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1

An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle  

PubMed Central

Essential amino acids (EAA) stimulate skeletal muscle mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis. It has recently been reported that an increase in amino acid (AA) transporter expression during anabolic conditions is rapamycin-sensitive. The purpose of this study was to determine whether an increase in EAA availability increases AA transporter expression in human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis of seven young adult subjects (3 male, 4 female) before and 1–3 h after EAA ingestion (10 g). Blood and muscle samples were analyzed for leucine kinetics using stable isotopic techniques. Quantitative RT-PCR, and immunoblotting were used to determine the mRNA and protein expression, respectively, of AA transporters and members of the general AA control pathway [general control nonrepressed (GCN2), activating transcription factor (ATF4), and eukaryotic initiation factor (eIF2) ?-subunit (Ser52)]. EAA ingestion increased blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle, intracellular muscle leucine concentration, ribosomal protein S6 (Ser240/244) phosphorylation, and muscle protein synthesis. This was followed with increased L-type AA transporter (LAT1), CD98, sodium-coupled neutral AA transporter (SNAT2), and proton-coupled amino acid transporter (PAT1) mRNA expression at 1 h (P < 0.05) and modest increases in LAT1 protein expression (3 h post-EAA) and SNAT2 protein expression (2 and 3 h post-EAA, P < 0.05). Although there were no changes in GCN2 expression and eIF2? phosphorylation, ATF4 protein expression reached significance by 2 h post-EAA (P < 0.05). We conclude that an increase in EAA availability upregulates human skeletal muscle AA transporter expression, perhaps in an mTORC1-dependent manner, which may be an adaptive response necessary for improved AA intracellular delivery.

Drummond, Micah J.; Glynn, Erin L.; Fry, Christopher S.; Timmerman, Kyle L.; Volpi, Elena

2010-01-01

2

Induction of amino acid transporters expression by endurance exercise in rat skeletal muscle  

SciTech Connect

Highlights: •Regulation of amino acid transporter expression in working muscle remains unclear. •Expression of amino acid transporters for leucine were induced by a bout of exercise. •Requirement of leucine in muscle cells might regulate expression of its transporters. •This information is beneficial for understanding the muscle remodeling by exercise. -- Abstract: We here investigated whether an acute bout of endurance exercise would induce the expression of amino acid transporters that regulate leucine transport across plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we observed that expression of mRNAs encoding L-type amino acid transporter 1 (LAT1) and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was also induced by the exercise in those three muscles. Expression of proton-assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced mRNA expression of these amino acid transporters appeared to be attenuated by repeated bouts of the exercise. These results suggested that the expression of amino acid transporters for leucine may be induced in response to an increase in the requirement for this amino acid in the cells of working skeletal muscles.

Murakami, Taro, E-mail: tamuraka@sgk.ac.jp; Yoshinaga, Mariko

2013-10-04

3

Age related profiles of free amino acids in human skeletal muscle.  

PubMed

Sarcopenia describes the involuntary decline in muscle mass with aging, coupled with fatigue, and loss of force and function. We investigated 113 human muscle biopsy specimens obtained from patients with neuromuscular diseases and controls. We measured 21 amino acids in these muscle biopsies. Age emerged as a significant negative predictor of cytosolic concentration ratio of glutamine to total branched chain amino acids and of glutamine to total aromatic amino acids using stepwise multiple linear regression analysis. This pattern of alteration corresponds well to documented alterations in skeletal muscle of critically ill patients and after immobilization. Additionally, in myositis, citrulline was significantly elevated, while glutamate, lysine and taurine were significantly reduced. Furthermore, in sporadic amyotrophic lateral sclerosis (sALS) the total aromatic amino acids, arginine, glutamate, threonine, and tyrosine were significantly elevated. This study provides evidence, that alteration of glutamine is correlated to aging and might reflect increased proteolysis in aged and diseased human skeletal muscle. PMID:16648814

Stuerenburg, Hans Joerg; Stangneth, Birgit; Schoser, Benedikt G H

2006-01-01

4

Exercise and Amino Acid Anabolic Cell Signaling and the Regulation of Skeletal Muscle Mass  

PubMed Central

A series of complex intracellular networks influence the regulation of skeletal muscle protein turnover. In recent years, studies have examined how cellular regulators of muscle protein turnover modulate metabolic mechanisms contributing to the loss, gain, or conservation of skeletal muscle mass. Exercise and amino acids both stimulate anabolic signaling potentially through several intracellular pathways including the mammalian target of rapamycin complex 1 and the mitogen activated protein kinase cell signaling cascades. As novel molecular regulators of muscle integrity continue to be explored, a contemporary analysis of the literature is required to understand the metabolic mechanisms by which contractile forces and amino acids affect cellular process that contribute to long-term adaptations and preservation of muscle mass. This article reviews the literature related to how exercise and amino acid availability affect cellular regulators of skeletal muscle mass, especially highlighting recent investigations that have identified mechanisms by which contractile forces and amino acids modulate muscle health. Furthermore, this review will explore integrated exercise and nutrition strategies that promote the maintenance of muscle health by optimizing exercise, and amino acid-induced cell signaling in aging adults susceptible to muscle loss.

Pasiakos, Stefan M.

2012-01-01

5

PGC-1?-Mediated Branched-Chain Amino Acid Metabolism in the Skeletal Muscle  

PubMed Central

Peroxisome proliferator-activated receptor (PPAR) ? coactivator 1? (PGC-1?) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1? in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1? and cultured cells, we investigated whether PGC-1? stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1? specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain ?-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1?. In C2C12 cells, the overexpression of PGC-1? significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1? in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

2014-01-01

6

Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.  

PubMed

Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting. PMID:24646715

Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

2014-01-01

7

PGC-1?-mediated branched-chain amino acid metabolism in the skeletal muscle.  

PubMed

Peroxisome proliferator-activated receptor (PPAR) ? coactivator 1? (PGC-1?) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1? in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1? and cultured cells, we investigated whether PGC-1? stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1? specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain ?-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1?. In C2C12 cells, the overexpression of PGC-1? significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1? in the skeletal muscle is considered to significantly contribute to BCAA metabolism. PMID:24638054

Hatazawa, Yukino; Tadaishi, Miki; Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

2014-01-01

8

Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals.  

PubMed Central

This study describes and analyzes sequential changes in plasma and skeletal muscle free amino acids following severe burn injury. Plasma free amino acids were determined in children (n = 9) with burns averaging 60% total body surface area and were compared with laboratory beagles (n = 44) which received a flame burn totaling 30% of their body surface area. In addition, needle biopsy specimens were obtained from the semitendonosus muscle in the animals to determine free intracellular amino acids. In both patients and animals the amount of total free amino acids in plasma fell following burn, suggesting relative protein deficiency. This drop was primarily due to a 47% drop in nonessential amino acids. However, plasma phenylalanine was consistently higher than normal following burn, and was strongly associated with death and weight loss in both animals and patients, especially when analyzed as a ratio with tyrosine. This finding suggested excessive catabolism, hepatic dysfunction, or both. Plasma levels of several amino acids correlated significantly with weight loss. Alterations in muscle free amino acids generally were similar to plasma amino acids. Exceptions were muscle alanine and glycine which strongly correlated with weight loss. However, the determination of muscle free amino acid profiles did not yield clinically useful information not available from plasma profiles. Plasma levels of liver enzymes suggested progressive hepatic dysfunction. These studies show that the laboratory beagle is a good model for studying the metabolic alterations of amino acids that accompany burn injury, since they mimic humans in many parameters which appear to be most useful with respect to clinical evaluation.

Stinnett, J D; Alexander, J W; Watanabe, C; MacMillan, B G; Fischer, J E; Morris, M J; Trocki, O; Miskell, P; Edwards, L; James, H

1982-01-01

9

Effect of insulin on system A amino acid transport in human skeletal muscle.  

PubMed Central

Transmembrane transport of neutral amino acids in skeletal muscle is mediated by at least four different systems (system A, ASC, L, and Nm), and may be an important target for insulin's effects on amino acid and protein metabolism. We have measured net amino acid exchanges and fractional rates of inward (k(in), min-1) and outward (kout, min-1) transmembrane transport of 2-methylaminoisobutyric acid (MeAIB, a nonmetabolizable amino acid analogue, specific for system A amino acid transport) in forearm deep tissues (skeletal muscle), by combining the forearm perfusion technique and a novel dual tracer ([1-H3]-D-mannitol and 2-[1-14C]-methylaminoisobutyric acid) approach for measuring in vivo the activity of system A amino acid transport. Seven healthy lean subjects were studied. After a baseline period, insulin was infused into the brachial artery to achieve local physiologic hyperinsulinemia (76 +/- 8 microU/ml vs 6.4 +/- 1.6 microU/ml in the basal period, P < 0.01) without affecting systemic hormone and substrate concentrations. Insulin switched forearm amino acid exchange from a net output (-2,630 +/- 1,100 nmol/min per kig of forearm tissue) to a net uptake (1,610 +/- 600 nmol/min per kg, P < 0.01 vs baseline). Phenylalanine and tyrosine balances simultaneously shifted from a net output (-146 +/- 47 and -173 +/- 34 nmol/min per kg, respectively) to a zero balance (16.3 +/- 51 for phenylalanine and 15.5 +/- 14.3 nmol/min per kg for tyrosine, P < 0.01 vs baseline for both), showing that protein synthesis and breakdown were in equilibrium during hyperinsulinemia. Net negative balances of alanine, methionine, glycine, threonine and asparagine (typical substrates for system A amino acid transport) also were decreased by insulin, whereas serine (another substrate for system A transport) shifted from a zero balance to net uptake. Insulin increased k(in) of MeAIB from a basal value of 11.8.10(-2) +/- 1.7.10(-2).min-1 to 13.7.10(-2) +/- 2.2.10(-2).min-1 (P < 0.02 vs the postabsorptive value), whereas kout was unchanged. We conclude that physiologic hyperinsulinemia stimulates the activity of system A amino acid transport in human skeletal muscle, and that this effect may play a role in determining the overall concomitant response of muscle amino acid/protein metabolism to insulin.

Bonadonna, R C; Saccomani, M P; Cobelli, C; DeFronzo, R A

1993-01-01

10

Effect of insulin on system A amino acid transport in human skeletal muscle.  

PubMed

Transmembrane transport of neutral amino acids in skeletal muscle is mediated by at least four different systems (system A, ASC, L, and Nm), and may be an important target for insulin's effects on amino acid and protein metabolism. We have measured net amino acid exchanges and fractional rates of inward (k(in), min-1) and outward (kout, min-1) transmembrane transport of 2-methylaminoisobutyric acid (MeAIB, a nonmetabolizable amino acid analogue, specific for system A amino acid transport) in forearm deep tissues (skeletal muscle), by combining the forearm perfusion technique and a novel dual tracer ([1-H3]-D-mannitol and 2-[1-14C]-methylaminoisobutyric acid) approach for measuring in vivo the activity of system A amino acid transport. Seven healthy lean subjects were studied. After a baseline period, insulin was infused into the brachial artery to achieve local physiologic hyperinsulinemia (76 +/- 8 microU/ml vs 6.4 +/- 1.6 microU/ml in the basal period, P < 0.01) without affecting systemic hormone and substrate concentrations. Insulin switched forearm amino acid exchange from a net output (-2,630 +/- 1,100 nmol/min per kig of forearm tissue) to a net uptake (1,610 +/- 600 nmol/min per kg, P < 0.01 vs baseline). Phenylalanine and tyrosine balances simultaneously shifted from a net output (-146 +/- 47 and -173 +/- 34 nmol/min per kg, respectively) to a zero balance (16.3 +/- 51 for phenylalanine and 15.5 +/- 14.3 nmol/min per kg for tyrosine, P < 0.01 vs baseline for both), showing that protein synthesis and breakdown were in equilibrium during hyperinsulinemia. Net negative balances of alanine, methionine, glycine, threonine and asparagine (typical substrates for system A amino acid transport) also were decreased by insulin, whereas serine (another substrate for system A transport) shifted from a zero balance to net uptake. Insulin increased k(in) of MeAIB from a basal value of 11.8.10(-2) +/- 1.7.10(-2).min-1 to 13.7.10(-2) +/- 2.2.10(-2).min-1 (P < 0.02 vs the postabsorptive value), whereas kout was unchanged. We conclude that physiologic hyperinsulinemia stimulates the activity of system A amino acid transport in human skeletal muscle, and that this effect may play a role in determining the overall concomitant response of muscle amino acid/protein metabolism to insulin. PMID:8432860

Bonadonna, R C; Saccomani, M P; Cobelli, C; DeFronzo, R A

1993-02-01

11

Morphometric changes induced by amino acid supplementation in skeletal and cardiac muscles of old mice.  

PubMed

Aging is associated with progressive structural disorganization of muscular and cardiac fibers, decreasing functional capacity, and increased rates of disease and death. Aging is also characterized by disturbances in protein synthesis with impaired cellular organelle functions, particularly in the mitochondria. The availability of amino acids is a key factor for the overall metabolism of mammals and exogenous supplements of amino acid mixtures (AAm) could be a valid therapeutic strategy to improve quality of life, avoiding malnutrition and muscle wasting in the elderly. We investigated the morphoquantitative effects of long-term AAm supplementation on the mitochondria and sarcomeres (by electron microscope) and on collagen matrix deposition (by histologic techniques) in both skeletal and cardiac muscles of young and aged mice. Our data showed that old animals have fewer mitochondria and massive fibrosis in both muscles. Long-term AAm supplementation increased the number and volume of mitochondria and sarcomeres and decreased fibrosis in both skeletal muscle and hearts in old rats. These findings indicate that AAm restored muscular morphologic parameters and probably improved the mechanical performance of these organs. PMID:18514623

Corsetti, Giovanni; Pasini, Evasio; D'Antona, Giuseppe; Nisoli, Enzo; Flati, Vincenzo; Assanelli, Deodato; Dioguardi, Francesco S; Bianchi, Rossella

2008-06-01

12

Ceramide down-regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells  

Microsoft Academic Search

Skeletal muscle is a major insulin target tissue and has a prominent role in the control of body amino acid economy, being the principal store of free and protein-bound amino acids and a dominant locus for amino acid metabolism. Interplay between diverse stimuli (e.g., hormonal\\/nutritional\\/mechanical) modulates muscle insulin action to serve physiological need through the action of factors such as

Russell Hyde; Eric Hajduch; Darren J. Powell; Peter M. Taylor; Harinder S. Hundal

2004-01-01

13

The role of amino acids in skeletal muscle adaptation to exercise.  

PubMed

The synthesis of new protein is necessary for both strength and endurance adaptations. While the proteins that are made might differ, myofibrillar proteins following resistance exercise and mitochondrial proteins and metabolic enzymes following endurance exercise, the basic premise of shifting to a positive protein balance after training is thought to be the same. What is less clear is the contribution of nutrition to the adaptive process. Following resistance exercise, proteins rich in the amino acid leucine increase the activation of mTOR, the rate of muscle protein synthesis (MPS), and the rate of muscle mass and strength gains. However, an effect of protein consumption during acute post-exercise recovery on mitochondrial protein synthesis has yet to be demonstrated. Protein ingestion following endurance exercise does facilitate an increase in skeletal MPS, supporting muscle repair, growth and remodeling. However, whether this results in improved performance has yet to be demonstrated. The current literature suggests that a strength athlete will experience an increased sensitivity to protein feeding for at least 24 h after exercise, but immediate consumption of 0.25 g/kg bodyweight of rapidly absorbed protein will enhance MPS rates and drive the skeletal muscle hypertrophic response. At rest, ?0.25 g/kg bodyweight of dietary protein should be consumed every 4-5 h and another 0.25-0.5 g/kg bodyweight prior to sleep to facilitate the postprandial muscle protein synthetic response. In this way, consuming dietary protein can complement intense exercise training and facilitate the skeletal muscle adaptive response. PMID:23899757

Aguirre, Nick; van Loon, Luc J C; Baar, Keith

2013-01-01

14

Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise  

PubMed Central

Amino acid transporters and mammalian target of rapamycin complex 1 (mTORC1) signaling are important contributors to muscle protein anabolism. Aging is associated with reduced mTORC1 signaling following resistance exercise, but the role of amino acid transporters is unknown. Young (n = 13; 28 ± 2 yr) and older (n = 13; 68 ± 2 yr) subjects performed a bout of resistance exercise. Skeletal muscle biopsies (vastus lateralis) were obtained at basal and 3, 6, and 24 h postexercise and were analyzed for amino acid transporter mRNA and protein expression and regulators of amino acid transporter transcription utilizing real-time PCR and Western blotting. We found that basal amino acid transporter expression was similar in young and older adults (P > 0.05). Exercise increased L-type amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, sodium-coupled neutral amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, and cationic amino acid transporter 1/SLC7A1 mRNA expression in both young and older adults (P < 0.05). L-type amino acid transporter 1 and CD98 protein increased only in younger adults (P < 0.05). eukaryotic initiation factor 2 ?-subunit (S52) increased similarly in young and older adults postexercise (P < 0.05). Ribosomal protein S6 (S240/244) and activating transcription factor 4 nuclear protein expression tended to be higher in the young, while nuclear signal transducer and activator of transcription 3 (STAT3) (Y705) was higher in the older subjects postexercise (P < 0.05). These results suggest that the rapid upregulation of amino acid transporter expression following resistance exercise may be regulated differently between the age groups, but involves a combination of mTORC1, activating transcription factor 4, eukaryotic initiation factor 2 ?-subunit, and STAT3. We propose an increase in amino acid transporter expression may contribute to enhanced amino acid sensitivity following exercise in young and older adults. In older adults, the increased nuclear STAT3 phosphorylation may be indicative of an exercise-induced stress response, perhaps to export amino acids from muscle cells.

Fry, Christopher S.; Glynn, Erin L.; Timmerman, Kyle L.; Dickinson, Jared M.; Walker, Dillon K.; Gundermann, David M.; Volpi, Elena; Rasmussen, Blake B.

2011-01-01

15

Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs  

PubMed Central

Background The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin and amino acids, especially leucine, modulate skeletal muscle protein synthesis and how this changes with development. In the current study, we identified mechanisms involved in protein degradation regulation. In experiment 1, 6- and 26-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic, 2) euinsulinemic-euglycemic-hyperaminoacidemic, and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h. In experiment 2, 5-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic-euleucinemic, 2) euinsulinemic-euglycemic-hypoaminoacidemic-hyperleucinemic, and 3) euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices of ubiquitin-proteasome, i.e., atrogin-1 (MAFbx) and muscle RING-finger protein-1 (MuRF1) and autophagy-lysosome systems, i.e., unc51-like kinase 1 (UKL1), microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (Lamp-2). For comparison, we measured ribosomal protein S6 (rpS6) and eukaryotic initiation factor 4E (eIF4E) activation, components of translation initiation. Results Abundance of atrogin-1, but not MuRF1, was greater in 26- than 6-d-old pigs and was not affected by insulin, amino acids, or leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment. The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased by insulin, amino acids, and leucine. These responses were more profound in younger pigs. Abundance of Lamp-2 was not affected by treatment or development. Abundance of eIF4E, but not rpS6, was higher in 6- than 26-d-old-pigs but unaffected by treatment. Phosphorylation of eIF4E was not affected by treatment, however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and the responses decreased with development. Conclusions The rapid growth of neonatal muscle is in part due to the positive balance between the activation of protein synthesis and degradation signaling. Insulin, amino acids, and, particularly, leucine, act as signals to modulate muscle protein synthesis and degradation in neonates.

2014-01-01

16

The complete amino acid sequence of chicken skeletal-muscle enolase.  

PubMed Central

The complete amino acid sequence of chicken skeletal-muscle enolase, comprising 433 residues, was determined. The sequence was deduced by automated sequencing of hydroxylamine-cleavage, CNBr-cleavage, o-iodosobenzoic acid-cleavage, clostripain-digest and staphylococcal-proteinase-digest fragments. The presence of several acid-labile peptide bonds and the tenacious aggregation of most CNBr-cleavage fragments meant that a commonly used sequencing strategy involving initial CNBr cleavage was unproductive. Cleavage at the single Asn-Gly peptide bond with hydroxylamine proved to be particularly useful. Comparison of the sequence of chicken enolase with the two yeast enolase isoenzyme sequences shows that the enzyme is strongly conserved, with 60% of the residues identical. The histidine and arginine residues implicated as being important for the activity of yeast enolase are conserved in the chicken enzyme. Secondary-structure predictions are analysed in an accompanying paper [Sawyer, Fothergill-Gilmore & Russell (1986) Biochem. J. 236, 127-130].

Russell, G A; Dunbar, B; Fothergill-Gilmore, L A

1986-01-01

17

Effect of Taurine Supplementation on the Alterations in Amino Acid Content in Skeletal Muscle with Exercise in Rat  

PubMed Central

Taurine included abundantly in skeletal muscle, particularly in the slow-twitch fibers, enhances exercise performance. However, the exact mechanisms for this effect have been unclear. The present study investigated the influence of taurine supplementation on amino acids profile in skeletal muscles as one of mechanisms in the enhancement of exercise performance induced by taurine. In the rats that received taurine solution, amino acids concentrations were comprehensively quantified in two portions with different fiber compositions in the fast-twitch fiber dominant (FFD) gastrocnemius muscle after 2 weeks, and in the gastrocnemius and additional other FFD muscles, liver, and plasma with exhausted exercise after 3 weeks. In the FFD muscles after 2 weeks, a common phenomenon that decreased concentrations of threonine (-16%), serine (-15~-16%), and glycine (-6~-16%) were observed, and they are categorized in the pyruvate precursors for hepatic gluconeogenesis rather than biosynthesis, polar, and side-chain structures. The decreases in the three amino acids were significantly emphasized after an additional week of taurine supplementation in the FFD muscles (p values in three amino acids in these tissues were less than 0.001-0.05), but not in the liver and plasma, accompanied with significantly increase of running time to exhaustion (p <0.05). In contrast, the three amino acids (threonine and serine; p < 0.05, glycine; p < 0.01) and alanine (p < 0.01) in the liver were significantly decreased and increased, respectively, following the exhaustive exercise. In conclusion, the taurine-induced reductions of these amino acids in skeletal muscle might be one of the mechanisms which underpin the enhancement of exercise performance by taurine. Key points Taurine ingestion significantly decreased certain amino acids in skeletal muscles accompanied with enhanced exercise performance. The decreased amino acids in common were threonine, serine, and glycine, but not alanine; pyruvate precursor for gluconeogenesis. The alteration of three amino acids in muscles was maintained after exhausted exercise. The muscular alterations of them might be one of taurine-induced roles on exercise performance.

Ishikura, Keisuke; Miyazaki, Teruo; Ra, Song-Gyu; Endo, Shoji; Nakamura, Yusuke; Matsuzaka, Takashi; Miyakawa, Shumpei; Ohmori, Hajime

2011-01-01

18

Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults  

PubMed Central

Skeletal muscle atrophy during bed rest is attributed, at least in part, to slower basal muscle protein synthesis (MPS). Essential amino acids (EAA) stimulate mammalian target of rapamycin (mTORC1) signaling, amino acid transporter expression, and MPS and are necessary for muscle mass maintenance, but there are no data on the effect of inactivity on this anabolic mechanism. We hypothesized that bed rest decreases muscle mass in older adults by blunting the EAA stimulation of MPS through reduced mTORC1 signaling and amino acid transporter expression in older adults. Six healthy older adults (67 ± 2 yr) participated in a 7-day bed rest study. We used stable isotope tracers, Western blotting, and real-time qPCR to determine the effect of bed rest on MPS, muscle mTORC1 signaling, and amino acid transporter expression and content in the postabsorptive state and after acute EAA ingestion. Bed rest decreased leg lean mass by ?4% (P < 0.05) and increased postabsorptive mTOR protein (P < 0.05) levels while postabsorptive MPS was unchanged (P > 0.05). Before bed rest acute EAA ingestion increased MPS, mTOR (Ser2448), S6 kinase 1 (Thr389, Thr421/Ser424), and ribosomal protein S6 (Ser240/244) phosphorylation, activating transcription factor 4, L-type amino acid transporter 1 and sodium-coupled amino acid transporter 2 protein content (P < 0.05). However, bed rest blunted the EAA-induced increase in MPS, mTORC1 signaling, and amino acid transporter protein content. We conclude that bed rest in older adults significantly attenuated the EAA-induced increase in MPS with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content. Together, our data suggest that a blunted EAA stimulation of MPS may contribute to muscle loss with inactivity in older persons.

Dickinson, Jared M.; Fry, Christopher S.; Walker, Dillon K.; Gundermann, David M.; Reidy, Paul T.; Timmerman, Kyle L.; Markofski, Melissa M.; Paddon-Jones, Douglas; Rasmussen, Blake B.; Volpi, Elena

2012-01-01

19

Effects of voluntary wheel running and amino acid supplementation on skeletal muscle of mice  

Microsoft Academic Search

The aims of the present study were as follows: (1) to examine the adaptational changes to chronic endurance voluntary exercise and (2) to investigate the effects of amino acid supplementation on the adaptational changes induced by endurance training in hindlimb (gastrocnemius, tibialis, soleus) and respiratory (diaphragm) muscles of mice. Male C57Bl6 mice were divided in four groups: control sedentary, sedentary

Maria Antonietta Pellegrino; Lorenza Brocca; Francesco Saverio Dioguardi; Roberto Bottinelli; Giuseppe D’Antona

2005-01-01

20

Comparison of the amino acid composition of the intracellular and extracellular matrix protein fractions isolated from avian skeletal muscles.  

PubMed

Intracellular and extracellular skeletal muscle protein fractions were isolated from the legs and breasts of young and adult White Leghorn chickens and quantified by detailed amino acid analysis. This involved repeated homogenization in the presence of 50 mM CaCl2, neutral phosphate-buffered saline (pH 7.4), solubilization by 2% sodium dodecyl sulfate (SDS), and centrifugation to separate all intracellular muscle proteins from the extracellular matrix. The total SDS-soluble intracellular muscle proteins in the adult and young birds ranged respectively from 93.2 to 94.5% in the leg and from 93.5 to 94.1% in the breast muscles. Collagen and collagen-like proteins in the extracellular matrix protein fractions were calculated from the amounts of 5-hydroxylysine found in their 96-h acid hydrolysates and elastin content from the amounts of desmosine present. Total collagen ranged from 3.42 to 5.18% in legs and from 2.91 to 3.89% in breasts. The elastin content of leg muscles represents only .061% of the total muscle protein. The calculated protein efficiency ratios for intracellular avian muscle proteins averaged 3.2 compared with a mean value of 1.4 for the extracellular matrix. PMID:2771847

Karatzas, C N; Zarkadas, C G

1989-06-01

21

Effects of eccentric exercise on branched-chain amino acid profiles in rat serum and skeletal muscle.  

PubMed

Supplementation of branched-chain amino acid (BCAA) is often used to attenuate exercise-induced skeletal muscle damage and promote adaptation, but no definitive conclusion on the benefits of BCAA on muscle recovery after injurious exercise can be drawn. Exploration of the systematic BCAA alteration in muscular injury-repair stage per se without any BCAA supplement should provide some useful information in favour of BCAA application in muscle regeneration after injury. One bout of 90-min downhill-running exercise was performed to cause rat skeletal muscle injury. After exercise, myofibrillar BCAA concentrations showed minor changes compared with exercise before, while serum concentrations of BCAA were lower after exercise. Especially, serum leucine, isoleucine and total BCAA concentrations 2 weeks post-run were significantly lower than normal values of exercise before (p = 0.008, p = 0.041, p = 0.015). The data demonstrate that a single eccentric exercise can significantly decrease the serum BCAA concentrations, which mean high utilization of BCAA for myogenesis after injurious exercise. PMID:23451863

Qun, Z; Xinkai, Y; Jing, W

2014-04-01

22

Structure of Skeletal Muscle  

MedlinePLUS

... Citation Help Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Muscular System » Structure of Skeletal Muscle Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life ...

23

Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle  

PubMed Central

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups (P < 0.05). However, the ingestion of the protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein (P < 0.05). Postexercise myofibrillar protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein.

Reidy, P. T.; Walker, D. K.; Dickinson, J. M.; Gundermann, D. M.; Drummond, M. J.; Timmerman, K. L.; Cope, M. B.; Mukherjea, R.; Jennings, K.; Volpi, E.

2014-01-01

24

Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle.  

PubMed

Increasing amino acid availability (via infusion or ingestion) at rest or postexercise enhances amino acid transport into human skeletal muscle. It is unknown whether alterations in amino acid availability, from ingesting different dietary proteins, can enhance amino acid transport rates and amino acid transporter (AAT) mRNA expression. We hypothesized that the prolonged hyperaminoacidemia from ingesting a blend of proteins with different digestion rates postexercise would enhance amino acid transport into muscle and AAT expression compared with the ingestion of a rapidly digested protein. In a double-blind, randomized clinical trial, we studied 16 young adults at rest and after acute resistance exercise coupled with postexercise (1 h) ingestion of either a (soy-dairy) protein blend or whey protein. Phenylalanine net balance and transport rate into skeletal muscle were measured using stable isotopic methods in combination with femoral arteriovenous blood sampling and muscle biopsies obtained at rest and 3 and 5 h postexercise. Phenylalanine transport into muscle and mRNA expression of select AATs [system L amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, system A amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, cationic amino acid transporter 1/SLC7A1] increased to a similar extent in both groups (P < 0.05). However, the ingestion of the protein blend resulted in a prolonged and positive net phenylalanine balance during postexercise recovery compared with whey protein (P < 0.05). Postexercise myofibrillar protein synthesis increased similarly between groups. We conclude that, while both protein sources enhanced postexercise AAT expression, transport into muscle, and myofibrillar protein synthesis, postexercise ingestion of a protein blend results in a slightly prolonged net amino acid balance across the leg compared with whey protein. PMID:24699854

Reidy, P T; Walker, D K; Dickinson, J M; Gundermann, D M; Drummond, M J; Timmerman, K L; Cope, M B; Mukherjea, R; Jennings, K; Volpi, E; Rasmussen, B B

2014-06-01

25

Probing the role of negatively charged amino acid residues in ion permeation of skeletal muscle ryanodine receptor.  

PubMed

Sequence comparison suggests that the ryanodine receptors (RyRs) have pore architecture similar to that of the bacterial K+ channel KcsA. The lumenal loop linking the two most C-terminal transmembrane spanning segments in the RyRs has a predicted pore helix and an amino acid motif (GGGIG) similar to the selectivity filter (TVGYG) of KcsA identified by x-ray analysis. The RyRs have many negatively charged amino acid residues in the two regions linking the GGGIG motif and predicted pore helix with the two most C-terminal transmembrane spanning segments. We tested the role of these residues by generating single-site mutants, focusing on amino acid residues conserved among the mammalian RyRs. Replacement of two acidic residues immediately after the GGGIG motif in skeletal muscle ryanodine receptor (RyR1-D4899 and -E4900) with asparagine and glutamine profoundly affected ion permeation and selectivity. By comparison, mutagenesis of aspartate and glutamate residues in the putative linker regions showed a K+ conductance and selectivity for Ca2+ compared to K+ (P(Ca)/P(K)) close to wild-type. The results show that the negatively charged carboxyl oxygens of D4899 and E4900 side chains are major determinants of RyR ion conductance and selectivity. PMID:15863483

Wang, Ying; Xu, Le; Pasek, Daniel A; Gillespie, Dirk; Meissner, Gerhard

2005-07-01

26

Impacts of birth weight on plasma, liver and skeletal muscle neutral amino acid profiles and intestinal amino acid transporters in suckling Huanjiang mini-piglets.  

PubMed

Genetic selection strategies towards increased prolificacy have resulted in more and more increased littler size and incidences of impaired fetal development. Low birth weight (LBW) piglets, with long-term alterations in structure, physiology and metabolism, have lower survival rates and poor growth performance. The aim of the study was to compare the plasma, liver and skeletal muscle contents of neutral amino acids (NAA) and the intestinal expression of NAA transporters between LBW and high birth weight (HBW) suckling Huanjiang mini-piglets. Forty piglets with either LBW or HBW (20 piglets per group) were sampled on day 0, 7, 14 and 21 of age to give 5 observations per day per group. The contents of NAA in plasma, liver and skeletal muscle were measured, and jejunal expression of transporters for NAA, including Slc6a19 (B(0)AT1) and Slc1a5 (ASCT2), were determined by real-time RT-PCR and Western Blot, respectively. Results showed that the suckling piglets with LBW had higher contents of Thr, Ser, Gly, Ala, Val, Met, Ile, Leu, Tyr, Phe and Pro in liver, and Gly in skeletal muscle, whereas lower contents of Met, Ser and Ala in plasma when compared with the HBW littermates. Consistent with the content differences in plasma NAA, the jejunal expression profiles of both Slc6a19 (B(0)AT1) and Slc1a5 (ASCT2) in the LBW piglets were lower in compared with the HBW littermates during the early suckling period. These findings suggested that intestinal dysfunction in the LBW piglets may be one of the reasons in altered physiology and metabolism states of other organs, which result in lower survival and growth rate. PMID:23236407

Yang, Huansheng; Fu, Dezhi; Shao, Hua; Kong, Xiangfeng; Wang, Wence; Yang, Xiaojian; Nyachoti, Charles M; Yin, Yulong

2012-01-01

27

Impacts of Birth Weight on Plasma, Liver and Skeletal Muscle Neutral Amino Acid Profiles and Intestinal Amino Acid Transporters in Suckling Huanjiang Mini-Piglets  

PubMed Central

Genetic selection strategies towards increased prolificacy have resulted in more and more increased littler size and incidences of impaired fetal development. Low birth weight (LBW) piglets, with long-term alterations in structure, physiology and metabolism, have lower survival rates and poor growth performance. The aim of the study was to compare the plasma, liver and skeletal muscle contents of neutral amino acids (NAA) and the intestinal expression of NAA transporters between LBW and high birth weight (HBW) suckling Huanjiang mini-piglets. Forty piglets with either LBW or HBW (20 piglets per group) were sampled on day 0, 7, 14 and 21 of age to give 5 observations per day per group. The contents of NAA in plasma, liver and skeletal muscle were measured, and jejunal expression of transporters for NAA, including Slc6a19 (B0AT1) and Slc1a5 (ASCT2), were determined by real-time RT-PCR and Western Blot, respectively. Results showed that the suckling piglets with LBW had higher contents of Thr, Ser, Gly, Ala, Val, Met, Ile, Leu, Tyr, Phe and Pro in liver, and Gly in skeletal muscle, whereas lower contents of Met, Ser and Ala in plasma when compared with the HBW littermates. Consistent with the content differences in plasma NAA, the jejunal expression profiles of both Slc6a19 (B0AT1) and Slc1a5 (ASCT2) in the LBW piglets were lower in compared with the HBW littermates during the early suckling period. These findings suggested that intestinal dysfunction in the LBW piglets may be one of the reasons in altered physiology and metabolism states of other organs, which result in lower survival and growth rate.

Shao, Hua; Kong, Xiangfeng; Wang, Wence; Yang, Xiaojian; Nyachoti, Charles M.; Yin, Yulong

2012-01-01

28

Hydrolyzed protein supplementation improves protein content and peroxidation of skeletal muscle by adjusting the plasma amino acid spectrums in rats after exhaustive swimming exercise: a pilot study  

PubMed Central

Background This study was designed to evaluate the effects of hydrolyzed protein supplementation upon skeletal muscle total protein and peroxidation in rats following exhaustive swimming exercise. Methods Twenty-four rats were randomized to 4 experimental groups (n?=?6 per group): control group fed standard diet without exercise (SD), exercise (EX), exercise plus standard diet for 72 hours (EX?+?SD), and exercise plus standard diet supplemented with hydrolyzed protein (2 g/kg/d) for 72 hours (EX?+?HP). Immediately following exercise, the EX group was euthanized for collecting plasma and skeletal muscle samples. The EX?+?SD and EX?+?HP groups were fed their respective diets for 72 hour still plasma and skeletal muscle collection. Skeletal muscle samples were used to measure levels of total protein (TP), malondialdehyde (MDA), and protein carbonyl (PC). Plasma samples were used to analyze the amino acids spectrum. Results Compared with the EX?+?SD, EX?+?HP presented the significantly increased TP (P?=?0.02) and decreased MDA and PC levels (P?=?0.035). MDA was negatively correlated with the methionine levels. Moreover, EX?+?HP maintained higher levels of plasmaleucine, isoleucine, and methionine than EX?+?SD, which may be associated with the increased skeletal muscle TP levels observed (P?skeletal muscle TP and ameliorate peroxidation damage in rats subjected to exhaustive exercise stress, which may be, at least in part, related with the maintenance of plasma leucine, isoleucine, and methionine levels.

2014-01-01

29

Skeletal muscle cell populations  

PubMed Central

Summary Cell suspensions from the breast muscles of 10-day old chicken embryos were separated into non-myogenic, fibroblast-like cell fractions and a mononucleated, myogenic cell fraction by Percoll™ density centrifugation. Isolated populations were characterized by their morphology in both mass cultures and individual macroscopic clones and by the immunocytochemical detection of skeletal muscle- and smooth muscle-specific proteins in individual cells. Cell populations were also characterized by their protein patterns using sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The less dense, non-myogenic cells comprised 16% of the cells. In culture they were predominantly flattened, stellate cells and gave rise to clones lacking myotubes. These fibroblast-like cells were negative for skeletal muscle myosin or muscle type creatine phosphokinase. Less than 0.1 % of these cells demonstrated strong fluorescence when stained with anti-desmin or anti-smooth muscle specific actin. This observation suggested that the vast majority of these cells were not related to vascular smooth muscle cells. Also, over 99% of the non-myogenic cells did not display characteristic properties of endothelial cells. The denser myogenic cell fraction comprised over 80% of the cells and in clonal cultures gave rise to about 70% myogenic clones. An additional 30% of clones from this fraction were non-myogenic indicating heterogeneity in this population. We conclude that Percoll centrifugation can be employed for the isolation of myogenic and non-myogenic cell populations directly from the embryonic muscle. Moreover, this procedure allows the direct analysis of cell-specific proteins (e.g., by gel electrophoresis) without the need for cell culturing. The results thus obtained closely reflect the status of the cells in the intact muscle.

Yablonka-Reuveni, Z.; Nameroff, M.

2014-01-01

30

Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice.  

