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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



Regulation of glutamate dehydrogenase by branched-chain amino acids in skeletal muscle from rats and chicks  

Microsoft Academic Search

Little information is available regarding the regulation of glutamate dehydrogenase in skeletal muscle. We investigated the regulation of glutamate dehydrogenase by branched-chain amino acids (BCAA) in skeletal muscles from rats and chicks and determined the effects of metabolic acidosis on the activity and regulation of this enzyme by BCAA in rat skeletal muscle. Skeletal muscle mitochondria were prepared from normal

Xiwu Zhou; James R. Thompson



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.



Skeletal muscle  

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Complete AminoAcid Sequence of Actin of Rabbit Skeletal Muscle  

Microsoft Academic Search

The complete amino-acid sequence of actin of rabbit skeletal muscle was determined. The actin polypeptide chain is composed of 374 residues, including one residue of the unusual amino acid Ntau-methyl histidine, and has a calculated molecular weight of 41,785. The sequence of actin was determined by isolating the peptides produced by cleavage of the protein with cyanogen bromide, determining the

Marshall Elzinga; John H. Collins; W. Michael Kuehl; Robert S. Adelstein



Regulation of Protein and Amino Acid Degradation in Skeletal Muscle.  

National Technical Information Service (NTIS)

The article reviews recent investigations on the following aspects of protein metabolism in muscle: (1) In muscle the average rates of protein catabolism vary under different physiological conditions, e.g. fasting. Several factors have been found to reduc...

A. L. Goldberg R. Odessey



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



Peptide Antibody Specific for the Amino Terminus of Skeletal Muscle ? -actin  

NASA Astrophysics Data System (ADS)

The NH2-terminal peptide of skeletal muscle ? -actin (S? N peptide), which contains a primary sequence unique to this actin isozyme, was used to prepare an isozyme-specific peptide antibody. S? N peptide was purified from chicken breast muscle actin by preparative reverse-phase HPLC and was coupled to hemocyanin. This complex was used to immunize rabbits in order to elicit actin antibodies specific for the skeletal muscle ? -actin isozyme. The antibody obtained, called S? N antibody, was reactive with S? N peptide and with skeletal muscle ? -actin as well as with cardiac muscle ? -actin. S? N antibody did not react with either of the actin isozymes present in smooth muscle (smooth muscle ? and ? ) or in brain (nonmuscle ? and ? ). S? N antibody was used to detect muscle-specific actin in differentiating mouse and human myoblasts by using immunoblots of myoblast extracts and immunofluorescent staining of fixed cells.

Bulinski, Jeannette Chloe; Kumar, Santosh; Titani, Koiti; Hauschka, Stephen D.



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



Nutraceutical effects of branched-chain amino acids on skeletal muscle.  


BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise. PMID:16424141

Shimomura, Yoshiharu; Yamamoto, Yuko; Bajotto, Gustavo; Sato, Juichi; Murakami, Taro; Shimomura, Noriko; Kobayashi, Hisamine; Mawatari, Kazunori



Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action  

PubMed Central

Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs), especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

Nicastro, Humberto; da Luz, Claudia Ribeiro; Chaves, Daniela Fojo Seixas; Bechara, Luiz Roberto Grassmann; Voltarelli, Vanessa Azevedo; Rogero, Marcelo Macedo; Lancha, Antonio Herbert



Myosin heavy chain 2A and ?-Actin expression in human and murine skeletal muscles at feeding; particularly amino acids  

PubMed Central

Background Protein dynamics during non-steady state conditions as feeding are complex. Such studies usually demand combinations of methods to give conclusive information, particularly on myofibrillar proteins with slow turnover. Therefore, time course transcript analyses were evaluated as possible means to monitor changes in myofibrillar biosynthesis in skeletal muscles in conditions with clinical nutrition; i.e. long term exposure of nutrients. Methods Muscle tissue from overnight intravenously fed surgical patients were used as a model combined with muscle tissue from starved and refed mice as well as cultured L6 muscle cells. Transcripts of acta 1 (?-actin), mhc2A (myosin) and slc38 a2/Snat 2 (amino acid transporter) were quantified (qPCR) as markers of muscle protein dynamics. Results Myosin heavy chain 2A transcripts decreased significantly in skeletal muscle tissue from overnight parenterally fed patients but did not change significantly in orally refed mice. Alpha-actin transcripts did not change significantly in muscle cells from fed patients, mice or cultured L6 cells during provision of AA. The AA transporter Snat 2 decreased in L6 cells refed by all AA and by various combinations of AA but did not change during feeding in muscle tissue from patients or mice. Conclusion Our results confirm that muscle cells are sensitive to alterations in extracellular concentrations of AA for induction of protein synthesis and anabolism. However, transcripts of myofibrillar proteins and amino acid transporters showed complex alterations in response to feeding with provision of amino acids. Therefore, muscle tissue transcript levels of actin and myosin do not reflect protein accretion in skeletal muscles at feeding.



No effect of short-term amino acid supplementation on variables related to skeletal muscle damage in 100 km ultra-runners - a randomized controlled trial  

PubMed Central

Background The purpose of this study was to investigate the effect of short-term supplementation of amino acids before and during a 100 km ultra-marathon on variables of skeletal muscle damage and muscle soreness. We hypothesized that the supplementation of amino acids before and during an ultra-marathon would lead to a reduction in the variables of skeletal muscle damage, a decrease in muscle soreness and an improved performance. Methods Twenty-eight experienced male ultra-runners were divided into two groups, one with amino acid supplementation and the other as a control group. The amino acid group was supplemented a total of 52.5 g of an amino acid concentrate before and during the 100 km ultra-marathon. Pre- and post-race, creatine kinase, urea and myoglobin were determined. At the same time, the athletes were asked for subjective feelings of muscle soreness. Results Race time was not different between the groups when controlled for personal best time in a 100 km ultra-marathon. The increases in creatine kinase, urea and myoglobin were not different in both groups. Subjective feelings of skeletal muscle soreness were not different between the groups. Conclusions We concluded that short-term supplementation of amino acids before and during a 100 km ultra-marathon had no effect on variables of skeletal muscle damage and muscle soreness.



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



Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein  

PubMed Central

Regardless of age or gender, resistance training or provision of adequate amounts of dietary protein (PRO) or essential amino acids (EAA) can increase muscle protein synthesis (MPS) in healthy adults. Combined PRO or EAA ingestion proximal to resistance training, however, can augment the post-exercise MPS response and has been shown to elicit a greater anabolic effect than exercise plus carbohydrate. Unfortunately, chronic/adaptive response data comparing the effects of different protein sources is limited. A growing body of evidence does, however, suggest that dairy PRO, and whey in particular may: 1) stimulate the greatest rise in MPS, 2) result in greater muscle cross-sectional area when combined with chronic resistance training, and 3) at least in younger individuals, enhance exercise recovery. Therefore, this review will focus on whey protein supplementation and its effects on skeletal muscle mass when combined with heavy resistance training.



The influence of amino-reactive substances on contraction threshold of frog skeletal muscle  

Microsoft Academic Search

Summary The action of the amino-reactive substances pyridoxal phosphate, 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid and 2,4,6-trinitrobenzene sulfonic acid on the contraction threshold, taken as parameter for the initiation of contraction, was investigated in fibers of the sartorius muscle of the frog. The contraction threshold was shifted by 1 to 11 mV tomore negative potentials with 1 to 20mm PDP. Similar shifts from 2

Marianne Dörrscheidt-Käfer



Amino acid sequence of myoglobin from emu (Dromaius novaehollandiae) skeletal muscle.  


The objective of the present study was to characterize the primary structure of emu myoglobin (Mb). Emu Mb was isolated from Iliofibularis muscle employing gel-filtration chromatography. Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry was employed to determine the exact molecular mass of emu Mb in comparison with horse Mb, and Edman degradation was utilized to characterize the amino acid sequence. The molecular mass of emu Mb was 17,380 Da and was close to those reported for ratite and poultry myoglobins. Similar to myoglobins from meat-producing livestock and birds, emu Mb has 153 amino acids. Emu Mb contains 9 histidines. Proximal and distal histidines, responsible for coordinating oxygen-binding property of Mb, are conserved in emu. Emu Mb shared more than 90% homology with ratite and chicken myoglobins, whereas it demonstrated only less than 70% sequence similarity with ruminant myoglobins. PMID:20621424

Suman, S P; Joseph, P; Li, S; Beach, C M; Fontaine, M; Steinke, L



The Effect of Branched Chain Amino Acids on Skeletal Muscle Mitochondrial Function in Young and Elderly Adults  

PubMed Central

Context: A reduction in maximal mitochondrial ATP production rate (MAPR) and mitochondrial DNA (mtDNA) abundance occurs with age in association with muscle weakness and reduced endurance in elderly people. Branched chain amino acids (BCAA) have been extensively used to improve physical performance. Objective: The objective was to determine whether an 8-h infusion of BCAA enhances MAPR equally in healthy young and elderly adults. Methods: Using a crossover study design, we compared the effect BCAA vs. saline infusion in 12 young (23.0 ± 0.8 yr) and 12 elderly (70.7 ± 1.1 yr) participants matched for sex and body mass index. Skeletal muscle MAPR and mtDNA abundance were measured in muscle biopsy samples obtained before and at the end of the 8-h infusion. Results: In young participants, MAPR with the substrates glutamate plus malate (supplying electrons to complex I) and succinate plus rotenone (complex II) increased in response to BCAA infusion, relative to a decline in MAPR in response to the saline infusion. In contrast, MAPR was unaffected by BCAA infusion in the elderly participants. Moreover, mtDNA abundance was lower in the elderly compared with the young participants but was unaffected by the BCAA infusion. Insulin and C-peptide concentrations declined over time during the saline infusion, but these declines were prevented by the BCAA infusion. Conclusions: BCAA increased skeletal muscle MAPR in the young participants in comparison with saline, but this effect was not seen in the elderly participants indicating, that unlike in the young, BCAA does not increase muscle mitochondrial function in the elderly.

Tatpati, Laura L.; Irving, Brian A.; Tom, Andrea; Bigelow, Maureen L.; Klaus, Katherine; Short, Kevin R.; Nair, K. Sreekumaran



Microcirculation in skeletal muscle  

PubMed Central

Summary The role of microcirculation in skeletal muscle is to provide the supply of oxygen and various nutrients and to remove waste products of muscle metabolism. As skeletal muscles are composed of different fibre types, this review tries to elucidate the question of capillary supply and flow with respect to these. It reviews the current knowledge of structure of microcirculation and its nervous, hormonal, and local (myogenic, metabolic and endothelial) control. It also discuss factors involved in the increase in blood flow and changes in microcirculation occurring during muscle contractions, exercise training, muscle hypertrophy and atrophy, hypoxia, ageing, hypertension, diabetes and limited blood supply.

Hudlicka, Olga



Skeletal muscle stem cells  

Microsoft Academic Search

Satellite cells are myogenic stem cells responsible for the post-natal growth, repair and maintenance of skeletal muscle. This review focuses on the basic biology of the satellite cell with emphasis on its role in muscle repair and parallels between embryonic myogenesis and muscle regeneration. Recent advances have altered the long-standing view of the satellite cell as a committed myogenic stem

Jennifer CJ Chen; David J Goldhamer



Muscle free amino acid profiles are related to differences in skeletal muscle growth between single and twin ovine fetuses near term.  


Twin sheep fetuses have reduced skeletal muscle weight near birth relative to singles as a result of restricted muscle hypertrophy. Intracellular free amino acids (FAA) are reported to regulate metabolic pathways which control muscle protein accretion, whereby reduced intracellular content of specific FAA may reduce their activation and therefore, muscle hypertrophy. The aim of this study was to determine whether differences in muscle weight between singleton and twin fetuses, under different maternal conditions is associated with reduced concentration of specific FAA. The FAA content in the semitendinosus muscle (ST) in singleton and twin fetuses (rank) at 140 days of gestation from heavy (H) or light (L) ewes fed ad libitum (A) or maintenance (M) level of nutrition was measured. Muscle weight was reduced in twin fetuses compared to singletons in all groups. Reduced concentrations of leucine, threonine and valine, but higher concentrations of methionine, ornithine, lysine and serine were found in twin fetuses compared to singletons. Maternal size and nutrition interaction with rank resulted in reduced glutamine in twins from HM-ewes (H-ewes under M nutrition) compared to their singleton counterparts. Maternal weight interaction with pregnancy rank reduced the concentration of arginine in twins, with a larger effect on H-ewes compared with L-ewes. Maternal size interaction with pregnancy rank resulted in twins from M-ewes to have lower alanine, while twins from A-ewes had lower aspartic acid concentration compared to singletons. The ST muscle weight was positively correlated only with arginine concentration after taking into account rank, size and nutrition. The present results indicate that reduced concentrations of specific intracellular FAA, such as arginine, leucine, valine, glutamine, which are known to play a role in muscle growth, could be acting as limiting factors for muscle hypertrophy in twin fetuses during late gestation. Ewe size and nutrition can influence the concentration of specific FAA in muscle and should be considered in any intervention plan to improve twin fetal muscle growth. PMID:24133643

Sales, Francisco; Pacheco, David; Blair, Hugh; Kenyon, Paul; McCoard, Sue



Branched-chain amino acid-containing dipeptides, identified from whey protein hydrolysates, stimulate glucose uptake rate in L6 myotubes and isolated skeletal muscles.  


In earlier studies we showed that dietary whey protein increased skeletal muscle and liver glycogen content in exercise-trained rats. However, little is known about whether ingredients of whey protein stimulate skeletal muscle glycogen accumulation. The aim of this study was to identify bioactive peptides in whey protein hydrolysates (WPH) which stimulated glucose uptake and glycogen synthesis rate in skeletal muscles. Branched-chain amino acid (BCAA)-containing dipeptides in WPH were identified using LC/MS/MS. L6 myotubes and isolated epitrochlearis muscles were used for the glucose uptake assays. The myotubes and muscles were incubated with or without 1 mM dipeptides, LY294002 a phosphoinositide 3-kinase (PI3-kinase) inhibitor, or GF102903X an atypical protein kinase C (aPKC) inhibitor, followed by measurement of 2-deoxyglucose uptake. Isolated muscles were incubated for 3 h with or without 1 mM Ile-Leu to determine glycogen synthesis rate. The BCAA-containing dipeptides, Ile-Val, Leu-Val, Val-Leu, Ile-Ile, Leu-Ile, Ile-Leu, and Leu-Leu were detected in the WPH by LC/MS/MS. These dipeptides caused significant stimulation in glucose uptake rate in the L6 myotubes. Ile-Leu, the main component in WPH, also stimulated glucose uptake in isolated skeletal muscles. Stimulation of glucose uptake by Ile-Leu was completely inhibited by treatment with either LY294002, or GF109203X in both L6 cells and isolated muscles. Ile-Leu increased glycogen contents in isolated muscles. These results suggest that BCAA-containing bioactive dipeptides in WPH stimulate glucose uptake in skeletal muscles via the PI3-kinase and aPKC pathways, resulting in increased skeletal muscle glycogen contents. PMID:19352067

Morifuji, Masashi; Koga, Jinichiro; Kawanaka, Kentaro; Higuchi, Mitsuru



Endogenous skeletal muscle antioxidants  

Microsoft Academic Search

Skeletal muscle is susceptible to oxidative deterioration due to a combination of lipid oxidation catalysts and membrane lipid systems that are high in unsaturated fatty acids. To prevent or delay oxidation reactions, several endogenous antioxidant systems are found in muscle tissue. These include ??tocopherol, histidine?containing dipeptides, and antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, and catalase. The contribution of

Kin M. Chan; Eric A. Decker; Cameron Feustman



Branched-chain amino acid interactions in skeletal muscle: isoleucine and L-alloisoleucine.  


Parenteral administration of a mixture of branched-chain amino acid (BCAA) solutions is known to alter plasma levels of the BCAA (ILE, LEU, VAL), their corresponding alpha-ketoacids (KMV, KIC, KIV) and L-alloisoleucine (ALLO), a stereoisomer of ILE. Although variously formulated mixtures of BCAA are administered, the metabolic implications of individual BCAA interactions have been only partially elucidated. Using the incubated, isolated, and intact rat epitrochlearis muscle, we measured the effect of graded increases (0.05, 0.10, 0.5, and 1.0 mM) in media concentrations of a single BCAA or ALLO on (1) the rate of decarboxylation of the other BCAA, and (2) the release of branched chain ketoacids from muscle. A graded increase of media ILE concentration to 1.0 mM changed the decarboxylation of LEU by -28%, and the release of KIC by +23%, but VAL decarboxylation increased by +25%, and the release of KIV declined by -56%. A graded increase of media LEU to 1.0 mM increased ILE decarboxylation by +146%, and its corresponding ketoacid (KMV) by +61%. However, VAL decarboxylation changed by only +25% and KIV release declined by -65%. A graded increase in media VAL to 1.0 mM accelerated ILE decarboxylation by +37%, but KMV release was unchanged. Similarly, LEU decarboxylation fell by -26%, and the release of KIC by only +6%. ALLO 0.025 mM increased ILE release by +55% but had an inconsistent effect on ILE decarboxylation and did not alter protein synthesis or degradation (estimated by phenylalanine incorporation and tyrosine release, respectively). Increasing ILE did not affect ALLO release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3093701

Downey, R S; Karl, I E; Bier, D M


Engineering skeletal muscle repair.  


Healthy skeletal muscle has a remarkable capacity for regeneration. Even at a mature age, muscle tissue can undergo a robust rebuilding process that involves the formation of new muscle cells and extracellular matrix and the re-establishment of vascular and neural networks. Understanding and reverse-engineering components of this process is essential for our ability to restore loss of muscle mass and function in cases where the natural ability of muscle for self-repair is exhausted or impaired. In this article, we will describe current approaches to restore the function of diseased or injured muscle through combined use of myogenic stem cells, biomaterials, and functional tissue-engineered muscle. Furthermore, we will discuss possibilities for expanding the future use of human cell sources toward the development of cell-based clinical therapies and in vitro models of human muscle disease. PMID:23711735

Juhas, Mark; Bursac, Nenad



Expression of Heat Shock Protein (Hsp90) Paralogues Is Regulated by Amino Acids in Skeletal Muscle of Atlantic Salmon  

PubMed Central

Heat shock proteins 90 (Hsp90) have an essential role in sarcomere formation and differentiation in skeletal muscle and also act as molecular chaperones during protein folding impacting a wide range of physiological processes. We characterised and provided a phylogenetically consistent nomenclature for the complete repertoire of six Hsp90 paralogues present in duplicated salmonid fish genomes (Hsp90?1a, Hsp90?1b, Hsp90?2a, Hsp90?2b, Hsp90ß1a and Hsp90ß1b). The expression of paralogues in fast skeletal muscle was investigated using in vivo fasting-feeding experiments and primary myogenic cultures. Fasted juvenile Atlantic salmon (Salmo salar) showed a transient 2 to 8-fold increase in the expression of all 4 Hsp90? paralogues within 24h of satiation feeding. Hsp90?1a and hsp90?1b also showed a pronounced secondary increase in expression after 10 days, concomitant with muscle differentiation and the expression of myogenin and sarcomeric proteins (mlc2, myhc). Hsp90ß1b was constitutively expressed whereas Hsp90ß1a expression was downregulated 10-fold between fasted and fed individuals. Hsp90?1a and Hsp90?1b were upregulated 10 to 15-fold concomitant with myotube formation and muscle differentiation in vitro whereas other Hsp90 paralogues showed no change in expression. In cells starved of amino acid (AA) and serum for 72h the addition of AA, but not insulin-like growth factor 1, increased phosphorylation of mTor and expression of all 4 hsp90? paralogues and associated co-chaperones including hsp30, tbcb, pdia4, pdia6, stga and fk504bp1, indicating a general activation of the protein folding response. In contrast, Hsp90ß1a expression in vitro was unresponsive to AA treatment indicating that some other as yet uncharacterised signal(s) regulate its expression in response to altered nutritional state.

Garcia de la serrana, Daniel; Johnston, Ian A.



Skeletal muscle stem cells  

PubMed Central

Satellite cells are myogenic stem cells responsible for the post-natal growth, repair and maintenance of skeletal muscle. This review focuses on the basic biology of the satellite cell with emphasis on its role in muscle repair and parallels between embryonic myogenesis and muscle regeneration. Recent advances have altered the long-standing view of the satellite cell as a committed myogenic stem cell derived directly from the fetal myoblast. The experimental basis for this evolving perspective will be highlighted as will the relationship between the satellite cell and other newly discovered muscle stem cell populations. Finally, advances and prospects for cell-based therapies for muscular dystrophies will be addressed.

Chen, Jennifer CJ; Goldhamer, David J



Noncontrast skeletal muscle oximetry.  


PURPOSE: The objective of this study was to develop a new noncontrast method to directly quantify regional skeletal muscle oxygenation. METHODS: The feasibility of the method was examined in five healthy volunteers using a 3 T clinical MRI scanner, at rest and during a sustained isometric contraction. The perfusion of skeletal muscle of the calf was measured using an arterial spin labeling method, whereas the oxygen extraction fraction of the muscle was measured using a susceptibility-based MRI technique. RESULTS: In all volunteers, the perfusion in soleus muscle increased significantly from 6.5?±?2.0 mL (100 g min)(-1) at rest to 47.9?±?7.7 mL (100 g min)(-1) during exercise (P?muscle but with greater oxygen extraction fraction increase than the soleus muscle. CONCLUSION: This is the first MR oximetry developed for quantification of regional skeletal muscle oxygenation. A broad range of medical conditions could benefit from these techniques, including cardiology, gerontology, kinesiology, and physical therapy. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc. PMID:23424006

Zheng, Jie; An, Hongyu; Coggan, Andrew R; Zhang, Xiaodong; Bashir, Adil; Muccigrosso, David; Peterson, Linda R; Gropler, Robert J



Vertebrate slow skeletal muscle actin — Conservation, distribution and conformational flexibility  

Microsoft Academic Search

The existence of a unique sarcomeric actin is demonstrated in teleosts that possess substantial amounts of slow skeletal muscle in the trunk. The slow skeletal isotype is conserved. There is one amino acid substitution between Atlantic herring slow skeletal actin and the equivalent in salmonids. Conversely, the intra-species variation is considerable; 13 substitutions between different herring skeletal isotypes (slow versus

Robert C. C. Mercer; Wasana A. K. A. Mudalige; Tolulope O. Ige; David H. Heeley



Effect of protein\\/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein  

Microsoft Academic Search

Regardless of age or gender, resistance training or provision of adequate amounts of dietary protein (PRO) or essential amino acids (EAA) can increase muscle protein synthesis (MPS) in healthy adults. Combined PRO or EAA ingestion proximal to resistance training, however, can augment the post-exercise MPS response and has been shown to elicit a greater anabolic effect than exercise plus carbohydrate.

Juha J Hulmi; Christopher M Lockwood; Jeffrey R Stout



Mechanisms of Skeletal Muscle Weakness  

Microsoft Academic Search

\\u000a Skeletal muscle weakness is an important feature of numerous ­pathological conditions and it may also be a component in normal\\u000a ageing. Decreased muscular strength can be due to decreased muscle mass and\\/or intrinsic defects in the muscle cells. In this\\u000a chapter we will discuss decreased force production due to mechanisms intrinsic to skeletal muscle cells. We will mainly use\\u000a data

Håkan Westerblad; Takashi Yamada


Kinetic properties of myosin heavy chain isoforms in mouse skeletal muscle: comparison with rat, rabbit, and human and correlation with amino acid sequence.  


Stretch activation kinetics were investigated in skinned mouse skeletal muscle fibers of known myosin heavy chain (MHC) isoform content to assess kinetic properties of different myosin heads while generating force. The time to peak of stretch-induced delayed force increase (t(3)) was strongly correlated with MHC isoforms [t(3) given in ms for fiber types containing specified isoforms; means +/- SD with n in parentheses: MHCI 680 +/- 108 (13), MHCIIa 110.5 +/- 10.7 (23), MHCIIx(d) 46.2 +/- 5.2 (20), MHCIIb 23.5 +/- 3.3 (76)]. This strong correlation suggests different kinetics of force generation of different MHC isoforms in the following order:MHCIIb > MHCIIx(d) > MHCIIa > MHCI. For rat, rabbit, and human skeletal muscles the same type of correlation was found previously. The kinetics decreases slightly with increasing body mass. Available amino acid sequences were aligned to quantify the structural variability of MHC isoforms of different animal species. The variation in t(3) showed a correlation with the structural variability of specific actin-binding loops (so-called loop 2 and loop 3) of myosin heads (r = 0.74). This suggests that alterations of amino acids in these loops contribute to the different kinetics of myosin heads of various MHC isoforms. PMID:15306546

Andruchov, Oleg; Andruchova, Olena; Wang, Yishu; Galler, Stefan



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



Addition of carbohydrate or alanine to an essential amino acid mixture does not enhance human skeletal muscle protein anabolism.  


