F.; Laitano, Orlando

    2016-01-01

    The only known function of NAD(P)H oxidases is to produce reactive oxygen species (ROS). Skeletal muscles express three isoforms of NAD(P)H oxidases (Nox1, Nox2, and Nox4) that have been identified as critical modulators of redox homeostasis. Nox2 acts as the main source of skeletal muscle ROS during contractions, participates insulin signaling and glucose transport, and mediates the myocyte response to osmotic stress. Nox2 and Nox4 contribute to skeletal muscle abnormalities elicited by angiotensin II, muscular dystrophy, heart failure, and high fat diet. Our review addresses the expression and regulation of NAD(P)H oxidases with emphasis on aspects that are relevant to skeletal muscle. We also summarize: i) the most widely used NAD(P)H oxidases activity assays and inhibitors, and ii) studies that have defined Nox enzymes as protagonists of skeletal muscle redox homeostasis in a variety of health and disease conditions. PMID:27184955

  12. Angiotensin II: role in skeletal muscle atrophy.

    PubMed

    Cabello-Verrugio, Claudio; Córdova, Gonzalo; Salas, José Diego

    2012-09-01

    Skeletal muscle, the main protein reservoir in the body, is a tissue that exhibits high plasticity when exposed to changes. Muscle proteins can be mobilized into free amino acids when skeletal muscle wasting occurs, a process called skeletal muscle atrophy. This wasting is an important systemic or local manifestation under disuse conditions (e.g., bed rest or immobilization), in starvation, in older adults, and in several diseases. The molecular mechanisms involved in muscle wasting imply the activation of specific signaling pathways which ultimately manage muscle responses to modulate biological events such as increases in protein catabolism, oxidative stress, and cell death by apoptosis. Many factors have been involved in the generation and maintenance of atrophy in skeletal muscle, among them angiotensin II (Ang-II), the main peptide of renin-angiotensin system (RAS). Together with Ang-II, the angiotensin-converting enzyme (ACE) and the Ang-II receptor type 1 (AT-1 receptor) are expressed in skeletal muscle, forming an important local axis that can regulate its function. In many of the conditions that lead to muscle wasting, there is an impairment of RAS in a global or local fashion. At this point, there are several pieces of evidence that suggest the participation of Ang-II, ACE, and AT-1 receptor in the generation of skeletal muscle atrophy. Interestingly, the Ang-II participation in muscle atrophy is strongly ligated to the regulation of hypertrophic activity of factors such as insulin-like growth factor 1 (IGF-1). In this article, we reviewed the current state of Ang-II and RAS function on skeletal muscle wasting and its possible use as a therapeutic target to improve skeletal muscle function under atrophic conditions.

  13. Redox control of skeletal muscle atrophy

    PubMed Central

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

    2016-01-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown. PMID:26912035

  14. Channelopathies of skeletal muscle excitability

    PubMed Central

    Cannon, Stephen C.

    2016-01-01

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

  15. [Molecular mechanisms of skeletal muscle hypertrophy].

    PubMed

    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. Skeletal muscle-smooth muscle interaction: an unusual myoelastic system.

    PubMed

    Hikida, R S; Peterson, W J

    1983-09-01

    The serratus superficialis metapatagialis (SSM) of pigeons is a skeletal muscle with unusual properties. It lies between the ribs and the trailing edge of the wing, where it is attached to the skin by a system of smooth muscles having elastic tendons. Wing movements during flight induce marked changes in this muscle's length. The SSM inserts onto the deep fascia, and at its termination the skeletal muscle contains large numbers of microtubules. Many myofibrils attach to leptomeric organelles, which then attach to the terminal end of the skeletal muscle fiber. The deep fascia next connects to the dermis of the skin by bundles of smooth muscles that have elastic tendons at both ends. This system allows large movements of the muscle while preventing its fibers from overstretching. The movements and presumed forces acting at this muscle make the presence of sensory receptors such as muscle spindles unlikely. Spindles are absent in this muscle.

  17. [In vitro construction of skeletal muscle tissues.

    PubMed

    Morimoto, Yuya; Takeuchi, Shoji

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

  18. Satellite cells in human skeletal muscle plasticity.

    PubMed

    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.

  19. Lipid droplet dynamics in skeletal muscle.

    PubMed

    Bosma, Madeleen

    2016-01-15

    The skeletal muscle is subjected to high mechanical and energetic demands. Lipid droplets are an important source of energy substrates for the working muscle. Muscle cells contain a variety of lipid droplets, which are fundamentally smaller than those found in adipocytes. This translates into a greater lipid droplet surface area serving as the interface for intracellular lipid metabolism. The skeletal muscle has a high plasticity, it is subjected to major remodeling following training and detraining. This coincides with adaptations in lipid droplet characteristics and dynamics. The majority of lipid droplets in skeletal muscle are located in the subsarcolemmal region or in-between the myofibrils, in close vicinity to mitochondria. The vastly organized nature of skeletal muscle fibers limits organelle mobility. The high metabolic rate and substrate turnover in skeletal muscle demands a strict coordination of intramyocellular lipid metabolism and LD dynamics, in which lipid droplet coat proteins play an important role. This review provides insights into the characteristics, diversity and dynamics of skeletal muscle lipid droplets.

  20. Cardiac and skeletal muscle myosin polymorphism.

    PubMed

    Lowey, S

    1986-06-01

    Skeletal muscles, unlike cardiac tissue, express several myosin isozymes during development which differ in primary structure from adult myosin. Monoclonal antibodies have shown the presence of at least two embryonic myosins, followed by a post-hatch myosin that persists until the appearance of adult myosin in chicken pectoralis muscle. Although the two major cardiac isozymes differ in enzymatic activity, the avian skeletal myosin isozymes all share the same high level of ATPase activity found for adult pectoralis myosin. The functional basis for the extensive myosin polymorphism in skeletal muscles thus remains to be determined.

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

    SciTech Connect

    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. Growth Factors and Tension-Induced Skeletal Muscle Growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1994-01-01

    have performed experiments to determine whether mechanical stimulation of cultured avian muscle cells alters their response to anabolic steroids or glucocorticoids. In static cultures, testosterone had no effect on muscle cell growth, but 5alpha-dihydrotestosterone and the synthetic steroid stanozolol increased cell growth by up to 18% and 30%, respectively, after a three day exposure. We completed development of a new IBM-based mechanical cell stimulator system to provide greater flexibility in operating and monitoring our experiments. Our previous long term studies on myofiber growth were designed around a perfusion system of our own design. We have recently changed to performing these studies using a modified CELLCO cartridge bioreactor system Z since it has been certified as the ground-based model for the Shuttle's Space Tissue Loss (STL) F= Cell Culture Module. The current goals of this aspect of the project are three fold: 1) to design a Z cell culture system for studying avian skeletal myofiber atrophy on the Shuttle and Space Station; 0 2) to expand the use of bioreactors to cells which do not grow in either suspension or attached to the hollow fibers; and 3) to combine the bioreactor system with our computerized mechanical cell stimulator to have a better in vitro model to study tension/gravity/stretch regulation of skeletal muscle size. Preliminary studies also reported on involved : (1) how release of tension can induce rapid atrophy of tissues cultured avian skeletal muscle cells, and (2) a mechanism to transfer and maintain avian skeletal muscle organoids in modified cartridges in the Space Tissue Loss Module.

  3. Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival.

    PubMed

    Carroll, C M; Carroll, S M; Overgoor, M L; Tobin, G; Barker, J H

    1997-07-01

    Ischemic preconditioning of the myocardium with repeated brief periods of ischemia and reperfusion prior to prolonged ischemia significantly reduces subsequent myocardial infarction. Following ischemic preconditioning, two "windows of opportunity" (early and late) exist, during which time prolonged ischemia can occur with reduced infarction size. The early window occurs at approximately 4 hours and the late window at 24 hours following ischemic preconditioning of the myocardium. We investigated if ischemic preconditioning of skeletal muscle prior to flap creation improved subsequent flap survival and perfusion immediately or 24 hours following ischemic preconditioning. Currently, no data exist on the utilization of ischemic preconditioning in this fashion. The animal model used was the latissimus dorsi muscle of adult male Sprague-Dawley rats. Animals were assigned to three groups, and the right or left latissimus dorsi muscle was chosen randomly in each animal. Group 1 (n = 12) was the control group, in which the entire latissimus dorsi muscle was elevated acutely without ischemic preconditioning. Group 2 (n = 8) investigated the effects of ischemic preconditioning in the early window. In this group, the latissimus dorsi muscle was elevated immediately following preconditioning. Group 3 (n = 8) investigated the effects of ischemic preconditioning in the late window, with elevation of the latissimus dorsi muscle 24 hours following ischemic preconditioning. The preconditioning regimen used in groups 2 and 3 was two 30-minute episodes of normothermic global ischemia with intervening 10-minute episodes of reperfusion. Latissimus dorsi muscle ischemia was created by occlusion of the thoracodorsal artery and vein and the intercostal perforators, after isolation of the muscle on these vessels. Muscle perfusion was assessed by a laser-Doppler perfusion imager. One week after flap elevation, muscle necrosis was quantified in all groups by means of computer-assisted digital

  4. Skeletal muscle vasodilatation during maximal exercise in health and disease

    PubMed Central

    Calbet, Jose A L; Lundby, Carsten

    2012-01-01

    Maximal exercise vasodilatation results from the balance between vasoconstricting and vasodilating signals combined with the vascular reactivity to these signals. During maximal exercise with a small muscle mass the skeletal muscle vascular bed is fully vasodilated. During maximal whole body exercise, however, vasodilatation is restrained by the sympathetic system. This is necessary to avoid hypotension since the maximal vascular conductance of the musculature exceeds the maximal pumping capacity of the heart. Endurance training and high-intensity intermittent knee extension training increase the capacity for maximal exercise vasodilatation by 20–30%, mainly due to an enhanced vasodilatory capacity, as maximal exercise perfusion pressure changes little with training. The increase in maximal exercise vascular conductance is to a large extent explained by skeletal muscle hypertrophy and vascular remodelling. The vasodilatory capacity during maximal exercise is reduced or blunted with ageing, as well as in chronic heart failure patients and chronically hypoxic humans; reduced vasodilatory responsiveness and increased sympathetic activity (and probably, altered sympatholysis) are potential mechanisms accounting for this effect. Pharmacological counteraction of the sympathetic restraint may result in lower perfusion pressure and reduced oxygen extraction by the exercising muscles. However, at the same time fast inhibition of the chemoreflex in maximally exercising humans may result in increased vasodilatation, further confirming a restraining role of the sympathetic nervous system on exercise-induced vasodilatation. This is likely to be critical for the maintenance of blood pressure in exercising patients with a limited heart pump capacity. PMID:23027820

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

    PubMed

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

    2015-11-01

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

  6. Skeletal muscle design to meet functional demands.

    PubMed

    Lieber, Richard L; Ward, Samuel R

    2011-05-27

    Skeletal muscles are length- and velocity-sensitive force producers, constructed of a vast array of sarcomeres. Muscles come in a variety of sizes and shapes to accomplish a wide variety of tasks. How does muscle design match task performance? In this review, we outline muscle's basic properties and strategies that are used to produce movement. Several examples are provided, primarily for human muscles, in which skeletal muscle architecture and moment arms are tailored to a particular performance requirement. In addition, the concept that muscles may have a preferred sarcomere length operating range is also introduced. Taken together, the case is made that muscles can be fine-tuned to perform specific tasks that require actuators with a wide range of properties.

  7. Skeletal muscle design to meet functional demands

    PubMed Central

    Lieber, Richard L.; Ward, Samuel R.

    2011-01-01

    Skeletal muscles are length- and velocity-sensitive force producers, constructed of a vast array of sarcomeres. Muscles come in a variety of sizes and shapes to accomplish a wide variety of tasks. How does muscle design match task performance? In this review, we outline muscle's basic properties and strategies that are used to produce movement. Several examples are provided, primarily for human muscles, in which skeletal muscle architecture and moment arms are tailored to a particular performance requirement. In addition, the concept that muscles may have a preferred sarcomere length operating range is also introduced. Taken together, the case is made that muscles can be fine-tuned to perform specific tasks that require actuators with a wide range of properties. PMID:21502118

  8. Heterogeneous ageing of skeletal muscle microvascular function.

    PubMed

    Muller-Delp, Judy M

    2016-04-15

    The distribution of blood flow to skeletal muscle during exercise is altered with advancing age. Changes in arteriolar function that are muscle specific underlie age-induced changes in blood flow distribution. With advancing age, functional adaptations that occur in resistance arterioles from oxidative muscles differ from those that occur in glycolytic muscles. Age-related adaptations of morphology, as well as changes in both endothelial and vascular smooth muscle signalling, differ in muscle of diverse fibre type. Age-induced endothelial dysfunction has been reported in most skeletal muscle arterioles; however, unique alterations in signalling contribute to the dysfunction in arterioles from oxidative muscles as compared with those from glycolytic muscles. In resistance arterioles from oxidative muscle, loss of nitric oxide signalling contributes significantly to endothelial dysfunction, whereas in resistance arterioles from glycolytic muscle, alterations in both nitric oxide and prostanoid signalling underlie endothelial dysfunction. Similarly, adaptations of the vascular smooth muscle that occur with advancing age are heterogeneous between arterioles from oxidative and glycolytic muscles. In both oxidative and glycolytic muscle, late-life exercise training reverses age-related microvascular dysfunction, and exercise training appears to be particularly effective in reversing endothelial dysfunction. Patterns of microvascular ageing that develop among muscles of diverse fibre type and function may be attributable to changing patterns of physical activity with ageing. Importantly, aerobic exercise training, initiated even at an advanced age, restores muscle blood flow distribution patterns and vascular function in old animals to those seen in their young counterparts.

  9. Male ironman triathletes lose skeletal muscle mass.

    PubMed

    Knechtle, Beat; Baumann, Barbara; Wirth, Andrea; Knechtle, Patrizia; Rosemann, Thomas

    2010-01-01

    We investigated whether male triathletes in an Ironman triathlon lose body mass in the form of fat mass or skeletal muscle mass in a field study at the Ironman Switzerland in 27 male Caucasian non-professional Ironman triathletes. Pre- and post-race body mass, fat mass and skeletal muscle mass were determined. In addition, total body water, hematological and urinary parameters were measured in order to quantify hydration status. Body mass decreased by 1.8 kg (p< 0.05), skeletal muscle decreased by 1.0 kg (p< 0.05) whereas fat mass showed no changes. Urinary specific gravity, plasma urea and plasma volume increased (p< 0.05). Pre- to post-race change (Delta) in body mass was not associated with ? skeletal muscle mass. Additionally, there was no association between Delta plasma urea and Delta skeletal muscle mass; Delta plasma volume was not associated with Delta total body water (p< 0.05). We concluded that male triathletes in an Ironman triathlon lose 1.8 kg of body mass and 1 kg of skeletal muscle mass, presumably due to a depletion of intramyocellular stored glycogen and lipids.

  10. ISOLATION OF SKELETAL MUSCLE NUCLEI

    PubMed Central

    Edelman, Jean C.; Edelman, P. Michael; Knigge, Karl M.; Schwartz, Irving L.

    1965-01-01

    A method employing aqueous media for isolation of nuclei from rat skeletal muscle is described. The technique involves (a) mincing and then homogenizing in a 0.32 M sucrose-salt solution with a Potter-Elvehjem type homogenizer using a Delrin (an acetal resin) pestle and a carefully controlled, relatively large pestle-to-glass clearance, (b) filtering through fiberglass and stainless steel screens of predetermined mesh size to remove myofibrils and connective tissue, and (c) centrifuging in a 2.15 M sucrose-salt solution containing 0.7 mM ATP. Electron and phase-contrast microscopic observations show that the nuclei are intact, unencumbered by cytoplasmic tags, and possess well preserved distinct nucleoli, nucleoplasm, and nuclear membranes. Cytoplasmic contamination is minimal and mainly mitochondrial. Chemical assays of the nuclear fraction show that the DNA/protein and RNA/DNA ratios are comparable to those obtained in other tissues. These ratios, as well as the low specific activity obtained for cytochrome c oxidase and the virtual absence of myofibrillar ATPase, indicate a high degree of purity with minimal mitochondrial and myofibrillar contamination. The steps comprising the technique and the reasons for their selection are discussed. PMID:4287141

  11. Skeletal muscle weakness in osteogeneis imperfecta mice

    PubMed Central

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

    2010-01-01

    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 (Po, Po/mg and Po/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased Po and an inability to sustain Po 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. PMID:20619344

  12. Do inflammatory cells influence skeletal muscle hypertrophy?

    PubMed

    Koh, Timothy J; Pizza, Francis X

    2009-06-01

    Most research on muscle hypertrophy has focused on the responses of muscle cells to mechanical loading; however, a number of studies also suggest that inflammatory cells may influence muscle hypertrophy. Neutrophils and macrophages accumulate in skeletal muscle following increased mechanical loading, and we have demonstrated that macrophages are essential for hypertrophy following synergist ablation. Whether neutrophils are required remains to be determined. Non-steroidal anti-inflammatory drugs impair adaptive responses of skeletal muscle in both human and animal experiments suggesting that the routine use of such drugs could impair muscle performance. Much remains to be learned about the role of inflammatory cells in muscle hypertrophy, including the molecular signals involved in calling neutrophils and macrophages to skeletal muscle as well as those that regulate their function in muscle. In addition, although we have demonstrated that macrophages produce growth promoting factors during muscle hypertrophy, the full range of functional activities involved in muscle hypertrophy remains to be determined. Further investigation should provide insight into the intriguing hypothesis that inflammatory cells play integral roles in regulating muscle hypertrophy.

  13. Pleiotropic effects of sphingolipids in skeletal muscle.

    PubMed

    Bruni, P; Donati, C

    2008-11-01

    Studies of the last two decades have demonstrated that sphingolipids are important signalling molecules exerting key roles in the control of fundamental biological processes including proliferation, differentiation, motility and survival. Here we review the role of bioactive sphingolipids such as ceramide, sphingosine, sphingosine 1-phosphate, ganglioside GM3, in the regulation of skeletal muscle biology. The emerging picture is in favour of a complex role of these molecules, which appear implicated in the activation of muscle resident stem cells, their proliferation and differentiation, finalized at skeletal muscle regeneration. Moreover, they are involved in the regulation of contractile properties, tissue responsiveness to insulin and muscle fiber trophism. Hopefully, this article will provide a framework for future investigation into the field, aimed at establishing whether altered sphingolipid metabolism is implicated in the onset of skeletal muscle diseases and identifying new pharmacological targets for the therapy of multiple illnesses, including muscular dystrophies and diabetes.

  14. Skeletal muscle tensile strain dependence: hyperviscoelastic nonlinearity

    PubMed Central

    Wheatley, Benjamin B; Morrow, Duane A; Odegard, Gregory M; Kaufman, Kenton R; Donahue, Tammy L Haut

    2015-01-01

    Introduction Computational modeling of skeletal muscle requires characterization at the tissue level. While most skeletal muscle studies focus on hyperelasticity, the goal of this study was to examine and model the nonlinear behavior of both time-independent and time-dependent properties of skeletal muscle as a function of strain. Materials and Methods Nine tibialis anterior muscles from New Zealand White rabbits were subject to five consecutive stress relaxation cycles of roughly 3% strain. Individual relaxation steps were fit with a three-term linear Prony series. Prony series coefficients and relaxation ratio were assessed for strain dependence using a general linear statistical model. A fully nonlinear constitutive model was employed to capture the strain dependence of both the viscoelastic and instantaneous components. Results Instantaneous modulus (p<0.0005) and mid-range relaxation (p<0.0005) increased significantly with strain level, while relaxation at longer time periods decreased with strain (p<0.0005). Time constants and overall relaxation ratio did not change with strain level (p>0.1). Additionally, the fully nonlinear hyperviscoelastic constitutive model provided an excellent fit to experimental data, while other models which included linear components failed to capture muscle function as accurately. Conclusions Material properties of skeletal muscle are strain-dependent at the tissue level. This strain dependence can be included in computational models of skeletal muscle performance with a fully nonlinear hyperviscoelastic model. PMID:26409235

  15. Systemic skeletal muscle necrosis induced by crotoxin.

    PubMed

    Salvini, T F; Amaral, A C; Miyabara, E H; Turri, J A; Danella, P M; Selistre de Araújo, H S

    2001-08-01

    Systemic skeletal muscle necrosis induced by crotoxin, the major component of the venom of Crotalus durissus terrificus, was investigated. Mice received an intramuscular injection of crotoxin (0.35mg/kg body weight) into the right tibialis anterior (TA) muscles, which were evaluated 3h, 24h and 3 days later. Control mice were injected with saline. Right and left TAs, gastrocnemius, soleus and right masseter and longissimus dorsi were removed and frozen. Histological sections were stained with Toluidine Blue or incubated for acidic phosphatase reaction. Three and 24h after the injection, signals of muscle fiber injury were found: (a) in the injected TA muscles; (b) in both right and contralateral soleus and red gastrocnemius; and (c) in the masseter muscles. Contralateral TA, longissimus dorsi and white gastrocnemius muscles were not injured. In conclusion, crotoxin induced a systemic and selective muscle injury in muscles or muscle regions composed by oxidative muscle fibers.

  16. Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Oyama, J.

    1981-01-01

    Rats induced into a hypermetabolic state by exposure to chronic (7 mo) centrifugation at 4.15 g exhibited increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. In order to determine the insulin sensitivity of specific tissues, the effect of exogenous insulin on glucose uptake by isolated perfused livers and hindlim skeletal muscle from rats adapted to chronic centrifugation for one year was compared with perfused tissue from 2.5 mo-old noncentrifuged control animals of equal body weight. Metabolic glucose clearance by skeletal muscle from hypergravic rats did not prove significantly greater than control muscle when perfused in the absence of insulin (10.6 vs 8.1 microliters/min-g-muscle), but was twice as fast (23.0 vs 9.5) at perfusate insulin levels of 35 micro-U/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P is less than 0.001) compared with control livers (10.3 vs 27.8) at perfusate insulin levels of 40 micro-U/ml. Results suggest that skeletal muscle rather than liver is primarily responsible for the enhanced sensitivity to insulin and the increased energy expenditure observed in rats subjected to hypergravity.

  17. Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Oyama, J.

    1981-01-01

    Rats induced into a hypermetabolic state by exposure to chronic (7 mo) centrifugation at 4.15 g exhibited increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. In order to determine the insulin sensitivity of specific tissues, the effect of exogenous insulin on glucose uptake by isolated perfused livers and hindlim skeletal muscle from rats adapted to chronic centrifugation for one year was compared with perfused tissue from 2.5 mo-old noncentrifuged control animals of equal body weight. Metabolic glucose clearance by skeletal muscle from hypergravic rats did not prove significantly greater than control muscle when perfused in the absence of insulin (10.6 vs 8.1 microliters/min-g-muscle), but was twice as fast (23.0 vs 9.5) at perfusate insulin levels of 35 micro-U/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P is less than 0.001) compared with control livers (10.3 vs 27.8) at perfusate insulin levels of 40 micro-U/ml. Results suggest that skeletal muscle rather than liver is primarily responsible for the enhanced sensitivity to insulin and the increased energy expenditure observed in rats subjected to hypergravity.

  18. Skeletal muscle aging and the mitochondria

    PubMed Central

    Johnson, Matthew L.; Robinson, Matthew M.; Nair, K. Sreekumaran

    2013-01-01

    The decline in human muscle mass and strength (sarcopenia) is a hallmark of the aging process. A growing body of research in the areas of bioenergetics and protein turnover has placed the mitochondria at the center of this process. It is now clear that unless an active life style is rigorously followed, skeletal muscle mitochondrial decline occurs as humans’ age. Increasing research on mitochondrial biology has elucidated the regulatory pathways involved in mitochondrial biogenesis, many of which are potential therapeutic targets, and highlight the beneficial effects of vigorous physical activity on skeletal muscle health for an aging population. PMID:23375520

  19. Impedance plethysmography: a new method for continuous muscle perfusion monitoring.

    PubMed

    Concannon, M J; Stewart, D H; Welsh, C F; Puckett, C L

    1991-08-01

    Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion.

  20. The benefits of coffee on skeletal muscle.

    PubMed

    Dirks-Naylor, Amie J

    2015-12-15

    Coffee is consumed worldwide with greater than a billion cups of coffee ingested every day. Epidemiological studies have revealed an association of coffee consumption with reduced incidence of a variety of chronic diseases as well as all-cause mortality. Current research has primarily focused on the effects of coffee or its components on various organ systems such as the cardiovascular system, with relatively little attention on skeletal muscle. Summary of current literature suggests that coffee has beneficial effects on skeletal muscle. Coffee has been shown to induce autophagy, improve insulin sensitivity, stimulate glucose uptake, slow the progression of sarcopenia, and promote the regeneration of injured muscle. Much more research is needed to reveal the full scope of benefits that coffee consumption may exert on skeletal muscle structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Coaxing stem cells for skeletal muscle repair

    PubMed Central

    McCullagh, Karl J.A.; Perlingeiro, Rita C. R.

    2014-01-01

    Skeletal muscle has a tremendous ability to regenerate, attributed to a well-defined population of muscle stem cells called satellite cells. However, this ability to regenerate diminishes with age and can also be dramatically affected by multiple types of muscle diseases, or injury. Extrinsic and/or intrinsic defects in the regulation of satellite cells are considered to be major determinants for the diminished regenerative capacity. Maintenance and replenishment of the satellite cell pool is one focus for muscle regenerative medicine, which will be discussed. There are other sources of progenitor cells with myogenic capacity, which may also support skeletal muscle repair. However, all of these myogenic cell populations have inherent difficulties and challenges in maintaining or coaxing their derivation for therapeutic purpose. This review will highlight recent reported attributes of these cells and new bioengineering approaches to creating a supply of myogenic stem cells or implants applicable for acute and/or chronic muscle disorders. PMID:25049085

  2. Denervation and reinnervation of skeletal muscle

    NASA Technical Reports Server (NTRS)

    Mayer, R. F.; Max, S. R.

    1983-01-01

    A review is presented of the physiological and biochemical changes that occur in mammalian skeletal muscle after denervation and reinnervation. These changes are compared with those observed after altered motor function. Also considered is the nature of the trophic influence by which nerves control muscle properties. Topics examined include the membrane and contractile properties of denervated and reinnervated muscle; the cholinergic proteins, such as choline acetyltransferase, acetylcholinesterase, and the acetylcholine receptor; and glucose-6-phosphate dehydrogenase.

  3. Regulation of Nucleocytoplasmic Transport in Skeletal Muscle

    PubMed Central

    Hall, Monica N.; Corbett, Anita H.; Pavlath, Grace K.

    2015-01-01

    Proper skeletal muscle function is dependent on spatial and temporal control of gene expression in multinucleated myofibers. In addition, satellite cells, which are tissue-specific stem cells that contribute critically to repair and maintenance of skeletal muscle, are also required for normal muscle physiology. Gene expression in both myofibers and satellite cells is dependent upon nuclear proteins that require facilitated nuclear transport. A unique challenge for myofibers is controlling the transcriptional activity of hundreds of nuclei in a common cytoplasm yet achieving nuclear selectivity in transcription at specific locations such as neuromuscular synapses and myotendinous junctions. Nucleocytoplasmic transport of macromolecular cargoes is regulated by a complex interplay among various components of the nuclear transport machinery, namely nuclear pore complexes, nuclear envelope proteins, and various soluble transport receptors. The focus of this review is to highlight what is known about the nuclear transport machinery and its regulation in skeletal muscle and to consider the unique challenges that multinucleated muscle cells as well as satellite cells encounter in regulating nucleocytoplasmic transport during cell differentiation and tissue adaptation. Understanding how regulated nucleocytoplasmic transport controls gene expression in skeletal muscle may lead to further insights into the mechanisms contributing to muscle growth and maintenance throughout the lifespan of an individual. PMID:21621074

  4. Leucine stimulation of skeletal muscle protein synthesis

    SciTech Connect

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

    1986-03-01

    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 /sup 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.

  5. Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.

    PubMed

    Râdegran, G; Blomstrand, E; Saltin, B

    1999-12-01

    The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O(2) uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233-249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the (133)Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O(2) uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 +/- 0.17 (range 1. 31-3.27) liters, corresponding to 2.48 +/- 0.18 (range 1.37-3.43) kg. Anthropometry overestimated the muscle volume by approximately 21-46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 +/- 7 (range 55-100) W rendered peak values for leg blood flow (thermodilution) of 5.99 +/- 0.66 (range 4.15-9.52) l/min and leg O(2) uptake of 856 +/- 109 (range 590-1,521) ml/min. Muscle perfusion and O(2) uptake reached peak values of 246 +/- 24 (range 149-373) and 35.2 +/- 3.7 (range 22.6-59. 6) ml. min(-1). 100 g muscle(-1), respectively. These peak values are approximately 19-33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O(2) uptake in human skeletal muscle may be up to approximately 30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow

  6. Generalized Model of a Skeletal Muscle

    NASA Astrophysics Data System (ADS)

    Shil'ko, S. V.; Chernous, D. A.; Bondarenko, K. K.

    2016-01-01

    A new phenomenological model of a skeletal muscle consisting of a contractile and two nonlinear viscoelastic elements is proposed. The corresponding system of differential equations of the model is obtained, which allows one to derive time-dependent relations between the axial stress and the longitudinal strain in passive and activated states of the muscle. Methods for determining the viscoelastic and functional characteristics of the muscle as input parameters of the equations mentioned above are developed. These methods are based on the joint application of known experimental relations for a single muscle fiber and the results of muscle indentation in vivo on a "Miometer UT 98-01" device.

  7. Human Skeletal Muscle Health with Spaceflight

    NASA Astrophysics Data System (ADS)

    Trappe, Scott

    2012-07-01

    This lecture will overview the most recent aerobic and resistance exercise programs used by crewmembers while aboard the International Space Station (ISS) for six months and examine its effectiveness for protecting skeletal muscle health. Detailed information on the exercise prescription program, whole muscle size, whole muscle performance, and cellular data obtained from muscle biopsy samples will be presented. Historically, detailed information on the exercise program while in space has not been available. These most recent exercise and muscle physiology findings provide a critical foundation to guide the exercise countermeasure program forward for future long-duration space missions.

  8. Molecular regulation of skeletal muscle mass.

    PubMed

    Russell, Aaron P

    2010-03-01

    1. The maintenance of skeletal muscle mass is determined by a fine balance between protein synthesis and protein degradation. Skeletal mass is increased when there is a net gain in protein synthesis, which can occur following progressive exercise training. In contrast, skeletal muscle mass is lost when degradation occurs more rapidly than synthesis and is observed in numerous conditions, including neuromuscular disease, chronic disease, ageing, as well as following limb immobilization or prolonged bed rest due to injury or trauma. 2. Understanding the molecular pathways that regulate skeletal muscle protein synthesis and degradation is vital for identifying potential therapeutic targets that can attenuate muscle atrophy during disease and disuse. 3. The regulation of skeletal mass is complex and involves the precise coordination of several intracellular signalling pathways. The present review focuses on the role and regulation of pathways involving Akt, atrogin-1 and muscle ring finger-1 (MuRF1; atrogenes), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) and striated activator of Rho signalling (STARS), with exercise and disease.

  9. Regulation and phylogeny of skeletal muscle regeneration.

    PubMed

    Baghdadi, Meryem B; Tajbakhsh, Shahragim

    2017-08-12

    One of the most fascinating questions in regenerative biology is why some animals can regenerate injured structures while others cannot. Skeletal muscle has a remarkable capacity to regenerate even after repeated traumas, yet limited information is available on muscle repair mechanisms and how they have evolved. For decades, the main focus in the study of muscle regeneration was on muscle stem cells, however, their interaction with their progeny and stromal cells is only starting to emerge, and this is crucial for successful repair and re-establishment of homeostasis after injury. In addition, numerous murine injury models are used to investigate the regeneration process, and some can lead to discrepancies in observed phenotypes. This review addresses these issues and provides an overview of the some of the main regulatory cellular and molecular players involved in skeletal muscle repair. Copyright © 2017. Published by Elsevier Inc.

  10. Lactate oxidation in human skeletal muscle mitochondria.

    PubMed

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

    2013-04-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we analyze the ability of skeletal muscle to respire lactate by using an in situ mitochondrial preparation that leaves the native tubular reticulum and subcellular interactions of the organelle unaltered. Skeletal muscle biopsies were obtained from vastus lateralis muscle in 16 human subjects. Samples were chemically permeabilized with saponin, which selectively perforates the sarcolemma and facilitates the loss of cytosolic content without altering mitochondrial membranes, structure, and subcellular interactions. High-resolution respirometry was performed on permeabilized muscle biopsy preparations. By use 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 the mitochondrial intermembrane space with the pyruvate subsequently taken into the mitochondrial matrix where it enters the TCA cycle and is ultimately oxidized.

  11. Role of skeletal muscle in lung development.

    PubMed

    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.

  12. Gene Regions Responding to Skeletal Muscle Atrophy

    NASA Technical Reports Server (NTRS)

    Booth, Frank W.

    1997-01-01

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

  13. Skeletal muscle as an endogenous nitrate reservoir

    PubMed Central

    Piknova, Barbora; Park, Ji Won; Swanson, Kathryn M.; Dey, Soumyadeep; Noguchi, Constance Tom; Schechter, Alan N

    2015-01-01

    The nitric oxide synthase (NOS) family of enzymes form nitric oxide (NO) from arginine in the presence of oxygen. At reduced oxygen availability NO is also generated from nitrate in a two step process by bacterial and mammalian molybdopterin proteins, and also directly from nitrite by a variety of five-coordinated ferrous hemoproteins. The mammalian NO cycle also involves direct oxidation of NO to nitrite, and both NO and nitrite to nitrate by oxy-ferrous hemoproteins. The liver and blood are considered the sites of active mammalian NO metabolism and nitrite and nitrate concentrations in the liver and blood of several mammalian species, including human, have been determined. However, the large tissue mass of skeletal muscle had not been generally considered in the analysis of the NO cycle, in spite of its long-known presence of significant levels of active neuronal NOS (nNOS or NOS1). We hypothesized that skeletal muscle participates in the NO cycle and, due to its NO oxidizing heme protein, oxymyoglobin, has high concentrations of nitrate ions. We measured nitrite and nitrate concentrations in rat and mouse leg skeletal muscle and found unusually high concentrations of nitrate but similar levels of nitrite, when compared to the liver. The nitrate reservoir in muscle is easily accessible via the bloodstream and therefore nitrate is available for transport to internal organs where it can be reduced to nitrite and NO. Nitrate levels in skeletal muscle and blood in nNOS−/− mice were dramatically lower when compared with controls, which support further our hypothesis. Although the nitrate reductase activity of xanthine oxidoreductase in muscle is less than that of liver, the residual activity in muscle could be very important in view of its total mass and the high basal level of nitrate. We suggest that skeletal muscle participates in overall NO metabolism, serving as a nitrate reservoir, for direct formation of nitrite and NO, and for determining levels of nitrate

  14. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent.