PubMed

Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival in eukaryotes. Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast. However, the role of these amino acids in mitochondrial biogenesis and longevity in mammals is unknown. Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation. All of the BCAAem-mediated effects were strongly attenuated in endothelial nitric oxide synthase null mutant mice. These data reveal an important antiaging role of BCAAs mediated by mitochondrial biogenesis in mammals. PMID:20889128

D'Antona, Giuseppe; Ragni, Maurizio; Cardile, Annalisa; Tedesco, Laura; Dossena, Marta; Bruttini, Flavia; Caliaro, Francesca; Corsetti, Giovanni; Bottinelli, Roberto; Carruba, Michele O; Valerio, Alessandra; Nisoli, Enzo

2010-10-01

31

Skeletal Muscle Na+ Channel Disorders  

PubMed Central

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

Simkin, Dina; Bendahhou, Said

2011-01-01

32

Paraplegia increases skeletal muscle autophagy  

PubMed Central

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.

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

2012-01-01

33

Origin and Possible Significance of Alanine Production by Skeletal Muscle.  

National Technical Information Service (NTIS)

These experiments were undertaken to determine the source of alanine released by skeletal muscle and to clarify the possible relationships between this process and the degradation of branched chain amino acids, the release of glutamine, and protein turnov...

R. Odessey E. A. Khairallah A. L. Goldberg

1974-01-01

34

Current Topics for Teaching Skeletal Muscle Physiology  

NSDL National Science Digital Library

Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifically and clinically. Injury, disease, and old age are among the factors that commonly contribute to impairment in skeletal muscle function. The goal of this article is to update current concepts of skeletal muscle physiology. Particular emphasis is placed on mechanisms of injury, repair, and adaptation in skeletal muscle as well as mechanisms underlying the declining skeletal muscle structure and function associated with aging. For additional materials please refer to the "Skeletal Muscle Physiology" presentation located on the American Physiological Society Archive of Teaching Resources Web site (http://www.apsarchive.org).

Susan V. Brooks (University of Michigan)

2003-12-01

35

Influences of carbohydrate plus amino acid supplementation on differing exercise intensity adaptations in older persons: skeletal muscle and endocrine responses  

PubMed Central

Losses in physiological function in healthy ageing occur partly as a consequence of reduced protein intake and partly as a consequence of less than 30-min/day of moderate to vigorous physical activity. The current study aimed to compare the effects of two different intensities of resistance training in healthy older adults, whose habitual dietary intake was supplemented with carbohydrate and amino acid preparations. We hypothesised that although intensive exercise with appropriate carbohydrate and amino acid supplementation would result in the most profound impact on in vivo markers of healthy physiologic and endocrine functions in previously sedentary older individuals, the effectiveness of the less intense exercise prescription with supplementation would also result in beneficial adaptations over and above findings of previous studies on low intensity exercise alone. Twenty-nine older adults (out of 32) completed the study after being randomly assigned to low (SUP_LowR, i.e., ?40% 1RM; n?=?16) versus high resistance training (SUP_HighR, i.e., ?80% 1RM; n?=?13) for 12 weeks. A carbohydrate supplement was ingested immediately before and during every exercise session and an amino acid cocktail was ingested post-exercise. Neither intervention significantly impacted upon body composition assessed using: Body mass index, waist/hip ratio and bioelectric impedance. Muscle strength increased similarly in the two groups with the SUP_HighR protocol showing 46?±?8%, 10.8?±?4.4% and 26.9?±?4.9% (P?muscle thickness however, showed a greater benefit of the SUP_LowR protocol (8.7?±?3.9% increase, P?muscle hypertrophy combined with increased habitual function. Supplementation plus high-intensity exercise regimen improved markers of strength, but not to a significantly greater extent than supplementation plus low intensity exercise.

Breen, Leigh; Stewart, Claire E.

2010-01-01

36

Skeletal muscle: an endocrine organ  

PubMed Central

Summary Tropism and efficiency of skeletal muscle depend on the complex balance between anabolic and catabolic factors. This balance gradually deteriorates with aging, leading to an age-related decline in muscle quantity and quality, called sarcopenia: this condition plays a central role in physical and functional impairment in late life. The knowledge of the mechanisms that induce sarcopenia and the ability to prevent or counteract them, therefore, can greatly contribute to the prevention of disability and probably also mortality in the elderly. It is well known that skeletal muscle is the target of numerous hormones, but only in recent years studies have shown a role of skeletal muscle as a secretory organ of cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived neurotrophic factor, and leukaemia inhibitory factor), which have autocrine, paracrine, or endocrine actions and are deeply involved in inflammatory processes. Physical inactivity promotes an unbalance between these substances towards a pro-inflammatory status, thus favoring the vicious circle of sarcopenia, accumulation of fat – especially visceral – and development of cardiovascular diseases, type 2 diabetes mellitus, cancer, dementia and depression, according to what has been called “the diseasome of physical inactivity”.

Pratesi, Alessandra; Tarantini, Francesca; Di Bari, Mauro

2013-01-01

37

Skeletal muscle: an endocrine organ.  

PubMed

Tropism and efficiency of skeletal muscle depend on the complex balance between anabolic and catabolic factors. This balance gradually deteriorates with aging, leading to an age-related decline in muscle quantity and quality, called sarcopenia: this condition plays a central role in physical and functional impairment in late life. The knowledge of the mechanisms that induce sarcopenia and the ability to prevent or counteract them, therefore, can greatly contribute to the prevention of disability and probably also mortality in the elderly. It is well known that skeletal muscle is the target of numerous hormones, but only in recent years studies have shown a role of skeletal muscle as a secretory organ of cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived neurotrophic factor, and leukaemia inhibitory factor), which have autocrine, paracrine, or endocrine actions and are deeply involved in inflammatory processes. Physical inactivity promotes an unbalance between these substances towards a pro-inflammatory status, thus favoring the vicious circle of sarcopenia, accumulation of fat - especially visceral - and development of cardiovascular diseases, type 2 diabetes mellitus, cancer, dementia and depression, according to what has been called "the diseasome of physical inactivity". PMID:23858303

Pratesi, Alessandra; Tarantini, Francesca; Di Bari, Mauro

2013-01-01

38

Effects of aestivation on skeletal muscle performance.  

PubMed

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. PMID:20069409

James, Rob S

2010-01-01

39

Proteomic profiling of skeletal muscle plasticity  

PubMed Central

Summary 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.

Ohlendieck, Kay

2011-01-01

40

Mammalian Target of Rapamycin Complex 1 Activation Is Required for the Stimulation of Human Skeletal Muscle Protein Synthesis by Essential Amino Acids123  

PubMed Central

The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser2448), ribosomal S6 kinase 1 (Thr389), and eukaryotic initiation factor 4E binding protein 1 (Thr37/46). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.

Dickinson, Jared M.; Fry, Christopher S.; Drummond, Micah J.; Gundermann, David M.; Walker, Dillon K.; Glynn, Erin L.; Timmerman, Kyle L.; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B.

2011-01-01

41

Skeletal muscle is an endocrine organ.  

PubMed

Skeletal muscle plays a key role in postural retention as well as locomotion for maintaining the physical activities of human life. Skeletal muscle has a second role as an elaborate energy production and consumption system that influences the whole body's energy metabolism. Skeletal muscle is a specific organ that engenders a physical force, and exercise training has been known to bring about multiple benefits for human health maintenance and/or improvement. The mechanisms underlying the improvement of the human physical condition have been revealed: skeletal muscle synthesizes and secretes multiple factors, and these muscle-derived factors, so-called as myokines, exert beneficial effects on peripheral and remote organs. In this short review, we focus on the third aspect of skeletal muscle function - namely, the release of multiple types of myokines, which constitute a broad network for regulating the function of remote organs as well as skeletal muscle itself. We conclusively show that skeletal muscle is one of the endocrine organs and that understanding the mechanisms of production and secretion of myokines may lead to a new pharmacological approach for treatment of clinical disorders. PMID:24859778

Iizuka, Kenji; Machida, Takuji; Hirafuji, Masahiko

2014-06-19

42

Human skeletal muscle sodium channelopathies.  

PubMed

Ion channels are transmembrane proteins that allow ions to flow in or out of the cell. Sodium and potassium channel activation and inactivation are the basis of action potential's production and conduction. During the past 15 years, ion channels have been implicated in diseases that have come to be known as the channelopathies. Over 30 mutations of the muscle channel gene SCN4A, which encodes the muscle voltage-gated sodium channel, have been described and associated with neuromuscular disorders like hypo- and hyper-kalaemic periodic paralyses (hypoPP and hyperPP), paramyotonia congenita, sodium channel myotonias and congenital myasthenic syndrome. Different mutations within the same gene (SCN4A) cause distinct clinical disorders, while mutations in different channel genes may result in similar phenotypes. In addition, identical sodium channel mutations can result in different clinical phenotypes (hyperPP or paramyotonia) in different members of the same family, suggesting that the genetic background and perhaps other epigenetic factors may influence the clinical expression of a particular mutation. This article reviews the clinical features of the skeletal muscle sodium channel diseases and highlights the phenotypic or genetic overlap in these disorders. PMID:16193245

Vicart, S; Sternberg, D; Fontaine, B; Meola, G

2005-10-01

43

Musclin, a novel skeletal muscle-derived secretory factor.  

PubMed

Skeletal muscle is involved in the homeostasis of glucose and lipid metabolism. We hypothesized that the skeletal muscle produces and secretes bioactive factor(s), similar to adipocytokines secreted by fat tissue. Here, we report the identification of a novel secretory factor, musclin, by signal sequence trap of mouse skeletal muscle cDNAs. Musclin cDNA encoded 130 amino acids, including NH(2)-terminal 30-amino acid signal sequence. Musclin protein contained a region homologous to natriuretic peptide family, and KKKR, a putative serine protease cleavage site, similar to the natriuretic peptide family. Full-length musclin protein and KKKR-dependent cleaved form were secreted in media of musclin cDNA-transfected mammalian cell cultures. Musclin mRNA was expressed almost exclusively in the skeletal muscle of mice. Musclin mRNA levels in skeletal muscle were markedly low in fasted, increased upon re-feeding, and were low in streptozotocin-treated insulin-deficient mice. Musclin mRNA expression was induced at late stage in the differentiation of C2C12 myocytes. In myocytes, insulin increased, while epinephrine, isoproterenol, and forskolin reduced musclin mRNA, all of which are known to increase the cellular content of cyclic AMP, a counter-regulator to insulin. Pathologically, overexpression of musclin mRNA was noted in the muscles of obese insulin-resistant KKAy mice. Functionally, recombinant musclin significantly attenuated insulin-stimulated glucose uptake and glycogen synthesis in myocytes. In conclusion, we identified musclin, a novel skeletal muscle-derived secretory factor. Musclin expression level is tightly regulated by nutritional changes and its physiological role could be linked to glucose metabolism. PMID:15044443

Nishizawa, Hitoshi; Matsuda, Morihiro; Yamada, Yukio; Kawai, Kenichiro; Suzuki, Emi; Makishima, Makoto; Kitamura, Toshio; Shimomura, Iichiro

2004-05-01

44

Diffuse skeletal muscle metastases from sacral chordoma.  

PubMed

Chordomas are rare, slow-growing tumors arising from cellular remnants of the notochord. They account for 1-4 % of primary malignant bone tumors and usually occur in the axial skeleton, most commonly the sacrum. Although typically locally recurrent, chordoma metastasis rates as high as 10-42 % have been reported. While spread to multiple organ systems has been documented, metastatic disease to skeletal muscle is extremely rare. We present a case of extensive, multifocal skeletal muscle metastases developing in the setting of recurrent sacral chordoma. Our literature search found only one additional case of metastatic chordoma to a single skeletal muscle. PMID:24407557

Carey, Kathleen; Bestic, Joseph; Attia, Steven; Cortese, Cherise; Jain, Manoj

2014-07-01

45

Regulation of skeletal muscle perfusion during exercise  

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

46

Skeletal Muscle Ischemia and Heat Shock Proteins.  

National Technical Information Service (NTIS)

Blood loss resulting in decreased organ perfusion and subsequent ischemic injury of cardiac and skeletal muscle presents a significant problem for the soldier in combat. Recent findings have indicated that different forms of noxious stress including expos...

W. H. Dillman

1994-01-01

47

PI3 Kinase Regulation of Skeletal Muscle Hypertrophy and Atrophy  

Microsoft Academic Search

\\u000a Activation of the PI3 kinase pathway can induce skeletal muscle hypertrophy, defined as an increase in skeletal muscle mass.\\u000a In mammals, skeletal muscle hypertrophy occurs as a result of an increase in the size, as opposed to the number, of pre-existing\\u000a skeletal muscle fibers. This pathway’s effects on skeletal muscle have been implicated most prominently downstream of Insulin-like\\u000a growth factor

David J. Glass

48

Skeletal muscle design to meet functional demands  

PubMed Central

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.

Lieber, Richard L.; Ward, Samuel R.

2011-01-01

49

[New perspectives in skeletal muscle tissue engineering].  

PubMed

Due to the enormous expansion of knowledge in the fields of stem cell research and biomaterials, skeletal muscle tissue engineering represents a rapidly developing field of biomedical research. This article provides a general overview of skeletal muscle tissue engineering, including a discussion of recent findings and future research perspectives. Additionally, the results of myogenic differentiation of human mesenchymal stem cells and satellite cells are presented. PMID:24916349

Stern-Straeter, J; Hörmann, K

2014-06-01

50

Skeletal muscle specific genes networks in cattle  

Microsoft Academic Search

While physiological differences across skeletal muscles have been described, the differential gene expression underlying them\\u000a and the discovery of how they interact to perform specific biological processes are largely to be elucidated. The purpose\\u000a of the present study was, firstly, to profile by cDNA microarrays the differential gene expression between two skeletal muscle\\u000a types, Psoas major (PM) and Flexor digitorum

Natalia Moreno-Sánchez; Julia Rueda; María J. Carabaño; Antonio Reverter; Sean McWilliam; Carmen González; Clara Díaz

2010-01-01

51

Whole body and skeletal muscle protein turnover in recovery from burns  

PubMed Central

Trauma and critical illness are associated with a stress response that results in increased skeletal muscle protein catabolism, which is thought to facilitate the synthesis of acute phase proteins in the liver as well as proteins involved in immune function. What makes burn injury a unique form of trauma is the existence of vast skin lesions, where the majority of afflicted tissue is often surgically excised post injury. Thereafter, recovery is dependent on the formation of a significant quantity of new skin, meaning that the burned patient requires a large and sustained supply of amino acids to facilitate wound healing. Skeletal muscle has the capacity to store surplus glucose and fatty acids within glycogen and triacylglycerol depots respectively, where glycogen and fatty acids can be mobilized during prolonged periods of caloric restriction or heightened metabolic demand (e.g., exercise), to be catabolized in order to maintain cellular ATP availability. Amino acids, on the other hand, are not generally considered to be stored in such a manner within skeletal muscle, i.e., in a temporary pool independent of structural proteins and cellular organelles etc. Subsequently, in response to severe thermal trauma, skeletal muscle assumes the role of an amino acid reserve where muscle protein breakdown and amino acid release from skeletal muscle serves to buffer plasma amino acid concentrations. Interestingly, it seems like aggressive feeding of the severely burned patient may not necessarily supply amino acids in sufficient abundance to normalize skeletal muscle protein metabolism, suggesting that skeletal muscle becomes an essential store of protein in patients suffering from severe burn trauma. In this article, the effects of burn injury on whole body and skeletal muscle protein metabolism will be discussed in an attempt to distill the current understanding of the impact of this debilitating injury on the redistribution of skeletal muscle protein stores.

Porter, Craig; Hurren, Nicholas M; Herndon, David N; B?rsheim, Elisabet

2013-01-01

52

How sex hormones promote skeletal muscle regeneration.  

PubMed

Skeletal muscle regeneration efficiency declines with age for both men and women. This decline impacts on functional capabilities in the elderly and limits their ability to engage in regular physical activity and to maintain independence. Aging is associated with a decline in sex hormone production. Therefore, elucidating the effects of sex hormone substitution on skeletal muscle homeostasis and regeneration after injury or disuse is highly relevant for the aging population, where sarcopenia affects more than 30 % of individuals over 60 years of age. While the anabolic effects of androgens are well known, the effects of estrogens on skeletal muscle anabolism have only been uncovered in recent times. Hence, the purpose of this review is to provide a mechanistic insight into the regulation of skeletal muscle regenerative processes by both androgens and estrogens. Animal studies using estrogen receptor (ER) antagonists and receptor subtype selective agonists have revealed that estrogens act through both genomic and non-genomic pathways to reduce leukocyte invasion and increase satellite cell numbers in regenerating skeletal muscle tissue. Although animal studies have been more conclusive than human studies in establishing a role for sex hormones in the attenuation of muscle damage, data from a number of recent well controlled human studies is presented to support the notion that hormonal therapies and exercise induce added positive effects on functional measures and lean tissue mass. Based on the fact that aging human skeletal muscle retains the ability to adapt to exercise with enhanced satellite cell activation, combining sex hormone therapies with exercise may induce additive effects on satellite cell accretion. There is evidence to suggest that there is a 'window of opportunity' after the onset of a hypogonadal state such as menopause, to initiate a hormonal therapy in order to achieve maximal benefits for skeletal muscle health. Novel receptor subtype selective ligands and selective estrogen and androgen receptor modulators (SERMs, SARMs) promise to reduce health risks associated with classical hormonal therapies, whilst maintaining the positive effects on muscle repair. Dietary supplements containing compounds with structural similarity to estrogens (phytoestrogens) are increasingly used as alternatives to classical hormone-replacement therapies (HRT), but the effects on skeletal muscle are currently largely unknown. Research has started to investigate the combined effects of exercise and alternative HRTs, such as soy isoflavones, on skeletal muscle regenerative processes to provide safer and more efficient therapies to promote muscle regeneration and maintenance of muscle mass and strength in the aging population. PMID:23888432

Velders, Martina; Diel, Patrick

2013-11-01

53

Aspects of skeletal muscle modelling.  

PubMed Central

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

Epstein, Marcelo; Herzog, Walter

2003-01-01

54

Adult and Embryonic Skeletal Muscle Microexplant Culture and Isolation of Skeletal Muscle Stem Cells  

PubMed Central

Cultured embryonic and adult skeletal muscle cells have a number of different uses. The micro-dissected explants technique described in this chapter is a robust and reliable method for isolating relatively large numbers of proliferative skeletal muscle cells from juvenile, adult or embryonic muscles as a source of skeletal muscle stem cells. The authors have used micro-dissected explant cultures to analyse the growth characteristics of skeletal muscle cells in wild-type and dystrophic muscles. Each of the components of tissue growth, namely cell survival, proliferation, senescence and differentiation can be analysed separately using the methods described here. The net effect of all components of growth can be established by means of measuring explant outgrowth rates. The micro-explant method can be used to establish primary cultures from a wide range of different muscle types and ages and, as described here, has been adapted by the authors to enable the isolation of embryonic skeletal muscle precursors. Uniquely, micro-explant cultures have been used to derive clonal (single cell origin) skeletal muscle stem cell (SMSc) lines which can be expanded and used for in vivo transplantation. In vivo transplanted SMSc behave as functional, tissue-specific, satellite cells which contribute to skeletal muscle fibre regeneration but which are also retained (in the satellite cell niche) as a small pool of undifferentiated stem cells which can be re-isolated into culture using the micro-explant method.

Merrick, Deborah; Chen, Hung-Chih; Larner, Dean; Smith, Janet

2010-01-01

55

Skeletal muscle regeneration and the mitotic clock  

Microsoft Academic Search

Regeneration of muscle fibers following damage requires activation of quiescent satellite cells, their proliferation and finally their differentiation and fusion into multinucleated myotubes, which after maturation will replace the damaged fiber. The regenerative potential of human skeletal muscle will be determined, at least partly, by the proliferative capacity of the satellite cells. In this study, we have measured the proliferative

V Renault; G Piron-Hamelin; C Forestier; S DiDonna; S Decary; F Hentati; G Saillant; G. S Butler-Browne; V Mouly

2000-01-01

56

Magnetic resonance elastography of skeletal muscle.  

PubMed

While the contractile properties of skeletal muscle have been studied extensively, relatively little is known about the elastic properties of muscle in vivo. Magnetic resonance elastography (MRE) is a phase contrast-based method for observing shear waves propagating in a material to determine its stiffness. In this work, MRE is applied to skeletal muscle under load to quantify the change in stiffness with loading. A mathematical model of muscle is developed that predicts a linear relationship between shear stiffness and muscle load. The MRE technique was applied to bovine muscle specimens (N = 10) and human biceps brachii in vivo (N = 5). Muscle stiffness increased linearly for both passive tension (14.5 +/- 1.77 kPa/kg) and active tension, in which the increase in stiffness was dependent upon muscle size, as predicted by the model. A means of noninvasively assessing the viscoelastic pro-perties of skeletal muscle in vivo may provide a useful method for studying muscle biomechanics in health and disease. PMID:11169834

Dresner, M A; Rose, G H; Rossman, P J; Muthupillai, R; Manduca, A; Ehman, R L

2001-02-01

57

Stem cells for skeletal muscle repair  

PubMed Central

Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.

Shadrach, Jennifer L.; Wagers, Amy J.

2011-01-01

58

Inactivity amplifies the catabolic response of skeletal muscle to cortisol  

NASA Technical Reports Server (NTRS)

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.

Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

1999-01-01

59

Gene Regions Responding to Skeletal Muscle Atrophy  

NASA Technical Reports Server (NTRS)

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

Booth, Frank W.

1997-01-01

60

Tissue engineering for skeletal muscle regeneration  

PubMed Central

Summary Stem cells and regenerative medicine have obtained a remarkable consent from the scientific community for their promising ability to recover aged, injured and diseased tissue. However, despite the noteworthy potential, hurdles currently hinder their use and clinical application: cell survival, immune response, tissue engraftment and efficient differentiation. Hence a new interdisciplinary scientific approach, such as tissue engineering, is going deep attempts to mimic neo-tissue-genesis as well as stem cell engraftment amelioration. Skeletal muscle tissue engineering represents a great potentiality in medicine for muscle regeneration exploiting new generation injectable hydrogel as scaffold supporting progenitor/stem cells for muscle differentiation reconstructing the natural skeletal muscle tissue architecture influenced by matrix mechanical and physical property and by a dynamic environment.

Rizzi, Roberto; Bearzi, Claudia; Mauretti, Arianna; Bernardini, Sergio; Cannata, Stefano; Gargioli, Cesare

2012-01-01

61

Skeletal muscle specific genes networks in cattle  

PubMed Central

While physiological differences across skeletal muscles have been described, the differential gene expression underlying them and the discovery of how they interact to perform specific biological processes are largely to be elucidated. The purpose of the present study was, firstly, to profile by cDNA microarrays the differential gene expression between two skeletal muscle types, Psoas major (PM) and Flexor digitorum (FD), in beef cattle and then to interpret the results in the context of a bovine gene coexpression network, detecting possible changes in connectivity across the skeletal muscle system. Eighty four genes were differentially expressed (DE) between muscles. Approximately 54% encoded metabolic enzymes and structural-contractile proteins. DE genes were involved in similar processes and functions, but the proportion of genes in each category varied within each muscle. A correlation matrix was obtained for 61 out of the 84 DE genes from a gene coexpression network. Different groups of coexpression were observed, the largest one having 28 metabolic and contractile genes, up-regulated in PM, and mainly encoding fast-glycolytic fibre structural components and glycolytic enzymes. In FD, genes related to cell support seemed to constitute its identity feature and did not positively correlate to the rest of DE genes in FD. Moreover, changes in connectivity for some DE genes were observed in the different gene ontologies. Our results confirm the existence of a muscle dependent transcription and coexpression pattern and suggest the necessity of integrating different muscle types to perform comprehensive networks for the transcriptional landscape of bovine skeletal muscle. Electronic supplementary material The online version of this article (doi:10.1007/s10142-010-0175-2) contains supplementary material, which is available to authorized users.

Rueda, Julia; Carabano, Maria J.; Reverter, Antonio; McWilliam, Sean; Gonzalez, Carmen; Diaz, Clara

2010-01-01

62

Overexpression of SMPX in Adult Skeletal Muscle Does not Change Skeletal Muscle Fiber Type or Size  

PubMed Central

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.

Eftest?l, Einar; Alver, Tine Norman; Gundersen, Kristian; Bruusgaard, Jo C.

2014-01-01

63

Skeletal Muscle Metabolism in Hypokinetic Rats.  

National Technical Information Service (NTIS)

This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular ...

M. E. Tischler

1993-01-01

64

Development of Sensory Receptors in Skeletal Muscle  

NASA Technical Reports Server (NTRS)

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.

DeSantis, Mark

2000-01-01

65

Transcriptional profile of postmortem skeletal muscle  

Microsoft Academic Search

Abstract Autopsy specimens are often used in molecular biological studies of disease pathophysiology.However, few analyses have focused specifically on postmortem changes in skeletal muscles, and almost all of those investigate protein or metabolic changes. While some structural and enzymatic changes have been described, the sequence of transcriptional events associated with these remains unclear. We analyzed a series of new and

Despina Sanoudou; Peter B. Kang; Judith N. Haslett; Mei Han; Louis M. Kunkel; Alan H. Beggs

2003-01-01

66

Skeletal muscle fibre types in the dog.  

PubMed Central

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

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

1993-01-01

67

Tissue engineering skeletal muscle for orthopaedic applications  

NASA Technical Reports Server (NTRS)

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.

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

68

Human skeletal muscle biochemical diversity.  

PubMed

The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy - titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to 'tune' the protein's mechanotransduction capability. PMID:22786631

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

2012-08-01

69

Human skeletal muscle biochemical diversity  

PubMed Central

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

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

2012-01-01

70

Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice  

PubMed Central

Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) female mice compared with age-matched ovary-intact adult female mice (sham). The OVX mice exhibited significant increases in body weight, visceral, and inguinal fat mass compared with sham mice. OVX mice also had significant increases in skeletal muscle intramyocellular lipids (IMCL) compared with the sham animals, which corresponded to significant increases in the protein content of the fatty acid transporters CD36/FAT and FABPpm. A targeted metabolic profiling approach identified significantly lower levels of specific acyl carnitine species and various amino acids in skeletal muscle from OVX mice compared with the sham animals, suggesting a potential dysfunction in lipid and amino acid metabolism, respectively. Basal and maximal mitochondrial oxygen consumption rates were significantly impaired in skeletal muscle fibers from OVX mice compared with sham animals. Collectively, these data indicate that loss of ovarian function results in increased IMCL storage that is coupled with alterations in mitochondrial function and changes in the skeletal muscle metabolic profile.

Jackson, Kathryn C.; Wohlers, Lindsay M.; Lovering, Richard M.; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.

2013-01-01

71

Skeletal muscle metabolism in hypokinetic rats  

NASA Technical Reports Server (NTRS)

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.

Tischler, M. E.

1984-01-01

72

Insulin Increases Ceramide Synthesis in Skeletal Muscle  

PubMed Central

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.

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

73

Treatment of Skeletal Muscle Injury: A Review  

PubMed Central

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-?1 antagonists behave as inhibitors of TGF-?1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved.

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

2012-01-01

74

Cellular Players in Skeletal Muscle Regeneration  

PubMed Central

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

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

2014-01-01

75

Primary structure of the receptor for calcium channel blockers from skeletal muscle  

Microsoft Academic Search

The complete amino-acid sequence of the receptor for dihydropyridine calcium channel blockers from rabbit skeletal muscle is predicted by cloning and sequence analysis of DNA complementary to its messenger RNA. Structural and sequence similarities to the voltage-dependent sodium channel suggest that in the transverse tubule membrane of skeletal muscle the dihydropyridine receptor may act both as voltage sensor in excitation-contraction

Tsutomu Tanabe; Hiroshi Takeshima; Atsushi Mikami; Veit Flockerzi; Hideo Takahashi; Kenji Kangawa; Masayasu Kojima; Hisayuki Matsuo; Tadaaki Hirose; Shosaku Numa

1987-01-01

76

Pannexin 1 channels in skeletal muscles  

PubMed Central

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 Ca2+ 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.

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

2014-01-01

77

Nutritional influences on age-related skeletal muscle loss.  

PubMed

Age-related muscle loss impacts on whole-body metabolism and leads to frailty and sarcopenia, which are risk factors for fractures and mortality. Although nutrients are integral to muscle metabolism the relationship between nutrition and muscle loss has only been extensively investigated for protein and amino acids. The objective of the present paper is to describe other aspects of nutrition and their association with skeletal muscle mass. Mechanisms for muscle loss relate to imbalance in protein turnover with a number of anabolic pathways of which the mechanistic TOR pathway and the IGF-1-Akt-FoxO pathways are the most characterised. In terms of catabolism the ubiquitin proteasome system, apoptosis, autophagy, inflammation, oxidation and insulin resistance are among the major mechanisms proposed. The limited research associating vitamin D, alcohol, dietary acid-base load, dietary fat and anti-oxidant nutrients with age-related muscle loss is described. Vitamin D may be protective for muscle loss; a more alkalinogenic diet and diets higher in the anti-oxidant nutrients vitamin C and vitamin E may also prevent muscle loss. Although present recommendations for prevention of sarcopenia focus on protein, and to some extent on vitamin D, other aspects of the diet including fruits and vegetables should be considered. Clearly, more research into other aspects of nutrition and their role in prevention of muscle loss is required. PMID:24229650

Welch, Ailsa A

2014-02-01

78

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

PubMed

Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including 479 potential novel sites. Most phosphorylation sites were detected in liver mitochondria (594), followed by heart (448) and skeletal muscle (336), and more phosphorylation sites were exclusively identified in liver mitochondria than in heart and skeletal muscle. Bioinformatics analysis pointed out enrichment for phosphoproteins involved in amino acid and fatty acid metabolism in liver mitochondria, whereas heart and skeletal muscle were enriched for phosphoproteins involved in energy metabolism, in particular, tricarboxylic acid cycle and oxidative phosphorylation. Multiple tissue-specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases in liver mitochondria. In conclusion, we provide a comprehensive map of mitochondrial phosphorylation sites, which covers approximately one-third of the mitochondrial proteome and can be targeted for the investigation of tissue-specific regulation of mitochondrial biological processes. PMID:23991683

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

2013-10-01

79

Expression of Midkine in Regenerating Skeletal Muscle Fibers and Cultured Myoblasts of Human Skeletal Muscle  

Microsoft Academic Search

Midkine is a member of a family of developmentally regulated neurotrophic and heparin-binding growth factors. The expression of midkine was examined immunohistochemically in biopsied muscle specimens from patients with various myopathies. The intense immunoreactivity of midkine was observed in the sarcoplasm at an early stage regenerating fibers of small diameter. Midkine immunoreactivity was also detected in cultured human skeletal muscle

Jing Hu; Itsuro Higuchi; Yoshihiro Yoshida; Tadafumi Shiraishi; Mitsuhiro Osame

2002-01-01

80

Reactive Oxygen Species in Skeletal Muscle Signaling  

PubMed Central

Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also—within certain concentrations—useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS hold a particular relevance. According to their hormetic nature, in muscles ROS may trigger different signaling pathways leading to diverging responses, from adaptation to cell death. Whether a “positive” or “negative” response will prevail depends on many variables such as, among others, the site of ROS production, the persistence of ROS flow or target cells' antioxidant status. In this light, a specific threshold of physiological ROS concentrations above which ROS exert negative, toxic effects is hard to determine, and the concept of “physiologically compatible” levels of ROS would better fit with such a dynamic scenario. In this review these concepts will be discussed along with the most relevant signaling pathways triggered and/or affected by ROS in skeletal muscle.

Barbieri, Elena; Sestili, Piero

2012-01-01

81

Human skeletal muscle sodium channelopathies  

Microsoft Academic Search

Ion channels are transmembrane proteins that allow ions to flow in or out of the cell. Sodium and potassium channel activation and inactivation are the basis of action potential’s production and conduction. During the past 15 years, ion channels have been implicated in diseases that have come to be known as the channelopathies. Over 30 mutations of the muscle channel

S. Vicart; D. Sternberg; B. Fontaine; G. Meola

2005-01-01

82

Structural alterations of skeletal muscle in copd  

PubMed Central

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.

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

2014-01-01

83

Tissue Engineered Strategies for Skeletal Muscle Injury  

PubMed Central

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

Longo, Umile Giuseppe; Loppini, Mattia; Berton, Alessandra; Spiezia, Filippo; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

84

Myosin types in human skeletal muscle fibers  

Microsoft Academic Search

By combining enzyme histochemistry for fiber typing with immunohistochemistry for slow and fast myosin a correlation between fiber type and myosin type was sought in human skeletal muscle. Fiber typing was done by staining for myofibrillar ATPases after preincubation at discriminating pH values. Myosin types were discriminated using type specific anti-rabbit myosin antibodies shown to cross-react with human myosin and

R. Billeter; H. Weber; H. Lutz; H. Howald; H. M. Eppenberger; E. Jenny

1980-01-01

85

Skeletal Muscle Mitochondria and Aging: A Review  

PubMed Central

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.

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

2012-01-01

86

The ribonucleases of bovine skeletal muscle.  

PubMed Central

Bovine skeletal muscle contains small amounts of at least six heat- and acid-stable RNA-degrading enzymes. Our results are the first evidence for multiple ribonucleases in skeletal muscle. Three of these have been highly purified, and each has been shown to be a pyrimidine-specific endoribonuclease by use of a rapid sequencing technique employing gel electrophoresis. However, synthetic co-polymers containing adenylate or guanylate residues in addition to pyrimidine residues are hydrolysed at higher rates than are the pyrimidine homopolymers. With 0.63 mM yeast RNA as substrate, all three enzymes (ribonucleases I, II and III) are optimally active in alkaline solution (pH 7.5-8.5) containing 0.05-0.15 M univalent salts, do not require bivalent cations, and have molecular weights of 13 000-20 000. The properties of muscle ribonuclease I are very similar to those of bovine pancreatic ribonuclease A. Muscle ribonucleases II and III have characteristics similar to those of ribonucleases found in various other bovine tissues. In common with all previously studied pyrimidine-specific endoribonucleases, the bovine muscle ribonucleases are inhibited by such purine homopolynucleotides as polyadenylate. Furthermore, polyamines, present in low concentrations, can reverse or regulate the amount of inhibition of enzyme activity.

Davies, G E; Karpetsky, T P; Levy, C C

1980-01-01

87

Development of Sensory Receptors in Skeletal Muscle  

NASA Technical Reports Server (NTRS)

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.

DeSantis, Mark

2000-01-01

88

Skeletal muscle disease: patterns of MRI appearances  

PubMed Central

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.

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

2012-01-01

89

Clinical assessment of skeletal muscle function.  

PubMed

A systematic clinical analysis of skeletal muscle function is presented. Tests range from assessment of muscle weakness with a new hand-held dynamometer (the "Hammersmith Myometer") to studies of the contractile properties of the quadriceps and adductor pollicis muscles described in terms of the force generated at different frequencies of stimulation of the motor nerve, the force-sustaining capability and the time course of relaxation following a brief tetanus. A new measure of the energy-exchanging capacity of muscle is given by the Myothermogram (MTG - so named by analogy with the Electromyogram - EMG). The technique measures metabolic heat production in muscles when maximally activated by voluntary effort or electrical stimulation and the heat changes during sustained contractions. The MTG offers a practical means for assessing in normal and diseased human muscle the metabolic capacity, economy of force maintenance and fatigue mechanisms. Needle biopsy provides safe, rapid and repeatable access to muscle for diagnosis, studies of chemical energy exchange and the correlation of function and metabolism with constituent muscle fibre types. This approach provides a possible basis for recognising the functional disorder and for evaluating the effects of physiotherapy and drug treatments in patients with neuromuscular disorders. PMID:667414

Edwards, R H

1978-03-01

90

Role of skeletal muscle in palate development.  

PubMed

The involvement of skeletal muscle in the process of palatal development in mammals is an example of Waddingtonian epigenetics. Our earlier study showed that the cleft palate develops in the complete absence of skeletal musculature during embryonic development in mice. This contrasts with previous beliefs that tongue obstruction prevents the elevation and fusion of the palatal shelves. We argue that the complete absence of mechanical stimuli from the adjacent muscle, i.e., the lack of both static and dynamic loading, results in disordered palatogenesis. We further suggest that proper fusion of the palatal shelves depends not only on mechanical but also on paracrine contributions from the muscle. The muscle's paracrine role in the process of palatal fusion is achieved through its being a source of certain secreted and/or circulatory proteins. A cDNA microarray analysis revealed differentially expressed genes in the cleft palate of amyogenic mouse fetuses and suggested candidate molecules with a novel function in palatogenesis (e.g., Tgfbr2, Bmp7, Trim71, E2f5, Ddx5, Gfap, Sema3f). In particular, we report on Gdf11 mutant mouse that has cleft palate, and on several genes whose distribution is normally restricted to the muscle (completely absent in our amyogenic mouse model), but which are found down-regulated in amyogenic mouse cleft palate. These molecules probably present a subset of paracrine cues that influence palatogenesis from the adjacent muscle. Future studies will elucidate the role of these genes in muscle-palate crosstalk, connecting the cues produced by the muscle with the cartilage and bone tissue's responses to these cues, through various degrees of cell proliferation, death, differentiation and tissue fusion. PMID:23233055

Rot, I; Kablar, B

2013-01-01

91

Metastases of esophageal carcinoma to skeletal muscle: Single center experience  

PubMed Central

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

Cincibuch, Jan; Myslivecek, Miroslav; Melichar, Bohuslav; Neoral, Cestmir; Metelkova, Iva; Zezulova, Michaela; Prochazkova-Studentova, Hana; Flodr, Patrik; Zlevorova, Miloslava; Aujesky, Rene; Cwiertka, Karel

2012-01-01

92

Extrarenal potassium adaptation: role of skeletal muscle  

SciTech Connect

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.

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

1986-08-01

93

Engineering of aligned skeletal muscle by micropatterning  

PubMed Central

Tissue engineered skeletal muscle has tremendous potential for the treatment of muscular injury or muscular dysfunction. However, in vitro methods to generate skeletal muscle with physiologically aligned myofiber structure remains limited. To develop a robust in vitro model that resembles the physiologically aligned structure of muscle fibers, we fabricated micropatterned polymer membranes of poly(dimethylsiloxane) (PDMS) with parallel microgrooves, and then examined the effect of micropatterning on myoblast cellular organization and the cell fusion process. In comparison to the myoblasts on non-patterned PDMS films, myoblasts on micropatterned PDMS films had well-organized F-actin assembly in close proximity to the direction of microgrooves, along with enhanced levels of myotube formation at early time points. The increase of cell cycle regulator p21WAF/Cip1 and the organized interactions of N-cadherin in myoblasts on micropatterned surfaces may contribute to the enhanced formation of myotubes. Similar results of cellular alignment was observed when myoblasts were cultured on microfluidically patterned poly(2-hydroxyethyl methacrylate) (pHEMA) microgrooves, and the micropatterns were found to detach from the Petri dish over time. To apply this technology for generating aligned tissue-like muscle constructs, we developed a methodology to transfer the aligned myotubes to biodegradable collagen gels. Histological analysis revealed the persistence of aligned cellular organization in the collagen gels. Together, these results demonstrate that micropatterned PDMS or pHEMA can promote cell alignment and fusion along the direction of the microgrooves, and this platform can be utilized to transfer aligned myotubes on biodegradable hydrogels. This study highlights the importance of spatial cues in creating aligned skeletal muscle for tissue engineering and muscular regeneration applications.