In humans, essential amino acids (EAAs) stimulate muscle protein synthesis (MPS) with no effect on muscle protein breakdown (MPB). Insulin can stimulate MPS, and carbohydrates (CHOs) and insulin decrease MPB. Net protein balance (NB; indicator of overall anabolism) is greatest when MPS is maximized and MPB is minimized. To determine whether adding CHO or a gluconeogenic amino acid to EAAs would improve NB compared with EAA alone, young men and women (n = 21) ingested 10 g EAA alone, with 30 g sucrose (EAA+CHO), or with 30 g alanine (EAA+ALA). The fractional synthetic rate and phenylalanine kinetics (MPS, MPB, NB) were assessed by stable isotopic methods on muscle biopsies at baseline and 60 and 180 min following nutrient ingestion. Insulin increased 30 min postingestion in all groups and remained elevated in the EAA+CHO and EAA+ALA groups for 60 and 120 min, respectively. The fractional synthetic rate increased from baseline at 60 min in all groups (P < 0.05; EAA = 0.053 ± 0.018 to 0.090 ± 0.039%?·?h(-1); EAA+ALA = 0.051 ± 0.005 to 0.087 ± 0.015%?·?h(-1); EAA+CHO = 0.049 ± 0.006 to 0.115 ± 0.024%?·?h(-1)). MPS and NB peaked at 30 min in the EAA and EAA+CHO groups but at 60 min in the EAA+ALA group and NB was elevated above baseline longer in the EAA+ALA group than in the EAA group (P < 0.05). Although responses were more robust in the EAA+CHO group and prolonged in the EAA+ALA group, AUCs were similar among all groups for fractional synthetic rate, MPS, MPB, and NB. Because the overall muscle protein anabolic response was not improved in either the EAA+ALA or EAA+CHO group compared with EAA, we conclude that protein nutritional interventions to enhance muscle protein anabolism do not require such additional energy. PMID:23343676

Glynn, Erin L; Fry, Christopher S; Timmerman, Kyle L; Drummond, Micah J; Volpi, Elena; Rasmussen, Blake B



Effects of resistance exercise combined with essential amino acid supplementation and energy deficit on markers of skeletal muscle atrophy and regeneration during bed rest and active recovery  

PubMed Central

INTRODUCTION Space flight and bed rest (BR) lead to muscle atrophy. This study assessed the effect of essential amino acid supplementation (EAA) and resistance training with decreased energy intake on molecular changes in skeletal muscle after 28d BR and 14d recovery. METHODS Thirty-one men (31–55yr) subjected to an 8±6% energy deficit were randomized to receive EAA without resistance training (AA, n=7), EAA 3 h after (RT, n=12), or 5 min before (AART, n=12) resistance training. RESULTS During BR, myostatin transcript levels increased 2-fold in the AA group. During recovery, IGF1 mRNA increased in all groups while Pax7, MyoD, myogenin and MRF4 transcripts increased in AA only (all p<0.05). MAFbx transcripts decreased 2-fold with AA and RT. Satellite cells did not change during BR or recovery. DISCUSSION This suggests that EAA alone is the least protective countermeasure to muscle loss, and several molecular mechanisms are proposed by which exercise attenuates muscle atrophy during bed rest with energy deficit.

Brooks, Naomi E.; Cadena, Samuel M.; Vannier, Edouard; Cloutier, Gregory; Carambula, Silvia; Myburgh, Kathryn H.; Roubenoff, Ronenn; Castaneda-Sceppa, Carmen



Muscle amino acid pattern in obese rats  

Microsoft Academic Search

OBJECTIVE: To determine how the ability of skeletal muscle to manage amino acids is conditioned by obesity. The test was performed in two different models of obese rats: diet-obese rats and genetically obese rats. SUBJECTS: Lean and genetically obese (fa\\/fa) male Zucker rats were used. DESIGN: For up to 60 d of life lean animals were fed with standard chow

MC Herrero; X Remesar; C Bladé; LI Arola



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 (

Susan V. Brooks (University of Michigan)



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


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

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




Microsoft Academic Search

ontractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function re- sults in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest both scientifi- cally and clinically. Injury, disease, and old age are among the factors that commonly contribute to

Susan V. Brooks



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



Skeletal muscle hypertrophy and atrophy signaling pathways  

Microsoft Academic Search

Skeletal muscle hypertrophy is defined as an increase in muscle mass, which in the adult animal comes as a result of an increase in the size, as opposed to the number, of pre-existing skeletal muscle fibers. The protein growth factor insulin-like growth factor 1 (IGF-1) has been demonstrated to be sufficient to induce skeletal muscle hypertrophy. Over the past few

David J. Glass



Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised  

Microsoft Academic Search

Taurine is the most abundant free amino acid in heart and skeletal muscle. In the present study, the effects of hereditary taurine deficiency on muscle function were examined in taurine transporter knockout (taut?\\/?) mice. These mice show an almost complete depletion of heart and skeletal muscle taurine levels. Treadmill experiments demonstrated that total exercise capacity of taut?\\/? mice was reduced

Ulrich Warskulat; Ulrich Flögel; Christoph Jacoby; Hans-Georg Hartwig; Michael Thewissen; Marc W. Merx; Andrej Molojavyi; Birgit Heller-Stilb; Jürgen Schrader; Dieter Häussinger



Occurrence of a novel acetylated amino acid, N(alpha)-acetylhistidine, in skeletal muscle of freshwater fish and other ectothermic vertebrates.  


The occurrence of N(alpha)-acetylhistidine (NAH) in skeletal muscle of 91 species of freshwater fish and 9 species of other ectothermic vertebrates was investigated, with consideration of phylogenetic relationships. Of the 91 freshwater fish species examined, 13 species (7 cichlids, 5 anabantids, and 1 catfish) contained considerable amounts (>1 micromol/g) of NAH in their skeletal muscles. The highest level (10.37 micromol/g) of NAH was found in the tissue of Betta splendens (Siamese fighting fish). Moreover, the NAH contents in the tissues of Trichogaster trichopterus (three spot gourami), Kryptopterus bicirrhis (glass catfish), Oreochromis niloticus (Nile tilapia), Mikrogeophagus ramirezi (ram cichlid) and Parachromis managuensis (Guapote tigre) were 3.17-6.16 micromol/g. The skeletal muscle of amphibians (5 species) and reptiles (4 species) had a low level (<0.25 micromol/g) of NAH. The present findings clearly demonstrate NAH as the fifth imidazole-related compound, in addition to histidine, carnosine, anserine and ophidine (balenine), recognized as a major non-protein nitrogenous constituent in the skeletal muscle of vertebrate animals. PMID:19100335

Yamada, Shoji; Kawashima, Kazuto; Baba, Kyoko; Oku, Takahiro; Ando, Seiichi



[Regeneration capacity of skeletal muscle].  


The organotypic stem cell of skeletal muscle has previously been known as satellite cell. They allow muscle fiber growth during ontogenesis, enable fiber hypertrophy and are responsible for the very efficient repair of muscle fibers. This efficient apparatus is to some degree counterbalanced by an enormous use of the satellite cell pool: fiber atrophy probably is accompanied by loss of myonuclei such that every reversal of atrophy is bound to use new myonuclei i.e. satellite cells. How often in life does this occur? Hard to say. Moreover, the potent repair capacity is challenged by an unexpected vulnerability of skeletal muscle fibers: Passive stretching of contracted muscles may cause multiple "microdamage," disruption of contractile elements or tiny areas of true necrosis (focal necrosis). How often does this happen? Well, for many of us at least once per year when we go up and down mountains during vacation time, followed by sour muscles. Others may decide to change his/her (locomotor) behaviour by severe onset of jogging; it may happen that they suffer kidney failure on Monday due to muscle microdamage and the transfer of myoproteins into the serum over weekend. Also 20 minutes of stepping up and down something like a chair will do: There is a remarkable increase in kreatin kinase and other muscle derived proteins which lasts for days and is bound to reflect some muscle damage. How about sportsmen and worker who repeatedly use their muscles in such a way? We don't have answers yet to most of these questions, but considerable amount of information has been collected over the last years both in animal and--less--in human. What is common in all cases of growth and repair is the proliferation of the satellite cells and their consequent incorporation and fusion with the parent fiber. This way focal damage is repaired often without visible reminders. We would run out of satellite cells were they not stem cells: After division one daughter remains a satellite cell while the other is free to divide. Divide how often? Important for the human cells since the cell ages and proliferates slower and slower till it stops to divide at all, at least in culture. The same is true for the new satellite cell. This we know from recent experiments in which human biopsies derived myogenic cells were grown in vitro and in vivo (by implanting them into skeletal muscles of immunoincompetent mice): Growth correlates negatively with age of the donor. Between age 2 and some 70 years, about two divisions are performed by each satellite cell in human vastus lateralis and biceps brachii muscle in 10 years in the average. Most important for the older among us: at age 76 there are still some 13 divisions left before complete exhaustion. However, there are diseases like Duchenne Muscular Dystrophy (DMD) in which muscle fibers lack a structural protein with the effect of enhanced vulnerability to mechanical stress. There the enhanced use of the satellite cell pool makes the remaining growth capacity in an 8-years-old child as low as otherwise found at age 80. Some time ago, implantation of genetically intact myoblasts obtained from healthy relatives has been proposed as a treatment of DMD. Every logic would have predicted that some local implantation of whatever numbers of cells was bound to fail rescue the complete masculature or at least the muscles for breathing. The human as guinea pig? Now, even years later, we still collect the basic information on growth of human myoblasts and start thinking of ways for systemic application and quantitatively relevant incorporation of the myogenic stem cell or other--possibly pluripotent--stem cells derived from bone marrow. PMID:12956031

Wernig, A



Inhibited muscle amino acid uptake in sepsis.  

PubMed Central

Amino acid uptake in vivo was determined in soleus (SOL) muscle, diaphragm, heart, and liver following intravenous injection of [3H]-alpha-amino-isobutyric acid ([3H]-AIB) in rats made septic by cecal ligation and puncture (CLP) and in sham-operated controls. Muscle amino acid transport was also measured in vitro by determining uptake of [3H]-AIB in incubated extensor digitorum longus (EDL) and SOL muscles. Results were expressed as distribution ratio between [3H]-AIB in intracellular and extracellular fluid. AIB uptake in vivo was reduced by 90% in SOL and cardiac muscle and by 45% in diaphragm 16 hours after CLP. In contrast, AIB uptake by liver was almost four times higher in septic than in control animals. AIB uptake in vitro was reduced by 18% in EDL 8 hours after CLP but was not significantly altered in SOL at the same time point. Sixteen hours after CLP, AIB uptake was significantly reduced in both muscles, i.e., by 17% in EDL and by 65% in SOL. When muscles from untreated rats were incubated in the presence of plasma from septic animals (16 hours CLP) or from animals injected with endotoxin (2 mg/kg body weight), AIB uptake was reduced. Addition of endotoxin in vitro (2-200 micrograms/ml) to incubated muscles did not affect AIB uptake. The results suggest that sepsis leads to marked impairment of amino acid transport system A in muscle and that this impairment is mediated by a circulating factor that is not endotoxin. Reduced uptake of amino acids by skeletal muscle during sepsis may divert amino acids to the liver for increased gluconeogenesis and protein synthesis.

Hasselgren, P O; James, J H; Fischer, J E



Phosphodiesterase 4 inhibition reduces skeletal muscle atrophy.  


Several GTP-binding protein (G-protein)-coupled receptors that signal through Galphas (GTP-binding protein alpha stimulatory) and the cyclic adenosine monophosphate (cAMP) pathway increase skeletal muscle mass. In order to further evaluate the role of the cAMP pathway in the regulation of skeletal muscle mass, we utilized inhibitors of phosphodiesterase 4 (PDE 4), the major cAMP-modifying PDE found in skeletal muscle, to modulate skeletal muscle cAMP levels. We found that PDE 4 inhibitors reduced the loss of muscle mass and force resulting from denervation and casting in rats and mice. These studies indicate that PDE 4 inhibitors may have a role in the treatment of skeletal muscle-wasting diseases. PMID:16116651

Hinkle, Richard T; Dolan, Elizabeth; Cody, David B; Bauer, Mary Beth; Isfort, Robert J



A carboxy-terminal ?-helical segment in the rat skeletal muscle voltage-dependent Na + channel is responsible for its interaction with the amino-terminus  

Microsoft Academic Search

Cytoplasmic segments of the adult rat skeletal muscle sodium channel ?-subunit (rSkM1) comprise a major portion (?40%) of the total protein and are involved in channel functions both general, such as inactivation, and isoform-specific, for example, protein kinase A modulation. Far ultraviolet circular dichroism measurements of synthetic peptides and overexpressed fusion proteins containing individual channel cytoplasmic segments suggest that cytoplasmic

Hui Zhang; Sylvia Kolibal; Jane M Vanderkooi; Sidney A Cohen; Roland G Kallen



Skeletal muscle stem cell birth and properties  

Microsoft Academic Search

Development and maintenance of an abundant tissue such as skeletal muscle poses several challenges. Curiously, not all skeletal muscle stem cells are born alike, since diverse genetic pathways can specify their birth. Stem and progenitor cells that establish the tissue during development, those that maintain its homeostasis, as well as participate in its regeneration have generated considerable interest. The ability

Ramkumar Sambasivan; Shahragim Tajbakhsh



Skeletal muscle excitation-contraction coupling I  

Microsoft Academic Search

Porcine skeletal muscle fibers were studied to determine if the defect in malignant hyperthermia involves transverse tubule (TT) to sarcoplasmic reticulum (SR) communication. Pelled (mechanically skinned) skeletal muscle fibers from normal and malignant hyperthermia susceptible (MHS) pigs were stimulated with Cl- to ionically depolarize transverse tubules and thereby trigger Ca2+ release from SR. Caffeine was used to directly stimulate the

Sue K. Donaldson; Esther M. Gallant; Daniel A. Huetteman



Human skeletal muscle releases leptin in vivo.  


Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle and adipose tissue leptin release in vivo. We recruited 16 healthy male human participants. Catheters were inserted into the femoral artery and vein draining skeletal muscle, as well as an epigastric vein draining the abdominal subcutaneous adipose tissue. By combining the veno-arterial differences in plasma leptin with measurements of blood flow, leptin release from both tissues was quantified. To induce changes in leptin, the participants were infused with either saline or adrenaline in normo-physiological concentrations. The presence of leptin in skeletal muscle was confirmed by western blotting. Leptin was released from leg skeletal muscle (50.6 ± 12 ng min(-1)) and the pattern of release was different from subcutaneous adipose tissue. Moreover, during adrenaline infusion the leptin release from leg skeletal muscle was strongly suppressed (20.5 ± 7.9 ng min(-1), p<0.017), whereas the release from fat was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater mass of muscle compared to fat. An understanding of the role that leptin plays in skeletal muscle metabolism may prove important in light of several late-phase trials with recombinant leptin as an anti-obesity drug. PMID:23010500

Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S; Pedersen, Bente K; van Hall, Gerrit



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.




Microsoft Academic Search

Satellite cells of adult skeletal muscle fibres are myogenic monoculeated cells that are closely attached to muscle fibres. These cells provide new myonuclei during growth and regeneration; myonuclei are postmitotic. Three to 11 of myonuclei seen by light microscopy in reality are satellite cell nuclei. Developing muscles contain up to 35% satellite cells. Their incidence decreases after denervation and possibly

Henning Schmalbruch



Growth factors in skeletal muscle regeneration  

Microsoft Academic Search

Adult skeletal muscles are able to regenerate after injury. This process is due to the activation of quiescent muscle precursor cells, also called satellite cells, which proliferate and differentiate to form new myotubes. In this regeneration process, several growth factors which come from the muscle and\\/or from the motor nerve and inflammatory cells have been shown to play key roles.

Irene Husmann; Laurent Soulet; Jean Gautron; Isabelle Martelly; Denis Barritault



Monitoring Murine Skeletal Muscle Function for Muscle Gene Therapy  

PubMed Central

The primary function of skeletal muscle is to generate force. Muscle force production is compromised in various forms of acquired and/or inherited muscle diseases. An important goal of muscle gene therapy is to recover muscle strength. Genetically engineered mice and spontaneous mouse mutants are readily available for preclinical muscle gene therapy studies. In this chapter, we outlined the methods commonly used for measuring murine skeletal muscle function. These include ex vivo and in situ analysis of the contractile profile of a single intact limb muscle (the extensor digitorium longus for ex vivo assay and the tibialis anterior muscle for in situ assay), grip force analysis, and downhill treadmill exercise. Force measurement in a single muscle is extremely useful for pilot testing of new gene therapy protocols by local gene transfer. Grip force and treadmill assessments offer body-wide evaluation following systemic muscle gene therapy.

Hakim, Chady H.; Li, Dejia; Duan, Dongsheng



Skeletal Muscle Ischemia and Heat Shock Proteins.  

National Technical Information Service (NTIS)

Blood loss testing in decreased organ perfusion and subsequent ischemic injury of cardiac and skeletal muscle presents a significant problem for the soldier in combat. Recent findings indicate that different forms of noxious stress including exposure to i...

W. H. Dillmann



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



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.



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


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



How sex hormones promote skeletal muscle regeneration.  


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



Biochemical Mechanisms and Physiological Effects of Work-induced Growth of Skeletal Muscle.  

National Technical Information Service (NTIS)

The effects of nutrients, hormones and muscular contraction on protein turnover in skeletal muscle were investigated. One interesting finding has been that the supply of branched chain amino acids promotes protein synthesis and retards protein catabolism ...

A. L. Goldberg



Electromechanical Coupling between Skeletal and Cardiac Muscle  

PubMed Central

Skeletal myoblasts form grafts of mature muscle in injured hearts, and these grafts contract when exogenously stimulated. It is not known, however, whether cardiac muscle can form electromechanical junctions with skeletal muscle and induce its synchronous contraction. Here, we report that undifferentiated rat skeletal myoblasts expressed N-cadherin and connexin43, major adhesion and gap junction proteins of the intercalated disk, yet both proteins were markedly downregulated after differentiation into myo-tubes. Similarly, differentiated skeletal muscle grafts in injured hearts had no detectable N-cadherin or connexin43; hence, electromechanical coupling did not occur after in vivo grafting. In contrast, when neonatal or adult cardiomyocytes were cocultured with skeletal muscle, ?10% of the skeletal myotubes contracted in synchrony with adjacent cardiomyocytes. Isoproterenol increased myotube contraction rates by 25% in coculture without affecting myotubes in monoculture, indicating the cardiomyocytes were the pacemakers. The gap junction inhibitor heptanol aborted myotube contractions but left spontaneous contractions of individual cardiomyocytes intact, suggesting myotubes were activated via gap junctions. Confocal microscopy revealed the expression of cadherin and connexin43 at junctions between myotubes and neonatal or adult cardiomyocytes in vitro. After microinjection, myotubes transferred dye to neonatal cardiomyocytes via gap junctions. Calcium imaging revealed synchronous calcium transients in cardiomyocytes and myotubes. Thus, cardiomyocytes can form electromechanical junctions with some skeletal myotubes in coculture and induce their synchronous contraction via gap junctions. Although the mechanism remains to be determined, if similar junctions could be induced in vivo, they might be sufficient to make skeletal muscle grafts beat synchronously with host myocardium.

Reinecke, Hans; MacDonald, Glen H.; Hauschka, Stephen D.; Murry, Charles E.



Sex hormones and skeletal muscle weakness.  


Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle. PMID:23636830

Sipilä, Sarianna; Narici, Marco; Kjaer, Michael; Pöllänen, Eija; Atkinson, Ross A; Hansen, Mette; Kovanen, Vuokko



Skeletal and Cardiac Muscle Contractile Activation: Tropomyosin \\  

Microsoft Academic Search

n encountering a saber-tooth tiger, the caveman was faced with two choices: to escape or to defend himself. Either strategy required rapid activation of skeletal muscles and adjustment of the performance of cardiac muscle to increase blood flow to support an increased muscular effort. Although saber-toothed tigers no longer exist, our physiological require- ments are no less demanding for performing

A. M. Gordon; M. Regnier; E. Homsher


Hypothermia and Blood Flow Through Skeletal Muscle.  

National Technical Information Service (NTIS)

The effect of hypothermia on the circulation of skeletal muscle was studied. All experiments utilized the gracilis muscle of the dog. The rate of production of hypothermia determines the vascular response, a fast rate (> 1C/min) causing vasodilatation and...

L. R. Yonce



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



Mechanisms regulating skeletal muscle growth and atrophy.  


Skeletal muscle mass increases during postnatal development through a process of hypertrophy, i.e. enlargement of individual muscle fibers, and a similar process may be induced in adult skeletal muscle in response to contractile activity, such as strength exercise, and specific hormones, such as androgens and ?-adrenergic agonists. Muscle hypertrophy occurs when the overall rates of protein synthesis exceed the rates of protein degradation. Two major signaling pathways control protein synthesis, the IGF1-Akt-mTOR pathway, acting as a positive regulator, and the myostatin-Smad2/3 pathway, acting as a negative regulator, and additional pathways have recently been identified. Proliferation and fusion of satellite cells, leading to an increase in the number of myonuclei, may also contribute to muscle growth during early but not late stages of postnatal development and in some forms of muscle hypertrophy in the adult. Muscle atrophy occurs when protein degradation rates exceed protein synthesis, and may be induced in adult skeletal muscle in a variety of conditions, including starvation, denervation, cancer cachexia, heart failure and aging. Two major protein degradation pathways, the proteasomal and the autophagic-lysosomal pathways, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These pathways involve a variety of atrophy-related genes or atrogenes, which are controlled by specific transcription factors, such as FoxO3, which is negatively regulated by Akt, and NF-?B, which is activated by inflammatory cytokines. PMID:23517348

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



Myoglobinuria and Skeletal Muscle Phosphorylase Deficiency  

PubMed Central

Investigation of a patient complaining of exercise-induced dark urine, pain, stiffness and tenderness of skeletal muscle revealed findings characteristic of McArdle's disease. The dark urine was attributable to the excretion of myoglobin, and an ischemic exercise test failed to demonstrate the usual rise and fall in blood lactate and pyruvate. Enzyme assays of skeletal muscle showed an absence of phosphorylase, a slight increase in phosphorylase b kinase and a slight decrease in phosphoglucomutase. Chemical and histochemical analyses demonstrated an increase in the skeletal muscle glycogen content and an enlargement of the muscle cells. No abnormality of liver glycogen metabolism was found. In the absence of specific therapy, an effective and practical form of treatment is reduction of exercise below the threshold of symptoms. ImagesFig. 1Fig. 2Fig. 6Fig. 7Fig. 8

Nixon, J. C.; Hobbs, W. K.; Greenblatt, J.



Stem cells for skeletal muscle repair.  


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. PMID:21727135

Shadrach, Jennifer L; Wagers, Amy J



Human Skeletal Muscle Health with Spaceflight  

NASA Astrophysics Data System (ADS)

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

Trappe, Scott



Insulin binding to individual rat skeletal muscles  

SciTech Connect

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

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



Autophagy and Skeletal Muscles in Sepsis  

PubMed Central

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

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



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


Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ?3 weeks to 2587±502??N/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy. PMID:23574457

Lee, Peter H U; Vandenburgh, Herman H



Skeletal muscle specific genes networks in cattle.  