    PubMed

    Jeppesen, J; Albers, P H; Rose, A J; Birk, J B; Schjerling, P; Dzamko, N; Steinberg, G R; Kiens, B

    2011-04-01

    The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat hindlimb. Exercise induced a similar increase in skeletal muscle cell surface membrane FAT/CD36 content in WT (+34%) and AMPK KD (+37%) mice. In contrast, 5-aminoimidazole-4-carboxamide ribonucleoside only induced an increase in cell surface FAT/CD36 content in WT (+29%) mice. Furthermore, in the perfused rat hindlimb, muscle contraction induced a rapid (1 min, +15%) and sustained (10 min, +24%) FAT/CD36 relocation to cell surface membranes. The increase in cell surface FAT/CD36 protein content with muscle contractions was associated with increased FA uptake, both in EDL and SOL muscle from WT and AMPK KD mice and in the perfused rat hindlimb. This suggests that AMPK is not essential in regulation of FAT/CD36 translocation and FA uptake in skeletal muscle during contractions. However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations.

  15. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    PubMed Central

    Jeppesen, J.; Albers, P. H.; Rose, A. J.; Birk, J. B.; Schjerling, P.; Dzamko, N.; Steinberg, G. R.; Kiens, B.

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat hindlimb. Exercise induced a similar increase in skeletal muscle cell surface membrane FAT/CD36 content in WT (+34%) and AMPK KD (+37%) mice. In contrast, 5-aminoimidazole-4-carboxamide ribonucleoside only induced an increase in cell surface FAT/CD36 content in WT (+29%) mice. Furthermore, in the perfused rat hindlimb, muscle contraction induced a rapid (1 min, +15%) and sustained (10 min, +24%) FAT/CD36 relocation to cell surface membranes. The increase in cell surface FAT/CD36 protein content with muscle contractions was associated with increased FA uptake, both in EDL and SOL muscle from WT and AMPK KD mice and in the perfused rat hindlimb. This suggests that AMPK is not essential in regulation of FAT/CD36 translocation and FA uptake in skeletal muscle during contractions. However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations. PMID:21297178

  16. Insulin binding to individual rat skeletal muscles

    SciTech Connect

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

    1990-10-01

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

  17. Transmission of polarized light in skeletal muscle

    NASA Astrophysics Data System (ADS)

    Shuaib, Ali; Li, Xin; Yao, Gang

    2011-02-01

    Experiments were conducted to study polarized light transmission in fresh bovine skeletal muscle of varying thicknesses. Two-dimensional polarization-sensitive transmission images were acquired and analyzed using a numerical parametric fitting algorithm. The total transmittance intensity and degree-of-polarization were calculated for both central ballistic and surrounding scattering regions. Full Mueller matrix images were derived from the raw polarization images and the polar decomposition algorithm was applied to extract polarization parameters. The results suggest that polarized light propagation through skeletal muscle is affected by strong birefringence, diattenuation, multiple scattering induced depolarization and the sarcomere diffraction effect.

  18. Satellite cells in human skeletal muscle plasticity

    PubMed Central

    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. PMID:26557092

  19. Mechanotransduction pathways in skeletal muscle hypertrophy.

    PubMed

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

    2012-02-01

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

  20. Regulation of skeletal muscle blood flow during exercise in ageing humans.

    PubMed

    Hearon, Christopher M; Dinenno, Frank A

    2016-04-15

    The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium-derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age-associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium-derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin-1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. 'functional sympatholysis'), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium-dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age-associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium-dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans.

  1. Laminin-211 in skeletal muscle function

    PubMed Central

    Holmberg, Johan; Durbeej, Madeleine

    2013-01-01

    A chain is no stronger than its weakest link is an old idiom that holds true for muscle biology. As the name implies, skeletal muscle’s main function is to move the bones. However, for a muscle to transmit force and withstand the stress that contractions give rise to, it relies on a chain of proteins attaching the cytoskeleton of the muscle fiber to the surrounding extracellular matrix. The importance of this attachment is illustrated by a large number of muscular dystrophies caused by interruption of the cytoskeletal-extracellular matrix interaction. One of the major components of the extracellular matrix is laminin, a heterotrimeric glycoprotein and a major constituent of the basement membrane. It has become increasingly apparent that laminins are involved in a multitude of biological functions, including cell adhesion, differentiation, proliferation, migration and survival. This review will focus on the importance of laminin-211 for normal skeletal muscle function. PMID:23154401

  2. YAP-Mediated Mechanotransduction in Skeletal Muscle

    PubMed Central

    Fischer, Martina; Rikeit, Paul; Knaus, Petra; Coirault, Catherine

    2016-01-01

    Skeletal muscle is not only translating chemical energy into mechanical work, it is also a highly adaptive and regenerative tissue whose architecture and functionality is determined by its mechanical and physical environment. Processing intra- and extracellular mechanical signaling cues contributes to the regulation of cell growth, survival, migration and differentiation. Yes-associated Protein (YAP), a transcriptional coactivator downstream of the Hippo pathway and its paralog, the transcriptional co-activator with PDZ-binding motif (TAZ), were recently found to play a key role in mechanotransduction in various tissues including skeletal muscle. Furthermore, YAP/TAZ modulate myogenesis and muscle regeneration and abnormal YAP activity has been reported in muscular dystrophy and rhabdomyosarcoma. Here, we summarize the current knowledge of mechanosensing and -signaling in striated muscle. We highlight the role of YAP signaling and discuss the different routes and hypotheses of its regulation in the context of mechanotransduction. PMID:26909043

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

    PubMed

    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.

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

    PubMed

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

    2017-09-16

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

  5. Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction.

    PubMed

    Sullo, Nikol; Roviezzo, Fiorentina; Matteis, Maria; Spaziano, Giuseppe; Del Gaudio, Stefania; Lombardi, Assunta; Lucattelli, Monica; Polverino, Francesca; Lungarella, Giuseppe; Cirino, Giuseppe; Rossi, Francesco; D'Agostino, Bruno

    2013-02-01

    Skeletal muscle dysfunction is a significant contributor to exercise limitation in pulmonary emphysema. This study investigated skeletal muscle oxidative metabolism before and after aerosol exposure to a long-acting β-agonist (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum α(1)-antitrypsin (α(1)-PI) and develops spontaneous pulmonary emphysema. C57 BL/6J and its congener pallid mice of 8-12 and 16 months of age were treated with vehicle or formoterol aerosol challenge for 120 seconds. Morphological and morphometric studies and evaluations of mitochondrial adenosine diphosphate-stimulated respiration and of cytochrome oxidase activity on skeletal muscle were performed. Moreover, the mtDNA content in skeletal muscle and the mediators linked to muscle mitochondrial function and biogenesis, as well as TNF-α and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), were also evaluated. The lungs of pallid mice at 12 and 16 months of age showed patchy areas of airspace enlargements, with the destruction of alveolar septa. No significant differences were observed in basal values of mitochondrial skeletal muscle oxidative processes between C57 BL/6J and pallid mice. Exposure to LABA significantly improved mitochondrial skeletal muscle oxidative processes in emphysematous mice, where the mtDNA content was significantly higher with respect to 8-month-old pallid mice. This effect was compared with a significant increase of PGC-1α in skeletal muscles of 16-month-old pallid mice, with no significant changes in TNF-α concentrations. In conclusion, in emphysematous mice that showed an increased mtDNA content, exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative processes. PGC-1α may serve as a possible mediator of this effect.

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

    PubMed

    Eftestøl, Einar; Alver, Tine Norman; Gundersen, Kristian; Bruusgaard, Jo C

    2014-01-01

    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.

  7. Oxidative proteome alterations during skeletal muscle ageing

    PubMed Central

    Lourenço dos Santos, Sofia; Baraibar, Martin A.; Lundberg, Staffan; Eeg-Olofsson, Orvar; Larsson, Lars; Friguet, Bertrand

    2015-01-01

    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. PMID:26073261

  8. Oxidative proteome alterations during skeletal muscle ageing.

    PubMed

    Lourenço dos Santos, Sofia; Baraibar, Martin A; Lundberg, Staffan; Eeg-Olofsson, Orvar; Larsson, Lars; Friguet, Bertrand

    2015-08-01

    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.

  9. Introduction to respiratory control in skeletal muscle.

    PubMed

    Starnes, J W

    1994-01-01

    It is well known that a linear relationship exists for submaximum exercise intensity and oxygen consumption. Most of the increase in oxygen consumption is by skeletal muscle mitochondria for the purpose of producing enough ATP to match the energy needs of the muscle. The control of mitochondrial ATP production in muscle when workload is varied is a complex process and remains a very active area of research. Thus, the purpose of this symposium is to discuss the factors involved in the coupling between increases in work and increased oxygen consumption by muscle. The program will begin with a consideration of the challenges faced by skeletal muscle when attempting to meet its energy demands and the intracellular strategies that have evolved to optimize energy delivery. Next the major control theories for mitochondrial respiration will be discussed. Finally, experiments will be presented that are designed to determine which of these theories are best suited for specific skeletal muscle fiber types. It is hoped that the information presented will increase our awareness of different energy supply-demand strategies among fiber types and how supply-demand strategies are optimized by endurance training.

  10. Development of Sensory Receptors in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    DeSantis, Mark

    2000-01-01

    The two major goals for this project is to (1) examine the hindlimb walking pattern of offspring from the Flight dams as compared with offspring of the ground control groups from initiation of walking up to two months thereafter; and (2) examine skeletal muscle.

  11. Skeletal muscle fibre types in the dog.

    PubMed Central

    Latorre, R; Gil, F; Vázquez, J M; Moreno, F; Mascarello, F; Ramirez, G

    1993-01-01

    Using a variety of histochemical methods we have investigated the mATPase reaction of skeletal muscle fibres in the dog. Types I, IIA, IIDog (peculiar to the dog) and IIC fibres were identified. The results reveal that the interpretation of the fibre type composition depends on the methods used. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8226288

  12. Tissue engineering skeletal muscle for orthopaedic applications

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  13. Metabolism and Skeletal Muscle Homeostasis in Lung Disease.

    PubMed

    Ceco, Ermelinda; Weinberg, Samuel E; Chandel, Navdeep S; Sznajder, Jacob I

    2017-07-01

    There is increased awareness that patients with lung diseases develop muscle dysfunction. Muscle dysfunction is a major contributor to a decreased quality of life in patients with chronic pulmonary diseases. Furthermore, muscle dysfunction exacerbates lung disease outcome, as a decrease in muscle mass and function are associated with increased morbidity, often long after critical illness or lung disease has been resolved. As we are learning more about the role of metabolism in health and disease, we are appreciating more the direct role of metabolism in skeletal muscle homeostasis. Altered metabolism is associated with numerous skeletal muscle pathologies and, conversely, skeletal muscle diseases are associated with significant changes in metabolic pathways. In this review, we highlight the role of metabolism in the regulation of skeletal muscle homeostasis. Understanding the metabolic pathways that underlie skeletal muscle wasting is of significant clinical interest for critically ill patients as well as patients with chronic lung disease, in which proper skeletal muscle function is essential to disease outcome.

  14. Study of photon migration in skeletal muscle

    NASA Astrophysics Data System (ADS)

    Ranasinghesagara, J.; Yao, G.

    2007-09-01

    A clear understanding of how light propagation in muscle is important for developing optical methods for muscle characterization. We investigated photon migration in muscle by imaging the optical reflectance from fresh prerigor skeletal muscles. We found the acquired reflectance patterns can not be described using existing theories. In order to quantify the equi-intensity contours of acquired reflectance images, we developed a numerical fitting function. Using this model, we studied the changes of reflectance profile during stretching and rigor process. The observed unique anisotropic features diminished after rigor completion. These results suggested that muscle sarcomere structures played important roles in modulating light propagation in whole muscle. To explain the observed patterns, we incorporated the sarcomere diffraction in a Monte Carlo model and we showed that the resulting reflectance profiles quantitatively resembled the experimental observation.

  15. Microcirculatory effects of melatonin in rat skeletal muscle after prolonged ischemia.

    PubMed

    Wang, Wei Z; Fang, Xin-Hua; Stephenson, Linda L; Baynosa, Richard C; Khiabani, Kayvan T; Zamboni, William A

    2005-08-01

    The purpose of this study was to determine microcirculatory effects and response of nitric oxide synthase (NOS) to melatonin in skeletal muscle after prolonged ischemia. A vascular pedicle isolated rat cremaster muscle model was used. Each muscle underwent 4 hr of zero-flow warm ischemia followed by 2 hr of reperfusion. Melatonin (10 mg/kg) or saline as a vehicle was given by intraperitoneal injection at 30 min prior to reperfusion and the same dose was given immediately after reperfusion. After reperfusion, microcirculation measurements including arteriole diameter, capillary perfusion and endothelial-dependent and -independent vasodilatation were performed. The cremaster muscle was then harvested to measure endothelial NOS (eNOS) and inducible NOS (iNOS) gene expression and enzyme activity. Three groups of rats were used: sham-ischemia/reperfusion (I/R), vehicle + I/R and melatonin + I/R. As compared with vehicle + I/R group, administration of melatonin significantly enhanced arteriole diameter, improved capillary perfusion, and attenuated endothelial dysfunction in the microcirculation of skeletal muscle after 4 hr warm ischemia. Prolonged warm ischemia followed by reperfusion significantly depressed eNOS gene expression and constitutive NOS activity and enhanced iNOS gene expression. Administration of melatonin did not significantly alter NOS gene expression or activity in skeletal muscle after prolonged ischemia and reperfusion. Melatonin provided a significant microvascular protection from reperfusion injury in skeletal muscle. This protection is probably attributable to the free radical scavenging effect of melatonin, but not to its anti-inflammatory effect.

  16. Effects of ACE inhibitors on skeletal muscle.

    PubMed

    Onder, Graziano; Vedova, Cecilia Della; Pahor, Marco

    2006-01-01

    Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity, mortality, hospital admissions, and decline in physical function and exercise capacity in congestive heart failure (CHF) patients. These therapeutic effects are attributed primarily to beneficial cardiovascular actions of these drugs. However, it has been suggested that ACE inhibitor-induced positive effects may also be mediated by direct action on the skeletal muscle. In particular, two recently published observational studies documented that among hypertensive subjects free of CHF, treatment with ACE inhibitors was associated with better performance and muscular outcomes and genetic studies also support the hypothesis that the ACE system may be involved in physical performance and skeletal muscle function. Effects on the skeletal muscle are probably mediated by mechanical, metabolic, anti-inflammatory, nutritional, neurological and angiogenetic actions of these drugs. These studies may have major public health implications for older adults, as consequence of the fact that, in this population, gradual loss of muscle mass and muscle strength can play a key role in the onset and progression of disability. Therefore, if findings of observational studies will be later confirmed in randomized controlled trials, ACE inhibitors could represent an effective intervention to prevent physical decline in the elderly, leading to greater autonomy in this growing population.

  17. Treatment of Skeletal Muscle Injury: A Review

    PubMed Central

    Baoge, L.; Van Den Steen, E.; Rimbaut, S.; Philips, N.; Witvrouw, E.; Almqvist, K. F.; Vanderstraeten, G.; Vanden Bossche, L. C.

    2012-01-01

    Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammatory phase in the healing of injured skeletal muscle. Furthermore, it remains controversial whether or not they have adverse effects on the healing process or on the tensile strength. However, several growth factors might promote the regeneration of injured skeletal muscle, many novel treatments have involved on enhancing complete functional recovery. Exogenous growth factors have been shown to regulate satellite cell proliferation, differentiation and fusion in myotubes in vivo and in vitro, TGF-β1 antagonists behave as inhibitors of TGF-β1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved. PMID:24977084

  18. Insulin Increases Ceramide Synthesis in Skeletal Muscle

    PubMed Central

    Hansen, M. E.; Tippetts, T. S.; Anderson, M. C.; Holub, Z. E.; Moulton, E. R.; Swensen, A. C.; Prince, J. T.; Bikman, B. T.

    2014-01-01

    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. PMID:24949486

  19. Photothermal imaging of skeletal muscle mitochondria

    PubMed Central

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

    2017-01-01

    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. PMID:28663919

  20. Oxidative system in aged skeletal muscle.

    PubMed

    Buonocore, Daniela; Rucci, Sara; Vandoni, Matteo; Negro, Massimo; Marzatico, Fulvio

    2011-07-01

    Aging is an inevitable biological process that is characterized by a general decline in the physiological and biochemical functions of the major systems. In the case of the neuromuscular system, reductions in strength and mobility cause a deterioration in motor performance, impaired mobility and disability. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS). As the level of oxidative stress in skeletal muscle increases with age, the age-process is characterized by an imbalance between an increase in ROS production in the organism, and antioxidant defences as a whole. We have reviewed the literature on oxidative stress in aging human skeletal muscles, and to assesss the impact of differences in physiological factors (sex, fiber composition, muscle type and function).

  1. Skeletal muscle adaptations and muscle genomics of performance horses.

    PubMed

    Rivero, José-Luis L; Hill, Emmeline W

    2016-03-01

    Skeletal muscles in horses are characterised by specific adaptations, which are the result of the natural evolution of the horse as a grazing animal, centuries of selective breeding and the adaptability of this tissue in response to training. These adaptations include an increased muscle mass relative to body weight, a great locomotor efficiency based upon an admirable muscle-tendon architectural design and an adaptable fibre-type composition with intrinsic shortening velocities greater than would be predicted from an animal of comparable body size. Furthermore, equine skeletal muscles have a high mitochondrial volume that permits a higher whole animal aerobic capacity, as well as large intramuscular stores of energy substrates (glycogen in particular). Finally, high buffer and lactate transport capacities preserve muscles against fatigue during anaerobic exercise. Many of these adaptations can improve with training. The publication of the equine genome sequence in 2009 has provided a major advance towards an improved understanding of equine muscle physiology. Equine muscle genomics studies have revealed a number of genes associated with elite physical performance and have also identified changes in structural and metabolic genes following exercise and training. Genes involved in muscle growth, muscle contraction and specific metabolic pathways have been found to be functionally relevant for the early performance evaluation of elite athletic horses. The candidate genes discussed in this review are important for a healthy individual to improve performance. However, muscle performance limiting conditions are widespread in horses and many of these conditions are also genetically influenced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Pannexin 1 channels in skeletal muscles.

    PubMed

    Cea, Luis A; Riquelme, Manuel A; Vargas, Anibal A; Urrutia, Carolina; Sáez, Juan C

    2014-01-01

    Normal myotubes and adult innervated skeletal myofibers express the glycoprotein pannexin1 (Panx1). Six of them form a "gap junction hemichannel-like" structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules. So far little is known about the role of Panx1 channels in muscles but skeletal muscles of Panx1(-/-) mice do not show an evident phenotype. Innervated adult fast and slow skeletal myofibers show Panx1 reactivity in close proximity to dihydropyridine receptors in the sarcolemma of T-tubules. These Panx1 channels are activated by electrical stimulation and extracellular ATP. Panx1 channels play a relevant role in potentiation of muscle contraction because they allow release of ATP and uptake of glucose, two molecules required for this response. In support of this notion, the absence of Panx1 abrogates the potentiation of muscle contraction elicited by repetitive electrical stimulation, which is reversed by exogenously applied ATP. Phosphorylation of Panx1 Thr and Ser residues might be involved in Panx1 channel activation since it is enhanced during potentiation of muscle contraction. Under denervation, Panx1 levels are upregulated and this partially explains the reduction in electrochemical gradient, however its absence does not prevent denervation-induced atrophy but prevents the higher oxidative state. Panx1 also forms functional channels at the cell surface of myotubes and their functional state has been associated with intracellular Ca(2+) signals and regulation of myotube plasticity evoked by electrical stimulation. We proposed that Panx1 channels participate as ATP channels and help to keep a normal oxidative state in skeletal muscles.

  3. Skeletal muscle vasodilation during systemic hypoxia in humans

    PubMed Central

    2015-01-01

    In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response. PMID:26023228

  4. Skeletal muscle vasodilation during systemic hypoxia in humans.

    PubMed

    Dinenno, Frank A

    2016-01-15

    In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response. Copyright © 2016 the American Physiological Society.

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

    PubMed

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

    2017-01-01

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

  6. Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

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

  8. Observations on autoregulation in skeletal muscle - The effects of arterial hypoxia

    NASA Technical Reports Server (NTRS)

    Pohost, G. M.; Newell, J. B.; Hamlin, N. P.; Powell, W. J., Jr.

    1976-01-01

    An experimental study was carried out on 25 mongrel dogs of both sexes to re-evaluate autoregulation of blood flow in skeletal muscle, with particular reference to the steady-state resistance and transient response in muscle blood flow following a square wave increase in arterial perfusion pressure and to the examination of the effect of arterial hypoxia on this transient response. The data emphasize the importance of considering the transient changes in blood flow in evaluating the autoregulatory response in skeletal muscle. For quantification purposes, a parameter termed alpha is introduced which represents the ratio between the increase in blood flow from baseline to peak and the return of blood flow from the peak to the new steady-state. Such a quantification of the transient response in flow with step increases in perfusion pressure demonstrates substantial transient responses under conditions of normal oxygenation and progressive attenuation of flow transients with increasing hypoxia.

  9. Coaxing stem cells for skeletal muscle repair.

    PubMed

    McCullagh, Karl J A; Perlingeiro, Rita C R

    2015-04-01

    Skeletal muscle has a tremendous ability to regenerate, attributed to a well-defined population of muscle stem cells called satellite cells. However, this ability to regenerate diminishes with age and can also be dramatically affected by multiple types of muscle diseases, or injury. Extrinsic and/or intrinsic defects in the regulation of satellite cells are considered to be major determinants for the diminished regenerative capacity. Maintenance and replenishment of the satellite cell pool is one focus for muscle regenerative medicine, which will be discussed. There are other sources of progenitor cells with myogenic capacity, which may also support skeletal muscle repair. However, all of these myogenic cell populations have inherent difficulties and challenges in maintaining or coaxing their derivation for therapeutic purpose. This review will highlight recent reported attributes of these cells and new bioengineering approaches to creating a supply of myogenic stem cells or implants applicable for acute and/or chronic muscle disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Wave biomechanics of the skeletal muscle

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

  11. Skeletal muscle proteomics in livestock production.

    PubMed

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

    2010-05-01

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

  12. Functional and metabolic consequences of skeletal muscle remodeling in hypothyroidism.

    PubMed

    McAllister, R M; Ogilvie, R W; Terjung, R L

    1991-02-01

    Functional and metabolic responses of hypothyroid skeletal muscle were evaluated during steady-state isometric contraction conditions, using an isolated perfused rat hindlimb preparation. Treating rats with propylthiouracil (PTU) for 4-5 mo resulted in a 55% decrease (P less than 0.001) in citrate synthase activity in plantaris muscle and phenotypic remodeling of the plantaris, evident by a threefold increase in type I fiber area and a 13% decrease in type II fiber area. Perfusion of PTU (n = 9) and control (n = 9) rat hindlimbs of similar size, with similar inflow (approximately 10 ml/min) and oxygen content (approximately 20 g/100 ml), resulted in similar oxygen deliveries to the contracting muscles (PTU 11.4 +/- 0.58, control 9.54 +/- 0.75 mumol.min-1.g-1; P greater than 0.05). Ten-minute tetanic contraction (100 ms at 100 Hz) periods at 4, 8, 15, 30, and 45 tetani/min were elicited in consecutive ascending order. Oxygen consumption (VO2) was lower in the PTU group at all contraction frequencies (P less than 0.005), with a decrease in peak VO2 of 44% (PTU 3.01 +/- 0.29, control 5.35 +/- 0.42 mumol.min-1.g-1; P less than 0.001). Oxygen extraction by the PTU muscle was only approximately 25% of that delivered. Developed tension was initially less (15%; P less than 0.05) in the PTU group but declined in a similar manner, as a percent of initial, to that of the control group. The slightly lower absolute tension development of the PTU muscle could not account for the large reduction in VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Conchotome and needle percutaneous biopsy of skeletal muscle.

    PubMed Central

    Dietrichson, P; Coakley, J; Smith, P E; Griffiths, R D; Helliwell, T R; Edwards, R H

    1987-01-01

    Percutaneous muscle biopsy is an important and acceptable technique in the study of conditions involving human skeletal muscle. A review of 436 conchotome and needle muscle biopsies obtained over 18 months in this centre is presented. Images PMID:3694206

  14. Characterization of muscle ankyrin repeat proteins in human skeletal muscle.

    PubMed

    Wette, Stefan G; Smith, Heather K; Lamb, Graham D; Murphy, Robyn M

    2017-09-01

    Muscle ankyrin repeat proteins (MARPs) are a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. In cardiac muscle, cardiac ankyrin repeat protein (CARP) and diabetes-related ankyrin repeat protein (DARP) reportedly redistribute from binding sites on titin to the nucleus following a prolonged stretch. However, it is unclear whether ankyrin repeat domain protein 2 (Ankrd 2) shows comparable stretch-induced redistribution to the nucleus. We measured the following in rested human skeletal muscle: 1) the absolute amount of MARPs and 2) the distribution of Ankrd 2 and DARP in both single fibers and whole muscle preparations. In absolute amounts, Ankrd 2 is the most abundant MARP in human skeletal muscle, there being ~3.1 µmol/kg, much greater than DARP and CARP (~0.11 and ~0.02 µmol/kg, respectively). All DARP was found to be tightly bound at cytoskeletal (or possibly nuclear) sites. In contrast, ~70% of the total Ankrd 2 is freely diffusible in the cytosol [including virtually all of the phosphorylated (p)Ankrd 2-Ser99 form], ~15% is bound to non-nuclear membranes, and ~15% is bound at cytoskeletal sites, likely at the N2A region of titin. These data are not consistent with the proposal that Ankrd 2, per se, or pAnkrd 2-Ser99 mediates stretch-induced signaling in skeletal muscle, dissociating from titin and translocating to the nucleus, because the majority of these forms of Ankrd 2 are already free in the cytosol. It will be necessary to show that the titin-associated Ankrd 2 is modified by stretch in some as-yet-unidentified way, distinct from the diffusible pool, if it is to act as a stretch-sensitive signaling molecule. Copyright © 2017 the American Physiological Society.

  15. Systemic Regulators of Skeletal Muscle Regeneration in Obesity

    PubMed Central

    Sinha, Indranil; Sakthivel, Dharaniya; Varon, David E.

    2017-01-01

    Skeletal muscle maintenance is a dynamic process and undergoes constant repair and regeneration. However, skeletal muscle regenerative capacity declines in obesity. In this review, we focus on obesity-associated changes in inflammation, metabolism, and impaired insulin signaling, which are pathologically dysregulated and ultimately result in a loss of muscle mass and function. In addition, we examine the relationships between skeletal muscle, liver, and visceral adipose tissue in an obese state. PMID:28261159

  16. Stretching Skeletal Muscle: Chronic Muscle Lengthening through Sarcomerogenesis

    PubMed Central

    Zöllner, Alexander M.; Abilez, Oscar J.; Böl, Markus; Kuhl, Ellen

    2012-01-01

    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 3.09m to 3.51m, 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 treatment for patients with ill proportioned limbs, tendon

  17. Exercise and the Skeletal Muscle Epigenome.

    PubMed

    McGee, Sean L; Walder, Ken R

    2017-03-20

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

  18. Role of skeletal muscle proteoglycans during myogenesis.

    PubMed

    Brandan, Enrique; Gutierrez, Jaime

    2013-08-08

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

  19. Autophagy and Skeletal Muscles in Sepsis

    PubMed Central

    Mofarrahi, Mahroo; Sigala, Ioanna; Guo, Yeting; Godin, Richard; Davis, Elaine C.; Petrof, Basil; Sandri, Marco

    2012-01-01

    Background Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles. Methodology/Principal Findings Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca++ retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor. Conclusion/Significance We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis

  20. ANG II is required for optimal overload-induced skeletal muscle hypertrophy

    NASA Technical Reports Server (NTRS)

    Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

    2001-01-01

    ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

  1. ANG II is required for optimal overload-induced skeletal muscle hypertrophy

    NASA Technical Reports Server (NTRS)

    Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

    2001-01-01

    ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

  2. Suturing of lacerations of skeletal muscle.

    PubMed

    Kragh, J F; Svoboda, S J; Wenke, J C; Ward, J A; Walters, T J

    2005-09-01

    Our aim was to compare the biomechanical properties of suturing methods to determine a better method for the repair of lacerated skeletal muscle. We tested Kessler stitches and the combination of Mason-Allen and perimeter stitches. Individual stitches were placed in the muscle belly of quadriceps femoris from a pig cadaver and were tensioned mechanically. The maximum loads and strains were measured and failure modes recorded. The mean load and strain for the Kessler stitches were significantly less than those for combination stitches. All five Kessler stitches tore out longitudinally from the muscle. All five combination stitches did not fail but successfully elongated. Our study has shown that the better method of repair for suturing muscle is the use of combination stitches.

  3. Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions.

    PubMed

    Jacobi, Bjoern; Bongartz, Georg; Partovi, Sasan; Schulte, Anja-Carina; Aschwanden, Markus; Lumsden, Alan B; Davies, Mark G; Loebe, Matthias; Noon, Georg P; Karimi, Sasan; Lyo, John K; Staub, Daniel; Huegli, Rolf W; Bilecen, Deniz

    2012-06-01

    Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail. Copyright © 2012 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-03-01

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

  5. De novo synthesis of purine nucleotides in different fiber types of rat skeletal muscle

    SciTech Connect

    Tullson, P.C.; John-Alder, H.; Hood, D.A.; Terjung, R.L.

    1986-03-01

    The contribution of de novo purine nucleotide synthesis to nucleotide metabolism in skeletal muscles is not known. The authors have determined rates of de novo synthesis in soleus (slow-twitch red), red gastrocnemius (fast-twitch red), and white gastrocnemius (fast-twitch white) using the perfused rat hindquarter. /sup 14/C glycine incorporation into ATP was linear after 1 and 2 hours of perfusion with 0.2 mM added glycine. The intracellular (I) and extracellular (E) specific activity of /sup 14/C glycine was determined by HPLC of phenylisothiocyanate derivatives of neutralized PCA extracts. The rates of de novo synthesis when expressed relative to muscle ATP content show slow and fast-twitch red muscles to be similar and about twice as great as fast-twitch white muscles. This could represent a greater turnover of the adenine nucleotide pool in more oxidative red muscle types.

  6. Skeletal Muscle Mitochondria and Aging: A Review

    PubMed Central

    Peterson, Courtney M.; Johannsen, Darcy L.; Ravussin, Eric

    2012-01-01

    Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline. PMID:22888430

  7. Development of Sensory Receptors in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    DeSantis, Mark

    2000-01-01

    There were two major goals for my project. One was to examine the hindlimb walking pattern of offspring from the Flight dams as compared with offspring of the ground control groups from initiation of walking up to two months thereafter. This initial goal was subsequently modified so that additional developmental measures were taken (e.g. body weight, eye opening) as the progeny developed, and the study period was lengthened to eighty days. Also videotapes taken shortly after the pregnant Flight dams returned to Earth were scored for locomotor activity and compared to those for the Synchronous control dams at the same stage of pregnancy. The second goal was to examine skeletal muscle. Selected hindlimb skeletal muscles were to be identified, weighed, and examined for the presence and integrity of muscle receptors, (both muscle spindles and tendon organs), at the level of the light and electron microscope. Muscles were examined from rats that were at fetal (G20), newborn (postnatal day 1 or P1, where P1 = day of birth), and young adult (approx. P100) stages. At the present time data from only the last group of rats (i.e. P100) has been completely examined.

  8. Skeletal muscle disease: patterns of MRI appearances.

    PubMed

    Theodorou, D J; Theodorou, S J; Kakitsubata, Y

    2012-12-01

    Although the presumptive diagnosis of skeletal muscle disease (myopathy) may be made on the basis of clinical-radiological correlation in many cases, muscle biopsy remains the cornerstone of diagnosis. Myopathy is suspected when patients complain that the involved muscle is painful and tender, when they experience difficulty performing tasks that require muscle strength or when they develop various systemic manifestations. Because the cause of musculoskeletal pain may be difficult to determine clinically in many cases, MRI is increasingly utilised to assess the anatomical location, extent and severity of several pathological conditions affecting muscle. Infectious, inflammatory, traumatic, neurological, neoplastic and iatrogenic conditions can cause abnormal signal intensity on MRI. Although diverse, some diseases have similar MRI appearances, whereas others present distinct patterns of signal intensity abnormality. In general, alterations in muscle signal intensity fall into one of three cardinal patterns: muscle oedema, fatty infiltration and mass lesion. Because some of the muscular disorders may require medical or surgical treatment, correct diagnosis is essential. In this regard, MRI features, when correlated with clinical and laboratory findings as well as findings from other methods such as electromyography, may facilitate correct diagnosis. This article will review and illustrate the spectrum of MRI appearances in several primary and systemic disorders affecting muscle, both common and uncommon. The aim of this article is to provide radiologists and clinicians with a collective, yet succinct and useful, guide to a wide array of myopathies.

  9. Effect of limb immobilization on skeletal muscle

    NASA Technical Reports Server (NTRS)

    Booth, F. W.

    1982-01-01

    Current knowledge and questions remaining concerning the effects of limb immobilization on skeletal muscle is reviewed. The most dramatic of these effects is muscle atrophy, which has been noted in cases of muscles fixed at or below their resting length. Immobilization is also accompanied by a substantial decrease in motoneuronal discharges, which results in the conversion of slow-twitch muscle to muscle with fast-twitch characteristics. Sarcolemma effects include no change or a decrease in resting membrane potential, the appearance of extrajunctional acetylcholine receptors, and no change in acetylcholinesterase activity. Evidence of changes in motoneuron after hyperpolarization characteristics suggests that the muscle inactivity is responsible for neuronal changes, rather than vice versa. The rate of protein loss from atrophying muscles is determined solely by the first-order rate constant for degradation. Various other biochemical and functional changes have been noted, including decreased insulin responsiveness and protein synthesis. The model of limb immobilization may also be useful for related studies of muscle adaptation.

  10. Nonmyogenic cells in skeletal muscle regeneration.

    PubMed

    Paylor, Ben; Natarajan, Anuradha; Zhang, Regan-Heng; Rossi, Fabio

    2011-01-01

    Although classical dogma dictates that satellite cells are the primary cell type involved in skeletal muscle regeneration, alternative cell types such as a variety of inflammatory and stromal cells are also actively involved in this process. A model describing myogenic cells as direct contributors to regeneration and nonmyogenic cells from other developmental sources as important accessories has emerged, with similar systems having been described in numerous other tissues in the body. Increasing evidence supports the notion that inflammatory cells function as supportive accessory cells, and are not merely involved in clearing damage following skeletal muscle injury. Additionally, recent studies have highlighted the role of tissue resident mesenchymal cell populations as playing a central role in regulating regeneration. These "accessory" cell populations are proposed to influence myogenesis via direct cell contact and secretion of paracrine trophic factors. The basic foundations of accessory cell understanding should be recognized as a crucial component to all prospects of regenerative medicine, and this chapter intends to provide a comprehensive background on the current literature describing immune and tissue-resident mesenchymal cells' role in skeletal muscle regeneration.