Huang, Ngan F; Lee, Randall J; Li, Song

2010-01-01

94

GLUT-3 expression in human skeletal muscle  

NASA Technical Reports Server (NTRS)

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.

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

2000-01-01

95

Dorsal root vasodilatation in cat skeletal muscle.  

PubMed Central

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.

Hilton, S M; Marshall, J M

1980-01-01

96

Capillarity and diffusion distances in skeletal muscles in birds  

Microsoft Academic Search

Tissue capillarity and diffusion distances were determined for red and white skeletal muscles of adult birds ranging in mass from 10.8 to 6200 g. In addition, literature values for capillarity and diffusion distances in skeletal muscles of mammals were incorporated into the data set. Muscle mass was closely coupled to body mass. However, no significant allometric relations were found for

Gregory K. Snyder

1990-01-01

97

Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation  

PubMed Central

The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids.

Haldar, Saptarsi M.; Jeyaraj, Darwin; Anand, Priti; Zhu, Han; Lu, Yuan; Prosdocimo, Domenick A.; Eapen, Betty; Kawanami, Daiji; Okutsu, Mitsuharu; Brotto, Leticia; Fujioka, Hisashi; Kerner, Janos; Rosca, Mariana G.; McGuinness, Owen P.; Snow, Rod J.; Russell, Aaron P.; Gerber, Anthony N.; Bai, Xiaodong; Yan, Zhen; Nosek, Thomas M.; Brotto, Marco; Hoppel, Charles L.; Jain, Mukesh K.

2012-01-01

98

Effects of regular exercise training on skeletal muscle contractile function  

NASA Technical Reports Server (NTRS)

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.

Fitts, Robert H.

2003-01-01

99

Nuclear Factor-kappa B Signaling in Skeletal Muscle Atrophy  

PubMed Central

Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-?B) is one of most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-?B in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-?B can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-?B in skeletal muscle with particular reference to different models of muscle-wasting and the development of novel therapy.

Li, Hong; Malhotra, Shweta; Kumar, Ashok

2008-01-01

100

The response of skeletal muscle to leptin.  

PubMed

There is now compelling evidence that, in addition to signaling to the central nervous system (CNS), leptin also exerts its metabolic effects acting directly on peripheral tissues. It has been demonstrated by in vivo and in vitro studies, that leptin increases glucose and fatty acid metabolism in skeletal muscle. These direct leptin effects are supported by the presence of the long form of the leptin receptor, considered to be capable of performing intracellular signaling, in peripheral tissues, including skeletal muscle. The exposure of soleus muscle to supra-physiological leptin concentrations stimulate the activity of both the pyruvate-dehydrogenase (PDH) complex and Krebs cycle. This could be due to a direct stimulation of PDH and krebs cycle by leptin or a consequence of an indirect effect of this hormone activating the mitochondrial uncoupling process. In addition, in soleus and extensor digitorum longus (EDL) muscles, leptin and insulin had opposite effects on lipid metabolism, with leptin favoring lipid oxidation and insulin favoring lipid storage as triglycerides (TG). The leptin effects on free fatty acid (FFA) oxidation were more pronounced in soleus than in EDL. The differences in response of soleus compared with that of EDL was probably due to differences in fiber type composition and metabolic characteristics. It has been demonstrated that leptin reduces the TG content of skeletal. When tissue TG content is severely depleted by hyperleptinemia in normal rats, there is a dramatic increase in insulin sensitivity. This lipopenic effect of leptin may protect from the development of insulin resistance and diabetes in animals. In humans, obesity is also associated with an increase in insulin resistance and the development of Type II diabetes, however, contrary to rats and mice, there is abundance of leptin, indicating a state of resistance to this hormone in humans. Future studies are necessary to investigate the reasons why lean subjects seem to respond properly to endogenous leptin while obese ones don't. The understanding of the putative direct leptin signaling pathway in skeletal muscle could be an important step towards the utilization of leptin or a leptin receptor agonist as therapeutic tools to treat obesity and its related metabolic disorders. PMID:11145919

Ceddia, R B; William, W N; Curi, R

2001-01-01

101

Modeling of the Skeletal Muscle Microcirculation  

NASA Astrophysics Data System (ADS)

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.

Jacobitz, Frank; Beth, Christophe; Salado, Jerome

2004-11-01

102

Interactive Classroom Demonstration of Skeletal Muscle Contraction  

NSDL National Science Digital Library

Students in a traditional lecture-style course often struggle to visualize the sequence of events in the molecular mechanism of skeletal muscle contraction as represented in anatomy and physiology textbooks (e.g., Ref. 1). The author of this article has successfully used the following interactive method with first-year nursing students. If the students are able to state the functions of calcium, troponin, tropomyosin, and cross-bridges, the demonstration requires only 15ÃÂ20 minutes of class time. The size of the actin and myosin filaments can be varied according to the class size.

Janice Meeking (Mount Royal College Department of Chemical, Biological); Katja Hoehn (Mount Royal College Department of Chemical, Biological)

2002-12-01

103

Analysis of skeletal muscle hypertrophy in models of increased loading.  

PubMed

Skeletal muscle is a highly adaptive tissue that modifies its size in response to a variety of external stimuli. In adult mammals, skeletal muscle hypertrophy occurs primarily as a response to increases in external loading. Here, we describe the methods that should be used for a comprehensive assessment of muscle hypertrophy in animal models. The methods include the measurement of muscle mass, fiber cross-sectional area, contractile function, and protein concentration. PMID:22130839

Bodine, Sue C; Baar, Keith

2012-01-01

104

Targeted Expression of IGF-1 Transgene to Skeletal Muscle Accelerates Muscle and Motor Neuron Regeneration  

Microsoft Academic Search

Currently, there is no known medical treatment that hastens the repair of damaged nerve and muscle. Using IGF-1 transgenic mice that specifically express human recombinant IGF-1 in skeletal muscle, we test the hypotheses that targeted gene expression of IGF-1 in skeletal muscle enhances motor nerve regeneration after a nerve crush injury. The IGF-1 transgene affects the initiation of the muscle

Eric D. Rabinovsky; Ethem Gelir; Seda Gelir; Hui Lui; Maan Kattash; Francesco J. DeMayo; Saleh M. Shenaq; Robert J. Schwartz

2003-01-01

105

Skeletal muscle responses to unloading in humans  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

106

Fine structure of tortoise skeletal muscle  

PubMed Central

1. The fine structure of tortoise skeletal muscle has been studied with the electron microscope. 2. The packing of the A filaments (1·6 ? long) and the I filaments (2·35 ? long) within the myofibril is similar to that in frog twitch fibres. 3. The position of the N line within the I band is found to vary with the sarcomere length. 4. The T-system tubules in these muscles form a three-dimensional network across the fibre at the level of the I band. On either side of the Z line it forms triad relationships with the other network of tubules of the sarco-plasmic reticulum. ImagesPlate 4Plate 1Plate 2Plate 3

Page, Sally G.

1968-01-01

107

Fine structure of tortoise skeletal muscle.  

PubMed

1. The fine structure of tortoise skeletal muscle has been studied with the electron microscope.2. The packing of the A filaments (1.6 mu long) and the I filaments (2.35 mu long) within the myofibril is similar to that in frog twitch fibres.3. The position of the N line within the I band is found to vary with the sarcomere length.4. The T-system tubules in these muscles form a three-dimensional network across the fibre at the level of the I band. On either side of the Z line it forms triad relationships with the other network of tubules of the sarco-plasmic reticulum. PMID:5666182

Page, S G

1968-08-01

108

Motor Force Homeostasis in Skeletal Muscle Contraction  

PubMed Central

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.

Chen, Bin; Gao, Huajian

2011-01-01

109

Motor force homeostasis in skeletal muscle contraction.  

PubMed

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. PMID:21767492

Chen, Bin; Gao, Huajian

2011-07-20

110

Muscular dysgenesis: a model system for studying skeletal muscle development  

Microsoft Academic Search

Muscular dysgenesis, caused by an autosomal recessive lethal mutation (mdg) in mice, is characterized by an absence of contraction of skeletal muscle. A historical review of the investigation of this disorder is presented. The early studies of the morphological and physiologi- cal aspects of the disorder in vivo and in vitro pre- sented evidence for dysfunction in the skeletal muscle

JEANNE A. POWELL

111

Role of titin in skeletal muscle function and disease.  

PubMed

This review covers recent developments in the titin field. Most recent reviews have discussed titin's role in cardiac function: here we will mainly focus on skeletal muscle, and discuss recent advances in the understanding of titin's role in skeletal muscle function and disease. PMID:20824522

Ottenheijm, Coen A C; Granzier, Henk

2010-01-01

112

Insulin increases mRNA abundance of the amino acid transporter SLC7A5/LAT1 via an mTORC1-dependent mechanism in skeletal muscle cells.  

PubMed

Abstract Amino acid transporters (AATs) provide a link between amino acid availability and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) activation although the direct relationship remains unclear. Previous studies in various cell types have used high insulin concentrations to determine the role of insulin on mTORC1 signaling and AAT mRNA abundance. However, this approach may limit applicability to human physiology. Therefore, we sought to determine the effect of insulin on mTORC1 signaling and whether lower insulin concentrations stimulate AAT mRNA abundance in muscle cells. We hypothesized that lower insulin concentrations would increase mRNA abundance of select AAT via an mTORC1-dependent mechanism in C2C12 myotubes. Insulin (0.5 nmol/L) significantly increased phosphorylation of the mTORC1 downstream effectors p70 ribosomal protein S6 kinase 1 (S6K1) and ribosomal protein S6 (S6). A low rapamycin dose (2.5 nmol/L) significantly reduced the insulin-(0.5 nmol/L) stimulated S6K1 and S6 phosphorylation. A high rapamycin dose (50 nmol/L) further reduced the insulin-(0.5 nmol/L) stimulated phosphorylation of S6K1 and S6. Insulin (0.5 nmol/L) increased mRNA abundance of SLC38A2/SNAT2 (P ? 0.043) and SLC7A5/LAT1 (P ? 0.021) at 240 min and SLC36A1/PAT1 (P = 0.039) at 30 min. High rapamycin prevented an increase in SLC38A2/SNAT2 (P = 0.075) and SLC36A1/PAT1 (P ? 0.06) mRNA abundance whereas both rapamycin doses prevented an increase in SLC7A5/LAT1 (P ? 0.902) mRNA abundance. We conclude that a low insulin concentration increases SLC7A5/LAT1 mRNA abundance in an mTORC1-dependent manner in skeletal muscle cells. PMID:24760501

Walker, Dillon K; Drummond, Micah J; Dickinson, Jared M; Borack, Michael S; Jennings, Kristofer; Volpi, Elena; Rasmussen, Blake B

2014-01-01

113

Insulin increases mRNA abundance of the amino acid transporter SLC7A5/LAT1 via an mTORC1-dependent mechanism in skeletal muscle cells  

PubMed Central

Abstract Amino acid transporters (AATs) provide a link between amino acid availability and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) activation although the direct relationship remains unclear. Previous studies in various cell types have used high insulin concentrations to determine the role of insulin on mTORC1 signaling and AAT mRNA abundance. However, this approach may limit applicability to human physiology. Therefore, we sought to determine the effect of insulin on mTORC1 signaling and whether lower insulin concentrations stimulate AAT mRNA abundance in muscle cells. We hypothesized that lower insulin concentrations would increase mRNA abundance of select AAT via an mTORC1?dependent mechanism in C2C12 myotubes. Insulin (0.5 nmol/L) significantly increased phosphorylation of the mTORC1 downstream effectors p70 ribosomal protein S6 kinase 1 (S6K1) and ribosomal protein S6 (S6). A low rapamycin dose (2.5 nmol/L) significantly reduced the insulin?(0.5 nmol/L) stimulated S6K1 and S6 phosphorylation. A high rapamycin dose (50 nmol/L) further reduced the insulin?(0.5 nmol/L) stimulated phosphorylation of S6K1 and S6. Insulin (0.5 nmol/L) increased mRNA abundance of SLC38A2/SNAT2 (P ? 0.043) and SLC7A5/LAT1 (P ? 0.021) at 240 min and SLC36A1/PAT1 (P = 0.039) at 30 min. High rapamycin prevented an increase in SLC38A2/SNAT2 (P = 0.075) and SLC36A1/PAT1 (P ? 0.06) mRNA abundance whereas both rapamycin doses prevented an increase in SLC7A5/LAT1 (P ? 0.902) mRNA abundance. We conclude that a low insulin concentration increases SLC7A5/LAT1 mRNA abundance in an mTORC1?dependent manner in skeletal muscle cells.

Walker, Dillon K.; Drummond, Micah J.; Dickinson, Jared M.; Borack, Michael S.; Jennings, Kristofer; Volpi, Elena; Rasmussen, Blake B.

2014-01-01

114

Frequency response model of skeletal muscle and its association with contractile properties of skeletal muscle.  

PubMed

The aims of the present study were to develop a mathematical model of the skeletal muscle based on the frequency transfer function, referred to as frequency response model, and to presume the relationship between the model elements and skeletal muscle contractile properties. Twitch force in elbow flexion was elicited by applying a single electrical stimulation to the motor point of biceps brachii muscles, and then analyzed visually by the Bode gain and phase diagram of the force signal. The frequency response model was represented by a frequency transfer function consisting of five basic control elements (proportional element, dead time element, and three first-order lag elements). The model element constants were estimated by best-fitting to the Bode gain and phase diagram of the twitch force signal. The proportional constant and the dead time in the frequency response model correlated significantly with the peak torque and the latency in the actual twitch force, respectively. In addition, the time constants of the three first-order lag elements in the model correlated strongly with the contraction time and the half relaxation time in the actual twitch force. The results suggested a possibility that the individual elements in the frequency response model would reflect the biochemical and biomechanical properties in the excitation-contraction coupling process of skeletal muscle. PMID:23265663

Itoh, Yasushi; Akataki, Kumi; Mita, Katsumi; Watakabe, Makoto; Nonaka, Hisako

2013-06-01

115

Growth factor involvement in tension-induced skeletal muscle growth  

NASA Technical Reports Server (NTRS)

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.

Vandenburgh, H. H.

1987-01-01

116

Molecular characterization and expression patterns of AMP deaminase1 (AMPD1) in porcine skeletal muscle.  

PubMed

AMPD1 is the muscle-specific form of the AMPD multigene families in mammals and plays an important role in the purine nucleotide cycle and energy metabolism in skeletal muscle. In this study, we cloned and characterized AMPD1 from Sus scrofa muscle. The promoter of porcine AMPD1 contained several putative muscle-specific transcription factor binding sites (E box, myogenin, MEF2, Spl-CTF/NF-l), one RORalpha2 binding motif and NF-kappaB site. The deduced amino acid sequence of porcine AMPD1 contains an AMP deaminase signature sequence (SLSTDDP). RT-PCR analyses showed that AMPD1 was expressed specifically in skeletal muscle. Expression of AMPD1 was up-regulated during the muscle development and was higher in Yorkshire than in Meishan pigs. AMPD1 gene was expressed at higher levels in longissimus dorsi and bicepsfemoris muscles compared with soleus and masseter muscles in both Yorkshire and Meishan pigs. Moreover, we found that a single nucleotide polymorphism (SNP, T/C(426)) in exon12 of the AMPD1 gene was significantly associated with loin muscle area trait (p<0.01), loin muscle height (p<0.01) and average backfat thickness (p<0.05). This result suggests that the AMPD1 gene might be a candidate gene of meat production trait and provides useful information for further studies on its roles in porcine skeletal muscle. PMID:18638563

Wang, Linjie; Mo, Xiaoyu; Xu, Yongjie; Zuo, Bo; Lei, Minggang; Li, Fenge; Jiang, Siwen; Deng, Changyan; Xiong, Yuanzhu

2008-10-01

117

Skeletal muscle insulin resistance in endocrine disease.  

PubMed

We summarize the existing literature data concerning the involvement of skeletal muscle (SM) in whole body glucose homeostasis and the contribution of SM insulin resistance (IR) to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS), adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism. PMID:20300436

Peppa, Melpomeni; Koliaki, Chrysi; Nikolopoulos, Panagiotis; Raptis, Sotirios A

2010-01-01

118

Autophagic cellular responses to physical exercise in skeletal muscle.  

PubMed

Autophagy is an evolutionarily conserved biological process that functions to recycle protein aggregate and malfunctioned organelles. The activation of autophagy can be stimulated by a number of ways including infection, caloric restriction, and physical exercise. In addition to cellular metabolism and cell survival/death machinery, autophagy plays an important role in the maintenance of cellular homeostasis in skeletal muscle especially during physical exercise in which energy demand can be extremely high. By degrading macromolecules and subcellular organelles through the fusion of autophagosomes and lysosomes, useful materials such as amino acids can be released and re-used to sustain normal metabolism in cells. Autophagy is suggested to be involved in glucose and lipid metabolism and is proposed to be a critical physiological process in the regulation of intracellular metabolism. The effects of physical exercise on autophagy have been investigated. Although physical exercise has been demonstrated to be an autophagic inducer, cellular autophagic responses to exercise in skeletal muscle appear to be varied in different exercise protocols and disease models. It is also not known whether the exercise-induced beneficial health consequences involve the favorable modulation of cellular autophagy. Furthermore, the cellular mechanisms of exercise-induced autophagy still remain largely unclear. In this review article, we discuss the general principle of autophagy, cellular signaling of autophagy, autophagic responses to acute and chronic aerobic exercise, and the potential cross-talks among autophagy, mitochondrial biogenesis, and ubiquitination. This article aims to stimulate further studies in exercise and autophagy. PMID:24549475

Tam, Bjorn T; Siu, Parco M

2014-05-01

119

Diffusional anisotropy is induced by subcellular barriers in skeletal muscle  

Microsoft Academic Search

The time- and orientational-dependence of phosphocreatine (PCr) diffusion was measured using pulsed-field gradient nuclear magnetic resonance (PFG-NMR) as a means of non-invasively probing the intracellular diffusive barriers of skeletal muscle. Red and white skeletal muscle from fish was used because fish muscle cells are very large, which facilitates the examination of diffusional barriers in the intracellular environment, and because they

Stephen T. Kinsey; Bruce R. Locke; Brigita Penke; Timothy S. Moerland

1999-01-01

120

The application of 2H2O to measure skeletal muscle protein synthesis  

Microsoft Academic Search

Skeletal muscle protein synthesis has generally been determined by the precursor:product labeling approach using labeled amino acids (e.g., [13C]leucine or [13C]-, [15N]-, or [2H]phenylalanine) as the tracers. Although reliable for determining rates of protein synthesis, this methodological approach requires experiments to be conducted in a controlled environment, and as a result, has limited our understanding of muscle protein renewal under

Heath G Gasier; James D Fluckey; Stephen F Previs

2010-01-01

121

Skeletal muscle metabolism in hypokinetic rats  

NASA Technical Reports Server (NTRS)

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

Tischler, Marc E.

1993-01-01

122

Applications of skeletal muscle progenitor cells for neuromuscular diseases.  

PubMed

Neuromuscular diseases affect skeletal muscle and/or nervous control resulting in direct disruption of skeletal muscle and muscle pathology, or nervous system disruption which indirectly disrupts muscle function. Stem cell-based therapy is well-recognized as a promising approach for several types of diseases including those affecting the neuromuscular system. To design a successful therapeutic strategy, it is important to choose the most appropriate stem cell type. Skeletal muscle progenitor cells (SMPCs), also called myogenic progenitors, can contribute to muscle regeneration, differentiate into skeletal muscles, and are valuable cells for therapeutic application. Different types of stem/progenitor cells, including satellite cells, side population cells, muscle derived stem cells, mesenchymal stem cells, myogenic pericytes, and mesoangioblasts, have been identified as possible cell resources of SMPCs. Furthermore, recent advances in stem cell biology allow us to use embryonic stem cells and induced pluripotent stem cells for SMPC derivation. When skeletal muscle is chosen as a target of cell transplantation, the possible criteria for choosing the "best" progenitor/stem cell include preparation strategies, efficiency of intramuscular integration, method of cellular delivery, and functional improvement of the muscle after cell transplantation. Here, we discuss recent findings on various types of SMPCs and their promise for future clinical translation in neuromuscular diseases. PMID:23671812

Hosoyama, Tohru; Van Dyke, Jonathan; Suzuki, Masatoshi

2012-01-01

123

IGF-1 Regulation of Skeletal Muscle Hypertrophy and Atrophy  

Microsoft Academic Search

\\u000a Insulin-like growth factor 1 (IGF-1) can induce skeletal muscle hypertrophy, defined as an increase in skeletal muscle mass.\\u000a Hypertrophy occurs as a result of an increase in the size, as opposed to the number, of pre-existing skeletal muscle fibers.\\u000a IGF-1's pro-hypertrophy activity comes predominantly through its ability to activate the Phosphoinositide 3-kinase (PI3K)\\/Akt\\u000a signaling pathway. Akt is a serine-threonine protein

David J. Glass

124

Methionine: a study of its catabolic pathway in skeletal muscle  

SciTech Connect

A recent study showed the possibility of utilization of methionine by skeletal muscle. The present communication gives more detail of this process. Rat hindquarters were perfused with a trace amount of U-/sup 14/C-methionine, and labeling of compounds in the organic- and amino acid fractions was determined. Thin layer chromatographic analysis of perfusate and tissue extracts showed incorporation of /sup 14/C into lactate (25% of radioactivity present in the organic acid fraction), and smaller amounts (3-6%) in malate and citrate. Methionine sulfoxide accounted for 60-80% of total radioactivity in the amino acid fraction. About 5-8% of radioactivity in this fraction was found in glutamine plus glutamate plus alanine. Studies of capacity of enzymes utilizing methionine by muscle homogenates were then carried out. The activities of type L glutamine transaminase (GT), (..mu..moles/g/h), 10; and type K-GT, 6. Comparison of these activities using oxoanalogues of methionine showed transamination involved in the degradation of methionine, methionine sulfoxide and methionine sulfone.

Scislowski, P.D.W.; Davis, E.J.

1986-05-01

125

Molecular events in skeletal muscle during disuse atrophy  

NASA Technical Reports Server (NTRS)

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.

Kandarian, Susan C.; Stevenson, Eric J.

2002-01-01

126

Lifting the nebula: novel insights into skeletal muscle contractility.  

PubMed

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. PMID:20940435

Ottenheijm, Coen A C; Granzier, Henk

2010-10-01

127

Finite element modelling of contracting skeletal muscle.  

PubMed Central

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

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

2003-01-01

128

Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma  

Microsoft Academic Search

mAbs specific for protein components of the surface membrane of rabbit skeletal muscle have been used as markers in the isolation and characteriza- tion of skeletal muscle sarcolemma membranes. Highly purified sarcolemma membranes from rabbit skeletal muscle were isolated from a crude surface membrane preparation by wheat germ agglutination. Immunoblot analysis of subcellular fractions from skeletal muscle revealed that dystrophin

Kay Ohlendieck; James M. Ervasti; Joseph B. Snook; Kevin P. Campbell

1991-01-01

129

AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle.  

PubMed

Deacetylases such as sirtuins (SIRTs) convert NAD to nicotinamide (NAM). Nicotinamide phosphoribosyl transferase (Nampt) is the rate-limiting enzyme in the NAD salvage pathway responsible for converting NAM to NAD to maintain cellular redox state. Activation of AMP-activated protein kinase (AMPK) increases SIRT activity by elevating NAD levels. As NAM directly inhibits SIRTs, increased Nampt activation or expression could be a metabolic stress response. Evidence suggests that AMPK regulates Nampt mRNA content, but whether repeated AMPK activation is necessary for increasing Nampt protein levels is unknown. To this end, we assessed whether exercise training- or 5-amino-1-?-D-ribofuranosyl-imidazole-4-carboxamide (AICAR)-mediated increases in skeletal muscle Nampt abundance are AMPK dependent. One-legged knee-extensor exercise training in humans increased Nampt protein by 16% (P < 0.05) in the trained, but not the untrained leg. Moreover, increases in Nampt mRNA following acute exercise or AICAR treatment (P < 0.05 for both) were maintained in mouse skeletal muscle lacking a functional AMPK ?2 subunit. Nampt protein was reduced in skeletal muscle of sedentary AMPK ?2 kinase dead (KD), but 6.5 weeks of endurance exercise training increased skeletal muscle Nampt protein to a similar extent in both wild-type (WT) (24%) and AMPK ?2 KD (18%) mice. In contrast, 4 weeks of daily AICAR treatment increased Nampt protein in skeletal muscle in WT mice (27%), but this effect did not occur in AMPK ?2 KD mice. In conclusion, functional ?2-containing AMPK heterotrimers are required for elevation of skeletal muscle Nampt protein, but not mRNA induction. These findings suggest AMPK plays a post-translational role in the regulation of skeletal muscle Nampt protein abundance, and further indicate that the regulation of cellular energy charge and nutrient sensing is mechanistically related. PMID:23918774

Brandauer, Josef; Vienberg, Sara G; Andersen, Marianne A; Ringholm, Stine; Risis, Steve; Larsen, Per S; Kristensen, Jonas M; Frøsig, Christian; Leick, Lotte; Fentz, Joachim; Jørgensen, Sebastian; Kiens, Bente; Wojtaszewski, Jørgen F P; Richter, Erik A; Zierath, Juleen R; Goodyear, Laurie J; Pilegaard, Henriette; Treebak, Jonas T

2013-10-15

130

Heparan sulfate in skeletal muscle development  

SciTech Connect

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.

Noonan, D.M.

1985-01-01

131

Extracellular matrix adaptation of tendon and skeletal muscle to exercise  

PubMed Central

The extracellular matrix (ECM) of connective tissues enables linking to other tissues, and plays a key role in force transmission and tissue structure maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by physical activity, and both collagen synthesis and metalloprotease activity increase with mechanical loading. This can be shown by determining propeptide and proteinase activity by microdialysis, as well as by verifying the incorporation of infused stable isotope amino acids in biopsies. Local tissue expression and release of growth factors for ECM such as IGF-1, TGF-beta and IL-6 is enhanced following exercise. For tendons, metabolic activity (e.g. detected by positron emission tomography scanning), circulatory responses (e.g. as measured by near-infrared spectroscopy and dye dilution) and collagen turnover are markedly increased after exercise. Tendon blood flow is regulated by cyclooxygenase-2 (COX-2)-mediated pathways, and glucose uptake is regulated by specific pathways in tendons that differ from those in skeletal muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as to some degree of net collagen synthesis. These changes modify the mechanical properties and the viscoelastic characteristics of the tissue, decrease its stress-susceptibility and probably make it more load-resistant. The mechanical properties of tendon fascicles vary within a given human tendon, and even show gender differences. The latter is supported by findings of gender-related differences in the activation of collagen synthesis with exercise. These findings may provide the basis for understanding tissue overloading and injury in both tendons and skeletal muscle.

Kjaer, Michael; Magnusson, Peter; Krogsgaard, Michael; M?ller, Jens Boysen; Olesen, Jens; Heinemeier, Katja; Hansen, Mette; Haraldsson, Bjarki; Koskinen, Satu; Esmarck, Birgitte; Langberg, Henning

2006-01-01

132

Skeletal muscle fibrosis develops in response to desmin deletion  

PubMed Central

Skeletal muscle is a dynamic composite of proteins that responds to both internal and external cues to facilitate muscle adaptation. In cases of disease or altered use, these messages can be distorted resulting in myopathic conditions such as fibrosis. In this work, we describe a mild and progressive fibrotic adaptation in skeletal muscle lacking the cytoskeletal intermediate filament protein desmin. Muscles lacking desmin become progressively stiffer, accumulate increased collagen, and increase expression of genes involved in extracellular matrix turnover. Additionally, in the absence of desmin, skeletal muscle is in an increased state of inflammation and regeneration as indicated by increased centrally nucleated fibers, elevated inflammation and regeneration related gene expression, and increased numbers of inflammatory cells. These data suggest a potential link between increased cellular damage and the development of fibrosis in muscles lacking the cytoskeletal support of the desmin filament network.

Meyer, Gretchen A.

2012-01-01

133

Neurotization improves contractile forces of tissue-engineered skeletal muscle.  

PubMed

Engineered functional skeletal muscle would be beneficial in reconstructive surgery. Our previous work successfully generated 3-dimensional vascularized skeletal muscle in vivo. Because neural signals direct muscle maturation, we hypothesized that neurotization of these constructs would increase their contractile force. Additionally, should neuromuscular junctions (NMJs) develop, indirect stimulation (via the nerve) would be possible, allowing for directed control. Rat myoblasts were cultured, suspended in fibrin gel, and implanted within silicone chambers around the femoral vessels and transected femoral nerve of syngeneic rats for 4 weeks. Neurotized constructs generated contractile forces 5 times as high as the non-neurotized controls. Indirect stimulation via the nerve elicited contractions of neurotized constructs. Curare administration ceased contraction in these constructs, providing physiologic evidence of NMJ formation. Histology demonstrated intact muscle fibers, and immunostaining positively identified NMJs. These results indicate that neurotization of engineered skeletal muscle significantly increases force generation and causes NMJs to develop, allowing indirect muscle stimulation. PMID:17822360

Dhawan, Vikas; Lytle, Ian F; Dow, Douglas E; Huang, Yen-Chih; Brown, David L

2007-11-01

134

Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice  

PubMed Central

Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a–independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a–independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3K?-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a–mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.

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

2013-01-01

135

Renal Function Alterations during Skeletal Muscle Disuse in Simulated Microgravity.  

National Technical Information Service (NTIS)

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. Th...

B. J. Tucker

1992-01-01

136

Ultrastructural Alterations in Skeletal Muscle Fibers of Rats after Exercise.  

National Technical Information Service (NTIS)

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 d...

M. Akuzawa M. Hataya

1982-01-01

137

The influence of skeletal muscle on systemic aging and lifespan.  

PubMed

Epidemiological studies in humans suggest that skeletal muscle aging is a risk factor for the development of several age-related diseases such as metabolic syndrome, cancer, Alzheimer's and Parkinson's disease. Here, we review recent studies in mammals and Drosophila highlighting how nutrient- and stress-sensing in skeletal muscle can influence lifespan and overall aging of the organism. In addition to exercise and indirect effects of muscle metabolism, growing evidence suggests that muscle-derived growth factors and cytokines, known as myokines, modulate systemic physiology. Myokines may influence the progression of age-related diseases and contribute to the intertissue communication that underlies systemic aging. PMID:23802635

Demontis, Fabio; Piccirillo, Rosanna; Goldberg, Alfred L; Perrimon, Norbert

2013-12-01

138

Skeletal muscle and bone: effect of sex steroids and aging  

NSDL National Science Digital Library

Both estrogen and testosterone are present in males and females. Both hormones contribute to the well being of skeletal muscle and bone in men and women, and there is evidence that the loss of sex hormones is associated with the age-related decline in bone and skeletal muscle mass. Hormonal supplementation of older adults to restore estrogen and testosterone levels to those of young men and women is not without penalty.

PhD Marybeth Brown (University of Missouri-Columbia Dept of Physical Therapy)

2008-02-14

139

Skeletal muscle dysfunction in chronic obstructive pulmonary disease  

Microsoft Academic Search

It has become increasingly recognized that skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary\\u000a disease (COPD). Muscle strength and endurance are decreased, whereas muscle fatigability is increased. There is a reduced\\u000a proportion of type I fibers and an increase in type II fibers. Muscle atrophy occurs with a reduction in fiber cross-sectional\\u000a area. Oxidative enzyme activity is

M Jeffery Mador; Erkan Bozkanat

2001-01-01

140

Rapamycin does not affect post-absorptive protein metabolism in human skeletal muscle  

PubMed Central

Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion. Objective To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle. Materials/Methods Six young (26±2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 2h basal periods. The trials were identical except during one trial a single oral dose (16mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2h basal period. Results During the Control trial, muscle protein synthesis, whole body protein breakdown (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar between both basal periods (p>0.05). During the Rapamycin trial, these variables were similar to the Control trial (p>0.05) and were unaltered by rapamycin administration (p>0.05). Thus, post-absorptive muscle protein metabolism and mTORC1 signaling were not affected by rapamycin administration. Conclusions Short-term rapamycin administration may only impair protein synthesis in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability.

Dickinson, Jared M.; Drummond, Micah J.; Fry, Christopher S.; Gundermann, David M.; Walker, Dillon K.; Timmerman, Kyle L.; Volpi, Elena; Rasmussen, Blake B.

2013-01-01

141

Renal function alterations during skeletal muscle disuse in simulated microgravity  

NASA Technical Reports Server (NTRS)

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.

Tucker, Bryan J.

1992-01-01

142

Cloning and characterization of fiber type-specific ryanodine receptor isoforms in skeletal muscles of fish.  

PubMed

We have cloned a group of cDNAs that encodes the skeletal ryanodine receptor isoform (RyR1) of fish from a blue marlin extraocular muscle library. The cDNAs encode a protein of 5,081 amino acids with a calculated molecular mass of 576,302 Da. The deduced amino acid sequence shows strong sequence identity to previously characterized RyR1 isoforms. An RNA probe derived from a clone of the full-length marlin RyR1 isoform hybridizes to RNA preparations from extraocular muscle and slow-twitch skeletal muscle but not to RNA preparations from fast-twitch skeletal or cardiac muscle. We have also isolated a partial RyR clone from marlin and toadfish fast-twitch muscles that shares 80% sequence identity with the corresponding region of the full-length RyR1 isoform, and a RNA probe derived from this clone hybridizes to RNA preparations from fast-twitch muscle but not to slow-twitch muscle preparations. Western blot analysis of slow-twitch muscles in fish indicates the presence of only a single high-molecular-mass RyR protein corresponding to RyR1. [3H]ryanodine binding assays revealed the fish slow-twitch muscle RyR1 had a greater sensitivity for Ca2+ than the fast-twitch muscle RyR1. The results indicate that, in fish muscle, fiber type-specific RyR1 isoforms are expressed and the two proteins are physiologically distinct. PMID:9688594

Franck, J P; Morrissette, J; Keen, J E; Londraville, R L; Beamsley, M; Block, B A

1998-08-01

143

Systems analysis of biological networks in skeletal muscle function  

PubMed Central

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 Ca2+ release. Ca2+ 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.

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

2014-01-01

144

Systems analysis of biological networks in skeletal muscle function.  

PubMed

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. PMID:23188744

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

2013-01-01

145

Na channel distribution in vertebrate skeletal muscle  

PubMed Central

The loose patch voltage clamp has been used to map Na current density along the length of snake and rat skeletal muscle fibers. Na currents have been recorded from (a) endplate membrane exposed by removal of the nerve terminal, (b) membrane near the endplate, (c) extrajunctional membrane far from both the endplate and the tendon, and (d) membrane near the tendon. Na current densities recorded directly on the endplate were extremely high, exceeding 400 mA/cm2 in some patches. The membrane adjacent to the endplate has a current density about fivefold lower than that of the endplate, but about fivefold higher than the membrane 100-200 micron from the endplate. Small local variations in Na current density are recorded in extrajunctional membrane. A sharp decrease in Na current density occurs over the last few hundred micrometers from the tendon. We tested the ability of tetrodotoxin to block Na current in regions close to and far from the endplate and found no evidence for toxin-resistant channels in either region. There was also no obvious difference in the kinetics of Na current in the two regions. On the basis of the Na current densities measured with the loose patch clamp, we conclude that Na channels are abundant in the endplate and near- endplate membrane and are sparse close to the tendon. The current density at the endplate is two to three orders of magnitude higher than at the tendon.

1986-01-01

146

ATP metabolism in skeletal muscle arterioles  

PubMed Central

Abstract The purpose of this study was to investigate the metabolism of Adenosine triphosphate (ATP) in skeletal muscle resistance arterioles and to determine whether this metabolism is altered during the rapid growth phase of the rat. We attempted to quantify ATP metabolism in gastrocnemius first?order arterioles from 8?, 10?, and 12?week?old rats. We measured ATP metabolism using an ATPase/GTPase assay with whole vessel segments as well as using a real?time adenosine biosensor following electric field stimulation. Our first method of measuring ATP metabolism allowed us to measure the amount of free phosphate produced with ATP as a substrate. When ecto?nucleotidase activity was inhibited by ARL67156, pyridoxal phosphate?6?azophenly?2?, 4??disulfonic acid (PPADS), or suramin prior to adding ATP, we found that the rate of phosphate production was significantly reduced by 27%, 21%, and 22%, respectively (P < 0.05). Our second method of measuring ATP metabolism allowed us to measure the amount of adenosine produced following electric field stimulation of the arteriole with and without nucleotidase inhibitors. Surprisingly, we found that adenosine overflow was not attenuated by nucleotidase inhibitors. We concluded that ecto?phosphodieterase/phyrophophatase (E?NPP), ecto?diadenosine polyphosphatase (ApnA), NTPDase1 and 2, and E5NT may be present on the gastrocnemius 1A arteriole and do play a role in ATP metabolism. Between the ages of 8 weeks and 12 weeks, however, overall ATP metabolism may not change.

Stone, Audrey J.; Evanson, Kirk W.; Kluess, Heidi A.

2014-01-01

147

Skeletal muscle denervation activates acetylcholine receptor genes  

PubMed Central

Transcriptional activity of acetylcholine receptor subunit genes was investigated in innervated and denervated chick skeletal muscle. The sciatic nerve of 3-d-old White Leghorn chicks was sectioned unilaterally; after various intervals, nuclei were isolated from operated and sham-operated animals, and run-on assays performed. Nuclei were incubated with 32P-UTP, and total RNA was extracted and hybridized onto filters containing an excess of subunit-specific DNA. Specific transcripts were detected by autoradiography and quantitated densitometrically. A sharp increase in transcriptional activity was observed to begin approximately 1/2 d after the operation and peak 1 d later when transcriptional rates reached approximately seven-, six-, and fivefold control levels for the alpha-, delta-, and gamma-subunit genes, respectively. The specificity of the effect was ascertained by normalization to total RNA synthesis and by the demonstration that several nonreceptor genes respond differently to denervation. These results suggest that a denervation signal reaches the genome to induce receptor expression. In addition, since the increase in mRNA levels significantly exceeds what can be accounted for by increased gene activity, posttranscriptional effects are suggested.

1989-01-01

148

Macrophage Plasticity in Skeletal Muscle Repair  

PubMed Central

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.