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. PMID:20524025

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



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



Regulation of Limulus skeletal muscle contraction  

Microsoft Academic Search

Skeletal muscle contraction of Limulus polyphemus, the horseshoe crab, seemed to be regulated in a dual manner, namely Ca2+ binding to the troponin complex as well phosphorylation of the myosin light chains (MLC) by a Ca2+\\/calmodulin-dependent myosin light chain kinase. We investigated muscle contraction in Limulus skinned fibers in the presence of Ca2+ and of Ca2+\\/calmodulin to find out which

Oliver Ritter; Hannelore Haase; Ingo Morano



Systemic skeletal muscle necrosis induced by crotoxin  

Microsoft Academic Search

Systemic skeletal muscle necrosis induced by crotoxin, the major component of the venom of Crotalus durissus terrificus, was investigated. Mice received an intramuscular injection of crotoxin (0.35mg\\/kg body weight) into the right tibialis anterior (TA) muscles, which were evaluated 3h, 24h and 3 days later. Control mice were injected with saline. Right and left TAs, gastrocnemius, soleus and right masseter

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



Heparan sulfates in skeletal muscle development and physiology  

Microsoft Academic Search

Recent years have seen an emerging interest in the composition of the skeletal muscle extracellular matrix (ECM) and in the developmental and physiological roles of its constituents. Many cell surface-associated and ECM-embedded molecules occur in highly organized spatiotemporal patterns, suggesting important roles in the development and functioning of skeletal muscle. Glycans are historically underrepresented in the study of skeletal muscle

Guido J. Jenniskens; Jacques H. Veerkamp; A. H. M. S. M. van Kuppevelt



Effect of skeletal muscle demand on cardiovascular function  

Microsoft Academic Search

HARMS, C. A. Effect of skeletal muscle demand on cardiovascular function. Med. Sci. Sports Exerc.,Vol. 32, No. 1, pp. 94 -99, 2000. Cardiac output is directed primarily to skeletal muscle during exercise. Recent investigations have examined how different groups of skeletal muscle compete for the cardiac output during exercise. To date, there is a lack of consistent findings on a




Phospholipid methylation in skeletal muscle membranes.  


Phospholipid methylation is thought to modulate such vital cellular processes as calcium transport, receptor function, and membrane microviscosity. As these processes are fundamental to the function of muscle cells and are thought to be altered in disease states, we have characterized several features of phospholipid methylation reactions in skeletal muscle and have defined appropriate assay conditions. In rat leg muscle, methyltransferase activity was assayed radiometrically by measuring the incorporation of methyl groups from S-adenosyl-L-[methyl-3H]methionine into membrane phospholipids, the methylated derivatives of which were separated by thin-layer chromatography. Contrary to previous investigations of whole muscle, phospholipid methyltransferase activity was clearly present in skeletal muscle membranes, being highly localized in sarcoplasmic reticulum and present to a lesser extent in sarcolemma. Both the reaction products and the reaction kinetics were consistent with sequential methylation of phospholipids by two methyltransferase enzymes. S-adenosylhomocysteine and its analogues were potent inhibitors of phospholipid methylation in sarcoplasmic reticulum. The predominant localization of phospholipid methyltransferase activity in sarcoplasmic reticulum suggests that its functional role in skeletal muscle may be in calcium transport. PMID:16758590

Kuncl, R W; Drachman, D B; Kishimoto, Y



Impaired skeletal muscle microcirculation in systemic sclerosis.  


ABSTRACT: INTRODUCTION: Muscle symptoms in systemic sclerosis (SSc) may originate from altered skeletal muscle microcirculation, which can be investigated by means of blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). METHODS: After ethics committee approval and written consent, 11 consecutive SSc patients (5 men, mean age 52.6 years, mean SSc disease duration 5.4 years) and 12 healthy volunteers (4 men, mean age 45.1 years) were included. Subjects with peripheral arterial occlusive disease were excluded. BOLD MRI was performed on calf muscles during cuff-induced ischemia and reactive hyperemia, using a 3-T whole-body scanner (Verio, Siemens, Erlangen, Germany) and fat-suppressed single-short multi-echo echo planar imaging (EPI) with four different effective echo times. Muscle BOLD signal time courses were obtained for gastrocnemius and soleus muscles: minimal hemoglobin oxygen saturation (T2*min) and maximal T2* values (T2*max), time to T2* peak (TTP), and slopes of oxygen normalization after T2* peaking. RESULTS: The vast majority of SSc patients lacked skeletal muscle atrophy, weakness or serum creatine kinase elevation. Nevertheless, more intense oxygen desaturation during ischemia was observed in calf muscles of SSc patients (mean T2*min -15.0%), compared with controls (-9.1%, P = 0.02). SSc patients also had impaired oxygenation during hyperemia (median T2*max 9.2% vs. 20.1%, respectively, P = 0.007). The slope of muscle oxygen normalization was significantly less steep and prolonged (TTP) in SSc patients (P<0.001 for both). Similar differences were found at a separate analysis of gastrocnemius and soleus muscles, with most pronounced impairment in the gastrocnemius. CONCLUSIONS: BOLD MRI demonstrates a significant impairment of skeletal muscle microcirculation in SSc. PMID:23036642

Partovi, Sasan; Schulte, Anja-Carina; Aschwanden, Markus; Staub, Daniel; Benz, Daniela; Imfeld, Stephan; Jacobi, Björn; Broz, Pavel; Jäger, Kurt A; Takes, Martin; Huegli, Rolf W; Bilecen, Deniz; Walker, Ulrich A



Skeletal Muscle Responses to Unloading in Humans.  

National Technical Information Service (NTIS)

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 imagin...

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



Mechanisms of Ischemic Preconditioning in Skeletal Muscle  

Microsoft Academic Search

Background. Ischemic preconditioning (IP) (one or more cycles each consisting of a short period of ischemia and a short period of reperfusion, before the sustained ischemia) reduces ischemia-related organ damage in heart and skeletal muscle but the underlying mechanisms are not clear. This study was intended to assess the possible involvement of KATP channels and of adenosine receptors in IP

L. Gürke; A. Mattei; K. Chaloupka; A. Marx; P. M. Sutter; P. Stierli; F. Harder; M. Heberer



Neural control of aging skeletal muscle  

Microsoft Academic Search

Summary Functional and structural decline in the neuromuscular system with aging has been recognized as a cause of impairment in physical performance and loss of inde- pendence in the elderly. Alterations in spinal cord motor neurones and at the neuromuscular junction have been identified as evidence of denervation in skeletal muscles from aging mammals, including humans. However, the reciprocal influences

Osvaldo Delbono



Training induced adaptation in horse skeletal muscle  

Microsoft Academic Search

It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transport, enzyme activity, etc) differ considerably between species. The major drawbacks in equine training physiological research are the

K. G. van Dam



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



Mammalian Skeletal Muscle Fiber Type Transitions  

Microsoft Academic Search

Mammalian skeletal muscle is an extremely heterogeneous tissue, composed of a large variety of fiber types. These fibers, however, are not fixed units but represent highly versatile entities capable of responding to altered functional demands and a variety of signals by changing their phenotypic profiles. This adaptive responsiveness is the basis of fiber type transitions. The fiber population of a

Dirk Pette; Robert S. Staron



IL-6-induced skeletal muscle atrophy.  


Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6. PMID:15542570

Haddad, F; Zaldivar, F; Cooper, D M; Adams, G R



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


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. PMID:23193112

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; Spangenburg, Espen E



Mitochondrial Bioenergetics of Skeletal Muscles  

Microsoft Academic Search

Myofibril is the main contractile structure of a muscle; sarcomere is a functional unit comprising thin actin and thick myosin\\u000a filaments. The process of muscular fiber shortening takes place through insertion of thin actinic filaments in between the\\u000a thick myosin ones. The whole process is regulated by regulatory proteins troponin and tropomyosin. Energy necessary for muscle\\u000a contraction is obtained from

Janka Lipková


The enzymology of skeletal muscle disorders.  


In myopathic disorders, abnormal serum enzyme activities are seen primarily in diseases of skeletal muscle where the condition involves the muscle fibers themselves. In denervation myopathies, serum enzyme activities are usually normal. The most dramatic increases of serum enzymes, particularly creatine kinase, are found in the dystrophic diseases, particularly Duchenne dystrophy. A review is given here of the many causes of abnormal serum enzyme activities where the source of enzymes is believed to be skeletal muscle. These include the dystrophies, various types of trauma, exercise, drug- and poison-induced causes including alcohol, malignant hyperthermia, inflammatory diseases, and miscellaneous causes. Tissue and serum activities are summarized for the commonly performed serum enzymes, i.e., CK, LD, AST, and aldolase. An extensive tabular and current description of the various types of dystrophies is given along with serum CK and pyruvate kinase activities. PMID:6373145

Lott, J A; Landesman, P W



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



Mice Lacking Skeletal Muscle Actin Show Reduced Muscle Strength and Growth Deficits and Die during the Neonatal Period  

PubMed Central

All four of the muscle actins (skeletal, cardiac, vascular, and enteric) in higher vertebrates show distinct expression patterns and display highly conserved amino acid sequences. While it is hypothesized that each of the muscle isoactins is specifically adapted to its respective tissue and that the minor variations among them have developmental and/or physiological relevance, the exact functional and developmental significance of these proteins remains largely unknown. In order to begin to assess these issues, we disrupted the skeletal actin gene by homologous recombination. All mice lacking skeletal actin die in the early neonatal period (day 1 to 9). These null animals appear normal at birth and can breathe, walk, and suckle, but within 4 days, they show a markedly lower body weight than normal littermates and many develop scoliosis. Null mice show a loss of glycogen and reduced brown fat that is consistent with malnutrition leading to death. Newborn skeletal muscles from null mice are similar to those of wild-type mice in size, fiber type, and ultrastructural organization. At birth, both hemizygous and homozygous null animals show an increase in cardiac and vascular actin mRNA in skeletal muscle, with no skeletal actin mRNA present in null mice. Adult hemizygous animals show an increased level of skeletal actin mRNA in hind limb muscle but no overt phenotype. Extensor digitorum longus (EDL) muscle isolated from skeletal-actin-deficient mice at day 2 to 3 showed a marked reduction in force production compared to that of control littermates, and EDL muscle from hemizygous animals displayed an intermediate force generation. Thus, while increases in cardiac and vascular smooth-muscle actin can partially compensate for the lack of skeletal actin in null mice, this is not sufficient to support adequate skeletal muscle growth and/or function.

Crawford, K.; Flick, R.; Close, L.; Shelly, D.; Paul, R.; Bove, K.; Kumar, A.; Lessard, J.



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


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



The mechanics of mouse skeletal muscle when shortening during relaxation  

Microsoft Academic Search

The dynamic properties of relaxing skeletal muscle have not been well characterised but are important for understanding muscle function during terrestrial locomotion, during which a considerable fraction of muscle work output can be produced during relaxation. The purpose of this study was to characterise the force–velocity properties of mouse skeletal muscle during relaxation. Experiments were performed in vitro (21°C) using

C. J. Barclay; G. A. Lichtwark



Effect of taurine depletion on excitation-contraction coupling and C1 ? conductance of rat skeletal muscle  

Microsoft Academic Search

The pharmacological action of taurine on skeletal muscle is to stabilize sarcolemma by increasing macroscopic conductance to Cl? (GC1), whereas a proposed physiological role for the amino acid is to modulate excitation-contraction coupling mechanism via Ca2+ availability. To get insight in the physiological role of taurine in skeletal muscle, the effects of its depletion were evaluated on voltage threshold for

Annamaria De Luca; Sabata Pierno; Diana Conte Camerino



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



Vitamin D and human skeletal muscle.  


Vitamin D deficiency is an increasingly described phenomenon worldwide, with well-known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both under-performance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue. PMID:19807897

Hamilton, B



Vitamin D and Human Skeletal Muscle  

PubMed Central

Vitamin D deficiency is an increasingly described phenomenon worldwide, with well-known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both underperformance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue.

Hamilton, B



Wave biomechanics of the skeletal muscle  

NASA Astrophysics Data System (ADS)

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

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



Program for the Study of Skeletal Muscle Catabolism Following Physical Trauma.  

National Technical Information Service (NTIS)

The purpose of this work was to attenuate skeletal muscle proteolysis in the post-traumatic period. In the initial study, amino acid solutions were administered with or without glutamine supplementation. Amino Acid administration at the dose of 0.624 gram...

D. Wilmore



Conchotome and needle percutaneous biopsy of skeletal muscle.  

PubMed Central

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

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



Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling  

PubMed Central

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

Drummond, Micah J.; Dreyer, Hans C.; Fry, Christopher S.; Glynn, Erin L.; Rasmussen, Blake B.




Technology Transfer Automated Retrieval System (TEKTRAN)

In adults, sepsis reduces protein synthesis in skeletal muscle by restraining translation. The effect of sepsis on amino acid-stimulated muscle protein synthesis has not been determined in neonates, a population who is highly anabolic and whose muscle protein synthesis rates are uniquely sensitive ...


Stretching Skeletal Muscle: Chronic Muscle Lengthening through Sarcomerogenesis  

PubMed Central

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

Zollner, Alexander M.; Abilez, Oscar J.; Bol, Markus; Kuhl, Ellen



Stretching skeletal muscle: chronic muscle lengthening through sarcomerogenesis.  


Skeletal muscle responds to passive overstretch through sarcomerogenesis, the creation and serial deposition of new sarcomere units. Sarcomerogenesis is critical to muscle function: It gradually re-positions the muscle back into its optimal operating regime. Animal models of immobilization, limb lengthening, and tendon transfer have provided significant insight into muscle adaptation in vivo. Yet, to date, there is no mathematical model that allows us to predict how skeletal muscle adapts to mechanical stretch in silico. Here we propose a novel mechanistic model for chronic longitudinal muscle growth in response to passive mechanical stretch. We characterize growth through a single scalar-valued internal variable, the serial sarcomere number. Sarcomerogenesis, the evolution of this variable, is driven by the elastic mechanical stretch. To analyze realistic three-dimensional muscle geometries, we embed our model into a nonlinear finite element framework. In a chronic limb lengthening study with a muscle stretch of 1.14, the model predicts an acute sarcomere lengthening from 3.09[Formula: see text]m to 3.51[Formula: see text]m, and a chronic gradual return to the initial sarcomere length within two weeks. Compared to the experiment, the acute model error was 0.00% by design of the model; the chronic model error was 2.13%, which lies within the rage of the experimental standard deviation. Our model explains, from a mechanistic point of view, why gradual multi-step muscle lengthening is less invasive than single-step lengthening. It also explains regional variations in sarcomere length, shorter close to and longer away from the muscle-tendon interface. Once calibrated with a richer data set, our model may help surgeons to prevent muscle overstretch and make informed decisions about optimal stretch increments, stretch timing, and stretch amplitudes. We anticipate our study to open new avenues in orthopedic and reconstructive surgery and enhance treatment for patients with ill proportioned limbs, tendon lengthening, tendon transfer, tendon tear, and chronically retracted muscles. PMID:23049683

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



BOLD magnetic resonance imaging of skeletal muscle.  


Blood-oxygen-level-dependent (BOLD) imaging was a concept introduced in 1990 for evaluating brain activation. The method relies on magnetic resonance imaging (MRI) contrast resulting from changes in the microvascular ratio of oxyhaemoglobin (oxyHb) to deoxyhaemoglobin (deoxyHb). OxyHb is diamagnetic, whereas deoxyHb is paramagnetic, which produces a local bulk magnetic susceptibility effect and subsequent MRI signal change. The changes are typically observed in T(2)*-weighted functional MRI scans. However, there has recently been interest in BOLD as a way to evaluate microcirculation of any normal or diseased tissue. This review focuses on the application of BOLD imaging in the understanding of normal and diseased skeletal muscle. In addition we present new findings showing the possible application of BOLD imaging with hyperoxia for evaluating skeletal muscle physiology. PMID:14735429

Noseworthy, Michael D; Bulte, Daniel P; Alfonsi, Jeff



PGC-1? regulates angiogenesis in skeletal muscle  

PubMed Central

Aerobic metabolism requires oxygen and carbon sources brought to tissues via the vasculature. Metabolically active tissues such as skeletal muscle can regulate blood vessel density to match metabolic needs; however, the molecular cues that coordinate these processes remain poorly understood. Here we report that the transcriptional coactivator peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?), a potent regulator of mitochondrial biology, induces angiogenesis in skeletal muscle. PGC-1? induces the expression of vascular endothelial growth factor (VEGF) in cell culture and in vivo. The induction of VEGF by PGC-1? requires coactivation of the orphan nuclear receptor estrogen-related receptor-? (ERR?) and is independent of the hypoxia-inducible factor (HIF) pathway. In coculture experiments, overexpression of PGC-1? in skeletal myotubes increases the migration of adjacent endothelial cells, and this depends on VEGF signaling. Transgenic expression of PGC-1? in skeletal myocytes dramatically increases muscular vessel density. Taken together, these data indicate that PGC-1? is a potent regulator of angiogenesis, thus providing a novel link between the regulations of oxidative metabolism and vascular density.

Rowe, Glenn C.; Jang, Cholsoon; Patten, Ian S.



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



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



Injury and adaptive mechanisms in skeletal muscle  

Microsoft Academic Search

Work-related musculoskeletal disorders (MSD) are a major concern in the United States. Overexertion and repetitive motion injuries dominate reporting of lost-time MSD incidents. Over the past three decades, there has been much study on contraction-induced skeletal muscle injury. The effect of the biomechanical loading signature that includes velocity, range of motion, the number of repetitions, force, work-rest cycle, and exposure

Robert G. Cutlip; Brent A. Baker; Melinda Hollander; James Ensey



PGC1?-mediated adaptations in skeletal muscle  

Microsoft Academic Search

Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects\\u000a of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative\\u000a effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the\\u000a transcriptional coactivator peroxisome

Jesper Olesen; Kristian Kiilerich; Henriette Pilegaard



Leptin receptors in human skeletal muscle  

Microsoft Academic Search

Abstract. Human skeletal muscle expresses leptin receptor mRNA, however it remains unknown whether leptin receptors (OB-R) are also expressed at the protein level. Fourteen, healthy men (age = 33.1 ± 2.0 yr, height = 175.9 ± 1.7 cm, body mass = 81.2 ± 3.8 kg, body fat = 22.5 ± 1.9%; mean,± s.e.m.) participated in this investigation. The expression of

Borja Guerra; Alfredo Santana; Teresa Fuentes; Safira Delgado-Guerra; A. Cabrera-Socorro; C. Dorado; J. A. L. Calbet



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



Nonmyogenic cells in skeletal muscle regeneration.  


Although classical dogma dictates that satellite cells are the primary cell type involved in skeletal muscle regeneration, alternative cell types such as a variety of inflammatory and stromal cells are also actively involved in this process. A model describing myogenic cells as direct contributors to regeneration and nonmyogenic cells from other developmental sources as important accessories has emerged, with similar systems having been described in numerous other tissues in the body. Increasing evidence supports the notion that inflammatory cells function as supportive accessory cells, and are not merely involved in clearing damage following skeletal muscle injury. Additionally, recent studies have highlighted the role of tissue resident mesenchymal cell populations as playing a central role in regulating regeneration. These "accessory" cell populations are proposed to influence myogenesis via direct cell contact and secretion of paracrine trophic factors. The basic foundations of accessory cell understanding should be recognized as a crucial component to all prospects of regenerative medicine, and this chapter intends to provide a comprehensive background on the current literature describing immune and tissue-resident mesenchymal cells' role in skeletal muscle regeneration. PMID:21621070

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



Metastases of esophageal carcinoma to skeletal muscle: single center experience.  


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. PMID:23002370

Cincibuch, Jan; Myslive?ek, Miroslav; Melichar, Bohuslav; Neoral, Cestmír; Metelková, Iva; Zezulová, Michaela; Procházková-Študentová, Hana; Flodr, Patrik; Zlevorová, Miloslava; Aujeský, René; Cwiertka, Karel



Proteomics of skeletal muscle aging.  


Extended human longevity has resulted in increasing numbers of elderly persons in the general population. However, old age is also associated with a variety of serious physical disorders. Frailty among sedentary elderly patients is related to the impaired structure and function of contractile fibers. Biochemical research into cellular mechanisms that underlie sarcopenia promises to acquire the scientific basis of evidence to aid the development of new diagnostic and therapeutic strategies. The recent application of MS-based proteomic methodology has identified a large cohort of disease-specific markers of sarcopenia. This review critically examines the biomedical implications of the results obtained from the proteomic screening of both aged human muscle and established animal models of sarcopenia. Substantial alterations in proteins involved in key metabolic pathways, regulatory and contractile elements of the actomyosin apparatus, myofibrillar remodeling and the cellular stress response are discussed. A multi-factorial etiology appears to be the basis for a slower-twitching aged fiber population, which exhibits a shift to more aerobic-oxidative metabolism. It is hoped that the detailed biomedical characterization of the newly identified biomarkers of sarcopenia will translate into better treatment options for reversing age-dependent muscle degeneration, which could improve the standard of living for a large portion of society. PMID:19180535

Doran, Philip; Donoghue, Pamela; O'Connell, Kathleen; Gannon, Joan; Ohlendieck, Kay



Hexokinase isozyme distribution in human skeletal muscle.  


Two isoforms of hexokinase (type I and type II) are expressed in skeletal muscle; however, the intracellular distribution of these hexokinase isoforms in human skeletal muscle is unclear. The current study was undertaken to assess this issue because binding of hexokinase to subcellular structures is considered to be an important mechanism in the regulation of glucose phosphorylation. Vastus lateralis muscle was obtained from healthy lean individuals. Muscle homogenate was separated at 45,000g into particulate and cytosolic fractions. The activity and subcellular distribution of hexokinase isozymes in human skeletal muscle was determined using ion-exchange chromatography and a highly sensitive high-performance liquid chromatography-based hexokinase assay. This criterion method was used to validate a modified thermal inactivation method for distinguishing type I and type II isoforms. Mean hexokinase activity was 3.88 +/- 0.65 U/g wet wt or 0.64 +/- 0.11 U/mU creatine kinase (CrK) in the particulate fraction and 0.45 +/- 0.22 U/g wet wt or 0.07 +/- 0.03 U/mU CrK in the cytosolic fraction. Hexokinase I and II accounted for 70-75 and 25-30% of total hexokinase activity, respectively. Nearly all (95%) of hexokinase I activity (0.52 +/- 0.09 U/mU CrK) was found in the particulate fraction, consistent with the known high affinity of hexokinase I for mitochondria. Hexokinase II activity was also largely bound to the particulate fraction (72%), but 28% was found within the cytosolic fraction. Thus, within the particulate fraction, the relative contributions of hexokinase I and hexokinase II were 81 and 19%, whereas within the cytosolic fraction, the relative contributions for hexokinase I and hexokinase II were 37 and 63%. PMID:11375324

Ritov, V B; Kelley, D E



Phosphorylation of human skeletal muscle myosin  

SciTech Connect

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

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



Circadian rhythms, skeletal muscle molecular clocks, and exercise.  


Skeletal muscle comprises approximately 40% of total body mass and, as such, contributes to maintenance of human health. In this review, we discuss the current state of knowledge regarding the role of molecular clocks in skeletal muscle. In addition, we discuss a new function for exercise as a time-setting cue for muscle and other peripheral tissues. PMID:23917214

Schroder, Elizabeth A; Esser, Karyn A



Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle  

Microsoft Academic Search

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.

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



Regulation of mechano growth factor in skeletal muscle and heart  

Microsoft Academic Search

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

M. Ottens



Nuclear proliferation (“nucleosis”) in damaged skeletal muscle A critical review  

Microsoft Academic Search

The formation of myotubes and their role in regeneration of skeletal muscle are discussed. It is pointed out that some recent observations and theories contradict each other. Furthermore, where early regeneration of transplanted skeletal muscle is described, no attention is given to the wanting nerve supply, thus assuming muscle regeneration in the absence of nerve supply.

Rudolf Altschul



Genetic determinism of fiber type proportion in human skeletal muscle  

Microsoft Academic Search

Skeletal muscle fiber type distribution is quite heterogeneous, with about 25% of North American Caucasian men and women having either less than 35% or more than 65% of type I fiber in their vastus lateralis muscle. To what extent human skeletal muscle fiber type proportion is under the control of genetic factors is examined in this paper. The results summarized



Working around the clock: circadian rhythms and skeletal muscle  

PubMed Central

The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to understand the contribution of circadian factors to normal metabolism, metabolic responses to muscle training, and contribution of the molecular clock in muscle-to-muscle disease (e.g., insulin resistance). Consistent with the potential for the skeletal muscle molecular clock modulating skeletal muscle physiology, there are findings in the literature that there is significant time-of-day effects for strength and metabolism. Additionally, there is some recent evidence that temporal specificity is important for optimizing training for muscular performance. While these studies do not prove that the molecular clock in skeletal muscle is important, they are suggestive of a circadian contribution to skeletal muscle function. The application of well-established models of skeletal muscle research in function and metabolism with available genetic models of molecular clock disruption will allow for more mechanistic understanding of potential relationships.