  11. Extrarenal potassium adaptation: role of skeletal muscle

    SciTech Connect

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

    1986-08-01

    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 /sup 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 /sup 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.

  12. Countercurrent compartmental models describe hind limb skeletal muscle helium kinetics at resting and low blood flows in sheep.

    PubMed

    Doolette, D J; Upton, R N; Grant, C

    2005-10-01

    This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood : tissue helium exchange in a predominantly skeletal muscle tissue bed in the sheep hind limb. Helium has different physiochemical properties from previously studied gases and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across skeletal muscle were determined during and after 20 min of helium inhalation, at separate resting and low steady-states of femoral vein blood flow in six sheep under isoflurane anaesthesia. Helium concentrations in arterial and femoral vein blood were determined using gas chromatographic analysis and femoral vein blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of skeletal muscle were estimated by simultaneous fitting of the models to the femoral vein helium concentrations for both blood flow states. A model comprising two parallel perfusion-limited compartment models fitted the data well but required a 51-fold difference in relative compartment perfusion that did not seem physiologically plausible. Models that allowed a countercurrent diffusion exchange of helium between arterial and venous vessels outside of the tissue compartments provided better overall fit of the data and credible parameter estimates. These results suggest a role of arterial-venous diffusion in blood : tissue helium equilibration in skeletal muscle.

  13. A pilot study of regional perfusion and oxygenation in calf muscles of individuals with diabetes with a noninvasive measure

    PubMed Central

    Zheng, Jie; Hasting, Mary K.; Zhang, Xiaodong; Coggan, Andrew; An, Hongyu; Snozek, Darrah; Curci, John; Mueller, Michael J.; St. Louis, Mo; Hill, Chapel

    2014-01-01

    Objective To assess alterations in the regional perfusion and oxygenation of the calf muscles in individuals with diabetes. Methods Age-matched individuals with (n = 5) and without diabetes (n = 6) were investigated. Skeletal muscle perfusion, oxygen extraction fraction, and oxygen consumption rate were measured by newly developed noncontrast magnetic resonance imaging (MRI) techniques. The subjects lay supine on the MRI table with their foot firmly strapped to a custom-built isometric exercise device. The measurements were performed at rest and during an isometric plantar flexion muscle contraction. Results Individuals without diabetes had up to a 10-fold increase in muscle perfusion, 25% elevation in muscle oxygen extraction fraction, and a 12-fold increase in oxygen consumption rate in the calf during the plantar flexion isometric contraction. In patients with diabetes, the increases in these parameters were only up to sixfold, 2%, and sixfold, respectively. Exercise oxygen consumption rate was inversely associated with blood HbA1c levels (r2 = .91). Conclusions This is the first study to quantify regional skeletal muscle oxygenation in patients with diabetes using noncontrast MRI and warrants additional study. Attenuation of perfusion and oxygenation during exercise may have implications for understanding diabetic complications in the lower extremities. PMID:24080129

  14. Regulatory T cells and skeletal muscle regeneration.

    PubMed

    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.

  15. Regulation of Skeletal Muscle Myoblast Differentiation and Proliferation by Pannexins.

    PubMed

    Langlois, Stéphanie; Cowan, Kyle N

    2017-01-01

    Pannexins are newly discovered channels that are now recognized as mediators of adenosine triphosphate release from several cell types allowing communication with the extracellular environment. Pannexins have been associated with various physiological and pathological processes including apoptosis, inflammation, and cancer. However, it is only recently that our work has unveiled a role for Pannexin 1 and Pannexin 3 as novel regulators of skeletal muscle myoblast proliferation and differentiation. Myoblast differentiation is an ordered multistep process that includes withdrawal from the cell cycle and the expression of key myogenic factors leading to myoblast differentiation and fusion into multinucleated myotubes. Eventually, myotubes will give rise to the diverse muscle fiber types that build the complex skeletal muscle architecture essential for body movement, postural behavior, and breathing. Skeletal muscle cell proliferation and differentiation are crucial processes required for proper skeletal muscle development during embryogenesis, as well as for the postnatal skeletal muscle regeneration that is necessary for muscle repair after injury or exercise. However, defects in skeletal muscle cell differentiation and/or deregulation of cell proliferation are involved in various skeletal muscle pathologies. In this review, we will discuss the expression of pannexins and their post-translational modifications in skeletal muscle, their known functions in various steps of myogenesis, including myoblast proliferation and differentiation, as well as their possible roles in skeletal muscle development, regeneration, and diseases such as Duchenne muscular dystrophy.

  16. 3D Cell Printing of Functional Skeletal Muscle Constructs Using Skeletal Muscle-Derived Bioink.

    PubMed

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

    2016-10-01

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

  17. GLUT-3 expression in human skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  18. Dorsal root vasodilatation in cat skeletal muscle.

    PubMed Central

    Hilton, S M; Marshall, J M

    1980-01-01

    1. A study has been made, in the cat anaesthetized with chloralose, of the effects of antidromic stimulation of dorsal roots L6-S1 on the blood flow through the gastrocnemius muscle. 2. Stimulation of the peripheral ends of the ligated dorsal roots with current pulses of 0.3-0.5 msec duration and at intensities most effective in activating the smaller afferent fibres, for periods of 15-20 sec, produced a 50-60% increase in muscle vascular conductance which was slow in onset and long outlasted the stimulus. 3. This muscle vasodilatation could be evoked in the paralysed animal and was unaffected by guanethidine or atropine. It was, however, greatly reduced or even abolished by the prostaglandin synthetase inhibitors, indomethacin or acetylsalicylic acid, in doses which had no effect on the dilatation produced by a local injection of acetylcholine or the functional hyperaemia induced by muscle contraction. 4. It is concluded that activity in the smaller myelinated or unmyelinated afferent fibres of skeletal muscle produces an increase in muscle blood flow which is mediated, at least in part, by prostaglandins locally synthesized within the muscle. PMID:7381769

  19. Satellite Cells and Skeletal Muscle Regeneration.

    PubMed

    Dumont, Nicolas A; Bentzinger, C Florian; Sincennes, Marie-Claude; Rudnicki, Michael A

    2015-07-01

    Skeletal muscles are essential for vital functions such as movement, postural support, breathing, and thermogenesis. Muscle tissue is largely composed of long, postmitotic multinucleated fibers. The life-long maintenance of muscle tissue is mediated by satellite cells, lying in close proximity to the muscle fibers. Muscle satellite cells are a heterogeneous population with a small subset of muscle stem cells, termed satellite stem cells. Under homeostatic conditions all satellite cells are poised for activation by stimuli such as physical trauma or growth signals. After activation, satellite stem cells undergo symmetric divisions to expand their number or asymmetric divisions to give rise to cohorts of committed satellite cells and thus progenitors. Myogenic progenitors proliferate, and eventually differentiate through fusion with each other or to damaged fibers to reconstitute fiber integrity and function. In the recent years, research has begun to unravel the intrinsic and extrinsic mechanisms controlling satellite cell behavior. Nonetheless, an understanding of the complex cellular and molecular interactions of satellite cells with their dynamic microenvironment remains a major challenge, especially in pathological conditions. The goal of this review is to comprehensively summarize the current knowledge on satellite cell characteristics, functions, and behavior in muscle regeneration and in pathological conditions.

  20. Phosphorylation of human skeletal muscle myosin

    SciTech Connect

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

    1986-03-01

    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/sup 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 (/sup 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.

  1. GLUT-3 expression in human skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  2. Translational control mechanisms modulate skeletal muscle gene expression during hypertrophy.

    PubMed

    Bolster, Douglas R; Kimball, Scot R; Jefferson, Leonard S

    2003-07-01

    Understanding the basic mechanisms regulating skeletal muscle hypertrophy is essential to providing strategies for optimizing and maintaining skeletal muscle mass. This review focuses on the importance of mRNA translation in mediating acute increases in protein synthesis after resistance exercise as well as the anabolic response of muscle growth.

  3. Effects of supplementation of BH4 after prolonged ischemia in skeletal muscle.

    PubMed

    Wang, Wei Z; Fang, Xin-Hua; Stephenson, Linda L; Khiabani, Kayvan T; Zamboni, William A

    2007-01-01

    To determine whether the supplementation of tetrahydrobiopterin (BH(4), an essential cofactor of nitric oxide synthase; NOS) could attenuate endothelial dysfunction and improve NOS activity and cell viability in skeletal muscle after ischemia/reperfusion (I/R). A vascular pedicle isolated rat cremaster muscle model was used. Cremaster muscles were subjected to 4 h of ischemia followed by 2 h of reperfusion. Rats were given either normal saline or BH(4) by intravenous injection at 1 min prior to reperfusion. After reperfusion, average arteriole diameter, capillary perfusion, endothelial-dependent/-independent vasodilatation, NOS activity, and muscle cell viability were evaluated. Supplementation of BH(4) prior to reperfusion significantly attenuated reperfusion-induced vasoconstriction, poor capillary perfusion, and endothelial dysfunction and enhanced cNOS activity and slightly improved cell viability in the skeletal muscle after I/R. Supplementation of BH(4) during reperfusion provided a significant protection against I/R injury in rat skeletal muscle. (c) 2007 Wiley-Liss, Inc.

  4. Skeletal muscle patch engineering on synthetic and acellular human skeletal muscle originated scaffolds.

    PubMed

    Ay, Birol; Karaoz, Erdal; Kesemenli, Cumhur C; Kenar, Halime

    2017-03-01

    The reconstruction of skeletal muscle tissue is currently performed by transplanting a muscle tissue graft from local or distant sites of the patient's body, but this practice leads to donor site morbidity in case of large defects. With the aim of providing an alternative treatment approach, skeletal muscle tissue formation potential of human myoblasts and human menstrual blood derived mesenchymal stem cells (hMB-MSCs) on synthetic [poly(l-lactide-co-caprolactone), 70:30] scaffolds with oriented microfibers, human muscle extracellular matrix (ECM), and their hybrids was investigated in this study. The reactive muscle ECM pieces were chemically crosslinked to the synthetic scaffolds to produce the hybrids. Cell proliferation assay WST-1, scanning electron microscopy (SEM), and immunostaining were carried out after culturing the cells on the scaffolds. The ECM and the synthetic scaffolds were effective in promoting spontaneous myotube formation from human myoblasts. Anisotropic muscle patch formation was more successful when human myoblasts were grown on the synthetic scaffolds. Nonetheless, spontaneous differentiation could not be induced in hMB-MSCs on any type of the scaffolds. Human myoblast-synthetic scaffold combination is promising as a skeletal muscle patch, and can be improved further to serve as a fast integrating functional patch by introducing vascular and neuronal networks to the structure. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 879-890, 2017.

  5. Contractile properties of esophageal striated muscle: comparison with cardiac and skeletal muscles in rats.

    PubMed

    Shiina, Takahiko; Shima, Takeshi; Masuda, Kazuaki; Hirayama, Haruko; Iwami, Momoe; Takewaki, Tadashi; Kuramoto, Hirofumi; Shimizu, Yasutake

    2010-01-01

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

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

    PubMed

    Aaker, Aaron; Laughlin, M H

    2002-09-01

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

  7. Effects of regular exercise training on skeletal muscle contractile function

    NASA Technical Reports Server (NTRS)

    Fitts, Robert H.

    2003-01-01

    Skeletal muscle function is critical to movement and one's ability to perform daily tasks, such as eating and walking. One objective of this article is to review the contractile properties of fast and slow skeletal muscle and single fibers, with particular emphasis on the cellular events that control or rate limit the important mechanical properties. Another important goal of this article is to present the current understanding of how the contractile properties of limb skeletal muscle adapt to programs of regular exercise.

  8. Effects of regular exercise training on skeletal muscle contractile function

    NASA Technical Reports Server (NTRS)

    Fitts, Robert H.

    2003-01-01

    Skeletal muscle function is critical to movement and one's ability to perform daily tasks, such as eating and walking. One objective of this article is to review the contractile properties of fast and slow skeletal muscle and single fibers, with particular emphasis on the cellular events that control or rate limit the important mechanical properties. Another important goal of this article is to present the current understanding of how the contractile properties of limb skeletal muscle adapt to programs of regular exercise.

  9. REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE

    PubMed Central

    Powers, Scott K.; Ji, Li Li; Kavazis, Andreas N.; Jackson, Malcolm J.

    2014-01-01

    It is well established that contracting muscles produce both reactive oxygen and nitrogen species. Although the sources of oxidant production during exercise continue to be debated, growing evidence suggests that mitochondria are not the dominant source. Regardless of the sources of oxidants in contracting muscles, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Further, oxidants regulate numerous cell signaling pathways and modulate the expression of many genes. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species result in contractile dysfunction and fatigue. Ongoing research continues to explore the redox-sensitive targets in muscle that are responsible for both redox-regulation of muscle adaptation and oxidant-mediated muscle fatigue. PMID:23737208

  10. Carbohydrate oxidation disorders of skeletal muscle.

    PubMed

    Vorgerd, Matthias; Zange, Jochen

    2002-11-01

    The major energy sources for muscle contraction are glycogen, glucose and fatty acids, and defects in their oxidative pathways cause metabolic myopathies. Eleven specific enzyme deficiencies of carbohydrate oxidation affect skeletal muscle alone or in combination with other tissues, such as liver, heart or red blood cells. These hereditary glycogen storage diseases cause two major clinical presentations: one characterized by fixed, often progressive muscle weakness, and the other by acute, intermittent, and reversible muscle dysfunction manifesting as exercise intolerance (myalgia on exertion, muscle contractures, myoglobinuria). The focus of this review is on recent developments in: clinical features, including a brief description of the newest identified glycogen storage disease type XIII; molecular genetic studies discussing genotype-phenotype correlations in some carbohydrate oxidation disorders; pathophysiological mechanisms, especially those assessed by non-invasive P magnetic resonance spectroscopy; and therapeutic approaches such as nutritional supplementation and gene therapy, including recombinant enzyme replacement. Although major progress has been made in an understanding of the molecular genetic bases of carbohydrate oxidation defects, the pathophysiology of exercise intolerance and muscle weakness remains to be further clarified. Gene therapy and dietary therapeutic regimes appear promising, but need to be actively investigated in the future.

  11. Increased Excitability of Acidified Skeletal Muscle

    PubMed Central

    Pedersen, Thomas H.; de Paoli, Frank; Nielsen, Ole B.

    2005-01-01

    Generation of the action potentials (AP) necessary to activate skeletal muscle fibers requires that inward membrane currents exceed outward currents and thereby depolarize the fibers to the voltage threshold for AP generation. Excitability therefore depends on both excitatory Na+ currents and inhibitory K+ and Cl− currents. During intensive exercise, active muscle loses K+ and extracellular K+ ([K+]o) increases. Since high [K+]o leads to depolarization and ensuing inactivation of voltage-gated Na+ channels and loss of excitability in isolated muscles, exercise-induced loss of K+ is likely to reduce muscle excitability and thereby contribute to muscle fatigue in vivo. Intensive exercise, however, also leads to muscle acidification, which recently was shown to recover excitability in isolated K+-depressed muscles of the rat. Here we show that in rat soleus muscles at 11 mM K+, the almost complete recovery of compound action potentials and force with muscle acidification (CO2 changed from 5 to 24%) was associated with reduced chloride conductance (1731 ± 151 to 938 ± 64 μS/cm2, P < 0.01) but not with changes in potassium conductance (405 ± 20 to 455 ± 30 μS/cm2, P < 0.16). Furthermore, acidification reduced the rheobase current by 26% at 4 mM K+ and increased the number of excitable fibers at elevated [K+]o. At 11 mM K+ and normal pH, a recovery of excitability and force similar to the observations with muscle acidification could be induced by reducing extracellular Cl− or by blocking the major muscle Cl− channel, ClC-1, with 30 μM 9-AC. It is concluded that recovery of excitability in K+-depressed muscles induced by muscle acidification is related to reduction in the inhibitory Cl− currents, possibly through inhibition of ClC-1 channels, and acidosis thereby reduces the Na+ current needed to generate and propagate an AP. Thus short term regulation of Cl− channels is important for maintenance of excitability in working muscle. PMID:15684096

  12. Regulation of blood flow distribution in skeletal muscle: role of erythrocyte-released ATP

    PubMed Central

    Ellsworth, Mary L; Sprague, Randy S

    2012-01-01

    The maintenance of adequate tissue O2 levels in skeletal muscle is vital for normal physiology and requires a well regulated and appropriately distributed convective O2 supply. Inherent in this fundamental physiological process is the requirement for a mechanism which both senses tissue O2 need and locally adjusts flow to appropriately meet that need. Over the past several years we and others have suggested that, in skeletal muscle, O2 carrying erythrocytes participate in the regulation of total blood flow and its distribution by releasing ATP. Importantly, the release of this vasoactive molecule must be both rapid and well controlled if it is to serve an important physiological role. Here we provide insights into three distinct regulated signalling pathways within the erythrocyte that are activated by exposure to reduced O2 tension or in response to binding of agonists to the prostacyclin or β-adrenergic receptors. Although much has been learned about the role of the erythrocyte in perfusion of skeletal muscle, much remains to be understood. However, what is clear is that the long established passive carrier of O2 also contributes to the regulation of the distribution of microvascular perfusion in skeletal muscle by virtue of its capacity to release ATP. PMID:22586223

  13. Regulation of blood flow distribution in skeletal muscle: role of erythrocyte-released ATP.

    PubMed

    Ellsworth, Mary L; Sprague, Randy S

    2012-10-15

    The maintenance of adequate tissue O(2) levels in skeletal muscle is vital for normal physiology and requires a well regulated and appropriately distributed convective O(2) supply. Inherent in this fundamental physiological process is the requirement for a mechanism which both senses tissue O(2) need and locally adjusts flow to appropriately meet that need. Over the past several years we and others have suggested that, in skeletal muscle, O(2) carrying erythrocytes participate in the regulation of total blood flow and its distribution by releasing ATP. Importantly, the release of this vasoactive molecule must be both rapid and well controlled if it is to serve an important physiological role. Here we provide insights into three distinct regulated signalling pathways within the erythrocyte that are activated by exposure to reduced O(2) tension or in response to binding of agonists to the prostacyclin or β-adrenergic receptors. Although much has been learned about the role of the erythrocyte in perfusion of skeletal muscle, much remains to be understood. However, what is clear is that the long established passive carrier of O(2) also contributes to the regulation of the distribution of microvascular perfusion in skeletal muscle by virtue of its capacity to release ATP.

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

    PubMed

    Harfmann, Brianna D; Schroder, Elizabeth A; Esser, Karyn A

    2015-04-01

    Circadian rhythms are the approximate 24-h biological cycles that function to prepare an organism for daily environmental changes. They are driven by the molecular clock, a transcriptional:translational feedback mechanism that in mammals involves the core clock genes Bmal1, Clock, Per1/2, and Cry1/2. The molecular clock is present in virtually all cells of an organism. The central clock in the suprachiasmatic nucleus (SCN) has been well studied, but the clocks in the peripheral tissues, such as heart and skeletal muscle, have just begun to be investigated. Skeletal muscle is one of the largest organs in the body, comprising approximately 45% of total body mass. More than 2300 genes in skeletal muscle are expressed in a circadian pattern, and these genes participate in a wide range of functions, including myogenesis, transcription, and metabolism. The circadian rhythms of skeletal muscle can be entrained both indirectly through light input to the SCN and directly through time of feeding and activity. It is critical for the skeletal muscle molecular clock not only to be entrained to the environment but also to be in synchrony with rhythms of other tissues. When circadian rhythms are disrupted, the observed effects on skeletal muscle include fiber-type shifts, altered sarcomeric structure, reduced mitochondrial respiration, and impaired muscle function. Furthermore, there are detrimental effects on metabolic health, including impaired glucose tolerance and insulin sensitivity, which skeletal muscle likely contributes to considering it is a key metabolic tissue. These data indicate a critical role for skeletal muscle circadian rhythms for both muscle and systems health. Future research is needed to determine the mechanisms of molecular clock function in skeletal muscle, identify the means by which skeletal muscle entrainment occurs, and provide a stringent comparison of circadian gene expression across the diverse tissue system of skeletal muscle.

  15. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

    Harfmann, Brianna D.; Schroder, Elizabeth A.; Esser, Karyn A.

    2015-01-01

    Circadian rhythms are the approximate 24-h biological cycles that function to prepare an organism for daily environmental changes. They are driven by the molecular clock, a transcriptional:translational feedback mechanism that in mammals involves the core clock genes Bmal1, Clock, Per1/2, and Cry1/2. The molecular clock is present in virtually all cells of an organism. The central clock in the suprachiasmatic nucleus (SCN) has been well studied, but the clocks in the peripheral tissues, such as heart and skeletal muscle, have just begun to be investigated. Skeletal muscle is one of the largest organs in the body, comprising approximately 45% of total body mass. More than 2300 genes in skeletal muscle are expressed in a circadian pattern, and these genes participate in a wide range of functions, including myogenesis, transcription, and metabolism. The circadian rhythms of skeletal muscle can be entrained both indirectly through light input to the SCN and directly through time of feeding and activity. It is critical for the skeletal muscle molecular clock not only to be entrained to the environment but also to be in synchrony with rhythms of other tissues. When circadian rhythms are disrupted, the observed effects on skeletal muscle include fiber-type shifts, altered sarcomeric structure, reduced mitochondrial respiration, and impaired muscle function. Furthermore, there are detrimental effects on metabolic health, including impaired glucose tolerance and insulin sensitivity, which skeletal muscle likely contributes to considering it is a key metabolic tissue. These data indicate a critical role for skeletal muscle circadian rhythms for both muscle and systems health. Future research is needed to determine the mechanisms of molecular clock function in skeletal muscle, identify the means by which skeletal muscle entrainment occurs, and provide a stringent comparison of circadian gene expression across the diverse tissue system of skeletal muscle. PMID:25512305

  16. Skeletal muscle inflammation and atrophy in heart failure.

    PubMed

    Lavine, Kory J; Sierra, Oscar L

    2017-03-01

    Heart failure represents a systemic disease with profound effects on multiple peripheral tissues including skeletal muscle. Within the context of heart failure, perturbations in skeletal muscle physiology, structure, and function strongly contribute to exercise intolerance and the morbidity of this devastating disease. There is growing evidence that chronic heart failure imparts specific pathological changes within skeletal muscle beds resulting in muscle dysfunction and tissue atrophy. Mechanistically, systemic and local inflammatory responses drive critical aspects of this pathology. In this review, we will discuss pathological mechanisms that drive skeletal muscle inflammation and highlight emerging roles for distinct innate immune subsets that reside within damage muscle tissue focusing on the recently described embryonic and monocyte-derived macrophage lineages. Within this context, we will discuss how immune mechanisms can be differentially targeted to stimulate skeletal muscle inflammation, catabolism, fiber atrophy, and regeneration.

  17. Looking beyond structure: membrane phospholipids of skeletal muscle mitochondria

    PubMed Central

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

    2016-01-01

    Skeletal muscle mitochondria are highly dynamic and capable of tremendous expansion to meet cellular energetic demands. Such proliferation in mitochondrial mass requires a synchronized supply of enzymes and structural phospholipids. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are generated in skeletal muscle. Herein we describe how each class of phospholipids that constitute mitochondrial membranes are synthesized and/or imported, and summarize genetic evidence indicating that membrane phospholipid composition represents a significant modulator of skeletal muscle mitochondrial respiratory function. We also discuss how skeletal muscle mitochondrial phospholipids may mediate the effect of diet and exercise on oxidative metabolism. PMID:27370525

  18. Amino acids in healthy aging skeletal muscle.

    PubMed

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

    2016-01-01

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

  19. Modeling of the Skeletal Muscle Microcirculation

    NASA Astrophysics Data System (ADS)

    Jacobitz, Frank; Beth, Christophe; Salado, Jerome

    2004-11-01

    Numerical simulations of blood flow in a microvascular network require extensive modeling. This contribution focuses on the reconstruction of a complete network topology from microscopic images of rat skeletal muscle and skeletal muscle fascia. The bifurcating network is composed of a feeding arterial network, a collecting venous network, and bundles of capillaries. Multiple topologies of each network component are recontructed and statistical properties of the network, such as distributions of vessel diameters, vessel lengths, and branching patters are determined. Particular attention has been paid to venous vessel loops that are observed only in the muscle fascia. The flow in the microvessel network is then computed. In the simulations, the microvessels are distensible by pressure, and the arterioles are actively contractile. The blood has non-Newtonian apparent viscosity. Models of each of these properties have previously been determined and are used in the computations. The method of indefinite admittances is used to compute the flow in the network. The apparent viscosity is computed from the local hematocrit, which is found using a combination of breadth first search and Dykstra's algorithms. The computations allow the determination of additional properties of the network, such as flow velocities, shear stresses, and hematocrit.

  20. Characterization of human skeletal muscle Ankrd2.

    PubMed

    Pallavicini, A; Kojić, S; Bean, C; Vainzof, M; Salamon, M; Ievolella, C; Bortoletto, G; Pacchioni, B; Zatz, M; Lanfranchi, G; Faulkner, G; Valle, G

    2001-07-13

    Human Ankrd2 transcript encodes a 37-kDa protein that is similar to mouse Ankrd2 recently shown to be involved in hypertrophy of skeletal muscle. These novel ankyrin-rich proteins are related to C-193/CARP/MARP, a cardiac protein involved in the control of cardiac hypertrophy. A human genomic region of 14,300 bp was sequenced revealing a gene organization similar to mouse Ankrd2 with nine exons, four of which encode ankyrin repeats. The intracellular localization of Ankrd2 was unknown since no protein studies had been reported. In this paper we studied the intracellular localization of the protein and its expression on differentiation using polyclonal and monoclonal antibodies produced to human Ankrd2. In adult skeletal muscle Ankrd2 is found in slow fibers; however, not all of the slow fibers express Ankrd2 at the same level. This is particularly evident in dystrophic muscles, where the expression of Ankrd2 in slow fibers seems to be severely reduced. Copyright 2001 Academic Press.

  1. Molecular networks in skeletal muscle plasticity.

    PubMed

    Hoppeler, Hans

    2016-01-01

    The skeletal muscle phenotype is subject to considerable malleability depending on use as well as internal and external cues. In humans, low-load endurance-type exercise leads to qualitative changes of muscle tissue characterized by an increase in structures supporting oxygen delivery and consumption, such as capillaries and mitochondria. High-load strength-type exercise leads to growth of muscle fibers dominated by an increase in contractile proteins. In endurance exercise, stress-induced signaling leads to transcriptional upregulation of genes, with Ca(2+) signaling and the energy status of the muscle cells sensed through AMPK being major input determinants. Several interrelated signaling pathways converge on the transcriptional co-activator PGC-1α, perceived to be the coordinator of much of the transcriptional and post-transcriptional processes. Strength training is dominated by a translational upregulation controlled by mTORC1. mTORC1 is mainly regulated by an insulin- and/or growth-factor-dependent signaling cascade as well as mechanical and nutritional cues. Muscle growth is further supported by DNA recruitment through activation and incorporation of satellite cells. In addition, there are several negative regulators of muscle mass. We currently have a good descriptive understanding of the molecular mechanisms controlling the muscle phenotype. The topology of signaling networks seems highly conserved among species, with the signaling outcome being dependent on the particular way individual species make use of the options offered by the multi-nodal networks. As a consequence, muscle structural and functional modifications can be achieved by an almost unlimited combination of inputs and downstream signaling events.

  2. Biophysical Stimulation for Engineering Functional Skeletal Muscle.

    PubMed

    Somers, Sarah; Spector, Alexander; DiGirolamo, Douglas; Grayson, Warren L

    2017-04-12

    Tissue engineering is a promising therapeutic strategy to regenerate skeletal muscle. However, ex vivo cultivation methods typically result in a low differentiation efficiency of stem cells as well as grafts that resemble the native tissues morphologically, but lack contractile function. The application of biomimetic tensile strain provides a potent stimulus for enhancing myogenic differentiation and engineering functional skeletal muscle grafts. We reviewed integrin-dependent mechanisms that potentially link mechanotransduction pathways to the upregulation of myogenic genes. Yet, gaps in our understanding make it challenging to use these pathways to theoretically determine optimal ex vivo strain regimens. A multitude of strain protocols have been applied to in vitro cultures for the cultivation of myogenic progenitors (adipose- and bone marrow-derived stem cells & satellite cells) and transformed murine myoblasts, C2C12s. Strain regimen are characterized by orientation, amplitude, and time-dependent factors (effective frequency, duration, and the rest period between successive strain cycles). Analysis of published data has identified possible minimum/maximum values for these parameters and suggests that uniaxial strains may be more potent than biaxial strains possibly because they more closely mimic physiologic strain profiles. The application of these biophysical stimuli for engineering 3D skeletal muscle grafts is non-trivial and typically requires custom-designed bioreactors used in combination with biomaterial scaffolds. Consideration of the physical properties of these scaffolds is critical for effective transmission of the applied strains to encapsulated cells. Taken together, these studies demonstrate that biomimetic tensile strain generally results in improved myogenic outcomes in myogenic progenitors and differentiated myoblasts. However, for 3D systems, the optimization of the strain regimen may require the entire system - cells, biomaterials, and

  3. Historical Perspectives: plasticity of mammalian skeletal muscle.

    PubMed

    Pette, D

    2001-03-01

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

  4. Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations.

    PubMed Central

    Hespel, P; Richter, E A

    1990-01-01

    1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control hindquarters; in supercompensated hindquarters it was 30% lower. When rats with similar muscle glycogen concentrations were compared, glucose uptake in hindquarters from rats that had exercised on the preceding day was approximately 20% higher than in hindquarters from rats that had not exercised on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O-methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular concentrations of free glucose and glucose-6-phosphate were higher at rest and during the entire 15-min stimulation period in supercompensated muscles than in glycogen-depleted muscles, and glucose uptake during contractions correlated negatively with free glucose (r = -0.52; P less than 0.01) as well as with glucose-6-phosphate (r = -0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the

  5. Strategies for skeletal muscle targeting in drug discovery.

    PubMed

    Ebner, David C; Bialek, Peter; El-Kattan, Ayman F; Ambler, Catherine M; Tu, Meihua

    2015-01-01

    The targeting of drugs to skeletal muscle is an emerging area of research. Driven by the need for new therapies to treat a range of muscle-associated diseases, these strategies aim to provide improved drug exposure at the site of action in skeletal muscle with reduced concentration in other tissues where unwanted side effects could occur. By interacting with muscle-specific cell surface recognition elements, both tissue localization and selective uptake into skeletal muscle cells can be achieved. The design of molecules that are substrates for muscle uptake transporters can provide concentration in m uscle tissue. For example, drug conjugates with carnitine can provide improved muscle uptake via OCTN2 transport. Binding to muscle surface recognition elements followed by endocytosis can allow even large molecules such as antibodies to enter muscle cells. Monoclonal antibody 3E10 demonstrated selective uptake into skeletal muscle in vivo. Hybrid adeno-associated viral vectors have recently shown promise for high skeletal muscle selectivity in gene transfer applications. Delivery technology methods, including electroporation of DNA plasmids, have also been investigated for selective muscle uptake. This review discusses challenges and opportunities for skeletal muscle targeting, highlighting specific examples and areas in need of additional research.

  6. FOXO1 delays skeletal muscle regeneration and suppresses myoblast proliferation.

    PubMed

    Yamashita, Atsushi; Hatazawa, Yukino; Hirose, Yuma; Ono, Yusuke; Kamei, Yasutomi

    2016-08-01

    Unloading stress, such as bed rest, inhibits the regenerative potential of skeletal muscles; however, the underlying mechanisms remain largely unknown. FOXO1 expression, which induces the upregulated expression of the cell cycle inhibitors p57 and Gadd45α, is known to be increased in the skeletal muscle under unloading conditions. However, there is no report addressing FOXO1-induced inhibition of myoblast proliferation. Therefore, we induced muscle injury by cardiotoxin in transgenic mice overexpressing FOXO1 in the skeletal muscle (FOXO1-Tg mice) and observed regeneration delay in skeletal muscle mass and cross-sectional area in FOXO1-Tg mice. Increased p57 and Gadd45α mRNA levels, and decreased proliferation capacity were observed in C2C12 myoblasts expressing a tamoxifen-inducible active form of FOXO1. These results suggest that decreased proliferation capacity of myoblasts by FOXO1 disrupts skeletal muscle regeneration under FOXO1-increased conditions, such as unloading.

  7. Skeletal muscle responses to unloading in humans

    NASA Technical Reports Server (NTRS)

    Dudley, G.; Tesch, P.; Hather, B.; Adams, G.; Buchanan, P.

    1992-01-01

    This study examined the effects of unloading on skeletal muscle structure. Method: Eight subjects walked on crutches for six weeks with a 110 cm elevated sole on the right shoe. This removed weight bearing by the left lower limb. Magnetic resonance imaging of both lower limbs and biopsies of the left m. vastus laterallis (VL) were used to study muscle structure. Results: Unloading decreased (P less than 0.05) muscle cross-sectional areas (CSA) of the knee extensors 16 percent. The knee flexors showed about 1/2 of this response (-7 percent, P less than 0.05). The three vasti muscles each showed decreases (P less than 0.05) of about 15 percent. M. rectus femoris did not change. Mean fiber CSA in VL decreased (P less than 0.05) 14 percent with type 2 and type 1 fibers showing reductions of 15 and 11 percent respectively. The ankle extensors showed a 20 percent decrease (P less than 0.05) in CSA. The reduction for the 'fast' m. gastrocnemius was 27 percent compared to the 18 percent decrease for the 'slow' soleus. Summary: The results suggest that decreases in muscle CSA are determined by the relative change in impact loading history because atrophy was (1) greater in extensor than flexor muscles, (2) at least as great in fast as compared to slow muscles or fibers, and (3) not dependent on single or multi-joint function. They also suggest that the atrophic responses to unloading reported for lower mammals are quantitatively but not qualitatively similar to those of humans.

  8. Regulation of skeletal muscle blood flow during exercise in ageing humans

    PubMed Central

    Hearon, Christopher M.

    2015-01-01

    Abstract The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium‐derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age‐associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium‐derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin‐1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. ‘functional sympatholysis’), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium‐dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age‐associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium‐dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans. PMID:26332887

  9. The regulation of glycolysis in perfused locust flight muscle

    PubMed Central

    Ford, W. C. L.; Candy, D. J.