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

2014-01-01

149

Functional Skeletal Muscle Formation with a Biologic Scaffold  

PubMed Central

Biologic scaffolds composed of extracellular matrix (ECM) have been used to reinforce or replace damaged or missing musculotendinous tissues in both preclinical studies and in human clinical applications. However, most studies have focused upon morphologic endpoints and few studies have assessed the in-situ functionality of newly formed tissue; especially new skeletal muscle tissue. The objective of the present study was to determine both the in-situ tetanic contractile response and histomorphologic characteristics of skeletal muscle tissue reconstructed using one of four test articles in a rodent abdominal wall model: 1) porcine small intestinal submucosa (SIS)-ECM; 2) carbodiimide-crosslinked porcine SIS-ECM; 3) autologous tissue; or 4) polypropylene mesh. Six months after surgery, the remodeled SIS-ECM showed almost complete replacement by islands and sheets of skeletal muscle, which generated a similar maximal contractile force to native tissue but with greater resistance to fatigue. The autologous tissue graft was replaced by a mixture of collagenous connective tissue, adipose tissue with fewer islands of skeletal muscle compared to SIS-ECM and a similar fatigue resistance to native muscle. Carbodiimide-crosslinked SIS-ECM and polypropylene mesh were characterized by a chronic inflammatory response and produced little or no measureable tetanic force. The findings of this study show that non-crosslinked xenogeneic SIS scaffolds and autologous tissue are associated with the restoration of functional skeletal muscle with histomorphologic characteristics that resemble native muscle.

Valentin, Jolene E.; Turner, Neill J.; Gilbert, Thomas W.; Badylak, Stephen F.

2010-01-01

150

Estimation of skeletal muscle mass from body creatine content  

NASA Technical Reports Server (NTRS)

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.

Pace, N.; Rahlmann, D. F.

1982-01-01

151

Premature Aging in Skeletal Muscle Lacking Serum Response Factor  

PubMed Central

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

Lahoute, Charlotte; Sotiropoulos, Athanassia; Favier, Marilyne; Guillet-Deniau, Isabelle; Charvet, Claude; Ferry, Arnaud; Butler-Browne, Gillian; Metzger, Daniel; Tuil, David; Daegelen, Dominique

2008-01-01

152

Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation.  

PubMed

Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apoB transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma insulin levels after 9 and 12 months, respectively, improved intra peritoneal glucose tolerance after 6 months, and a trend towards increased insulin-stimulated glucose uptake in isolated skeletal muscle. Conclusions. The data suggests that overexpression of apoB decreases skeletal muscle lipid accumulation and attenuates peripheral insulin resistance in obese mice. PMID:24673444

Bartels, Emil D; Ploug, Thorkil; Størling, Joachim; Mandrup-Poulsen, Thomas; Nielsen, Lars B

2014-06-01

153

Nutritive and non-nutritive blood flow in skeletal muscle  

Microsoft Academic Search

The vascular structure of mammalian skeletal muscle has been intensively investigated for the last seventy years. Since the early work of Pappenheimer and Barlow, the existence of a parallel dual vascular pathway has been suggested to explain the differences between total flow and clearance rates of a variety of infused substances. Direct microscopy studies using superficial muscles have shown that

Andrew James Hoy

2004-01-01

154

Functional Morphology of Force Transmission in Skeletal Muscle  

Microsoft Academic Search

The work done by the contractile proteins of muscle in accelerating, decelerating, or maintaining the positions of skeletal elements requires the efficient transmission of tension across the surface membranes of the fibers. The most widely studied sites of tension transmission are the ends of muscle fibers where they contact either connective or epithelial tissues. In most animals, regardless of phylum,

J. A. Trotter

1993-01-01

155

Skeletal Muscle as a Peripheral Modifier of Behavior  

ERIC Educational Resources Information Center

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)

Jenkins, Robert R.

1978-01-01

156

Skeletal muscle cells: from local inflammatory response to active immunity  

Microsoft Academic Search

The skeletal muscles are the major living component of the human body. They are constituted by stable cells, the myofibres, and by adult multipotent stem cells, the satellite cells, which can multiply to regenerate and repair the damaged tissues. Injections of DNA in muscle cells have been used to produce recombinant proteins with opposite goals: somatic reparation of genetic defects,

M Marino; F Scuderi; C Provenzano; E Bartoccioni

2011-01-01

157

Essential Amino Acid Sensing, Signaling, and Transport in the Regulation of Human Muscle Protein Metabolism  

PubMed Central

Purpose of the Review To highlight recent research pertaining to the cellular mechanisms linking amino acid availability, mTORC1 signaling, and muscle protein metabolism. Recent Findings Activation of the mTORC1 pathway in response to amino acids may be dependent upon cellular re-localizaiton of mTORC1, a process that appears to involve the Rag GTPases. Recent studies have also identified other intracellular proteins, such as hVps34 and MAP4K3, and specific amino acid transporters as necessary links between amino acid availablity and mTORC1. In human skeletal muscle, it appears that mTORC1 activity increases the expression of several amino acid transporters, which may be an important adaptive response to sensitize muscle to a subsequent increase in amino acid availability. Summary The precise cellular mechansims linking amino acids to mTORC1 signaling and muscle protein metabolism are currently not well understood. More defined cellular mechansims are beginning to emerge suggesting a role for several intracellular proteins including hVps34, MAP4K3, and the Rag GTPases. Additionally, specific amino acid transporters may have a role both upstream and downstream of mTORC1. Continued investigation into the precise cellular mechanisms linking amino acid availablity and muscle protein metabolsim will help facilitate improvements in existing therapies for conditions of muscle wasting.

Dickinson, Jared M.; Rasmussen, Blake B.

2012-01-01

158

[Skeletal muscle metastasis of rectal carcinoma--a case report].  

PubMed

Skeletal muscle metastasis of carcinoma is comparatively rare. We report a case of metastasis to the quadriceps femoris muscle after the operation for rectal carcinoma. A 70-year-old man underwent rectal amputation in May 2007 due to rectal carcinoma. In May 2008, he noticed a painful tumor in the right femoral region. We obtained the diagnosis of recurrent rectal carcinoma by open biopsy. Simultaneously, lung metastasis was revealed by a close examination. Metastatic tumor resection was performed before chemotherapy, because it was important to preserve his performance status. From June 2008, chemotherapy was started. A year after the second operation, lung metastatic lesions were gradually progressed. At present, new skeletal muscle metastasis is not found. He is receiving chemotherapy in outpatient care. The resection of skeletal muscle metastasis made a contribution to his quality of life. PMID:20037385

Okada, Toshimasa; Nishimura, Taku; Nakamura, Mitsuo; Sakata, Koichiro; Setoguchi, Mihoko; Ihara, Kouichiro

2009-11-01

159

Gene Expression Profiling of Skeletal Muscle of Nursing Piglets  

PubMed Central

To gain insight into the regulation mechanism associated with the rapid gain in skeletal muscle during neonatal period, gene expression profiles of skeletal muscle of nursing pigs was investigated using Affymetrix Porcine GeneChip. A total of 1094 transcripts were detected as differential expression over time course tested (p<0.01, q<0.05). With combinative use of partitioning around medoid and hierarchical clustering, three clusters of transcripts with distinct temporal expression were defined. Gene functional categories and pathways, particularly involved in cell signaling, cell cycle, cell adhesion, ECM-receptor interaction, glycolysis, protein synthesis and degradation, and intracellular transport, were identified. Moreover, we showed 49 of the differentially expressed genes within published QTL regions or with marked deletion effects. Our study demonstrates previously uncharacterized changes in transcription accompanying early postnatal growth of skeletal muscle of pigs. It has highlighted potential cascades and important candidates for further investigation on controlling of postnatal muscle growth.

Jiang, Caode; Shi, Ping; Li, Shun; Dong, Ranran; Tian, Jiawei; Wei, Jin; Luo, Shuang

2010-01-01

160

Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies  

PubMed Central

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

Grumati, Paolo; Bonaldo, Paolo

2012-01-01

161

Systemic Gene Transfer to Skeletal Muscle Using Reengineered AAV Vectors  

PubMed Central

Gene therapy of musculoskeletal disorders warrants efficient gene transfer to a wide range of muscle groups. Reengineered adeno-associated viral (AAV) vectors that selectively transduce muscle tissue following systemic administration are attractive candidates for such applications. Here we provide examples of several lab-derived AAV vectors that display systemic tissue tropism in mice. Methods to evaluate the efficiency of gene transfer to skeletal muscle following intravenous or isolated limb infusion of AAV vectors in mice are discussed in detail.

Phillips, Jana L.; Hegge, Julia; Wolff, Jon A.; Samulski, R. Jude; Asokan, Aravind

2011-01-01

162

Systemic gene transfer to skeletal muscle using reengineered AAV vectors.  

PubMed

Gene therapy of musculoskeletal disorders warrants efficient gene transfer to a wide range of muscle groups. Reengineered adeno-associated viral (AAV) vectors that selectively transduce muscle tissue following systemic administration are attractive candidates for such applications. Here we provide examples of several lab-derived AAV vectors that display systemic tissue tropism in mice. Methods to evaluate the efficiency of gene transfer to skeletal muscle following intravenous or isolated limb infusion of AAV -vectors in mice are discussed in detail. PMID:21194026

Phillips, Jana L; Hegge, Julia; Wolff, Jon A; Samulski, R Jude; Asokan, Aravind

2011-01-01

163

Functional classification of skeletal muscle networks. I. Normal physiology  

PubMed Central

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+ fluxes to bind Ca2+ to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling.

Wang, Yu; Winters, Jack

2012-01-01

164

Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications.  

PubMed

Skeletal muscles contain resident immune cell populations and their abundance and type is altered in inflammatory myopathies, endotoxemia or different types of muscle injury/insult. Within tissues, monocytes differentiate into macrophages and polarize to acquire pro- or anti-inflammatory phenotypes. Skeletal muscle macrophages play a fundamental role in repair and pathogen clearance. These events require a precisely regulated cross-talk between myofibers and immune cells, involving paracrine/autocrine and contact interactions. Skeletal muscle also undergoes continuous repair as a result of contractile activity that involves participation of myokines and anti-inflammatory input. Finally, skeletal muscle is the major site of dietary glucose disposal; therefore, muscle insulin resistance is essential to the development of whole body insulin resistance. Notably, muscle inflammation is emerging as a potential contributor to insulin resistance. Recent reports show that inflammatory macrophage numbers within muscle are elevated during obesity and that muscle cells in vitro can mount autonomous inflammatory responses under metabolic challenge. Here, we review the nature of skeletal muscle inflammation associated with muscle exercise, damage, and regeneration, endotoxin presence, and myopathies, as well as the new evidence of local inflammation arising with obesity that potentially contributes to insulin resistance. PMID:23277185

Pillon, Nicolas J; Bilan, Philip J; Fink, Lisbeth N; Klip, Amira

2013-03-01

165

Energetics of lengthening in mouse and toad skeletal muscles.  

PubMed Central

1. The energetics of lengthening were studied in amphibian and mammalian skeletal muscle. The aims were to determine whether energy absorption during stretch is a general property of skeletal muscle and to investigate the influence of lengthening velocity on energy absorption. 2. Experiments were performed in vitro (21 degrees C) using bundles of muscle fibres from fast-twitch extensor digitorum longus and slow-twitch soleus muscles of the mouse and tibialis anterior muscles of a toad, Bufo marinus. Initial heat production and mechanical work done on muscles were measured during isovelocity lengthening. Enthalpy output during lengthening was calculated as the difference between the amount of heat produced and the work done. 3. For all three muscle types, more energy was put into muscles as work than was produced as heat. Thus, part of the energy put into muscles to stretch them must have been absorbed. 4. For all three muscle types, the amount of energy absorbed was constant at velocities exceeding approximately 0.5 Vmax (Vmax is the maximum shortening velocity), but was significantly lower at slow velocities of lengthening. The same amount of energy was absorbed by all three muscles when lengthened at > or = 0.5 Vmax. 5. It was concluded that absorption of energy during lengthening occurs in mammalian as well as amphibian muscle and that lengthening velocity has only a small effect on the amount of energy absorbed.

Constable, J K; Barclay, C J; Gibbs, C L

1997-01-01

166

COX-2 inhibitor reduces skeletal muscle hypertrophy in mice  

PubMed Central

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.

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

2009-01-01

167

Hypodynamic and hypokinetic condition of skeletal muscles  

NASA Technical Reports Server (NTRS)

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.

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

1980-01-01

168

Growth Factors and Tension-Induced Skeletal Muscle Growth  

NASA Technical Reports Server (NTRS)

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

Vandenburgh, Herman H.

1994-01-01

169

Assessment of calcium sparks in intact skeletal muscle fibers.  

PubMed

Maintaining homeostatic Ca(2+) signaling is a fundamental physiological process in living cells. Ca(2+) sparks are the elementary units of Ca(2+) signaling in the striated muscle fibers that appear as highly localized Ca(2+) release events mediated by ryanodine receptor (RyR) Ca(2+) release channels on the sarcoplasmic reticulum (SR) membrane. Proper assessment of muscle Ca(2+) sparks could provide information on the intracellular Ca(2+) handling properties of healthy and diseased striated muscles. Although Ca(2+) sparks events are commonly seen in resting cardiomyocytes, they are rarely observed in resting skeletal muscle fibers; thus there is a need for methods to generate and analyze sparks in skeletal muscle fibers. Detailed here is an experimental protocol for measuring Ca(2+) sparks in isolated flexor digitorm brevis (FDB) muscle fibers using fluorescent Ca(2+) indictors and laser scanning confocal microscopy. In this approach, isolated FDB fibers are exposed to transient hypoosmotic stress followed by a return to isotonic physiological solution. Under these conditions, a robust Ca(2+) sparks response is detected adjacent to the sarcolemmal membrane in young healthy FDB muscle fibers. Altered Ca(2+) sparks response is detected in dystrophic or aged skeletal muscle fibers. This approach has recently demonstrated that membrane-delimited signaling involving cross-talk between inositol (1,4,5)-triphosphate receptor (IP3R) and RyR contributes to Ca(2+) spark activation in skeletal muscle. In summary, our studies using osmotic stress induced Ca(2+) sparks showed that this intracellular response reflects a muscle signaling mechanism in physiology and aging/disease states, including mouse models of muscle dystrophy (mdx mice) or amyotrophic lateral sclerosis (ALS model). PMID:24638093

Park, Ki Ho; Weisleder, Noah; Zhou, Jingsong; Gumpper, Kristyn; Zhou, Xinyu; Duann, Pu; Ma, Jianjie; Lin, Pei-Hui

2014-01-01

170

Skeletal muscle as a regulator of the longevity protein, Klotho  

PubMed Central

Klotho is a powerful longevity protein that has been linked to the prevention of muscle atrophy, osteopenia, and cardiovascular disease. Similar anti-aging effects have also been ascribed to exercise and physical activity. While an association between muscle function and Klotho expression has been previously suggested from longitudinal cohort studies, a direct relationship between circulating Klotho and skeletal muscle has not been investigated. In this paper, we present a review of the literature and preliminary evidence that, together, suggests Klotho expression may be modulated by skeletal muscle activity. Our pilot clinical findings performed in young and aged individuals suggest that circulating Klotho levels are upregulated in response to an acute exercise bout, but that the response may be dependent on fitness level. A similar upregulation of circulating Klotho is also observed in response to an acute exercise in young and old mice, suggesting that this may be a good model for mechanistically probing the role of physical activity on Klotho expression. Finally, we highlight overlapping signaling pathways that are modulated by both Klotho and skeletal muscle and propose potential mechanisms for cross-talk between the two. It is hoped that this review will stimulate further consideration of the relationship between skeletal muscle activity and Klotho expression, potentially leading to important insights into the well-documented systemic anti-aging effects of exercise.

Avin, Keith G.; Coen, Paul M.; Huang, Wan; Stolz, Donna B.; Sowa, Gwendolyn A.; Dube, John J.; Goodpaster, Bret H.; O'Doherty, Robert M.; Ambrosio, Fabrisia

2014-01-01

171

Kelch proteins: emerging roles in skeletal muscle development and diseases  

PubMed Central

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.

2014-01-01

172

Smad7 promotes and enhances skeletal muscle differentiation.  

PubMed

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. PMID:16880533

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

2006-08-01

173

Localisation of AMPK ? subunits in cardiac and skeletal muscles.  

PubMed

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 ? subunits cause inherited disorders of either cardiac or skeletal muscle. AMPK?2 mutations cause hypertrophic cardiomyopathy with glycogen deposition and conduction abnormalities; mutations in AMPK?3 result in increased skeletal muscle glycogen. In order to gain further insight into the roles of the different ? subunits in muscle and into possible disease mechanisms, we localised the ?2 and ?3 subunits, along with the more abundant ?1 subunit, by immunofluorescence in cardiomyocytes and skeletal muscle fibres. The predominant cardiac ?2 variant, ?2-3B, 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 AMPK?3 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 ?2-3B- and ?3-containing AMPK suggests that these trimers may have similar functions in the different muscles. AMPK containing ?2-3B was detected in oxidative skeletal muscles which had low expression of ?3, 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 ? subunit and this differential localisation may direct substrate selection and specify particular functional roles. PMID:24037260

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

2013-12-01

174

Establishment of bipotent progenitor cell clone from rat skeletal muscle.  

PubMed

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. PMID:22111633

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

2011-12-01

175

Growth factor involvement in tension-induced skeletal muscle growth  

NASA Technical Reports Server (NTRS)

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.

Vandenburgh, Herman H.

1993-01-01

176

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

PubMed

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. PMID:23437068

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

177

Estradiol stimulates mitochondrial biogenesis and adiponectin expression in skeletal muscle.  

PubMed

Sexual dimorphism has been found in mitochondrial features of skeletal muscle, with female rats showing greater mitochondrial mass and function compared with males. Adiponectin is an insulin-sensitizing adipokine whose expression has been related to mitochondrial function and that is also expressed in skeletal muscle, where it exerts local metabolic effects. The aim of this research was to elucidate the role of sex hormones in modulation of mitochondrial function, as well as its relationship with adiponectin production in rat skeletal muscle. An in vivo study with ovariectomized Wistar rats receiving or not receiving 17?-estradiol (E2) (10??g/kg per 48?h for 4 weeks) was carried out, in parallel with an assay of cultured myotubes (L6E9) treated with E2 (10?nM), progesterone (Pg; 1??M), or testosterone (1??M). E2 upregulated the markers of mitochondrial biogenesis and dynamics, and also of mitochondrial function in skeletal muscle and L6E9. Although in vivo E2 supplementation only partially restored the decreased adiponectin expression levels induced by ovariectomy, these were enhanced by E2 and Pg treatment in cultured myotubes, whereas testosterone showed no effects. Adiponectin receptor 1 expression was increased by E2 treatment, both in vivo and in vitro, but testosterone decreased it. In conclusion, our results are in agreement with the sexual dimorphism previously reported in skeletal muscle mitochondrial function and indicate E2 to be its main effector, as it enhances mitochondrial function and diminishes oxidative stress. Moreover, our data support the idea of the existence of a link between mitochondrial function and adiponectin expression in skeletal muscle, which could be modulated by sex hormones. PMID:24681828

Capllonch-Amer, Gabriela; Sbert-Roig, Miquel; Galmés-Pascual, Bel M; Proenza, Ana M; Lladó, Isabel; Gianotti, Magdalena; García-Palmer, Francisco J

2014-06-01

178

Exercise-Induced Skeletal Muscle Damage.  

ERIC Educational Resources Information Center

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)

Evans, William J.

1987-01-01

179

Biochemical Events during Hypertrophy of Skeletal Muscle.  

National Technical Information Service (NTIS)

Using a previously developed technique for inducing rapid hypertrophy of the soleus and plantaris muscle it was demonstrated that work-induced hypertrophy does not require pituitary hormones. Gain in weight of the soleus muscle occurs primarily through an...

A. L. Goldberg

1971-01-01

180

Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle  

PubMed Central

Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hematopoetic (CD45-) cells were evaluated in wild type (WT) and ?7 integrin transgenic (?7Tg) mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1+CD45? stem cells were increased 2-fold in WT muscle post-exercise. The ?7 integrin regulated the presence of Sca-1+ cells, with expansion occurring in ?7Tg muscle and minimal cells present in muscle lacking the ?7 integrin. Sca-1+CD45? cells isolated from ?7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs), predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7+ cells and facilitated formation of eMHC+DiI? fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an ?7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the ?7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy.

Valero, M. Carmen; Huntsman, Heather D.; Liu, Jianming; Zou, Kai; Boppart, Marni D.

2012-01-01

181

Functional heterogeneity of side population cells in skeletal muscle  

SciTech Connect

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.

Uezumi, Akiyoshi [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan); Ojima, Koichi [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan); Fukada, So-ichiro [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan); Ikemoto, Madoka [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan); Masuda, Satoru [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan); Miyagoe-Suzuki, Yuko [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan); Takeda, Shin'ichi [Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502 (Japan)]. E-mail: takeda@ncnp.go.jp

2006-03-17

182

Diffraction Ellipsometry Studies of Skeletal Muscle Structure  

Microsoft Academic Search

Many of the techniques used to study the structure and contraction mechanism of muscle rely on the interaction of light or other electromagnetic radiation with the muscle. Some of the most important of these techniques are light and electron microscopy, x-ray diffraction, spectroscopy of muscle fibers \\

William Lloyd Kerr

1991-01-01

183

Evaluation systems of generated forces of skeletal muscle cell-based bio-actuators.  

PubMed

Skeletal muscle is the most abundant tissue in the body, and its capability of generating an active force is one of the most significant features. In order to study the physiology and disorders related to the skeletal muscle using cells in vitro, the active force should be evaluated, in addition to molecular and cell biological experiments performed. This article reviews an evaluation system for the active tension generated by cultured skeletal muscle cells or tissue-engineered skeletal muscles. First, we focused on experimental models involving a single or several myotubes. Then, we focused on the systems for tissue-engineered skeletal muscles consisting of much larger numbers of myotubes. Such systems can be used to study the physiology of the skeletal muscle, screen drug candidates for skeletal muscle-related disorders, and improve the function of tissue-engineered skeletal muscle. PMID:23026451

Shimizu, Kazunori; Fujita, Hideaki; Nagamori, Eiji

2013-02-01

184

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

PubMed Central

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.

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

185

Essential role for Dicer during skeletal muscle development  

PubMed Central

microRNAs (miRNAs) regulate gene expression post-transcriptionally by targeting mRNAs for degradation or by inhibiting translation. Dicer is an RNase III endonuclease which processes miRNA precursors into functional 21-23 nucleotide RNAs that are subsequently incorporated into the RNA-induced silencing complex. miRNA-mediated gene regulation is important for organogenesis of a variety of tissues including limb, lung and skin. To gain insight into the roles of Dicer and miRNAs in mammalian skeletal muscle development, we eliminated Dicer activity specifically in the myogenic compartment during embryogenesis. Dicer activity is essential for normal muscle development during embryogenesis and Dicer muscle mutants have reduced muscle miRNAs, die perinatally and display decreased skeletal muscle mass accompanied by abnormal myofiber morphology. Dicer mutant muscles also show increased apoptosis and Cre-mediated loss of Dicer in Myod-converted myoblasts results in enhanced cell death. These observations demonstrate key roles for Dicer in skeletal muscle and implicate miRNAs as critical components required for embryonic myogenesis.

O'Rourke, Jason R.; Georges, Sara A.; Seay, Howard R.; Tapscott, Stephen J.; McManus, Michael T.; Goldhamer, David J.; Swanson, Maurice S.; Harfe, Brian D.

2009-01-01

186

Monocarboxylate transporter expression at the onset of skeletal muscle regeneration  

PubMed Central

The onset of skeletal muscle regeneration is characterized by proliferating myoblasts. Proliferating myoblasts have an increased energy demand and lactate exchange across the sarcolemma can be used to address this increased demand. Monocarboxylate transporters (MCTs) are involved in lactate transport across the sarcolemma and are known to be affected by various physiological stimuli. However, MCT expression at the onset of skeletal muscle regeneration has not been determined. The purpose of this study was to determine if skeletal muscle regeneration altered MCT expression in regenerating tibialis anterior (TA) muscle. Male C57/BL6 mice were randomly assigned to either a control (uninjured) or bupivacaine (injured) group. Three days post injection, the TA was extracted for determination of protein and gene expression. A 21% decrease in muscle mass to tibia length (2.4 ± 0.1 mg/mm vs. 1.9 ± 0.2 mg/mm, P < 0.02) was observed. IGF-1 and MyoD gene expression increased 5.0-fold (P < 0.05) and 3.5-fold (P < 0.05), respectively, 3 days post bupivacaine injection. MCT-1 protein was decreased 32% (P < 0.03); however, MCT-1 gene expression was not altered. There was no difference in MCT4 protein or gene expression. Lactate dehydrogenase (LDH)-A protein expression increased 71% (P < 0.0004). Protein levels of LDH-B and mitochondrial enzyme cytochrome C oxidase subunit decreased 3 days post bupivacaine injection. CD147 and PKC-? protein increased 64% (P < 0.03) and 79% (P < 0.02), respectively. MCT1 but not MCT4 expression is altered at the onset of skeletal muscle regeneration possibly in an attempt to regulate lactate uptake and use by skeletal muscle cells.

Washington, Tyrone A; Brown, Lemuel; Smith, Dameon A; Davis, Gina; Baum, Jamie; Bottje, Walter

2013-01-01

187

TGF-?1 enhances contractility in engineered skeletal muscle  

PubMed Central

Scaffoldless engineered 3D skeletal muscle tissue created from satellite cells offers the potential to replace muscle tissue that is lost due to severe trauma or disease. Transforming growth factor-beta 1 (TGF-?1) plays a vital role in mediating migration and differentiation of satellite cells during the early stages of muscle development. Additionally, TGF-?1 promotes collagen type I synthesis in the extracellular matrix (ECM) of skeletal muscle, which provides a passive elastic substrate to support myofibres and facilitate the transmission of force. To determine the role of TGF-?1 in skeletal muscle construct formation and contractile function in vitro, we created tissue-engineered 3D skeletal muscle constructs with varying levels of recombinant TGF-?1 added to the cell culture medium. Prior to the addition of TGF-?1, the primary cell population was composed of 75% Pax7-positive cells. The peak force for twitch, tetanus and spontaneous force were significantly increased in the presence of 2.0 ng/ml TGF-?1 when compared to 0, 0.5 and 1.0 ng/ml TGF-?1. Visualization of the cellular structure with H&E and with immunofluorescence staining for sarcomeric myosin heavy chains and collagen type I showed denser regions of better organized myofibres in the presence of 2.0 ng/ml TGF-?1 versus 0, 0.5 and 1.0 ng/ml. The addition of 2.0 ng/ml TGF-?1 to the culture medium of engineered 3D skeletal muscle constructs enhanced contractility and extracellular matrix organization.

Weist, Michael R.; Wellington, Michael S.; Bermudez, Jacob E.; Kostrominova, Tatiana Y.; Mendias, Christopher L.; Arruda, Ellen M.; Larkin, Lisa M.

2014-01-01

188

Monocarboxylate transporter expression at the onset of skeletal muscle regeneration.  

PubMed

The onset of skeletal muscle regeneration is characterized by proliferating myoblasts. Proliferating myoblasts have an increased energy demand and lactate exchange across the sarcolemma can be used to address this increased demand. Monocarboxylate transporters (MCTs) are involved in lactate transport across the sarcolemma and are known to be affected by various physiological stimuli. However, MCT expression at the onset of skeletal muscle regeneration has not been determined. The purpose of this study was to determine if skeletal muscle regeneration altered MCT expression in regenerating tibialis anterior (TA) muscle. Male C57/BL6 mice were randomly assigned to either a control (uninjured) or bupivacaine (injured) group. Three days post injection, the TA was extracted for determination of protein and gene expression. A 21% decrease in muscle mass to tibia length (2.4 ± 0.1 mg/mm vs. 1.9 ± 0.2 mg/mm, P < 0.02) was observed. IGF-1 and MyoD gene expression increased 5.0-fold (P < 0.05) and 3.5-fold (P < 0.05), respectively, 3 days post bupivacaine injection. MCT-1 protein was decreased 32% (P < 0.03); however, MCT-1 gene expression was not altered. There was no difference in MCT4 protein or gene expression. Lactate dehydrogenase (LDH)-A protein expression increased 71% (P < 0.0004). Protein levels of LDH-B and mitochondrial enzyme cytochrome C oxidase subunit decreased 3 days post bupivacaine injection. CD147 and PKC-? protein increased 64% (P < 0.03) and 79% (P < 0.02), respectively. MCT1 but not MCT4 expression is altered at the onset of skeletal muscle regeneration possibly in an attempt to regulate lactate uptake and use by skeletal muscle cells. PMID:24303150

Washington, Tyrone A; Brown, Lemuel; Smith, Dameon A; Davis, Gina; Baum, Jamie; Bottje, Walter

2013-09-01

189

Functional classification of skeletal muscle networks. II. Applications to pathophysiology  

PubMed Central

In our preceding companion paper (Wang Y, Winters J, Subramaniam S. J Appl Physiol. doi: 10.1152/japplphysiol.01514.2011), we used extensive expression profile data on normal human subjects, in combination with legacy knowledge to classify skeletal muscle function into four models, namely excitation-activation, mechanical, metabolic, and signaling-production model families. In this paper, we demonstrate how this classification can be applied to study two well-characterized myopathies: amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Using skeletal muscle profile data from ALS and DMD patients compared with that from normal subjects, normal young in the case of DMD, we delineate molecular mechanisms that are causative and consequential to skeletal muscle dysfunction. In ALS, our analysis establishes the metabolic role and specifically identifies the mechanisms of calcium dysregulation and defects in mitochondrial transport of materials as important for muscle dysfunction. In DMD, we illustrate how impaired mechanical function is strongly coordinated with other three functional networks, resulting in transformation of the skeletal muscle into hybrid forms as a compensatory mechanism. Our functional models also provide, in exquisite detail, the mechanistic role of myriad proteins in these four families in normal and disease function.

Wang, Yu; Winters, Jack

2012-01-01

190

Time course of skeletal muscle regeneration after severe trauma  

PubMed Central

Background and purpose Animal models of skeletal muscle injury should be thoroughly described and should mimic the clinical situation. We established a model of a critical size crush injury of the soleus muscle in rats. The aim was to describe the time course of skeletal muscle regeneration using mechanical, histological, and magnetic resonance (MR) tomographic methods. Methods Left soleus muscles of 36 Sprague-Dawley rats were crushed in situ in a standardized manner. We scanned the lower legs of 6 animals by 7-tesla MR one week, 4 weeks, and 8 weeks after trauma. Regeneration was evaluated at these times by in vivo measurement of muscle contraction forces after fast-twitch and tetanic stimulation (groups 1W, 4W, 8W; 6 per group). Histological and immunohistological analysis was performed and the amount of fibrosis within the injured muscles was determined histomorphologically. Results MR signals of the traumatized soleus muscles showed a clear time course concerning microstructure and T1 and T2 signal intensity. Newly developed neural endplates and myotendinous junctions could be seen in the injured zones of the soleus. Tetanic force increased continuously, starting at 23% (SD 4) of the control side (p < 0.001) 1 week after trauma and recovering to 55% (SD 23) after 8 weeks. Fibrotic tissue occupied 40% (SD 4) of the traumatized muscles after the first week, decreased to approximately 25% after 4 weeks, and remained at this value until 8 weeks. Interpretation At both the functional level and the morphological level, skeletal muscle regeneration follows a distinct time course. Our trauma model allows investigation of muscle regeneration after a standardized injury to muscle fibers.

2011-01-01

191

Skeletal Muscle Catabolism in TNBS-Induced Murine Colitis  

PubMed Central

The present study determined whether the muscle atrophy produced by colitis is associated with altered rates of muscle protein synthesis or degradation, as well as the potential role of the local (e.g., muscle) insulin-like growth factor (IGF) system and muscle-specific ubiquitin E3 ligases atrogin-1 and MuRF1 in mediating altered muscle protein balance. Colitis was induced in C57BL/6 mice by intra-rectal administration of trinitrobenzne sulfonic acid (TNBS), and blood and tissues collected on day 10. Mice with inflammatory bowel disease (IBD) demonstrated reduced skeletal muscle mass and protein content, whereas colonic segment weight and gross damage score were both increased in mice with colitis, compared to time-matched control values. There was no change in muscle protein synthesis in mice with IBD, but there was an increased protein breakdown (45%), proteasome activity (85%), and mRNA expression for atrogin-1 and MuRF1 (200–300%) in muscle. These changes were associated with a reduction in liver (but not muscle) IGF-I mRNA as well as a reduction in both total and free IGF-I in the blood. Colitis decreased the hepatic content of IGF binding protein (IGFBP)-3 mRNA by 40% and increased IGFBP-1 mRNA by 100%. In contrast, colitis did alter IGFBP mRNAs in muscle. The TNF?, IL-6 and NOS2 mRNA content of both liver and skeletal muscle was increased in TNBS-treated mice, and plasma TNF? and IL-6 concentrations were also elevated. These data suggest TNBS-induced colitis is independent of a change in muscle protein synthesis but dependent on stimulation of protein degradation via increased expression of muscle-specific atrogenes, which may be mediated in part by the reduction in circulating concentration of IGF-I and the concomitant increase in inflammatory mediators observed in the blood and muscle per se.

Puleo, Frances; Meirelles, Katia; Navaratnarajah, Maithili; Fitzpatrick, Leo; Shumate, Margaret L.; Cooney, Robert N.; Lang, Charles H.

2010-01-01

192

Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading  

NASA Technical Reports Server (NTRS)

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.

Howard, G.; Steffen, J. M.; Geoghegan, T. E.

1989-01-01

193

Glucocorticoid-induced skeletal muscle atrophy.  

PubMed

Many pathological states characterized by muscle atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy is characterized by fast-twitch, glycolytic muscles atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced muscle atrophy results from increased protein breakdown and decreased protein synthesis. Increased muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in muscle protein turnover could be explained by changes in the muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a muscle anabolic growth factor and Myostatin, a muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced muscle atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. PMID:23806868

Schakman, O; Kalista, S; Barbé, C; Loumaye, A; Thissen, J P

2013-10-01

194

Glyconeogenic pathway in isolated skeletal muscles of rats.  

PubMed

Although the conversion of lactate to glycogen (glyconeogenesis) in muscle was demonstrated a long time ago, the biochemical reactions responsible for this process are still a controversial matter. In the present study, advantage was taken from the specific inhibition induced by phenylalanine on muscle pyruvate kinase (PK) to investigate the role of reverse PK activity in muscle glyconeogenesis. Addition of phenylalanine to the incubation medium of a preparation of isolated, intact skeletal muscles that maintain metabolic activity for several hours reduced by 50% the rate of incorporation of [14C]lactate or [14C]bicarbonate into muscle glycogen. Muscle extracts presented high levels of maximal activity of PK in the reverse direction, which was completely blocked in the presence of phenylalanine. In contrast, mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), did not affect the incorporation of 14C from either lactate or bicarbonate into muscle glycogen. Maximal PEPCK activity was much lower in muscle extracts than in gluconeogenic or glyceroneogenic tissues and was suppressed in the presence of mercaptopicolinic acid. The data suggest that a reversal of the metabolic flux through the reaction catalyzed by PK contributes to the accumulation of lactate-derived glycogen that occurs in skeletal muscle under certain physiological conditions. PMID:11934259

Xavier, Analúcia Rampazzo; Roselino, José Eduardo de Salles; Resano, Neusa Maria Zanon; Garófalo, Maria Antonieta Rissato; Migliorini, Renato Helios; Kettelhut, Isis do Carmo

2002-02-01

195

Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture.  

PubMed

Syncoilin is a striated muscle-specific intermediate filament-like protein, which is part of the dystrophin-associated protein complex (DPC) at the sarcolemma and provides a link between the extracellular matrix and the cytoskeleton through its interaction with alpha-dystrobrevin and desmin. Its upregulation in various neuromuscular diseases suggests that syncoilin may play a role in human myopathies. To study the functional role of syncoilin in cardiac and skeletal muscle in vivo, we generated syncoilin-deficient (syncoilin-/-) mice. Our detailed analysis of these mice up to 2 yr of age revealed that syncoilin is entirely dispensable for cardiac and skeletal muscle development and maintenance of cellular structure but is required for efficient lateral force transmission during skeletal muscle contraction. Notably, syncoilin-/- skeletal muscle generates less maximal isometric stress than wild-type (WT) muscle but is as equally susceptible to eccentric contraction-induced injury as WT muscle. This suggests that syncoilin may play a supportive role for desmin in the efficient coupling of mechanical stress between the myofibril and fiber exterior. It is possible that the reduction in isometric stress production may predispose the syncoilin skeletal muscle to a dystrophic condition. PMID:18367591

Zhang, Jianlin; Bang, Marie-Louise; Gokhin, David S; Lu, Yingchun; Cui, Li; Li, Xiaodong; Gu, Yusu; Dalton, Nancy D; Scimia, Maria Cecilia; Peterson, Kirk L; Lieber, Richard L; Chen, Ju

2008-05-01

196

Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture  

PubMed Central

Syncoilin is a striated muscle-specific intermediate filament-like protein, which is part of the dystrophin-associated protein complex (DPC) at the sarcolemma and provides a link between the extracellular matrix and the cytoskeleton through its interaction with ?-dystrobrevin and desmin. Its upregulation in various neuromuscular diseases suggests that syncoilin may play a role in human myopathies. To study the functional role of syncoilin in cardiac and skeletal muscle in vivo, we generated syncoilin-deficient (syncoilin?/?) mice. Our detailed analysis of these mice up to 2 yr of age revealed that syncoilin is entirely dispensable for cardiac and skeletal muscle development and maintenance of cellular structure but is required for efficient lateral force transmission during skeletal muscle contraction. Notably, syncoilin?/? skeletal muscle generates less maximal isometric stress than wild-type (WT) muscle but is as equally susceptible to eccentric contraction-induced injury as WT muscle. This suggests that syncoilin may play a supportive role for desmin in the efficient coupling of mechanical stress between the myofibril and fiber exterior. It is possible that the reduction in isometric stress production may predispose the syncoilin skeletal muscle to a dystrophic condition.

Zhang, Jianlin; Bang, Marie-Louise; Gokhin, David S.; Lu, Yingchun; Cui, Li; Li, Xiaodong; Gu, Yusu; Dalton, Nancy D.; Scimia, Maria Cecilia; Peterson, Kirk L.; Lieber, Richard L.; Chen, Ju

2009-01-01

197

Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle.  