Zhang, Xiping; Dube, Thomas J.



Analysis of lipid profiles in skeletal muscles.  


The lipidome of skeletal muscles is a worthwhile target of research, as it affects a multitude of biological functions, and is, in turn, affected by factors such as diet, physical activity, and development. We present two methods for the analysis of the main lipid classes in skeletal muscles of humans and other animals, that is, triacylglycerols and phospholipids. The methods differ in that the former concerns total phospholipids, while the latter concerns individual phospholipids. In both methods, lipids are extracted from muscle after the addition of internal standards, and they are separated by one-dimensional (1D) thin-layer chromatography (TLC). This is sufficient for the separation of triacylglycerols and total phospholipids. In the first method, the two classes are subsequently subjected to methanolysis to produce methyl esters of fatty acids (and, to a lesser extent, dimethyl acetals of fatty aldehydes derived from plasmalogens), which are analyzed by gas chromatography (GC). Quantitation is achieved on the basis of the internal standards. In the second method, 1D TLC is used for the analysis of triacylglycerols only, whereas individual phospholipids are separated by two-dimensional TLC. This results in the isolation of phosphatidyl choline, lysophosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol, cardiolipin, and sphingomyelin. Methanolysis and subsequent analysis by GC results in the determination of the fatty acid and aldehyde profiles of the individual muscle phospholipids. PMID:22130846

Mougios, Vassilis; Petridou, Anatoli



FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension  

PubMed Central

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

Eash, John; Olsen, Aaron; Breur, Gert; Gerrard, Dave; Hannon, Kevin



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.



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


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. PMID:22493257

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



Skeletal Muscle Insulin Resistance in Endocrine Disease  

PubMed Central

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.

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



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

PubMed Central

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

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



Skeletal muscle fiber composition of the English sparrow ( Passer domesticus)  

Microsoft Academic Search

Substrate utilization by English sparrow skeletal muscle has been extensively studied in our lab. However, there are few published studies on the muscle fiber composition of English sparrow wing and gastrocnemius muscles. The objective of the present study was to examine the fiber type composition of a variety of muscles in the English sparrow. The classification of a muscle fiber

Jennifer Marquez; Karen L. Sweazea; Eldon J. Braun



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



Osmoregulatory processes and skeletal muscle metabolism  

NASA Astrophysics Data System (ADS)

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

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


Unidentified cells reside in fish skeletal muscle  

Microsoft Academic Search

Cell cultures were established from the skeletal muscle tissue of 6–13 months old rainbow trout and 12–14 months old yellow\\u000a perch. Approximately 27,000 ± 5,000 cells\\/g (trout; N = 5) and 5,000 ± 1,200 cells\\/g of tissue (perch; N = 4) were obtained. Isolation and propagation were qualitatively greater for both species when the cells (younger fish producer\\u000a more cells than older fish) were exposed to DMEM + 15% FBS, rather than L-15 + 15% FBS,

M. V. Dodson; A. Kinkel; J. L. Vierck; K. Cain; M. Wick; J. Ottobre



Metabolic functions of glucocorticoid receptor in skeletal muscle.  


Glucocorticoids (GCs) exert key metabolic influences on skeletal muscle. GCs increase protein degradation and decrease protein synthesis. The released amino acids are mobilized from skeletal muscle to liver, where they serve as substrates for hepatic gluconeogenesis. This metabolic response is critical for mammals' survival under stressful conditions, such as fasting and starvation. GCs suppress insulin-stimulated glucose uptake and utilization and glycogen synthesis, and play a permissive role for catecholamine-induced glycogenolysis, thus preserving the level of circulating glucose, the major energy source for the brain. However, chronic or excess exposure of GCs can induce muscle atrophy and insulin resistance. GCs convey their signal mainly through the intracellular glucocorticoid receptor (GR). While GR can act through different mechanisms, one of its major actions is to regulate the transcription of its primary target genes through genomic glucocorticoid response elements (GREs) by directly binding to DNA or tethering onto other DNA-binding transcription factors. These GR primary targets trigger physiological and pathological responses of GCs. Much progress has been made to understand how GCs regulate protein and glucose metabolism. In this review, we will discuss how GR primary target genes confer metabolic functions of GCs, and the mechanisms governing the transcriptional regulation of these targets. Comprehending these processes not only contributes to the fundamental understanding of mammalian physiology, but also will provide invaluable insight for improved GC therapeutics. PMID:23523565

Kuo, Taiyi; Harris, Charles A; Wang, Jen-Chywan



[Involvement of Akt in regulation of skeletal muscle metabolism].  


The enzyme Akt 1 is a member of serine/threonine specific protein kinases family. Akt plays an important role in the transmission of extracellular signals and mechanical stimuli via phosphorylation of its numerous substrates involved in anabolic and catabolic processes as well as mechanical responses of skeletal muscle. Expression of the Akt is increased during skeletal muscle hypertrophy and decreased during muscle atrophy. The G205T polymorphism of Akt is associated with transcriptional activity of the gene in muscle cells and, respectively, with skeletal muscle phenotypes. PMID:23862392

Druzhevskaia, A M; Akhmetov, I I; Rogozkin, V A



Residual force enhancement in skeletal muscle  

PubMed Central

Residual force enhancement has been observed consistently in skeletal muscles following active stretching. However, its underlying mechanism(s) remain elusive, and it cannot be explained readily within the framework of the cross-bridge theory. Traditionally, residual force enhancement has been attributed to the development of sarcomere length non-uniformities. However, recent evidence suggests that this might not be the case. Rather, it appears that residual force enhancement has an active and a passive component. The active component is tentatively associated with changes in the cross-bridge kinetics that might be reflected in decreased detachment rates following active muscle stretching, while the passive component possibly originates from a structural protein, such as titin, whose stiffness might be regulated by calcium.

Herzog, W; Lee, E J; Rassier, D E



Local calcium release in mammalian skeletal muscle  

PubMed Central

Fluo-3 fluorescence associated with Ca2+ release was recorded with confocal microscopy in single muscle fibres mechanically dissected from fast twitch muscle of rats or frogs, voltage clamped in a two Vaseline-gap chamber.Interventions that elicited Ca2+ sparks in frog skeletal muscle (low voltage depolarizations, application of caffeine) generated in rat fibres images consistent with substantial release from triadic regions, but devoid of resolvable discrete events. Ca2+ sparks were never observed in adult rat fibres. In contrast, sparks of standard morphology were abundant in myotubes from embryonic mice.Depolarization-induced gradients of fluorescence between triadic and surrounding regions (which are proportional to Ca2+ release flux) peaked at about 20 ms and then decayed to a steady level. Gradients were greater in frog fibres than in rat fibres. The ratio of peak over steady gradient (R) was steeply voltage dependent in frogs, reaching a maximum of 4.8 at ?50 mV (n = 7). In rats, R had an essentially voltage-independent value of 2.3 (n = 5).Ca2+-induced Ca2+ release, resulting in concerted opening of several release channels, is thought to underlie Ca2+ sparks and the peak phase of release in frog skeletal muscle. A diffuse ‘small event’ release, similar to that observed in these rats, is also present in frogs and believed to be directly activated by voltage. The present results suggest that in these rat fibres there is little contribution by CICR to Ca2+ release triggered by depolarization, and a lack of concerted channel opening.

Shirokova, Natalia; Garcia, Jesus; Rios, Eduardo



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



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



Lactate transporters (MCT proteins) in heart and skeletal muscles  

Microsoft Academic Search

BONEN, A. Lactate transporters (MCT proteins) in heart and skeletal muscles. Med. Sci. Sports Exerc.,Vol. 32, No. 4, pp. 778 -789, 2000. Lactate traverses the cell membranes of many tissues, including the heart and skeletal muscle via a facilitated monocarboxylate transport system that functions as a proton symport and is stereoselective for L-lactate. In the past few years, seven monocarboxylate




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



Thermodynamic and Mechanical Properties of Skeletal Muscle Contraction  

Microsoft Academic Search

Thermodynamic parameters such as the change of entropy, internal energy, and enthalpy were calculated as a function of the relative skeletal muscle strain within the framework of a proposed thermodynamic model. A value for the Young’s modulus for the skeletal muscle was also estimated. The obtained theoretical values are in a good agreement with available experimental results for the frog

Yu. I. Prylutskyy; A. M. Shut; M. S. Miroshnychenko; A. D. Suprun



Cardiomyopathy is independent of skeletal muscle disease in muscular dystrophy  

Microsoft Academic Search

Dystrophin and its associated proteins, the sarcoglycans, are normally expressed in heart and skeletal muscle. Mutations that alter the expression of these membrane-associated proteins lead to muscular dystrophy (MD) and cardiomyopathy in humans. Because of the timing and nature of the accompanying cardiomyopathy, it has been suggested that cardiomyopathy develops as a secondary consequence of skeletal muscle dysfunction in the

Xiaolei Zhu; Matthew T. Wheeler; Michele Hadhazy; Man-Yee J. Lam




Technology Transfer Automated Retrieval System (TEKTRAN)

Lipid accumulation in skeletal muscle is highly correlated with the development of insulin resistance and type 2 diabetes mellitus. It has been postulated that lipotoxicity of skeletal muscle cells is responsible for impaired insulin signaling. Many studies do not account for the localization of l...


Skeletal muscle bioenergetics in the chronic fatigue syndrome  

Microsoft Academic Search

Skeletal muscle bioenergetics and control of intracellular pH have been investigated in 46 patients with chronic fatigue syndrome by phosphorus magnetic resonance spectroscopy. The results have been compared with those from healthy controls and from a group of patients with mitochondrial cytopathies affecting skeletal muscle. No consistent abnormalities of glycolysis, mitochondrial metabolism or pH regulation were identified in the group

P R Barnes; D J Taylor; G J Kemp; G K Radda



Functional skeletal muscle regeneration from differentiating embryonic stem cells  

Microsoft Academic Search

Little progress has been made toward the use of embryonic stem (ES) cells to study and isolate skeletal muscle progenitors. This is due to the paucity of paraxial mesoderm formation during embryoid body (EB) in vitro differentiation and to the lack of reliable identification and isolation criteria for skeletal muscle precursors. Here we show that expression of the transcription factor

Radbod Darabi; Kimberly Gehlbach; Robert M Bachoo; Shwetha Kamath; Mitsujiro Osawa; Kristine E Kamm; Michael Kyba; Rita C R Perlingeiro



Influence of Temperature on Isometric Contractions of Rat Skeletal Muscles  

Microsoft Academic Search

THE influence of temperature on isometric contractions of rat skeletal muscles in vitro has been determined for fast extensor digitorum longus muscles (EDL) and slow soleus muscles (SOL) from 4 week old female Wistar rats. Isometric contractions were recorded with the long axis of the muscle vertical, with one tendon tied to the frame below and the other tendon tied

R. Close; J. F. Y. Hoh



Identification of a novel tropomodulin isoform, skeletal tropomodulin, that caps actin filament pointed ends in fast skeletal muscle.  


Tropomodulin (E-Tmod) is an actin filament pointed end capping protein that maintains the length of the sarcomeric actin filaments in striated muscle. Here, we describe the identification and characterization of a novel tropomodulin isoform, skeletal tropomodulin (Sk-Tmod) from chickens. Sk-Tmod is 62% identical in amino acid sequence to the previously described chicken E-Tmod and is the product of a different gene. Sk-Tmod isoform sequences are highly conserved across vertebrates and constitute an independent group in the tropomodulin family. In vitro, chicken Sk-Tmod caps actin and tropomyosin-actin filament pointed ends to the same extent as does chicken E-Tmod. However, E- and Sk-Tmods differ in their tissue distribution; Sk-Tmod predominates in fast skeletal muscle fibers, lens, and erythrocytes, while E-Tmod is found in heart and slow skeletal muscle fibers. Additionally, their expression is developmentally regulated during chicken breast muscle differentiation with Sk-Tmod replacing E-Tmod after hatching. Finally, in skeletal muscle fibers that coexpress both Sk- and E-Tmod, they are recruited to different actin filament-containing cytoskeletal structures within the cell: myofibrils and costameres, respectively. All together, these observations support the hypothesis that vertebrates have acquired different tropomodulin isoforms that play distinct roles in vivo. PMID:10497209

Almenar-Queralt, A; Lee, A; Conley, C A; Ribas de Pouplana, L; Fowler, V M



Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways?  

PubMed Central

Coordination of skeletal muscle growth and metabolism with nutrient availability is critical for metabolic homeostasis. To establish the role of insulin-like signaling in this process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac muscle. In 2-week-old mice, skeletal muscle masses and insulin responses were slightly affected by Irs1, but not Irs2, deficiency. In contrast, the combined deficiency of Irs1 and Irs2 (MDKO mice) severely reduced skeletal muscle growth and Akt?mTOR signaling and caused death by 3 weeks of age. Autopsy of MDKO mice revealed dilated cardiomyopathy, reflecting the known requirement of insulin-like signaling for cardiac function (P. G. Laustsen et al., Mol. Cell. Biol. 27:1649-1664, 2007). Impaired growth and function of MDKO skeletal muscle were accompanied by increased Foxo-dependent atrogene expression and amino acid release. MDKO mice were resistant to injected insulin, and their isolated skeletal muscles showed decreased insulin-stimulated glucose uptake. Glucose utilization in MDKO mice and isolated skeletal muscles was shifted from oxidation to lactate production, accompanied by an elevated AMP/ATP ratio that increased AMP-activated protein kinase (AMPK)?acetyl coenzyme A carboxylase (ACC) phosphorylation and fatty acid oxidation. Thus, insulin-like signaling via Irs1/2 is essential to terminate skeletal muscle catabolic/fasting pathways in the presence of adequate nutrition.

Long, Yun Chau; Cheng, Zhiyong; Copps, Kyle D.; White, Morris F.



Cryopreservation of human skeletal muscle impairs mitochondrial function.  


Previous studies have investigated if cryopreservation is a viable approach for functional mitochondrial analysis. Different tissues have been studied, and conflicting results have been published. The aim of the present study was to investigate if mitochondria in human skeletal muscle maintain functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity of oxidative phosphorylation was significantly (P < 0.05) reduced in cryopreserved human skeletal muscle samples. Cryopreservation impaired respiration with substrates linked to Complex I more than for Complex II (P < 0.05). Addition of cytochrome c revealed an increase in respiration indicating cytochrome c loss from the mitochondria. The results from this study demonstrate that normal mitochondrial functionality is not maintained in cryopreserved human skeletal muscle samples. PMID:22825783

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


AICAR inhibits ceramide biosynthesis in skeletal muscle  

PubMed Central

Background The worldwide prevalence of obesity has lead to increased efforts to find therapies to treat obesity-related pathologies. Ceramide is a well-established mediator of several health problems that arise from adipose tissue expansion. The purpose of this study was to determine whether AICAR, an AMPK-activating drug, selectively reduces skeletal muscle ceramide synthesis. Methods Murine myotubes and rats were challenged with palmitate and high-fat diet, respectively, to induce ceramide accrual, in the absence or presence of AICAR. Transcript levels of the rate-limiting enzyme in ceramide biosynthesis, serine palmitoyltransferase 2 (SPT2) were measured, in addition to lipid analysis. Student’s t-test and ANOVA were used to assess the association between outcomes and groups. Results Palmitate alone induced an increase in serine palmitoyltransferase 2 (SPT2) expression and an elevation of ceramide levels in myotubes. Co-incubation with palmitate and AICAR prevented both effects. However, ceramide and SPT2 increased with the addition of compound C, an AMPK inhibitor. In rats fed a high-fat diet (HFD), soleus SPT2 expression increased compared with normal chow-fed littermates. Moreover, rats on HFD that received daily AICAR injections had lower SPT2 levels and reduced muscle ceramide content compared with those on HFD only. Conclusions These results suggest that AICAR reduces ceramide synthesis by targeting SPT2 transcription, likely via AMPK activation as AMPK inhibition prevented the AICAR-induced improvements. Given the role of skeletal muscle ceramide in insulin resistance, it is tempting to speculate that interventions that activate AMPK may lead to long-term ceramide reduction and improved metabolic function.



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


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



Anomalous ion diffusion within skeletal muscle transverse tubule networks  

Microsoft Academic Search

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

Paul R Shorten; Tanya K Soboleva



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



Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man  

Microsoft Academic Search

Although insulin stimulates protein synthesis and inhibits protein breakdown in skeletal muscle in vitro, the actual contribution of these actions to its anabolic effects in man remains unknown. Using the forearm perfusion method together with systemic infusion of L-(ring-2,6-3H)phenylalanine and L-(1-¹⁴C)leucine, we measured steady state amino acid exchange kinetics across muscle in seven normal males before and in response to

R. A. Gelfand; E. J. Barrett



Re-patterning of Skeletal Muscle Energy Metabolism by Fat Storage-inducing Transmembrane Protein 2*  

PubMed Central

Triacylglyceride stored in cytosolic lipid droplets (LDs) constitutes a major energy reservoir in most eukaryotes. The regulated turnover of triacylglyceride in LDs provides fatty acids for mitochondrial ?-oxidation and ATP generation in physiological states of high demand for energy. The mechanisms for the formation of LDs in conditions of energy excess are not entirely understood. Fat storage-inducing transmembrane protein 2 (FIT2/FITM2) is the anciently conserved member of the fat storage-inducing transmembrane family of proteins implicated to be important in the formation of LDs, but its role in energy metabolism has not been tested. Here, we report that expression of FIT2 in mouse skeletal muscle had profound effects on muscle energy metabolism. Mice with skeletal muscle-specific overexpression of FIT2 (CKF2) had significantly increased intramyocellular triacylglyceride and complete protection from high fat diet-induced weight gain due to increased energy expenditure. Mass spectrometry-based metabolite profiling suggested that CKF2 skeletal muscle had increased oxidation of branched chain amino acids but decreased oxidation of fatty acids. Glucose was primarily utilized in CKF2 muscle for synthesis of the glycerol backbone of triacylglyceride and not for glycogen production. CKF2 muscle was ATP-deficient and had activated AMP kinase. Together, these studies indicate that FIT2 expression in skeletal muscle plays an unexpected function in regulating muscle energy metabolism and indicates an important role for lipid droplet formation in this process.

Miranda, Diego A.; Koves, Timothy R.; Gross, David A.; Chadt, Alexandra; Al-Hasani, Hadi; Cline, Gary W.; Schwartz, Gary J.; Muoio, Deborah M.; Silver, David L.



Direct Isolation of Satellite Cells for Skeletal Muscle Regeneration  

Microsoft Academic Search

Muscle satellite cells contribute to muscle regeneration. We have used a Pax3GFP\\/+ mouse line to directly isolate (Pax3)(green fluorescent protein)-expressing muscle satellite cells, by flow cytometry from adult skeletal muscles, as a homogeneous population of small, nongranular, Pax7+, CD34+, CD45-, Sca1- cells. The flow cytometry parameters thus established enabled us to isolate satellite cells from wild-type muscles. Such cells, grafted

Didier Montarras; Jennifer Morgan; Charlotte Collins; Frédéric Relaix; Stéphane Zaffran; Ana Cumano; Terence Partridge; Margaret Buckingham



The hyper-reinnervation of rat skeletal muscle  

Microsoft Academic Search

This study examines muscle recovery and related changes in the motor unit population of ‘hyper-reinnervated’ rat skeletal muscle. Medial gastrocnemius (MG) muscles were hyper-reinnervated by either cutting the MG nerve and implanting it on the MG muscle together with additional hind limb nerves, or by crushing the MG nerve and excising the medial portion (50–70%) of the MG muscle. Our

Todd A. Kuiken; Dudley S. Childress; W. Zev Rymer



SIRT1 signaling as potential modulator of skeletal muscle diseases.  


Skeletal muscle diseases heavily impair the strength and the movement of patients. Muscles loose their adaptive capacity, undergoing atrophy or wasting, due to a number of pathological insults. Metabolic changes, such as those occurring during aging, contribute to the progressive reduction of myofiber size and decline of skeletal muscle performance that is typically observed in the elderly. The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 has been involved in the protection against metabolic disorders, against cancers and in the enhancement of life span. Here we discuss the current evidence placing SIRT1 at the crossroad between energy homeostasis, fiber strength, and regeneration from damage in the skeletal muscle. Furthermore, we underline how cell type specific targeting of SIRT1 could be beneficial in the treatment of skeletal muscle diseases. PMID:22401932

Tonkin, Joanne; Villarroya, Francesc; Puri, Pier Lorenzo; Vinciguerra, Manlio



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), (, 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.



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


Regulation of Skeletal Muscle Sarcomere Integrity and Postnatal Muscle Function by Mef2c  

Microsoft Academic Search

Myocyte enhancer factor 2 (MEF2) transcription factors cooperate with the MyoD family of basic helix- loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of MEF2 factors in postnatal skeletal muscle. Here we show that skeletal muscle-specific deletion of Mef2c in mice results in disorganized myofibers and perinatal lethality. In

Matthew J. Potthoff; Michael A. Arnold; John McAnally; James A. Richardson; Rhonda Bassel-Duby; Eric N. Olson



Insulin stimulates L-carnitine accumulation in human skeletal muscle  

Microsoft Academic Search

ABSTRACT Increasing skeletal muscle ,carnitine content may alleviate the decline in muscle ,fat oxidation seen during intense exercise. Studies to date, however, have failed to increase muscle carnitine content, in healthy humans, by dietary or intravenous L-carnitine administration. We hypothesized that insulin could augment,Na, 1

Francis B. Stephens; Dumitru Constantin-teodosiu; David Laithwaite; Elizabeth J. Simpson; Paul L. Greenhaff



Lifting the Nebula: Novel Insights into Skeletal Muscle Contractility  

NSDL National Science Digital Library

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 myoptahy.

Coen AC Ottenheijm (University of Arizona); Henk Granzier (VU University Medical Center)



Skeletal muscle function in malnutrition1'2  

Microsoft Academic Search

Skeletal muscle function was studied in 10 malnourished patients with various gastrointestinal disorders and in 22 normal subjects. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. The objective parameters of muscle function measured were: 1) Force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10,

Jose Lopes; Jocelyn Whitwell; Khursheed N Jeejeebhoy


Postnatal ontogeny of skeletal muscle protein synthesis in pigs  

Technology Transfer Automated Retrieval System (TEKTRAN)

The neonatal period is characterized by rapid growth and elevated rates of synthesis and accretion of skeletal muscle proteins. The fractional rate of muscle protein synthesis is very high at birth and declines rapidly with age. The elevated capacity for muscle protein synthesis in the neonatal pig ...


The role of diet components, gastrointestinal factors, and muscle innervation on activation of protein synthesis in skeletal muscles following oral refeeding  

Microsoft Academic Search

The aim of this study was to quantify the effect of oral refeeding on the synthesis of soluble and contractile proteins in skeletal muscles, and to evaluate to what extent diet components (carbohydrate, fat, amino acids), hormones (insulin, IGF-I, GIP), Ca2+ flux, polyamine synthesis, cyclooxygenase activity, and muscle innervation are related to activation of protein synthesis at the translational level

Elisabeth Svanberg; Claes Ohlsson; Anders Hyltander; Kent G Lundholm



The activation of nutrient signaling components leading to mRNA translation in skeletal muscle of neonatal pigs is developmentally regulated  

Technology Transfer Automated Retrieval System (TEKTRAN)

Insulin and amino acids (AA) can act independently to stimulate skeletal muscle protein synthesis in neonatal pigs. To elucidate the role of development in the AA-induced activation of nutrient signaling components leading to translation in skeletal muscle, a balanced AA mixture was infused into fa...


The activation of insulin signaling components leading to mRNA translation in skeletal muscle of neonatal pigs is developmentally regulated  

Technology Transfer Automated Retrieval System (TEKTRAN)

Insulin and amino acids can act independently to stimulate skeletal muscle protein synthesis in neonatal pigs. The purpose of this study was to elucidate the developmental regulation of the activation of signaling components leading to protein synthesis in skeletal muscle that is induced by insulin...


Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers.  