    1972-01-01

    Concentrations of glycolytic intermediates, amino acids and possible regulator substances were measured in extracts from locust thoracic muscles perfused under different conditions. The conversion of [14C]glucose into intermediates and CO2 by muscle preparations was also followed. When muscles perfused with glucose were made anaerobic changes in metabolite concentrations occurred that could be accounted for by an activation of phosphofructokinase and pyruvate kinase. When butyrate and glucose were present in the perfusion medium the rate of glycolytic flux was lower than with glucose alone, and the aldolase reaction appeared to be inhibited. When butyrate alone was supplied to the muscle the concentrations of most glycolytic intermediates were similar to those found when glucose was supplied. Iodoacetate caused changes in concentrations of intermediates that appeared to result from inhibition of glyceraldehyde 3-phosphate dehydrogenase. Fluoroacetate-poisoned muscles showed a high citrate concentration, but no obvious site of inhibition by citrate was apparent in the glycolytic pathway. Mechanisms for control of glycolysis in locust flight muscle are discussed and related to the known properties of isolated enzymes. It is proposed that trehalase, hexokinase, phosphofructokinase, aldolase, and pyruvate kinase may be control enzymes in this tissue. PMID:4266373

  10. [Effect of taurine on the microvessel exchange function and adrenergic response of veins and arteries in the cat skeletal muscle].

    PubMed

    Kudriashov, Iu A; Denisov, P I

    2001-01-01

    In cats anesthetized with Uretan and perfused with a constant blood volume, Taurine induced responses of neither arterial nor venous vessels of the skeletal muscle but increased the capillary filtration coefficient without any significant change of the capillary pressure in the skeletal muscle's microvessels. Taurine also increased both the constrictor and the dilatory responses of the arterial and venous vessels. The mechanism of the Taurine effects upon the smooth muscle elements of arteries and veins as well as upon proper mechanisms of capillary pressure control and capillary filtration coefficient, seems to be calcium-dependent.

  11. Motor force homeostasis in skeletal muscle contraction.

    PubMed

    Chen, Bin; Gao, Huajian

    2011-07-20

    In active biological contractile processes such as skeletal muscle contraction, cellular mitosis, and neuronal growth, an interesting common observation is that multiple motors can perform coordinated and synchronous actions, whereas individual myosin motors appear to randomly attach to and detach from actin filaments. Recent experiment has demonstrated that, during skeletal muscle shortening at a wide range of velocities, individual myosin motors maintain a force of ~6 pN during a working stroke. To understand how such force-homeostasis can be so precisely regulated in an apparently chaotic system, here we develop a molecular model within a coupled stochastic-elastic theoretical framework. The model reveals that the unique force-stretch relation of myosin motor and the stochastic behavior of actin-myosin binding cause the average number of working motors to increase in linear proportion to the filament load, so that the force on each working motor is regulated at ~6 pN, in excellent agreement with experiment. This study suggests that it might be a general principle to use catch bonds together with a force-stretch relation similar to that of myosin motors to regulate force homeostasis in many biological processes. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Three dimensional multi-cellular muscle-like tissue engineering in perfusion-based bioreactors.

    PubMed

    Cerino, Giulia; Gaudiello, Emanuele; Grussenmeyer, Thomas; Melly, Ludovic; Massai, Diana; Banfi, Andrea; Martin, Ivan; Eckstein, Friedrich; Grapow, Martin; Marsano, Anna

    2016-01-01

    Conventional tissue engineering strategies often rely on the use of a single progenitor cell source to engineer in vitro biological models; however, multi-cellular environments can better resemble the complexity of native tissues. Previous described co-culture models used skeletal myoblasts, as parenchymal cell source, and mesenchymal or endothelial cells, as stromal component. Here, we propose instead the use of adipose tissue-derived stromal vascular fraction cells, which include both mesenchymal and endothelial cells, to better resemble the native stroma. Percentage of serum supplementation is one of the crucial parameters to steer skeletal myoblasts toward either proliferation (20%) or differentiation (5%) in two-dimensional culture conditions. On the contrary, three-dimensional (3D) skeletal myoblast culture often simply adopts the serum content used in monolayer, without taking into account the new cell environment. When considering 3D cultures of mm-thick engineered tissues, homogeneous and sufficient oxygen supply is paramount to avoid formation of necrotic cores. Perfusion-based bioreactor culture can significantly improve the oxygen access to the cells, enhancing the viability and the contractility of the engineered tissues. In this study, we first investigated the influence of different serum supplementations on the skeletal myoblast ability to proliferate and differentiate during 3D perfusion-based culture. We tested percentages of serum promoting monolayer skeletal myoblast-proliferation (20%) and differentiation (5%) and suitable for stromal cell culture (10%) with a view to identify the most suitable condition for the subsequent co-culture. The 10% serum medium composition resulted in the highest number of mature myotubes and construct functionality. Co-culture with stromal vascular fraction cells at 10% serum also supported the skeletal myoblast differentiation and maturation, hence providing a functional engineered 3D muscle model that resembles

  14. Satellite cell proliferation in adult skeletal muscle

    NASA Technical Reports Server (NTRS)

    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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. ANG1 treatment reduces muscle pathology and prevents a decline in perfusion in DMD mice

    PubMed Central

    Tasevski, Nikola; Wong, Boaz; Hrinivich, William Thomas; Su, Feng; Hadway, Jennifer; Desjardins, Lise; Lee, Ting-Yim; Hoffman, Lisa Marie

    2017-01-01

    Vascular endothelial growth factor (VEGF) and other pro-angiogenic growth factors have been investigated to enhance muscle tissue perfusion and repair in Duchenne muscular dystrophy (DMD). Current understanding is limited by a lack of functional data following in vivo delivery of these growth factors. We previously used dynamic contrast-enhanced computed tomography to monitor disease progression in murine models of DMD, but no study to date has utilized this imaging technique to assess vascular therapy in a preclinical model of DMD. In the current study, we locally delivered VEGF and ANG1 alone or in combination to dystrophic hind limb skeletal muscle. Using functional imaging, we found the combination treatment as well as ANG1 alone prevented decline in muscle perfusion whereas VEGF alone had no effect compared to controls. These findings were validated histologically as demonstrated by increased alpha-smooth muscle actin-positive vessels in muscles that received either VEGF+ANG1 or ANG1 alone compared to the sham group. We further show that ANG1 alone slows progression of fibrosis compared to either sham or VEGF treatment. The findings from this study shed new light on the functional effects of vascular therapy and suggest that ANG1 alone may be a candidate therapy in the treatment of DMD. PMID:28334037

  17. Regulation of glucose transport in skeletal muscle.

    PubMed

    Barnard, R J; Youngren, J F

    1992-11-01

    The entry of glucose into muscle cells is achieved primarily via a carrier-mediated system consisting of protein transport molecules. GLUT-1 transporter isoform is normally found in the sarcolemmal (SL) membrane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 transporters from an intracellular pool out to the T-tubule and SL membranes. Activation of transporters to increase the turnover number may also be involved, but the evidence is far from conclusive. When insulin binds to its receptor, it autophosphorylates tyrosine and serine residues on the beta-subunit of the receptor. The tyrosine residues are thought to activate tyrosine kinases, which in turn phosphorylate/activate as yet unknown second messengers. Insulin receptor antibodies, however, have been reported to increase glucose transport without increasing kinase activity. Insulin resistance in skeletal muscle is a major characteristic of obesity and diabetes mellitus, especially NIDDM. A decrease in the number of insulin receptors and the ability of insulin to activate receptor tyrosine kinase has been documented in muscle from NIDDM patients. Most studies report no change in the intracellular pool of GLUT-4 transporters available for translocation to the SL. Both the quality and quantity of food consumed can regulate insulin sensitivity. A high-fat, refined sugar diet, similar to the typical U.S. diet, causes insulin resistance when compared with a low-fat, complex-carbohydrate diet. On the other hand, exercise increases insulin sensitivity. After an acute bout of exercise, glucose transport in muscle increases to the same level as with maximum insulin stimulation. Although the number of GLUT-4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved. After an initial acute phase, which may involve calcium as the activator, a secondary phase of increased

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

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman W.

    1987-01-01

    New muscle tissue culture techniques were developed to grow embryonic skeletal myofibers which are able to differentiate into more adultlike myofibers. Studies on mechanical simulation of cultured muscle cell growth will now be more directly applicable to mechanically-induced growth in adult muscle, and lead to better models for understanding muscle tissue atrophy caused by disuse in the microgravity of space.

  19. Cryopreservation of human skeletal muscle impairs mitochondrial function.

    PubMed

    Larsen, S; Wright-Paradis, C; Gnaiger, E; Helge, J W; Boushel, R

    2012-01-01

    Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity of oxidative phosphorylation was significantly (P < 0.05) reduced in cryopreserved human skeletal muscle samples. Cryopreservation impaired respiration with substrates linked to Complex I more than for Complex II (P < 0.05). Addition of cytochrome c revealed an increase in respiration indicating cytochrome c loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples.

  20. [Research progress of scaffold materials in skeletal muscle tissue engineering].

    PubMed

    Huang, Weiyi; Liao, Hua

    2010-11-01

    To review the current researches of scaffold materials for skeletal muscle tissue engineering, to predict the development trend of scaffold materials in skeletal muscle tissue engineering in future. The related literature on skeletal muscle tissue engineering, involving categories and properties of scaffold materials, preparative technique and biocompatibility, was summarized and analyzed. Various scaffold materials were used in skeletal muscle tissue engineering, including inorganic biomaterials, biodegradable polymers, natural biomaterial, and biomedical composites. According to different needs of the research, various scaffolds were prepared due to different biomaterials, preparative techniques, and surface modifications. The development trend and perspective of skeletal muscle tissue engineering are the use of composite materials, and the preparation of composite scaffolds and surface modification according to the specific functions of scaffolds.

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

    PubMed

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

    2015-11-19

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

  2. Omega-3 Fatty Acids and Skeletal Muscle Health

    PubMed Central

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

    2015-01-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal 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. PMID:26610527

  3. Strategies for functional bioscaffold-based skeletal muscle reconstruction

    PubMed Central

    Sicari, Brian M.; Dziki, Jenna L.

    2015-01-01

    Tissue engineering and regenerative medicine-based strategies for the reconstruction of functional skeletal muscle tissue have included cellular and acellular approaches. The use of acellular biologic scaffold material as a treatment for volumetric muscle loss (VML) in five patients has recently been reported with a generally favorable outcome. Further studies are necessary for a better understanding of the mechanism(s) behind acellular bioscaffold-mediated skeletal muscle repair, and for combination cell-based/bioscaffold based approaches. The present overview highlights the current thinking on bioscaffold-based remodeling including the associated mechanisms and the future of scaffold-based skeletal muscle reconstruction. PMID:26605302

  4. [Calcium leak of sarcoplasmic reticulum induces degradation of troponin I in skeletal muscle fibers.].

    PubMed

    Li, Quan; Wang, Yun-Ying; Li, Hui; Jiao, Bo; Yu, Zhi-Bin

    2009-06-25

    The troponin I subunit (TnI) was used as a molecular marker to explore the relationship between the resting intracellular Ca(2+) concentration and myofibril degradation in muscle fibers. The isolated soleus muscle strips of rats were treated by caffeine and H2O2. Caffeine is an opener to increase the calcium release channel open probability of sarcoplasmic reticulum (SR) in contraction phase. H2O2 induces a calcium leak of SR calcium release channel in relaxation phase. The expression and degradation of TnI were detected by Western blot. The resting tension of tetanic contraction and expression of TnI were not changed, but the developed tension was lowered in isolated soleus muscle strips during 40 min of calcium-free Krebs perfusion. Low concentrations of caffeine (1 and 5 mmol/L) perfusion induced a transient increase in resting tension during fatigue period, but did not alter the extent of fatigue, recovery rate after fatigue and expression of TnI in muscle strips. High concentration of caffeine (10 mmol/L) perfusion induced a progressive increase in resting tension, a higher rate of fatigue and a decrease in recovery rate after fatigue in muscle strips. There was a detectable degradation of TnI in soleus after 10 mmol/L caffeine treatment. H2O2 perfusion facilitated a progressive increase in resting tension in a dose-dependent manner, but did not influence the fatigue rate of tetanic contraction. The recovery rate after fatigue showed a quick resumption before decline during H2O2 perfusion. Degradation of TnI occurred in 5 and 10 mmol/L H2O2-treated soleus muscles. Since resting tension is dependent on intracellular Ca(2+) concentration, the above-mentioned results suggest that SR Ca(2+) leakage in relaxation phase may induce a degradation of TnI in skeletal muscle fibers.

  5. Acute skeletal muscle wasting in critical illness.

    PubMed

    Puthucheary, Zudin A; Rawal, Jaikitry; McPhail, Mark; Connolly, Bronwen; Ratnayake, Gamunu; Chan, Pearl; Hopkinson, Nicholas S; Phadke, Rahul; Padhke, Rahul; Dew, Tracy; Sidhu, Paul S; Velloso, Cristiana; Seymour, John; Agley, Chibeza C; Selby, Anna; Limb, Marie; Edwards, Lindsay M; Smith, Kenneth; Rowlerson, Anthea; Rennie, Michael John; Moxham, John; Harridge, Stephen D R; Hart, Nicholas; Montgomery, Hugh E

    2013-10-16

    Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment. To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown. Sixty-three critically ill patients (59% male; mean age: 54.7 years [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay. Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized. There were significant reductions in the rectus femoris CSA observed at day 10 (−17.7% [95% CI, −25.9% to 8.1%]; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1% to 14.5%), the fiber CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5% (95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (−15.7%; 95% CI, −27.7% to 11.4%) compared with single organ failure (−3.0%; 95% CI, −5.3% to 2.1%) (P < .001), even by day 3 (−8.7% [95% CI, −59.3% to 50.6%] vs −1.8% [95% CI, −12.3% to 10.5%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37

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

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.

    1987-01-01

    Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

  7. Na,K-ATPase regulation in skeletal muscle.

    PubMed

    Pirkmajer, Sergej; Chibalin, Alexander V

    2016-07-01

    Skeletal muscle contains one of the largest and the most dynamic pools of Na,K-ATPase (NKA) in the body. Under resting conditions, NKA in skeletal muscle operates at only a fraction of maximal pumping capacity, but it can be markedly activated when demands for ion transport increase, such as during exercise or following food intake. Given the size, capacity, and dynamic range of the NKA pool in skeletal muscle, its tight regulation is essential to maintain whole body homeostasis as well as muscle function. To reconcile functional needs of systemic homeostasis with those of skeletal muscle, NKA is regulated in a coordinated manner by extrinsic stimuli, such as hormones and nerve-derived factors, as well as by local stimuli arising in skeletal muscle fibers, such as contractions and muscle energy status. These stimuli regulate NKA acutely by controlling its enzymatic activity and/or its distribution between the plasma membrane and the intracellular storage compartment. They also regulate NKA chronically by controlling NKA gene expression, thus determining total NKA content in skeletal muscle and its maximal pumping capacity. This review focuses on molecular mechanisms that underlie regulation of NKA in skeletal muscle by major extrinsic and local stimuli. Special emphasis is given to stimuli and mechanisms linking regulation of NKA and energy metabolism in skeletal muscle, such as insulin and the energy-sensing AMP-activated protein kinase. Finally, the recently uncovered roles for glutathionylation, nitric oxide, and extracellular K(+) in the regulation of NKA in skeletal muscle are highlighted. Copyright © 2016 the American Physiological Society.

  8. Expanding roles for AMPK in skeletal muscle plasticity.

    PubMed

    Mounier, Rémi; Théret, Marine; Lantier, Louise; Foretz, Marc; Viollet, Benoit

    2015-06-01

    Skeletal muscle possesses a remarkable plasticity and responds to environmental and physiological challenges by changing its phenotype in terms of size, composition, and metabolic properties. Muscle fibers rapidly adapt to drastic changes in energy demands during exercise through fine-tuning of the balance between catabolic and anabolic processes. One major sensor of energy demand in exercising muscle is AMP-activated protein kinase (AMPK). Recent advances have shed new light on the relevance of AMPK both as a multitask gatekeeper and as an energy regulator in skeletal muscle. Here we summarize recent findings on the function of AMPK in skeletal muscle adaptation to contraction and highlight its role in the regulation of energy metabolism and the control of skeletal muscle regeneration post-injury.

  9. The effect of ischemic preconditioning on the recovery of skeletal muscle following tourniquet ischemia.

    PubMed

    Whetzel, T P; Stevenson, T R; Sharman, R B; Carlsen, R C

    1997-12-01

    It has been well documented that ischemic preconditioning limits ischemic-reperfusion injury in cardiac muscle, but the ability of ischemic preconditioning to limit skeletal muscle injury is less clear. Previous reports have emphasized the beneficial effects of ischemic preconditioning on skeletal muscle structure and capillary perfusion but have not evaluated muscle function. We investigated the morphologic and functional consequences of ischemic preconditioning, followed by a 2-hour period of tourniquet ischemia on muscles in the rat hindlimb. The 2-hour ischemia was imposed without preconditioning, or was preceded by three brief (10 minutes on/10 minutes off) preischemic conditioning intervals. We compared muscle morphology, isometric contractile function, and muscle fatigue properties in predominantly fast-twitch, tibialis anterior muscles 3 (n = 8) and 7 (n = 8) days after ischemia-reperfusion. Two hours of ischemia, followed by reperfusion, results in a 20 percent reduction of muscle mass (p < 0.05) and a 33 percent reduction in tetanic tension (p < 0.05) when compared with controls (n = 8) at 3 days. The same protocol, when preceded by ischemic preconditioning, results in similar decreases in muscle mass and contractile function. Neuromuscular transmission was also impaired in both ischemic groups 7 days after ischemia. Nerve-evoked maximum tetanic tension was 69 percent of the tension produced by direct muscle stimulation in the ischemia group and 65 percent of direct tension in the ischemic preconditioning/ischemia group. In summary, ischemic preconditioning, using the same protocol reported to be effective in limiting infarct size in porcine muscle, had no significant benefit in limiting injury or improving recovery in the ischemic rat tibialis anterior. The value of ischemic preconditioning in reducing imposed ischemic-reperfusion-induced functional deficits in skeletal muscle remains to be demonstrated.

  10. [Morphometric characteristics of neuromuscular spindles in hypertrophied skeletal muscle].

    PubMed

    Mytskan, B M; Mel'man, E P

    1986-11-01

    Skeletal muscle hypertrophy in young male rats was found to be accompanied by adaptive changes in neuromuscular spindles. The changes consisted in connective capsule thickening, increased diameter of NMS and intrafusal muscle fibers, expanded afferent and efferent nerve terminals, increased microcirculatory bed capacity. The quantitative and qualitative shifts observed in NMS structure are morphologically equivalent to the rise in their functional potential, which forms the basis for the functional changes in conditions of increasing skeletal muscle hypertrophy.

  11. Skeletal muscle dedifferentiation during salamander limb regeneration.

    PubMed

    Wang, Heng; Simon, András

    2016-10-01

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

  12. Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis

    PubMed Central

    Tierney, Matthew T.; Sacco, Alessandra

    2016-01-01

    The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity. PMID:26948993

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

    PubMed

    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 < 0.01) and an increased expression of glycolytic enzymes (lactate dehydrogenase activity, p < 0.05). These findings were supported by abnormal mitochondrial morphology on electronic microscopy, lower citrate synthase activity (p < 0.01) and lower expression of the transcription factor A of the mitochondria (p < 0.05), confirming a more glycolytic 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.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Developmentally regulated alternative splicing is perturbed in type 1 diabetic skeletal muscle.

    PubMed

    Nutter, Curtis A; Jaworski, Elizabeth; Verma, Sunil K; Perez-Carrasco, Yareli; Kuyumcu-Martinez, Muge N

    2017-02-06

    Type 1 diabetic patients can develop skeletal muscle weakness and atrophy by molecular mechanisms that are not well understood. Alternative splicing (AS) is critical for gene expression in the skeletal muscle, and its dysregulation is implicated in muscle weakness and atrophy. Therefore, we investigated whether AS patterns are affected in type 1 diabetic skeletal muscle contributing to skeletal muscle defects. AS patterns were determined by reverse transcription-polymerase chain reaction and levels of RNA binding proteins were assessed by Western blot in type 1 diabetic mouse skeletal muscle and during normal mouse skeletal muscle development. Five genes with critical functions in the skeletal muscle are misspliced in type 1 diabetic skeletal muscle, resembling their AS patterns at embryonic stages. AS of these genes undergoes dramatic transitions during skeletal muscle development, correlating with changes in specific RNA binding proteins. Embryonic spliced variants are inappropriately expressed in type 1 diabetic skeletal muscle. Muscle Nerve, 2017. © 2017 Wiley Periodicals, Inc.

  17. Imaging of skeletal muscle in vitamin D deficiency

    PubMed Central

    Bignotti, Bianca; Cadoni, Angela; Martinoli, Carlo; Tagliafico, Alberto

    2014-01-01

    Elderly people are prone to accidental falls and one of the main risk factor is considered muscle weakness. Several studies focused on muscle weakness and muscle morphology changes in the elderly that may be associated with vitamin D deficiency. The prevalence of vitamin D deficiency is higher than previously though representing an important issue for public health and prevention. There is an increased interest in vitamin D effects in skeletal muscle and imaging modalities are particularly involved in this field. In patients with vitamin D deficiency, ultrasound, computed tomography, densitometry and magnetic resonance imaging (MRI) can efficiently describe changes in muscle morphology and size. Moreover, new imaging modalities, such as MRI spectroscopy, may improve knowledge about the metabolic effects of vitamin D in skeletal muscle. In this narrative review we will discuss the role of skeletal muscle imaging in vitamin D-deficient individuals. The aim of this paper is to improve and encourage the role of radiologists in this field. PMID:24778774

  18. Exercise and the Regulation of Skeletal Muscle Hypertrophy.

    PubMed

    McGlory, Chris; Phillips, Stuart M

    2015-01-01

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

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

    PubMed

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

    2017-01-01

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

  20. Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

    PubMed Central

    Shankaran, Mahalakshmi; King, Chelsea L.; Angel, Thomas E.; Holmes, William E.; Li, Kelvin W.; Colangelo, Marc; Price, John C.; Turner, Scott M.; Bell, Christopher; Hamilton, Karyn L.; Miller, Benjamin F.; Hellerstein, Marc K.

    2015-01-01

    Here, we have described and validated a strategy for monitoring skeletal muscle protein synthesis rates in rodents and humans over days or weeks from blood samples. We based this approach on label incorporation into proteins that are synthesized specifically in skeletal muscle and escape into the circulation. Heavy water labeling combined with sensitive tandem mass spectrometric analysis allowed integrated synthesis rates of proteins in muscle tissue across the proteome to be measured over several weeks. Fractional synthesis rate (FSR) of plasma creatine kinase M-type (CK-M) and carbonic anhydrase 3 (CA-3) in the blood, more than 90% of which is derived from skeletal muscle, correlated closely with FSR of CK-M, CA-3, and other proteins of various ontologies in skeletal muscle tissue in both rodents and humans. Protein synthesis rates across the muscle proteome generally changed in a coordinate manner in response to a sprint interval exercise training regimen in humans and to denervation or clenbuterol treatment in rodents. FSR of plasma CK-M and CA-3 revealed changes and interindividual differences in muscle tissue proteome dynamics. In human subjects, sprint interval training primarily stimulated synthesis of structural and glycolytic proteins. Together, our results indicate that this approach provides a virtual biopsy, sensitively revealing individualized changes in proteome-wide synthesis rates in skeletal muscle without a muscle biopsy. Accordingly, this approach has potential applications for the diagnosis, management, and treatment of muscle disorders. PMID:26657858

  1. Polyplex nanomicelle promotes hydrodynamic gene introduction to skeletal muscle.

    PubMed

    Itaka, Keiji; Osada, Kensuke; Morii, Katsue; Kim, Pilhan; Yun, Seok-Hyun; Kataoka, Kazunori

    2010-04-02

    Skeletal muscle is an interesting target for gene therapy. To achieve effective gene introduction in skeletal muscle, a hydrodynamic approach by intravenous injection of plasmid DNA (pDNA) with transient isolation of the limb has attracted attention. In this study, we demonstrated that polyplex nanomicelle, composed of poly(ethyleneglycol) (PEG)-block-polycation and pDNA, showed excellent capacity of gene introduction to skeletal muscle. The evaluation of luciferase expression in the muscle revealed that the nanomicelle provided higher and sustained profiles of transgene expression compared with naked pDNA. Real-time in vivo imaging using a video-rate confocal imaging system suggested that the nanomicelle showed tolerability in the intracellular environment, resulting in the slow but sustained transgene expression. The nanomicelle induced less TNFalpha induction in the muscle than naked pDNA, indicating the safety of nanomicelle-based gene delivery into the skeletal muscle. Moreover, the nanomicelle showed significant tumor growth suppression for almost a month by introducing a pDNA expressing a soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1) to skeletal muscle to obtain anti-angiogenic effect on tumor growth. This feature of sustained effect gives an important advantage of gene therapy, especially on the points of cost effectiveness and high compliance. These results suggest that the hydrodynamic gene introduction to skeletal muscle using polyplex nanomicelle system possesses the potential for effective gene therapy. Copyright 2009 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  3. Molecular events in skeletal muscle during disuse atrophy

    NASA Technical Reports Server (NTRS)

    Kandarian, Susan C.; Stevenson, Eric J.

    2002-01-01

    This review summarizes the current knowledge of the molecular processes underlying skeletal muscle atrophy due to disuse. Because the processes involved with muscle wasting due to illness are similar to disuse, this literature is used for comparison. Areas that are ripe for further study and that will advance our understanding of muscle atrophy are suggested.

  4. Molecular events in skeletal muscle during disuse atrophy

    NASA Technical Reports Server (NTRS)

    Kandarian, Susan C.; Stevenson, Eric J.

    2002-01-01

    This review summarizes the current knowledge of the molecular processes underlying skeletal muscle atrophy due to disuse. Because the processes involved with muscle wasting due to illness are similar to disuse, this literature is used for comparison. Areas that are ripe for further study and that will advance our understanding of muscle atrophy are suggested.

  5. Muscle Tissue Saturation Compared With Muscle Tissue Perfusion During Low Blood Flows: An Experimental Study.

    PubMed

    Thomassen, Sisse Anette; Kjærgaard, Benedict; Olsen Alstrup, Aage Kristian; Munk, Ole Lajord; Frøkiær, Jørgen; Larsson, Anders; Rasmussen, Bodil Steen

    2017-03-22

    To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model. A prospective, randomized study. Research laboratory, single institution. Eight pigs (69-71 kg). In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with (15)O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels. The results showed profound systemic ischemia during low CPB blood flow. StO2 remained high until muscle tissue perfusion decreased to about 50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion. In an experimental CPB animal model, StO2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO2 and muscle tissue perfusion. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Rabbit Erythrocytes Release ATP and Dilate Skeletal Muscle Arterioles in the Presence of Reduced Oxygen Tension

    PubMed Central

    Sprague, Randy S.; Hanson, Madelyn S.; Achilleus, David; Bowles, Elizabeth A.; Stephenson, Alan H.; Sridharan, Meera; Adderley, Shaquria; Ellsworth, Mary L.

    2010-01-01

    In skeletal muscle, oxygen (O2) delivery to appropriately meet metabolic need requires mechanisms for detection of the magnitude of O2 demand and the regulation of O2 delivery. Erythrocytes, when exposed to decreases in O2 tension, release both O2 and the vasodilator, adenosine triphosphate (ATP). The aims of this study were to establish that erythrocytes release ATP in response to reduced O2 tension and determine if erythrocytes are necessary for dilation of isolated skeletal muscle arterioles exposed to reduced extra-luminal O2 tension. Rabbit erythrocytes exposed to reduced O2 tension in a tonometer (n = 5, PO2 = 27 ± 3, p<0.01) released ATP in response to reduced O2 tension. ATP release increased proportional to the decrease in O2 tension. The contribution of erythrocytes to the response of skeletal muscle arterioles to reduced extra-luminal O2 tension was determined using isolated hamster cheek pouch retractor muscle arterioles perfused with buffer (n = 11, mean diameter 52 ± 3 μm) in the absence and presence of rabbit erythrocytes. Without erythrocytes, arterioles did not dilate when exposed to reduced extra-luminal O2 tension (PO2 = 32 ± 4 mm Hg). In contrast, when rabbit erythrocytes were present in the perfusate (hematocrit 15%) the same decrease in O2 tension resulted in a 20 ± 4% dilation (p<0.01). These results provide support for the hypothesis that erythrocytes, via their ability to release O2 along with ATP in response to exposure to reduced O2 tension, can participate in the matching of O2 delivery with metabolic need in skeletal muscle. PMID:19307706

  7. Heparan sulfate in skeletal muscle development

    SciTech Connect

    Noonan, D.M.

    1985-01-01

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

  8. Role of autophagy in COPD skeletal muscle dysfunction.

    PubMed

    Hussain, Sabah N A; Sandri, Marco

    2013-05-01

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

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

    PubMed

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

    2014-01-01

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

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

    SciTech Connect

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

    1986-03-05

    After injection of 10/sup 6/ Walker 256 carcinoma cells labelled with /sup 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/sup 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.

  11. The impact of severe burns on skeletal muscle mitochondrial function.

    PubMed

    Porter, Craig; Herndon, David N; Sidossis, Labros S; Børsheim, Elisabet

    2013-09-01

    Severe burns induce a pathophysiological response that affects almost every physiological system within the body. Inflammation, hypermetabolism, muscle wasting, and insulin resistance are all hallmarks of the pathophysiological response to severe burns, with perturbations in metabolism known to persist for several years post injury. Skeletal muscle is the principal depot of lean tissue within the body and as the primary site of peripheral glucose disposal, plays an important role in metabolic regulation. Following a large burn, skeletal muscle functions as and endogenous amino acid store, providing substrates for more pressing functions, such as the synthesis of acute phase proteins and the deposition of new skin. Subsequently, burn patients become cachectic, which is associated with poor outcomes in terms of metabolic health and functional capacity. While a loss of skeletal muscle contractile proteins per se will no doubt negatively impact functional capacity, detriments in skeletal muscle quality, i.e. a loss in mitochondrial number and/or function may be quantitatively just as important. The goal of this review article is to summarise the current understanding of the impact of thermal trauma on skeletal muscle mitochondrial content and function, to offer direction for future research concerning skeletal muscle mitochondrial function in patients with severe burns, and to renew interest in the role of these organelles in metabolic dysfunction following severe burns.

  12. Glucose deprivation attenuates sortilin levels in skeletal muscle cells.

    PubMed

    Ariga, Miyako; Yoneyama, Yosuke; Fukushima, Toshiaki; Ishiuchi, Yuri; Ishii, Takayuki; Sato, Hitoshi; Hakuno, Fumihiko; Nedachi, Taku; Takahashi, Shin-Ichiro

    2017-03-31

    In skeletal muscle, sortilin plays a predominant role in the sorting of glucose transporter 4 (Glut4), thereby controlling glucose uptake. Moreover, our previous study suggested that the sortilin expression levels are also implicated in myogenesis. Despite the importance of sortilin in skeletal muscle, however, the regulation of sortilin expression has not been completely understood. In the present study, we analyzed if the sortilin expression is regulated by glucose in C2C12 myocytes and rat skeletal muscles in vivo. Sortilin protein expression was elevated upon C2C12 cell differentiation and was further enhanced in the presence of a high concentration of glucose. The gene expression and protein degradation of sortilin were not affected by glucose. On the other hand, rapamycin partially reduced sortilin induction by a high concentration of glucose, which suggested that sortilin translation could be regulated by glucose, at least in part. We also examined if the sortilin regulation by glucose was also observed in skeletal muscles that were obtained from fed or fasted rats. Sortilin expression in both gastrocnemius and extensor digitorum longus (EDL) muscle was significantly decreased by 17-18h of starvation. On the other hand, pathological levels of high blood glucose did not alter the sortilin expression in rat skeletal muscle. Overall, the present study suggests that sortilin protein levels are reduced under hypoglycemic conditions by post-transcriptional control in skeletal muscles.

  13. Skeletal muscle: a brief review of structure and function.

    PubMed

    Frontera, Walter R; Ochala, Julien

    2015-03-01

    Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40% of total body weight and contains 50-75% of all body proteins. In general, muscle mass depends on the balance between protein synthesis and degradation and both processes are sensitive to factors such as nutritional status, hormonal balance, physical activity/exercise, and injury or disease, among others. In this review, we discuss the various domains of muscle structure and function including its cytoskeletal architecture, excitation-contraction coupling, energy metabolism, and force and power generation. We will limit the discussion to human skeletal muscle and emphasize recent scientific literature on single muscle fibers.

  14. Calcium signaling in skeletal muscle development, maintenance and regeneration.

    PubMed

    Tu, Michelle K; Levin, Jacqueline B; Hamilton, Andrew M; Borodinsky, Laura N

    2016-03-01

    Skeletal muscle-specific stem cells are pivotal for tissue development and regeneration. Muscle plasticity, inherent in these processes, is also essential for daily life activities. Great advances and efforts have been made in understanding the function of the skeletal muscle-dedicated stem cells, called muscle satellite cells, and the specific signaling mechanisms that activate them for recruitment in the repair of the injured muscle. Elucidating these signaling mechanisms may contribute to devising therapies for muscular injury or disease. Here we review the studies that have contributed to our understanding of how calcium signaling regulates skeletal muscle development, homeostasis and regeneration, with a focus on the calcium dynamics and calcium-dependent effectors that participate in these processes.

  15. Contrast-enhancement influences skeletal muscle density, but not skeletal muscle mass, measurements on computed tomography.

    PubMed

    van Vugt, Jeroen L A; Coebergh van den Braak, Robert R J; Schippers, Henk J W; Veen, Kevin M; Levolger, Stef; de Bruin, Ron W F; Koek, Marcel; Niessen, Wiro J; IJzermans, Jan N M; Willemsen, François E J A

    2017-07-14

    Low skeletal muscle mass and density have recently been discovered as prognostic and predictive parameters to guide interventions in various populations, including cancer patients. The gold standard for body composition analysis in cancer patients is computed tomography (CT). To date, the effect of contrast-enhancement on muscle composition measurements has not been established. The aim of this study was to determine the effect of contrast-enhancement on skeletal muscle mass and density measurements on four-phase CT studies. In this observational study, two observers measured cross-sectional skeletal muscle area corrected for patients' height (skeletal muscle index [SMI]) and density (SMD) at the level of the third lumbar vertebra on 50 randomly selected CT examinations with unenhanced, arterial, and portal-venous phases. The levels of agreement between enhancement phases for SMI and SMD were calculated using intra-class correlation coefficients (ICCs). Mean SMI was 42.5 (±9.9) cm(2)/m(2) on the unenhanced phase, compared with 42.8 (±9.9) and 43.6 (±9.9) cm(2)/m(2) for the arterial and portal-venous phase, respectively (both p < 0.01). Mean SMD was lower for the unenhanced phase (30.9 ± 8.0 Hounsfield units [HU]) compared with the arterial (38.0 ± 9.9 HU) and portal-venous (38.7 ± 9.2 HU) phase (both p < 0.001). No significant difference was found between SMD in the portal-venous and arterial phase (p = 0.161). The ICCs were excellent (≥0.992) for all SMIs and for SMD between the contrast-enhanced phases (0.949). The ICCs for the unenhanced phase compared with the arterial (0.676) and portal-venous (0.665) phase were considered fair to good. Statistically significant differences in SMI were observed between different enhancement phases. However, further work is needed to assess the clinical relevance of these small differences. Contrast-enhancement strongly influenced SMD values. Studies using this measure should therefore use the portal

  16. Angiopoietin-1 enhances skeletal muscle regeneration in mice.

    PubMed

    Mofarrahi, Mahroo; McClung, Joseph M; Kontos, Christopher D; Davis, Elaine C; Tappuni, Bassman; Moroz, Nicolay; Pickett, Amy E; Huck, Laurent; Harel, Sharon; Danialou, Gawiyou; Hussain, Sabah N A

    2015-04-01

    Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang-1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle satellite cell survival; however, its role in skeletal muscle regeneration after injury is unknown. We assessed the effects of Ang-1 on fiber regeneration, myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA) in mice. We also assessed endogenous Ang-1 levels and localization in intact and injured TA muscles. TA fiber injury was triggered by cardiotoxin injection. Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin then increased during the 2 wk. Ang-1 protein was expressed in satellite cells, both in noninjured and recovering TA muscles. Positive Ang-1 staining was present in blood vessels but not in nerve fibers. Four days after the initiation of injury, injection of adenoviral Ang-1 into injured muscles resulted in significant increases in in situ TA muscle contractility, muscle fiber regeneration, and capillary density. In cultured human skeletal myoblasts, recombinant Ang-1 protein increased survival, proliferation, migration, and differentiation into myotubes. The latter effect was associated with significant upregulation of the expression of the myogenic regulatory factors MyoD and Myogenin and certain genes involved in cell cycle regulation. We conclude that Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angiogenesis program in endothelial cells.