PubMed

Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connecting skeletal muscle to the lateral white matter of the spinal cord by grafting the distal stump of the transected motor nerve produced functional muscle reinnervation. The restored neuromuscular activity became resistant to common curare blockers but sensitive to the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Analysis of the regenerated nerve disclosed new glutamatergic axons and the disappearance of cholinergic fibers. Many axons belonged to the supraspinal neurons located in the red nucleus and the brainstem nuclei. Finally, the innervated muscle displayed high expression and clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits glutamate receptors 1 and 2. Our data suggest that supraspinal neurons can target skeletal muscle, which retains the plasticity to generate functional glutamatergic NMJ. PMID:15937120

Brunelli, Giorgio; Spano, Pierfranco; Barlati, Sergio; Guarneri, Bruno; Barbon, Alessandro; Bresciani, Roberto; Pizzi, Marina

2005-06-14

198

Protection of heart and skeletal muscle by heat shock proteins.  

PubMed

This introduction includes a brief description of 4 papers that were prepared after the symposium The stress response in muscle: mechanisms and functional implications, which was presented at the Canadian Society for Exercise Physiology (CSEP) annual meeting in the autumn of 2006. These papers discuss the role heat-shock proteins (HSPs) play in protecting both cardiac and skeletal muscle from ischemic injury, contraction-induced injury, and aging, and focus on the molecular basis for the cytoprotective effects of HSPs. PMID:18923579

Tupling, A Russell

2008-10-01

199

Prion Protein Expression and Functional Importance in Skeletal Muscle  

PubMed Central

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.

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

2011-01-01

200

Myodulin is a novel potential angiogenic factor in skeletal muscle  

Microsoft Academic Search

We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in

Didier F Pisani; Patricia M Pierson; Ali Massoudi; Lilian Leclerc; Angèle Chopard; Jean-François Marini; Claude A Dechesne

2004-01-01

201

Ultrastructural alterations in skeletal muscle fibers of rats after exercise  

NASA Technical Reports Server (NTRS)

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.

Akuzawa, M.; Hataya, M.

1982-01-01

202

Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington's disease mutation  

Microsoft Academic Search

Huntington's disease (HD) is a neurodegenerative disorder with complex symptoms dominated by progressive motor dysfunction. Skeletal muscle atrophy is common in HD patients. Because the HD mutation is expressed in skeletal muscle as well as brain, we wondered whether the muscle changes arise from primary pathology. We used R6 ? 2 transgenic mice for our studies. Unlike denervation atrophy, skeletal

Richard R. Ribchester; Derek Thomson; Nigel I. Wood; Tim Hinks; Thomas H. Gillingwater; Thomas M. Wishart; Felipe A. Court; A. Jennifer Morton

2004-01-01

203

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

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence suggests involvement of the peroxisome proliferator- activated receptors (PPARs) and PPAR-c coactivator (PGC)-1a in regulation of skeletal muscle morphology and metabolism,

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

2007-01-01

204

Validation of shear wave elastography in skeletal muscle.  

PubMed

Skeletal muscle is a very dynamic tissue, thus accurate quantification of skeletal muscle stiffness throughout its functional range is crucial to improve the physical functioning and independence following pathology. Shear wave elastography (SWE) is an ultrasound-based technique that characterizes tissue mechanical properties based on the propagation of remotely induced shear waves. The objective of this study is to validate SWE throughout the functional range of motion of skeletal muscle for three ultrasound transducer orientations. We hypothesized that combining traditional materials testing (MTS) techniques with SWE measurements will show increased stiffness measures with increasing tensile load, and will correlate well with each other for trials in which the transducer is parallel to underlying muscle fibers. To evaluate this hypothesis, we monitored the deformation throughout tensile loading of four porcine brachialis whole-muscle tissue specimens, while simultaneously making SWE measurements of the same specimen. We used regression to examine the correlation between Young's modulus from MTS and shear modulus from SWE for each of the transducer orientations. We applied a generalized linear model to account for repeated testing. Model parameters were estimated via generalized estimating equations. The regression coefficient was 0.1944, with a 95% confidence interval of (0.1463-0.2425) for parallel transducer trials. Shear waves did not propagate well for both the 45° and perpendicular transducer orientations. Both parallel SWE and MTS showed increased stiffness with increasing tensile load. This study provides the necessary first step for additional studies that can evaluate the distribution of stiffness throughout muscle. PMID:23953670

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

2013-09-27

205

Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation  

PubMed Central

Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (“pain-sensing” nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2– 4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain.

Tague, Sarah E.; Clarke, Gwenaelle L.; Winter, Michelle K.; McCarson, Kenneth E.; Wright, Douglas E.; Smith, Peter G.

2012-01-01

206

Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle.  

PubMed Central

Skeletal muscle protein and amino acid metabolism change after surgical trauma during a period characterized by skeletal muscle protein catabolism. Available total parenteral nutrition (TPN) not containing glutamine does not prevent these changes, while TPN enriched with glutamine has been shown to have beneficial effects on postoperative skeletal muscle protein metabolism. Glutamine, in the form of a dipeptide, alanyl-glutamine, was added to TPN. Patients undergoing elective cholecystectomy were given postoperative TPN. Two groups received isocaloric and isonitrogenous conventional TPN, one group with (n = 8) and the other without an addition of alanyl-glutamine (n = 8). Skeletal muscle protein metabolism was studied in muscle biopsy specimens from which the muscle free amino acid pattern and the concentration and size distribution of ribosomes, serving as a measure of protein synthesis, were determined. In the control group, muscle free glutamine decreased by 38.8% +/- 6.6% and the polyribosome concentration per mg of DNA decreased by 21% +/- 5.2% after operation. In the group given TPN supplemented with alanyl-glutamine, these two parameters of muscle protein and amino acid metabolism did not change significantly. Compared to the control group, whole-body nitrogen balance was improved after operation by the addition of alanyl-glutamine to TPN (p less than 0.01). Muscle free glutamine and muscle protein synthesis were preserved after operation and the whole-body nitrogen balance was improved by adding glutamine in the form of alanyl-glutamine to TPN. The dipeptide alanyl-glutamine seems to be a suitable means of providing glutamine in a stable form.

Hammarqvist, F; Wernerman, J; von der Decken, A; Vinnars, E

1990-01-01

207

Skeletal muscle: Energy metabolism, fiber types, fatigue and adaptability  

Microsoft Academic Search

Skeletal muscles cope with a large range of activities, from being able to support the body weight during long periods of upright standing to perform explosive movements in response to an unexpected threat. This requires systems for energy metabolism that can provide energy during long periods of moderately increased energy consumption as well as being able to rapidly increasing the

Håkan Westerblad; Joseph D. Bruton; Abram Katz

2010-01-01

208

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

Microsoft Academic Search

BACKGROUND: Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential

Kay Ohlendieck

2011-01-01

209

Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates  

Microsoft Academic Search

Recent studies have shown that cells from the bone marrow can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved have remained unknown, and the validity of the observation has been questioned. Here, we use transplantation of single CD45+ hematopoietic stem cells (HSCs) to demonstrate that the entire circulating myogenic activity in

Fernando D Camargo; Rahshaana Green; Yassemi Capetenaki; Kathyjo A Jackson; Margaret A Goodell

2003-01-01

210

Lateral force transmission across costameres in skeletal muscle.  

PubMed

In skeletal muscle, contractile force can be transmitted laterally between the z-disks and M-lines of neighboring myofibrils, across the sarcolemma, and through the extracellular matrix to the tendon. Here we examine the data that support this model and the sarcolemmal properties and structures, termed "costameres," that are consistent with it. PMID:12715970

Bloch, Robert J; Gonzalez-Serratos, Hugo

2003-04-01

211

ISOLATION AND CHARACTERIZATION OF THE SARCOPLASMIC RETICULUM OF SKELETAL MUSCLE  

Microsoft Academic Search

The sarcoplasmic reticulum (SR) of rabbit skeletal muscle was studied after isolation of a vesicle fraction and of vesicular subfractions by means of differential and density gradient centrifugations . The different fractions were examined electron microscopically by negative and positive staining ; their content in protein and phospholipid and their ability to bind Ca++ were determined . After homogenization, differential

JEANINE-ANNE HEUSON-STIENNON; JEAN-CLAUDE WANSON; PIERRE DROCHMANS

1972-01-01

212

Studies of Regeneration of Mammalian Skeletal Muscle.  

National Technical Information Service (NTIS)

Muscles of rat hind limbs were minced into 1mm fragments and transplanted. A transplant of tibialis anterior into its own bed was more likely to regenerate than one into a recipient rat. Spinal transection or prior deveration of the muscle also resulted i...

A. J. Buller J. Hodgson D. M. Lewis B. Salafsky

1974-01-01

213

Differential global gene expression in red and white skeletal muscle  

NASA Technical Reports Server (NTRS)

The differences in gene expression among the fiber types of skeletal muscle have long fascinated scientists, but for the most part, previous experiments have only reported differences of one or two genes at a time. The evolving technology of global mRNA expression analysis was employed to determine the potential differential expression of approximately 3,000 mRNAs between the white quad (white muscle) and the red soleus muscle (mixed red muscle) of female ICR mice (30-35 g). Microarray analysis identified 49 mRNA sequences that were differentially expressed between white and mixed red skeletal muscle, including newly identified differential expressions between muscle types. For example, the current findings increase the number of known, differentially expressed mRNAs for transcription factors/coregulators by nine and signaling proteins by three. The expanding knowledge of the diversity of mRNA expression between white and mixed red muscle suggests that there could be quite a complex regulation of phenotype between muscles of different fiber types.

Campbell, W. G.; Gordon, S. E.; Carlson, C. J.; Pattison, J. S.; Hamilton, M. T.; Booth, F. W.

2001-01-01

214

Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation  

Microsoft Academic Search

ABSTRACT Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced,sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight fasted 7-day-old piglets were,treated with rapamycin,(an inhibitor of mammalian,target of rapamycin,complex 1\\/mTORC1) for 1 h and then infused with

Agus Suryawan; Asumthia S. Jeyapalan; Renan A. Orellana; Fiona A. Wilson; Hanh V. Nguyen; Teresa A. Davis

2008-01-01

215

Functional classification of skeletal muscle networks. I. Normal physiology.  

PubMed

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca(2+) fluxes to bind Ca(2+) to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling. PMID:23085959

Wang, Yu; Winters, Jack; Subramaniam, Shankar

2012-12-15

216

The effect of heat stress on skeletal muscle contractile properties.  

PubMed

An elevated heat-shock protein (HSP) content protects cells and tissues, including skeletal muscles, from certain stressors. We determined if heat stress and the elevated HSP content that results is correlated with protection of contractile characteristics of isolated fast and slow skeletal muscles when contracting at elevated temperatures. To elevate muscle HSP content, one hindlimb of Sprague-Dawley rats (21-28 days old, 70-90 g) was subjected to a 15 min 42 °C heat-stress. Twenty-four hours later, both extensor digitorum longus (EDL) and soleus muscles were removed, mounted in either 20 °C or 42 °C Krebs-Ringer solution, and electrically stimulated. Controls consisted of the same muscles from the contra-lateral (non-stressed) hindlimbs as well as muscles from other (unstressed) animals. Isolated muscles were twitched and brought to tetanus every 5 min for 30 min. As expected, HSP content was elevated in muscles from the heat-stressed limbs when compared with controls. Regardless of prior treatment, both EDL and soleus twitch tensions were lower at 42 °C when compared with 20 °C. In addition, when incubated at 42 °C, both muscles showed a drop in twitch tension between 5 and 30 min. For tetanic tension, both muscles also showed an increase in tension between 5 and 30 min when stimulated at 20 °C regardless of treatment but when stimulated at 42 °C no change was observed. No protective effect of an elevated HSP content was observed for either muscle. In conclusion, although heat stress caused an elevation in HSP content, no protective effects were conferred to isolated contracting muscles. PMID:24264930

Locke, Marius; Celotti, Carlo

2014-07-01

217

Carnosine loading and washout in human skeletal muscles.  

PubMed

Carnosine (beta-alanyl-L-histidine) is present in high concentrations in human skeletal muscles. The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content both in trained and untrained humans. Little human data exist about the dynamics of the muscle carnosine content, its metabolic regulation, and its dependence on muscle fiber type. The present study aimed to investigate in three skeletal muscle types the supplementation-induced amplitude of carnosine synthesis and its subsequent elimination on cessation of supplementation (washout). Fifteen untrained males participated in a placebo-controlled double-blind study. They were supplemented for 5-6 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine was quantified in soleus, tibialis anterior, and medial head of the gastrocnemius by proton magnetic resonance spectroscopy (MRS), before and after supplementation and 3 and 9 wk into washout. The beta-alanine supplementation significantly increased the carnosine content in soleus by 39%, in tibialis by 27%, and in gastrocnemius by 23% and declined post-supplementation at a rate of 2-4%/wk. Average muscle carnosine remained increased compared with baseline at 3 wk of washout (only one-third of the supplementation-induced increase had disappeared) and returned to baseline values within 9 wk at group level. Following subdivision into high responders (+55%) and low responders (+15%), washout period was 15 and 6 wk, respectively. In the placebo group, carnosine remained relatively constant with variation coefficients of 9-15% over a 3-mo period. It can be concluded that carnosine is a stable compound in human skeletal muscle, confirming the absence of carnosinase in myocytes. The present study shows that washout periods for crossover designs in supplementation studies for muscle metabolites may sometimes require months rather than weeks. PMID:19131472

Baguet, Audrey; Reyngoudt, Harmen; Pottier, Andries; Everaert, Inge; Callens, Stefanie; Achten, Eric; Derave, Wim

2009-03-01

218

Localization and function of Xin? in mouse skeletal muscle.  

PubMed

The Xin repeat-containing proteins were originally found in the intercalated discs of cardiac muscle with implicated roles in cardiac development and function. A pair of paralogous genes, Xin? (Xirp1) and Xin? (Xirp2), is present in mammals. Ablation of the mouse Xin? (mXin?) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXin? and mXin? are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXin? in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXin? but not mXin? was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXin? with talin, vinculin, and filamin, but not ?-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXin? with vinculin. Loss of mXin? in mXin?-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXin?-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXin? exhibited no overt change in contractile and relaxation velocities or maximum force development but better tolerance to fatigue. Loaded fatigue contractions generated stretch injury in wild-type EDL muscle as indicated by a fragmentation of troponin T. This effect was blunted in mXin?-null EDL muscle. The results suggest that mXin? play a role in MTJ conductance of contractile and stretching forces. PMID:23485711

Feng, Han-Zhong; Wang, Qinchuan; Reiter, Rebecca S; Lin, Jenny L-C; Lin, Jim J-C; Jin, J-P

2013-05-15

219

Localization and function of Xin? in mouse skeletal muscle  

PubMed Central

The Xin repeat-containing proteins were originally found in the intercalated discs of cardiac muscle with implicated roles in cardiac development and function. A pair of paralogous genes, Xin? (Xirp1) and Xin? (Xirp2), is present in mammals. Ablation of the mouse Xin? (mXin?) did not affect heart development but caused late-onset adulthood cardiac hypertrophy and cardiomyopathy with conductive defects. Both mXin? and mXin? are also found in the myotendinous junction (MTJ) of skeletal muscle. Here we investigated the structural and functional significance of mXin? in skeletal muscle. In addition to MTJ and the contact sites between muscle and perimysium, mXin? but not mXin? was found in the blood vessel walls, whereas both proteins were absent in neuromuscular junctions and nerve fascicles. Coimmunoprecipitation suggested association of mXin? with talin, vinculin, and filamin, but not ?-catenin, in adult skeletal muscle, consistent with our previous report of colocalization of mXin? with vinculin. Loss of mXin? in mXin?-null mice had subtle effects on the MTJ structure and the levels of several MTJ components. Diaphragm muscle of mXin?-null mice showed hypertrophy. Compared with wild-type controls, mouse extensor digitorum longus (EDL) muscle lacking mXin? exhibited no overt change in contractile and relaxation velocities or maximum force development but better tolerance to fatigue. Loaded fatigue contractions generated stretch injury in wild-type EDL muscle as indicated by a fragmentation of troponin T. This effect was blunted in mXin?-null EDL muscle. The results suggest that mXin? play a role in MTJ conductance of contractile and stretching forces.

Feng, Han-Zhong; Wang, Qinchuan; Reiter, Rebecca S.; Lin, Jenny L.-C.; Lin, Jim J.-C.

2013-01-01

220

Anomalous ion diffusion within skeletal muscle transverse tubule networks  

PubMed Central

Background Skeletal muscle fibres contain transverse tubular (t-tubule) networks that allow electrical signals to rapidly propagate into the fibre. These electrical signals are generated by the transport of ions across the t-tubule membranes and this can result in significant changes in ion concentrations within the t-tubules during muscle excitation. During periods of repeated high-frequency activation of skeletal muscle the t-tubule K+ concentration is believed to increase significantly and diffusive K+ transport from the t-tubules into the interstitial space provides a mechanism for alleviating muscle membrane depolarization. However, the tortuous nature of the highly branched space-filling t-tubule network impedes the diffusion of material through the network. The effective diffusion coefficient for ions in the t-tubules has been measured to be approximately five times lower than in free solution, which is significantly different from existing theoretical values of the effective diffusion coefficient that range from 2–3 times lower than in free solution. To resolve this discrepancy, in this paper we study the process of diffusion within electron microscope scanned sections of the skeletal muscle t-tubule network using mathematical modelling and computer simulation techniques. Our model includes t-tubule geometry, tautness, hydrodynamic and non-planar network factors. Results Using our model we found that the t-tubule network geometry reduced the K+ diffusion coefficient to 19–27% of its value in free solution, which is consistent with the experimentally observed value of 21% and is significantly smaller than existing theoretical values that range from 32–50%. We also found that diffusion in the t-tubules is anomalous for skeletal muscle fibres with a diameter of less than approximately 10–20 ?m as a result of obstructed diffusion. We also observed that the [K+] within the interior of the t-tubule network during high-frequency activation is greater for fibres with a larger diameter. Smaller skeletal muscle fibres are therefore more resistant to membrane depolarization. Because the t-tubule network is anisotropic and inhomogeneous, we also found that the [K+] distribution generated within the network was irregular for fibres of small diameter. Conclusion Our model explains the measured effective diffusion coefficient for ions in skeletal muscle t-tubules.

Shorten, Paul R; Soboleva, Tanya K

2007-01-01

221

Passive in vivo elastography from skeletal muscle noise  

SciTech Connect

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

Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A. [Marine Physical Laboratory, Scripps Institution of Oceanography, University of California San Diego, San Diego, California 92093-0238 (United States)

2007-05-07

222

mTor Signaling in Skeletal Muscle During Sepsis and Inflammation: Where Does It All Go Wrong?  

NSDL National Science Digital Library

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that exquisitely regulates protein metabolism in skeletal muscle. mTOR integrates input from amino acids, growth factors, and intracellular cues to make or break muscle protein. mTOR accomplishes this task by stimulating the phosphorylation of substrates that control protein translation while simultaneously inhibiting proteasomal and autophagic protein degradation. In a metabolic twist of fate, sepsis induces muscle atrophy in part by the aberrant regulation of mTOR. In this review, we track the steps of normal mTOR signaling in muscle and examine where they go astray in sepsis and inflammation.

Robert A Frost (Pennsylvania State University College of Medicine Department of Cellular and Molecular Physiology); Charles H Lang (Pennsylvania State University College of Medicine Department of Cellular and Molecular Physiology)

2011-04-01

223

Studies of Regeneration of Mammalian Skeletal Muscle.  

National Technical Information Service (NTIS)

The report details the results of experiments designed to measure physiological characteristics of regenerating rat muscle. Twitch time to peak and time to half relaxation, the ratio of twitch to tetanic tension and the rate of development of tetanic tens...

A. J. Buller J. Hodgson D. M. Lewis

1975-01-01

224

Mitochondria in Degenerating and Regenerating Skeletal Muscle.  

National Technical Information Service (NTIS)

Ultrastructural modifications of mitochondria are observed during degeneration and regeneration of myofibers following either acute ischemia in the rabbit or cold injury in the mouse. In the preexisting myofibers near a site of muscle necrosis, vast numbe...

M. Reznik J. L. Hansen

1969-01-01

225

Compartmentalization of NO signaling cascade in skeletal muscles  

SciTech Connect

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

Buchwalow, Igor B. [Gerhard Domagk Institute of Pathology, University of Muenster, Muenster (Germany)]. E-mail: buchwalo@uni-muenster.de; Minin, Evgeny A. [Gerhard Domagk Institute of Pathology, University of Muenster, Muenster (Germany); Samoilova, Vera E. [Gerhard Domagk Institute of Pathology, University of Muenster, Muenster (Germany); Boecker, Werner [Gerhard Domagk Institute of Pathology, University of Muenster, Muenster (Germany); Wellner, Maren [Franz Volhard Clinic, Medical Faculty of the Charite, Humboldt University of Berlin, Berlin (Germany); Schmitz, Wilhelm [Institute for Pharmacology and Toxicology, University of Muenster, Muenster (Germany); Neumann, Joachim [Institute for Pharmacology and Toxicology, Martin-Luther University Halle-Wittenberg, Halle/Saale (Germany); Punkt, Karla [Institute of Anatomy, University of Leipzig, Leipzig (Germany)

2005-05-06

226

Prospective identification of myogenic endothelial cells in human skeletal muscle.  

PubMed

We document anatomic, molecular and developmental relationships between endothelial and myogenic cells within human skeletal muscle. Cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry. These myoendothelial cells regenerate myofibers in the injured skeletal muscle of severe combined immunodeficiency mice more effectively than CD56+ myogenic progenitors. They proliferate long term, retain a normal karyotype, are not tumorigenic and survive better under oxidative stress than CD56+ myogenic cells. Clonally derived myoendothelial cells differentiate into myogenic, osteogenic and chondrogenic cells in culture. Myoendothelial cells are amenable to biotechnological handling, including purification by flow cytometry and long-term expansion in vitro, and may have potential for the treatment of human muscle disease. PMID:17767154

Zheng, Bo; Cao, Baohong; Crisan, Mihaela; Sun, Bin; Li, Guangheng; Logar, Alison; Yap, Solomon; Pollett, Jonathan B; Drowley, Lauren; Cassino, Theresa; Gharaibeh, Burhan; Deasy, Bridget M; Huard, Johnny; Péault, Bruno

2007-09-01

227

Characteristics of impala ( Aepyceros melampus) skeletal muscles  

Microsoft Academic Search

The aim of this study was to determine citrate synthase (CS), phosphofructokinase (PFK) activities and myosin heavy chain (MHC) isoform contents in four muscle groups (semimembranosus (S), deltoideus (D), longissimus lumborum (LL), and psoas major (PM)) of impala (n=6). All four muscle groups expressed predominantly MHC IIa (means of 55±22–93±12%). MHC IIx was only expressed in D. In D, positive

Tertius A. Kohn; Brian Kritzinger; Louw C. Hoffman; Kathryn H. Myburgh

2005-01-01

228

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

PubMed

Isolated toad gastrocnemius muscle is a typical skeletal muscle tissue that is frequently used to study the motor system because it is an important component of the motor system. This study investigates the effects of cordycepin on the skeletal muscle contractile function of isolated toad gastrocnemius muscles by electrical field stimulation. Results showed that cordycepin (20 mg/l to 100 mg/l) significantly decreased the contractile responses in a concentration-dependent manner. Cordycepin (50 mg/l) also produced a rightward shift of the contractile amplitude-stimulation intensity relationship, as indicated by the increases in the threshold stimulation intensity and the saturation stimulation intensity. However, the most notable result was that the maximum amplitude of the muscle contractile force was significantly increased under cordycepin application (122±3.4% of control). This result suggests that the skeletal muscle contractile function and muscle physical fitness to the external stimulation were improved by the decreased response sensitivity in the presence of cordycepin. Moreover, cordycepin also prevented the repetitive stimulation-induced decrease in muscle contractile force and increased the recovery amplitude and recovery ratio of muscle contraction. However, these anti-fatigue effects of cordycepin on muscle contraction during long-lasting muscle activity were absent in Ca2+-free medium or in the presence of all Ca2+ channels blocker (0.4 mM CdCl2). These results suggest that cordycepin can positively affect muscle performance and provide ergogenic and prophylactic benefits in decreasing skeletal muscle fatigue. The mechanisms involving excitation-coupled Ca2+ influxes are strongly recommended. PMID:24447979

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

2014-03-01

229

Structural and regulatory roles of muscle ankyrin repeat protein family in skeletal muscle.  

PubMed

The biological response of muscle to eccentric contractions (ECs) results in strengthening and protection from further injury. However, the cellular basis for this response remains unclear. Previous studies identified the muscle ankyrin repeat protein (MARP) family, consisting of cardiac ankyrin repeat protein (CARP), ankyrin repeat domain 2/ankyrin repeat protein with PEST and proline-rich region (Ankrd2/Arpp), and diabetes-associated ankyrin repeat protein (DARP), as rapidly and specifically upregulated in mice after a single bout of EC. To determine the role of these genes in skeletal muscle, a survey of skeletal muscle structural and functional characteristics was performed on mice lacking all three MARP family members (MKO). There was a slight trend toward MKO muscles having a slower fiber type distribution but no differences in muscle fiber size. Single MKO fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that these proteins may play a role in the passive mechanical behavior of muscle. Finally, MKO mice showed a greater degree of torque loss after a bout of ECs compared with wild-type mice, although they recovered from the injury with the same or even improved time course. This recovery was associated with enhanced expression of the muscle regulatory genes MyoD and muscle LIM protein (MLP), suggesting that the MARP family may play both important structural and gene regulatory roles in skeletal muscle. PMID:17392382

Barash, Ilona A; Bang, Marie-Louise; Mathew, Liby; Greaser, Marion L; Chen, Ju; Lieber, Richard L

2007-07-01

230

Hormonal Receptors in Skeletal Muscles of Dystrophic Mdx Mice  

PubMed Central

Introduction. Several evidences show that muscles have an endocrine function. Glucocorticoid, estrogen, progesterone, and testosterone receptors have already been found in normal skeletal muscles, but not in dystrophic muscles. Methods. The gene expression of hormone receptors was compared between dystrophic and healthy muscles in mdx and C57BL6 mice strains. Results. The mdx mice showed a significant increase in the steroid receptors mRNA when compared to the C57BL6 mice: levels of androgen(s) receptors in the heart, estrogen receptors alpha in the EDL, and estrogen receptors beta in the quadriceps were increased. In addition, significant lowered levels of some other hormone receptors were found: corticosteroid receptors in the EDL and estrogen receptors alpha in the quadriceps. Conclusion. Dystrophic muscles bear significant differences in the expression of hormone receptors when compared to the C57BL6 mice strain. The importance of such differences is yet to be better understood.

Feder, David; Rodrigues Barros Godoy, Ivan; Guimaraes Pereira, Maira Lazzarini; Silva, Cledson Silveira; Nogueira Silvestre, Diego; Fonseca, Fernando Luiz Affonso; Alves de Siqueira Carvalho, Alzira; Aparecida dos Santos, Rosangela; Catteli Carvalho, Maria Helena

2013-01-01

231

Abnormal glucose homeostasis in skeletal muscle-specific PGC-1? knockout mice reveals skeletal muscle-pancreatic ? cell crosstalk  

PubMed Central

The transcriptional coactivator PPAR? coactivator 1? (PGC-1?) is a strong activator of mitochondrial biogenesis and oxidative metabolism. While expression of PGC-1? and many of its mitochondrial target genes are decreased in the skeletal muscle of patients with type 2 diabetes, no causal relationship between decreased PGC-1? expression and abnormal glucose metabolism has been established. To address this question, we generated skeletal muscle–specific PGC-1? knockout mice (MKOs), which developed significantly impaired glucose tolerance but showed normal peripheral insulin sensitivity. Surprisingly, MKOs had expanded pancreatic ? cell mass, but markedly reduced plasma insulin levels, in both fed and fasted conditions. Muscle tissue from MKOs showed increased expression of several proinflammatory genes, and these mice also had elevated levels of the circulating IL-6. We further demonstrated that IL-6 treatment of isolated mouse islets suppressed glucose-stimulated insulin secretion. These data clearly illustrate a causal role for muscle PGC-1? in maintenance of glucose homeostasis and highlight an unexpected cytokine-mediated crosstalk between skeletal muscle and pancreatic islets.

Handschin, Christoph; Choi, Cheol Soo; Chin, Sherry; Kim, Sheene; Kawamori, Dan; Kurpad, Amarnath J.; Neubauer, Nicole; Hu, Jiang; Mootha, Vamsi K.; Kim, Young-Bum; Kulkarni, Rohit N.; Shulman, Gerald I.; Spiegelman, Bruce M.

2007-01-01

232

Neuromuscular Electrical Stimulation for Skeletal Muscle Function  

PubMed Central

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

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

2012-01-01

233

Mechanical characterization of skeletal muscle myofibrils.  

PubMed Central

A new instrument, based on a technique described previously, is presented for studying mechanics of micron-scale preparations of two to three myofibrils or single myofibrils from muscle. Forces in the nanonewton to micronewton range are measurable with 0.5-ms time resolution. Programmed quick (200-microseconds) steps or ramp length changes are applied to contracting myofibrils to test their mechanical properties. Individual striations can be monitored during force production and shortening. The active isometric force, force-velocity relationship, and force transients after rapid length steps were obtained from bundles of two to three myofibrils from rabbit psoas muscle. Contrary to some earlier reports on myofibrillar mechanics, these properties are generally similar to expectations from studies on intact and skinned muscle fibers. Our experiments provide strong evidence that the mechanical properties of a fiber result from a simple summation of the myofibrillar force and shortening of independently contracting sarcomeres. Images FIGURE 1 FIGURE 2

Friedman, A L; Goldman, Y E

1996-01-01

234

Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency  

NASA Technical Reports Server (NTRS)

To define the adaptations that conserve amino acids and muscle protein when dietary protein intake is inadequate, rats (60-70 g final wt) were fed a normal or protein-deficient (PD) diet (18 or 1% lactalbumin), and their muscles were studied in vitro. After 7 days on the PD diet, both protein degradation and synthesis fell 30-40% in skeletal muscles and atria. This fall in proteolysis did not result from reduced amino acid supply to the muscle and preceded any clear decrease in plasma amino acids. Oxidation of branched-chain amino acids, glutamine and alanine synthesis, and uptake of alpha-aminoisobutyrate also fell by 30-50% in muscles and adipose tissue of PD rats. After 1 day on the PD diet, muscle protein synthesis and amino acid uptake decreased by 25-40%, and after 3 days proteolysis and leucine oxidation fell 30-45%. Upon refeeding with the normal diet, protein synthesis also rose more rapidly (+30% by 1 day) than proteolysis, which increased significantly after 3 days (+60%). These different time courses suggest distinct endocrine signals for these responses. The high rate of protein synthesis and low rate of proteolysis during the first 3 days of refeeding a normal diet to PD rats contributes to the rapid weight gain ("catch-up growth") of such animals.

Tawa, N. E. Jr; Goldberg, A. L.

1992-01-01

235

Decrease of muscle volume in chronic kidney disease: the role of mitochondria in skeletal muscle.  

PubMed

Reduced muscle volume and impaired exercise endurance are well-documented phenomena in chronic kidney disease, and the relevant molecular mechanisms have been gradually unveiled. Tamaki et al. demonstrate a reduction of mitochondria content in skeletal muscles as a novel mechanism of reduced exercise endurance in renal insufficiency. In addition, they show that a high-protein diet reduces exercise endurance through an inhibition of muscle pyruvate dehydrogenase. PMID:24875545

Yokoi, Hideki; Yanagita, Motoko

2014-06-01

236

Human skeletal muscle fiber type specific protein content.  

PubMed

The aim of this project was to develop a method to assess fiber type specific protein content across the continuum of human skeletal muscle fibers. Individual vastus lateralis muscle fibers (n = 264) were clipped into two portions: one for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) fiber typing and one for Western blot protein identification. Following fiber type determination, fiber segments were combined into fiber type specific pools (?20 fibers/pool) and measured for total protein quantity, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), citrate synthase (CS), and total p38 content. GAPDH content was 64, 54, 160, and 138% more abundant in myosin heavy chain (MHC) I/IIa, MHC IIa, MHC IIa/IIx, and MHC IIx fibers, respectively, when compared with MHC I. Inversely, CS content was 528, 472, 242, and 47% more abundant in MHC I, MHC I/IIa, MHC IIa, and MHC IIa/IIx fibers, respectively, when compared with MHC IIx. Total p38 content was 87% greater in MHC IIa versus MHC I fibers. These data and this approach establish a reliable method for human skeletal muscle fiber type specific protein analysis. Initial results show that particular proteins exist in a hierarchal fashion throughout the continuum of human skeletal muscle fiber types, further highlighting the necessity of fiber type specific analysis. PMID:22469996

Galpin, Andrew J; Raue, Ulrika; Jemiolo, Bozena; Trappe, Todd A; Harber, Matthew P; Minchev, Kiril; Trappe, Scott

2012-06-15

237

Cardiovascular regulation by skeletal muscle reflexes in health and disease  

PubMed Central

Heart rate and blood pressure are elevated at the onset and throughout the duration of dynamic or static exercise. These neurally mediated cardiovascular adjustments to physical activity are regulated, in part, by a peripheral reflex originating in contracting skeletal muscle termed the exercise pressor reflex. Mechanically sensitive and metabolically sensitive receptors activating the exercise pressor reflex are located on the unencapsulated nerve terminals of group III and group IV afferent sensory neurons, respectively. Mechanoreceptors are stimulated by the physical distortion of their receptive fields during muscle contraction and can be sensitized by the production of metabolites generated by working skeletal myocytes. The chemical by-products of muscle contraction also stimulate metaboreceptors. Once activated, group III and IV sensory impulses are transmitted to cardiovascular control centers within the brain stem where they are integrated and processed. Activation of the reflex results in an increase in efferent sympathetic nerve activity and a withdrawal of parasympathetic nerve activity. These actions result in the precise alterations in cardiovascular hemodynamics requisite to meet the metabolic demands of working skeletal muscle. Coordinated activity by this reflex is altered after the development of cardiovascular disease, generating exaggerated increases in sympathetic nerve activity, blood pressure, heart rate, and vascular resistance. The basic components and operational characteristics of the reflex, the techniques used in human and animals to study the reflex, and the emerging evidence describing the dysfunction of the reflex with the advent of cardiovascular disease are highlighted in this review.

Murphy, Megan N.; Mizuno, Masaki; Mitchell, Jere H.

2011-01-01

238

Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration  

PubMed Central

During forelimb regeneration in the newt Notophthalmus viridescens, the dynamic expression of a transitional matrix rich in hyaluronic acid, tenascin-C, and fibronectin controls muscle cell behavior in vivo and in vitro. However, the influence of extracellular matrix (ECM) remodeling on tissue stiffness and the cellular response to mechanical variations during regeneration was unknown. By measuring the transverse stiffness of tissues in situ, we found undifferentiated regenerative blastemas were less stiff than differentiated stump muscle (13.3±1.6 vs. 16.6±1.2 kPa). To directly determine how ECM and stiffness combine to affect skeletal muscle fragmentation, migration, and fusion, we coated silicone-based substrates ranging from 2 to 100 kPa with matrices representative of transitional (tenascin-C and fibronectin) and differentiated environments (laminin and Matrigel). Using live-cell imaging, we found softer tenascin-C-coated substrates significantly enhanced migration and fragmentation of primary newt muscle cells. In contrast, stiffer substrates coated with laminin, Matrigel, or fibronectin increased differentiation while suppressing migration and fragmentation. These data support our in vivo observations that a transitional matrix of reduced stiffness regulates muscle plasticity and progenitor cell recruitment into the regenerative blastema. These new findings will enable the determination of how biochemical and mechanical cues from the ECM control genetic pathways that drive regeneration.—Calve, S., Simon, H.-G. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration.

Calve, Sarah; Simon, Hans-Georg

2012-01-01

239

Regeneration of injured skeletal muscle after the injury  

PubMed Central

Summary Muscle injuries are one of the most common traumas occurring in sports. Despite their clinical importance, few clinical studies exist on the treatment of these traumas. Thus, the current treatment recommendations for muscle injuries have either been derived from experimental studies or been tested only empirically. Although non operative treatment should almost always be the 1st choice as it results in good functional outcomes in the majority of athletes with muscle injuries, the consequences of failed treatment can be very dramatic, possibly postponing an athlete’s return to sports for weeks or even months. Moreover, the recognition of some basic principles of skeletal muscle regeneration and healing processes can considerably help in both avoiding the imminent dangers and accelerating the return to competition. Accordingly, in this review, the authors have summarized the prevailing understanding on the biology of muscle regeneration in hopes of extending these findings to clinical practice in an attempt to propose an evidence-based approach for the diagnosis and optimal treatment of skeletal muscle injuries.

Jarvinen, Tero AH; Jarvinen, Markku; Kalimo, Hannu

2013-01-01

240

Neurofibromin (Nf1) is required for skeletal muscle development  

PubMed Central

Neurofibromatosis type 1 (NF1) is a multi-system disease caused by mutations in the NF1 gene encoding a Ras-GAP protein, neurofibromin, which negatively regulates Ras signaling. Besides neuroectodermal malformations and tumors, the skeletal system is often affected (e.g. scoliosis and long bone dysplasia) demonstrating the importance of neurofibromin for development and maintenance of the musculoskeletal system. Here, we focus on the role of neurofibromin in skeletal muscle development. Nf1 gene inactivation in the early limb bud mesenchyme using Prx1-cre (Nf1Prx1) resulted in muscle dystrophy characterized by fibrosis, reduced number of muscle fibers and reduced muscle force. This was caused by an early defect in myogenesis affecting the terminal differentiation of myoblasts between E12.5 and E14.5. In parallel, the muscle connective tissue cells exhibited increased proliferation at E14.5 and an increase in the amount of connective tissue as early as E16.5. These changes were accompanied by excessive mitogen-activated protein kinase pathway activation. Satellite cells isolated from Nf1Prx1 mice showed normal self-renewal, but their differentiation was impaired as indicated by diminished myotube formation. Our results demonstrate a requirement of neurofibromin for muscle formation and maintenance. This previously unrecognized function of neurofibromin may contribute to the musculoskeletal problems in NF1 patients.

Kossler, Nadine; Stricker, Sigmar; Rodelsperger, Christian; Robinson, Peter N.; Kim, Johnny; Dietrich, Carola; Osswald, Monika; Kuhnisch, Jirko; Stevenson, David A.; Braun, Thomas; Mundlos, Stefan; Kolanczyk, Mateusz

2011-01-01

241

Neurofibromin (Nf1) is required for skeletal muscle development.  