Decreased plasma amino acid concentrations and increased net release of amino acids from skeletal muscle, especially for glutamine, are common features in critically ill patients. A low dose of endotoxin administered to healthy volunteers was used as a human model for the initial phase of sepsis to study the early metabolic response to sepsis. Six healthy male volunteers were studied in the postabsorptive state. Blood samples from the forearm artery and femoral vein were taken during 4 h before and 4 h after an intravenous endotoxin injection (4 ng/kg body wt). In addition, muscle biopsies from the leg muscle were taken. Plasma concentration of the total sum of amino acids decreased by 19% (P = 0.001) and of glutamine by 25% (P = 0.004) the 3rd h after endotoxin administration. At the same time, muscle concentrations of the sum of amino acids and glutamine decreased by 11% (P = 0.05) and 9% (P = 0.09), respectively. In parallel, the efflux from the leg increased by 35% (P = 0.004) for the total sum of amino acids and by 43% (P = 0.05) for glutamine. In conclusion, intravenous endotoxin administration to healthy volunteers, used as a model for the initial phase of sepsis, resulted in a decrease in plasma amino acid concentrations. At the same time, amino acid concentrations in muscle tissue decreased, whereas the efflux of amino acids from leg skeletal muscle increased. PMID:15367399

Vesali, Rokhsareh F; Klaude, Maria; Rooyackers, Olav; Wernerman, Jan



Role of autophagy in COPD skeletal muscle dysfunction.  


Chronic obstructive pulmonary disease (COPD) is a debilitating disease caused by parenchymal damage and irreversible airflow limitation. In addition to lung dysfunction, patients with COPD develop weight loss, malnutrition, poor exercise performance, and skeletal muscle atrophy. The latter has been attributed to an imbalance between muscle protein synthesis and protein degradation. Several reports have confirmed that enhanced protein degradation and atrophy of limb muscles of COPD patient is mediated in part through activation of the ubiquitin-proteasome pathway and that this activation is triggered by enhanced production of reactive oxygen species. Until recently, the importance of the autophagy-lysosome pathway in protein degradation of skeletal muscles has been largely ignored, however, recent evidence suggests that this pathway is actively involved in recycling of cytosolic proteins, organelles, and protein aggregates in normal skeletal muscles. The protective role of autophagy in the regulation of muscle mass has recently been uncovered in mice with muscle-specific suppression of autophagy. These mice develop severe muscle weakness, atrophy, and decreased muscle contractility. No information is yet available about the involvement of the autophagy in the regulation of skeletal muscle mass in COPD patients. Pilot experiments on vastus lateralis muscle samples suggest that the autophagy-lysosome system is induced in COPD patients compared with control subjects. In this review, we summarize recent progress related to molecular structure, regulation, and roles of the autophagy-lysosome pathway in normal and diseased skeletal muscles. We also speculate about regulation and functional importance of this system in skeletal muscle dysfunction in COPD patients. PMID:23085958

Hussain, Sabah N A; Sandri, Marco



Glucose stimulates protein synthesis in skeletal muscle of neonatal pigs through an AMPK- and mTOR-independent process  

Technology Transfer Automated Retrieval System (TEKTRAN)

Skeletal muscle protein synthesis is elevated in neonates in part due to an enhanced response to the rise in insulin and amino acids after eating. In vitro studies suggest that glucose plays a role in protein synthesis regulation. To determine whether glucose, independently of insulin and amino acid...


Dissemination of Walker 256 carcinoma cells to rat skeletal muscle  

SciTech Connect

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

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



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



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.



The extracellular compartments of frog skeletal muscle.  

PubMed Central

1. Detailed studies of solute efflux from frog sartorius muscle and single muscle fibres were carried out in order to characterize a 'special region' (Harris, 1963) in the extracellular space of muscle and determine whether this 'special region' is the sarcoplasmic reticulum. 2. The efflux of radioactive Na, Cl, glusose, 3-O-methylglucose, xylose, glycine, leucine, cycloleucine, Rb, K, inulin (mol. wt. 5000) and dextran (mol. wt. 17,000) from previously loaded muscles was studied. In all cases except dextran the curve had three components, a rapid (A) component which could be equated with efflux from the extracellular space proper, a slow (C) component representing cellular solute and an intermediate (B) component. The distribution space for the B component was 8% of muscle volume in summer frogs and 12% in winter frogs and appeared to be equal for all compounds studied. We tested the hypothesis that the B component originated from the sarcoplasmic reticulum. 3. The C component was missing from the dextran curves. Both dextran and inulin entered the compartment of origin of the B component (compartment B) to the same extent as small molecules. 4. For all compounds studies, the efflux rate constant for the A component could be predicted from the diffusion coefficient. For the B component the efflux rate constant was 6--10 times slower than that for the A component but was still proportional to the diffusion coefficient for the solute in question. 5. When Na and sucrose efflux from single fibres was followed, a B component was usually observed. The average distribution space for this component was small, averaging 1.5% of fibre volume. There was no difference between the average efflux rate constants for Na and sucrose. 6. In an appendix, the constraints placed on the properties of a hypothetical channel between the sarcoplasmic reticulum and the T-system by the linear electrical parameters of frog skeletal muscle are derived. It is shown that the conductance of such a channel must be less than 0.06 x 10(-3) mohs/cm2 of fibre membrane. 7. The conductance between compartment B and the extracellular space can be calculated from the efflux rate constants for Na, K and Cl. The value obtained was 5 x 10(-3) mhos/cm2 of fibre membrane or 100 times the limiting value for the conductance of the T-SR junction. 8. The finding that there is a B component in the efflux curves for large molecular weight substances like inulin and dextran and the small size of the B component in efflux curves from single muscle fibres indicate that the 'speical region' of the extra-cellular space of frog muscle is not the sarcoplasmic reticulum. This conclusion is confirmed by a calculation of the conductance between the B compartment and the extracellular space. The value obtained is incompatible with predicted electrical properteis of the SR-T-tubule junction...

Neville, M C; Mathias, R T



Mitochondrial and skeletal muscle health with advancing age.  


With increasing age there is a temporal relationship between the decline of mitochondrial and skeletal muscle volume, quality and function (i.e., health). Reduced mitochondrial mRNA expression, protein abundance, and protein synthesis rates appear to promote the decline of mitochondrial protein quality and function. Decreased mitochondrial function is suspected to impede energy demanding processes such as skeletal muscle protein turnover, which is critical for maintaining protein quality and thus skeletal muscle health with advancing age. The focus of this review was to discuss promising human physiological systems underpinning the decline of mitochondrial and skeletal muscle health with advancing age while highlighting therapeutic strategies such as aerobic exercise and caloric restriction for combating age-related functional impairments. PMID:23684888

Konopka, Adam R; Sreekumaran Nair, K



Growth Factors and Tension-Induced Skeletal Muscle Growth.  

National Technical Information Service (NTIS)

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. ...

H. H. Vandenburgh



Growth Factor Involvement in Tension-Induced Skeletal Muscle Growth.  

National Technical Information Service (NTIS)

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...

H. H. Vandenburgh



Nerve Clamp Electrode Design for Indirect Stimulation of Skeletal Muscle.  

National Technical Information Service (NTIS)

A nerve clamp electrode was developed to indirectly stimulate skeletal muscle innervated by alpha motor neurons as an alternative to conventional electrodes. The stimulating electrode device consists of a spring coil-activated nerve clamp mounted inside a...

C. J. Hilmas J. W. Scherer P. T. Williams



Na+-K+ Pump Regulation and Skeletal Muscle Contractility  

NSDL National Science Digital Library

The present review is written with the specific purpose of analyzing how regulation of the activity and the capacity of the Na+-K+ pumps influences excitability and contractile performance in skeletal muscle.

MD Torben Clausen (University of Aarhus Department of Physiology)



Skeletal Muscle Glucose Uptake During Exercise: How is it Regulated?  

NSDL National Science Digital Library

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

Adam J. Rose (University of Copenhagen Department of Human Physiology); Erik A. Richter (University of Copenhagen Department of Human Physiology)



Malignant lymphoma in skeletal muscle with rhabdomyolysis: a report of two cases  

Microsoft Academic Search

.  ?Malignant lymphoma is rarely found in skeletal muscle. In this article, we present two cases of malignant lymphomas that\\u000a were located in skeletal muscle and caused rhabdomyolysis. One case was a primary skeletal muscle lymphoma (which is quite\\u000a rare), and the other was a skeletal muscle metastasis of lymphoma. The patient with primary skeletal muscle lymphoma was diagnosed\\u000a with a

Satoru Masaoka; Tatsuo Fu



Structure and Function of the Skeletal Muscle Extracellular Matrix  

PubMed Central

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

Gillies, Allison R.; Lieber, Richard L.



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)



Nuclear factor-kappa B signaling in skeletal muscle atrophy  

Microsoft Academic Search

Skeletal muscle atrophy\\/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse,\\u000a AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer.\\u000a Emerging evidence suggests that nuclear factor-kappa B (NF-?B) is one of the most important signaling pathways linked to the\\u000a loss of skeletal muscle mass in various

Hong Li; Shweta Malhotra; Ashok Kumar



Dihydropyridine Receptor-Ryanodine Receptor Uncoupling in Aged Skeletal Muscle  

Microsoft Academic Search

.   The mechanisms underlying skeletal muscle functional impairment and structural changes with advanced age are only partially\\u000a understood. In the present study, we support and expand our theory about alterations in sarcolemmal excitation-sarcoplasmic\\u000a reticulum Ca2+ release-contraction uncoupling as a primary skeletal muscle alteration and major determinant of weakness and fatigue in mammalian\\u000a species including humans. To test the hypothesis that

M. Renganathan; M. L. Messi; O. Delbono



Alterations in Mitochondria and Their Impact in Aging Skeletal Muscle  

Microsoft Academic Search

\\u000a There is an abundance of studies examining the involvement of mitochondria in aging, including their role in the functional\\u000a and structural deterioration of skeletal muscle with aging. Despite years of study, the precise involvement of mitochondria\\u000a in the aging of skeletal muscle remains to be fully understood. This chapter provides some context for the current knowledge\\u000a in this area and

Russell T. Hepple


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

PubMed Central

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



Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis  

Microsoft Academic Search

Skeletal muscle is the dominant organ system in locomotion and energy metabolism. Postnatal muscle grows and adapts largely by remodelling pre-existing fibres, whereas embryonic muscle grows by the proliferation of myogenic cells. Recently, the genetic hierarchies of the myogenic transcription factors that control vertebrate muscle development — by myoblast proliferation, migration, fusion and functional adaptation into fast-twitch and slow-twitch fibres

Thomas Braun; Mathias Gautel



Protein Kinase C Signaling Controls Skeletal Muscle Fiber Types  

Microsoft Academic Search

Slow myosin heavy chain 2 (MyHC2) gene expression in fetal avian skeletal muscle fibers is regulated by innervation and protein kinase C (PKC) activity. Fetal chick muscle fibers derived from the slow twitch medial adductor (MA) muscle express slow MyHC2 when innervated in vitro. The same pattern of slow MyHC2 regulation occurs in MA muscle fibers in which PKC activity

Joseph X. DiMario



Contribution of Human Muscle-Derived Cells to Skeletal Muscle Regeneration in Dystrophic Host Mice  

Microsoft Academic Search

BackgroundStem cell transplantation is a promising potential therapy for muscular dystrophies, but for this purpose, the cells need to be systemically-deliverable, give rise to many muscle fibres and functionally reconstitute the satellite cell niche in the majority of the patient's skeletal muscles. Human skeletal muscle-derived pericytes have been shown to form muscle fibres after intra-arterial transplantation in dystrophin-deficient host mice.

Jinhong Meng; Carl F. Adkin; Shi-Wen Xu; Francesco Muntoni; Jennifer E. Morgan; Marcello Rota



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.



Quantitative studies of skeletal muscle lactate metabolism  

SciTech Connect

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

Pagliassotti, M.J.



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.



Glucocorticoid-mediated induction of glutamine synthetase in skeletal muscle.  


We studied the effect of glucocorticoids on glutamine synthetase in rat skeletal muscle in culture and in vivo. Dexamethasone, a synthetic glucocorticoid, caused striking, receptor-mediated increases in both glutamine synthetase activity and the steady-state glutamine synthetase mRNA level. This effect was observed in rat skeletal muscle cells in culture, as well as in rat muscles in vivo. Glucocorticoid-mediated induction of glutamine synthetase was blocked by androgenic/anabolic steroids at high doses, suggesting that anabolic steroids might have an anticatabolic mode of action in enhancing skeletal muscle mass in athletes. Further studies of the control of glutamine synthetase expression may shed light on mechanisms of muscle atrophy and hypertrophy. PMID:1974319

Max, S R



Bex1 knock out mice show altered skeletal muscle regeneration  

PubMed Central

Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca2+/CaM may be involved in skeletal muscle regeneration.

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



Urocortin II Treatment Reduces Skeletal Muscle Mass and Function Loss During Atrophy and Increases Nonatrophying Skeletal Muscle Mass and Function  

Microsoft Academic Search

Two corticotropin-releasing factor 2 receptor (CRF2R)-selec- tive peptides have been recently described, urocortin II (also known as stresscopin-related peptide) and urocortin III (stresscopin). We have used urocortin II to evaluate the effects of activation of the CRF2R on skeletal muscle-related physi- ological processes. Administration of urocortin II to mice pre- vented the loss of skeletal muscle mass resulting from disuse




Stable Integration of an mdx Skeletal Muscle Cell Line into Dystrophic (mdx) Skeletal Muscle: Evidence for Stem Cell Statu  

Microsoft Academic Search

We have previously described a method for the derivation of long term cuftures of undifferentiated myoblasts from the skeletal muscle of dystrophic (mdx) mice (J. Smith and P. N. Schofield, Exp. Cell Res., 210 86-93, 1994). We now show that a clonal mdx-derived skeletal muscle cell line labeled with a retrovirus conferring fi-galactosidase actMty and G418 resistance (PD5OA)is capable of

Janet Smith; Paul N. Schofield



Nuclear factor-kappa B signaling in skeletal muscle atrophy.  


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-kappaB) is one of the most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-kappaB 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-kappaB 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-kappaB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy. PMID:18574572

Li, Hong; Malhotra, Shweta; Kumar, Ashok



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.



Release of ?-actin into serum after skeletal muscle damage  

PubMed Central

Objective: The skeletal muscle protein ?-actin was investigated in the serum of subjects with severe skeletal muscle damage to assess its utility as a reliable and predictive marker of muscle damage. Methods: Serum samples were obtained from 33 healthy controls and 33 patients with severe skeletal muscle damage, defined by a total creatine kinase value of >500 IU/l (Rosalki method). Troponin I, troponin T, and myoglobin concentrations were determined by immunoassay and ?-actin concentrations by Western blot and densitometry. Results: The mean serum concentration of ?-actin in controls and patients with skeletal muscle damage was 600.9 and 1968.51 ng/ml, respectively, a statistically significant difference. Sera of patients with muscle damage showed higher levels of ?-actin than of troponin or myoglobin. No significant difference in troponin I levels was observed between the groups. Conclusions: According to these results, ?-actin was the most significant skeletal muscle damage marker analysed and may be an ideal candidate for the identification of all types of myofibre injury, including sports injuries. Our findings support the use of ?-actin as a marker alongside other currently used biological proteins.

Martinez-Amat, A; Boulaiz, H; Prados, J; Marchal, J; Padial, P; Caba, O; Rodriguez-Serrano, F; Aranega, A



Correlation between polymerizability and conformation in scallop beta-like actin and rabbit skeletal muscle alpha-actin.  


In order to investigate the structural basis for functional differences among actin isoforms, we have compared the polymerization properties and conformations of scallop adductor muscle beta-like actin and rabbit skeletal muscle alpha-actin. Polymerization of scallop Ca(2+)-actin was slower than that of skeletal muscle Ca(2+)-actin. Cleavage of the actin polypeptide chain between Gly-42 and Val-43 with Escherichia coli protease ECP 32 impaired the polymerization of scallop Mg(2+)-actin to a greater extent than skeletal muscle Mg(2+)-actin. When monomeric scallop and skeletal muscle Ca(2+)-actins were subjected to limited proteolysis with trypsin, subtilisin, or ECP 32, no differences in the conformation of actin subdomain 2 were detected. At the same time, local differences in the conformations of scallop and skeletal muscle actin subdomains 1 were revealed as intrinsic fluorescence differences. Replacement of tightly bound Ca(2+) with Mg(2+) resulted in more extensive proteolysis of segment 61-69 of scallop actin than in the case of skeletal muscle actin. Furthermore, segment 61-69 was more accessible to proteolysis with subtilisin in polymerized scallop Ca(2+)-actin than in polymerized skeletal muscle Ca(2+)-actin, indicating that, in the polymeric form, the nucleotide-containing cleft is in a more open conformation in beta-like scallop actin than in skeletal muscle alpha-actin. We suggest that this difference between scallop and skeletal muscle actins is due to a less efficient shift of scallop actin subdomain 2 to the position it has in the polymer. The possible consequences of amino acid substitutions in actin subdomain 1 in the allosteric regulation of the actin cleft, and hence in the different stabilities of polymers formed by different actins, are discussed. PMID:10415117

Khaitlina, S; Antropova, O; Kuznetsova, I; Turoverov, K; Collins, J H



Skeletal muscle denervation causes skeletal muscle atrophy through a pathway that involves both Gadd45a and HDAC4.  


Skeletal muscle denervation causes muscle atrophy via complex molecular mechanisms that are not well understood. To better understand these mechanisms, we investigated how muscle denervation increases growth arrest and DNA damage-inducible 45? (Gadd45a) mRNA in skeletal muscle. Previous studies established that muscle denervation strongly induces Gadd45a mRNA, which increases Gadd45a, a small myonuclear protein that is required for denervation-induced muscle fiber atrophy. However, the mechanism by which denervation increases Gadd45a mRNA remained unknown. Here, we demonstrate that histone deacetylase 4 (HDAC4) mediates induction of Gadd45a mRNA in denervated muscle. Using mouse models, we show that HDAC4 is required for induction of Gadd45a mRNA during muscle denervation. Conversely, forced expression of HDAC4 is sufficient to increase skeletal muscle Gadd45a mRNA in the absence of muscle denervation. Moreover, Gadd45a mediates several downstream effects of HDAC4, including induction of myogenin mRNA, induction of mRNAs encoding the embryonic nicotinic acetylcholine receptor, and, most importantly, skeletal muscle fiber atrophy. Because Gadd45a induction is also a key event in fasting-induced muscle atrophy, we tested whether HDAC4 might also contribute to Gadd45a induction during fasting. Interestingly, however, HDAC4 is not required for fasting-induced Gadd45a expression or muscle atrophy. Furthermore, activating transcription factor 4 (ATF4), which contributes to fasting-induced Gadd45a expression, is not required for denervation-induced Gadd45a expression or muscle atrophy. Collectively, these results identify HDAC4 as an important regulator of Gadd45a in denervation-induced muscle atrophy and elucidate Gadd45a as a convergence point for distinct upstream regulators during muscle denervation and fasting. PMID:23941879

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



Influence of cell heterogeneity on skeletal muscle lactate kinetics  

SciTech Connect

Lactate and (14C)lactate kinetics were studied in three rabbit skeletal muscle preparations with distinct fiber type profiles, glycolytic (99.1 +/- 0.2% type IIb fibers), oxidative (97.5 +/- 0.6% type I fibers), and mixed (type I, IIa, and IIb fibers). Single-pass perfusions were carried out for 2 h in the presence of lactate (1 mM), glucose (5 mM), (6-3H)glucose, and (U-14C)lactate. All preparations displayed net lactate release, (14C)lactate removal, and 14CO2 release. Net lactate release was greatest in the glycolytic preparation, 9.7 +/- 0.5 mumol.100 g-1.min-1, and least in the oxidative preparation, 3.7 +/- 0.2 mumol.100 g-1.min-1. (14C)lactate arteriovenous difference was greatest in the mixed preparation, 1,688 +/- 58 (disintegrations/min)/ml (dpm/ml), and least in the glycolytic preparation, 505 +/- 10.3 dpm/ml. Steady-state incorporation of (14C)lactate was observed in CO2, amino acids, and pyruvate. Tissue lactate specific activity (LSA) in all preparations was significantly lower than arterial LSA, but not significantly different from venous LSA. Estimates of lactate removal based on venous LSA were not significantly different from net glycolytic flux. In conclusion, (1) under basal, resting conditions net lactate release and (14C)lactate removal are properties of all fiber types, and (2) tracer estimates of lactate turnover in skeletal muscle reflect net glycolytic flux through pyruvate.

Pagliassotti, M.J.; Donovan, C.M. (Univ. of Southern California, Los Angeles (USA))



Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle.  


This review describes the current literature on the interaction between insulin-like growth factors, endocrine hormones, and branched-chain amino acids on muscle physiology in healthy young individuals and during select pathologic conditions. Emphasis is placed on the mechanism by which physical and hormonal signals are transduced at the cellular level to either grow or atrophy skeletal muscle. The key role of the mammalian target of rapamycin and its ability to respond to hypertrophic and atrophic signals informs our understanding how a combination of physical, nutritional, and pharmacologic therapies may be used in tandem to prevent or ameliorate reductions in muscle mass. PMID:22682632

Frost, Robert A; Lang, Charles H



Low intrinsic running capacity is associated with reduced skeletal muscle substrate oxidation and lower mitochondrial content in white skeletal muscle  

PubMed Central

Chronic metabolic diseases develop from the complex interaction of environmental and genetic factors, although the extent to which each contributes to these disorders is unknown. Here, we test the hypothesis that artificial selection for low intrinsic aerobic running capacity is associated with reduced skeletal muscle metabolism and impaired metabolic health. Rat models for low- (LCR) and high- (HCR) intrinsic running capacity were derived from genetically heterogeneous N:NIH stock for 20 generations. Artificial selection produced a 530% difference in running capacity between LCR/HCR, which was associated with significant functional differences in glucose and lipid handling by skeletal muscle, as assessed by hindlimb perfusion. LCR had reduced rates of skeletal muscle glucose uptake (?30%; P = 0.04), glucose oxidation (?50%; P = 0.04), and lipid oxidation (?40%; P = 0.02). Artificial selection for low aerobic capacity was also linked with reduced molecular signaling, decreased muscle glycogen, and triglyceride storage, and a lower mitochondrial content in skeletal muscle, with the most profound changes to these parameters evident in white rather than red muscle. We show that a low intrinsic aerobic running capacity confers reduced insulin sensitivity in skeletal muscle and is associated with impaired markers of metabolic health compared with high intrinsic running capacity. Furthermore, selection for high running capacity, in the absence of exercise training, endows increased skeletal muscle insulin sensitivity and oxidative capacity in specifically white muscle rather than red muscle. These data provide evidence that differences in white muscle may have a role in the divergent aerobic capacity observed in this generation of LCR/HCR.

Rivas, Donato A.; Lessard, Sarah J.; Saito, Misato; Friedhuber, Anna M.; Koch, Lauren G.; Britton, Steven L.; Yaspelkis, Ben B.



Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells  

Microsoft Academic Search

Skeletal muscle fibres form by fusion of mesoderm progenitors called myoblasts. After birth, muscle fibres do not increase in number but continue to grow in size because of fusion of satellite cells, the postnatal myogenic cells, responsible for muscle growth and regeneration. Numerous studies suggest that, on transplantation, non-myogenic cells also may contribute to muscle regeneration. However, there is currently

A. Dellavalle; G. Maroli; D. Covarello; E. Azzoni; A. Innocenzi; L. Perani; S. Antonini; R. Sambasivan; S. Brunelli; S. Tajbakhsh; G. Cossu



The effect of muscle architecture on the biomechanical failure properties of skeletal muscle under passive extension  

Microsoft Academic Search

This study investigates the biomechanical failure prop erties of five architecturally different skeletal muscles and examines the role muscle structure plays in the passive extension characteristics of musculotendinous units. The muscles used in this study fall into four morphologic categories: fusiform, unipennate, bipen nate, and multipennate.Each muscle was pulled to failure at three different rates of strain (1, 10, and

William E. Garrett; Pantelis K. Nikolaou; Beth M. Ribbeck; Richard R. Glisson; Anthony V. Seaber



A submaximal dose of insulin promotes net skeletal muscle protein synthesis in patients with severe burns.  