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

    PubMed

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

    2016-08-01

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

  18. Epigallocatechin gallate promotes GLUT4 translocation in skeletal muscle.

    PubMed

    Ueda, Manabu; Nishiumi, Shin; Nagayasu, Hironobu; Fukuda, Itsuko; Yoshida, Ken-ichi; Ashida, Hitoshi

    2008-12-05

    In this study, we investigated whether epigallocatechin gallate (EGCg) affects glucose uptake activity and the translocation of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle. A single oral administration of EGCg at 75 mg/kg body weight promoted GLUT4 translocation in skeletal muscle of rats. EGCg significantly increased glucose uptake accompanying GLUT4 translocation in L6 myotubes at 1 nM. The translocation of GLUT4 was also observed both in skeletal muscle of mice and rats ex vivo and in insulin-resistant L6 myotubes. Wortmannin, an inhibitor of phosphatidylinositol 3'-kinase, inhibited both EGCg- and insulin-increased glucose uptakes, while genistein, an inhibitor of tyrosine kinase, failed to inhibit the EGCg-increased uptake. Therefore, EGCg may improve hyperglycemia by promoting GLUT4 translocation in skeletal muscle with partially different mechanism from insulin.

  19. Skeletal muscle transverse strain during isometric contraction at different lengths.

    PubMed

    van Donkelaar, C C; Willems, P J; Muijtjens, A M; Drost, M R

    1999-08-01

    An important assumption in 2D numerical models of skeletal muscle contraction involves deformation in the third dimension of the included muscle section. The present paper studies the often used plane strain description. Therefore, 3D muscle surface deformation is measured from marker displacements during isometric contractions at various muscle lengths. Longitudinal strains at superficial muscle fibers ( - 14 +/- 2.6% at L0, n = 57) and aponeurosis (0.8 +/- 0.9% at L0) decrease with increasing muscle length. The same holds for transverse muscle surface strains in superficial muscle fibers and aponeurosis, which are comparable at intermediate muscle length, but differ at long and short muscle length. Because transverse strains during isometric contraction change with initial muscle length, it is concluded that the effect of muscle length on muscle deformation cannot be studied in plane strain models. These results do not counteract the use of these models to study deformation in contractions with approximately - 9 % longitudinal muscle fiber strain, as transverse strain in superficial muscle fibers and in aponeurosis tissue is minimal in that case. Aponeurosis surface area change decreases with increasing initial muscle length, but muscle fiber surface area change is - 11%, independent of muscle length. Assuming incompressible muscle material, this means that strain perpendicular to the muscle surface equals 11%. Taking the relationship between transverse and longitudinal muscle fiber strain into account, it is hypothesized that superficial muscle fibers flatten during isometric contractions.

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

    PubMed

    Gillies, Allison R; Lieber, Richard L

    2011-09-01

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

  1. Structure and Function of the Skeletal Muscle Extracellular Matrix

    PubMed Central

    Gillies, Allison R.; Lieber, Richard L.

    2011-01-01

    The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a property thathas clinical manifestations and alters muscle function. Here, we review the structure, composition, and mechanical properties of skeletal muscle ECM, describe the cells that contribute to the maintenance of the ECM and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure-function relationships. Detailed structure-function relationships of the ECM have yet to be defined and, as a result, we propose areas for future studies. PMID:21949456

  2. Expression and functional roles of angiopoietin-2 in skeletal muscles.

    PubMed

    Mofarrahi, Mahroo; Hussain, Sabah N A

    2011-01-01

    Angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2 regulatory factors and the effects of ANGPT2 on proliferation, migration, differentiation and survival were identified in cultured primary skeletal myoblasts. The cellular networks involved in the actions of ANGPT2 on skeletal muscle cells were also analyzed. Primary skeletal myoblasts were isolated from human and mouse muscles. Skeletal myoblast survival, proliferation, migration and differentiation were measured in-vitro in response to recombinant ANGPT2 protein and to enhanced ANGPT2 expression delivered with adenoviruses. Real-time PCR and ELISA measurements revealed the presence of constitutive ANGPT2 expression in these cells. This expression increased significantly during myoblast differentiation into myotubes. In human myoblasts, ANGPT2 expression was induced by H(2)O(2), but not by TNFα, IL1β or IL6. ANGPT2 significantly enhanced myoblast differentiation and survival, but had no influence on proliferation or migration. ANGPT2-induced survival was mediated through activation of the ERK1/2 and PI-3 kinase/AKT pathways. Microarray analysis revealed that ANGPT2 upregulates genes involved in the regulation of cell survival, protein synthesis, glucose uptake and free fatty oxidation. Skeletal muscle precursors constitutively express ANGPT2 and this expression is upregulated during differentiation into myotubes. Reactive oxygen species exert a strong stimulatory influence on muscle ANGPT2 expression while pro-inflammatory cytokines do not. ANGPT2 promotes skeletal myoblast survival and differentiation. These results

  3. Distraction of skeletal muscle: evolution of a rat model.

    PubMed

    Green, Stuart A; Horton, Eric; Baker, Michael; Utkan, Ali; Caiozzo, Vincent

    2002-10-01

    To better study the effects of limb lengthening on skeletal muscle, the authors developed a rat model that uses a miniature external skeletal fixator applied to the tibia of an adult Sprague-Dawley rat. The mounting and lengthening protocols follow the principles developed by Ilizarov. With the initial version of the fixator, the rats had progressive equinus contractures develop because the calf muscles resisted elongation. By incorporating a footplate in the distraction apparatus, tibial lengthening can be achieved without concomitant equinus.

  4. Anisotropic Materials for Skeletal-Muscle-Tissue Engineering.

    PubMed

    Jana, Soumen; Levengood, Sheeny K Lan; Zhang, Miqin

    2016-12-01

    Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity of the native tissue. Current clinical approaches are not optimal for the treatment of large volumetric skeletal-muscle loss. As an alternative, tissue engineering represents a promising approach for the functional restoration of damaged muscle tissue. A typical tissue-engineering process involves the design and fabrication of a scaffold that closely mimics the native skeletal-muscle extracellular matrix (ECM), allowing organization of cells into a physiologically relevant 3D architecture. In particular, anisotropic materials that mimic the morphology of the native skeletal-muscle ECM, can be fabricated using various biocompatible materials to guide cell alignment, elongation, proliferation, and differentiation into myotubes. Here, an overview of fundamental concepts associated with muscle-tissue engineering and the current status of muscle-tissue-engineering approaches is provided. Recent advances in the development of anisotropic scaffolds with micro- or nanoscale features are reviewed, and how scaffold topographical, mechanical, and biochemical cues correlate to observed cellular function and phenotype development is examined. Finally, some recent developments in both the design and utility of anisotropic materials in skeletal-muscle-tissue engineering are highlighted, along with their potential impact on future research and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Mimicking exercise in three-dimensional bioengineered skeletal muscle to investigate cellular and molecular mechanisms of physiological adaptation.

    PubMed

    Kasper, Andreas M; Turner, Daniel C; Martin, Neil R W; Sharples, Adam P

    2017-02-03

    Bioengineering of skeletal muscle in vitro in order to produce highly aligned myofibres in relevant three dimensional (3D) matrices have allowed scientists to model the in vivo skeletal muscle niche. This review discusses essential experimental considerations for developing bioengineered muscle in order to investigate exercise mimicking stimuli. We identify current knowledge for the use of electrical stimulation and co-culture with motor neurons to enhance skeletal muscle maturation and contractile function in bioengineered systems in vitro. Importantly, we provide a current opinion on the use of acute and chronic exercise mimicking stimuli (electrical stimulation and mechanical overload) and the subsequent mechanisms underlying physiological adaptation in 3D bioengineered muscle. We also identify that future studies using the latest bioreactor technology, providing simultaneous electrical and mechanical loading and flow perfusion in vitro, may provide the basis for advancing knowledge in the future. We also envisage, that more studies using genetic, pharmacological, and hormonal modifications applied in human 3D bioengineered skeletal muscle may allow for an enhanced discovery of the in-depth mechanisms underlying the response to exercise in relevant human testing systems. Finally, 3D bioengineered skeletal muscle may provide an opportunity to be used as a pre-clinical in vitro test-bed to investigate the mechanisms underlying catabolic disease, while modelling disease itself via the use of cells derived from human patients without exposing animals or humans (in phase I trials) to the side effects of potential therapies. © 2017 Wiley Periodicals, Inc.

  6. Role of skeletal muscle in ear development.

    PubMed

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

    2017-03-08

    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.

  7. Renal function alterations during skeletal muscle disuse in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1992-01-01

    This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

  8. The Impact of Shiftwork on Skeletal Muscle Health

    PubMed Central

    Aisbett, Brad; Condo, Dominique; Zacharewicz, Evelyn; Lamon, Séverine

    2017-01-01

    (1) Background: About one in four workers undertake shift rosters that fall outside the traditional 7 a.m.–6 p.m. scheduling. Shiftwork alters workers’ exposure to natural and artificial light, sleep patterns, and feeding patterns. When compared to the rest of the working population, shiftworkers are at a greater risk of developing metabolic impairments over time. One fundamental component of metabolic health is skeletal muscle, the largest organ in the body. However, cause-and-effect relationships between shiftwork and skeletal muscle health have not been established; (2) Methods: A critical review of the literature was completed using online databases and reference lists; (3) Results: We propose a conceptual model drawing relationships between typical shiftwork consequences; altered light exposure, sleep patterns, and food and beverage consumption, and drivers of skeletal muscle health—protein intake, resistance training, and hormone release. At present, there is no study investigating the direct effect of shiftwork on skeletal muscle health. Instead, research findings showing that acute consequences of shiftwork negatively influence skeletal muscle homeostasis support the validity of our model; (4) Conclusion: Further research is required to test the potential relationships identified in our review, particularly in shiftwork populations. Part of this testing could include skeletal muscle specific interventions such as targeted protein intake and/or resistance-training. PMID:28282858

  9. Adipokines in Healthy Skeletal Muscle and Metabolic Disease.

    PubMed

    Coles, C A

    2016-01-01

    Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross-talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease.

  10. ACTIVATION OF CASPASE-3 IN THE SKELETAL MUSCLE DURING HEMODIALYSIS

    PubMed Central

    Boivin, Michel A; Battah, Shadi I; Dominic, Elizabeth A; Kalantar-Zadeh, Kamyar; Ferrando, Arny; Tzamaloukas, Antonios H; Dwivedi, Rama; Ma, Thomas A; Moseley, Pope; Raj, Dominic SC

    2010-01-01

    Background Muscle atrophy in end-stage renal disease (ESRD) may be due to the activation of apoptotic and proteolytic pathways. Objective We hypothesized that activation of caspase-3 in the skeletal muscle mediates apoptosis and proteolysis during hemodialysis (HD). Materials and Methods Eight ESRD patients were studied before (pre-HD) and during HD and the finding were compared with those from six healthy volunteers. Protein kinetics was determined by primed constant infusion of L-(ring 13C6) Phenylalanine. Results Caspase-3 activity in the skeletal muscle was higher in ESRD patients pre-HD than in controls (24966.0±4023.9 vs. 15293.3±2120.0 units, p<0.01) and increased further during HD (end-HD) (37666.6±4208.3 units) (p<0.001). 14 kDa actin fragments generated by caspase-3 mediated cleavage of actinomyosin was higher in the skeletal muscle pre-HD (68%) and during HD (164%) compared to controls. The abundance of ubiquitinized carboxy-terminal actin fragment was also significantly increased during HD. Skeletal muscle biopsies obtained at the end of HD exhibited augmented apoptosis, which was higher than that observed in pre-HD and control samples (p<0.001). IL-6 content in the soluble fraction of the muscle skeletal muscle was increased significantly during HD. Protein kinetic studies showed that catabolism was higher in ESRD patients during HD compared to pre-HD and control subjects. Muscle protein catabolism was positively associated with caspase-3 activity and skeletal muscle IL-6 content. Conclusion Muscle atrophy in ESRD may be due to IL-6 induced activation of caspase-3 resulting in apoptosis as well as muscle proteolysis during HD. PMID:20636378

  11. cGMP phosphodiesterase inhibition improves the vascular and metabolic actions of insulin in skeletal muscle.

    PubMed

    Genders, A J; Bradley, E A; Rattigan, S; Richards, S M

    2011-08-01

    There is considerable support for the concept that insulin-mediated increases in microvascular blood flow to muscle impact significantly on muscle glucose uptake. Since the microvascular blood flow increases with insulin have been shown to be nitric oxide-dependent inhibition of cGMP-degrading phosphodiesterases (cGMP PDEs) is predicted to enhance insulin-mediated increases in microvascular perfusion and muscle glucose uptake. Therefore, we studied the effects of the pan-cGMP PDE inhibitor zaprinast on the metabolic and vascular actions of insulin in muscle. Hyperinsulinemic euglycemic clamps (3 mU·min(-1)·kg(-1)) were performed in anesthetized rats and changes in microvascular blood flow assessed from rates of 1-methylxanthine metabolism across the muscle bed by capillary xanthine oxidase in response to insulin and zaprinast. We also characterized cGMP PDE isoform expression in muscle by real-time PCR and immunostaining of frozen muscle sections. Zaprinast enhanced insulin-mediated microvascular perfusion by 29% and muscle glucose uptake by 89%, while whole body glucose infusion rate during insulin infusion was increased by 33% at 2 h. PDE2, -9, and -10 were the major isoforms expressed at the mRNA level in muscle, while PDE1B, -9A, -10A, and -11A proteins were expressed in blood vessels. Acute administration of the cGMP PDE inhibitor zaprinast enhances muscle microvascular blood flow and glucose uptake response to insulin. The expression of a number of cGMP PDE isoforms in skeletal muscle suggests that targeting specific cGMP PDE isoforms may provide a promising avenue for development of a novel class of therapeutics for enhancing muscle insulin sensitivity.

  12. Evidence that lysosomes are not involved in the degradation of myofibrillar proteins in rat skeletal muscle.

    PubMed Central

    Lowell, B B; Ruderman, N B; Goodman, M N

    1986-01-01

    To examine the role of lysosomes in the degradation of skeletal-muscle myofibrillar proteins, we measured the release of N tau-methylhistidine from perfused muscle of starved and fed rats in the presence or absence of agents that inhibit lysosomal proteinase activity. After 1 day of starvation, the release of N tau-methylhistidine by perfused muscle of 4-, 8- and 24-week-old rats increased by 322, 159 and 134% respectively. On the other hand, total protein breakdown, assessed by tyrosine release, increased by 62, 20 and 20% respectively. Inhibitors of lysosomal proteinases as well as high concentrations of insulin or amino acids failed to diminish the release of N tau-methylhistidine by perfused muscle of starved and fed rats, despite a 25-35% inhibition of total protein breakdown. The data strongly suggest that the complete breakdown of myofibrillar proteins occurs via a non-lysosomal pathway. They also suggest that total proteolysis, which primarily reflects non-myofibrillar protein breakdown, occurs at least in part within lysosomes. PMID:3707546

  13. Costameric proteins in human skeletal muscle during muscular inactivity

    PubMed Central

    Anastasi, Giuseppe; Cutroneo, Giuseppina; Santoro, Giuseppe; Arco, Alba; Rizzo, Giuseppina; Bramanti, Placido; Rinaldi, Carmen; Sidoti, Antonina; Amato, Aldo; Favaloro, Angelo

    2008-01-01

    Costameres are regions that are associated with the sarcolemma of skeletal muscle fibres and comprise proteins of the dystrophin–glycoprotein complex and vinculin–talin–integrin system. Costameres play both a mechanical and a signalling role, transmitting force from the contractile apparatus to the extracellular matrix in order to stabilize skeletal muscle fibres during contraction and relaxation. Recently, it was shown that bidirectional signalling occurs between sarcoglycans and integrins, with muscle agrin potentially interacting with both types of protein to enable signal transmission. Although numerous studies have been carried out on skeletal muscle diseases, such as Duchenne muscular dystrophy, recessive autosomal muscular dystrophies and other skeletal myopathies, insufficient data exist on the relationship between costameres and the pathology of the second motor nerve and between costameric proteins and muscle agrin in other conditions in which skeletal muscle atrophy occurs. Previously, we carried out a preliminary study on skeletal muscle from patients with sensitive-motor polyneuropathy, in which we analysed the distribution of sarcoglycans, integrins and agrin by immunostaining only. In the present study, we have examined the skeletal muscle fibres of ten patients with sensitive-motor polyneuropathy. We used immunofluorescence and reverse transcriptase PCR to examine the distribution of vinculin, talin and dystrophin, in addition to that of those proteins previously studied. Our aim was to characterize in greater detail the distribution and expression of costameric proteins and muscle agrin during this disease. In addition, we used transmission electron microscopy to evaluate the structural damage of the muscle fibres. The results showed that immunostaining of α7B-integrin, β1D-integrin and muscle agrin appeared to be severely reduced, or almost absent, in the muscle fibres of the diseased patients, whereas staining of α7A-integrin appeared

  14. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    PubMed Central

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

    2015-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1−/− and ClockΔ19 mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle. PMID:21621073

  15. Macrophage Plasticity in Skeletal Muscle Repair

    PubMed Central

    Rigamonti, Elena; Sciorati, Clara; Rovere-Querini, Patrizia

    2014-01-01

    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. PMID:24860823

  16. Systems analysis of biological networks in skeletal muscle function.

    PubMed

    Smith, Lucas R; Meyer, Gretchen; Lieber, Richard L

    2013-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation-contraction coupling enabling Ca(2+) release. Ca(2+) then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. Copyright © 2012 Wiley Periodicals, Inc.

  17. Skeletal muscle degeneration and regeneration in mice and flies.

    PubMed

    Rai, Mamta; Nongthomba, Upendra; Grounds, Miranda D

    2014-01-01

    Many aspects of skeletal muscle biology are remarkably similar between mammals and tiny insects, and experimental models of mice and flies (Drosophila) provide powerful tools to understand factors controlling the growth, maintenance, degeneration (atrophy and necrosis), and regeneration of normal and diseased muscles, with potential applications to the human condition. This review compares the limb muscles of mice and the indirect flight muscles of flies, with respect to the mechanisms of adult myofiber formation, homeostasis, atrophy, hypertrophy, and the response to muscle degeneration, with some comment on myogenic precursor cells and common gene regulatory pathways. There is a striking similarity between the species for events related to muscle atrophy and hypertrophy, without contribution of any myoblast fusion. Since the flight muscles of adult flies lack a population of reserve myogenic cells (equivalent to satellite cells), this indicates that such cells are not required for maintenance of normal muscle function. However, since satellite cells are essential in postnatal mammals for myogenesis and regeneration in response to myofiber necrosis, the extent to which such regeneration might be possible in flight muscles of adult flies remains unclear. Common cellular and molecular pathways for both species are outlined related to neuromuscular disorders and to age-related loss of skeletal muscle mass and function (sarcopenia). The commonality of events related to skeletal muscles in these disparate species (with vast differences in size, growth duration, longevity, and muscle activities) emphasizes the combined value and power of these experimental animal models.

  18. Bex1 knock out mice show altered skeletal muscle regeneration

    PubMed Central

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

    2008-01-01

    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 Ca2+/CaM may be involved in skeletal muscle regeneration. PMID:17884015

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

    PubMed

    Musarò, Antonio; Carosio, Silvia

    2017-01-01

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

  20. Anabolic and catabolic pathways regulating skeletal muscle mass

    PubMed Central

    McCarthy, John J.; Esser, Karyn A.

    2010-01-01

    Purpose of review the purpose of this review is to discuss recent findings as they pertain to anabolic and catabolic signaling pathways involved in the regulation of adult skeletal muscle mass. Recent findings research conducted over the past few years has continued to refine our understanding of the pathways that govern skeletal muscle mass, in particular the mTOR, FoxO and NF-κB pathways. Alternative signaling pathways have also emerged as important regulators of muscle mass such as the β-catenin pathway. Summary a better understanding of the anabolic and catabolic processes which regulate skeletal muscle mass is critical for the development of more effective therapeutics to prevent the loss of muscle with disuse, aging and disease. PMID:20154608

  1. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

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

    2007-11-16

    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{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  2. Skeletal muscle tissue in movement and health: positives and negatives.

    PubMed

    Lindstedt, Stan L

    2016-01-01

    The history of muscle physiology is a wonderful lesson in 'the scientific method'; our functional hypotheses have been limited by our ability to decipher (observe) muscle structure. The simplistic understanding of how muscles work made a large leap with the remarkable insights of A. V. Hill, who related muscle force and power to shortening velocity and energy use. However, Hill's perspective was largely limited to isometric and isotonic contractions founded on isolated muscle properties that do not always reflect how muscles function in vivo. Robert Josephson incorporated lengthening contractions into a work loop analysis that shifted the focus to dynamic muscle function, varying force, length and work done both by and on muscle during a single muscle work cycle. It became apparent that muscle is both a force generator and a spring. Titin, the missing filament in the sliding filament model, is a muscle spring, which functions very differently in cardiac versus skeletal muscle; its possible role in these two muscle types is discussed relative to their contrasting function. The good news for those of us who choose to work on skeletal muscle is that muscle has been reluctant to reveal all of its secrets. © 2016. Published by The Company of Biologists Ltd.

  3. Desmin-regulated Lentiviral Vectors for Skeletal Muscle Gene Transfer

    PubMed Central

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

    2009-01-01

    Lentiviral vectors (LVs) are highly attractive as a gene therapy agent as they are able to stably integrate their genomes in both dividing and nondividing cells and, in principle, provide long-term therapeutic benefit. However, their performance in skeletal muscle in adult animals has, to date, been disappointing. In order to gain clearer insight into their utility in this tissue type, we have conducted an extensive quantitative comparison of constitutive and muscle-specific promoter activities in skeletal muscle and nonmuscle systems following LV delivery in cell lines and neonatal mice. Our data show that LV delivery to hind leg skeletal muscle of neonatal mouse results in long-term transgene expression in adulthood. We find that the human desmin (DES) promoter/enhancer is the first muscle-specific control region to match the activity of the highly active constitutive human cytomegalovirus (hCMV) promoter/enhancer in skeletal muscle within a LV context both in vitro and in vivo. Furthermore, the DES promoter/enhancer provides six- to eightfold greater expression per viral copy than the muscle-specific human muscle creatine kinase (CKM) promoter/enhancer. DES also confers a more reproducible and tissue-specific transgene expression profile compared to CKM and is therefore a highly attractive regulatory element for use in muscle gene therapy vectors. PMID:19935780

  4. Activation of the erythropoietin receptor in human skeletal muscle.

    PubMed

    Rundqvist, Helene; Rullman, Eric; Sundberg, Carl Johan; Fischer, Helene; Eisleitner, Katarina; Ståhlberg, Marcus; Sundblad, Patrik; Jansson, Eva; Gustafsson, Thomas

    2009-09-01

    Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise. Ten healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated. The EPOR protein was localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased. Interaction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.

  5. Mitochondrial energetics is impaired in vivo in aged skeletal muscle.

    PubMed

    Gouspillou, Gilles; Bourdel-Marchasson, Isabelle; Rouland, Richard; Calmettes, Guillaume; Biran, Marc; Deschodt-Arsac, Véronique; Miraux, Sylvain; Thiaudiere, Eric; Pasdois, Philippe; Detaille, Dominique; Franconi, Jean-Michel; Babot, Marion; Trézéguet, Véronique; Arsac, Laurent; Diolez, Philippe

    2014-02-01

    With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with (31) P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness ('elasticity') of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.

  6. Estimation of skeletal muscle mass from body creatine content

    NASA Technical Reports Server (NTRS)

    Pace, N.; Rahlmann, D. F.

    1982-01-01

    Procedures have been developed for studying the effect of changes in gravitational loading on skeletal muscle mass through measurements of the body creatine content. These procedures were developed for studies of gravitational scale effects in a four-species model, comprising the hamster, rat, guinea pig, and rabbit, which provides a sufficient range of body size for assessment of allometric parameters. Since intracellular muscle creatine concentration varies among species, and with age within a given species, the concentration values for metabolically mature individuals of these four species were established. The creatine content of the carcass, skin, viscera, smooth muscle, and skeletal muscle was determined for each species. In addition, the skeletal muscle mass of the major body components was determined, as well as the total and fat-free masses of the body and carcass, and the percent skeletal muscle in each. It is concluded that these procedures are particularly useful for studying the effect of gravitational loading on the skeletal muscle content of the animal carcass, which is the principal weight-bearing organ of the body.

  7. Estimation of skeletal muscle mass from body creatine content

    NASA Technical Reports Server (NTRS)

    Pace, N.; Rahlmann, D. F.

    1982-01-01

    Procedures have been developed for studying the effect of changes in gravitational loading on skeletal muscle mass through measurements of the body creatine content. These procedures were developed for studies of gravitational scale effects in a four-species model, comprising the hamster, rat, guinea pig, and rabbit, which provides a sufficient range of body size for assessment of allometric parameters. Since intracellular muscle creatine concentration varies among species, and with age within a given species, the concentration values for metabolically mature individuals of these four species were established. The creatine content of the carcass, skin, viscera, smooth muscle, and skeletal muscle was determined for each species. In addition, the skeletal muscle mass of the major body components was determined, as well as the total and fat-free masses of the body and carcass, and the percent skeletal muscle in each. It is concluded that these procedures are particularly useful for studying the effect of gravitational loading on the skeletal muscle content of the animal carcass, which is the principal weight-bearing organ of the body.

  8. Skeletal muscle mitochondrial health and spinal cord injury

    PubMed Central

    O’Brien, Laura C; Gorgey, Ashraf S

    2016-01-01

    Mitochondria are the main source of cellular energy production and are dynamic organelles that undergo biogenesis, remodeling, and degradation. Mitochondrial dysfunction is observed in a number of disease states including acute and chronic central or peripheral nervous system injury by traumatic brain injury, spinal cord injury (SCI), and neurodegenerative disease as well as in metabolic disturbances such as insulin resistance, type II diabetes and obesity. Mitochondrial dysfunction is most commonly observed in high energy requiring tissues like the brain and skeletal muscle. In persons with chronic SCI, changes to skeletal muscle may include remarkable atrophy and conversion of muscle fiber type from oxidative to fast glycolytic, combined with increased infiltration of intramuscular adipose tissue. These changes contribute to a proinflammatory environment, glucose intolerance and insulin resistance. The loss of metabolically active muscle combined with inactivity predisposes individuals with SCI to type II diabetes and obesity. The contribution of skeletal muscle mitochondrial density and electron transport chain activity to the development of the aforementioned comorbidities following SCI is unclear. A better understanding of the mechanisms involved in skeletal muscle mitochondrial dynamics is imperative to designing and testing effective treatments for this growing population. The current editorial will review ways to study mitochondrial function and the importance of improving skeletal muscle mitochondrial health in clinical populations with a special focus on chronic SCI. PMID:27795944

  9. Mitochondrial energetics is impaired in vivo in aged skeletal muscle

    PubMed Central

    Gouspillou, Gilles; Bourdel-Marchasson, Isabelle; Rouland, Richard; Calmettes, Guillaume; Biran, Marc; Deschodt-Arsac, Véronique; Miraux, Sylvain; Thiaudiere, Eric; Pasdois, Philippe; Detaille, Dominique; Franconi, Jean-Michel; Babot, Marion; Trézéguet, Véronique; Arsac, Laurent; Diolez, Philippe

    2014-01-01

    With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with 31P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness (‘elasticity’) of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon. PMID:23919652

  10. Skeletal muscle contractility and fatigability in adults with cystic fibrosis.

    PubMed

    Gruet, Mathieu; Decorte, Nicolas; Mely, Laurent; Vallier, Jean-Marc; Camara, Boubou; Quetant, Sébastien; Wuyam, Bernard; Verges, Samuel

    2016-01-01

    Recent discovery of cystic fibrosis transmembrane conductance regulator expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities potentially leading to functional impairments. The aim of the present study was to determine whether CF patients with mild to moderate lung disease have altered skeletal muscle contractility and greater muscle fatigability compared to healthy controls. Thirty adults (15 CF and 15 controls) performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations. Electromyographic and mechanical parameters during voluntary and magnetically-evoked contractions were recorded at rest, during and after a fatiguing isometric task. Quadriceps cross-sectional area was determined by magnetic resonance imaging. Some indexes of muscle contractility tended to be reduced at rest in CF compared to controls (e.g., mechanical response to doublets stimulation at 100 Hz: 74±30 Nm vs. 97±28 Nm, P=0.06) but all tendencies disappeared when expressed relative to quadriceps cross-sectional area (P>0.5 for all parameters). CF and controls had similar alterations in muscle contractility with fatigue, similar endurance and post exercise recovery. We found similar skeletal muscle endurance and fatigability in CF adults and controls and only trends for reduced muscle strength in CF which disappeared when normalized to muscle cross-sectional area. These results indicate small quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF with mild to moderate lung disease. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  11. No-dependent signaling pathways in unloaded skeletal muscle

    PubMed Central

    Shenkman, Boris S.; Nemirovskaya, Tatiana L.; Lomonosova, Yulia N.

    2015-01-01

    The main focus of the current review is the nitric oxide (NO)-mediated signaling mechanism in unloaded skeletal. Review of the published data describing muscles during physical activity and inactivity demonstrates that NO is an essential trigger of signaling processes, which leads to structural and metabolic changes of the muscle fibers. The experiments with modulation of NO-synthase (NOS) activity during muscle unloading demonstrate the ability of an activated enzyme to stabilize degradation processes and prevent development of muscle atrophy. Various forms of muscle mechanical activity, i.e., plantar afferent stimulation, resistive exercise and passive chronic stretch increase the content of neural NOS (nNOS) and thus may facilitate an increase in NO production. Recent studies demonstrate that NO-synthase participates in the regulation of protein and energy metabolism in skeletal muscle by fine-tuning and stabilizing complex signaling systems which regulate protein synthesis and degradation in the fibers of inactive muscle. PMID:26582991

  12. Naturally derived and synthetic scaffolds for skeletal muscle reconstruction.

    PubMed

    Wolf, Matthew T; Dearth, Christopher L; Sonnenberg, Sonya B; Loboa, Elizabeth G; Badylak, Stephen F

    2015-04-01

    Skeletal muscle tissue has an inherent capacity for regeneration following injury. However, severe trauma, such as volumetric muscle loss, overwhelms these natural muscle repair mechanisms prompting the search for a tissue engineering/regenerative medicine approach to promote functional skeletal muscle restoration. A desirable approach involves a bioscaffold that simultaneously acts as an inductive microenvironment and as a cell/drug delivery vehicle to encourage muscle ingrowth. Both biologically active, naturally derived materials (such as extracellular matrix) and carefully engineered synthetic polymers have been developed to provide such a muscle regenerative environment. Next generation naturally derived/synthetic "hybrid materials" would combine the advantageous properties of these materials to create an optimal platform for cell/drug delivery and possess inherent bioactive properties. Advances in scaffolds using muscle tissue engineering are reviewed herein.

  13. Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles.

    PubMed

    Cerletti, Massimiliano; Jurga, Sara; Witczak, Carol A; Hirshman, Michael F; Shadrach, Jennifer L; Goodyear, Laurie J; Wagers, Amy J

    2008-07-11

    Satellite cells reside beneath the basal lamina of skeletal muscle fibers and include cells that act as precursors for muscle growth and repair. Although they share a common anatomical localization and typically are considered a homogeneous population, satellite cells actually exhibit substantial heterogeneity. We used cell-surface marker expression to purify from the satellite cell pool a distinct population of skeletal muscle precursors (SMPs) that function as muscle stem cells. When engrafted into muscle of dystrophin-deficient mdx mice, purified SMPs contributed to up to 94% of myofibers, restoring dystrophin expression and significantly improving muscle histology and contractile function. Transplanted SMPs also entered the satellite cell compartment, renewing the endogenous stem cell pool and participating in subsequent rounds of injury repair. Together, these studies indicate the presence in adult skeletal muscle of prospectively isolatable muscle-forming stem cells and directly demonstrate the efficacy of myogenic stem cell transplant for treating muscle degenerative disease.

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

    PubMed

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

    2015-06-01

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

  15. Action of Obestatin in Skeletal Muscle Repair: Stem Cell Expansion, Muscle Growth, and Microenvironment Remodeling

    PubMed Central

    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

  16. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin.

    PubMed

    Reisz-Porszasz, Suzanne; Bhasin, Shalender; Artaza, Jorge N; Shen, Ruoqing; Sinha-Hikim, Indrani; Hogue, Aimee; Fielder, Thomas J; Gonzalez-Cadavid, Nestor F

    2003-10-01

    Mutations in the myostatin gene are associated with hypermuscularity, suggesting that myostatin inhibits skeletal muscle growth. We postulated that increased tissue-specific expression of myostatin protein in skeletal muscle would induce muscle loss. To investigate this hypothesis, we generated transgenic mice that overexpress myostatin protein selectively in the skeletal muscle, with or without ancillary expression in the heart, utilizing cDNA constructs in which a wild-type (MCK/Mst) or mutated muscle creatine kinase (MCK-3E/Mst) promoter was placed upstream of mouse myostatin cDNA. Transgenic mice harboring these MCK promoters linked to enhanced green fluorescent protein (EGFP) expressed the reporter protein only in skeletal and cardiac muscles (MCK) or in skeletal muscle alone (MCK-3E). Seven-week-old animals were genotyped by PCR of tail DNA or by Southern blot analysis of liver DNA. Myostatin mRNA and protein, measured by RT-PCR and Western blot, respectively, were significantly higher in gastrocnemius, quadriceps, and tibialis anterior of MCK/Mst-transgenic mice compared with wild-type mice. Male MCK/Mst-transgenic mice had 18-24% lower hind- and forelimb muscle weight and 18% reduction in quadriceps and gastrocnemius fiber cross-sectional area and myonuclear number (immunohistochemistry) than wild-type male mice. Male transgenic mice with mutated MCK-3E promoter showed similar effects on muscle mass. However, female transgenic mice with either type of MCK promoter did not differ from wild-type controls in either body weight or skeletal muscle mass. In conclusion, increased expression of myostatin in skeletal muscle is associated with lower muscle mass and decreased fiber size and myonuclear number, decreased cardiac muscle mass, and increased fat mass in male mice, consistent with its role as an inhibitor of skeletal muscle mass. The mechanism of gender specificity remains to be clarified.