PubMed

Neurofibromatosis type 1 (NF1) is a multi-system disease caused by mutations in the NF1 gene encoding a Ras-GAP protein, neurofibromin, which negatively regulates Ras signaling. Besides neuroectodermal malformations and tumors, the skeletal system is often affected (e.g. scoliosis and long bone dysplasia) demonstrating the importance of neurofibromin for development and maintenance of the musculoskeletal system. Here, we focus on the role of neurofibromin in skeletal muscle development. Nf1 gene inactivation in the early limb bud mesenchyme using Prx1-cre (Nf1(Prx1)) resulted in muscle dystrophy characterized by fibrosis, reduced number of muscle fibers and reduced muscle force. This was caused by an early defect in myogenesis affecting the terminal differentiation of myoblasts between E12.5 and E14.5. In parallel, the muscle connective tissue cells exhibited increased proliferation at E14.5 and an increase in the amount of connective tissue as early as E16.5. These changes were accompanied by excessive mitogen-activated protein kinase pathway activation. Satellite cells isolated from Nf1(Prx1) mice showed normal self-renewal, but their differentiation was impaired as indicated by diminished myotube formation. Our results demonstrate a requirement of neurofibromin for muscle formation and maintenance. This previously unrecognized function of neurofibromin may contribute to the musculoskeletal problems in NF1 patients. PMID:21478499

Kossler, Nadine; Stricker, Sigmar; Rödelsperger, Christian; Robinson, Peter N; Kim, Johnny; Dietrich, Carola; Osswald, Monika; Kühnisch, Jirko; Stevenson, David A; Braun, Thomas; Mundlos, Stefan; Kolanczyk, Mateusz

2011-07-15

242

Identification of New Dystroglycan Complexes in Skeletal Muscle  

PubMed Central

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

Johnson, Eric K.; Li, Bin; Yoon, Jung Hae; Flanigan, Kevin M.; Martin, Paul T.; Ervasti, James; Montanaro, Federica

2013-01-01

243

Altered Ca2+ sparks in aging skeletal and cardiac muscle.  

PubMed

Ca2+ sparks are the fundamental units that comprise Ca2+-induced Ca2+ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca2+ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca2+ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca2+ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca2+ spark activity in aged cardiomyocytes. Ca2+ spark responses reflect the integrated function of the intracellular Ca2+ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca2+ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca2+ spark signaling during aging of striated muscles. PMID:18272434

Weisleder, Noah; Ma, Jianjie

2008-07-01

244

Clinical application of diffusion tensor magnetic resonance imaging in skeletal muscle  

PubMed Central

Summary Diffusion tensor magnetic resonance imaging (DTI) is increasingly applied in the detection and characterization of skeletal muscle. This promising technique has aroused much enthusiasm and generated high expectations, because it is able to provide some specific information of skeletal muscle that is not available from other imaging modalities. Compared with conventional MRI, DTI could reconstruct the trajectories of skeletal muscle fibers. It makes it possible to non-invasively detect several physiological values (diffusion values), like fractional anisotropy (FA) and apparent diffusion coefficient (ADC), which have a great association with the muscle physiology and pathology. Furthermore, other advantages of DTI are the capability of investigating the muscle biomechanics and also investigate the pathological condition of skeletal muscle. Finally, several challenges, which limit the wide application of DTI in skeletal muscle, were discussed. It is believed that this review may arouse in-depth studies on the clinical application of DTI in skeletal muscle in future.

Longwei, Xu

2012-01-01

245

Development of polyglucosan inclusions in skeletal muscle  

Microsoft Academic Search

Muscle samples from 24 horses with polysaccharide storage myopathy were stained with periodic acid-Schiff (PAS) stain and were immunostained for ubiquitin. Abnormalities detected with PAS stain were coarse granular cytoplasmic aggregates of amylase sensitive glycogen, subsarcolemmal aggregates of glycogen, central amylase sensitive bodies, and a variety of subsarcolemmal to intracytoplasmic amylase resistant polyglucosan inclusions. All amylase resistant inclusions were positive

Beth A. Valentine; Barry J. Cooper

2006-01-01

246

Activity Dependent Signal Transduction in Skeletal Muscle  

NASA Technical Reports Server (NTRS)

The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

Hamilton, Susan L.

1999-01-01

247

Role of the Occult Insulin Receptors in the Regulation of Atrophy and Hypertrophy of Skeletal Muscles.  

National Technical Information Service (NTIS)

Insulin levels in the plasma are variable, as are insulin receptor numbers on the surface of skeletal muscles. Increased blood supply to the muscle during exercise delivers more insulin to the muscles even though insulin levels are suppressed by epinephri...

M. J. McLeod

1980-01-01

248

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy  

NASA Technical Reports Server (NTRS)

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.

Spangenburg, E. E.; Williams, J. H.; Roy, R. R.; Talmadge, R. J.; Spangenberg, E. E. (Principal Investigator)

2001-01-01

249

Myodulin is a novel potential angiogenic factor in skeletal muscle.  

PubMed

We examined the expression and function of a gene we previously cloned from its downregulation in a muscle atrophy model. The encoded protein was named myodulin because of sequence homologies with the cartilage-specific chondromodulin-I (ChM-I) protein, its restricted expression in skeletal muscle tissue, and its modulating properties on vascular endothelial cells described here. We investigated the expression of myodulin in muscle fibers and cultured muscle cells. Myodulin RNA messengers were found in muscle fibers and their tendon extensions. Overexpression of myodulin fused to a FLAG peptide showed evidence of a muscle cell surface protein. Myodulin functions were assessed from similarities with chondromodulin-I. Coculture experiments using C(2)C(12) mouse myoblasts or myotubes, which stably overexpress myodulin, with H5V mouse cardiac vascular endothelial cells revealed that myodulin had a very active role in the invasive action of endothelial cells, without any evidence of extracellular myodulin secretion. Our results suggest that myodulin may be a muscle angiogenic factor operating through direct cell-to-cell interactions. This role is consistent with the correlation between modulations in myodulin expression and modifications in muscle microvascularization associated with activity-dependent muscle mass variations. PMID:14720505

Pisani, Didier F; Pierson, Patricia M; Massoudi, Ali; Leclerc, Lilian; Chopard, Angèle; Marini, Jean-François; Dechesne, Claude A

2004-01-01

250

Exercise, GLUT4, and skeletal muscle glucose uptake.  

PubMed

Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions. Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose uptake relies on GLUT4 translocation, glucose uptake also depends on muscle GLUT4 expression which is increased following exercise. AMPK and CaMKII are key signaling kinases that appear to regulate GLUT4 expression via the HDAC4/5-MEF2 axis and MEF2-GEF interactions resulting in nuclear export of HDAC4/5 in turn leading to histone hyperacetylation on the GLUT4 promoter and increased GLUT4 transcription. Exercise training is the most potent stimulus to increase skeletal muscle GLUT4 expression, an effect that may partly contribute to improved insulin action and glucose disposal and enhanced muscle glycogen storage following exercise training in health and disease. PMID:23899560

Richter, Erik A; Hargreaves, Mark

2013-07-01

251

PI3 kinase regulation of skeletal muscle hypertrophy and atrophy.  

PubMed

Activation of the PI3 kinase pathway can induce skeletal muscle hypertrophy, defined as an increase in skeletal muscle mass. In mammals, skeletal muscle hypertrophy occurs as a result of an increase in the size, as opposed to the number, of pre-existing skeletal muscle fibers. This pathway's effects on skeletal muscle have been implicated most prominently downstream of Insulin-like growth factor 1 signaling. IGF-1's pro-hypertrophy activity comes predominantly through its ability to activate the Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Akt is a serine-threonine protein kinase that can induce protein synthesis and block the transcriptional upregulation of key mediators of skeletal muscle atrophy, the E3 ubiquitin ligases MuRF1 and MAFbx (also called Atrogin-1), by phosphorylating and thereby inhibiting the nuclear translocation of the FOXO (also called "forkhead") family of transcription factors. Once phosphorylated by Akt, the FOXOs are excluded from the nucleus, and upregulation of MuRF1 and MAFbx is blocked. MuRF1 and MAFbx mediate atrophy by ubiquitinating particular protein substrates, causing them to undergo degradation by the proteasome. MuRF1's substrates include several components of the sarcomeric thick filament, including Myosin Heavy Chain (MyHC). Thus, by blocking MuRF1 activation, IGF-1 helps prevent the breakdown of the thick filament under atrophy conditions.IGF1/PI3K/Akt signaling also can dominantly inhibit the effects of a secreted protein called "myostatin," which is a member of the TGF? family of proteins. Deletion or inhibition of myostatin causes an increase in skeletal muscle size, because myostatin acts both to inhibit myoblast differentiation and to block the Akt pathway. Thus by blocking myostatin, PI3K/Akt activation stimulates differentiation and protein synthesis by this distinct mechanism. Myostatin induces the phosphorylation and activation of the transcription factors of Smad2 and Smad3, downstream of the ActRII (Activin Receptor type II)/Alk (Activin Receptor-like kinase) receptor complex. Other TGF?-like molecules can also block differentiation, including TGF-b1, GDF-11, activinA, BMP-2 and BMP-7. As mentioned, myostatin also downregulates the Akt/mTOR/p70S6 protein synthesis pathway, which mediates both differentiation in myoblasts and hypertrophy in myotubes. Blockade of the Akt/mTOR pathway, using siRNA to RAPTOR, a component of "TORC1" (TOR signaling Complex 1), increases myostatin-induced phosphorylation of Smad2; this establishes a "feed-forward mechanism," because myostatin can downregulates TORC1, and this downregulation in turn amplifies myostatin signaling. Blockade of RAPTOR also facilitates myostatin's inhibition of muscle differentiation. When added to post-differentiated myotubes, myostatin causes a decrease in their diameter - however, this does not happen through the normal "atrophy pathway." Rather than causing upregulation of the E3 ubiquitin ligases MuRF1 and MAFbx, previously shown to mediate skeletal muscle atrophy, myostatin decreases expression of these atrophy markers in differentiated myotubes, as well as other genes normally upregulated during differentiation, such as MyoD and myogenin. These findings show that myostatin signaling acts by blocking genes induced during differentiation, even in a myotube, as opposed to activating the distinct "atrophy program." PMID:20593312

Glass, David J

2010-01-01

252

Adaptations of mouse skeletal muscle to low intensity vibration training  

PubMed Central

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

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

2013-01-01

253

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis  

NASA Technical Reports Server (NTRS)

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Ferrando, A. A.; Lane, H. W.; Stuart, C. A.; Davis-Street, J.; Wolfe, R. R.

1996-01-01

254

Transduction of Skeletal Muscles with Common Reporter Genes Can Promote Muscle Fiber Degeneration and Inflammation  

PubMed Central

Recombinant adeno-associated viral vectors (rAAV vectors) are promising tools for delivering transgenes to skeletal muscle, in order to study the mechanisms that control the muscle phenotype, and to ameliorate diseases that perturb muscle homeostasis. Many studies have employed rAAV vectors carrying reporter genes encoding for ?-galactosidase (?-gal), human placental alkaline phosphatase (hPLAP), and green fluorescent protein (GFP) as experimental controls when studying the effects of manipulating other genes. However, it is not clear to what extent these reporter genes can influence signaling and gene expression signatures in skeletal muscle, which may confound the interpretation of results obtained in experimentally manipulated muscles. Herein, we report a strong pro-inflammatory effect of expressing reporter genes in skeletal muscle. Specifically, we show that the administration of rAAV6:hPLAP vectors to the hind limb muscles of mice is associated with dose- and time-dependent macrophage recruitment, and skeletal muscle damage. Dose-dependent expression of hPLAP also led to marked activity of established pro-inflammatory IL-6/Stat3, TNF?, IKK? and JNK signaling in lysates obtained from homogenized muscles. These effects were independent of promoter type, as expression cassettes featuring hPLAP under the control of constitutive CMV and muscle-specific CK6 promoters both drove cellular responses when matched for vector dose. Importantly, the administration of rAAV6:GFP vectors did not induce muscle damage or inflammation except at the highest doses we examined, and administration of a transgene-null vector (rAAV6:MCS) did not cause damage or inflammation at any of the doses tested, demonstrating that GFP-expressing, or transgene-null vectors may be more suitable as experimental controls. The studies highlight the importance of considering the potential effects of reporter genes when designing experiments that examine gene manipulation in vivo.

Winbanks, Catherine E.; Beyer, Claudia; Qian, Hongwei; Gregorevic, Paul

2012-01-01

255

Diffraction Ellipsometry Studies of Skeletal Muscle Structure  

NASA Astrophysics Data System (ADS)

Many of the techniques used to study the structure and contraction mechanism of muscle rely on the interaction of light or other electromagnetic radiation with the muscle. Some of the most important of these techniques are light and electron microscopy, x-ray diffraction, spectroscopy of muscle fibers "labelled" with spin or fluorescent probes, visible spectrum diffraction, and transmission birefringence. Chapter I of this dissertation reviews these techniques, focussing on what they have to tell us about muscle structure. In Chapter II, we discuss experiments in which the microstructural features of relaxed, skinned fibers compressed with polyvinylpyrollidone were examined by optical diffraction ellipsometry. The change in polarization state of light after interacting with the muscle is described by the differential field ratio (DFR) and birefringence (Deltan). Compression of single fibers with 0%-21% PVP caused an increase in up to 23% and 31% for DFR and Deltan, respectively. Theoretical modelling suggests that the average S-1 tilt angle may be reduced upon compression of the filament lattice. This is supported by experiments in which S-1 was cleaved with alpha-chymotrypsin. Experiments comparing fibers with intact membranes and skinned fibers compressed to an equivalent lattice spacing showed little difference in DFR or Deltan. Chapter III deals with experiments on contracting, intact fibers. The differential field ratio (DFR) was monitored for tetanically contracting muscle fibers subject to rapid (<0.4 msec) release or stretch. Upon stimulation, DFR decreases 14% from its resting value; the half-time for the decrease leads that of tension rise by 10 msecs. This suggests that the movement of cross -bridges precedes tension development and that the average cross-bridge angle is more perpendicular in the contracting state. Upon rapid release of 0.5% of the fiber length, DFR decreases 9.5% further simultaneous with the length step. Rapid and slow recovery phases were observed. A smaller decrease in DFR was seen upon 0.5% rapid stretch, but a rapid recovery phase was not observed. Our discussion of these results suggests that a crossbridge has internal flexibility, and that an undamped elastic element may reside somewhere in the crossbridge itself.

Kerr, William Lloyd

256

Characteristics of impala (Aepyceros melampus) skeletal muscles.  

PubMed

The aim of this study was to determine citrate synthase (CS), phosphofructokinase (PFK) activities and myosin heavy chain (MHC) isoform contents in four muscle groups (semimembranosus (S), deltoideus (D), longissimus lumborum (LL), and psoas major (PM)) of impala (n=6). All four muscle groups expressed predominantly MHC IIa (means of 55±22-93±12%). MHC IIx was only expressed in D. In D, positive correlations were found between MHC I and age (r=0.93; P<0.05) and the weight of the animals (r=0.94; P<0.01). PFK (means of 175±179-374±181), CS (means of 100±23-126±38 ?mol/min/gdw) and MHC content indicated that energy provision in the impala is produced to a large extent via oxidative pathways and fibre types vary with animal characteristics. PMID:22062819

Kohn, Tertius A; Kritzinger, Brian; Hoffman, Louw C; Myburgh, Kathryn H

2005-02-01

257

Regulation of glucose transport in skeletal muscle  

Microsoft Academic Search

The entry of glucose into muscle cells is achieved primarilyviaa carrier-mediatedsystem consist- ing of protein transport molecules. GLUT-i transporter isoform is normally found in the sarcolemmal (SL) mem- brane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 trans- porters from an intracellular pooi out to the

R. JAMES BARNARD; JACX F. YOUNGREN

258

Mastoparan binds to glycogen phosphorylase to regulate sarcoplasmic reticular Ca2+ release in skeletal muscle.  

PubMed Central

The ryanodine receptor, a Ca(2+)-releasing channel in sarcoplasmic reticulum (SR), plays an important role in the excitation-contraction coupling of skeletal muscle. In a previous study [Hirata, Nakahata and Ohizumi (2000) Mol. Pharmacol. 57, 1235-1242], we reported that mastoparan caused Ca(2+) release through ryanodine receptor from the heavy fraction of SR (HSR) isolated from rabbit skeletal muscle, and that it specifically bound to a 97 kDa protein which was distinct from Ca(2+)-pump or triadin. The present study was undertaken to identify and characterize the 97 kDa mastoparan-binding protein. The 97 kDa protein was purified from solubilized HSR by DEAE-Sepharose column chromatography and preparative SDS/PAGE. The partial amino acid sequence of the purified 97 kDa protein was matched with that of glycogen phosphorylase (GP). The proteolytic cleavage pattern of the 97 kDa protein was identical with that of GP. Furthermore, [(125)I-Tyr(3)]mastoparan specifically bound to GP. Interestingly, mastoparan-induced Ca(2+) release was inhibited by exogenous addition of GP-a, and mastoparan dissociated GP from HSR. These results indicate that the 97 kDa mastoparan-binding protein is GP, which negatively regulates Ca(2+) release from HSR. There may be a functional cross-talk between Ca(2+) release from HSR and glycogenolysis for energy supply mediated through GP in skeletal muscles.

Hirata, Yutaka; Atsumi, Masanori; Ohizumi, Yasushi; Nakahata, Norimichi

2003-01-01

259

Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance  

PubMed Central

OBJECTIVE Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.

Amati, Francesca; Dube, John J.; Alvarez-Carnero, Elvis; Edreira, Martin M.; Chomentowski, Peter; Coen, Paul M.; Switzer, Galen E.; Bickel, Perry E.; Stefanovic-Racic, Maja; Toledo, Frederico G.S.; Goodpaster, Bret H.

2011-01-01

260

Bone marrow-derived cell regulation of skeletal muscle regeneration  

PubMed Central

Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2?/? mice into irradiated WT or CCR2?/? host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2?/? BM. Furthermore, numbers of MPCs (CD34+/Sca-1?/CD45? cells) were significantly increased in mice receiving CCR2?/? BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration.—Sun, D., Martinez, C. O., Ochoa, O., Ruiz-Willhite, L., Bonilla, J. R., Centonze, V. E., Waite, L. L., Michalek, J. E., McManus, L. M., Shireman, P. K. Bone marrow-derived cell regulation of skeletal muscle regeneration.

Sun, Dongxu; Martinez, Carlo O.; Ochoa, Oscar; Ruiz-Willhite, Lourdes; Bonilla, Jose R.; Centonze, Victoria E.; Waite, Lindsay L.; Michalek, Joel E.; McManus, Linda M.; Shireman, Paula K.

2009-01-01

261

Regulation of protein synthesis by amino acids in muscle of neonates  

PubMed Central

The marked increase in skeletal muscle mass during the neonatal period is largely due to a high rate of postprandial protein synthesis that is modulated by an enhanced sensitivity to insulin and amino acids. The amino acid signaling pathway leading to the stimulation of protein synthesis has not been fully elucidated. Among the amino acids, leucine is considered to be a principal anabolic agent that regulates protein synthesis. mTORC1, which controls protein synthesis, has been implicated as a target for leucine. Until recently, there have been few studies exploring the role of amino acids in enhancing muscle protein synthesis in vivo. In this review, we discuss amino acid-induced protein synthesis in muscle in the neonate, focusing on current knowledge of the role of amino acids in the activation of mTORC1 leading to mRNA translation. The role of the amino acid transporters, SNAT2, LAT1, and PAT, in the modulation of mTORC1 activation and the role of amino acids in the activation of putative regulators of mTORC1, i.e., raptor, Rheb, MAP4K3, Vps34, and Rag GTPases, are discussed.

Suryawan, Agus; Davis, Teresa A.

2011-01-01

262

Regulation of protein synthesis by amino acids in muscle of neonates.  

PubMed

The marked increase in skeletal muscle mass during the neonatal period is largely due to a high rate of postprandial protein synthesis that is modulated by an enhanced sensitivity to insulin and amino acids. The amino acid signaling pathway leading to the stimulation of protein synthesis has not been fully elucidated. Among the amino acids, leucine is considered to be a principal anabolic agent that regulates protein synthesis. mTORC1, which controls protein synthesis, has been implicated as a target for leucine. Until recently, there have been few studies exploring the role of amino acids in enhancing muscle protein synthesis in vivo. In this review, we discuss amino acid-induced protein synthesis in muscle in the neonate, focusing on current knowledge of the role of amino acids in the activation of mTORC1 leading to mRNA translation. The role of the amino acid transporters, SNAT2, LAT1, and PAT, in the modulation of mTORC1 activation and the role of amino acids in the activation of putative regulators of mTORC1, i.e., raptor, Rheb, MAP4K3, Vps34, and Rag GTPases, are discussed. PMID:21196241

Suryawan, Agus; Davis, Teresa A

2011-01-01

263

Imaging of calcium transients in skeletal muscle fibers.  

PubMed Central

Epifluorescence images of Ca2+ transients elicited by electrical stimulation of single skeletal muscle fibers were studied with fast imaging techniques that take advantage of the large fluorescence signals emitted at relatively long wavelengths by the dyes fluo-3 and rhod-2 in response to binding of Ca2+ ions, and of the suitable features of a commercially available CCD video camera. The localized release of Ca2+ in response to microinjection of InsP3 was also monitored to demonstrate the adequate space and time resolutions of the imaging system. The time resolution of the imager system, although limited to the standard video frequency response, still proved to be adequate to investigate the fast Ca2+ release process in skeletal muscle fibers at low temperatures. Images FIGURE 4 FIGURE 5 FIGURE 6

Vergara, J; DiFranco, M; Compagnon, D; Suarez-Isla, B A

1991-01-01

264

Antidiabetic sulphonylureas activate mitochondrial permeability transition in rat skeletal muscle.  

PubMed

Antidiabetic sulphonylureas can bind to various intracellular organelles including mitochondria. The aim of this study was to monitor the influence of antidiabetic sulphonylureas on membrane permeability in mitochondria isolated from rat skeletal muscle. The effects of glibenclamide (and other sulphonylurea derivatives) on mitochondrial function were studied by measuring mitochondrial swelling, mitochondrial membrane potential, respiration rate and Ca2+ transport into mitochondria. We observed that glibenclamide induced mitochondrial swelling (EC50 = 8.2 +/- 2.5 microM), decreased the mitochondrial membrane potential and evoked Ca2+ efflux from the mitochondrial matrix. These effects were blocked by 2 microM cyclosporin A, an inhibitor of the mitochondrial permeability transition. Moreover, 30 microM glibenclamide accelerated the respiratory rate in the presence of glutamate/malate, substrates of complex I of the mitochondrial respiratory chain. In conclusion, we postulate that the antidiabetic sulphonylureas activate the mitochondrial permeability transition in skeletal muscle by increasing its sensitivity to Ca2+. PMID:15895111

Skalska, Jolanta; Debska, Grazyna; Kunz, Wolfram S; Szewczyk, Adam

2005-07-01

265

Angiotensin II, Oxidative Stress and Skeletal Muscle Wasting  

PubMed Central

Muscle atrophy (cachexia) is a muscle wasting syndrome associated with several pathological conditions in humans such as congestive heart failure, diabetes, AIDS, cancer and renal failure, and the presence of cachexia worsens outcome. Many of the conditions associated with cachexia are accompanied by stimulation of the reninangiotensin system and elevation in angiotensin II (ang II) levels. Ang II infusion induces skeletal muscle atrophy in rodents and mechanisms include increased expression of the E3 ligases atrogin-1/MuRF-1, an elevated rate of ubiquitin-proteasome mediated proteolysis and increased reactive oxygen species (ROS) levels, closely mimicking conditions of human cachexia. Ang II-induced oxidative stress contributes to muscle atrophy in a mouse model. Nicotinamide adenine dinucleotide phosphate oxidase- and mitochondria-derived ROS contribute to ang II-induced oxidative stress. Specific targeting of ROS and nicotinamide adenine dinucleotide phosphate oxidase/mitochondria cross-talk could be a beneficial, novel therapy to treat cachexia.

Sukhanov, Sergiy; Semprun-Prieto, Laura; Yoshida, Tadashi; Tabony, A. Michael; Higashi, Yusuke; Galvez, Sarah; Delafontaine, Patrice

2011-01-01

266

Developmental Programming of Fetal Skeletal Muscle and Adipose Tissue Development  

PubMed Central

All important developmental milestones are accomplished during the fetal stage, and nutrient fluctuation during this stage produces lasting effects on offspring health, so called fetal programming or developmental programming. The fetal stage is critical for skeletal muscle development, as well as adipose and connective tissue development. Maternal under-nutrition at this stage affects the proliferation of myogenic precursor cells and reduces the number of muscle fibers formed. Maternal over-nutrition results in impaired myogenesis and elevated adipogenesis. Because myocytes, adipocytes and fibrocytes are all derived from mesenchymal stem cells, molecular events which regulate the commitment of stem cells to different lineages directly impact fetal muscle and adipose tissue development. Recent studies indicate that microRNA is intensively involved in myogenic and adipogenic differentiation from mesenchymal stem cells, and epigenetic changes such as DNA methylation are expected to alter cell lineage commitment during fetal muscle and adipose tissue development.

Yan, Xu; Zhu, Mei-Jun; Dodson, Michael V.; Du, Min

2013-01-01

267

NOTE: Anisotropic photon migration in human skeletal muscle  

NASA Astrophysics Data System (ADS)

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

Binzoni, T.; Courvoisier, C.; Giust, R.; Tribillon, G.; Gharbi, T.; Hebden, J. C.; Leung, T. S.; Roux, J.; Delpy, D. T.

2006-03-01

268

Attenuation of contraction-induced skeletal muscle injury by bromelain.  

PubMed

The proteolytic enzyme, bromelain, reportedly has therapeutic effects in the treatment of inflammation and soft tissue injuries. We tested the hypothesis that bromelain attenuates skeletal muscle injury induced by lengthening contractions. The left extensor digitorum longus (EDL) muscle of anesthetized hamsters was injured using a motorized foot pedal which repeatedly flexed/extended the foot through a range of 125 degrees. The EDL muscle was electrically stimulated for 400 ms during plantarflexion. Animals were assigned randomly to either a 0-d group (evaluated 3-h post-injury) or to untreated (UT) or bromelain-treated (T) groups, evaluated 3, 7, or 14 d post-injury. Following injury, T received 5 mg.kg-1 b.w. of bromelain, twice daily. Maximum isometric tetanic force (Po) was measured in vitro, then muscles were fixed, sectioned, and examined for evidence of fiber damage. The Po of injured muscles from T were higher than Po of injured muscles from UT at 3 (18.7 +/- 0.4 vs 16.5 +/- N.cm-2 and 14 d (20.5 +/- 0.6 vs 18.2 +/- 0.6 N.cm-2) (P less than 0.05), but not 7 d (19.5 +/-0.7 vs 17.7 +/- 0.8 N.cm-2). The Po of UT injured muscles were significantly lower than Po of contralateral control muscles at all time periods. Po of injured muscles from T were lower than Po from control muscles at 3 and 7 d (P less than 0.05), but not 14 d. The number of intact fibers of 3-d UT injured muscles was lower than the number of intact fibers in control muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1548991

Walker, J A; Cerny, F J; Cotter, J R; Burton, H W

1992-01-01

269

Effect of implantation on engineered skeletal muscle constructs.  

PubMed

The development of engineered skeletal muscle would provide a viable tissue for replacement and repair of muscle damaged by disease or injury. Our current tissue-engineering methods result in three-dimensional (3D) muscle constructs that generate tension but do not advance phenotypically beyond neonatal characteristics. To develop to an adult phenotype, innervation and vascularization of the construct must occur. In this study, 3D muscle constructs were implanted into the hindlimb of a rat, along the sciatic nerve, with the sural nerve isolated, transected and sutured to the construct to encourage innervation. Aortic ring anchors were sutured to the tendons of the biceps femoris muscle so that the construct would move dynamically with the endogenous muscle. After 1?week in vivo, the constructs were explanted, evaluated for force production and stained for muscle, nerve and collagen markers. Implanted muscle constructs showed a developing capillary system, an epimysium-like outer layer of connective tissue and an increase in myofibre content. The beginning of ?-bungarotoxin clustering suggests that neuromuscular junctions (NMJs) could form on the implanted muscle, given more time in vivo. Additionally, the constructs increased maximum isometric force from 192?±?41 ?N to 549?±?103 ?N (245% increase) compared to in vitro controls, which increased from 276?±?23 ?N to 329?±?27?N (25% increase). These findings suggest that engineered muscle tissue survives 1?week of implantation and begins to develop the necessary interfaces needed to advance the phenotype toward adult muscle. However, in terms of force production, the muscle constructs need longer implantation times to fully develop an adult phenotype. PMID:22328229

Williams, Michael L; Kostrominova, Tatiana Y; Arruda, Ellen M; Larkin, Lisa M

2013-06-01

270

Methods for the Organogenesis of Skeletal Muscle in Tissue Culture  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

271

Effect of Implantation on engineered skeletal muscle constructs  

PubMed Central

The development of engineered skeletal muscle would provide a viable tissue for replacement and repair of muscle damaged by disease or injury. Current tissue engineering methods result in three-dimensional (3-D) muscle constructs that generate tension, but do not advance phenotypically beyond neonatal characteristics (Larkin et al., 2006). To develop to an adult phenotype, innervation and vascularization of the construct must occur. In this study, 3-D muscle constructs were implanted into the hindlimb of a rat along the sciatic nerve with the sural nerve isolated, transected and sutured to the construct to encourage innervation. Aortic ring anchors were sutured to the tendons of the biceps femoris muscle so that the construct would move dynamically with the endogenous muscle. After 1 week in vivo, constructs were explanted, evaluated for force production, and stained for muscle, nerve, and collagen markers. Implanted muscle constructs showed a developing capillary system, an epimysium-like outer layer of connective tissue, and an increase in myofiber content. The beginning of alpha-bungarotoxin clustering suggests that neuromuscular junctions (NMJ) could form on the implanted muscle given more time in vivo. Additionally, the constructs increased maximum isometric force from 192±41?N to 549±103?N (245% increase) compared to in vitro controls that increased from 276±23?N to 329±27?N (25% increase). These findings suggest that engineered muscle tissue survives 1 week implantation and begins to develop the necessary interfaces needed to advance the phenotype toward adult muscle. However, in terms of force production, the muscle constructs need longer implantation times to fully develop an adult phenotype.

Williams, Michael L; Kostrominova, Tatiana Y; Arruda, Ellen M.; Larkin, Lisa M.

2011-01-01

272

[Calcium in the developing skeletal muscles of the chick embryo].  

PubMed

The osmium-pyroantimonate technique was used for the ultrastructural study of Ca2+-localization in two types of chick embryo skeletal muscles: m. pectoralis and m. soleus. In 8- and 12-day old embryos the pyroantimonate precipitate was found on plasmalemma, condensed chromatine and ribosomes and in N-lines of I-band. During myogenesis (15-, 21-day old embryos) the calcium precipitate is redistributed from the above mentioned sites to terminal cisternae and N-line of I-band. It is proposed that calcium of N-lines may be involved in the glycogenolysis, its association with the muscle contraction occurring particularly at early developmental stages. PMID:6753275

Samosudova, N V; Enenko, S O; Larin, Iu S; Shungskaia, V E

1982-07-01

273

Delayed Rectification and Anomalous Rectification in Frog's Skeletal Muscle Membrane  

Microsoft Academic Search

A B s T R A C T Delayed rectification was elicited in frog's skeletal muscles bathed in choline-Ringer's solution, in normal Ringer's solution with tetrodotoxin, in 40 mM NasSO~ solution with tetrodotoxin, and even in 40 mM K,SO4 solution when the membrane had been previously hyperpolarized. However, after a sustained depolarization current-voltage relations in 40 mM K2SO4 and in

SHIGEHIRO NAKAJIMA; SHIZUKO IWASAKI; KUNIHIKO OBATA

2009-01-01

274

Calcium regulation of oxidative phosphorylation in rat skeletal muscle mitochondria  

Microsoft Academic Search

Activation of oxidative phosphorylation by physiological levels of calcium in mitochondria from rat skeletal muscle was analysed using top-down elasticity and regulation analysis. Oxidative phosphorylation was conceptually divided into three subsystems (substrate oxidation, proton leak and phosphorylation) connected by the membrane potential or the protonmotive force. Calcium directly activated the phosphorylation subsystem and (with sub-saturating 2-oxoglutarate) the substrate oxidation subsystem

N. Irene Kavanagh; Edward K. Ainscow; Martin D. Brand

2000-01-01

275

A novel in vitro three-dimensional skeletal muscle model  

Microsoft Academic Search

A novel three-dimensional (3D) skeletal muscle model composed of C2C12 mouse myoblasts is described. This model was generated\\u000a by cultivating myoblasts in suspension using the rotary cell culture system (RCCS), a unique culture environment. Single-cell\\u000a suspensions of myoblasts were seeded at 5???105\\/ml in growth medium without exogenous support structures or substrates. Cell aggregation occurred in both RCCS and suspension\\u000a control

Michele L. Marquette; Diane Byerly; Marguerite Sognier

2007-01-01

276

Myostatin and the control of skeletal muscle mass.  

PubMed

The mechanisms by which tissue size is controlled are poorly understood. Over 30 years ago, Bullough proposed the existence of chalones, which act as tissue-specific negative growth regulators. The recent discovery of myostatin suggests that negative regulation of tissue growth may be an important mechanism for controlling skeletal muscle mass and raises the possibility that growth inhibitors may also be involved in regulating the size of other tissues. PMID:10508689

Lee, S J; McPherron, A C

1999-10-01

277

The role of mitochondria in aging of skeletal muscle  

Microsoft Academic Search

Aging can be characterized as a time dependent decline of maximal functionality that affects tissues and organs of the whole\\u000a body. Such is induced by the progressive loss of redundant components and leads to an increased susceptibility to disease\\u000a and risk of death. Regarding the aging of skeletal muscle, it has been pointed out that mitochondria is a key factor

Pedro Alexandre Figueiredo; Maria P. Mota; Hans Joachim Appell; José Alberto Duarte

2008-01-01

278

Lovastatin increases exercise-induced skeletal muscle injury  

Microsoft Academic Search

This study tested the hypothesis that exercise in combination with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor produces greater creatine kinase (CK) elevations, an index of skeletal muscle injury, than exercise alone, using a double-blind, placebo-controlled design. Fifty-nine healthy men aged 18 to 65 years with low-density lipoprotein cholesterol (LDL-C) levels greater than 3.36 mmol\\/L (130 mg\\/dL) despite diet therapy

Paul D. Thompson; Joseph M. Zmuda; Leslie J. Domalik; Richard J. Zimet; Joan Staggers; John R. Guyton

1997-01-01

279

Receptor Expression in Rat Skeletal Muscle Cell Cultures  

NASA Technical Reports Server (NTRS)

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

Young, Ronald B.

1996-01-01

280

Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.  

PubMed

Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting. PMID:12019153

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

2002-05-15

281

Signalling and the control of skeletal muscle size  

SciTech Connect

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

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

2010-11-01

282

Xirp Proteins Mark Injured Skeletal Muscle in Zebrafish  

PubMed Central

Myocellular regeneration in vertebrates involves the proliferation of activated progenitor or dedifferentiated myogenic cells that have the potential to replenish lost tissue. In comparison little is known about cellular repair mechanisms within myocellular tissue in response to small injuries caused by biomechanical or cellular stress. Using a microarray analysis for genes upregulated upon myocellular injury, we identified zebrafish Xin-actin-binding repeat-containing protein1 (Xirp1) as a marker for wounded skeletal muscle cells. By combining laser-induced micro-injury with proliferation analyses, we found that Xirp1 and Xirp2a localize to nascent myofibrils within wounded skeletal muscle cells and that the repair of injuries does not involve cell proliferation or Pax7+ cells. Through the use of Xirp1 and Xirp2a as markers, myocellular injury can now be detected, even though functional studies indicate that these proteins are not essential in this process. Previous work in chicken has implicated Xirps in cardiac looping morphogenesis. However, we found that zebrafish cardiac morphogenesis is normal in the absence of Xirp expression, and animals deficient for cardiac Xirp expression are adult viable. Although the functional involvement of Xirps in developmental and repair processes currently remains enigmatic, our findings demonstrate that skeletal muscle harbours a rapid, cell-proliferation-independent response to injury which has now become accessible to detailed molecular and cellular characterizations.

Otten, Cecile; van der Ven, Peter F.; Lewrenz, Ilka; Paul, Sandeep; Steinhagen, Almut; Busch-Nentwich, Elisabeth; Eichhorst, Jenny; Wiesner, Burkhard; Stemple, Derek; Strahle, Uwe; Furst, Dieter O.; Abdelilah-Seyfried, Salim

2012-01-01

283

A reservoir of brown adipocyte progenitors in human skeletal muscle.  

PubMed

Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-gamma (PPARgamma) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPARgamma agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation. PMID:18617684

Crisan, Mihaela; Casteilla, Louis; Lehr, Lorenz; Carmona, Mamen; Paoloni-Giacobino, Ariane; Yap, Solomon; Sun, Bin; Léger, Bertrand; Logar, Alison; Pénicaud, Luc; Schrauwen, Patrick; Cameron-Smith, David; Russell, Aaron Paul; Péault, Bruno; Giacobino, Jean-Paul

2008-09-01

284

Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats  

PubMed Central

In exercising skeletal muscle, vasoconstrictor responses to ?-adrenoceptor activation are attenuated in part by nitric oxide (NO) produced by the neuronal isoform of NO synthase (nNOS), which is expressed constitutively in skeletal muscle cells. In skeletal muscle of pregnant animals, nNOS mRNA is upregulated, suggesting that muscle nNOS expression is modulated by the steroid hormone oestrogen. Whether oestrogen-induced changes in nNOS expression have measurable effects on vasoregulation in skeletal muscle is unknown. In this study, we hypothesized that oestrogen deficiency would reduce muscle nNOS expression, resulting in impaired modulation of sympathetic vasoconstriction in exercising skeletal muscle. Compared to gonadally intact rats, we found that ovariectomized (OVX) rats were characterized by greater sympathetic vasoconstriction in contracting hindlimb and reduced nNOS, but not eNOS, in skeletal muscle. In addition, NOS inhibition resulted in a greater enhancement of sympathetic vasoconstriction in contracting hindlimbs of intact compared to OVX rats. These effects of oestrogen deficiency were prevented by chronic treatment of OVX rats with 17?-oestradiol, but not with chronic progesterone or acute oestradiol. Further analysis revealed that skeletal muscle nNOS correlated directly with plasma 17?-oestradiol and inversely with the magnitude of sympathetic vasoconstrictor responses in contracting hindlimbs. These data indicate that NO-dependent attenuation of sympathetic vasoconstriction in contracting skeletal muscle is impaired in oestrogen-deficient female rats, and suggest that this impairment may be mediated by reduced skeletal muscle nNOS expression.