PubMed Central

OBJECTIVE: To investigate the hypothesis that a submaximal insulin dose reverses the net muscle catabolism associated with severe burns, and to determine its effects on amino acid kinetics. SUMMARY BACKGROUND DATA: The authors previously showed that a maximal dose of insulin administered to patients with severe burns promoted skeletal muscle glucose uptake and net protein synthesis. However, this treatment was associated with caloric overload resulting from the large quantities of exogenous glucose required to maintain euglycemia, and hypoglycemia was a potential problem. METHODS: Thirteen patients were studied after severe burn injury (>60% total body surface area). Patients were randomly treated by standard care (n = 5) or with exogenous insulin (n = 8). Data were derived from an arteriovenous model with primed-continuous infusions of stable isotopes and biopsies of the vastus lateralis muscle. RESULTS: Net amino acid balance was significantly improved with insulin treatment. Skeletal muscle protein synthesis was significantly greater in the group receiving insulin, whereas muscle protein breakdown was not different between the groups. This submaximal dose of insulin did not affect glucose or amino acid uptake or require a greater caloric intake to avoid hypoglycemia. CONCLUSIONS: Submaximal insulin can promote muscle anabolism without eliciting a hypoglycemic response.

Ferrando, A A; Chinkes, D L; Wolf, S E; Matin, S; Herndon, D N; Wolfe, R R




PubMed Central

Introduction Absence of functional myostatin (MSTN) during fetal development results in adult skeletal muscle hypertrophy and hyperplasia. Methods To more fully characterize MSTN loss in hindlimb muscles, the morphology and contractile function of the soleus, plantaris, gastrocnemius, tibialis anterior and quadriceps muscles in male and female null (Mstn ?/?), heterozygous (Mstn +/?) and wildtype (Mstn +/+) mice were investigated. Results Muscle weights of Mstn ?/? mice were greater than Mstn +/+ and Mstn +/?. Fiber cross-sectional area (CSA) was increased in female Mstn ?/? soleus and gastrocnemius muscles and in the quadriceps of male Mstn ?/? mice; peak tetanic force in Mstn ?/? mice did not parallel the increased muscle weight or CSA. Male Mstn ?/? muscle exhibited moderate degeneration. Discussion Visible pathology in male mice and decreased contractile strength relative to increased muscle weight suggest MSTN loss results in muscle impairment which is dose, sex and muscle dependent.

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



FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension  

Microsoft Academic Search

BACKGROUND: Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs) and their receptors

John Eash; Aaron Olsen; Gert Breur; Dave Gerrard; Kevin Hannon



Structure and Function of the Sarcolemma of Skeletal Muscle  

Microsoft Academic Search

THE functions of the sarcolemma of skeletal muscle are still uncertain, because of our lack of knowledge of its structure and detailed distribution over the entire surface of the muscle cell. Most of our knowledge is derived from electron microscope investigations and the sarcolemma is regarded as a semi-permeable unit membrane about 100 Å thick, which directly encloses the contents

R. Reed; T. W. Houston; P. M. Todd



Heparan sulfates in skeletal muscle development and physiology  

Microsoft Academic Search

Heparan sulfate proteoglycans (HSPGs) are major components of the skeletal muscle cell surface and of the basal lamina (BL) surrounding muscle cells. HSPGs consist of a protein core to which multiple heparan sulfate (HS) chains are attached. Individual HSPGs, notably agrin and perlecan, have been intensely studied in recent years. However, these studies focused on the protein core, ignoring the

Guido John Jenniskens



Implications of skeletal muscle creatine kinase to meat quality  

Microsoft Academic Search

Creatine kinase (CK) is a key enzyme for the energetic metabolism of tissues with high and fl uctuating energy demands in vivo, as it is the case of the skeletal muscle tissue, which is the most important for the meat industry. This enzyme is generally utilized as an indicator of physical stress and\\/or muscle damage in animal production. However, CK

D. J. Daroit; A. Brandelli


Gender difference of androgen actions on skeletal muscle transcriptome  

Microsoft Academic Search

Sarcopenia is related to metabolic syndrome in postmenopausal women. Hormone replacement therapies with androgens improve muscle functions by molecular mechanisms that are still unknown, at least partly because the skeletal muscle transcriptome has been less characterized in females. We performed the serial analysis of gene expression method in six experimental groups, intact (male and female), ovariectomy (OVX), OVXCdihydrotestosterone (DHT) injection

Mayumi Yoshioka; A. Boivin; C. Bolduc; J. St-Amand



Structure and Composition of Tubular Aggregates of Skeletal Muscle Fibres  

Microsoft Academic Search

Unusual regions of densely packed membranous tubules known as tubu- lar aggregates (TAs) have been observed in skeletal muscle bres of mammals under numerous pathological conditions but also in health. Their causality is unclear. It is neither known whether TAs are destructive and should be treated or whether they have a compensating function in an endangered muscle. In spite of

M. PavloviovÆ; I. ZahradnÌk


Signalling aspects of insulin resistance in skeletal muscle  

Microsoft Academic Search

A reduced capacity for insulin to elicit increases in glucose uptake and metabolism in target tissues such as skeletal muscle is a common feature of obesity and diabetes. The association between lipid oversupply and such insulin resistance is well established, and evidence for mechanisms through which lipids could play a causative role in the generation of muscle insulin resistance is

Carsten Schmitz-Peiffer



Ultrastructural localization of anionic phospholipids in skeletal muscle plasma membrane  

Microsoft Academic Search

Polymyxin B was used as a probe to label anionic phospholipids in skeletal muscle plasma membrane. This antibiotic produces muscle surface membrane lesions that can be identified in both thin sections and freeze-fracture replicas. The membrane perturbations assumed a patchy distribution with a preferential localization at the level of the I band and A-I bands junction. Intramembraneous particles were also

M. Moggio; E. Bonilla



Implantable electrode for chronic recording from skeletal muscle  

Microsoft Academic Search

An implantable electrode has been developed for recording chronically from skeletal muscle, It consists of two Pt-Ir wires embedded on a silicone rubber block. The electrode was implanted on the longissimus thoracis muscle of rabbit. The impedance changes of the implanted electrode that take place over time were studied. After about two months the impedance value of the implanted electrode

R. Munoz; L. Leija; J. Alvarez; P. R. Hernandez; J. L. Reyes



Long-term leucine induced stimulation of muscle protein synthesis is amino acid dependent  

Technology Transfer Automated Retrieval System (TEKTRAN)

Infusing leucine for 1 h increases skeletal muscle protein synthesis in the neonate, but this is not sustained for 2 h unless the corresponding fall in amino acids is prevented. This study aimed to determine whether a continuous leucine infusion can stimulate protein synthesis for a prolonged period...


Aligned electrospun polymer fibres for skeletal muscle regeneration.  


Skeletal muscle repair is often overlooked in surgical procedures and in serious burn victims. Creating a tissue-engineered skeletal muscle would not only provide a grafting material for these clinical situations, but could also be used as a valuable true-to-life research tool into diseases affecting muscle tissue. Electrospinning of the elastomer PLGA produced aligned fibres that had the correct topology to provide contact guidance for myoblast elongation and alignment. In addition, the electrospun scaffold required no surface modifications or incorporation of biologic material for adhesion, elongation, and differentiation of C2C12 murine myoblasts. PMID:20467965

Aviss, K J; Gough, J E; Downes, S



Thin-filament-binding domains of cardiac and fast skeletal muscle troponin I isoforms as studied by epitope tagging  

Microsoft Academic Search

We examined the binding domains of cardiac and fast skeletal muscle troponin I (CTnI and FTnI, respectively) to myofibrils (MFs). Deletion mutants containing CTnI amino acid residues 1–79, 43–207 and 80–207 (CTnI-head, CTnI-tail-1 and CTnI-tail-2, respectively) and FTnI amino acid residues 1–54 and 55–182 (FTnI-head and FTnI-tail, respectively) were transiently expressed in cardiac and fast skeletal muscle cells. To monitor

Naoji Toyota; Hidenori Uzawa; Masatoshi Komiyama; Yutaka Shimada



Characterization of skeletal muscle effects associated with daptomycin in rats.  


Daptomycin is a lipopeptide antibiotic with strong bactericidal effects against Gram-positive bacteria and minor side effects on skeletal muscles. The type and magnitude of the early effect of daptomycin on skeletal muscles of rats was quantified by histopathology, examination of contractile properties, Evans Blue Dye uptake, and effect on the patch repair process. A single dose of daptomycin of up to 200 mg/kg had no effect on muscle fibers. A dose of 150 mg/kg of daptomycin, twice per day for 3 days, produced a small number of myofibers (skeletal muscles of rats. Some fibers were Evans Blue Dye-positive but were not yet infiltrated by neutrophils. This suggests that the sarcolemma may be the primary target for the observed effects. PMID:20544940

Kostrominova, Tatiana Y; Hassett, Cheryl A; Rader, Erik P; Davis, Carol; Larkin, Lisa M; Coleman, Scott; Oleson, Frederick B; Faulkner, John A



A method for preparing skeletal muscle fiber basal laminae  

SciTech Connect

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

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



Skeletal Muscle Performance in Adults with Growth Hormone Deficiency  

Microsoft Academic Search

Skeletal muscle mass and function were assessed in 24 adults (16 males, 8 females) with severe, longstanding GH deficiency. Compared to 41 untrained controls (26 males, 15 females), adults with GH deficiency had reduced cross-sectional area of thigh muscle\\/body weight (p = 0.01), reduced quadriceps force\\/weight (males: p = 0.002; females: p < 0.0001), and reduced quadriceps force\\/muscle area (males:

Ross C. Cuneo; Franco Salomon; Mark Wiles; P. H. Sönksen



Functional and ionic changes accompanying magnesium penetration in skeletal muscle  

Microsoft Academic Search

The penetration of magnesium from high-Mg Ringer's solution into skeletal muscle, and accompanying effects on intrafibre electrolyte composition, muscle contractility and Ca-exchange have been studied in isolated preparations of whole sartorius ofRana temporaria. Muscle magnesium, corrected for extracellular space, rose rapidly and then more slowly, and at 60 min in 20 mM Mg-Ringer it was calculated that intrafibre unbound Mg

J. M. O'Donnell; T. Kovács



A mathematical model of fatigue in skeletal muscle force contraction  

Microsoft Academic Search

The ability for muscle to repeatedly generate force is limited by fatigue. The cellular mechanisms behind muscle fatigue are\\u000a complex and potentially include breakdown at many points along the excitation–contraction pathway. In this paper we construct\\u000a a mathematical model of the skeletal muscle excitation–contraction pathway based on the cellular biochemical events that link\\u000a excitation to contraction. The model includes descriptions

Paul R. Shorten; Paul O’Callaghan; John B. Davidson; Tanya K. Soboleva



Force Transmission between Synergistic Skeletal Muscles through Connective Tissue Linkages  

PubMed Central

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

Maas, Huub; Sandercock, Thomas G.



Analysis of gene transfer and expression in skeletal muscle using enhanced EIAV lentivirus vectors  

Microsoft Academic Search

Skeletal muscle is an attractive target tissue for gene therapy involving both muscle and nonmuscle disorders. HIV-1-based vectors transduce mature skeletal muscle; however, the use of these vectors for human gene therapy may be limited by biosafety concerns. In this study, we investigated gene transfer using lentivirus vectors based on the equine infectious anemia virus (EIAV) in skeletal muscle in

J P O'Rourke; H Hiraragi; K Urban; M Patel; J C Olsen; B A Bunnell



Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics  

ERIC Educational Resources Information Center

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

Ianuzzo, C. D.; Chen, V.



Investigative study of radiopharmaceuticals useful for imaging skeletal muscle injury in experimental animals  

SciTech Connect

An experimental animal model for studying skeletal muscle injury is described. Tc-99m PYP is accumulated on the skeletal muscle injury, but its uptake on the adjacent bone obscures its usefulness in delineating the extent of the muscle injury. In-111 antimyosin accumulates and delineates the extent of the skeletal muscle injury and does not accumulate on the adjacent bone. Hence, In-111 antimyosin is a good radiopharmaceutical for studying the severity and prognosis of skeletal muscle injury.

Owunwanne, A.; Malki, A.; Sadek, S.; el-Gazzar, A.; Yacoub, T.; Abdel-Dayem, H.M. (Kuwait Univ., Safat)



Sensitivity of skeletal muscle to pro-apoptotic factors.  


In mononuclear cells, apoptosis leads to DNA fragmentation and cell destruction, regardless of the activated pathway. As regards multinuclear cells, e.g. skeletal muscle fibers, apoptosis rarely induces the death of the entire cell, and it generally affects single nuclei. This process, referred to as nuclear apoptosis, has a negative effect on the expression of genes in the myonuclear domain. Apoptosis may be initiated in muscle cells by external stimuli which activate cell membrane death receptors as well as by internal stimuli which stimulate the mitochondrial release of pro-apoptotic proteins. Reactive oxygen species also play an important role in the initiation of apoptosis. In muscle cells, ROS are produced in response to extracellular reactions or by cell mitochondria. It is, therefore, believed that mitochondria play a central role in apoptosis within skeletal muscle. Skeletal muscles have a well-developed system that protects them against oxidative damage. Myogenic stem cells are an integral part of multinucleated myofibers, and they are critically important for the maintenance of normal muscle mass, muscle growth, regeneration and hypertrophy. The latest research results indicate that myogenic cells are more sensitive to oxidative stress and pro-apoptotic factors than well-differentiated cells, such as myotubes. The complex structure and activity of skeletal muscle prompted research into the role of apoptosis and its intensity under various physiological and pathological conditions. This review summarizes the results of research investigating control mechanisms and the apoptosis process in skeletal muscle fibers, and indicates unresearched areas where further work is required. PMID:22439346

Otrocka-Domaga?a, I



Overexpression of muscle uncoupling protein 2 content in human obesity associates with reduced skeletal muscle lipid utilization  

Microsoft Academic Search

Uncoupling proteins (UCP) may influ- ence thermogenesis. Since skeletal muscle plays an important role in energy homeostasis and substrate oxidation, this study was undertaken to test the hy- potheses that skeletal muscle UCP2 content is altered in obesity and could be linked to basal energy expen- diture, insulin sensitivity, or substrate oxidation within skeletal muscle under postabsorptive (fasting) conditions. To



Localization of 3H-diethylstilbestrol in skeletal muscle  

SciTech Connect

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

Gruber, B.; Cohen, L.



Bone and skeletal muscle: neighbors with close ties.  


The musculoskeletal system evolved in mammals to perform diverse functions that include locomotion, facilitating breathing, protecting internal organs, and coordinating global energy expenditure. Bone and skeletal muscles involved with locomotion are both derived from somitic mesoderm and accumulate peak tissue mass synchronously, according to genetic information and environmental stimuli. Aging results in the progressive and parallel loss of bone (osteopenia) and skeletal muscle (sarcopenia) with profound consequences for quality of life. Age-associated sarcopenia results in reduced endurance, poor balance, and reduced mobility that predispose elderly individuals to falls, which more frequently result in fracture because of concomitant osteoporosis. Thus, a better understanding of the mechanisms underlying the parallel development and involution of these tissues is critical to developing new and more effective means to combat osteoporosis and sarcopenia in our increasingly aged population. This perspective highlights recent advances in our understanding of mechanisms coupling bone and skeletal muscle mass, and identify critical areas where further work is needed. PMID:23630111

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



Antioxidants and Skeletal Muscle Performance: "Common Knowledge" vs. Experimental Evidence.  


Antioxidants are assumed to provide numerous benefits, including better health, a reduced rate of aging, and improved exercise performance. Specifically, antioxidants are commonly "prescribed" by the media, supplement industry, and "fitness experts" for individuals prior to training and performance, with assumed benefits of improved fatigue resistance and recovery. This has provoked expansion of the supplement industry which responded by creation of a plethora of products aimed at facilitating the needs of the active individual. However, what does the experimental evidence say about the efficacy of antioxidants on skeletal muscle function? Are antioxidants actually as beneficial as the general populous believes? Or, could they in fact lead to deleterious effects on skeletal muscle function and performance? This Mini Review addresses these questions with an unbiased look at what we know about antioxidant effects on skeletal muscle, and what we still need to know before conclusions can be made. PMID:22416234

Hernández, Andrés; Cheng, Arthur; Westerblad, Håkan



Ultrastructural analysis of the transdifferentiation of smooth muscle to skeletal muscle in the murine esophagus  

Microsoft Academic Search

The ultrastructure of the mouse esophagus at the level of the diaphragm was studied from embryo day 17 to adult. The transdifferentiation of smooth muscle into skeletal muscle was categorized into seven ultrastructural stages: during phase I normal smooth muscle myogenesis was observed. In phase II subpopulations of cells changed into aggregates of myoblast-like cells. At the center of these

C. J. Stratton; Yulia Bayguinov; Kenton M. Sanders; Sean M. Ward



Hyperinnervation of Skeletal Muscle Fibers: Dependence on Muscle Activity  

Microsoft Academic Search

After the motor nerve to the rat soleus muscle was blocked reversibly by local anesthesia, individual muscle fibers became innervated by a transplanted motor nerve without losing their original innervation. Such cross-innervation of the denervated soleus muscle by the same foreign nerve was largely reduced by direct electrical stimulation of the muscle. The results demonstrate the importance of muscle activity

Jan K. S. Jansen; Terje Lmo; Kare Nicolaysen; Rolf H. Westgaard



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.



Skeletal muscle titin: physiology and pathophysiology  

Microsoft Academic Search

Titins are a family of gigantic filamentous muscle proteins essential for muscle structure, function and development. Most of their sequence consists of repetitive modules of two superfamily motifs, immunoglobulin and fibronectin, interspersed with unique sequences. A special feature is that many regions are differentially expressed in different muscle types, providing unique characteristics. Titin is evolutionarily old, and many regions are

G. O. Skeie



Eccentric exercise facilitates mesenchymal stem cell appearance in skeletal muscle.  


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. PMID:22253772

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



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.



Focal adhesion kinase regulates insulin resistance in skeletal muscle  

Microsoft Academic Search

Aims\\/hypothesis  On the basis of our previous studies, we investigated the possible role of focal adhesion kinase (FAK) in the development\\u000a of insulin resistance in skeletal muscle, a major organ responsible for insulin-stimulated glucose uptake.\\u000a \\u000a \\u000a \\u000a Materials and methods  Insulin-resistant C2C12 skeletal muscle cells were transfected with FAK wild-type or FAK mutant plasmids, knocked down using\\u000a small interfering RNA (siRNA), and their effects

B. Bisht; H. L. Goel; C. S. Dey



Carnitine deficiency of skeletal muscle: report of a treated case.  


We studied a 10-year-old girl with an insidious muscle disease beginning at age 7. Muscle biopsy showed that the majority of type I fibers were vacuolated and contained lipid excess. Carnitine deficiency was found in skeletal muscle. The patient was treated with 3.0 gm L-carnitine per day and with a medium-chain triglyceride diet. She showed a rapid improvement and recovery of strength. A muscle biopsy 8 months later showed a decreased lipid content. Oral carnitine replacement represents an effective treatment for the disease. PMID:945511

Angelini, C; Lücke, S; Cantarutti, F



Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles.  


Autophagy is required for cellular survival and for the clearance of damaged proteins and altered organelles. Excessive autophagy activation contributes to muscle loss in different catabolic conditions. However, the function of basal autophagy for homeostasis of skeletal muscle was unknown. To clarify this issue we have generated conditional and inducible knockout mice for the critical gene Atg7, to block autophagy specifically in skeletal muscle. Atg7 null muscles reveal an unexpected phenotype which is characterized by muscle atrophy, weakness and features of myofiber degeneration. Morphological, biochemical and molecular analyses of our autophagy knockout mice show the presence of protein aggregates, abnormal mitochondria, accumulation of membrane bodies, sarcoplasmic reticulum distension, vacuolization, oxidative stress and apoptosis. Moreover, autophagy inhibition does not protect skeletal muscles from atrophy during denervation and fasting, but instead promotes greater muscle loss. In conclusion, autophagy plays a critical role for myofiber maintenance and its activation is crucial to avoid accumulation of toxic proteins and dysfunctional organelles that, in the end, would lead to atrophy and weakness. PMID:20104028

Masiero, Eva; Sandri, Marco



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.



Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.  


The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle. PMID:21796708

Sinclair, C D J; Morrow, J M; Hanna, M G; Reilly, M M; Yousry, T A; Golay, X; Thornton, J S



Burn injury causes mitochondrial dysfunction in skeletal muscle  

PubMed Central

Severe burn trauma is generally followed by a catabolic response that leads to muscle wasting and weakness affecting skeletal musculature. Here, we perform whole-genome expression and in vivo NMR spectroscopy studies to define respectively the full set of burn-induced changes in skeletal muscle gene expression and the role of mitochondria in the altered energy expenditure exhibited by burn patients. Our results show 1,136 genes differentially expressed in a mouse hind limb burn model and identify expression pattern changes of genes involved in muscle development, protein degradation and biosynthesis, inflammation, and mitochondrial energy and metabolism. To assess further the role of mitochondria in burn injury, we performed in vivo 31P NMR spectroscopy on hind limb skeletal muscle, to noninvasively measure high-energy phosphates and the effect of magnetization transfer on inorganic phosphate (Pi) and phosphocreatine (PCr) resonances during saturation of ?ATP resonance, mediated by the ATP synthesis reactions. Although local burn injury does not alter high-energy phosphates or pH, apart from PCr reduction, it does significantly reduce the rate of ATP synthesis, to further implicate a role for mitochondria in burn trauma. These results, in conjunction with our genomic results showing down-regulation of mitochondrial oxidative phosphorylation and related functions, strongly suggest alterations in mitochondrial-directed energy expenditure reactions, advancing our understanding of skeletal muscle dysfunction suffered by burn injury patients.

Padfield, Katie E.; Astrakas, Loukas G.; Zhang, Qunhao; Gopalan, Suresh; Dai, George; Mindrinos, Michael N.; Tompkins, Ronald G.; Rahme, Laurence G.; Tzika, A. Aria



Avoidance of skeletal muscle atrophy in spontaneous and facultative hibernators.  


Smooth and skeletal muscle changes were compared from overwintering white-tailed prairie dogs, spontaneous hibernators that undergo regular, low-temperature torpor bouts, and black-tailed prairie dogs, facultative hibernators that use sporadic, moderate-temperature torpor bouts. The objectives were to assess the abilities of these two species with dramatically different torpor patterns (1) to conserve skeletal muscle morphology, protein, and strength and (2) to use labile protein in the small intestine and liver during the winter season of reduced activity and food intake. Mass and protein concentration of the extensor digitorum longus (EDL), soleus, liver, and small intestine, as well as skeletal muscle strength and fiber morphology for the EDL and soleus, were compared before and after hibernation in both species. Both species appeared to be similar to overwintering black bears and underwent very little strength and protein loss, as compared with euthermic models of immobility and long-term fasting. Although the two species used vastly different hibernation strategies, none of the changes in parameters related to muscle atrophy and labile-protein use during the hibernation season differed significantly between them. Therefore, it appears that regardless of the phenotypic expressions of hibernation, the outcome is the conservation of skeletal muscle. PMID:20337528

Cotton, Clark J; Harlow, Henry J


Unclassified polysaccharidosis of the heart and skeletal muscle in siblings  

PubMed Central

We describe a 15-year-old boy and his 19-year-old sister with progressive dilated cardiomyopathy and mild non-progressive proximal lower limb myopathy, secondary to the accumulation of amylopectin-like fibrillar glycogen, (polyglucosan) bodies, in heart and skeletal muscle. Evidence of idiopathic amylopectinosis or polysaccharidosis was demonstrated in heart and skeletal muscle tissue by histology, electron microscopy, biochemical, and genetic analysis. In both siblings the heart muscle stored PAS-positive, proteinase-k resistant and partly diastase resistant granulo-filamentous material, simulating polyglucosan bodies. Glycogen branching enzyme activity, and phosphofructokinase enzyme activity, measured in skeletal muscle tissue and explanted heart tissue were all within the normal limits, however glycogen content was elevated. Furthermore, GBE1, PRKAG2, desmin, ?B-crystallin, ZASP, myotilin, and LAMP-2 gene sequencing revealed no mutation, excluding e.g. glycogen storage disease type 4 and desmin-related myofibrillar cardiomyopathies. In both patients the diagnosis of an idiopathic polysaccharidois with progressive dilated cardiomyopathy was made, requiring heart transplantation at age 13 and 14 respectively. Both patients belong to an autosomal recessive group of biochemically and genetically unclassified severe vacuolar glycogen storage disease of the heart and skeletal muscle. Up to now unidentified glycogen synthesis or glycogen degradation pathways are supposed to contribute to this idiopathic glycogen storage disease.