  17. Biomimetic Scaffolds for Regeneration of Volumetric Muscle Loss in Skeletal Muscle Injuries

    PubMed Central

    Grasman, Jonathan M.; Zayas, Michelle J.; Page, Ray; Pins, George D.

    2015-01-01

    Skeletal muscle injuries typically result from traumatic incidents such as combat injuries where soft-tissue extremity injuries are present in one of four cases. Further, about 4.5 million reconstructive surgical procedures are performed annually as a result of car accidents, cancer ablation, or cosmetic procedures. These combat- and trauma-induced skeletal muscle injuries are characterized by volumetric muscle loss (VML), which significantly reduces the functionality of the injured muscle. While skeletal muscle has an innate repair mechanism, it is unable to compensate for VML injuries because large amounts of tissue including connective tissue and basement membrane are removed or destroyed. This results in in a significant need to develop off-the-shelf biomimetic scaffolds to direct skeletal muscle regeneration. Here, the structure and organization of native skeletal muscle tissue is described in order to reveal clear design parameters that are necessary for scaffolds to mimic in order to successfully regenerate muscular tissue. We review the literature with respect to the materials and methodologies used to develop scaffolds for skeletal muscle tissue regeneration as well as the limitations of these materials. We further discuss the variety of cell sources and different injury models to provide some context for the multiple approaches used to evaluate these scaffold materials. Recent findings are highlighted to address the state of the field and directions are outlined for future strategies, both in scaffold design and in the use of different injury models to evaluate these materials, for regenerating functional skeletal muscle. PMID:26219862

  18. Erythropoietin improves skeletal muscle microcirculation and tissue bioenergetics in a mouse sepsis model

    PubMed Central

    Kao, Raymond; Xenocostas, Anargyros; Rui, Tao; Yu, Pei; Huang, Weixiong; Rose, James; Martin, Claudio M

    2007-01-01

    Introduction The relationship between oxygen delivery and consumption in sepsis is impaired, suggesting a microcirculatory perfusion defect. Recombinant human erythropoietin (rHuEPO) regulates erythropoiesis and also exerts complex actions promoting the maintenance of homeostasis of the organism under stress. The objective of this study was to test the hypothesis that rHuEPO could improve skeletal muscle capillary perfusion and tissue oxygenation in sepsis. Methods Septic mice in three experiments received rHu-EPO 400 U/kg subcutaneously 18 hours after cecal ligation and perforation (CLP). The first experiment measured the acute effects of rHuEPO on hemodynamics, blood counts, and arterial lactate level. The next two sets of experiments used intravital microscopy to observe capillary perfusion and nicotinamide adenine dinucleotide (NADH) fluorescence post-CLP after treatment with rHuEPO every 10 minutes for 40 minutes and at 6 hours. Perfused capillary density during a three-minute observation period and NADH fluorescence were measured. Results rHuEPO did not have any effects on blood pressure, lactate level, or blood cell numbers. CLP mice demonstrated a 22% decrease in perfused capillary density compared to the sham group (28.5 versus 36.6 capillaries per millimeter; p < 0.001). Treatment of CLP mice with rHuEPO resulted in an immediate and significant increase in perfused capillaries in the CLP group at all time points compared to baseline from 28.5 to 33.6 capillaries per millimeter at 40 minutes; p < 0.001. A significant increase in baseline NADH, suggesting tissue hypoxia, was noted in the CLP mice compared to the sham group (48.3 versus 43.9 fluorescence units [FU]; p = 0.03) and improved with rHuEPO from 48.3 to 44.4 FU at 40 minutes (p = 0.02). Six hours after treatment with rHuEPO, CLP mice demonstrated a higher mean perfused capillary density (39.4 versus 31.7 capillaries per millimeter; p < 0.001) and a lower mean NADH fluorescence as compared to CLP

  19. Molecular responses to moderate endurance exercise in skeletal muscle

    USDA-ARS?s Scientific Manuscript database

    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...

  20. Skeletal Muscle as a Peripheral Modifier of Behavior

    ERIC Educational Resources Information Center

    Jenkins, Robert R.

    1978-01-01

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

  1. Physiologic and biochemical aspects of skeletal muscle denervation and reinnervation

    NASA Technical Reports Server (NTRS)

    Max, S. R.; Mayer, R. F.

    1984-01-01

    Some of the physiologic and biochemical changes that occur in mammalian skeletal muscle following denervation and reinnervation are considered and some comparisons are made with changes observed following altered motor function. The nature of the trophic influence by which nerves control muscle properties are discussed, including the effects of choline acetyltransferase and acetylcholinesterase and the role of the acetylcholine receptor.

  2. Vitamin D and its role in skeletal muscle

    USDA-ARS?s Scientific Manuscript database

    This review discusses the clinical and laboratory studies that have examined a role of vitamin D in skeletal muscle. Many observational studies, mainly in older populations, indicate that vitamin D status is positively associated with muscle strength and physical performance and inversely associated...

  3. The impact of vitamin D on skeletal muscle function

    USDA-ARS?s Scientific Manuscript database

    This review discusses the clinical and laboratory studies that have examined a role of vitamin D in skeletal muscle. Many observational studies, mainly in older populations, indicate that vitamin D status is positively associated with muscle strength and physical performance and inversely associated...

  4. Acylcarnitines: potential implications for skeletal muscle insulin resistance

    USDA-ARS?s Scientific Manuscript database

    Insulin resistance is linked to increased acylcarnitine species in a number of tissues including skeletal muscle, due to incomplete fatty acid oxidation (FAO). It is not known if acylcarnitines participate in muscle insulin resistance or simply reflect dysregulated metabolism. The aim of this stud...

  5. Prion protein expression and functional importance in skeletal muscle.

    PubMed

    Smith, Jeffrey D; Moylan, Jennifer S; Hardin, Brian J; Chambers, Melissa A; Estus, Steven; Telling, Glenn C; Reid, Michael B

    2011-11-01

    Skeletal muscle expresses prion protein (PrP) that buffers oxidant activity in neurons. We hypothesize that PrP deficiency would increase oxidant activity in skeletal muscle and alter redox-sensitive functions, including contraction and glucose uptake. We used real-time polymerase chain reaction and Western blot analysis to measure PrP mRNA and protein in human diaphragm, five murine muscles, and muscle-derived C2C12 cells. Effects of PrP deficiency were tested by comparing PrP-deficient mice versus wild-type mice and morpholino-knockdown versus vehicle-treated myotubes. Oxidant activity (dichlorofluorescin oxidation) and specific force were measured in murine diaphragm fiber bundles. PrP content differs among mouse muscles (gastrocnemius>extensor digitorum longus, EDL>tibialis anterior, TA; soleus>diaphragm) as does glycosylation (di-, mono-, nonglycosylated; gastrocnemius, EDL, TA=60%, 30%, 10%; soleus, 30%, 40%, 30%; diaphragm, 30%, 30%, 40%). PrP is predominantly di-glycosylated in human diaphragm. PrP deficiency decreases body weight (15%) and EDL mass (9%); increases cytosolic oxidant activity (fiber bundles, 36%; C2C12 myotubes, 7%); and depresses specific force (12%) in adult (8-12 mos) but not adolescent (2 mos) mice. This study is the first to directly assess a role of prion protein in skeletal muscle function. PrP content varies among murine skeletal muscles and is essential for maintaining normal redox homeostasis, muscle size, and contractile function in adult animals.

  6. Ultrastructure of skeletal muscle capillaries under conditions of space mission.

    PubMed

    Volodina, A V; Pozdnyakov, O M

    2006-06-01

    Capillaries of the rat forepaw skeletal muscles were examined on day 14 of space mission and on days 1 and 14 after landing. Ultrastructural studies revealed apoptosis caused by muscle fiber atrophy and necrobiotic changes eventuating in coagulation or monocellular necrosis of endothelial cells. Formation of capillaries was detected, which can be regarded as an adaptive reaction to injuries caused by space mission factors.

  7. Skeletal Muscle as a Peripheral Modifier of Behavior

    ERIC Educational Resources Information Center

    Jenkins, Robert R.

    1978-01-01

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

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

    PubMed

    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.

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

    PubMed

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

    2013-08-15

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

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

    PubMed

    Murray, Iain R; Baily, James E; Chen, William C W; Dar, Ayelet; Gonzalez, Zaniah N; Jensen, Andrew R; Petrigliano, Frank A; Deb, Arjun; Henderson, Neil C

    2017-03-01

    Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.

  11. Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle

    SciTech Connect

    Ploug, T.; Stallknecht, B.M.; Pedersen, O.; Kahn, B.B.; Ohkuwa, T.; Vinten, J.; Galbo, H. )

    1990-12-01

    The effect of 10 wk endurance swim training on 3-O-methylglucose (3-MG) uptake (at 40 mM 3-MG) in skeletal muscle was studied in the perfused rat hindquarter. Training resulted in an increase of approximately 33% for maximum insulin-stimulated 3-MG transport in fast-twitch red fibers and an increase of approximately 33% for contraction-stimulated transport in slow-twitch red fibers compared with nonexercised sedentary muscle. A fully additive effect of insulin and contractions was observed both in trained and untrained muscle. Compared with transport in control rats subjected to an almost exhaustive single exercise session the day before experiment both maximum insulin- and contraction-stimulated transport rates were increased in all muscle types in trained rats. Accordingly, the increased glucose transport capacity in trained muscle was not due to a residual effect of the last training session. Half-times for reversal of contraction-induced glucose transport were similar in trained and untrained muscles. The concentrations of mRNA for GLUT-1 (the erythrocyte-brain-Hep G2 glucose transporter) and GLUT-4 (the adipocyte-muscle glucose transporter) were increased approximately twofold by training in fast-twitch red muscle fibers. In parallel to this, Western blot demonstrated a approximately 47% increase in GLUT-1 protein and a approximately 31% increase in GLUT-4 protein. This indicates that the increases in maximum velocity for 3-MG transport in trained muscle is due to an increased number of glucose transporters.

  12. Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice.

    PubMed

    Benoit, Bérengère; Meugnier, Emmanuelle; Castelli, Martina; Chanon, Stéphanie; Vieille-Marchiset, Aurélie; Durand, Christine; Bendridi, Nadia; Pesenti, Sandra; Monternier, Pierre-Axel; Durieux, Anne-Cécile; Freyssenet, Damien; Rieusset, Jennifer; Lefai, Etienne; Vidal, Hubert; Ruzzin, Jérôme

    2017-08-01

    The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro. These effects were not elicited by FGF21, a closely related endocrine FGF member. Both in vitro and in vivo, FGF19 stimulates the phosphorylation of the extracellular-signal-regulated protein kinase 1/2 (ERK1/2) and the ribosomal protein S6 kinase (S6K1), an mTOR-dependent master regulator of muscle cell growth. Moreover, mice with a skeletal-muscle-specific genetic deficiency of β-Klotho (KLB), an obligate co-receptor for FGF15/19 (refs. 2,3), were unresponsive to the hypertrophic effect of FGF19. Finally, in mice, FGF19 ameliorates skeletal muscle atrophy induced by glucocorticoid treatment or obesity, as well as sarcopenia. Taken together, these findings provide evidence that the enterokine FGF19 is a novel factor in the regulation of skeletal muscle mass, and that it has therapeutic potential for the treatment of muscle wasting.

  13. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  14. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    PubMed

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

    2016-02-01

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

  16. Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle.

    PubMed

    Porter, Craig; Reidy, Paul T; Bhattarai, Nisha; Sidossis, Labros S; Rasmussen, Blake B

    2015-09-01

    Loss of mitochondrial competency is associated with several chronic illnesses. Therefore, strategies that maintain or increase mitochondrial function will likely be of benefit in numerous clinical settings. Endurance exercise has long been known to increase mitochondrial function in the skeletal muscle. Comparatively little is known regarding the effect of resistance exercise training (RET) on skeletal muscle mitochondrial respiratory function. The purpose of the current study was to determine the effect of chronic resistance training on skeletal muscle mitochondrial respiratory capacity and function. Here, we studied the effect of a 12-wk RET program on skeletal muscle mitochondrial function in 11 young healthy men. Muscle biopsies were collected before and after the 12-wk training program, and mitochondrial respiratory capacity was determined in permeabilized myofibers by high-resolution respirometry. RET increased lean body mass and quadriceps muscle strength by 4% and 15%, respectively (P < 0.001). Coupled mitochondrial respiration supported by complex I, and complex I and II substrates increased by 2- and 1.4-fold, respectively (P < 0.01). The ratio of coupled complex I-supported respiration to maximal respiration increased with RET (P < 0.05), as did complex I protein abundance (P < 0.05), whereas the substrate control ratio for succinate was reduced after RET (P < 0.001). Transcripts responsible for proteins critical to electron transfer and NAD production increased with training (P < 0.05), whereas transcripts involved in mitochondrial biogenesis were unaltered. Collectively, 12 wk of RET resulted in qualitative and quantitative changes in skeletal muscle mitochondrial respiration. This adaptation was accompanied by modest changes in mitochondrial proteins and transcript expression. RET seems to be a means to augment the respiratory capacity and intrinsic function of skeletal muscle mitochondria.

  17. The MyomiR network in skeletal muscle plasticity.

    PubMed

    McCarthy, John J

    2011-07-01

    MicroRNA (miRNA) are a class of noncoding RNA involved in regulating gene expression by a posttranscriptional mechanism. Based on work from our laboratory, this review explores the hypothesis that a recently described muscle-specific miRNA, myomiR, network has a central role in the regulation of skeletal muscle plasticity by coordinating changes in fiber type and muscle mass in response to altered contractile activity.

  18. Insulin-sensitive regulation of glucose transport and GLUT4 translocation in skeletal muscle of GLUT1 transgenic mice.

    PubMed Central

    Etgen, G J; Zavadoski, W J; Holman, G D; Gibbs, E M

    1999-01-01

    Skeletal muscle glucose transport was examined in transgenic mice overexpressing the glucose transporter GLUT1 using both the isolated incubated-muscle preparation and the hind-limb perfusion technique. In the absence of insulin, 2-deoxy-d-glucose uptake was increased approximately 3-8-fold in isolated fast-twitch muscles of GLUT1 transgenic mice compared with non-transgenic siblings. Similarly, basal glucose transport activity was increased approximately 4-14-fold in perfused fast-twitch muscles of transgenic mice. In non-transgenic mice insulin accelerated glucose transport activity approximately 2-3-fold in isolated muscles and to a much greater extent ( approximately 7-20-fold) in perfused hind-limb preparations. The observed effect of insulin on glucose transport in transgenic muscle was similarly dependent upon the technique used for measurement, as insulin had no effect on isolated fast-twitch muscle from transgenic mice, but significantly enhanced glucose transport in perfused fast-twitch muscle from transgenic mice to approximately 50-75% of the magnitude of the increase observed in non-transgenic mice. Cell-surface glucose transporter content was assessed via 2-N-4-(l-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(d -mannos-4-yloxy)-2-propylamine photolabelling methodology in both isolated and perfused extensor digitorum longus (EDL). Cell-surface GLUT1 was enhanced by as much as 70-fold in both isolated and perfused EDL of transgenic mice. Insulin did not alter cell-surface GLUT1 in either transgenic or non-transgenic mice. Basal levels of cell-surface GLUT4, measured in either isolated or perfused EDL, were similar in transgenic and non-transgenic mice. Interestingly, insulin enhanced cell-surface GLUT4 approximately 2-fold in isolated EDL and approximately 6-fold in perfused EDL of both transgenic and non-transgenic mice. In summary, these results reveal differences between isolated muscle and perfused hind-limb techniques, with the latter method showing a

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

    PubMed Central

    Porzionato, Andrea; Sfriso, Maria Martina; Pontini, Alex; Macchi, Veronica; Petrelli, Lucia; Pavan, Piero G.; Natali, Arturo N.; Bassetto, Franco; Vindigni, Vincenzo; De Caro, Raffaele

    2015-01-01

    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. PMID:26140375

  20. Cation pumps in skeletal muscle: potential role in muscle fatigue.

    PubMed

    Green, H J

    1998-03-01

    Two membrane bound pumps in skeletal muscle, the sarcolemma Na+-K+ adenosine triphosphatase (ATPase) and the sarcoplasmic reticulum Ca2+-ATPase, provide for the maintenance of transmembrane ionic gradients necessary for excitation and activation of the myofibrillar apparatus. The rate at which the pumps are capable of establishing ionic homeostasis depends on the maximal activity of the enzyme and the potential of the metabolic pathways for supplying adenosine triphosphate (ATP). The activity of the Ca2+-ATPase appears to be expressed in a fibre type specific manner with both the amount of the enzyme and the isoform type related to the speed of contraction. In contrast, only minimal differences exist between slow-twitch and fast-twitch fibres in Na+-K+ ATPase activity. Evidence is accumulating that both active transport of Na+ and K+ across the sarcolemma and Ca2+-uptake by the sarcoplasmic reticulum may be impaired in vivo in a task specific manner resulting in loss of contractile function. In contrast to the Ca2+-ATPase, the Na+-K+ ATPase can be rapidly upregulated soon after the onset of a sustained pattern of activity. Similar programmes of activity result in a downregulation of Ca2+-ATPase but at a much later time point. The manner in which the metabolic pathways reorganize following chronic activity to meet the changes in ATP demand by the cation pumps and the degree to which these adaptations are compartmentalized is uncertain.

  1. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    ERIC Educational Resources Information Center

    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…

  2. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    ERIC Educational Resources Information Center

    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…

  3. Hypodynamic and hypokinetic condition of skeletal muscles

    NASA Technical Reports Server (NTRS)

    Katinas, G. S.; Oganov, V. S.; Potapov, A. N.

    1980-01-01

    Data are presented in regard to the effect of unilateral brachial amputation on the physiological characteristics of two functionally different muscles, the brachial muscle (flexor of the brachium) and the medial head of the brachial triceps muscle (extensor of the brachium), which in rats represents a separate muscle. Hypokinesia and hypodynamia were studied.

  4. COX-2 inhibitor reduces skeletal muscle hypertrophy in mice.

    PubMed

    Novak, Margaret L; Billich, William; Smith, Sierra M; Sukhija, Kunal B; McLoughlin, Thomas J; Hornberger, Troy A; Koh, Timothy J

    2009-04-01

    Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced muscle growth in mice. COX-2 was expressed in plantaris muscles during compensatory hypertrophy and was localized mainly in or near muscle cell nuclei. Treatment with NS-398 blunted the increases in mass and protein content in overloaded muscles compared with vehicle-treated controls. Additionally, the COX-2 inhibitor decreased activity of the urokinase type plasminogen activator, macrophage accumulation, and cell proliferation, all of which are required for hypertrophy after synergist ablation. Expression of insulin-like growth factor-1 and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were increased following synergist ablation, but were not affected by NS-398. Additionally, expression of atrogin-1 was reduced during hypertrophy, but was also not affected by NS-398. These results demonstrate that COX-2 activity is required for skeletal muscle hypertrophy, possibly through facilitation of extracellular protease activity, macrophage accumulation, and cell proliferation.

  5. Circadian clock regulation of skeletal muscle growth and repair

    PubMed Central

    Chatterjee, Somik; Ma, Ke

    2016-01-01

    Accumulating evidence indicates that the circadian clock, a transcriptional/translational feedback circuit that generates ~24-hour oscillations in behavior and physiology, is a key temporal regulatory mechanism involved in many important aspects of muscle physiology. Given the clock as an evolutionarily-conserved time-keeping mechanism that synchronizes internal physiology to environmental cues, locomotor activities initiated by skeletal muscle enable entrainment to the light-dark cycles on earth, thus ensuring organismal survival and fitness. Despite the current understanding of the role of molecular clock in preventing age-related sarcopenia, investigations into the underlying molecular pathways that transmit clock signals to the maintenance of skeletal muscle growth and function are only emerging. In the current review, the importance of the muscle clock in maintaining muscle mass during development, repair and aging, together with its contribution to muscle metabolism, will be discussed. Based on our current understandings of how tissue-intrinsic muscle clock functions in the key aspects muscle physiology, interventions targeting the myogenic-modulatory activities of the clock circuit may offer new avenues for prevention and treatment of muscular diseases. Studies of mechanisms underlying circadian clock function and regulation in skeletal muscle warrant continued efforts. PMID:27540471

  6. Quantitative force comparison of polyacrylonitrile fibers with skeletal muscle

    NASA Astrophysics Data System (ADS)

    Gonzalez, Roger V.; Lee, Christopher Y.

    1998-07-01

    The possibility of using certain polymer gels as artificial skeletal muscle was investigated due to its ability to shorten or contract when saturated in acidic or basic solutions, respectively. Polyacrylonitrile (PAN) fiber is such an example of a polymer gel. Mechanical performance characteristics of PAN fibers were studied and compared to voluntary muscle mechanical properties. The experimental methods used to determine the mechanical properties of the PAN fibers were modeled after A. V. Hill's classic experiments of the force-length and force-velocity properties of voluntary muscle. In addition, the force-molarity, length-molarity, and force-time characteristics were measured for the PAN fibers. These characteristics were quantitatively and qualitatively compared to voluntary muscle properties when relevant and used to determine the feasibility of implementing PAN fibers as artificial skeletal muscle in modeling movement across the human elbow joint. The results indicated qualitative similarities with the mechanical characteristics of voluntary muscle, especially force-velocity property. The force capabilities of the PAN fibers were at the lower end of voluntary muscle force generation. (i.e. 20 - 200 N/cm2) Activation- contraction time was also substantially larger than skeletal muscle. Based on these data, it was concluded that using PAN fibers as artificial muscles in modeling the human elbow joint is feasible only under certain conditions. Additional characterization studies are needed to determine if individual PAN fibers can generate higher forces using a different experimental protocol or a different architectural arrangement of the fibers.

  7. Circadian clock regulation of skeletal muscle growth and repair.

    PubMed

    Chatterjee, Somik; Ma, Ke

    2016-01-01

    Accumulating evidence indicates that the circadian clock, a transcriptional/translational feedback circuit that generates ~24-hour oscillations in behavior and physiology, is a key temporal regulatory mechanism involved in many important aspects of muscle physiology. Given the clock as an evolutionarily-conserved time-keeping mechanism that synchronizes internal physiology to environmental cues, locomotor activities initiated by skeletal muscle enable entrainment to the light-dark cycles on earth, thus ensuring organismal survival and fitness. Despite the current understanding of the role of molecular clock in preventing age-related sarcopenia, investigations into the underlying molecular pathways that transmit clock signals to the maintenance of skeletal muscle growth and function are only emerging. In the current review, the importance of the muscle clock in maintaining muscle mass during development, repair and aging, together with its contribution to muscle metabolism, will be discussed. Based on our current understandings of how tissue-intrinsic muscle clock functions in the key aspects muscle physiology, interventions targeting the myogenic-modulatory activities of the clock circuit may offer new avenues for prevention and treatment of muscular diseases. Studies of mechanisms underlying circadian clock function and regulation in skeletal muscle warrant continued efforts.

  8. De novo synthesis of adenine nucleotides in different skeletal muscle fiber types

    SciTech Connect

    Tullson, P.C.; John-Alder, H.B.; Hood, D.A.; Terjung, R.L.

    1988-09-01

    Management of adenine nucleotide catabolism differs among skeletal muscle fiber types. This study evaluated whether there are corresponding differences in the rates of de novo synthesis of adenine nucleotide among fiber type sections of skeletal muscle using an isolated perfused rat hindquarter preparation. Label incorporation into adenine nucleotides from the (1-14C)glycine precursor was determined and used to calculate synthesis rates based on the intracellular glycine specific radioactivity. Results show that intracellular glycine is closely related to the direct precursor pool. Rates of de novo synthesis were highest in fast-twitch red muscle (57.0 +/- 4.0, 58.2 +/- 4.4 nmol.h-1.g-1; deep red gastrocnemius and vastus lateralis), relatively high in slow-twitch red muscle (47.0 +/- 3.1; soleus), and low in fast-twitch white muscle (26.1 +/- 2.0 and 21.6 +/- 2.3; superficial white gastrocnemius and vastus lateralis). Rates for four mixed muscles were intermediate, ranging between 32.3 and 37.3. Specific de novo synthesis rates exhibited a strong correlation (r = 0.986) with muscle section citrate synthase activity. Turnover rates (de novo synthesis rate/adenine nucleotide pool size) were highest in high oxidative muscle (0.82-1.06%/h), lowest in low oxidative muscle (0.30-0.35%/h), and intermediate in mixed muscle (0.44-0.55%/h). Our results demonstrate that differences in adenine nucleotide management among fiber types extends to the process of de novo adenine nucleotide synthesis.

  9. Hypermethylation: Causes and Consequences in Skeletal Muscle Myopathy.

    PubMed

    Majumder, Avisek; JyotirmayaBehera; Jeremic, Navena; Tyagi, Suresh C

    2016-12-16

    A detrimental consequence of hypermethylation is hyperhomocysteinemia (HHcy), that causes oxidative stress, inflammation and matrix degradation, which leads to multi-pathology in different organs. Although, it is well known that hypermethylation leads to overall gene silencing and hypomethylation leads to overall gene activation, the role of such process in skeletal muscle dysfunction during HHcy condition is unclear. In this study, we emphasized the multiple mechanisms including epigenetic alteration by which HHcy causes skeletal muscle myopathy. This review also highlights possible role of methylation, histone modification and RNA interference in skeletal muscle dysfunction during HHcy condition and potential therapeutic molecules, putative challenges, and methodologies to deal with HHcy mediated skeletal muscle dysfunction. We also highlighted that B vitamins (mainly B12 and B6) with folic acid supplementation, could be useful as an adjuvant therapy to reverse these consequences associated with this HHcy conditions in skeletal muscle. However, we would recommend to further study involving long-term trials could help to assess efficacy of the use of these therapeutic agents. This article is protected by copyright. All rights reserved.

  10. Reduced passive force in skeletal muscles lacking protein arginylation

    PubMed Central

    Minozzo, Fábio C.; Kalganov, Albert; Cornachione, Anabelle S.; Cheng, Yu-Shu; Leu, Nicolae A.; Han, Xuemei; Saripalli, Chandra; Yates, John R.; Granzier, Henk; Kashina, Anna S.

    2015-01-01

    Arginylation is a posttranslational modification that plays a global role in mammals. Mice lacking the enzyme arginyltransferase in skeletal muscles exhibit reduced contractile forces that have been linked to a reduction in myosin cross-bridge formation. The role of arginylation in passive skeletal myofibril forces has never been investigated. In this study, we used single sarcomere and myofibril measurements and observed that lack of arginylation leads to a pronounced reduction in passive forces in skeletal muscles. Mass spectrometry indicated that skeletal muscle titin, the protein primarily linked to passive force generation, is arginylated on five sites located within the A band, an important area for protein-protein interactions. We propose a mechanism for passive force regulation by arginylation through modulation of protein-protein binding between the titin molecule and the thick filament. Key points are as follows: 1) active and passive forces were decreased in myofibrils and single sarcomeres isolated from muscles lacking arginyl-tRNA-protein transferase (ATE1). 2) Mass spectrometry revealed five sites for arginylation within titin molecules. All sites are located within the A-band portion of titin, an important region for protein-protein interactions. 3) Our data suggest that arginylation of titin is required for proper passive force development in skeletal muscles. PMID:26511365

  11. Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischaemic injury.

    PubMed

    Kuraitis, D; Ebadi, D; Zhang, P; Rizzuto, E; Vulesevic, B; Padavan, D T; Al Madhoun, A; McEwan, K A; Sofrenovic, T; Nicholson, K; Whitman, S C; Mesana, T G; Skerjanc, I S; Musarò, A; Ruel, M; Suuronen, E J

    2012-09-12

    Biomaterial-guided regeneration represents a novel approach for the treatment of myopathies. Revascularisation and the intramuscular extracellular matrix are important factors in stimulating myogenesis and regenerating muscle damaged by ischaemia. In this study, we used an injectable collagen matrix, enhanced with sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration. The elastic properties of collagen and sLeX-collagen matrices were similar to those of skeletal muscle, and culture of pluripotent mESCs on the matrices promoted their differentiation into myocyte-like cells expressing Pax3, MHC3, myogenin and Myf5. The regenerative properties of matrices were evaluated in ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and IGF binding protein-2 and -5 after 3 days. This was followed by muscle regeneration, including a greater number of regenerating myofibres and increased transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days. Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment of bone marrow-derived progenitor cells, the development of larger arterioles and the restoration of tissue perfusion. Both matrix treatments tended to reduce maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of force and also prevented muscle fatigue. Only sLeX-matrix treatment improved mobility of mice on a treadmill. Together, these results suggest a novel approach for regenerative myogenesis, whereby treatment only with a matrix, which possesses an inherent ability to guide myogenic differentiation of pluripotent stem cells, can enhance the endogenous vascular and myogenic regeneration of skeletal muscle, thus holding promise for future clinical use.

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

    PubMed Central

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

    PubMed

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

    2011-09-01

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

  14. Uncovering the exercise-related proteome signature in skeletal muscle.

    PubMed

    Padrão, Ana Isabel; Ferreira, Rita; Amado, Francisco; Vitorino, Rui; Duarte, José Alberto

    2016-03-01

    Exercise training has been recommended as a nonpharmacological strategy for the prevention and attenuation of skeletal muscle atrophy in distinct pathophysiological conditions. Despite the well-established phenotypic alterations, the molecular mechanisms underlying exercise-induced skeletal muscle remodeling are poorly characterized. Proteomics based on mass spectrometry have been successfully applied for the characterization of skeletal muscle proteome, representing a pivotal approach for the wide characterization of the molecular networks that lead to skeletal muscle remodeling. Nevertheless, few studies were performed to characterize the exercise-induced proteome remodeling of skeletal muscle, with only six research papers focused on the cross-talk between exercise and pathophysiological conditions. In order to add new insights on the impact of distinct exercise programs on skeletal muscle proteome, molecular network analysis was performed with bioinformatics tools. This analysis highlighted an exercise-related proteome signature characterized by the up-regulation of the capacity for ATP generation, oxygen delivery, antioxidant capacity and regulation of mitochondrial protein synthesis. Chronic endurance training up-regulates the tricarboxylic acid cycle and oxidative phosphorylation system, whereas the release of calcium ion into cytosol and amino acid metabolism are the biological processes up-regulated by a single bout of exercise. Other issues as exercise intensity, load, mode and regimen as well as muscle type also influence the exercise-induced proteome signature. The comprehensive analysis of the molecular networks modulated by exercise training in health and disease, taking in consideration all these variables, might not only support the therapeutic effect of exercise but also highlight novel targets for the development of enhanced pharmacological strategies.

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

    SciTech Connect

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

    2010-09-24

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

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

    PubMed

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

    2017-07-01

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

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2010-09-01

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

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

    PubMed

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

    2017-04-08

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

  2. Kelch proteins: emerging roles in skeletal muscle development and diseases

    PubMed Central

    2014-01-01

    Our understanding of genes that cause skeletal muscle disease has increased tremendously over the past three decades. Advances in approaches to genetics and genomics have aided in the identification of new pathogenic mechanisms in rare genetic disorders and have opened up new avenues for therapeutic interventions by identification of new molecular pathways in muscle disease. Recent studies have identified mutations of several Kelch proteins in skeletal muscle disorders. The Kelch superfamily is one of the largest evolutionary conserved gene families. The 66 known family members all possess a Kelch-repeat containing domain and are implicated in diverse biological functions. In skeletal muscle development, several Kelch family members regulate the processes of proliferation and/or differentiation resulting in normal functioning of mature muscles. Importantly, many Kelch proteins function as substrate-specific adaptors for Cullin E3 ubiquitin ligase (Cul3), a core component of the ubiquitin-proteasome system to regulate the protein turnover. This review discusses the emerging roles of Kelch proteins in skeletal muscle function and disease. PMID:24959344

  3. Effects of prolonged space flight on rat skeletal muscle.

    PubMed

    Nesterov, V P; Zheludkova, Z P; Kuznetsova, L A

    1979-10-01

    The effect of a 20-day space flight on water, Na+, K+, Mg2+, Ca2+ and glycogen contents as well as on activities of glycogen metabolism enzymes--glycogen synthetase and glycogen phosphorylase--of rat skeletal muscles was studied. This data is regarded as an integral test characterizing the state of contractile tissue of the animals at the final stage of flight aboard biosatellites. The measurements indicate that there were no significant changes of cations and glycogen contents nor of the enzymic activities in fast-twitch muscles during the 20-day spaceflight. At the same time dehydration in these muscles was observed, which disappeared on the 25th postflight day. In slow-twitch antigravitational skeletal muscle (m. soleus) there was a decrease of K+ and increase of Na+ in the tissue contents. The changes disappeared at the end of the on-earth readaptation period. From the pattern of these observations, we can conclude that the 20-day space flight leads to some reversible biochemical changes of the rat skeletal muscles. A conclusion can be drawn about necessity of creating, aboard the spaceship, an artificial load on antigravitational skeletal muscles.

  4. Smad7 promotes and enhances skeletal muscle differentiation.

    PubMed

    Kollias, Helen D; Perry, Robert L S; Miyake, Tetsuaki; Aziz, Arif; McDermott, John C

    2006-08-01

    Transforming growth factor beta1 (TGF-beta1) and myostatin signaling, mediated by the same Smad downstream effectors, potently repress skeletal muscle cell differentiation. Smad7 inhibits these cytokine signaling pathways. The role of Smad7 during skeletal muscle cell differentiation was assessed. In these studies, we document that increased expression of Smad7 abrogates myostatin- but not TGF-beta1-mediated repression of myogenesis. Further, constitutive expression of exogenous Smad7 potently enhanced skeletal muscle differentiation and cellular hypertrophy. Conversely, targeting of endogenous Smad7 by small interfering RNA inhibited C2C12 muscle cell differentiation, indicating an essential role for Smad7 during myogenesis. Congruent with a role for Smad7 in myogenesis, we observed that the muscle regulatory factor (MyoD) binds to and transactivates the Smad7 proximal promoter region. Finally, we document that Smad7 directly interacts with MyoD and enhances MyoD transcriptional activity. Thus, Smad7 cooperates with MyoD, creating a positive loop to induce Smad7 expression and to promote MyoD driven myogenesis. Taken together, these data implicate Smad7 as a fundamental regulator of differentiation in skeletal muscle cells.