Fadel, Paul J; Zhao, Weiying; Thomas, Gail D

2003-01-01

285

Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles.  

PubMed Central

The skeletal isoform of Ca2+ release channel, RyR1, plays a central role in activation of skeletal muscle contraction. Another isoform, RyR3, has been observed recently in some mammalian skeletal muscles, but whether it participates in regulating skeletal muscle contraction is not known. The expression of RyR3 in skeletal muscles was studied in mice from late fetal stages to adult life. RyR3 was found to be expressed widely in murine skeletal muscles during the post-natal phase of muscle development, but was not detectable in muscles of adult mice, with the exception of the diaphragm and soleus muscles. RyR3 knockout mice were generated, and it was shown that skeletal muscle contraction in these mice was impaired during the first weeks after birth. In skeletal muscles isolated from newborn RyR3(-/- )mice, but not in those from adult mice, the twitch elicited by electrical stimulation and the contracture induced by caffeine were strongly depressed. These results provide the first evidence that RyR3 has a physiological role in excitation-contraction coupling of neonatal skeletal muscles. The disproportion between the low amount of RyR3 and the large impact of the RyR3 knockout suggests that this isoform contributes to the amplification of Ca2+ released by the existing population of ryanodine receptors (RyR1).

Bertocchini, F; Ovitt, C E; Conti, A; Barone, V; Scholer, H R; Bottinelli, R; Reggiani, C; Sorrentino, V

1997-01-01

286

Laser-inflicted injury of zebrafish embryonic skeletal muscle.  

PubMed

Various experimental approaches have been used in mouse to induce muscle injury with the aim to study muscle regeneration, including myotoxin injections (bupivacaine, cardiotoxin or notexin), muscle transplantations (denervation-devascularization induced regeneration), intensive exercise, but also murine muscular dystrophy models such as the mdx mouse (for a review of these approaches see). In zebrafish, genetic approaches include mutants that exhibit muscular dystrophy phenotypes (such as runzel or sapje) and antisense oligonucleotide morpholinos that block the expression of dystrophy-associated genes. Besides, chemical approaches are also possible, e.g. with Galanthamine, a chemical compound inhibiting acetylcholinesterase, thereby resulting in hypercontraction, which eventually leads to muscular dystrophy. However, genetic and pharmacological approaches generally affect all muscles within an individual, whereas the extent of physically inflicted injuries are more easily controlled spatially and temporally. Localized physical injury allows the assessment of contralateral muscle as an internal control. Indeed, we recently used laser-mediated cell ablation to study skeletal muscle regeneration in the zebrafish embryo, while another group recently reported the use of a two-photon laser (822 nm) to damage very locally the plasma membrane of individual embryonic zebrafish muscle cells. Here, we report a method for using the micropoint laser (Andor Technology) for skeletal muscle cell injury in the zebrafish embryo. The micropoint laser is a high energy laser which is suitable for targeted cell ablation at a wavelength of 435 nm. The laser is connected to a microscope (in our setup, an optical microscope from Zeiss) in such a way that the microscope can be used at the same time for focusing the laser light onto the sample and for visualizing the effects of the wounding (brightfield or fluorescence). The parameters for controlling laser pulses include wavelength, intensity, and number of pulses. Due to its transparency and external embryonic development, the zebrafish embryo is highly amenable for both laser-induced injury and for studying the subsequent recovery. Between 1 and 2 days post-fertilization, somitic skeletal muscle cells progressively undergo maturation from anterior to posterior due to the progression of somitogenesis from the trunk to the tail. At these stages, embryos spontaneously twitch and initiate swimming. The zebrafish has recently been recognized as an important vertebrate model organism for the study of tissue regeneration, as many types of tissues (cardiac, neuronal, vascular etc.) can be regenerated after injury in the adult zebrafish. PMID:23407156

Otten, Cécile; Abdelilah-Seyfried, Salim

2013-01-01

287

Exercise influences circadian gene expression in equine skeletal muscle.  

PubMed

Circadian rhythms are endogenously generated 24-h oscillations that coordinate numerous aspects of mammalian physiology, metabolism and behaviour. The existence of a molecular circadian clock in equine skeletal muscle has previously been demonstrated. This study investigates how the circadian 24-h expression of exercise-relevant genes in skeletal muscle is influenced by a regular exercise regime. Mid-gluteal, percutaneous muscle biopsies were obtained over a 24-h period from six Thoroughbred mares before and after an 8-week exercise programme. Real-time qPCR assays were used to assess the expression patterns of core clock genes ARNTL, PER2, NR1D1, clock-controlled gene DBP, and muscle genes MYF6, UCP3, VEGFA, FOXO1, MYOD1, PPARGC1A, PPARGC1B, FBXO32 and PDK4. Two-way repeated measures ANOVA revealed a significant interaction between circadian time and exercise for muscle genes MYF6, UCP3, MYOD1 and PDK4. A significant effect of time was observed for all genes with the exception of VEGFA, where a main effect of exercise was observed. By cosinor analysis, the core clock genes, ARNTL (P?<0.01) and NR1D1 (P?<0.05), showed 24-h rhythmicity both pre- and post-exercise, while PER2 expression was rhythmic post-exercise (P?<0.05) but not pre-exercise. The expression profiles of muscle genes MYOD1 and MYF6 showed significant fits to a 24-h cosine waveform indicative of circadian rhythmicity post-exercise only (P?<0.01). This study suggests that the metabolic capacity of muscle is influenced by scheduled exercise and that optimal athletic performance may be achieved when exercise times and competition times coincide. PMID:24888677

Murphy, B A; Wagner, A L; McGlynn, O F; Kharazyan, F; Browne, J A; Elliott, J A

2014-07-01

288

Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles  

PubMed Central

Described here is a method to measure contractility of isolated skeletal muscles. Parameters such as muscle force, muscle power, contractile kinetics, fatigability, and recovery after fatigue can be obtained to assess specific aspects of the excitation-contraction coupling (ECC) process such as excitability, contractile machinery and Ca2+ handling ability. This method removes the nerve and blood supply and focuses on the isolated skeletal muscle itself. We routinely use this method to identify genetic components that alter the contractile property of skeletal muscle though modulating Ca2+ signaling pathways. Here, we describe a newly identified skeletal muscle phenotype, i.e., mechanic alternans, as an example of the various and rich information that can be obtained using the in vitro muscle contractility assay. Combination of this assay with single cell assays, genetic approaches and biochemistry assays can provide important insights into the mechanisms of ECC in skeletal muscle.

Park, Ki Ho; Brotto, Leticia; Lehoang, Oanh; Brotto, Marco; Ma, Jianjie; Zhao, Xiaoli

2012-01-01

289

Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases.  

PubMed

The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin-proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross-sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS-driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization. PMID:20082419

Baptista, Igor L; Leal, Marcelo L; Artioli, Guilherme G; Aoki, Marcelo S; Fiamoncini, Jarlei; Turri, Antonio O; Curi, Rui; Miyabara, Elen H; Moriscot, Anselmo S

2010-06-01

290

Non-viral gene delivery in skeletal muscle: a protein factory  

Microsoft Academic Search

Ever since the publication of the first reports in 1990 using skeletal muscle as a direct target for expressing foreign transgenes, an avalanche of papers has identified a variety of proteins that can be synthesized and correctly processed by skeletal muscle. The impetus to the development of such applications is not only amelioration of muscle diseases, but also a range

Q L Lu; G Bou-Gharios; T A Partridge

2003-01-01

291

Metabolic adaptations to repeated periods of contraction with reduced blood flow in canine skeletal muscle  

Microsoft Academic Search

BACKGROUND: Patients suffering from Intermittent Claudication (IC) experience repeated periods of muscle contraction with low blood flow, throughout the day and this may contribute to the hypothesised skeletal muscle abnormalities. However, no study has evaluated the consequences of intermittent contraction with low blood flow on skeletal muscle tissue. Our aim was to generate this basic physiological data, determining the 'normal'

Alan MacInnes; James A Timmons

2005-01-01

292

In vivo monitoring of norepinephrine and its metabolites in skeletal muscle  

Microsoft Academic Search

Although skeletal muscle sympathetic nerve activity plays an important role in the regulation of vascular tone and glucose metabolism, relatively little is known about regional norepinephrine (NE) kinetics in the skeletal muscle. With use of the dialysis technique, we implanted dialysis probes in the adductor muscle of anesthetized rabbits and examined whether dialysate NE and its metabolites were influenced by

Noriyuki Tokunaga; Toji Yamazaki; Tsuyoshi Akiyama; Shunji Sano; Hidezo Mori

2003-01-01

293

Skeletal muscle extracellular matrix remodelling after aestivation in the green striped burrowing frog, Cyclorana alboguttata  

Microsoft Academic Search

Connective tissue has recently been found to play a role in mediating mammalian skeletal muscle atrophy. We investigated connective tissue remodelling in the skeletal muscle of a species of the Australian burrowing frog, Cyclorana alboguttata. Despite being inactive whilst aestivating, the frog shows an inhibition of muscle atrophy. Connective tissue size and distribution was measured in histological sections of the

Nicholas J. Hudson; Gregory S. Harper; Peter G. Allingham; Craig E. Franklin; W. Barris; Sigrid A. Lehnert

2007-01-01

294

LongSAGE analysis of skeletal muscle at three prenatal stages in Tongcheng and Landrace pigs  

Microsoft Academic Search

BACKGROUND: Obese and lean pig breeds show obvious differences in muscle growth; however, the molecular mechanism underlying phenotype variation remains unknown. Prenatal muscle development programs postnatal performance. Here, we describe a genome-wide analysis of differences in prenatal skeletal muscle between Tongcheng (a typical indigenous Chinese breed) and Landrace (a leaner Western breed) pigs. RESULTS: We generated transcriptome profiles of skeletal

Zhonglin Tang; Yong Li; Ping Wan; Xiaoping Li; Shuhong Zhao; Bang Liu; Bin Fan; Mengjin Zhu; Mei Yu; Kui Li

2007-01-01

295

Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture  

Microsoft Academic Search

Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of

Yan Wei; Yuan Li; Chao Chen; Katharina Stoelzel; Andreas M. Kaufmann; Andreas E. Albers

2011-01-01

296

Expression of TPM1?, a Novel Sarcomeric Isoform of the TPM1 Gene, in Mouse Heart and Skeletal Muscle  

PubMed Central

We have investigated the expression of TPM1? and TPM1? in mouse striated muscles. TPM1? and TMP1? were amplified from the cDNA of mouse heart by using conventional RT-PCR. We have cloned the PCR amplified DNA and determined the nucleotide sequences. Deduced amino acid sequences show that there are three amino acid changes in mouse exon 2a when compared with the human TPM1?. However, the deduced amino acid sequences of human TPM1? and mouse TPM1? are identical. Conventional RT-PCR data as well as qRT-PCR data, calculating both absolute copy number and relative expression, revealed that the expression of TPM1? is significantly lower compared to TPM1? in both mouse heart and skeletal muscle. It was also found that the expression level of TPM1? transcripts in mouse heart is higher than it is in skeletal muscle. To the best of our knowledge, this is the first report of the expression of TPM1? in mammalian skeletal muscle.

Dube, Syamalima; Panebianco, Lauren; Matoq, Amr A.; Chionuma, Henry N.; Denz, Christopher R.; Poiesz, Bernard J.; Dube, Dipak K.

2014-01-01

297

Skeletal muscle plasticity with marathon training in novice runners.  

PubMed

The purpose of this study was to investigate leg muscle adaptation in runners preparing for their first marathon. Soleus and vastus lateralis (VL) biopsies were obtained from six recreational runners (23 ± 1 years, 61 ± 3 kg) before (T1), after 13 weeks of run training (T2), and after 3 weeks of taper and marathon (T3). Single muscle fiber size, contractile function (strength, speed, and power) and oxidative enzyme activity [citrate synthase (CS)] were measured at all three time points, and fiber type distribution was determined before and after the 16-week intervention. Training increased VO(2max) ?9% (P<0.05). All soleus parameters were unchanged. VL MHC I fiber diameter increased (+8%; P<0.05) from T1 to T2. VL MHC I V(o) (-12%), MHC I power (-22%) and MHC IIa power (-29%) were reduced from T1 to T2 (P<0.05). No changes in VL single fiber contractile properties were observed from T2 to T3. No change was observed in soleus CS activity, whereas VL CS activity increased 66% (P<0.05). Our observations indicate that modest marathon training elicits very specific skeletal muscle adaptations that likely support the ability to perform 42.2 km of continuous running - further strengthening the existing body of evidence for skeletal muscle specificity. PMID:21477203

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

2012-10-01

298

Skeletal muscle vasodilatation during maximal exercise in health and disease  

PubMed Central

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.

Calbet, Jose A L; Lundby, Carsten

2012-01-01

299

Free Radical Formation after Intensive Exercise in Thoroughbred Skeletal Muscles  

PubMed Central

Although high oxygen consumption in skeletal muscle may result in severe oxidative stress, there are no direct studies that have documented free radical production in horse muscles after intensive exercise. To find a new parameter indicating the muscle adaptation state for the training of Thoroughbred horses, we examined free radical formation in the muscle by using electron paramagnetic resonance (EPR). Ten male Thoroughbred horses received conventional training for 18 weeks. Before and after the training period, all horses performed an exhaustive incremental load exercise on a 6% incline treadmill. Muscle samples of the middle gluteal muscle were taken pre-exercise and 1 min, 1 hr, and 1 day after exercise. Muscle fiber type composition was also determined in the pre-exercise samples by immunohistochemical staining with monoclonal antibody to myosin heavy chain. We measured the free radical in the muscle homogenate using EPR at room temperature, and the amount was expressed as relative EPR signal intensity. There was a significant increase in Type IIA muscle fiber composition and a decrease in Type IIX fiber composition after the training period. Before the training period, the mean value of the relative EPR signal intensity showed a significant increase over the pre-exercise value at 1 min after the exercise and an incomplete recovery at 24 hr after the exercise. While no significant changes were found in the relative EPR signal intensity after the training period. There was a significant relationship between percentages of Type IIA fiber and change rates in EPR signal intensity at 1 min after exercise. The measurement of free radicals may be useful for determining the muscle adaptation state in the training of Thoroughbred horses.

MINAMI, Yoshio; KAWAI, Minako; MIGITA, Taiko C.; HIRAGA, Atsushi; MIYATA, Hirofumi

2011-01-01

300

Sarcolemmal carbonic anhydrase in red and white rabbit skeletal muscle.  

PubMed

Sarcolemmal vesicles of white and red skeletal muscles of the rabbit were prepared by consecutive density gradient centrifugations in sucrose and dextran according to Seiler and Fleischer (1982, J. Biol. Chem. 257, 13,862-13,871). White and red muscle membrane fractions enriched in sarcolemma were characterized by high ouabain-sensitive Na+, K(+)-ATPase, by high Mg2(+)-ATPase activity, and by a high cholesterol content. Ca2(+)-ATPase activity, a marker enzyme for sarcoplasmic reticulum, was not detectable in the highly purified white and red muscle sarcolemmal fractions. White and red muscle sarcolemmal fractions exhibited no significant differences with regard to Na+, K(+)-ATPase, Mg2(+)-ATPase, and cholesterol. Specific activity of carbonic anhydrase in white muscle sarcolemmal fractions was 38 U.ml/mg and was 17.6 U.ml/mg in red muscle sarcolemma. Inhibition properties of sarcolemmal carbonic anhydrase were analyzed for acetazolamide, chlorzolamide, and cyanate. White muscle sarcolemmal carbonic anhydrase is characterized by inhibition constants, KI, toward acetazolamide of 4.6 X 10(-8) M, toward chlorzolamide of 0.75 X 10(-8) M, and toward cyanate of 1.3 X 10(-4) M. Red muscle sarcolemmal carbonic anhydrase is characterized by KI values toward acetazolamide of 8.1 X 10(-8) M, toward chlorzolamide of 6.3 X 10(-8) M, and toward cyanate of 0.81 X 10(-4) M. In contrast to the high specific carbonic anhydrase activities in sarcolemma, carbonic anhydrase activity in sarcoplasmic reticulum from white muscle varied between values of only 0.7 and 3.3 U.ml/mg. Carbonic anhydrase of red muscle sarcoplasmic reticulum ranged from 2.4 to 3.7 U.ml/mg. PMID:2112370

Wetzel, P; Gros, G

1990-06-01

301

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

PubMed Central

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

2014-01-01

302

Engineering skeletal muscle tissue--new perspectives in vitro and in vivo.  

PubMed

Muscle tissue engineering (TE) has not yet been clinically applied because of several problems. However, the field of skeletal muscle TE has been developing tremendously and new approaches and techniques have emerged. This review will highlight recent developments in the field of nanotechnology, especially electrospun nanofibre matrices, as well as potential cell sources for muscle TE. Important developments in cardiac muscle TE and clinical studies on Duchenne muscular dystrophy (DMD) will be included to show their implications on skeletal muscle TE. PMID:21091904

Klumpp, Dorothee; Horch, Raymund E; Kneser, Ulrich; Beier, Justus P

2010-11-01

303

Cardiac Myosin Binding Protein-C Plays No Regulatory Role in Skeletal Muscle Structure and Function  

PubMed Central

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

Lin, Brian; Govindan, Suresh; Lee, Kyounghwan; Zhao, Piming; Han, Renzhi; Runte, K. Elisabeth; Craig, Roger; Palmer, Bradley M.; Sadayappan, Sakthivel

2013-01-01

304

On a phenomenological model for fatigue effects in skeletal muscles.  

PubMed

This work deals with the development and implementation of a new fatigue model for simulating fatigue effects in skeletal muscles. Basic idea of this modelling strategy is an approach that divides the fibres of a muscle into three groups: fibres in the active state, those that are already fatigued and fibres in the resting state. All fibres are able to switch between the different groups by defining adequate rates. In this way a continuous transfer of fibres between those three states has been described. Rooted on an incompressible, hyperelastic constitutive law with transversely isotropic characteristics the fatigue model has been implemented in the framework of the finite element method. Numerical examples are given in order to illustrate the ability of this model. Further, we validate the model by fatigue experiments of the rat soleus muscle. In doing so, it proves that the model is able to predict physiological observations and mechanical test results. PMID:20211632

Böl, Markus; Stark, Heiko; Schilling, Nadja

2011-07-21

305

Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats.  

PubMed

Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats. PMID:24652515

Garvey, Sean M; Dugle, Janis E; Kennedy, Adam D; McDunn, Jonathan E; Kline, William; Guo, Lining; Guttridge, Denis C; Pereira, Suzette L; Edens, Neile K

2014-06-01

306

Activated Protein Synthesis and Suppressed Protein Breakdown Signaling in Skeletal Muscle of Critically Ill Patients  

PubMed Central

Background Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3? (GSK3?) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls. Methodology/Principal Findings ICU patients were systemically inflamed, moderately hyperglycemic, received insulin therapy, and showed a tendency to lower plasma branched chain amino acids compared with controls. Using Western blotting we measured Akt, GSK3?, mTOR, ribosomal protein S6 kinase (S6k), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and muscle ring finger protein 1 (MuRF1); and by RT-PCR we determined mRNA expression of, among others, insulin-like growth factor 1 (IGF-1), FoxO 1, 3 and 4, atrogin1, MuRF1, interleukin-6 (IL-6), tumor necrosis factor ? (TNF-?) and myostatin. Unexpectedly, in critically ill ICU patients Akt-mTOR-S6k signaling was substantially higher compared with controls. FoxO1 mRNA was higher in patients, whereas FoxO3, atrogin1 and myostatin mRNAs and MuRF1 protein were lower compared with controls. A moderate correlation (r2?=?0.36, p<0.05) between insulin infusion dose and phosphorylated Akt was demonstrated. Conclusions/Significance We present for the first time muscle protein turnover signaling in critically ill ICU patients, and we show signaling pathway activity towards a stimulation of muscle protein synthesis and a somewhat inhibited proteolysis.

Jespersen, Jakob G.; Nedergaard, Anders; Reitelseder, S?ren; Mikkelsen, Ulla R.; Dideriksen, Kasper J.; Agergaard, Jakob; Kreiner, Frederik; Pott, Frank C.; Schjerling, Peter; Kjaer, Michael

2011-01-01

307

Identification and characterization of a membrane receptor for proteolysis-inducing factor on skeletal muscle.  

PubMed

Proteolysis-inducing factor (PIF) is a sulfated glycoprotein produced by cachexia-inducing tumors, which induces atrophy of skeletal muscle. PIF has been shown to bind specifically with high affinity (K(d), in nanomolar) to sarcolemma membranes from skeletal muscle of both the mouse and the pig, as well as murine myoblasts and a human muscle cell line. Ligand binding was abolished after enzymatic deglycosylation, suggesting that binding was mediated through the oligosaccharide chains in PIF. Chondroitin sulfate, but not heparan or dermatan sulfate, showed competitive inhibition (K(d), 1.1 x 10(-7) mol/L) of binding of PIF to the receptor, suggesting an interaction with the sulfated oligosaccharide chains. Ligand blotting of [(35)S]PIF to triton solublized membranes from C(2)C(12) cells provided evidence for a binding protein of apparent M(r) of approximately 40,000. Amino acid sequence analysis showed the PIF receptor to be a DING protein. Antisera reactive to a 19mer from the N-terminal amino acid residues of the binding protein attenuated protein degradation and activation of the ubiquitin-proteasome pathway induced by PIF in murine myotubes. In addition, the antisera was highly effective in attenuating the decrease in body weight in mice bearing the MAC16 tumor, with a significant increase in muscle wet weight due to an increase in the rate of protein synthesis, together with a reduction in protein degradation through attenuation of the increased proteasome expression and activity. These results confirm that the PIF binding protein has a functional role in muscle protein atrophy in cachexia and that it represents a potential new therapeutic target. PMID:18056470

Todorov, Penio T; Wyke, Stacey M; Tisdale, Michael J

2007-12-01

308

Three-dimensionally printed biological machines powered by skeletal muscle  

PubMed Central

Combining biological components, such as cells and tissues, with soft robotics can enable the fabrication of biological machines with the ability to sense, process signals, and produce force. An intuitive demonstration of a biological machine is one that can produce motion in response to controllable external signaling. Whereas cardiac cell-driven biological actuators have been demonstrated, the requirements of these machines to respond to stimuli and exhibit controlled movement merit the use of skeletal muscle, the primary generator of actuation in animals, as a contractile power source. Here, we report the development of 3D printed hydrogel “bio-bots” with an asymmetric physical design and powered by the actuation of an engineered mammalian skeletal muscle strip to result in net locomotion of the bio-bot. Geometric design and material properties of the hydrogel bio-bots were optimized using stereolithographic 3D printing, and the effect of collagen I and fibrin extracellular matrix proteins and insulin-like growth factor 1 on the force production of engineered skeletal muscle was characterized. Electrical stimulation triggered contraction of cells in the muscle strip and net locomotion of the bio-bot with a maximum velocity of ?156 ?m s?1, which is over 1.5 body lengths per min. Modeling and simulation were used to understand both the effect of different design parameters on the bio-bot and the mechanism of motion. This demonstration advances the goal of realizing forward-engineered integrated cellular machines and systems, which can have a myriad array of applications in drug screening, programmable tissue engineering, drug delivery, and biomimetic machine design.

Cvetkovic, Caroline; Raman, Ritu; Chan, Vincent; Williams, Brian J.; Tolish, Madeline; Bajaj, Piyush; Sakar, Mahmut Selman; Asada, H. Harry; Saif, M. Taher A.; Bashir, Rashid

2014-01-01

309

Three-dimensionally printed biological machines powered by skeletal muscle.  

PubMed

Combining biological components, such as cells and tissues, with soft robotics can enable the fabrication of biological machines with the ability to sense, process signals, and produce force. An intuitive demonstration of a biological machine is one that can produce motion in response to controllable external signaling. Whereas cardiac cell-driven biological actuators have been demonstrated, the requirements of these machines to respond to stimuli and exhibit controlled movement merit the use of skeletal muscle, the primary generator of actuation in animals, as a contractile power source. Here, we report the development of 3D printed hydrogel "bio-bots" with an asymmetric physical design and powered by the actuation of an engineered mammalian skeletal muscle strip to result in net locomotion of the bio-bot. Geometric design and material properties of the hydrogel bio-bots were optimized using stereolithographic 3D printing, and the effect of collagen I and fibrin extracellular matrix proteins and insulin-like growth factor 1 on the force production of engineered skeletal muscle was characterized. Electrical stimulation triggered contraction of cells in the muscle strip and net locomotion of the bio-bot with a maximum velocity of ?156 ?m s(-1), which is over 1.5 body lengths per min. Modeling and simulation were used to understand both the effect of different design parameters on the bio-bot and the mechanism of motion. This demonstration advances the goal of realizing forward-engineered integrated cellular machines and systems, which can have a myriad array of applications in drug screening, programmable tissue engineering, drug delivery, and biomimetic machine design. PMID:24982152

Cvetkovic, Caroline; Raman, Ritu; Chan, Vincent; Williams, Brian J; Tolish, Madeline; Bajaj, Piyush; Sakar, Mahmut Selman; Asada, H Harry; Saif, M Taher A; Bashir, Rashid

2014-07-15

310

Absence of Aquaporin4 in Skeletal Muscle Alters Proteins Involved in Bioenergetic Pathways and Calcium Handling  

Microsoft Academic Search

Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4

Davide Basco; Grazia Paola Nicchia; Angelo D'Alessandro; Lello Zolla; Maria Svelto; Antonio Frigeri; Eliana Saul Furquim Werneck Abdelhay

2011-01-01

311

Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass  

Microsoft Academic Search

Skeletal muscle hypertrophy is a result of increased load, such as functional and stretch-overload. Activation of satellite\\u000a cells and proliferation, differentiation and fusion are required for hypertrophy of overloaded skeletal muscles. On the contrary,\\u000a a dramatic loss of skeletal muscle mass determines atrophy settings. The epigenetic changes involved in gene regulation at\\u000a DNA and chromatin level are critical for the

Mattia Quattrocelli; Stefania Crippa; Ilaria Perini; Flavio Ronzoni; Maurilio Sampaolesi

2009-01-01

312

Insulin Action on Heart and Skeletal Muscle FDG Uptake in Patients with Hypertriglyceridemia  

Microsoft Academic Search

Abnormal heart and skeletal muscle 18F-fluorodeoxyglucose (FDG) uptake in patients with insulin resistance has been demonstrated. Although the existence of whole-body insulin resistance has been reported in hypertriglyceridemics, its spe cific role in heart and skeletal muscle FDG uptake in hypertriglyc eridemics has not been clarified. Methods: We compared heart and skeletal muscle FDG uptake using PET and the whole-body

Ikuo Yokoyama; Tohru Ohtake; Shin-ichi Momomura; Katsunori Yonekura; Naoshi Kobayakawa; Teruhiko Aoyagi; Seiryo Sugiura; Nobuhiro Yamada; Kuni Ohtomo; Yasuhito Sasaki; Masao Ornat; Yoshio Yazaki

313

Myocarditis and diffuse skeletal muscle oedema: new features of neuromyelitis optica spectrum disorder? A case report.  

PubMed

We present a case report of newly diagnosed neuromyelitis optica spectrum disorder (NMOSD) with associated myocarditis and diffuse oedema of the pelvic and anterior compartment thigh muscles on magnetic resonance imaging. Aquaporin 4 antibodies are expressed in skeletal myofibres but involvement of skeletal muscle is rarely reported in NMOSD and myocarditis has not previously been described in this context. This case highlights the need for further research into the involvement of cardiac and skeletal muscle in NMOSD. PMID:23846353

Cosgrove, Jeremy; Alli, Saira; Ramadan, Hawraman; Ford, Helen L

2014-01-01

314

Effects of leucine and its metabolite ?-hydroxy-?-methylbutyrate on human skeletal muscle protein metabolism.  

PubMed

Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is 'sensed' have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-(13)C2]Leu and [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling 90 min vs. 30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; -57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu. PMID:23551944

Wilkinson, D J; Hossain, T; Hill, D S; Phillips, B E; Crossland, H; Williams, J; Loughna, P; Churchward-Venne, T A; Breen, L; Phillips, S M; Etheridge, T; Rathmacher, J A; Smith, K; Szewczyk, N J; Atherton, P J

2013-06-01

315

Myocardin is a bifunctional switch for smooth versus skeletal muscle differentiation  

PubMed Central

Skeletal and smooth muscle can mutually transdifferentiate, but little molecular insight exists as to how each muscle program may be subverted to the other. The myogenic basic helix–loop–helix transcription factors MyoD and myogenin (Myog) direct the development of skeletal muscle and are thought to be dominant over the program of smooth muscle cell (SMC) differentiation. Myocardin (Myocd) is a serum response factor (SRF) coactivator that promotes SMC differentiation through transcriptional stimulation of SRF-dependent smooth muscle genes. Here we show by lineage-tracing studies that Myocd is expressed transiently in skeletal muscle progenitor cells of the somite, and a majority of skeletal muscle is derived from Myocd-expressing cell lineages. However, rather than activating skeletal muscle-specific gene expression, Myocd functions as a transcriptional repressor of Myog, inhibiting skeletal muscle differentiation while activating SMC-specific genes. This repressor function of Myocd is complex, involving histone deacetylase 5 silencing of the Myog promoter and Myocd's physical contact with MyoD, which undermines MyoD DNA binding and transcriptional synergy with MEF2. These results reveal a previously unrecognized role for Myocd in repressing the skeletal muscle differentiation program and suggest that this transcriptional coregulator acts as a bifunctional molecular switch for the smooth versus skeletal muscle phenotypes.

Long, Xiaochun; Creemers, Esther E.; Wang, Da-Zhi; Olson, Eric N.; Miano, Joseph M.

2007-01-01

316

Human skeletal muscle protein breakdown during spaceflight  

NASA Technical Reports Server (NTRS)

Human spaceflight is associated with a loss of body protein. Excretion of 3-methylhistidine (3-MH) in the urine is a useful measurement of myofibrillar protein breakdown. Bed rest, particularly with 6 degrees head-down tilt, is an accepted ground-based model for human spaceflight. The objectives of this report were to compare 3-MH excretion from two Life Sciences shuttle missions (duration 9.5 and 15 days, n = 9) and from 17 days of bed rest (n = 7) with 6 degrees head-down tilt. The bed rest study was designed to mimic an actual Life Sciences spaceflight and so incorporated an extensive battery of physiological tests focused on the musculoskeletal system. Results showed that nitrogen retention, based on excretion of nitrogen in the urine, was reduced during both bed rest [from 22 +/- 1 to 1 +/- 5 mg N x kg(-1) x day(-1) (n = 7; P < 0.05)] and spaceflight [from 57 +/- 9 to 19 +/- 3 mg N x kg(-1) x day(-1) (n = 9; P < 0.05)]. 3-MH excretion was unchanged with either bed rest [pre-bed rest 5.30 +/- 0.29 vs. bed rest 5.71 +/- 0.30 micromol 3-MH x kg(-1) x day(-1), n = 7; P = not significant (NS)] or spaceflight [preflight 4.98 +/- 0.37 vs. 4.59 +/- 0.39 micromol 3-MH x kg(-1) x day(-1) in-flight, n = 9; P = NS]. We conclude that 1) 3-MH excretion was unaffected by spaceflight on the shuttle or with bed rest plus exercise, and 2) because protein breakdown (elevated 3-MH) was increased on Skylab but not on the shuttle, it follows that muscle protein breakdown is not an inevitable consequence of spaceflight.

Stein, T. P.; Schluter, M. D.

1997-01-01

317

Viscoelasticity-based MR elastography of skeletal muscle  

NASA Astrophysics Data System (ADS)

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

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

2010-11-01

318

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles  

NASA Technical Reports Server (NTRS)

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

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

1986-01-01

319

Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae  

PubMed Central

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

2012-01-01

320

Hedgehog can drive terminal differentiation of amniote slow skeletal muscle  

PubMed Central

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

Li, Xiaopeng; Blagden, Christopher S; Bildsoe, Heidi; Bonnin, Marie Ange; Duprez, Delphine; Hughes, Simon M

2004-01-01

321

Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions  

PubMed Central

We have defined regions of the skeletal muscle ryanodine receptor (RyR1) essential for bidirectional signaling with dihydropyridine receptors (DHPRs) and for the organization of DHPR into tetrad arrays by expressing RyR1–RyR3 chimerae in dyspedic myotubes. RyR1–RyR3 constructs bearing RyR1 residues 1–1681 restored wild-type DHPR tetrad arrays and, in part, skeletal-type excitation–contraction (EC) coupling (orthograde signaling) but failed to enhance DHPR Ca2+ currents (retrograde signaling) to WT RyR1 levels. Within this region, the D2 domain (amino acids 1272–1455), although ineffective on its own, dramatically enhanced the formation of tetrads and EC coupling rescue by constructs that otherwise are only partially effective. These findings suggest that the orthograde signal and DHPR tetrad formation require the contributions of numerous RyR regions. Surprisingly, we found that RyR3, although incapable of supporting EC coupling or tetrad formation, restored a significant level of Ca2+ current, revealing a functional interaction with the skeletal muscle DHPR. Thus, our data support the hypotheses that (i) the structural/functional link between RyR1 and the skeletal muscle DHPR requires multiple interacting regions, (ii) the D2 domain of RyR1 plays a key role in stabilizing this interaction, and (iii) a form of retrograde signaling from RyR3 to the DHPR occurs in the absence of direct protein–protein interactions.

Sheridan, David C.; Takekura, Hiroaki; Franzini-Armstrong, Clara; Beam, Kurt G.; Allen, Paul D.; Perez, Claudio F.

2006-01-01

322

Diffuse skeletal muscles uptake of [18F] fluorodeoxyglucose on positron emission tomography in primary muscle peripheral T-cell lymphoma.  

PubMed

A 40-year-old man presented with weakness of neck extensor muscles. Cervical magnetic resonance imaging showed high-intensity areas in muscles of the left lateral cervical region on T2-weighted images. Fluorodeoxyglucose-positron emission tomography scan demonstrated striking fluorodeoxyglucose uptake by multiple skeletal muscles of the neck, chest, and abdominal region. Muscle biopsy demonstrated peripheral T-cell lymphoma, unspecified. The diagnosis was primary skeletal muscle peripheral T-cell lymphoma. Primary skeletal muscle non-Hodgkin's lymphoma of T-cell immunophenotype is extremely rare and fluorodeoxyglucose-positron emission tomography demonstrated striking fluorodeoxyglucose uptake in multiple skeletal muscles and served as a quite useful modality for the diagnosis of this patient. PMID:21921389

Tanaka, Yuji; Hayashi, Yuichi; Kato, Jun'ichi; Yamada, Megumi; Koumura, Akihiro; Sakurai, Takeo; Kimura, Akio; Hozumi, Isao; Hatano, Yuichiro; Hirose, Yoshinobu; Takami, Tsuyoshi; Nakamura, Hiroshi; Kasahara, Senji; Tsurumi, Hisashi; Moriwaki, Hisataka; Inuzuka, Takashi

2011-01-01

323

Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment  

Microsoft Academic Search

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripo- tent, mesenchymal cells into myogenic lineage, we hypothe- sized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was

INDRANI SINHA-HIKIM; WAYNE E. TAYLOR; NESTOR F. GONZALEZ-CADAVID; WEI ZHENG; SHALENDER BHASIN

324

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

PubMed

Hereditary muscle channelopathies are caused by dominant mutations in the genes encoding for subunits of muscle voltage-gated ion channels. Point mutations on the human skeletal muscle Na+ channel (Nav1.4) give rise to hyperkalemic periodic paralysis, potassium aggravated myotonia, paramyotonia congenita and hypokalemic periodic paralysis type 2. Point mutations on the human skeletal muscle Ca2+ channel give rise to hypokalemic periodic paralysis and malignant hyperthermia. Point mutations in the human skeletal chloride channel CIC-1 give rise to myotonia congenita. Point mutations in the inwardly rectifying K+ channel Kir2.1 give rise to a syndrome characterized by periodic paralysis, severe cardiac arrhythmias and skeletal alterations (Andersen's syndrome). Involvement of the same ion channel can thus give rise to different phenotypes. In addition, the same mutation can lead to different phenotypes or similar phenotypes can be caused by different mutations on the same or on different channel subtypes. Bearing in mind, the complexity of this field, the growing number of potential channelopathies (such as the myotonic dystrophies), and the time and cost of the genetic procedures, before a biomolecular approach is addressed, it is mandatory to apply strict diagnostic protocols to screen the patients. In this study we propose a protocol to be applied in the diagnosis of the hereditary muscle channelopathies and we demonstrate that muscle biopsy studies and muscle cell cultures may significantly contribute towards the correct diagnosis of the channel involved. DNA-based diagnosis is now a reality for many of the channelopathies. This has obvious genetic counselling, prognostic and therapeutic implications. PMID:12685554

Meola, G; Sansone, V; Rotondo, G; Mancinelli, E

2003-01-01

325

Genetic architecture of gene expression in ovine skeletal muscle  

PubMed Central

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

2011-01-01

326

Skeletal muscle protein reserve after bone marrow transplantation in children.  

PubMed

To evaluate the long-term profile of nutritional status in children undergoing BMT, we carried out a 1-year follow-up of 42 consecutive patients. The skeletal muscle protein reserve was assessed by ultrasonography, and by calculating the mid-arm muscle area from skinfold and arm circumference measurements. Ultrasonography proved to be superior to anthropometry. During the first month after BMT, the skeletal muscle protein reserve decreased by 11% (95% CI -20 to -4%), and only began to recover gradually several months after BMT. The serum transferrin concentration decreased significantly during the first post-transplant month, then slowly returned to normal by the end of the first post-transplant year. The 23 patients with allogeneic transplants and 19 with autologous transplants were fully comparable in nutritional respects. Despite total parenteral nutrition the total energy intake did not reach the weight-based target level. The patients in whom pretransplant protein energy reserves were severely reduced, were at increased risk of dying of relapse. We conclude that ultrasonography is a valuable method for assessing protein energy reserves in BMT patients. Pretransplant nutritional status has a considerable impact on post-transplant survival. We emphasize the importance of both pre- and post-transplant nutritional support. PMID:8932848

Taskinen, M; Saarinen, U M

1996-11-01

327

Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle  

PubMed Central

A unique property of mitochondria in mammalian cells is their ability to physically interact and undergo dynamic events of fusion/fission that remodel their morphology and possibly their function. In cultured cells, metabolic perturbations similar to those incurred during exercise influence mitochondrial fusion and fission processes, but it is unknown whether exercise acutely alters mitochondrial morphology and/or membrane interactions in vivo. To study this question, we subjected mice to a 3-h voluntarily exercise intervention following their normal physical activity patterns, and quantified mitochondrial morphology and membrane interactions in the soleus using a quantitative electron microscopy approach. A single exercise bout effectively decreased blood glucose (P < 0.05) and intramyocellular lipid content (P < 0.01), indicating increased muscle metabolic demand. The number of mitochondria spanning Z-lines and proportion of electron-dense contact sites (EDCS) between adjacent mitochondrial membranes were increased immediately after exercise among both subsarcolemmal (+116%, P < 0.05) and intermyofibrillar mitochondria (+191%, P < 0.001), indicating increased physical interactions. Mitochondrial morphology, and abundance of the mitochondrial pro-fusion proteins Mfn2 and OPA1 were unchanged. Collectively, these results support the notion that mitochondrial membrane dynamics are actively remodelled in skeletal muscle, which may be regulated by contractile activity and the metabolic state. Future studies are required to understand the implications of mitochondrial dynamics in skeletal muscle physiology during exercise and inactivity.