Schoser, Benedikt; Bruno, Claudio; Schneider, Hans-Christian; Shin, Yoon S.; Podskarbi, Teodor; Goldfarb, Lev; Muller-Felber, Wolfgang; Muller-Hocker, Josef



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


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. PMID:23085957

Wang, Yu; Winters, Jack; Subramaniam, Shankar



Identification of Ankrd2, a novel skeletal muscle gene coding for a stretch-responsive ankyrin-repeat protein.  


Mechanically induced hypertrophy of skeletal muscles involves shifts in gene expression leading to increases in the synthesis of specific proteins. Full characterization of the regulation of muscle hypertrophy is a prerequisite for the development of novel therapies aimed at treating muscle wasting (atrophy) in human aging and disease. Using suppression subtractive hybridization, cDNAs corresponding to mRNAs that increase in relative abundance in response to mechanical stretch of mouse skeletal muscles in vivo were identified. A novel 1100-bp transcript was detected exclusively in skeletal muscle. This exhibited a fourfold increase in expression after 7 days of stretch. The transcript had an open reading frame of 328 amino acids encoding an ATP/GTP binding domain, a nuclear localization signal, two PEST protein-destabilization motifs, and a 132-amino-acid ankyrin-repeat region. We have named this gene ankyrin-repeat domain 2 (stretch-responsive muscle) (Ankrd2). We hypothesize that Ankrd2 plays an important role in skeletal muscle hypertrophy. PMID:10873377

Kemp, T J; Sadusky, T J; Saltisi, F; Carey, N; Moss, J; Yang, S Y; Sassoon, D A; Goldspink, G; Coulton, G R



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.



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

PubMed Central

Background Heart failure (HF), a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFB-5) appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single–skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure. Materials and methods To investigate these molecules during “early” events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA) Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size. Results There were more (P < 0.05) single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7%) compared to the control subjects (13% ± 2%). IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05), respectively. Strikingly, there was a correlation in IGF-1 expression and muscle cross-sectional area (P < 0.05) resulting in a decrease in whole-muscle quality (P < 0.05) in the HF patients, despite no significant decrease in isometric strength or whole-muscle size. Conclusion These data indicate that molecular alterations in myosin heavy chain isoforms, IGF-1, and IGFB-5 levels precede the gross morphological and functional deficits that have previously been associated with HF, and may be used as a predictor of functional outcome in patients.

Godard, Michael P; Whitman, Samantha A; Song, Yao-Hua; Delafontaine, Patrice



Low frequency sounds from sustained contraction of human skeletal muscle.  

PubMed Central

Low frequency audible vibrations are produced by human skeletal muscles undergoing sustained contraction. The effect is easily demonstrable with an electronic stethoscope which amplifies sound below 50 Hz. Autocorrelation analysis of the signal shows that it is periodic with a frequency 25 +/- 2.5 Hz. The quality of the sound is the same for all the skeletal muscles tested and is unaffected by changes in tension, ambient temperature, and blood flow. Electrically-stimulated contraction produces a sound which is indistinguishable from voluntary contraction. The amplitude of the sound increases linearly with tension. The sound signals are uncorrelated both in frequency and phase with electromyographic signals obtained simultaneously while the muscle is contacted. Arguments are presented to show that the sounds may be an intrinsic property of muscle contraction.

Oster, G; Jaffe, J S



AMP decreases the efficiency of skeletal-muscle mitochondria.  

PubMed Central

Mitochondrial proton leak in rat muscle is responsible for approx. 15% of the standard metabolic rate, so its modulation could be important in regulating metabolic efficiency. We report in the present paper that physiological concentrations of AMP (K(0.5)=80 microM) increase the resting respiration rate and double the proton conductance of rat skeletal-muscle mitochondria. This effect is specific for AMP. AMP also doubles proton conductance in skeletal-muscle mitochondria from an ectotherm (the frog Rana temporaria), suggesting that AMP activation is not primarily for thermogenesis. AMP activation in rat muscle mitochondria is unchanged when uncoupling protein-3 is doubled by starvation, indicating that this protein is not involved in the AMP effect. AMP activation is, however, abolished by inhibitors and substrates of the adenine nucleotide translocase (ANT), suggesting that this carrier (possibly the ANT1 isoform) mediates AMP activation. AMP activation of ANT could be important for physiological regulation of metabolic rate.

Cadenas, S; Buckingham, J A; St-Pierre, J; Dickinson, K; Jones, R B; Brand, M D



Skeletal Muscle Strength and Endurance in Recipients of Lung Transplants  

PubMed Central

Purpose: Exercise limitation in recipients of lung transplant may be a result of abnormalities in the skeletal muscle. However, it is not clear whether these abnormalities are merely a reflection of the changes observed in the pretransplant condition. The purpose of this paper was to compare thigh muscle volume and composition, strength, and endurance in lung transplant recipients to people with chronic obstructive pulmonary disease (COPD). Methods: Single lung transplant recipients (n=6) and people with COPD (n=6), matched for age, sex, and BMI participated in the study. Subjects underwent MRI to determine muscle size and composition, lower extremity strength testing and an isometric endurance test of the quadriceps. Results: Lung transplant recipients had similar muscle volumes and intramuscular fat infiltration of their thigh muscles and similar strength of the quadriceps and hamstrings to people with COPD who had not undergone transplant. However, quadriceps endurance tended to be lower in transplant recipients compared to people with COPD (15 ± 7 seconds in transplant versus 31 ± 12 seconds in COPD, p = 0.08). Conclusions: Recipients of lung transplant showed similar changes in muscle size and strength as people with COPD, however muscle endurance tended to be lower in people with lung transplants. Impairments in muscle endurance may reflect the effects of immunosuppressant medications on skeletal muscle in people with lung transplant.

Levy, Robert D; Reid, W. Darlene



Myo1c Regulates Glucose Uptake in Mouse Skeletal Muscle*  

PubMed Central

Contraction and insulin promote glucose uptake in skeletal muscle through GLUT4 translocation to cell surface membranes. Although the signaling mechanisms leading to GLUT4 translocation have been extensively studied in muscle, the cellular transport machinery is poorly understood. Myo1c is an actin-based motor protein implicated in GLUT4 translocation in adipocytes; however, the expression profile and role of Myo1c in skeletal muscle have not been investigated. Myo1c protein abundance was higher in more oxidative skeletal muscles and heart. Voluntary wheel exercise (4 weeks, 8.2 ± 0.8 km/day), which increased the oxidative profile of the triceps muscle, significantly increased Myo1c protein levels by ?2-fold versus sedentary controls. In contrast, high fat feeding (9 weeks, 60% fat) significantly reduced Myo1c by 17% in tibialis anterior muscle. To study Myo1c regulation of glucose uptake, we expressed wild-type Myo1c or Myo1c mutated at the ATPase catalytic site (K111A-Myo1c) in mouse tibialis anterior muscles in vivo and assessed glucose uptake in vivo in the basal state, in response to 15 min of in situ contraction, and 15 min following maximal insulin injection (16.6 units/kg of body weight). Expression of wild-type Myo1c or K111A-Myo1c had no effect on basal glucose uptake. However, expression of wild-type Myo1c significantly increased contraction- and insulin-stimulated glucose uptake, whereas expression of K111A-Myo1c decreased both contraction-stimulated and insulin-stimulated glucose uptake. Neither wild-type nor K111A-Myo1c expression altered GLUT4 expression, and neither affected contraction- or insulin-stimulated signaling proteins. Myo1c is a novel mediator of both insulin-stimulated and contraction-stimulated glucose uptake in skeletal muscle.

Toyoda, Taro; An, Ding; Witczak, Carol A.; Koh, Ho-Jin; Hirshman, Michael F.; Fujii, Nobuharu; Goodyear, Laurie J.



Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles  

Microsoft Academic Search

BackgroundAngiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2

Mahroo Mofarrahi; Sabah N. A. Hussain



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.



Differential Proteome Analysis of Hagfish Dental and Somatic Skeletal Muscles  

Microsoft Academic Search

Hagfish, the plesiomorphic sister group of all vertebrates, are deep-sea scavengers. The large musculus (m.) longitudinalis linguae (dental muscle) is a specialized element of the feeding apparatus that facilitates the efficient ingestion of food. In this\\u000a article, we compare the protein expression in hagfish dental and somatic (the m. parietalis) skeletal muscles via two-dimensional gel electrophoresis and mass spectrometry in

Kuo-Hsun Chiu; Hurng-Wern Huang; Hin-Kiu Mok



Myo1c regulates glucose uptake in mouse skeletal muscle.  


Contraction and insulin promote glucose uptake in skeletal muscle through GLUT4 translocation to cell surface membranes. Although the signaling mechanisms leading to GLUT4 translocation have been extensively studied in muscle, the cellular transport machinery is poorly understood. Myo1c is an actin-based motor protein implicated in GLUT4 translocation in adipocytes; however, the expression profile and role of Myo1c in skeletal muscle have not been investigated. Myo1c protein abundance was higher in more oxidative skeletal muscles and heart. Voluntary wheel exercise (4 weeks, 8.2 ± 0.8 km/day), which increased the oxidative profile of the triceps muscle, significantly increased Myo1c protein levels by ?2-fold versus sedentary controls. In contrast, high fat feeding (9 weeks, 60% fat) significantly reduced Myo1c by 17% in tibialis anterior muscle. To study Myo1c regulation of glucose uptake, we expressed wild-type Myo1c or Myo1c mutated at the ATPase catalytic site (K111A-Myo1c) in mouse tibialis anterior muscles in vivo and assessed glucose uptake in vivo in the basal state, in response to 15 min of in situ contraction, and 15 min following maximal insulin injection (16.6 units/kg of body weight). Expression of wild-type Myo1c or K111A-Myo1c had no effect on basal glucose uptake. However, expression of wild-type Myo1c significantly increased contraction- and insulin-stimulated glucose uptake, whereas expression of K111A-Myo1c decreased both contraction-stimulated and insulin-stimulated glucose uptake. Neither wild-type nor K111A-Myo1c expression altered GLUT4 expression, and neither affected contraction- or insulin-stimulated signaling proteins. Myo1c is a novel mediator of both insulin-stimulated and contraction-stimulated glucose uptake in skeletal muscle. PMID:21127070

Toyoda, Taro; An, Ding; Witczak, Carol A; Koh, Ho-Jin; Hirshman, Michael F; Fujii, Nobuharu; Goodyear, Laurie J



Insulin inhibits inducible nitric oxide synthase in skeletal muscle cells  

Microsoft Academic Search

Summary   Recent studies have shown that cytokines and endotoxins impair insulin-stimulated glucose transport by activating the expression\\u000a of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in skeletal muscle cells. In this study, we investigated\\u000a whether iNOS induction is modulated by insulin in L6 myocytes. Long term exposure of muscle cells to tumour necrosis factor-?\\u000a (TNF-?), interferon-? (IFN-?)

S. Bédard; B. Marcotte; A. Marette



Skeletal muscle inflammation and nitric oxide in patients with COPD  

Microsoft Academic Search

In chronic obstructive pulmonary disease (COPD) the presence of systemic inflammation has been associated with peripheral muscle abnormalities and weight loss. To study whether inflammatory factors are important in these processes, the present study compared the skeletal muscle levels of nitrite, nitrate, nitrotyrosine, neuronal, endothelial and inducible nitric oxide synthases (nNOS, eNOS, and iNOS, respectively), and inflammatory markers (tumour necrosis

M. Montes de Oca; S. H. Torres; A. Mata; N. Hernandez; C. Talamo



Analysis of skeletal muscle development in Drosophila.  


The Drosophila system has been invaluable in providing important insights into mesoderm specification, muscle specification, myoblast fusion, muscle differentiation, and myofibril assembly. Here, we present a series of Drosophila protocols that enable the researcher to visualize muscle precursors and differentiated muscles, at all stages of development. In doing so, we also highlight the variety of techniques that are used to create these findings. These protocols are directly used for the Drosophila system, and are provided with explanatory detail to enable the researcher to apply them to other systems. PMID:22130835

Morriss, Ginny R; Bryantsev, Anton L; Chechenova, Maria; LaBeau, Elisa M; Lovato, TyAnna L; Ryan, Kathryn M; Cripps, Richard M



On the Importance of Exchangeable NH Protons in Creatine for the Magnetic Coupling of Creatine Methyl Protons in Skeletal Muscle  

NASA Astrophysics Data System (ADS)

The methyl protons of creatine in skeletal muscle exhibit a strong off-resonance magnetization transfer effect. The mechanism of this process is unknown. We previously hypothesized that the exchangeable amide/amino protons of creatine might be involved. To test this the characteristics of the creatine magnetization transfer effect were investigated in excised rat hindleg skeletal muscle that was equilibrated in either H2O or D2O solutions containing creatine. The efficiency of off-resonance magnetization transfer to the protons of mobile creatine in excised muscle was similar to that previously reported in intact muscle in vivo. Equilibrating the isolated muscle in D2O solution had no effect on the magnetic coupling to the immobile protons. It is concluded that exchangeable protons play a negligible role in the magnetic coupling of creatine methyl protons in muscle.

Kruiskamp, M. J.; Nicolay, K.



The effects of apelin treatment on skeletal muscle mitochondrial content.  


Adipose tissue is recognized as a key player in the regulation of whole body metabolism. Apelin, is a recently identified adipokine that when given to mice results in increases in skeletal muscle uncoupling protein 3 (UCP3) content. Similarly, acute apelin treatment has been shown to increase the activity of 5'-AMP-activated protein kinase (AMPK), a reputed mediator of skeletal muscle mitochondrial biogenesis. Given these findings, we sought to determine the effects of apelin on skeletal muscle mitochondrial content. Male Wistar rats were given daily intraperitoneal injections of apelin-13 (100 nmol/kg) for 2 wk. We made the novel observation that the activities of citrate synthase, cytochrome c oxidase, and beta-hydroxyacyl coA dehydrogenase (betaHAD) were increased in triceps but not heart and soleus muscles from apelin-treated rats. When confirming these results we found that both nuclear and mitochondrial-encoded subunits of the respiratory chain were increased in triceps from apelin-treated rats. Similarly, apelin treatment increased the protein content of components of the mitochondrial import and assembly pathway. The increases in mitochondrial marker proteins were associated with increases in proliferator-activated receptor-gamma coactivator-1 (PGC-1beta) but not PGC-1alpha or Pgc-1-related co-activator (PRC) mRNA expression. Chronic and acute apelin treatment did not increase the protein content and/or phosphorylation status of AMPK and its downstream substrate acetyl-CoA carboxylase. These findings are the first to demonstrate that apelin treatment can induce skeletal muscle mitochondrial content. Given the lack of an effect of apelin on AMPK signaling and PGC-1alpha mRNA expression, these results suggest that apelin increases skeletal muscle mitochondrial content through a mechanism that is distinct from that of more robust physiological stressors. PMID:19793954

Frier, Bruce C; Williams, Deon B; Wright, David C



Adiponectin Upregulates Ferritin Heavy Chain in Skeletal Muscle Cells  

PubMed Central

OBJECTIVE—Adiponectin is an adipocyte-derived protein that acts to reduce insulin resistance in the liver and muscle and also inhibits atherosclerosis. Although adiponectin reportedly enhances AMP-activated protein kinase and inhibits tumor necrosis factor-? action downstream from the adiponectin signal, the precise physiological mechanisms by which adiponectin acts on skeletal muscles remain unknown. RESEARCH DESIGN AND METHODS—We treated murine primary skeletal muscle cells with recombinant full-length human adiponectin for 12 h and searched, using two-dimensional electrophoresis, for proteins upregulated more than threefold by adiponectin compared with untreated cells. RESULTS—We found one protein that was increased 6.3-fold with adiponectin incubation. MALDI-TOF (matrix-assisted laser desorption/ionization?top of flight) mass spectrometric analysis identified this protein as ferritin heavy chain (FHC). When murine primary skeletal muscle cells were treated with adiponectin, I?B-? phosphorylation was observed, suggesting that adiponectin stimulates nuclear factor (NF)-?B activity. In addition, FHC upregulation by adiponectin was inhibited by NF-?B inhibitors. These results suggest NF-?B activation to be involved in FHC upregulation by adiponectin. Other NF-?B target genes, manganese superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS), were also increased by adiponectin treatment. We performed a reactive oxygen species (ROS) assay using CM-H2DCFDA fluorescence and found that ROS-reducing effects of adiponectin were abrogated by FHC or MnSOD small-interfering RNA induction. CONCLUSIONS—We have demonstrated that adiponectin upregulates FHC in murine skeletal muscle tissues, suggesting that FHC elevation might partially explain how adiponectin protects against oxidative stress in skeletal muscles.

Ikegami, Yuichi; Inukai, Kouichi; Imai, Kenta; Sakamoto, Yasushi; Katagiri, Hideki; Kurihara, Susumu; Awata, Takuya; Katayama, Shigehiro



Heart failure: a model of cardiac and skeletal muscle energetic failure  

Microsoft Academic Search

Chronic heart failure (CHF), the new epidemic in cardiology, is characterized by energetic failure of both cardiac and skeletal muscles. The failing heart wastes energy due to anatomical changes that include cavity enlargement, altered geometry, tachycardia, mitral insufficiency and abnormal loading, while skeletal muscle undergoes atrophy. Cardiac and skeletal muscles also have altered high-energy phosphate production and handling in CHF.

B. Mettauer; J. Zoll; A. Garnier; R. Ventura-Clapier



Microbial decomposition of skeletal muscle tissue ( Ovis aries) in a sandy loam soil at different temperatures  

Microsoft Academic Search

A laboratory experiment was conducted to determine the effect of temperature (2, 12, 22°C) on the rate of aerobic decomposition of skeletal muscle tissue (Ovis aries) in a sandy loam soil incubated for a period of 42 days. Measurements of decomposition processes included skeletal muscle tissue mass loss, carbon dioxide (CO2) evolution, microbial biomass, soil pH, skeletal muscle tissue carbon

David O. Carter; Mark Tibbett



Increased Ischemia-Reperfusion Blood Flow Impairs the Skeletal Muscle Contractile Function  

Microsoft Academic Search

Background. The ultimate aim of replantations and transplantations of skeletal muscle is to improve impaired function. The purpose of this study was to examine the contribution of varying durations of ischemia to postischemic blood flow in the skeletal muscle and the contribution of modulation of postischemic blood flow to skeletal muscle function and viability, using an ischemic revascularized hind limb

Kenshiro Ikebe; Teiji Kato; Makio Yamaga; Jun Hirose; Toru Tsuchida; Katsumasa Takagi



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



Electromechanical Coupling between Skeletal and Cardiac Muscle: Implications for Infarct Repair  

Microsoft Academic Search

Skeletal myoblasts form grafts of mature muscle in injured hearts, and these grafts contract when exogenously stimulated. It is not known, however, whether cardiac muscle can form electromechanical junctions with skeletal muscle and induce its synchro- nous contraction. Here, we report that undifferentiated rat skeletal myoblasts expressed N-cadherin and connexin43, major adhesion and gap junction proteins of the intercalated disk,

Hans Reinecke; Glen H. MacDonald; Stephen D. Hauschka; Charles E. Murry



Development of Sensory Receptors in Skeletal Muscle.  

National Technical Information Service (NTIS)

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 ...

M. DeSantis



Validation of shear wave elastography in skeletal muscle.  


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



Emphysema-induced reductions in locomotory skeletal muscle contractile function.  


Patients with COPD suffer from locomotory skeletal muscle contractile dysfunction. This may be due to the disease per se or as a result of some confounding factor. Therefore, the purpose of this investigation was to determine whether emphysema: (1) reduces force production; (2) increases fatigability; and (3) impairs the speed of recovery in locomotory skeletal muscle in an accepted animal model in which many confounding variables can be controlled. To explore this issue, in situ mechanical properties of gastrocnemius were measured in Syrian Golden hamsters 8 months after intratracheal instillation of either saline (control, n = 5) or elastase (emphysema, n = 7). Emphysema increased excised lung volume (80%; P < 0.01), increased fatigability (control, 25% reduction in maximal strength after 4 min of repeated contractions; emphysema, 55% reduction; P < 0.05) and decreased the recovery rate (half-times of recovery: control, 7 +/- 7 s; emphysema, 92 +/- 92 s; P < 0.05) of gastrocnemius muscle. In contrast, emphysema had no effect on maximal force, whether related to body mass or muscle mass, or force-velocity characteristics of gastrocnemius muscle. These data demonstrate that emphysema, independent of physical activity levels, pharmacological intervention, and/or nutritional status, can increase fatigability and impair the speed of recovery of locomotory skeletal muscle contractile function which may contribute to exercise intolerance of COPD patients. PMID:15755817

Mattson, John P; Martin, James C



Characterization of a 6K oligonucleotide turkey skeletal muscle microarray.  


Consumer demand for lean, inexpensive meat products has driven the domestic turkey (Meleagris gallopavo) industry to unprecedented production; however, this has coincided with an increase in growth-induced myopathies and meat quality defects. With the aim of developing a new tool for the study of turkey growth and development at the muscle transcriptome level, a 6K oligonucleotide microarray was constructed, the Turkey Skeletal Muscle Long Oligo (TSKMLO) microarray. Skeletal muscle samples were collected at three critical stages in muscle development: 18-day embryo (hyperplasia), 1-day post-hatch (hypertrophy), and 16-week (market age) from two genetic lines of turkeys: RBC2, a line maintained without selection pressure, and F, a line selected from the RBC2 line for increased 16-week body weight. Oligonucleotides were designed from sequences obtained from skeletal muscle cDNA libraries from the three developmental stages. Several unique controls, including mismatch and distance controls and scrambled sequences, were designed for 30 genes. Quality control hybridizations were completed, confirming the validity and repeatability of the array. Control features were evaluated across two larger experiments comparing developmental stage within genetic line or genetic line within each developmental stage, totaling 70 arrays. Mismatch and scrambled sequences appeared to be useful controls of specific hybridization for most genes. In addition, quantitative real-time RT-PCR confirmed microarray results. This creation and assessment of the TSKMLO array provides a valuable community resource for the study of gene expression changes related to turkey muscle growth and development. PMID:20528844

Sporer, K R B; Chiang, W; Tempelman, R J; Ernst, C W; Reed, K M; Velleman, S G; Strasburg, G M



Quantitation of postischemic skeletal muscle necrosis: histochemical and radioisotope techniques  

SciTech Connect

Skeletal muscle necrosis will result from prolonged periods of ischemia. The purpose of this study was to develop a method to estimate the extent of necrosis using nitroblue tetrazolium staining and technetium scanning. The bilateral canine gracilis muscle preparation with total vascular isolation was exposed to 4 hr of complete normothermic ischemia followed by reperfusion. After 45 hr of reperfusion /sup 99m/Tc pyrophosphate (PYP) was injected and 3 hr later the muscles were harvested, cut into six slices, and stained with nitroblue tetrazolium. Biopsies were taken from tetrazolium-positive and -negative areas for electron microscopy to confirm the ability of the stain to distinguish viable from necrotic muscle. Computerized planimetry of the staining pattern was used to estimate the extent of necrosis as a percentage of the total muscle. Electron microscopy confirmed the validity of nitroblue tetrazolium to discriminate between viable and necrotic skeletal muscle in this experimental model. After 4 hr of ischemia the percentage necrosis was 30.2 +/- 6.1% (mean +/- SEM, n = 12), there was no difference in the extent of necrosis in left vs right paired muscles, using tetrazolium staining or technetium PYP uptake. There was a statistically significant correlation between the percentage necrosis and the density of 99mTc PYP uptake per muscle (r = 0.83, P less than 0.001) and per slice (r = 0.94, P less than 0.001). This study demonstrates the ability of tetrazolium staining to accurately differentiate between viable and necrotic skeletal muscle and provides a reproducible method for estimating the extent of necrosis in the gracilis muscle model.

Labbe, R.; Lindsay, T.; Gatley, R.; Romaschin, A.; Mickle, D.; Wilson, G.; Houle, S.; Walker, P.