  5. Lkb1 regulation of skeletal muscle development, metabolism and muscle progenitor cell homeostasis.

    PubMed

    Shan, Tizhong; Xu, Ziye; Liu, Jiaqi; Wu, Weiche; Wang, Yizhen

    2017-10-01

    Liver kinase B1 (Lkb1), also named as Serine/Threonine protein kinase 11 (STK11), is a serine/threonine kinase that plays crucial roles in various cellular processes including cell survival, cell division, cellular polarity, cell growth, cell differentiation, and cell metabolism. In metabolic tissues, Lkb1 regulates glucose homeostasis and energy metabolism through phosphorylating and activating the AMPK subfamily proteins. In skeletal muscle, Lkb1 affects muscle development and postnatal growth, lipid and fatty acid oxidation, glucose metabolism, and insulin sensitivity. Recently, the regulatory roles of Lkb1 in regulating division, self-renew, proliferation, and differentiation of skeletal muscle progenitor cells have been reported. In this review, we discuss the roles of Lkb1 in regulating skeletal muscle progenitor cell homeostasis and skeletal muscle development and metabolism. © 2017 Wiley Periodicals, Inc.

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

    PubMed

    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.

  7. Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries.

    PubMed

    Grasman, Jonathan M; Zayas, Michelle J; Page, Raymond L; Pins, George D

    2015-10-01

    Skeletal muscle injuries typically result from traumatic incidents such as combat injuries where soft-tissue extremity injuries are present in one of four cases. Further, about 4.5 million reconstructive surgical procedures are performed annually as a result of car accidents, cancer ablation, or cosmetic procedures. These combat- and trauma-induced skeletal muscle injuries are characterized by volumetric muscle loss (VML), which significantly reduces the functionality of the injured muscle. While skeletal muscle has an innate repair mechanism, it is unable to compensate for VML injuries because large amounts of tissue including connective tissue and basement membrane are removed or destroyed. This results in a significant need to develop off-the-shelf biomimetic scaffolds to direct skeletal muscle regeneration. Here, the structure and organization of native skeletal muscle tissue is described in order to reveal clear design parameters that are necessary for scaffolds to mimic in order to successfully regenerate muscular tissue. We review the literature with respect to the materials and methodologies used to develop scaffolds for skeletal muscle tissue regeneration as well as the limitations of these materials. We further discuss the variety of cell sources and different injury models to provide some context for the multiple approaches used to evaluate these scaffold materials. Recent findings are highlighted to address the state of the field and directions are outlined for future strategies, both in scaffold design and in the use of different injury models to evaluate these materials, for regenerating functional skeletal muscle. Volumetric muscle loss (VML) injuries result from traumatic incidents such as those presented from combat missions, where soft-tissue extremity injuries are represented in one of four cases. These injuries remove or destroy large amounts of skeletal muscle including the basement membrane and connective tissue, removing the structural

  8. Are antioxidants useful for treating skeletal muscle atrophy?

    PubMed

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

    2009-10-01

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

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

    PubMed

    Murphy, Sandra; Dowling, Paul; Ohlendieck, Kay

    2016-09-09

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

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

    PubMed Central

    Murphy, Sandra; Dowling, Paul; Ohlendieck, Kay

    2016-01-01

    The pioneering work by Patrick H. O’Farrell established two-dimensional gel electrophoresis as one of the most important high-resolution protein separation techniques of modern biochemistry (Journal of Biological Chemistry 1975, 250, 4007–4021). The application of two-dimensional gel electrophoresis has played a key role in the systematic identification and detailed characterization of the protein constituents of skeletal muscles. Protein changes during myogenesis, muscle maturation, fibre type specification, physiological muscle adaptations and natural muscle aging were studied in depth by the original O’Farrell method or slightly modified gel electrophoretic techniques. Over the last 40 years, the combined usage of isoelectric focusing in the first dimension and sodium dodecyl sulfate polyacrylamide slab gel electrophoresis in the second dimension has been successfully employed in several hundred published studies on gel-based skeletal muscle biochemistry. This review focuses on normal and physiologically challenged skeletal muscle tissues and outlines key findings from mass spectrometry-based muscle proteomics, which was instrumental in the identification of several thousand individual protein isoforms following gel electrophoretic separation. These muscle-associated protein species belong to the diverse group of regulatory and contractile proteins of the acto-myosin apparatus that forms the sarcomere, cytoskeletal proteins, metabolic enzymes and transporters, signaling proteins, ion-handling proteins, molecular chaperones and extracellular matrix proteins. PMID:28248237

  11. Impaired Adaptive Response to Mechanical Overloading in Dystrophic Skeletal Muscle

    PubMed Central

    Joanne, Pierre; Hourdé, Christophe; Ochala, Julien; Caudéran, Yvain; Medja, Fadia; Vignaud, Alban; Mouisel, Etienne; Hadj-Said, Wahiba; Arandel, Ludovic; Garcia, Luis; Goyenvalle, Aurélie; Mounier, Rémi; Zibroba, Daria; Sakamato, Kei; Butler-Browne, Gillian; Agbulut, Onnik; Ferry, Arnaud

    2012-01-01

    Dystrophin contributes to force transmission and has a protein-scaffolding role for a variety of signaling complexes in skeletal muscle. In the present study, we tested the hypothesis that the muscle adaptive response following mechanical overloading (ML) would be decreased in MDX dystrophic muscle lacking dystrophin. We found that the gains in muscle maximal force production and fatigue resistance in response to ML were both reduced in MDX mice as compared to healthy mice. MDX muscle also exhibited decreased cellular and molecular muscle remodeling (hypertrophy and promotion of slower/oxidative fiber type) in response to ML, and altered intracellular signalings involved in muscle growth and maintenance (mTOR, myostatin, follistatin, AMPKα1, REDD1, atrogin-1, Bnip3). Moreover, dystrophin rescue via exon skipping restored the adaptive response to ML. Therefore our results demonstrate that the adaptive response in response to ML is impaired in dystrophic MDX muscle, most likely because of the dystrophin crucial role. PMID:22511986

  12. Localisation of AMPK γ subunits in cardiac and skeletal muscles.

    PubMed

    Pinter, Katalin; Grignani, Robert T; Watkins, Hugh; Redwood, Charles

    2013-12-01

    The trimeric protein AMP-activated protein kinase (AMPK) is an important sensor of energetic status and cellular stress, and mutations in genes encoding two of the regulatory γ subunits cause inherited disorders of either cardiac or skeletal muscle. AMPKγ2 mutations cause hypertrophic cardiomyopathy with glycogen deposition and conduction abnormalities; mutations in AMPKγ3 result in increased skeletal muscle glycogen. In order to gain further insight into the roles of the different γ subunits in muscle and into possible disease mechanisms, we localised the γ2 and γ3 subunits, along with the more abundant γ1 subunit, by immunofluorescence in cardiomyocytes and skeletal muscle fibres. The predominant cardiac γ2 variant, γ2-3B, gave a striated pattern in cardiomyocytes, aligning with the Z-disk but with punctate staining similar to T-tubule (L-type Ca(2+) channel) and sarcoplasmic reticulum (SERCA2) markers. In skeletal muscle fibres AMPKγ3 localises to the I band, presenting a uniform staining that flanks the Z-disk, also coinciding with the position of Ca(2+) influx in these muscles. The localisation of γ2-3B- and γ3-containing AMPK suggests that these trimers may have similar functions in the different muscles. AMPK containing γ2-3B was detected in oxidative skeletal muscles which had low expression of γ3, confirming that these two regulatory subunits may be co-ordinately regulated in response to metabolic requirements. Compartmentalisation of AMPK complexes is most likely dependent on the regulatory γ subunit and this differential localisation may direct substrate selection and specify particular functional roles.

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

    PubMed

    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.

  14. Bone and skeletal muscle: neighbors with close ties.

    PubMed

    DiGirolamo, Douglas J; Kiel, Douglas P; Esser, Karyn A

    2013-07-01

    The musculoskeletal system evolved in mammals to perform diverse functions that include locomotion, facilitating breathing, protecting internal organs, and coordinating global energy expenditure. Bone and skeletal muscles involved with locomotion are both derived from somitic mesoderm and accumulate peak tissue mass synchronously, according to genetic information and environmental stimuli. Aging results in the progressive and parallel loss of bone (osteopenia) and skeletal muscle (sarcopenia) with profound consequences for quality of life. Age-associated sarcopenia results in reduced endurance, poor balance, and reduced mobility that predispose elderly individuals to falls, which more frequently result in fracture because of concomitant osteoporosis. Thus, a better understanding of the mechanisms underlying the parallel development and involution of these tissues is critical to developing new and more effective means to combat osteoporosis and sarcopenia in our increasingly aged population. This perspective highlights recent advances in our understanding of mechanisms coupling bone and skeletal muscle mass, and identify critical areas where further work is needed.

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

    PubMed

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

    2017-03-01

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

  16. Skeletal Muscle Cell Behavior After Physical Agent Treatments.

    PubMed

    Battistelli, Michela; Salucci, Sara; Guescini, Michele; Curzi, Davide; Stocchi, Vilberto; Falcieri, Elisabetta

    2015-01-01

    Apoptosis is essential for skeletal muscle development and homeostasis. It has been frequently involved in several muscle myopathies and sarcopenia, as well as in denervation, in disuse and acute strenuous or eccentric physical exercise. In this work skeletal muscle cell death, induced in vitro by a variety of physical triggers, has been investigated. C2C12 myoblasts and myotubes were exposed to UVB for 30 min, hyperthermia for 1 h at 43 °C, low pH for 3 h, hypothermia for 4h at 0 - 6°C, all followed by 2 - 4 h recovery. Their effects have been analysed by means of morpho- functional and molecular approaches. After UVB radiation, hyperthermia and acidosis, morphological apoptotic features and in situ DNA fragmentation appeared, more evident in myoblasts. Interestingly, apoptotic, non apoptotic and necrotic nuclei could be occasionally observed within the same myotube. Low pH induced apoptosis and necrosis, both characterized by swollen nuclei. In all these experimental conditions, the molecular investigations revealed a caspase pathway involvement in inducing cell death. Differently, hypothermia showed a scant and initial chromatin margination, in the presence of a diffused autophagic component. In this case, in situ DNA fragmentation and caspase activation have not been detected. Myoblasts and myotubes appeared sensitive to physical agents, some of which, induced apoptotic cell death. Moreover, hypothermia exposure seemed to enhance autophagic response, thus representing a way to delay trauma-correlated muscle inflammation. This study permits to highlight skeletal muscle cell behavior in response to physical agents, by adding important information to muscle cell death knowledge. UVB radiation and hyperthermia, usually used in clinical therapy, have also adverse effects on skeletal muscle such as myonuclei loss and cell death, contributing to muscle mass decrease. Acidosis occurs physiologically in muscular fatigue, reducing not only the athlete performance, but

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

    PubMed

    Andrade, Bruno M; Baldanza, Marcelo R; Ribeiro, Karla C; Porto, Anderson; Peçanha, Ramon; Fortes, Fabio S A; Zapata-Sudo, Gisele; Campos-de-Carvalho, Antonio C; Goldenberg, Regina C S; Werneck-de-Castro, João Pedro

    2015-01-01

    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.

  18. Bone Marrow Mesenchymal Cells Improve Muscle Function in a Skeletal Muscle Re-Injury Model

    PubMed Central

    Ribeiro, Karla C.; Porto, Anderson; Peçanha, Ramon; Fortes, Fabio S. A.; Zapata-Sudo, Gisele; Campos-de-Carvalho, Antonio C.; Goldenberg, Regina C. S.; Werneck-de-Castro, João Pedro

    2015-01-01

    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. PMID:26039243

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

    PubMed

    Lee, Eun-Jeong; De Winter, Josine M; Buck, Danielle; Jasper, Jeffrey R; Malik, Fady I; Labeit, Siegfried; Ottenheijm, Coen A; Granzier, Henk

    2013-01-01

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

  20. Exercise-Induced Skeletal Muscle Damage.

    ERIC Educational Resources Information Center

    Evans, William J.

    1987-01-01

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

  1. Exercise-Induced Skeletal Muscle Damage.

    ERIC Educational Resources Information Center

    Evans, William J.

    1987-01-01

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

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

    USDA-ARS?s Scientific Manuscript database

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

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

    NASA Technical Reports Server (NTRS)

    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.

  4. Functional and biochemical modifications in skeletal muscles from malarial mice.

    PubMed

    Brotto, Marco A P; Marrelli, Mauro T; Brotto, Leticia S; Jacobs-Lorena, Marcelo; Nosek, Thomas M

    2005-05-01

    Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (T(max)) produced by intact control and malaria-infected muscles before, during and after fatigue. Triton-skinned muscle fibres were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analysed by silver-enhanced SDS-PAGE. We found that the T(max) of intact muscles and the maximal Ca2+-activated force (F(max)) of Triton-skinned muscle fibres were reduced by approximately 50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton-skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton-skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.

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

    PubMed

    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

  6. Structural alterations of skeletal muscle in copd

    PubMed Central

    Mathur, Sunita; Brooks, Dina; Carvalho, Celso R. F.

    2014-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with a systemic inflammatory response. Peripheral muscle dysfunction has been well characterized in individuals with COPD and results from a complex interaction between systemic and local factors. Objective: In this narrative review, we will describe muscle wasting in people with COPD, the associated structural changes, muscle regenerative capacity and possible mechanisms for muscle wasting. We will also discuss how structural changes relate to impaired muscle function and mobility in people with COPD. Key Observations: Approximately 30–40% of individuals with COPD experience muscle mass depletion. Furthermore, muscle atrophy is a predictor of physical function and mortality in this population. Associated structural changes include a decreased proportion and size of type-I fibers, reduced oxidative capacity and mitochondrial density mainly in the quadriceps. Observations related to impaired muscle regenerative capacity in individuals with COPD include a lower proportion of central nuclei in the presence or absence of muscle atrophy and decreased maximal telomere length, which has been correlated with reduced muscle cross-sectional area. Potential mechanisms for muscle wasting in COPD may include excessive production of reactive oxygen species (ROS), altered amino acid metabolism and lower expression of peroxisome proliferator-activated receptors-gamma-coactivator 1-alpha mRNA. Despite a moderate relationship between muscle atrophy and function, impairments in oxidative metabolism only seems weakly related to muscle function. Conclusion: This review article demonstrates the cellular modifications in the peripheral muscle of people with COPD and describes the evidence of its relationship to muscle function. Future research will focus on rehabilitation strategies to improve muscle wasting and maximize function. PMID:24678302

  7. Pericapillary basement membrane thickening in human skeletal muscles.

    PubMed

    Baum, Oliver; Bigler, Marius

    2016-09-01

    The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases. Copyright © 2016 the American Physiological Society.

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

    PubMed

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

    2008-09-01

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

  9. Noninvasive skeletal muscle lactate detection between periods of intense exercise in humans.

    PubMed

    Mercier, B; Granier, P; Mercier, J; Foucat, L; Bielicki, G; Pradere, J; Renou, J P; Prefaut, C

    1998-06-01

    We investigated whether localized 1H nuclear magnetic resonance spectroscopy (NMRS) using stimulated echoes (STEAM) with a long mixing time (t(m)) allowed the suppression of the fat signal and detection of lactate in skeletal muscle. The 1H NMRS sequence was first validated in three isolated and perfused rabbit biceps brachii muscles. Spectra were obtained on a wide-bore spectrometer using a dual-tuned probe (1H and 31P). Death was simulated by ceasing the muscle perfusion, which allowed post-mortem changes to be followed. During and after the simulated death, changes in levels of pH and in content of energy-rich compounds were observed with 31P NMRS. Our results showed an inverse linear relationship between pH and lactate in each of the three rabbits (r = 0.93, P < 0.001; r = 0.92, P < 0.01; r = 0.89, P < 0.01) and a decrease in phosphocreatine and concomitant increase in lactate. We then investigated whether this sequence allowed repeated detection of lactate in human soleus muscle during the recovery between periods of intense exercise (force-velocity test, F-v test). Seven subjects mean age 25.1 (SEM 0.8) years participated in this study. Soleus muscle lactate was detected at rest and for 3 min 30 s of the 5-min recovery between periods using a 2.35-T 40-cm bore magnet spectrometer. Arm venous plasma lactate concentration was measured at rest, during the F-v test when the subject stopped pedalling (S1), and at the end of each 5-min recovery between periods (S2). Results showed that the venous plasma lactate concentration at S1 and S2 increased significantly from the beginning of the F-v test to peak anaerobic power (W(an,peak)) (P < 0.001). The spectra showed that muscle lactate resonance intensity rose markedly when W(an,peak) was achieved. The muscle lactate resonance intensity plotted as a percentage of the resting value increased significantly at W(an,peak) compared with submaximal braking forces (P < 0.05). We concluded from these results that localized 1H

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

    PubMed Central

    Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

    2016-01-01

    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. PMID:27529282

  11. Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway.

    PubMed

    Fang, Penghua; Yu, Mei; He, Biao; Guo, Lili; Huang, Xiaoli; Kong, Guimei; Shi, Mingyi; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

    2017-03-01

    Insulin resistance of skeletal muscle plays an important role in the pathogenesis of type 2 diabetes. Galanin, a 29/30-amino-acid neuropeptide, plays multiple biological actions, including anti-diabetic effects. Although recent results of our study showed that administration of galanin could mitigate insulin resistance by promoting glucose transporter 4 (GLUT4) expression and translocation in skeletal muscle of rats, there is no literature available regarding to the effect of type 1 of galanin receptors (GALR1) on insulin resistance in skeletal muscle of type 2 diabetic rats. Herein, we intended to survey the central effect of GALR1 agonist M617 on insulin resistance in skeletal muscle and its underlying mechanisms. We found that the intracerebroventricular injection of M617 increased glucose infusion rates in hyperinsulinemic euglycemic clamp tests, but attenuated the plasma insulin and glucose concentrations of diabetic rats. Furthermore, administration of M617 markedly increased GLUT4 mRNA expression and GLUT4 translocation in skeletal muscle of diabetic rats. Last, perfusion of M617 increased phosphorylated Akt and phosphorylated AS160 levels in the skeletal muscle of diabetic rats. In conclusion, central injection of M617 mitigated insulin resistance of skeletal muscle by enhancing GLUT4 translocation from intracellular pools to plasma membranes via the activation of the Akt/AS160/GLUT4 signaling pathway. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Functional heterogeneity of side population cells in skeletal muscle

    SciTech Connect

    Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro; Ikemoto, Madoka; Masuda, Satoru; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi . E-mail: takeda@ncnp.go.jp

    2006-03-17

    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{sup -}CD45{sup -} 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{sup -}CD45{sup -} 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{sup -}CD45{sup -} SP cells participate in muscle regeneration.

  13. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

    Muscle growth, protein metabolism, and amino acid metabolism were studied in various groups of rats. Certain groups were adrenaliectomized; some rats were suspended while others (the controls) were weight bearing. Results show that: (1) metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating glucocorticoids; (2) metabolic changes in the soleus muscle due to higher steroid levels are probably potentiated by greater numbers of steroid receptors; and (3) not all metabolic responses of the soleus muscle to unloading are due to the elevated levels of glucocorticoids or the increased sensitivity of this muscle to these hormones.

  14. Fat cell invasion in long-term denervated skeletal muscle.

    PubMed

    de Castro Rodrigues, Antonio; Andreo, Jesus Carlos; Rosa, Geraldo Marco; dos Santos, Nícolas Bertolaccini; Moraes, Luis Henrique Rapucci; Lauris, José Roberto P

    2007-01-01

    There are several differences between red and white muscles submitted to different experimental conditions, especially following denervation: a) denervation atrophy is more pronounced in red than white muscles; b) the size of the fibers in the red muscles does not vary between different parts of the muscle before and after denervation, when compared to white muscles; c) the regional difference in the white muscles initially more pronounced after denervation than red muscle; d) red muscle fibers and fibers of the deep white muscle present degenerative changes such as disordered myofibrils and sarcolemmal folds after long-term denervation; e) myotube-like fibers with central nuclei occur in the red muscle more rapidly than white after denervation. Denervation of skeletal muscles causes, in addition to fibers atrophy, loss of fibers with subsequent regeneration, but the extent of fat cell percentage invasion is currently unknown. The present article describes a quantitative study on fat cell invasion percentage in red m. soleus and white m. extensor digitorum longus (EDL) rat muscles at 7 weeks for up to 32 weeks postdenervation. The results indicate that the percentage of fat cells increase after denervation and it is steeper than the age-related fat invasion in normal muscles. The fat percentage invasion is more pronounced in red compared with white muscle. All experimental groups present a statistically significant difference as regard fat cell percentage invasion.

  15. Maintenance of skeletal muscle intracellular glutamine during standard surgical trauma.

    PubMed

    Kapadia, C R; Colpoys, M F; Jiang, Z M; Johnson, D J; Smith, R J; Wilmore, D W

    1985-01-01

    Skeletal muscle glutamine (GLN) concentration falls following injury and infection. In an attempt to prevent this decline and to characterize its influence on the efflux of amino acid (AA) from skeletal muscle, we administered varying quantities of AA (0,2, and 4 g/kg X day) as saline or AA solutions with or without GLN enrichment to 22 postoperative dogs. Plasma and muscle AA were determined before and 24 hr after standard laparotomy. Hindquarter AA efflux was measured at 6 and 24 hr. Skeletal muscle nitrogen declined in saline controls (69.8 +/- 8.5 vs 52.8 +/- 8.4 mmol/liter; p less than 0.01), largely due to the fall in intracellular GLN (21.48 +/- 3.21 vs 15.86 +/- 3.80; p less than 0.05). Similar alterations were seen in the animals receiving 2 g/kg. However, both intracellular nitrogen and GLN were maintained in animals receiving 4 g/kg, whether the AA solutions contained GLN or not (skeletal muscle nitrogen before 64.3 +/- 8.6 mmol/l vs 65.4 +/- 7.0 after, GLN 19.2 +/- 3.4 vs 19.9 +/- 3.0). Hindquarter AA efflux was reduced in those animals at 6 hr compared with saline-treated animals (-6.52 +/- 1.8 and -7.70 +/- 5.90 vs -19.05 +/- 4.06 mumol/kg X min; p less than 0.05). Intracellular GLN can be maintained during operative stress with adequate nitrogen infusion. Replacing 50% of the balanced AA solution with GLN resulted in equally effective maintenance of intracellular GLN levels and a comparable reduction in skeletal muscle AA efflux. Preservation of normal intracellular GLN levels with adequate AA nutrition may be essential for the conservation of muscle protein.

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

    PubMed Central

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

    2012-01-01

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

  17. Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males.

    PubMed

    Gheller, Brandon J F; Riddle, Emily S; Lem, Melinda R; Thalacker-Mercer, Anna E

    2016-07-17

    Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.

  18. Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy.

    PubMed

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

    2014-05-23

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

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

    PubMed Central

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

    2014-01-01

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

  20. Road to exercise mimetics: targeting nuclear receptors in skeletal muscle.

    PubMed

    Fan, Weiwei; Atkins, Annette R; Yu, Ruth T; Downes, Michael; Evans, Ronald M

    2013-12-01

    Skeletal muscle is the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including the metabolic syndrome and cancer. Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate major biological processes such as reproduction, development, and metabolism. Recent studies have demonstrated crucial roles for NRs and their co-regulators in the regulation of skeletal muscle energy metabolism and exercise-induced muscle remodeling. While nothing can fully replace exercise, development of exercise mimetics that enhance or even substitute for the beneficial effects of physical exercise would be of great benefit. The unique property of NRs that allows modulation by endogenous or synthetic ligands makes them bona fide therapeutic targets. In this review, we present an overview of the current understanding of the role of NRs and their co-regulators in skeletal muscle oxidative metabolism and summarize recent progress in the development of exercise mimetics that target NRs and their co-regulators.

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

    PubMed

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

    2014-01-01

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

  2. Altered cross-bridge properties in skeletal muscle dystrophies

    PubMed Central

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

    2014-01-01

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

  3. The role of taurine on skeletal muscle cell differentiation.

    PubMed

    Miyazaki, Teruo; Honda, Akira; Ikegami, Tadashi; Matsuzaki, Yasushi

    2013-01-01

    Taurine abundantly contained in the skeletal muscle has been considered as one of essential factors for the differentiation and growth of skeletal muscles. The previous studies in the taurine transporter knockout mice showed that deficiency of taurine content in the skeletal muscle caused incomplete muscular developments, morphological abnormalities, and exercise abilities. In fetal and neonatal periods, taurine must be an essential amino acid due to no biosynthesis capacity, and therefore, taurine should be endogenously supplied through placenta and maternal milk. In general cell culture condition, taurine contained in the culture medium is absent or few, and therefore, most of cultured cells are in taurine-deficient condition. In the present study, we confirmed, in cultured mouse differentiable myoblast, taurine treatment significantly enhanced the differentiation to myotube in a dose-dependent manner, while these effects were abrogated by inhibitions of taurine transport and Ca(2+) signaling pathway.The present study suggested that exogenous taurine might play a key role on the mature differentiation/growth of the skeletal muscle during development period through Ca(2+) signaling pathway, and therefore, taurine would contribute the muscle recovery after damages.

  4. Regulation of skeletal muscle stem cells by fibroblast growth factors.

    PubMed

    Pawlikowski, Bradley; Vogler, Thomas Orion; Gadek, Katherine; Olwin, Bradley B

    2017-03-01

    Fibroblast growth factors (FGFs) are essential for self-renewal of skeletal muscle stem cells (satellite cells) and required for maintenance and repair of skeletal muscle. Satellite cells express high levels of FGF receptors 1 and 4, low levels of FGF receptor 3, and little or no detectable FGF receptor 2. Of the multiple FGFs that influence satellite cell function in culture, FGF2 and FGF6 are the only members that regulate satellite cell function in vivo by activating ERK MAPK, p38α/β MAPKs, PI3 kinase, PLCγ and STATs. Regulation of FGF signaling is complex in satellite cells, requiring Syndecan-4, a heparan sulfate proteoglycan, as well as ß1-integrin and fibronectin. During aging, reduced responsiveness to FGF diminishes satellite cell self-renewal, leading to impaired skeletal muscle regeneration and depletion of satellite cells. Mislocalization of ß1-integrin, reductions in fibronectin, and alterations in heparan sulfate content all contribute to reduced FGF responsiveness in satellite cells. How these cell surface proteins regulate satellite cell self-renewal is incompletely understood. Here we summarize the current knowledge, highlighting the role(s) for FGF signaling in skeletal muscle regeneration, satellite cell behavior, and age-induced muscle wasting. Developmental Dynamics, 2017. © 2017 Wiley Periodicals, Inc.

  5. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury.

    PubMed

    Sen, Chandan K; Khanna, Savita; Harris, Hallie; Stewart, Richard; Balch, Maria; Heigel, Mallory; Teplitsky, Seth; Gnyawali, Surya; Rink, Cameron

    2017-03-01

    The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT(-)) or RAMT(+) groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14. RAMT(+) increased perfusion 1.5-fold in stroke-affected gastrocnemius as compared to RAMT(-) controls. Furthermore, RAMT(+) rats demonstrated improved poststroke track width (11% wider), stride length (21% longer), and travel distance (61% greater), as objectively measured using software-automated testing platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal muscle. Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP-10/CXCL10) were identified from a cytokine array. Taken together, outcomes suggest stroke acutely influences signal transduction in hindlimb skeletal muscle. Regimens based on mechanical therapy have the clear potential to protect hindlimb function from such adverse influence.-Sen, C. K., Khanna, S., Harris, H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury. © FASEB.

  6. PPARδ agonism inhibits skeletal muscle PDC activity, mitochondrial ATP production and force generation during prolonged contraction

    PubMed Central

    Constantin-Teodosiu, Dumitru; Baker, David J; Constantin, Despina; Greenhaff, Paul L

    2009-01-01

    We have recently shown that PPARδ agonism, used clinically to treat insulin resistance, increases fat oxidation and up-regulates mitochondrial PDK4 mRNA and protein expression in resting skeletal muscle. We hypothesized that PDK4 up-regulation, which inhibits pyruvate dehydrogenase complex (PDC)-dependent carbohydrate (CHO) oxidation, would negatively affect muscle function during sustained contraction where the demand on CHO is markedly increased. Three groups of eight male Wistar rats each received either vehicle or a PPARδ agonist (GW610742X) at two doses (5 and 100 mg (kg body mass (bm))−1 orally for 6 days. On the seventh day, the gastrocnemius–soleus–plantaris muscle group was isolated and snap frozen, or underwent 30 min of electrically evoked submaximal intensity isometric contraction using a perfused hindlimb model. During contraction, the rate of muscle PDC activation was significantly lower at 100 mg (kg bm)−1 compared with control (P < 0.01). Furthermore, the rates of muscle PCr hydrolysis and lactate accumulation were significantly increased at 100 mg (kg bm)−1 compared with control, reflecting lower mitochondrial ATP generation. Muscle tension development during contraction was significantly lower at 100 mg (kg bm)−1 compared with control (25%; P < 0.05). The present data demonstrate that PPARδ agonism inhibits muscle CHO oxidation at the level of PDC during prolonged contraction, and is paralleled by the activation of anaerobic metabolism, which collectively impair contractile function. PMID:19001043

  7. Diffusion-Tensor MRI Based Skeletal Muscle Fiber Tracking.

    PubMed

    Damon, Bruce M; Buck, Amanda K W; Ding, Zhaohua

    2011-11-01

    A skeletal muscle's function is strongly influenced by the internal organization and geometric properties of its fibers, a property known as muscle architecture. Diffusion-tensor magnetic resonance imaging-based fiber tracking provides a powerful tool for non-invasive muscle architecture studies, has three-dimensional sensitivity, and uses a fixed frame of reference. Significant advances have been made in muscle fiber tracking technology, including defining seed points for fiber tracking, quantitatively characterizing muscle architecture, implementing denoising procedures, and testing validity and repeatability. Some examples exist of how these data can be integrated with those from other advanced MRI and computational methods to provide novel insights into muscle function. Perspectives are offered regarding future directions in muscle diffusion-tensor imaging, including needs to develop an improved understanding for the microstructural basis for reduced and anisotropic diffusion, establish the best practices for data acquisition and analysis, and integrate fiber tracking with other physiological data.

  8. Focal adhesion kinase and its role in skeletal muscle

    PubMed Central

    Graham, Zachary A.; Gallagher, Philip M.; Cardozo, Christopher P.

    2015-01-01

    Skeletal muscle has a remarkable ability to respond to different physical stresses. Loading muscle through exercise, either anaerobic or aerobic, can lead to increases in muscle size and function while, conversely, the absence of muscle loading stimulates rapid decreases in size and function. A principal mediator of this load-induced change is focal adhesion kinase (FAK), a downstream non-receptor tyrosine kinase that translates the cytoskeletal stress and strain signals transmitted across the cytoplasmic membrane by integrins to activate multiple anti-apoptotic and cell growth pathways. Changes in FAK expression and phosphorylation have been found to correlate to specific developmental states in myoblast differentiation, muscle fiber formation and muscle size in response to loading and unloading. With the capability to regulate costamere formation, hypertrophy and glucose metabolism, FAK is a molecule with diverse functions that are important in regulating muscle cell health. PMID:26142360

  9. Diffusion-Tensor MRI Based Skeletal Muscle Fiber Tracking

    PubMed Central

    Damon, Bruce M.; Buck, Amanda K. W.; Ding, Zhaohua

    2014-01-01

    A skeletal muscle's function is strongly influenced by the internal organization and geometric properties of its fibers, a property known as muscle architecture. Diffusion-tensor magnetic resonance imaging-based fiber tracking provides a powerful tool for non-invasive muscle architecture studies, has three-dimensional sensitivity, and uses a fixed frame of reference. Significant advances have been made in muscle fiber tracking technology, including defining seed points for fiber tracking, quantitatively characterizing muscle architecture, implementing denoising procedures, and testing validity and repeatability. Some examples exist of how these data can be integrated with those from other advanced MRI and computational methods to provide novel insights into muscle function. Perspectives are offered regarding future directions in muscle diffusion-tensor imaging, including needs to develop an improved understanding for the microstructural basis for reduced and anisotropic diffusion, establish the best practices for data acquisition and analysis, and integrate fiber tracking with other physiological data. PMID:25429308

  10. Human skeletal muscle responses to spaceflight and possible countermeasures

    NASA Technical Reports Server (NTRS)

    Gollnick, Philip D.; Edgerton, V. Reggie; Saltin, Bengt

    1990-01-01

    The current status of knowledge concerning the effects of unweighting skeletal muscle is summarized. The results of both ground-based and space-based animal studies are reviewed which show that there is rapid loss in muscle mass, primarily in slow-twitch muscle, of the rat during unweighting of muscle. There is also a shift in the myosin isoforms with muscles such that slow-twitch muscles take on many of the characteristics of fast-twitch muscles. Ground-based studies in human suggest that programs of electrical stimulation can be developed to simulate normal muscular contractions. Attempts to develop countermeasures to the adverse effects of space travel on muscular functions in humans have not been successful to date.

  11. Focal adhesion kinase and its role in skeletal muscle.

    PubMed

    Graham, Zachary A; Gallagher, Philip M; Cardozo, Christopher P

    2015-10-01

    Skeletal muscle has a remarkable ability to respond to different physical stresses. Loading muscle through exercise, either anaerobic or aerobic, can lead to increases in muscle size and function while, conversely, the absence of muscle loading stimulates rapid decreases in size and function. A principal mediator of this load-induced change is focal adhesion kinase (FAK), a downstream non-receptor tyrosine kinase that translates the cytoskeletal stress and strain signals transmitted across the cytoplasmic membrane by integrins to activate multiple anti-apoptotic and cell growth pathways. Changes in FAK expression and phosphorylation have been found to correlate to specific developmental states in myoblast differentiation, muscle fiber formation and muscle size in response to loading and unloading. With the capability to regulate costamere formation, hypertrophy and glucose metabolism, FAK is a molecule with diverse functions that are important in regulating muscle cell health.

  12. Human skeletal muscle responses to spaceflight and possible countermeasures

    NASA Technical Reports Server (NTRS)

    Gollnick, Philip D.; Edgerton, V. Reggie; Saltin, Bengt

    1990-01-01

    The current status of knowledge concerning the effects of unweighting skeletal muscle is summarized. The results of both ground-based and space-based animal studies are reviewed which show that there is rapid loss in muscle mass, primarily in slow-twitch muscle, of the rat during unweighting of muscle. There is also a shift in the myosin isoforms with muscles such that slow-twitch muscles take on many of the characteristics of fast-twitch muscles. Ground-based studies in human suggest that programs of electrical stimulation can be developed to simulate normal muscular contractions. Attempts to develop countermeasures to the adverse effects of space travel on muscular functions in humans have not been successful to date.