Gentil, Benoit J.; McManus, Meagan J.; White, Kathryn; St. Louis, Kyle; Gartside, Sarah E.; Wallace, Douglas C.; Turnbull, Douglass M.

2013-01-01

328

Palisade endings and proprioception in extraocular muscles: a comparison with skeletal muscles.  

PubMed

This article describes current views on motor and sensory control of extraocular muscles (EOMs) based on anatomical data. The special morphology of EOMs, including their motor innervation, is described in comparison to classical skeletal limb and trunk muscles. The presence of proprioceptive organs is reviewed with emphasis on the palisade endings (PEs), which are unique to EOMs, but the function of which is still debated. In consideration of the current new anatomical data about the location of cell bodies of PEs, a hypothesis on the function of PEs in EOMs and the multiply innervated muscle fibres they are attached to is put forward. PMID:23053430

Lienbacher, Karoline; Horn, Anja K E

2012-12-01

329

Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?  

PubMed

First reported formally in 1980, the frequent ability of infectious fever to relieve autistic behavior, often dramatically (and rarely aggravate), has long tantalized parents, practitioners, and researchers - yet its physiology and biochemistry have never been investigated, to judge from the literature. Fever is a complex interplay of immune, metabolic, and stress responses, yet its benefit in autistic disorders (ASD) may derive largely from a single response - release of the amino acid glutamine from skeletal muscles as provisional fuel. This proposal is based on evidence of low blood and brain glutamine in ASD children and adults, notable lack of autistic behavior in children with high brain glutamine from urea cycle disorders, and other events that elicit dramatic improvements - fasting, panic, pain, and the corticosteroid prednisone - that release or synthesize glutamine. Glutamine released from muscles is metabolized by the intestines like ingested glutamine. If glutamine released by fever rarely aggravates autistic behavior, why would supplemental glutamine? PMID:23098376

Good, Peter

2013-01-01

330

Scheduled Exercise Phase Shifts the Circadian Clock in Skeletal Muscle  

PubMed Central

Purpose It has been well established in mammals that circadian behavior as well as the molecular clockwork can be synchronized to the light-dark (LD) cycle via the suprachiasmatic nucleus of the hypothalamus (SCN). In addition to light, it has been demonstrated that non-photic time cues, such as restricting the time of food availability, can alter circadian behavior and clock gene expression in selected peripheral tissues such as liver. Studies have also suggested that scheduled physical activity (exercise) can alter circadian rhythms in behavior and clock gene expression, however currently the effects of exercise alone are largely unknown and have not been explored in skeletal muscle. Methods Period2?Luciferase (Per2?Luc) mice were maintained under 12 hours of light followed by 12 hours of darkness (12L:12D) then exposed to 2 hours of voluntary or involuntary exercise during the light phase for 4 weeks. Control mice were left in home cages or moved to the exercise environment (sham). A second group of mice had restricted access to food (4 hours per day for 2 weeks) in order to compare the effects of two non-photic cues on PER2?LUC bioluminescence. Skeletal muscles, lung and SCN tissue explants were cultured for 5-6 days to study molecular rhythms. Results In the exercised mice, the phase of peak PER2?LUC bioluminescence was shifted in the skeletal muscle and lung explants but not the SCN suggesting a specific synchronizing effect of exercise on the molecular clockwork in peripheral tissues. Conclusions These data provide evidence that the molecular circadian clock in peripheral tissues can respond to the time of exercise suggesting that physical activity contributes important timing information for synchronization of circadian clocks throughout the body.

Wolff, Gretchen; Esser, Karyn A.

2012-01-01

331

Chemokine-like receptor 1 regulates skeletal muscle cell myogenesis  

PubMed Central

The chemokine-like receptor-1 (CMKLR1) is a G protein-coupled receptor that is activated by chemerin, a secreted plasma leukocyte attractant and adipokine. Previous studies identified that CMKLR1 is expressed in skeletal muscle in a stage-specific fashion during embryogenesis and in adult mice; however, its function in skeletal muscle remains unclear. Based on the established function of CMKLR1 in cell migration and differentiation, we investigated the hypothesis that CMKLR1 regulates the differentiation of myoblasts into myotubes. In C2C12 mouse myoblasts, CMKLR1 expression increased threefold with differentiation into multinucleated myotubes. Decreasing CMKLR1 expression by adenoviral-delivered small-hairpin RNA (shRNA) impaired the differentiation of C2C12 myoblasts into mature myotubes and reduced the mRNA expression of myogenic regulatory factors myogenin and MyoD while increasing Myf5 and Mrf4. At embryonic day 12.5 (E12.5), CMKLR1 knockout (CMKLR1?/?) mice appeared developmentally delayed and displayed significantly lower wet weights and a considerably diminished myotomal component of somites as revealed by immunolocalization of myosin heavy chain protein compared with wild-type (CMKLR1+/+) mouse embryos. These changes were associated with increased Myf5 and decreased MyoD protein expression in the somites of E12.5 CMKLR1?/? mouse embryos. Adult male CMKLR1?/? mice had significantly reduced bone-free lean mass and weighed less than the CMKLR1+/+ mice. We conclude that CMKLR1 is essential for myogenic differentiation of C2C12 cells in vitro, and the CMKLR1 null mice have a subtle skeletal muscle deficit beginning from embryonic life that persists during postnatal life.

Issa, Mark E.; Muruganandan, Shanmugam; Ernst, Matthew C.; Parlee, Sebastian D.; Zabel, Brian A.; Butcher, Eugene C.; Sinal, Christopher J.

2012-01-01

332

Chemokine-like receptor 1 regulates skeletal muscle cell myogenesis.  

PubMed

The chemokine-like receptor-1 (CMKLR1) is a G protein-coupled receptor that is activated by chemerin, a secreted plasma leukocyte attractant and adipokine. Previous studies identified that CMKLR1 is expressed in skeletal muscle in a stage-specific fashion during embryogenesis and in adult mice; however, its function in skeletal muscle remains unclear. Based on the established function of CMKLR1 in cell migration and differentiation, we investigated the hypothesis that CMKLR1 regulates the differentiation of myoblasts into myotubes. In C(2)C(12) mouse myoblasts, CMKLR1 expression increased threefold with differentiation into multinucleated myotubes. Decreasing CMKLR1 expression by adenoviral-delivered small-hairpin RNA (shRNA) impaired the differentiation of C(2)C(12) myoblasts into mature myotubes and reduced the mRNA expression of myogenic regulatory factors myogenin and MyoD while increasing Myf5 and Mrf4. At embryonic day 12.5 (E12.5), CMKLR1 knockout (CMKLR1(-/-)) mice appeared developmentally delayed and displayed significantly lower wet weights and a considerably diminished myotomal component of somites as revealed by immunolocalization of myosin heavy chain protein compared with wild-type (CMKLR1(+/+)) mouse embryos. These changes were associated with increased Myf5 and decreased MyoD protein expression in the somites of E12.5 CMKLR1(-/-) mouse embryos. Adult male CMKLR1(-/-) mice had significantly reduced bone-free lean mass and weighed less than the CMKLR1(+/+) mice. We conclude that CMKLR1 is essential for myogenic differentiation of C(2)C(12) cells in vitro, and the CMKLR1 null mice have a subtle skeletal muscle deficit beginning from embryonic life that persists during postnatal life. PMID:22460713

Issa, Mark E; Muruganandan, Shanmugam; Ernst, Matthew C; Parlee, Sebastian D; Zabel, Brian A; Butcher, Eugene C; Sinal, Christopher J; Goralski, Kerry B

2012-06-01

333

Myocardial and skeletal muscle glucose uptake during exercise in humans  

PubMed Central

The purpose of this study was to investigate the effects of exercise on myocardial glucose uptake and whether the pattern of glucose uptake is the same as in skeletal muscle. Glucose uptake was measured using positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). Twelve healthy men were studied during rest, while 14 subjects were studied after 35 min of bicycle exercise corresponding to 30, 55 and 75 % of maximal oxygen consumption (V?O2,max) on three separate days. [18F]FDG was injected 10 min after the start of exercise and exercise continued for a further 25 min. Myocardial and skeletal muscle PET scanning was commenced directly after the completion of the exercise bout. As compared to the resting state, exercise doubled myocardial glucose uptake at the 30 % (P = 0.056) and 55 % intensity levels (P < 0.05), while at the 75 % intensity level glucose uptake was reduced significantly compared to the lower exercise intensities. There was no significant difference between the highest intensity level and the resting state (P = 0.18). At rest and during low-intensity exercise, myocardial glucose uptake was inversely associated with circulating levels of free fatty acids. However, during higher exercise intensities when plasma lactate concentrations increased significantly, this association disappeared. In contrast to myocardial responses, skeletal muscle glucose uptake rose in parallel with exercise intensity from rest to 30 % and then 55 % V?O2,max (P < 0.001) and tended to increase further at the intensity of 75 % V?O2,max (P = 0.065). In conclusion, these results demonstrate that myocardial glucose uptake is increased during mild- and moderate-intensity exercise, but is decreased during high-intensity exercise. This finding suggests that the increased myocardial energy that is needed during high-intensity exercise is supplied by substrates other than glucose.

Kemppainen, Jukka; Fujimoto, Toshihiko; Kalliokoski, Kari K; Viljanen, Tapio; Nuutila, Pirjo; Knuuti, Juhani

2002-01-01

334

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of ?-hydroxy-?-methylbutyrate.  

PubMed

Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite ?-hydroxy-?-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 ?mol·kg body wt(-1)·h(-1) for 1 h (HMB 0, HMB 20, HMB 100, or HMB 400). Plasma HMB concentrations increased with infusion and were 10, 98, 316, and 1,400 nmol/ml in the HMB 0, HMB 20, HMB 100, and HMB 400 pigs. Protein synthesis rates in the longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles, lung, and spleen were greater in HMB 20 than in HMB 0, and in the LD were greater in HMB 100 than in HMB 0. HMB 400 had no effect on protein synthesis. Eukaryotic initiation factor (eIF)4E·eIF4G complex formation and ribosomal protein S6 kinase-1 and 4E-binding protein-1 phosphorylation increased in LD, gastrocnemius, and soleus muscles with HMB 20 and HMB 100 and in diaphragm with HMB 20. Phosphorylation of eIF2? and elongation factor 2 and expression of system A transporter (SNAT2), system L transporter (LAT1), muscle RING finger 1 protein (MuRF1), muscle atrophy F-box (atrogin-1), and microtubule-associated protein light chain 3 (LC3-II) were unchanged. Results suggest that supplemental HMB enhances protein synthesis in skeletal muscle of neonates by stimulating translation initiation. PMID:24192287

Wheatley, Scott M; El-Kadi, Samer W; Suryawan, Agus; Boutry, Claire; Orellana, Renán A; Nguyen, Hanh V; Davis, Steven R; Davis, Teresa A

2014-01-01

335

Effect of nandrolone decanoate on skeletal muscle repair.  

PubMed

This study analyzed the effect of nandrolone decanoate (ND) on muscle repair and the expression of myogenic regulatory factors following cryoinjury in rat skeletal muscle. Adult male Wistar rats were randomly divided into 4 groups: control group, sham group, cryoinjured group treated with ND and non-injured group treated with ND. Treatment consisted of subcutaneous injections of ND (5 mg/kg) twice a week. After sacrifice, the tibialis anterior muscle was removed for the isolation of total RNA and analysis of myogenic regulatory factors using real-time PCR as well as morphological analysis using the hematoxylin-eosin assay. There was a significant increase in MyoD mRNA after 7 days and in myogenin mRNA after 21 days in the cryoinjured ND group in comparison to other groups in the same period. The morphological analysis revealed no edema or myonecrosis after 7 days as well as no edema or inflammatory infiltrate after 14 days in the cryoinjured ND group. In conclusion the anabolic steroid nandrolone decanoate can modulate the muscle repair process in rats following cryoinjury by influencing the expression of regulatory myogenic factors and phases of muscle repair. PMID:22791621

Piovesan, R F; Fernandes, K P S; Alves, A N; Teixeira, V P; Silva Junior, J A; Martins, M D; Bussadori, S K; Albertini, R; Mesquita-Ferrari, R A

2013-01-01

336

Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise  

PubMed Central

High-intensity exercise can result in up to a 1,000-fold increase in the rate of ATP demand compared to that at rest (Newsholme et al., 1983). To sustain muscle contraction, ATP needs to be regenerated at a rate complementary to ATP demand. Three energy systems function to replenish ATP in muscle: (1) Phosphagen, (2) Glycolytic, and (3) Mitochondrial Respiration. The three systems differ in the substrates used, products, maximal rate of ATP regeneration, capacity of ATP regeneration, and their associated contributions to fatigue. In this exercise context, fatigue is best defined as a decreasing force production during muscle contraction despite constant or increasing effort. The replenishment of ATP during intense exercise is the result of a coordinated metabolic response in which all energy systems contribute to different degrees based on an interaction between the intensity and duration of the exercise, and consequently the proportional contribution of the different skeletal muscle motor units. Such relative contributions also determine to a large extent the involvement of specific metabolic and central nervous system events that contribute to fatigue. The purpose of this paper is to provide a contemporary explanation of the muscle metabolic response to different exercise intensities and durations, with emphasis given to recent improvements in understanding and research methodology.

Baker, Julien S.; McCormick, Marie Clare; Robergs, Robert A.

2010-01-01

337

Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy  

PubMed Central

Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD.

Rezk, Bashir M.; Yoshida, Tadashi; Semprun-Prieto, Laura; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

2012-01-01

338

Mechanical Stimulation of Skeletal Muscle Generates Lipid-Related Second Messengers by Phospholipase Activation.  

National Technical Information Service (NTIS)

Repetitive mechanical stimulation of cultured avian skeletal muscle increases the synthesis of prostaglandins E2 and F2(alpha) which regulate protein turnover rates and muscle cell growth. Mechnical stimulation significantly increases the breakdown rate o...

H. H. Vandenburgh J. Shansky P. Karlisch R. L. Solerssi

1991-01-01

339

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

PubMed

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. PMID:10983674

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

2000-08-01

340

Membrane Sealing in Frog Skeletal-Muscle Fibers  

PubMed Central

Self-sealing, not found in frog skeletal muscle fibers immersed in Ringer's solution, can be induced by solutions rich in calcium ion. Strontium replaced calcium on the sealing process, but magnesium did not. The sealing accomplished in high-calcium media was preserved in those fibers reimmersed in normal Ringer's solution. Measurements of the rate of sealing at different temperatures indicated that self-sealing induced by calcium has a high activation energy. Phospholipase C, an enzyme that hydrolyzes membrane phospholipids, produced a marked depression on the rate of sealing. Trypsin or chymotrypsin had no influence on the sealing process.

De Mello, W. C.

1973-01-01

341

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy  

NASA Technical Reports Server (NTRS)

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

342

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy  

NASA Technical Reports Server (NTRS)

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

343

BMP-9-induced muscle heterotopic ossification requires changes to the skeletal muscle microenvironment.  

PubMed

Heterotopic ossification (HO) is defined as the formation of bone inside soft tissue. Symptoms include joint stiffness, swelling, and pain. Apart from the inherited form, the common traumatic form generally occurs at sites of injury in damaged muscles and is often associated with brain injury. We investigated bone morphogenetic protein 9 (BMP-9), which possesses a strong osteoinductive capacity, for its involvement in muscle HO physiopathology. We found that BMP-9 had an osteoinductive influence on mouse muscle resident stromal cells by increasing their alkaline phosphatase activity and bone-specific marker expression. Interestingly, BMP-9 induced HO only in damaged muscle, whereas BMP-2 promoted HO in skeletal muscle regardless of its state. The addition of the soluble form of the ALK1 protein (the BMP-9 receptor) significantly inhibited the osteoinductive potential of BMP-9 in cells and HO in damaged muscles. BMP-9 thus should be considered a candidate for involvement in HO physiopathology, with its activity depending on the skeletal muscle microenvironment. PMID:21611960

Leblanc, Elisabeth; Trensz, Frédéric; Haroun, Sonia; Drouin, Geneviève; Bergeron, Eric; Penton, Christopher M; Montanaro, Federica; Roux, Sophie; Faucheux, Nathalie; Grenier, Guillaume

2011-06-01

344

Effect of spaceflight on skeletal muscle: Mechanical properties and myosin isoform content of a slow muscle  

NASA Technical Reports Server (NTRS)

This study examined changes in contractile, biochemical, and histochemical properties of slow antigravity skeletal muscle after a 6-day spaceflight mission. Twelve male Sprague-Dawley rats were randomly divided into two groups: flight and ground-based control. Approximately 3 h after the landing, in situ contractile measurements were made on the soleus muscles of the flight animals. The control animals were studied 24 h later. The contractile measurements included force-velocity relationship, force-frequency relationship, and fatigability. Biochemical measurements focused on the myosin heavy chain (MHC) and myosin light chain profiles. Adenosinetriphosphatase histochemistry was performed to identify cross-sectional area of slow and fast muscle fibers and to determine the percent fiber type distribution. The force-velocity relationships of the flight muscles were altered such that maximal isometric tension P(sub o) was decreased by 24% and maximal shortening velocity was increased by 14% (P less than 0.05). The force-frequency relationship of the flight muscles was shifted to the right of the control muscles. At the end of the 2-min fatigue test, the flight muscles generated only 34% of P(sub o), whereas the control muscles generated 64% of P(sub o). The flight muscles exhibited de novo expression of the type IIx MHC isoform as well as a slight decrease in the slow type I and fast type IIa MHC isoforms. Histochemical analyses of flight muscles demonstrated a small increase in the percentage of fast type II fibers and a greater atrophy of the slow type I fibers. The results demonstrate that contractile properties of slow antigravity skeletal muscle are sensitive to the microgravity environment and that changes begin to occur within the 1st wk. These changes were at least, in part, associated with changes in the amount and type of contractile protein expressed.

Caiozzo, Vincent J.; Baker, Michael J.; Herrick, Robert E.; Tao, Ming; Baldwin, Kenneth M.

1994-01-01

345

Autocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle  

NASA Technical Reports Server (NTRS)

Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.

Adams, Gregory R.

2002-01-01

346

Myocardial and Skeletal Muscle Concentrations of Digoxin in Patients on Long-term Therapy  

Microsoft Academic Search

The digoxin content was measured in samples of left ventricular papillary muscle, skeletal muscle, and plasma obtained during mitral valve replacement from eight patients on maintenance treatment with the drug. The content in papillary muscle ranged from 15·5 to 132 ng\\/g (mean 77·7) and in skeletal muscle from 7·5 to 23 ng\\/g (mean 11·3). The ratio of myocardial digoxin concentration

John Coltart; Michael Howard; Douglas Chamberlain

1972-01-01

347

Computer aided mechanogenesis of skeletal muscle organs from single cells in vitro  

NASA Technical Reports Server (NTRS)

Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased skeletal muscle.

Vandenburgh, Herman H.; Swasdison, Somporn; Karlisch, Patricia

1990-01-01

348

Complex polysaccharide inclusions in the skeletal muscle of stranded cetaceans.  

PubMed

Skeletal muscle samples were examined post-mortem in 148 cetaceans over a 12-year period. Histological analysis included haematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining with and without diastase digestion. In addition, histological muscle sections were immunostained for ubiquitin and fast and slow heavy-chain myosin isoforms. PAS-positive, diastase-resistant inclusions were detected in 26 animals from 11 different species. Older cetaceans were preferentially affected. These intrafibre inclusions varied from large aggregates to multiple coarse granules and were typically associated with type II fibres. All diastase-resistant inclusions were positive for ubiquitin. These features resembled those inclusions described as complex polysaccharide in horses. Based on these histological findings and the ubiquitin staining pattern, a morphological diagnosis of complex polysaccharide storage myopathy is proposed. PMID:22079146

Sierra, E; Fernández, A; Espinosa de Los Monteros, A; Jaber, J R; Andrada, M; Herráez, P

2012-07-01

349

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

NASA Astrophysics Data System (ADS)

Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

1984-02-01

350

Arginase Promotes Skeletal Muscle Arteriolar Endothelial Dysfunction in Diabetic Rats  

PubMed Central

Endothelial dysfunction is a characteristic feature in diabetes that contributes to the development of vascular disease. Recently, arginase has been implicated in triggering endothelial dysfunction in diabetic patients and animals by competing with endothelial nitric oxide synthase for substrate l-arginine. While most studies have focused on the coronary circulation and large conduit blood vessels, the role of arginase in mediating diabetic endothelial dysfunction in other vascular beds has not been fully investigated. In the present study, we determined whether arginase contributes to endothelial dysfunction in skeletal muscle arterioles of diabetic rats. Diabetes was induced in male Sprague Dawley rats by streptozotocin injection. Four weeks after streptozotocin administration, blood glucose, glycated hemoglobin, and vascular arginase activity were significantly increased. In addition, a significant increase in arginase I and II mRNA expression was detected in gracilis muscle arterioles of diabetic rats compared to age-matched, vehicle control animals. To examine endothelial function, first-order gracilis muscle arterioles were isolated, cannulated in a pressure myograph system, exposed to graded levels of luminal flow, and internal vessel diameter measured. Increases in luminal flow (0–50??L/min) caused progressive vasodilation in arterioles isolated from control, normoglycemic animals. However, flow-induced vasodilation was absent in arterioles obtained from streptozotocin-treated rats. Acute in vitro pretreatment of blood vessels with the arginase inhibitors N?-hydroxy-nor-l-arginine or S-(2-boronoethyl)-l-cysteine restored flow-induced responses in arterioles from diabetic rats and abolished differences between diabetic and control animals. Similarly, acute in vitro pretreatment with l-arginine returned flow-mediated vasodilation in vessels from diabetic animals to that of control rats. In contrast, d-arginine failed to restore flow-induced dilation in arterioles isolated from diabetic animals. Administration of sodium nitroprusside resulted in a similar degree of dilation in arterioles isolated from control or diabetic rats. In conclusion, the present study identifies arginase as an essential mediator of skeletal muscle arteriolar endothelial dysfunction in diabetes. The ability of arginase to induce endothelial dysfunction in skeletal muscle arterioles may further compromise glucose utilization and facilitate the development of hypertension in diabetes.

Johnson, Fruzsina K.; Johnson, Robert A.; Peyton, Kelly J.; Shebib, Ahmad R.; Durante, William

2013-01-01

351

Robust Internal Elastic Lamina Fenestration in Skeletal Muscle Arteries  

PubMed Central

Holes within the internal elastic lamina (IEL) of blood vessels are sites of fenestration allowing for passage of diffusible vasoactive substances and interface of endothelial cell membrane projections with underlying vascular smooth muscle. Endothelial projections are sites of dynamic Ca2+ events leading to endothelium dependent hyperpolarization (EDH)-mediated relaxations and the activity of these events increase as vessel diameter decreases. We tested the hypothesis that IEL fenestration is greater in distal vs. proximal arteries in skeletal muscle, and is unlike other vascular beds (mesentery). We also determined ion channel protein composition within the endothelium of intramuscular and non-intramuscular skeletal muscle arteries. Popliteal arteries, subsequent gastrocnemius feed arteries, and first and second order intramuscular arterioles from rat hindlimb were isolated, cut longitudinally, fixed, and imaged using confocal microscopy. Quantitative analysis revealed a significantly larger total fenestration area in second and first order arterioles vs. feed and popliteal arteries (58% and 16% vs. 5% and 3%; N?=?10 images/artery), due to a noticeably greater average size of holes (9.5 and 3.9 µm2 vs 1.5 and 1.9 µm2). Next, we investigated via immunolabeling procedures whether proteins involved in EDH often embedded in endothelial cell projections were disparate between arterial segments. Specific proteins involved in EDH, such as inositol trisphosphate receptors, small and intermediate conductance Ca2+-activated K+ channels, and the canonical (C) transient receptor potential (TRP) channel TRPC3 were present in both popliteal and first order intramuscular arterioles. However due to larger IEL fenestration in first order arterioles, a larger spanning area of EDH proteins is observed proximal to the smooth muscle cell plasma membrane. These observations highlight the robust area of fenestration within intramuscular arterioles and indicate that the anatomical architecture and endothelial cell hyperpolarizing apparatus for distinct vasodilatory signaling is potentially present.

Sullivan, Michelle N.; Francis, Michael; Dinenno, Frank A.; Earley, Scott

2013-01-01

352

Monoamine oxidase-A is a major target gene for glucocorticoids in human skeletal muscle cells  

Microsoft Academic Search

Skeletal myopathy is a common complication of endogenous and exogenous glucocorticoid excess, yet its pathogenetic mechanisms remain unclear. There is accumulating evidence that mitochondrial dysfunction and oxidative stress are involved in this process. To explore the glucocorticoid-induced transcriptional adaptations that may affect mitochondrial function in skeletal muscle, we studied gene expression profiles in dexamethasone-treated primary human skeletal myocytes using a

Irini Manoli; Hanh Le; Salvatore Alesci; Kimberly K. McFann; Yan A. Su; Tomoshige Kino; George P. Chrousos; Marc R. Blackman

2005-01-01

353

Oriented surfaces of adsorbed cellulose nanowhiskers promote skeletal muscle myogenesis.  

PubMed

Cellulose nanowhiskers (CNWs) are high-aspect-ratio rod-like nanoparticles prepared via partial hydrolysis of cellulose. For the first time, CNWs have been extracted from the marine invertebrate Ascidiella aspersa, yielding animal-derived CNWs with particularly small diameters of only a few nanometres. Oriented surfaces of adsorbed CNWs were prepared using a flexible and facile spin-coating method, allowing the modulation of CNW adsorption and relative orientation. Due to the shape and nanoscale dimensions of the CNWs, C2C12 myoblasts adopted increasingly oriented morphologies in response to more densely adsorbed and oriented CNW surfaces. In addition, the degree of myoblast fusion was greatest on the highly oriented CNW surfaces, and even low-orientation CNW surfaces promoted more extensive fusion than flat control surfaces. Highly oriented multinuclear myotubes formed on the oriented CNW surfaces and fibrillar fibronectin deposited on the surfaces was also modelled in a highly oriented arrangement after only 4 days in culture. With a mean feature height of only 5-6 nm, the CNW surfaces present the smallest features ever reported to induce contact guidance in skeletal muscle myoblasts, highlighting the potential for nanoscale materials for engineering oriented tissues such as skeletal muscle. PMID:22963849

Dugan, James M; Collins, Richard F; Gough, Julie E; Eichhorn, Stephen J

2013-01-01

354

Large fiber size in skeletal muscle is metabolically advantageous  

PubMed Central

Skeletal muscle fiber size is highly variable, and while diffusion appears to limit maximal fiber size, there is no paradigm for the control of minimal size. The optimal fiber size hypothesis posits that the reduced surface area to volume (SA:V) in larger fibers reduces the metabolic cost of maintaining the membrane potential, and so fibers attain an optimal size that minimizes metabolic cost while avoiding diffusion limitation. Here we examine changes during hypertrophic fiber growth in metabolic cost and activity of the Na+-K+-ATPase in white skeletal muscle from crustaceans and fishes. We provide evidence for a major tenet of the optimal fiber size hypothesis by demonstrating that larger fibers are metabolically cheaper to maintain, and the cost of maintaining the membrane potential is proportional to fiber SA:V. The influence of SA:V on metabolic cost is apparent during growth in 16 species spanning a 20-fold range in fiber size, suggesting that this principle may apply widely.

Jimenez, Ana Gabriela; Dillaman, Richard M.; Kinsey, Stephen T.

2013-01-01

355

Effects of ethanol on rat heart and skeletal muscles  

SciTech Connect

Chronic alcoholism causes myopathy of both cardiac and skeletal muscles. In order to evaluate acute effects, the authors infused ethanol intravenously in anesthetized rats, and, 10 min later, monitored the electrocardiogram, and the compound action potential and isometric tension of the anterior tibialis evoked by sciatic nerve stimulation. Ethanol at 0.1, 0.2 and 0.5 g/kg decreased the heart rate by 12%, 22% and 69%, increased the P-R interval by 5%, 25%, and 116%, and reduced the QRS amplitude by 1% , 2% and 10%, respectively. Within 5 min after infusing 0.5 g/kg ethanol, breathing was stopped. Ethanol increased the amplitude of the compound action potential and tension of the anterior tibialis by 25% at 0.1 and 0.2 g/kg, while it decreased the compound action potential by 5% and tension by 35% at 0.5 g/kg. At this dose, ethanol caused 70% decrement in amplitude of the compound action potentials and 50% fade of tetanic tensions evoked by a train of nerve stimulations at 100 Hz for 0.5 sec. When ethanol was injected intraperitoneally, about 10 times greater doses were required to produce effects equivalent to intravenous administration. These results indicate that ethanol reduces cardiac output dose-dependently, and potentiates skeletal muscle function at subintoxication doses and reduces it at higher doses.

Pagala, M.; Ravindran, K.; Namba, T.; Grob, D. (Maimonides Medical Center, Brooklyn, NY (United States) State Univ. of New York, Brooklyn (United States))

1991-03-11

356

A Simplified Immunohistochemical Classification of Skeletal Muscle Fibres in Mouse  

PubMed Central

The classification of muscle fibres is of particular interest for the study of the skeletal muscle properties in a wide range of scientific fields, especially animal phenotyping. It is therefore important to define a reliable method for classifying fibre types. The aim of this study was to establish a simplified method for the immunohistochemical classification of fibres in mouse. To carry it out, we first tested a combination of several anti myosin heavy chain (MyHC) antibodies in order to choose a minimum number of antibodies to implement a semi-automatic classification. Then, we compared the classification of fibres to the MyHC electrophoretic pattern on the same samples. Only two anti MyHC antibodies on serial sections with the fluorescent labeling of the Laminin were necessary to classify properly fibre types in Tibialis Anterior and Soleus mouse muscles in normal physiological conditions. This classification was virtually identical to the classification realized by the electrophoretic separation of MyHC. This immuno-histochemical classification can be applied to the total area of Tibialis Anterior and Soleus mouse muscles. Thus, we provide here a useful, simple and time-efficient method for immunohistochemical classification of fibres, applicable for research in mouse.

Kammoun, M.; Cassar-Malek, I.; Meunier, B.; Picard, B.

2014-01-01

357

A lesion of the transverse tubules of skeletal muscle  

PubMed Central

1. A method is described by which a selective lesion can be made in vitro in the transverse tubules of frog skeletal muscle. 2. The method consists of exposing the muscle for 1 hr or more to a buffered salt solution made hypertonic by the inclusion of 400 mM glycerol and then returning the muscle to an isotonic salt solution. The lesion is induced during the washout of the glycerol. 3. Electron micrographs reveal that the lesion consists of a rearrangement of the T-system membranes in such a way that the continuity of the tubules is lost. The membranes appear to coalesce into large vesicles scattered irregularly throughout the sarcoplasm. 4. The glycerol treatment results in a depression of the resting potential of up to 30 mV. The treated fibres are depolarized by high concentrations of K as are normal muscle fibres. 5. T-tubule lesioned fibres are unable to respond mechanically either to electrical stimulation or to elevated K but they do contract in the presence of caffeine and relax when the caffeine is removed. 6. Problems concerning the variability of the procedure are presented and certain considerations concerning the mechanism of the effect are discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 1Fig. 2Fig. 1Fig. 2Fig. 3

Howell, J. N.

1969-01-01

358

Skeletal Muscle Metastasis from Transitional Cell Carcinoma of the Urinary Bladder: Clinicoradiological Features  

Microsoft Academic Search

AIM: To define the clinicoradiological characteristics of skeletal muscle metastasis from transitional cell carcinoma of the urinary bladder.MATERIALS AND METHODS: A retrospective review of all patients with skeletal muscle metastasis was undertaken between January 1999 to December 2001. Patients suspected of having a metastasis on radiological examinations, and subsequently proven to have metastatic disease on histological examination were included in

G Nabi; N. P Gupta; D Gandhi

2003-01-01

359

Effect of High-Frequency Resistance Exercise on Adaptive Responses in Skeletal Muscle  

Microsoft Academic Search

COFFEY, V. G., D. W. REEDER, G. I. LANCASTER, W. K. YEO, M. A. FEBBRAIO, B. B. YASPELKIS III, and J. A. HAWLEY. Effect of High-Frequency Resistance Exercise on Adaptive Responses in Skeletal Muscle. Med. Sci. Sports Exerc., Vol. 39, No. 12, pp. 2135-2144, 2007. Purpose: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of

VERNON G. COFFEY; DONALD W. REEDER; GRAEME I. LANCASTER; WEE KIAN YEO; MARK A. FEBBRAIO; BEN B. YASPELKIS; JOHN A. HAWLEY

2007-01-01

360

Characterization of the human skeletal muscle glycogen synthase gene (GYS1) promoter  

Microsoft Academic Search

Background Impaired activation of the human skeletal muscle glycogen synthase by insulin is typical for type 2 diabetic patients. Regulation of glycogen synthase occurs mainly by phosphorylation\\/dephoshorylation but little is known whether there also is transcriptional regulation. Therefore we studied transcriptional regulation of the human skeletal muscle glycogen synthase gene ( GYS1 ) and evaluated the effects of insulin and

J. Fredriksson; M. Ridderstrale; L. Groop; M. Orho-Melander

2004-01-01

361

Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training  

Microsoft Academic Search

BACKGROUND: Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the gluteus medius at

Beatrice A McGivney; Paul A McGettigan; John A Browne; Alexander CO Evans; Rita G Fonseca; Brendan J Loftus; Amanda Lohan; David E MacHugh; Barbara A Murphy; Lisa M Katz; Emmeline W Hill

2010-01-01

362

Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells  

Microsoft Academic Search

Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP+ cells. Unlike canonical myogenic precursors (satellite cells), pericyte-derived cells express myogenic markers

Arianna Dellavalle; Maurilio Sampaolesi; Rossana Tonlorenzi; Enrico Tagliafico; Benedetto Sacchetti; Laura Perani; Anna Innocenzi; Beatriz G. Galvez; Graziella Messina; Roberta Morosetti; Sheng Li; Marzia Belicchi; Giuseppe Peretti; Jeffrey S. Chamberlain; Woodring E. Wright; Yvan Torrente; Stefano Ferrari; Paolo Bianco; Giulio Cossu

2007-01-01

363

The effect of glucose load on both cardiac and skeletal muscle FDG uptake  

Microsoft Academic Search

Background: The augmentation of the myocardial FDG uptake after a glucose load is very well established. However, the response of the skeletal muscle to the same glucose load has not been clearly demonstrated. The aim of this study is to demonstrate an increased skeletal muscle FDG uptake after a standard oral glucose load. To this end, we compared myocardial and

G. G Bural; G El-Haddad; A Mavi; A Alavi; L Araujo

2004-01-01

364

Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers  

Microsoft Academic Search

uchenne muscular dystrophy results from the lack of dystrophin, a cytoskeletal protein associated with the inner surface membrane, in skeletal muscle. The absence of dystrophin induces an abnormal increase of sarcolemmal calcium influx through cationic channels in adult skeletal muscle fibers from dystrophic ( mdx ) mice. We observed that the activity of these channels was increased after depletion of

Clarisse Vandebrouck; Dominique Martin; Monique Colson-Van Schoor; Huguette Debaix; Philippe Gailly

2002-01-01

365

Skeletal muscle munc18c and syntaxin 4 in human obesity  

Microsoft Academic Search

BACKGROUND: Animal and cell culture data suggest a critical role for Munc18c and Syntaxin 4 proteins in insulin mediated glucose transport in skeletal muscle, but no studies have been published in humans. METHODS: We investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects.

Bryan C Bergman; Marc-Andre Cornier; Tracy J Horton; Daniel H Bessesen; Robert H Eckel

2008-01-01

366

Cancer usurps skeletal muscle as an energy repository.  

PubMed

Cancer cells produce energy through aerobic glycolysis, but contributions of host tissues to cancer energy metabolism are unclear. In this study, we aimed to elucidate the cancer-host energy production relationship, in particular, between cancer energy production and host muscle. During the development and progression of colorectal cancer, expression of the secreted autophagy-inducing stress protein HMGB1 increased in the muscle of tumor-bearing animals. This effect was associated with decreased expression of pyruvate kinase PKM1 and pyruvate kinase activity in muscle via the HMGB1 receptor for advanced glycation endproducts (RAGE). However, muscle mitochondrial energy production was maintained. In contrast, HMGB1 addition to colorectal cancer cells increased lactate fermentation. In the muscle, HMGB1 addition induced autophagy by decreasing levels of active mTOR and increasing autophagy-associated proteins, plasma glutamate, and (13)C-glutamine incorporation into acetyl-CoA. In a mouse model of colon carcinogenesis, a temporal increase in HMGB1 occurred in serum and colonic mucosa with an increase in autophagy associated with altered plasma free amino acid levels, increased glutamine, and decreased PKM1 levels. These differences were abolished by administration of an HMGB1 neutralizing antibody. Similar results were obtained in a mouse xenograft model of human colorectal cancer. Taken together, our findings suggest that HMGB1 released during tumorigenesis recruits muscle to supply glutamine to cancer cells as an energy source. PMID:24197136

Luo, Yi; Yoneda, Junya; Ohmori, Hitoshi; Sasaki, Takamitsu; Shimbo, Kazutaka; Eto, Sachise; Kato, Yumiko; Miyano, Hiroshi; Kobayashi, Tsuyoshi; Sasahira, Tomonori; Chihara, Yoshitomo; Kuniyasu, Hiroki

2014-01-01

367

Biodesign of a Skeletal Muscle Flap as a Model for Cardiac Assistance  

Microsoft Academic Search

In using autologous muscles for cardiac assis- tance, it is crucial to reduce ischemia-reperfusion injury in the surgically traumatized skeletal muscle. In adult sheep, we developed a simple model of surgically designed 2 latis- simus dorsi muscle leaflets by modifying the vascular sup- ply to these leaflets. Three pockets with graded injury were established, and muscle morphology and vascular re-