  13. Lactate and force production in skeletal muscle

    PubMed Central

    Kristensen, Michael; Albertsen, Janni; Rentsch, Maria; Juel, Carsten

    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. However, incubation with 20 mm lactic acid reduces the pH gradient across the sarcolemma, whereas the gradient is increased during muscle activity. Furthermore, unlike active muscle the Na+–K+ pump is not activated. We therefore hypothesized that lactic acid does not protect against fatigue in active muscle. Three incubation solutions were used: 20 mm Na-lactate (which acidifies internal pH), 12 mm Na-lactate +8 mm lactic acid (which mimics the pH changes during muscle activity), and 20 mm lactic acid (which acidifies external pH more than internal pH). All three solutions improved force in K+-depressed rat soleus muscle. The pH regulation associated with lactate incubation accelerated the Na+–K+ pump. To study whether the protective effect of lactate/lactic acid is a general mechanism, we stimulated muscles to fatigue with and without pre-incubation. None of the incubation solutions improved force development in repetitively stimulated muscle (Na-lactate had a negative effect). It is concluded that although lactate/lactic acid incubation regains force in K+-depressed resting muscle, a similar incubation has no or a negative effect on force development in active muscle. It is suggested that the difference between the two situations is that lactate/lactic acid removes the negative consequences of an unusual large depolarization in the K+-treated passive muscle, whereas the depolarization is less pronounced in active muscle. PMID:15550457

  14. Lactate and force production in skeletal muscle.

    PubMed

    Kristensen, Michael; Albertsen, Janni; Rentsch, Maria; Juel, Carsten

    2005-01-15

    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. However, incubation with 20 mm lactic acid reduces the pH gradient across the sarcolemma, whereas the gradient is increased during muscle activity. Furthermore, unlike active muscle the Na(+)-K(+) pump is not activated. We therefore hypothesized that lactic acid does not protect against fatigue in active muscle. Three incubation solutions were used: 20 mM Na-lactate (which acidifies internal pH), 12 mM Na-lactate +8 mm lactic acid (which mimics the pH changes during muscle activity), and 20 mM lactic acid (which acidifies external pH more than internal pH). All three solutions improved force in K(+)-depressed rat soleus muscle. The pH regulation associated with lactate incubation accelerated the Na(+)-K(+) pump. To study whether the protective effect of lactate/lactic acid is a general mechanism, we stimulated muscles to fatigue with and without pre-incubation. None of the incubation solutions improved force development in repetitively stimulated muscle (Na-lactate had a negative effect). It is concluded that although lactate/lactic acid incubation regains force in K(+)-depressed resting muscle, a similar incubation has no or a negative effect on force development in active muscle. It is suggested that the difference between the two situations is that lactate/lactic acid removes the negative consequences of an unusual large depolarization in the K(+)-treated passive muscle, whereas the depolarization is less pronounced in active muscle.

  15. Parvalbumin gene transfer impairs skeletal muscle contractility in old mice.

    PubMed

    Murphy, Kate T; Ham, Daniel J; Church, Jarrod E; Naim, Timur; Trieu, Jennifer; Williams, David A; Lynch, Gordon S

    2012-08-01

    Sarcopenia is the progressive age-related loss of skeletal muscle mass associated with functional impairments that reduce mobility and quality of life. Overt muscle wasting with sarcopenia is usually preceded by a slowing of the rate of relaxation and a reduction in maximum force production. Parvalbumin (PV) is a cytosolic Ca(2+) buffer thought to facilitate relaxation in muscle. We tested the hypothesis that restoration of PV levels in muscles of old mice would increase the magnitude and hasten relaxation of submaximal and maximal force responses. The tibialis anterior (TA) muscles of young (6 month), adult (13 month), and old (26 month) C57BL/6 mice received electroporation-assisted gene transfer of plasmid encoding PV or empty plasmid (pcDNA3.1). Contractile properties of TA muscles were assessed in situ 14 days after transfer. In old mice, muscles with increased PV expression had a 40% slower rate of tetanic force development (p<0.01), and maximum twitch and tetanic force were 22% and 16% lower than control values, respectively (p<0.05). Muscles with increased PV expression from old mice had an 18% lower maximum specific (normalized) force than controls, and absolute force was `26% lower at higher stimulation frequencies (150-300 Hz, p<0.05). In contrast, there was no effect of increased PV expression on TA muscle contractile properties in young and adult mice. The impairments in skeletal muscle function in old mice argue against PV overexpression as a therapeutic strategy for ameliorating aspects of contractile dysfunction with sarcopenia and help clarify directions for therapeutic interventions for age-related changes in skeletal muscle structure and function.

  16. Parvalbumin Gene Transfer Impairs Skeletal Muscle Contractility in Old Mice

    PubMed Central

    Murphy, Kate T.; Ham, Daniel J.; Church, Jarrod E.; Naim, Timur; Trieu, Jennifer; Williams, David A.

    2012-01-01

    Abstract Sarcopenia is the progressive age-related loss of skeletal muscle mass associated with functional impairments that reduce mobility and quality of life. Overt muscle wasting with sarcopenia is usually preceded by a slowing of the rate of relaxation and a reduction in maximum force production. Parvalbumin (PV) is a cytosolic Ca2+ buffer thought to facilitate relaxation in muscle. We tested the hypothesis that restoration of PV levels in muscles of old mice would increase the magnitude and hasten relaxation of submaximal and maximal force responses. The tibialis anterior (TA) muscles of young (6 month), adult (13 month), and old (26 month) C57BL/6 mice received electroporation-assisted gene transfer of plasmid encoding PV or empty plasmid (pcDNA3.1). Contractile properties of TA muscles were assessed in situ 14 days after transfer. In old mice, muscles with increased PV expression had a 40% slower rate of tetanic force development (p<0.01), and maximum twitch and tetanic force were 22% and 16% lower than control values, respectively (p<0.05). Muscles with increased PV expression from old mice had an 18% lower maximum specific (normalized) force than controls, and absolute force was ∼26% lower at higher stimulation frequencies (150–300 Hz, p<0.05). In contrast, there was no effect of increased PV expression on TA muscle contractile properties in young and adult mice. The impairments in skeletal muscle function in old mice argue against PV overexpression as a therapeutic strategy for ameliorating aspects of contractile dysfunction with sarcopenia and help clarify directions for therapeutic interventions for age-related changes in skeletal muscle structure and function. PMID:22455364

  17. Characteristics of locomotion, muscle strength, and muscle tissue in regenerating rat skeletal muscles.

    PubMed

    Iwata, Akira; Fuchioka, Satoshi; Hiraoka, Koichi; Masuhara, Mitsuhiko; Kami, Katsuya

    2010-05-01

    Although numerous studies have aimed to elucidate the mechanisms used to repair the structure and function of injured skeletal muscles, it remains unclear how and when movement recovers following damage. We performed a temporal analysis to characterize the changes in movement, muscle function, and muscle structure after muscle injury induced by the drop-mass technique. At each time-point, movement recovery was determined by ankle kinematic analysis of locomotion, and functional recovery was represented by isometric force. As a histological analysis, the cross-sectional area of myotubes was measured to examine structural regeneration. The dorsiflexion angle of the ankle, as assessed by kinematic analysis of locomotion, increased after injury and then returned to control levels by day 14 post-injury. The isometric force returned to normal levels by day 21 post-injury. However, the size of the myotubes did not reach normal levels, even at day 21 post-injury. These results indicate that recovery of locomotion occurs prior to recovery of isometric force and that functional recovery occurs earlier than structural regeneration. Thus, it is suggested that recovery of the movement and function of injured skeletal muscles might be insufficient as markers for estimating the degree of neuromuscular system reconstitution.

  18. Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading

    NASA Technical Reports Server (NTRS)

    Howard, G.; Steffen, J. M.; Geoghegan, T. E.

    1989-01-01

    The regulatory role of transcriptional alterations in unloaded skeletal muscles was investigated by determining levels of total muscle RNA and mRNA fractions in soleus, gastrocnemius, and extensor digitorum longus (EDL) of rats subjected to whole-body suspension for up to 7 days. After 7 days, total RNA and mRNA contents were lower in soleus and gastrocnemius, compared with controls, but the concentrations of both RNAs per g muscle were unaltered. Alpha-actin mRNA (assessed by dot hybridization) was significantly reduced in soleus after 1, 3, and 7 days of suspension and in gastrocnemius after 3 and 7 days, but was unchanged in EDL. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked alteration in mRNAs coding for several small proteins. Results suggest that altered transcription and availability of specific mRNAs contribute significantly to the regulation of protein synthesis during skeletal muscle unloading.

  19. Low frequency sounds from sustained contraction of human skeletal muscle.

    PubMed Central

    Oster, G; Jaffe, J S

    1980-01-01

    Low frequency audible vibrations are produced by human skeletal muscles undergoing sustained contraction. The effect is easily demonstrable with an electronic stethoscope which amplifies sound below 50 Hz. Autocorrelation analysis of the signal shows that it is periodic with a frequency 25 +/- 2.5 Hz. The quality of the sound is the same for all the skeletal muscles tested and is unaffected by changes in tension, ambient temperature, and blood flow. Electrically-stimulated contraction produces a sound which is indistinguishable from voluntary contraction. The amplitude of the sound increases linearly with tension. The sound signals are uncorrelated both in frequency and phase with electromyographic signals obtained simultaneously while the muscle is contacted. Arguments are presented to show that the sounds may be an intrinsic property of muscle contraction. PMID:7260260

  20. Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading

    NASA Technical Reports Server (NTRS)

    Howard, G.; Steffen, J. M.; Geoghegan, T. E.

    1989-01-01

    The regulatory role of transcriptional alterations in unloaded skeletal muscles was investigated by determining levels of total muscle RNA and mRNA fractions in soleus, gastrocnemius, and extensor digitorum longus (EDL) of rats subjected to whole-body suspension for up to 7 days. After 7 days, total RNA and mRNA contents were lower in soleus and gastrocnemius, compared with controls, but the concentrations of both RNAs per g muscle were unaltered. Alpha-actin mRNA (assessed by dot hybridization) was significantly reduced in soleus after 1, 3, and 7 days of suspension and in gastrocnemius after 3 and 7 days, but was unchanged in EDL. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked alteration in mRNAs coding for several small proteins. Results suggest that altered transcription and availability of specific mRNAs contribute significantly to the regulation of protein synthesis during skeletal muscle unloading.

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

    PubMed

    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.

  2. Biomaterial-based delivery for skeletal muscle repair

    PubMed Central

    Cezar, Christine A.; Mooney, David J.

    2015-01-01

    Skeletal muscle possesses a remarkable capacity for regeneration in response to minor damage, but severe injury resulting in a volumetric muscle loss can lead to extensive and irreversible fibrosis, scarring, and loss of muscle function. In early clinical trials, the intramuscular injection of cultured myoblasts was proven to be a safe but ineffective cell therapy, likely due to rapid death, poor migration, and immune rejection of the injected cells. In recent years, appropriate therapeutic cell types and culturing techniques have improved progenitor cell engraftment upon transplantation. Importantly, the identification of several key biophysical and biochemical cues that synergistically regulate satellite cell fate has paved the way for the development of cell-instructive biomaterials that serve as delivery vehicles for cells to promote in vivo regeneration. Material carriers designed to spatially and temporally mimic the satellite cell niche may be of particular importance for the complete regeneration of severely damaged skeletal muscle. PMID:25271446

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

    PubMed

    Godard, Michael P; Whitman, Samantha A; Song, Yao-Hua; Delafontaine, Patrice

    2012-01-01

    Heart failure (HF), a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFB-5) appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single-skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure. To investigate these molecules during "early" events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA) Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size. There were more (P < 0.05) single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7%) compared to the control subjects (13% ± 2%). IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05), respectively. Strikingly, there was a correlation in IGF-1 expression and muscle cross-sectional area (P < 0.05) resulting in a decrease in whole-muscle quality (P < 0.05) in the HF patients, despite no significant decrease in isometric strength or whole-muscle size. These data indicate that molecular alterations in myosin heavy chain isoforms, IGF-1, and IGFB-5 levels precede the gross morphological and functional deficits that have previously been associated with HF, and may be used as a predictor of functional outcome in patients.

  4. Changes in skeletal muscle with aging: effects of exercise training.

    PubMed

    Rogers, M A; Evans, W J

    1993-01-01

    There is an approximate 30% decline in muscle strength and a 40% reduction in muscle area between the second and seventh decades of life. Thus, the loss of muscle mass with aging appears to be the major factor in the age-related loss of muscle strength. The loss of muscle mass is partially due to a significant decline in the numbers of both Type I and Type II muscle fibers plus a decrease in the size of the muscle cells, with the Type II fibers showing a preferential atrophy. There appears to be no loss of glycolytic capacity in senescent skeletal muscle whereas muscle oxidative enzyme activity and muscle capillarization decrease by about 25%. Vigorous endurance exercise training in older people, where the stimulus is progressively increased, elicits a proliferation of muscle capillaries, an increase in oxidative enzyme activity, and a significant improvement in VO2max. Likewise, progressive resistive training in older individuals results in muscle hypertrophy and increased strength, if the training stimulus is of a sufficient intensity and duration. Since older individuals adapt to resistive and endurance exercise training in a similar fashion to young people, the decline in the muscle's metabolic and force-producing capacity can no longer be considered as an inevitable consequence of the aging process. Rather, the adaptations in aging skeletal muscle to exercise training may prevent sarcopenia, enhance the ease of carrying out the activities of daily living, and exert a beneficial effect on such age-associated diseases as Type II diabetes, coronary artery disease, hypertension, osteoporosis, and obesity.

  5. Prostaglandin E2/cyclooxygenase pathway in human skeletal muscle: influence of muscle fiber type and age.

    PubMed

    Liu, Sophia Z; Jemiolo, Bozena; Lavin, Kaleen M; Lester, Bridget E; Trappe, Scott W; Trappe, Todd A

    2016-03-01

    Prostaglandin E2 (PGE2) produced by the cyclooxygenase (COX) pathway regulates skeletal muscle protein turnover and exercise training adaptations. The purpose of this study was twofold: 1) define the PGE2/COX pathway enzymes and receptors in human skeletal muscle, with a focus on type I and II muscle fibers; and 2) examine the influence of aging on this pathway. Muscle biopsies were obtained from the soleus (primarily type I fibers) and vastus lateralis (proportionally more type II fibers than soleus) of young men and women (n = 8; 26 ± 2 yr), and from the vastus lateralis of young (n = 8; 25 ± 1 yr) and old (n = 12; 79 ± 2 yr) men and women. PGE2/COX pathway proteins [COX enzymes (COX-1 and COX-2), PGE2 synthases (cPGES, mPGES-1, and mPGES-2), and PGE2 receptors (EP1, EP2, EP3, and EP4)] were quantified via Western blot. COX-1, cPGES, mPGES-2, and all four PGE2 receptors were detected in all skeletal muscle samples examined. COX-1 (P < 0.1) and mPGES-2 were ∼20% higher, while EP3 was 99% higher and EP4 57% lower in soleus compared with vastus lateralis (P < 0.05). Aging did not change the level of skeletal muscle COX-1, while cPGES increased 45% and EP1 (P < 0.1), EP3, and EP4 decreased ∼33% (P < 0.05). In summary, PGE2 production capacity and receptor levels are different in human skeletal muscles with markedly different type I and II muscle fiber composition. In aging skeletal muscle, PGE2 production capacity is elevated and receptor levels are downregulated. These findings have implications for understanding the regulation of skeletal muscle adaptations to exercise and aging by the PGE2/COX pathway and related inhibitors. Copyright © 2016 the American Physiological Society.

  6. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  7. Progression of inflammation during immunodeficient mouse skeletal muscle regeneration.

    PubMed

    Grabowska, Iwona; Mazur, Magdalena A; Kowalski, K; Helinska, A; Moraczewski, Jerzy; Stremińska, Władysława; Hoser, Grażyna; Kawiak, Jerzy; Ciemerych, Maria A; Brzoska, Edyta

    2015-12-01

    The skeletal muscle injury triggers the inflammatory response which is crucial for damaged muscle fiber degradation and satellite cell activation. Immunodeficient mice are often used as a model to study the myogenic potential of transplanted human stem cells. Therefore, it is crucial to elucidate whether such model truly reflects processes occurring under physiological conditions. To answer this question we compared skeletal muscle regeneration of BALB/c, i.e. animals producing all types of inflammatory cells, and SCID mice. Results of our study documented that initial stages of muscles regeneration in both strains of mice were comparable. However, lower number of mononucleated cells was noticed in regenerating SCID mouse muscles. Significant differences in the number of CD14-/CD45+ and CD14+/CD45+ cells between BALB/c and SCID muscles were also observed. In addition, we found important differences in M1 and M2 macrophage levels of BALB/c and SCID mouse muscles identified by CD68 and CD163 markers. Thus, our data show that differences in inflammatory response during muscle regeneration, were not translated into significant modifications in muscle regeneration.

  8. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  9. Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania infantum).

    PubMed

    Vamvakidis, C D; Koutinas, A F; Kanakoudis, G; Georgiadis, G; Saridomichelakis, M

    2000-06-10

    Twenty-four dogs with a parasitologically and serologically established diagnosis of leishmaniasis were studied to investigate the atrophy of the masticatory muscles which commonly occurs in this disease, and to compare the lesions in the masticatory muscles with those in the cranial tibial muscles. The 24 animals were divided into three groups of eight, group A dogs with no muscular atrophy, group B dogs with different degrees of atrophy in the masticatory and skeletal muscles, and group C dogs with similar degrees of atrophy in the masticatory and skeletal muscles. Increased activities of creatine phosphokinase and lactate dehydrogenase were recorded in only some of the dogs in groups B and C, but there were no significant differences between the mean activities in the three groups. Electromyographic changes indicating myopathy and involving both the temporalis and cranial tibial muscles, were observed in two of the dogs in group A, seven of those in group B, and in all the dogs in group C. Muscle histopathology revealed a variable degree of muscle fibre necrosis and atrophy, mononuclear infiltrates and neutrophilic vasculitis in all the dogs except two in group A. Leishmanial amastigotes were found within macrophages and myofibres in 16 of the dogs, some in each group. IgG immune complexes were detected in muscle samples, and circulating antibodies against myofibres were detected in serum samples from all the 24 dogs.

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

    PubMed

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

    2015-12-01

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

  11. CONTRAST-ENHANCED ULTRASOUND ASSESSMENT OF IMPAIRED ADIPOSE TISSUE AND MUSCLE PERFUSION IN INSULIN-RESISTANT MICE

    PubMed Central

    Belcik, J. Todd; Davidson, Brian P.; Foster, Ted; Qi, Yue; Zhao, Yan; Peters, Dawn; Lindner, Jonathan R.

    2015-01-01

    Background In diabetes mellitus reduced perfusion and capillary surface area in skeletal muscle, which is a major glucose storage site, contributes to abnormal glucose homeostasis. Using contrast-enhanced ultrasound (CEU) we investigated whether abdominal adipose tissue perfusion is abnormal in insulin resistance (IR) and correlates with glycemic control. Methods and Results Abdominal adipose tissue and skeletal muscle CEU perfusion imaging was performed in obese IR (db/db) mice at 11-12 or 14-16 weeks of age, and in control lean mice. Time-intensity data were analyzed to quantify microvascular blood flow (MBF) and capillary blood volume (CBV). Blood glucose response over one hour was measured after insulin challenge (1 u/Kg, I.P.). Compared to control mice, db/db mice at 11-12 and 14-16 weeks had a higher glucose concentration area-under-the-curve after insulin (11.8±2.8, 20.6±4.3, and 28.4±5.9 mg·min/dL [×1000], respectively, p=0.0002), and also had lower adipose MBF (0.094±0.038, 0.035±0.010, and 0.023±0.01 mL/min/g, p=0.0002) and CBV (1.6±0.6, 1.0±0.3, and 0.5±0.1 mL/100 g, p=0.0017). The glucose area-under-the-curve correlated in a non-linear fashion with both adipose and skeletal muscle MBF and CBV. There were significant linear correlations between adipose and muscle MBF (r=0.81) and CBV (r=0.66). Adipocyte cell volume on histology was 25-fold higher in 14-16 week db/db versus control mice. Conclusions Abnormal adipose MBF and CBV in IR can be detected by CEU and correlates with the degree of impairment in glucose storage. Abnormalities in adipose tissue and muscle appear to be coupled. Impaired adipose tissue perfusion is in part explained by an increase in adipocyte size without proportional vascular response. PMID:25855669

  12. Antifibrotic effects of suramin in injured skeletal muscle after laceration.

    PubMed

    Chan, Yi-Sheng; Li, Yong; Foster, William; Horaguchi, Takashi; Somogyi, George; Fu, Freddie H; Huard, Johnny

    2003-08-01

    Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-beta1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 microg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (alpha-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.

  13. Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow

    PubMed Central

    Heinonen, Ilkka; Brothers, R. Matthew; Kemppainen, Jukka; Knuuti, Juhani; Kalliokoski, Kari K.

    2011-01-01

    For decades it was believed that direct and indirect heating (the latter of which elevates blood and core temperatures without directly heating the area being evaluated) increases skin but not skeletal muscle blood flow. Recent results, however, suggest that passive heating of the leg may increase muscle blood flow. Using the technique of positron-emission tomography, the present study tested the hypothesis that both direct and indirect heating increases muscle blood flow. Calf muscle and skin blood flows were evaluated from eight subjects during normothermic baseline, during local heating of the right calf [only the right calf was exposed to the heating source (water-perfused suit)], and during indirect whole body heat stress in which the left calf was not exposed to the heating source. Local heating increased intramuscular temperature of the right calf from 33.4 ± 1.0°C to 37.4 ± 0.8°C, without changing intestinal temperature. This stimulus increased muscle blood flow from 1.4 ± 0.5 to 2.3 ± 1.2 ml·100 g−1·min−1 (P < 0.05), whereas skin blood flow under the heating source increased from 0.7 ± 0.3 to 5.5 ± 1.5 ml·100 g−1·min−1 (P < 0.01). While whole body heat stress increased intestinal temperature by ∼1°C, muscle blood flow in the calf that was not directly exposed to the water-perfused suit (i.e., indirect heating) did not increase during the whole body heat stress (normothermia: 1.6 ± 0.5 ml·100 g−1·min−1; heat stress: 1.7 ± 0.3 ml·100 g−1·min−1; P = 0.87). Whole body heating, however, reflexively increased calf skin blood flow (to 4.0 ± 1.5 ml·100 g−1·min−1) in the area not exposed to the water-perfused suit. These data show that local, but not indirect, heating increases calf skeletal muscle blood flow in humans. These results have important implications toward the reconsideration of previously accepted blood flow distribution during whole body heat stress. PMID:21680875

  14. Bradykinin does not acutely sensitize the reflex pressor response during hindlimb skeletal muscle stretch in decerebrate rats.

    PubMed

    Rollins, Korynne S; Smith, Joshua R; Esau, Peter J; Kempf, Evan A; Hopkins, Tyler D; Copp, Steven W

    2017-10-01

    Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechanogated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that injection of bradykinin into the arterial supply of a hindlimb in decerebrate, unanesthetized rats would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with a freely perfused femoral artery. The pressor response during static hindlimb muscle stretch was compared before and after hindlimb arterial injection of 0.5 µg of bradykinin. Injection of bradykinin increased blood pressure to a greater extent in "ligated" (n = 10) than "freely perfused" (n = 10) rats. The increase in blood pressure during hindlimb muscle stretch, however, was not different before vs. after bradykinin injection in freely perfused (14 ± 2 and 15 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.62) or ligated (15 ± 3 and 14 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.80) rats. Likewise, the increase in renal sympathetic nerve activity during stretch was not different before vs. after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in freely perfused or ligated decerebrate rats. Copyright © 2017 the American Physiological Society.

  15. The Role of Epimysium in Suturing Skeletal Muscle Lacerations

    DTIC Science & Technology

    2005-01-01

    connective tissue in bovine skeletal muscle. A demonstration using the cell-maceration/ scanning electron microscope method. Acta Anatomica 1994;151:250...demonstration using the cell-maceration/scanning electron microscope method. Acta Anatomica 1994;151:250–257, with permission). 42 Kragh et al Surgical...did not focus on issues related to regional variability of the epimysium,14 myofiber types, or super- ficial or deep muscles, although these could

  16. Prion Protein Expression and Functional Importance in Skeletal Muscle

    PubMed Central

    Smith, Jeffrey D.; Moylan, Jennifer S.; Hardin, Brian J.; Chambers, Melissa A.; Estus, Steven; Telling, Glenn C.

    2011-01-01

    Abstract Skeletal muscle expresses prion protein (PrP) that buffers oxidant activity in neurons. Aims We hypothesize that PrP deficiency would increase oxidant activity in skeletal muscle and alter redox-sensitive functions, including contraction and glucose uptake. We used real-time polymerase chain reaction and Western blot analysis to measure PrP mRNA and protein in human diaphragm, five murine muscles, and muscle-derived C2C12 cells. Effects of PrP deficiency were tested by comparing PrP-deficient mice versus wild-type mice and morpholino-knockdown versus vehicle-treated myotubes. Oxidant activity (dichlorofluorescin oxidation) and specific force were measured in murine diaphragm fiber bundles. Results PrP content differs among mouse muscles (gastrocnemius>extensor digitorum longus, EDL>tibialis anterior, TA; soleus>diaphragm) as does glycosylation (di-, mono-, nonglycosylated; gastrocnemius, EDL, TA=60%, 30%, 10%; soleus, 30%, 40%, 30%; diaphragm, 30%, 30%, 40%). PrP is predominantly di-glycosylated in human diaphragm. PrP deficiency decreases body weight (15%) and EDL mass (9%); increases cytosolic oxidant activity (fiber bundles, 36%; C2C12 myotubes, 7%); and depresses specific force (12%) in adult (8–12 mos) but not adolescent (2 mos) mice. Innovation This study is the first to directly assess a role of prion protein in skeletal muscle function. Conclusions PrP content varies among murine skeletal muscles and is essential for maintaining normal redox homeostasis, muscle size, and contractile function in adult animals. Antioxid. Redox Signal. 15, 2465—2475. PMID:21453198

  17. Ultrastructural alterations in skeletal muscle fibers of rats after exercise

    NASA Technical Reports Server (NTRS)

    Akuzawa, M.; Hataya, M.

    1982-01-01

    Ultrastructural alterations in skeletal muscle fibers were electron microscopically studied in rats forced to run on the treadmill until all-out. When they were mild and limited to relatively small areas, the reconstruction of filaments ensued within 10 days without infiltration of cells. When they were severe and extensive, phagocytes infiltrated in the lesions and removed degenerative sacroplasmic debris from muscle fibers. A little later, myoblasts appeared and regeneration was accomplished in 30 days in much the same manner as in myogenesis.

  18. Endurance Exercise and the Regulation of Skeletal Muscle Metabolism.

    PubMed

    Booth, Frank W; Ruegsegger, Gregory N; Toedebusch, Ryan G; Yan, Zhen

    2015-01-01

    Almost a half century ago, regular endurance exercise was shown to improve the capacity of skeletal muscle to oxidize substrates to produce ATP for muscle work. Since then, adaptations in skeletal muscle mRNA level were shown to happen with a single bout of exercise. Protein changes occur within days if daily endurance exercise continues. Some of the mRNA and protein changes cause increases in mitochondrial concentrations. One mitochondrial adaptation that occurs is an increase in fatty acid oxidation at a given absolute, submaximal workload. Mechanisms have been described as to how endurance training increases mitochondria. Importantly, Pgc-1α is a master regulator of mitochondrial biogenesis by increasing many mitochondrial proteins. However, not all adaptations to endurance training are associated with increased mitochondrial concentrations. Recent evidence suggests that the energetic demands of muscle contraction are by themselves stronger controllers of body weight and glucose control than is muscle mitochondrial content. Endurance exercise has also been shown to regulate the processes of mitochondrial fusion and fission. Mitophagy removes damaged mitochondria, a process that maintains mitochondrial quality. Skeletal muscle fibers are composed of different phenotypes, which are based on concentrations of mitochondria and various myosin heavy chain protein isoforms. Endurance training at physiological levels increases type IIa fiber type with increased mitochondria and type IIa myosin heavy chain. Endurance training also improves capacity of skeletal muscle blood flow. Endurance athletes possess enlarged arteries, which may also exhibit decreased wall thickness. VEGF is required for endurance training-induced increases in capillary-muscle fiber ratio and capillary density. © 2015 Elsevier Inc. All rights reserved.

  19. Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle.

    PubMed

    Thornton, Angela M; Zhao, Xiaoli; Weisleder, Noah; Brotto, Leticia S; Bougoin, Sylvain; Nosek, Thomas M; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome; Brotto, Marco

    2011-06-01

    Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca(2+) to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca(2+) release channel-mediated Ca(2+) release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca(2+) entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.

  20. Store-Operated Ca2+ Entry (SOCE) Contributes to Normal Skeletal Muscle Contractility in young but not in aged skeletal muscle

    PubMed Central

    Brotto, Leticia S.; Bougoin, Sylvain; Nosek, Thomas M.; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome

    2011-01-01

    Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca2+ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle. PMID:21666285

  1. Comparison of protein synthesis and degradation in incubated and perfused muscle.

    PubMed Central

    Clark, A S; Mitch, W E

    1983-01-01

    Rates of muscle protein synthesis and degradation measured in the perfused hindquarter were compared with those in incubated epitrochlearis muscles. With fed or starved mature rats, results without insulin treatment were identical. With insulin treatment, protein synthesis in perfused hindquarters was greater, though protein degradation was the same. Thus rates of muscle protein degradation estimated by these two methods in vitro correspond closely. PMID:6349623

  2. Exercise training in chronic heart failure: improving skeletal muscle O2 transport and utilization

    PubMed Central

    Hirai, Daniel M.; Musch, Timothy I.

    2015-01-01

    Chronic heart failure (CHF) impairs critical structural and functional components of the O2 transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O2 delivery and utilization (Q̇mO2 and V̇mO2, respectively). The Q̇mO2/V̇mO2 ratio determines the microvascular O2 partial pressure (PmvO2), which represents the ultimate force driving blood-myocyte O2 flux (see Fig. 1). Improvements in perfusive and diffusive O2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster V̇mO2 kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal V̇mO2). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved Q̇mO2/V̇mO2 matching (and enhanced PmvO2) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2 convection within the skeletal muscle microcirculation, O2 diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary

  3. Exercise training in chronic heart failure: improving skeletal muscle O2 transport and utilization.

    PubMed

    Hirai, Daniel M; Musch, Timothy I; Poole, David C

    2015-11-01

    Chronic heart failure (CHF) impairs critical structural and functional components of the O2 transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O2 delivery and utilization (Q̇mO2 and V̇mO2 , respectively). The Q̇mO2 /V̇mO2 ratio determines the microvascular O2 partial pressure (PmvO2 ), which represents the ultimate force driving blood-myocyte O2 flux (see Fig. 1). Improvements in perfusive and diffusive O2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster V̇mO2 kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal V̇mO2 ). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved Q̇mO2 /V̇mO2 matching (and enhanced PmvO2 ) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2 convection within the skeletal muscle microcirculation, O2 diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  6. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    PubMed

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located.

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

    PubMed

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

    2016-01-01

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

  8. Macrophage depletion impairs skeletal muscle regeneration: The roles of regulatory factors for muscle regeneration.

    PubMed

    Liu, Xiaoguang; Liu, Yu; Zhao, Linlin; Zeng, Zhigang; Xiao, Weihua; Chen, Peijie

    2017-03-01

    Though macrophages are essential for skeletal muscle regeneration, which is a complex process, the roles and mechanisms of the macrophages in the process of muscle regeneration are still not fully understood. The objective of this study is to explore the roles of macrophages and the mechanisms involved in the regeneration of injured skeletal muscle. One hundred and twelve C57BL/6 mice were randomly divided into muscle contusion and macrophages depleted groups. Their gastrocnemius muscles were harvested at the time points of 12 h, 1, 3, 5, 7, 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin and eosin (HE) stain. The gene expression was analyzed by real-time polymerase chain reaction. The data showed that CL-liposomes treatment did affect the expression of myogenic regulatory factors (MyoD, myogenin) after injury. In addition, CL-liposomes treatment decreased the expression of regulatory factors of muscle regeneration (HGF, uPA, COX-2, IGF-1, MGF, FGF6) and increased the expression of inflammatory cytokines (TGF-β1, TNF-α, IL-1β, RANTES) in the late stage of regeneration. Moreover, there were significant correlations between macrophages and some regulatory factors (such as HGF, uPA) for muscle regeneration. These results suggested that macrophages depletion impairs skeletal muscle regeneration and that the regulatory factors for muscle regeneration may play important roles in this process.

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

    PubMed

    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

  10. Regenerated rat skeletal muscle after periodic contusions.

    PubMed

    Minamoto, V B; Bunho, S R; Salvini, T F

    2001-11-01

    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.

  11. Skeletal muscle respiratory capacity, endurance, and glycogen utilization.

    PubMed

    Fitts, R H; Booth, F W; Winder, W W; Holloszy, J O

    1975-04-01

    This study was undertaken to evaluate the relationship between physical performance capacity and the mitochondrial content of skeletal muscle. Four groups of rats were trained by means of treadmill running 5 days/wk for 13 wk. One group ran 10 min/day, a second group ran 30 min/day, a third group ran 60 min/day, and a fourth group ran 120 min/day. The magnitude of the exercise-induced adaptive increase in gastrocnemius muscle respiratory capacity varied over a twofold range in the four groups. There were significant correlations between the levels of three mitochondrial markers (cytochrome c, citrate synthase, respiratory capacity) in the animals' gastrocnemius muscles and the duration of a run to exhaustion. There was also a significant correlation between the amounts of glycogen remaining in liver and skeletal muscle after a 30-min-long exercise test and the respiratory capacity of the animal's leg muscles. These findings are compatible with the interpretation that a close relationshiop exists between skeletal muscle mitochondrial content and the capacity to perform endurance exercise.

  12. Myopathic changes in murine skeletal muscle lacking synemin

    PubMed Central

    García-Pelagio, Karla P.; Muriel, Joaquin; O'Neill, Andrea; Desmond, Patrick F.; Lovering, Richard M.; Lund, Linda; Bond, Meredith

    2015-01-01

    Diseases of striated muscle linked to intermediate filament (IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. PMID:25567810

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

    PubMed

    Brown, Laura D; Hay, William W

    2016-11-05

    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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. CD13 Regulates Anchorage and Differentiation of the Skeletal Muscle Satellite Stem Cell Population in Ischemic Injury

    PubMed Central

    Rahman, M. Mamunur; Ghosh, Mallika; Subramani, Jaganathan; Fong, Guo-Hua; Carlson, Morgan E.; Shapiro, Linda H.

    2014-01-01

    CD13 is a multifunctional cell surface molecule that regulates inflammatory and angiogenic mechanisms in vitro, but its contribution to these processes in vivo or potential roles in stem cell biology remains unexplored. We investigated the impact of loss of CD13 on a model of ischemic skeletal muscle injury that involves angiogenesis, inflammation and stem cell mobilization. Consistent with its role