Role of pericytes in skeletal muscle regeneration and fat accumulation.  


Stem cells ensure tissue regeneration, while overgrowth of adipogenic cells may compromise organ recovery and impair function. In myopathies and muscle atrophy associated with aging, fat accumulation increases dysfunction, and after chronic injury, the process of fatty degeneration, in which muscle is replaced by white adipocytes, further compromises tissue function and environment. Some studies suggest that pericytes may contribute to muscle regeneration as well as fat formation. This work reports the presence of two pericyte subpopulations in the skeletal muscle and characterizes their specific roles. Skeletal muscle from Nestin-GFP/NG2-DsRed mice show two types of pericytes, Nestin-GFP-/NG2-DsRed+ (type-1) and Nestin-GFP+/NG2-DsRed+ (type-2), in close proximity to endothelial cells. We also found that both Nestin-GFP-/NG2-DsRed+ and Nestin-GFP+/NG2-DsRed+ cells colocalize with staining of two pericyte markers, PDGFR? and CD146, but only type-1 pericyte express the adipogenic progenitor marker PDGFR?. Type-2 pericytes participate in muscle regeneration, while type-1 contribute to fat accumulation. Transplantation studies indicate that type-1 pericytes do not form muscle in vivo, but contribute to fat deposition in the skeletal muscle, while type-2 pericytes contribute only to the new muscle formation after injury, but not to the fat accumulation. Our results suggest that type-1 and type-2 pericytes contribute to successful muscle regeneration which results from a balance of myogenic and nonmyogenic cells activation. PMID:23517218

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



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

Microsoft Academic Search

This paper presents a three-dimensional finite element model of skeletal muscle which was developed to simulate active and passive non-linear mechanical behaviours of the muscle during lengthening or shortening under either quasi-static or dynamic condition. Constitutive relation of the muscle was determined by using a strain energy approach, while active contraction behaviour of the muscle fibre was simulated by establishing

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



Disruption of Dag1 in Differentiated Skeletal Muscle Reveals a Role for Dystroglycan in Muscle Regeneration  

Microsoft Academic Search

Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in loss of the dystrophin-glycoprotein complex in differentiated muscle and a remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis. We find that satellite cells, expressing dystroglycan, support continued efficient regeneration of skeletal muscle along with transient expression of dystroglycan in regenerating muscle fibers. We demonstrate a similar phenomenon of

Ronald D. Cohn; Michael D. Henry; Daniel E. Michele; Rita Barresi; Fumiaki Saito; Steven A. Moore; Jason D. Flanagan; Mark W. Skwarchuk; Michael E. Robbins; Jerry R. Mendell; Roger A. Williamson; Kevin P. Campbell



Distinct Troponin C Isoform Requirements in Cardiac and Skeletal Muscle  

PubMed Central

The zebrafish mutant silent partner is characterized by a dysmorphic, non-contractile ventricle resulting in an inability to generate normal blood flow. We have identified the genetic lesion in the zebrafish homolog of the slow twitch skeletal/cardiac troponin C gene. Although human troponin C1 (TNNC1) is expressed in both cardiac and skeletal muscle, duplication of this gene in zebrafish has resulted in tissue specific partitioning of troponin C expression and function. Mutation of the zebrafish paralog tnnc1a, which is expressed predominantly in the heart, results in a loss of contractility and myofibrillar organization within ventricular cardiomyocytes, while skeletal muscle remains functional and intact. We further show that defective contractility in the developing heart results in abnormal atrial and ventricular chamber morphology. Together, our results suggest that tnnc1a is required both for the function and structural integrity of the contractile machinery in cardiomyocytes, helping to clarify potential mechanisms of troponin C mediated cardiomyopathy.

Sogah, Vanessa M.; Serluca, Fabrizio C.; Fishman, Mark C.; Yelon, Deborah L.; MacRae, Calum A.; Mably, John D.



Myogenesis and rhabdomyosarcoma the Jekyll and Hyde of skeletal muscle.  


Rhabdomyosarcoma, a neoplasm composed of skeletal myoblast-like cells, represents the most common soft tissue sarcoma in children. The application of intensive chemotherapeutics and refined surgical and radiation therapy approaches have improved survival for children with localized disease over the past 3 decades; however, these approaches have not improved the dismal outcome for children with metastatic and recurrent rhabdomyosarcoma. Elegant studies have defined the molecular mechanisms driving skeletal muscle lineage commitment and differentiation, and the machinery that couples differentiation with irreversible cell proliferation arrest. Further, detailed molecular analyses indicate that rhabdomyosarcoma cells have lost the capacity to fully differentiate when challenged to do so in experimental models. We review the intersection of normal skeletal muscle developmental biology and the molecular genetic defects in rhabdomyosarcoma with the underlying premise that understanding how the differentiation process has gone awry will lead to new treatment strategies aimed at promoting myogenic differentiation and concomitant cell cycle arrest. PMID:21295688

Saab, Raya; Spunt, Sheri L; Skapek, Stephen X



Skeletal muscle excitation-contraction coupling II  

Microsoft Academic Search

Bundles of cells, intact from tendon to tendon, were dissected from muscles of normal and malignant hyperthermia susceptible (MHS) pigs. Intact bundles were stimulated either (1) electrically, to elicit twitches and tetani, or (2) ionically with elevated extracellular K+ (K0+), to elicit K-contractures. Maximal tetanic force was the same for MHS and normal intact bundles. In MHS muscles, when responses

Esther M. Gallant; Sue K. Donaldson



Neuromuscular Mechanisms of a Locust Skeletal Muscle  

Microsoft Academic Search

The physiology of neuromuscular transmission of the three motor nerve fibres supplying the extensor tibialis muscle of the jumping leg of the locust Locusta migratoria migratorioides R. & F. is studied with the aid of intracellular microelectrodes. The largest axon, supplied by the crural nerve trunk, branches repeatedly to innervate every muscle fibre at several points. Single impulses produce large

G. Hoyle



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



Skeletal Muscle Water and Electrolytes in Chronic Renal Failure  

Microsoft Academic Search

Skeletal muscle water, Cl, Na and K were studied in 24 patients with predialysis chronic renal failure (CRF) and in 16 patients under regular dialysis treatment (RDT) for 8–16 years; 35 healthy controls were also examined. Total Cl, Na and water (Clm, Nam, TW) were high in both CRF and RDT groups (p < 0.001); high TW in CRF was

Alberto Montanari; Giorgio Graziani; Loris Borghi; Alberto Cantaluppi; Isabella Simoni; Elettra Lorenzano; Claudio Ponticelli; Almerico Novarini



Antidiabetic sulphonylureas activate mitochondrial permeability transition in rat skeletal muscle  

Microsoft Academic Search

1 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. 2 The effects of glibenclamide (and other sulphonylurea derivatives) on mitochondrial function were studied by measuring mitochondrial swelling, mitochondrial membrane potential, respiration rate and Ca2 þ

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



STAT3 Regulation of Skeletal Muscle Wasting in Cancer Cachexia  

Microsoft Academic Search

Cachexia is a highly complex syndrome identified by metabolic, hormonal and cytokine-related abnormalities, but can be shortly characterized as accelerated skeletal muscle and adipose tissue loss in the context of a chronic inflammatory response. Cachexia is a debilitating complication of several diseases such as AIDS, sepsis, diabetes, renal failure, burn injury and cancer. Cachexia is responsible for 25-30% of cancer

Tufan Aydogdu



Sepsis alters pyruvate dehydrogenase kinase activity in skeletal muscle  

Microsoft Academic Search

Chronic sepsis promotes a stable increase in pyruvate dehydrogenase kinase (PDHK) activity in skeletal muscle. PDHK is found tightly bound to the pyruvate dehydrogenase (PDH) complex and as free kinase. We investigated the ability of sepsis to modify the activity of the PDHK intrinsic to the PDH and free PDHK. Sepsis was induced by the intraabdominal introduction of a fecal-agar

Thomas C. Vary; Stacy Hazen



Regulation of Pyruvate Dehydrogenase Activity In Human Skeletal Muscle  

Microsoft Academic Search

Regulation of the flux-generating enzyme complex pyruvate dehydrogenase (PDHc) was examined in the context of its physiological function in human skeletal muscle. In the first two studies, the role of PDHc in intramuscular fuel selection and the mechanisms regulating PDHc transformation from its inactive form (PDHb) to its active form (PDHa) and PDHa activity were examined. In a third study,

Charles Theodore Putman




Microsoft Academic Search

Summary The aim of this study was to investigate the effects of whole-body vibrations (WBV) on the mechanical behaviour of human skeletal muscle. For this purpose, six female volleyball players at national level were recruited voluntarily. They were tested with maximal dynamic leg press exercise on a slide machine with extra loads of 70, 90, 110 and 130 kg. After

C. Bosco; R. Colli; E. Introini; M. Cardinale; M. Iacovelli; A. Madella; J. Tihanyi; A. Viru



Characterization of human carbonic anhydrase III from skeletal muscle  

Microsoft Academic Search

A third form of human carbonic anhydrase (CA III), found at high concentrations in skeletal muscle, has been purified and characterized. This isozyme shows relatively poor hydratase and esterase activities compared to the red cell isozymes, CA I and CA II, but is similar to these isozymes in subunit structure (monomer) and molecular size (28,000). CA III is liable to

Nicholas Carter; Stephen Jeffery; Alan Shiels; Yvonne Edwards; Terry Tipler; David A. Hopkinson



Imaging Elementary Events of Calcium Release in Skeletal Muscle Cells  

Microsoft Academic Search

In skeletal muscle cells, calcium release to trigger contraction occurs at triads, specialized junctions where sarcoplasmic reticulum channels are opened by voltage sensors in the transverse tubule. Scanning confocal microscopy was used in cells under voltage clamp to measure the concentration of intracellular calcium, [Ca2+]_i, at individual triads and [Ca2+]_i gradients that were proportional to calcium release. In cells stimulated

Alexander Tsugorka; Eduardo Rios; Lothar A. Blatter



Skeletal muscle vascular responses in human limbs to isometric handgrip  

Microsoft Academic Search

Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously

Tage N. Jacobsen; Jim Hansen; Henrik V. Nielsen; Gordon Wildschiødtz; Eli Kassis; Bjørn Larsen; Ole Amtorp



Calcium Sparks in Intact Skeletal Muscle Fibers of the Frog  

Microsoft Academic Search

Calcium sparks were studied in frog intact skeletal muscle fibers using a home-built confocal scanner whose point-spread function was estimated to be ? 0.21 ? m in x and y and ? 0.51 ? m in z. Observations were made at 17-20 ? C on fibers from Rana pipiens and Rana temporaria . Fibers were studied in two external solutions:

S. Hollingworth; J. Peet; W. K Chandler; S. M. Baylor



Adipose tissue and skeletal muscle blood flow during mental stress  

SciTech Connect

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

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



Metabolic switching of human skeletal muscle cells in vitro  

Microsoft Academic Search

In this review we will focus on external factors that may modify energy metabolism in human skeletal muscle cells (myotubes) and the ability of the myotubes to switch between lipid and glucose oxidation. We describe the metabolic parameters suppressibility, adaptability and substrate-regulated flexibility, and show the influence of nutrients such as fatty acids and glucose (chronic hyperglycemia), and some pharmacological

G. H. Thoresen; N. P. Hessvik; S. S. Bakke; V. Aas; A. C. Rustan



Physical injuries, contractures and rigidity of skeletal muscle  

SciTech Connect

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

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



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



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

Microsoft Academic Search

The goals of this study were to describe the clinical course of skeletal, cardiac, and gastrointestinal muscle manifestations and trends in age at diagnosis and survival of Duchenne muscular dystrophy (DMD) patients. A retrospective cohort of 33 male patients with DMD, born between 1953 and 1983 and followed at the Mayo Clinic during their second decade of life, was studied.

Benoit J. Boland; Peter L. Silbert; Robert V. Groover; Peter C. Wollan; Marc D. Silverstein



Apoptotic adaptations from exercise training in skeletal and cardiac muscles  

Microsoft Academic Search

The effect of exercise on apoptosis in postmitotic tissues is not known. In this study, we investigated the effect of regular moderate physical activity (i.e., exercise training) on the extent of apoptosis in rat skeletal and cardiac muscles. Adult Sprague Dawley rats were trained (TR) 5 days weekly for 8 wk on treadmill. Sedentary rats served as controls (CON). An

Parco M. Siu; Randall W. Bryner; Julie K. Martyn; Stephen E. Alway



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



Glucose utilization and disposition by skeletal muscle during unrestricted feeding.  

PubMed Central

We measured glucose utilization index (GUI) values in individual skeletal muscles of conscious rats during the light (quiescent) and dark (feeding/activity) phases. There was a 2-3-fold variation in muscle GUI values, with peak values observed at the end of the dark phase and minimum values observed at 6-9 h into the light phase. GUI values in working muscles (soleus and adductor longus) were consistently higher than in non-working muscles (tibialis anterior and extensor digitorum longus), indicating that working muscles make the major contribution of the total skeletal muscle mass to glucose disposal during unrestricted feeding. There was a clear overall increase in muscle glycogen deposition during the first 9 h of the dark phase; this was concomitant with an increase in food consumption. Peak glycogen concentrations were reached after 9 h of darkness, but subsequently declined. The pattern of changes in muscle GUI values during the light and dark phases is discussed in relation to the role of insulin in facilitating glucose clearance.

Holness, M J; Howard, R M; Sugden, M C



Hematopoietic potential of stem cells isolated from murine skeletal muscle  

PubMed Central

We have discovered that cells derived from the skeletal muscle of adult mice contain a remarkable capacity for hematopoietic differentiation. Cells prepared from muscle by enzymatic digestion and 5-day in vitro culture were harvested, and 18 × 103 cells were introduced into each of six lethally irradiated recipients together with 200 × 103 distinguishable whole bone marrow cells. After 6 or 12 weeks, all recipients showed high-level engraftment of muscle-derived cells representing all major adult blood lineages. The mean total contribution of muscle cell progeny to peripheral blood was 56 ± 20% (SD), indicating that the cultured muscle cells generated approximately 10- to 14-fold more hematopoietic activity than whole bone marrow. When bone marrow from one mouse was harvested and transplanted into secondary recipients, all recipients showed high-level multilineage engraftment (mean 40%), establishing the extremely primitive nature of these stem cells. We also show that muscle contains a population of cells with several characteristics of bone marrow-derived hematopoietic stem cells, including high efflux of the fluorescent dye Hoechst 33342 and expression of the stem cell antigens Sca-1 and c-Kit, although the cells lack the hematopoietic marker CD45. We propose that this population accounts for the hematopoietic activity generated by cultured skeletal muscle. These putative stem cells may be identical to muscle satellite cells, some of which lack myogenic regulators and could be expected to respond to hematopoietic signals.

Jackson, Kathyjo Ann; Mi, Tiejuan; Goodell, Margaret A.



Androgens Regulate Gene Expression in Avian Skeletal Muscles  

PubMed Central

Circulating androgens in adult reproductively active male vertebrates influence a diversity of organ systems and thus are considered costly. Recently, we obtained evidence that androgen receptors (AR) are expressed in several skeletal muscles of three passeriform birds, the golden-collared manakin (Manacus vitellinus), zebra finch (Taenopygia guttata), and ochre-bellied flycatcher (Mionectes oleagieus). Because skeletal muscles that control wing movement make up the bulk of a bird’s body mass, evidence for widespread effects of androgen action on these muscles would greatly expand the functional impact of androgens beyond their well-characterized effects on relatively discrete targets throughout the avian body. To investigate this issue, we use quantitative PCR (qPCR) to determine if androgens alter gene mRNA expression patterns in wing musculature of wild golden-collared manakins and captive zebra finches. In manakins, the androgen testosterone (T) up-regulated expression of parvalbumin (PV) and insulin-like growth factor I (IGF-I), two genes whose products enhance cellular Ca2+ cycling and hypertrophy of skeletal muscle fibers. In T-treated zebra finches, the anti-androgen flutamide blunted PV and IGF-I expression. These results suggest that certain transcriptional effects of androgen action via AR are conserved in passerine skeletal muscle tissue. When we examined wing muscles of manakins, zebra finches and ochre-bellied flycatchers, we found that expression of PV and IGF-I varied across species and in a manner consistent with a function for AR-dependent gene regulation. Together, these findings imply that androgens have the potential to act on avian muscle in a way that may enhance the physicality required for successful reproduction.

Fuxjager, Matthew J.; Barske, Julia; Du, Sienmi; Day, Lainy B.; Schlinger, Barney A.



Elevated nuclear Foxo1 suppresses excitability of skeletal muscle fibers.  


Forkhead box O 1 (Foxo1) controls the expression of proteins that carry out processes leading to skeletal muscle atrophy, making Foxo1 of therapeutic interest in conditions of muscle wasting. The transcription of Foxo1-regulated proteins is dependent on the translocation of Foxo1 to the nucleus, which can be repressed by insulin-like growth factor-1 (IGF-1) treatment. The role of Foxo1 in muscle atrophy has been explored at length, but whether Foxo1 nuclear activity affects skeletal muscle excitation-contraction (EC) coupling has not yet been examined. Here, we use cultured adult mouse skeletal muscle fibers to investigate the effects of Foxo1 overexpression on EC coupling. Fibers expressing Foxo1-green fluorescent protein (GFP) exhibit an inability to contract, impaired propagation of action potentials, and ablation of calcium transients in response to electrical stimulation compared with fibers expressing GFP alone. Evaluation of the transverse (T)-tubule system morphology, the membranous system involved in the radial propagation of the action potential, revealed an intact T-tubule network in fibers overexpressing Foxo1-GFP. Interestingly, long-term IGF-1 treatment of Foxo1-GFP fibers, which maintains Foxo1-GFP outside the nucleus, prevented the loss of normal calcium transients, indicating that Foxo1 translocation and the atrogenes it regulates affect the expression of proteins involved in the generation and/or propagation of action potentials. A reduction in the sodium channel Nav1.4 expression in fibers overexpressing Foxo1-GFP was also observed in the absence of IGF-1. We conclude that increased nuclear activity of Foxo1 prevents the normal muscle responses to electrical stimulation and that this indicates a novel capability of Foxo1 to disable the functional activity of skeletal muscle. PMID:23804205

Hernández-Ochoa, Erick O; Schachter, Tova Neustadt; Schneider, Martin F



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


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



Biomimetic model of skeletal muscle isometric contraction: I. an energetic–viscoelastic model for the skeletal muscle isometric force twitch  

Microsoft Academic Search

This paper describes a revision of the Hill-type muscle model so that it will describe the chemo-mechanical energy conversion process (energetic) and the internal-element stiffness variation (viscoelastic) during a skeletal muscle isometric force twitch contraction. The derivation of this energetic–viscoelastic model is described by a first-order linear ordinary differential equation with constant energetic and viscoelastic coefficients. The model has been

C. A. Phillips; D. W. Repperger; A. T. Neidhard-Doll; D. B. Reynolds



Influence of spaceflight on rat skeletal muscle.  


The size, succinate dehydrogenase (SDH) and alpha-glycerolphosphate dehydrogenase (GPD) activities, and alkaline myofibrillar adenosinetriphosphatase (ATPase) staining properties were determined from quantitative histochemical analyses of single fibers from five hindlimb muscles of six male rats exposed to a 7-day National Aeronautics and Space Administration spaceflight mission (SL-3). These same properties were determined in a group of ground-based control rats housed under simulated environmental conditions. The wet weight of each of the flight muscles was significantly reduced relative to control. However, the loss of mass varied from 36% in the soleus to 15% in the extensor digitorum longus. The cross-sectional areas of fibers in the flight muscles also were reduced, except for the dark ATPase fibers in the medial gastrocnemius. The greatest relative fiber atrophy occurred in the muscles with the highest proportion of light ATPase fibers. An increase in the percentage of dark ATPase fibers also was observed in flight muscles with a predominance of light ATPase fibers. Also, there was an increase in the biochemically determined myofibrillar ATPase activity of tissue sections of the flight soleus. No changes in histochemical or biochemical measures of ATPase activity were observed in the flight extensor digitorum longus. In general, the SDH activity of flight muscles was maintained, whereas GPD activity either was maintained or increased. Based on a metabolic profile of ATPase, SDH, and GPD, there was an increase in the proportion of fast oxidative-glycolytic fibers in some muscles. PMID:2974847

Martin, T P; Edgerton, V R; Grindeland, R E



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



Localization and function of Xin? in mouse skeletal muscle.  


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



Vitamin D and its role in skeletal muscle.  


This review discusses the clinical and laboratory studies that have examined a role of vitamin D in skeletal muscle. Many observational studies, mainly in older populations, indicate that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Clinical trials of vitamin D supplementation in older adults with low vitamin D status mostly report improvements in muscle performance and reductions in falls. The underlying mechanisms are probably both indirect via calcium and phosphate and direct via activation of the vitamin D receptor (VDR) on muscle cells by 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. VDR activation at the genomic level regulates transcription of genes involved in calcium handling and muscle cell differentiation and proliferation. A putative membrane-associated VDR activates intracellular signaling pathways also involved in calcium handling and signaling and myogenesis. Additional evidence comes from VDR knockout mouse models with abnormal muscle morphology and physical function, and VDR polymorphisms which are associated with differences in muscle strength. Recent identification of CYP27B1 bioactivity in skeletal muscle cells and in regenerating adult mouse muscle lends support to the direct action of both 25-hydroxyvitamin D and 1,25(OH)(2)D in muscle. Despite these research advances, many questions remain. Further research is needed to fully characterize molecular mechanisms of vitamin D action on muscle cells downstream of the VDR, describe the effects on muscle morphology and contractility, and determine whether these molecular and cellular effects translate into clinical improvements in physical function. PMID:22968766

Ceglia, Lisa; Harris, Susan S



Post-exercise carbohydrate plus whey protein hydrolysates supplementation increases skeletal muscle glycogen level in rats.  


Recent studies showed that a combination of carbohydrate and protein was more effective than carbohydrate alone for replenishing muscle glycogen after exercise. However, it remains to be unclear whether the source or degree of hydrolysis of dietary protein influences post-exercise glycogen accumulation. The aim of this study was to compare the effect of dietary protein type on glycogen levels in the post-exercise phase, and to investigate the effects of post-exercise carbohydrate and protein supplementation on phosphorylated enzymes of Akt/PKB and atypical PKCs. Male Sprague-Dawley rats, trained for 3 days, swam with a 2% load of body weight for 4 h to deplete skeletal muscle glycogen. Immediately after the glycogen-depleting exercise, one group was killed, whereas the other groups were given either glucose or glucose plus protein (whey protein, whey protein hydrolysates (WPH), casein hydrolysates or branched-chain amino acid (BCAA) solutions. After 2 h, the rats were killed, and the triceps muscles quickly excised. WPH caused significant increases in skeletal muscle glycogen level (5.01 +/- 0.24 mg/g), compared with whey protein (4.23 +/- 0.24 mg/g), BCAA (3.92 +/- 0.18 mg/g) or casein hydrolysates (2.73 +/- 0.22 mg/g). Post-exercise ingestion of glucose plus WPH significantly increased both phosphorylated Akt/PKB (131%) and phosphorylated PKCzeta (154%) levels compared with glucose only. There was a significant positive correlation between skeletal muscle glycogen content and phosphorylated Akt/PKB (r = 0.674, P < 0.001) and PKCzeta (r = 0.481, P = 0.017). Post-exercise supplementation with carbohydrate and WPH increases skeletal muscle glycogen recovery by activating key enzymes such as Akt/PKB and atypical PKCs. PMID:19593593

Morifuji, Masashi; Kanda, Atsushi; Koga, Jinichiro; Kawanaka, Kentaro; Higuchi, Mitsuru



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



Tomographic elastography of contracting skeletal muscles from their natural vibrations  

NASA Astrophysics Data System (ADS)

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

Sabra, Karim G.; Archer, Akibi



Vasodilator Response to Epinephrine in Skeletal Muscle.  

National Technical Information Service (NTIS)

Injections of epinephrine into the jugular vein (dog) produced an initial vasodilatation in the gracilis muscle after ca. 5-20 sec. delay. At higher doses the vasodilatation was followed by vasoconstriction. The purpose of the experiments is to determine ...

L. R. Yonce J. W. McGee J. F. Sanderson G. Beer



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



Skeletal muscle analysis of wheelchair athletes  

Microsoft Academic Search

The present study reports the results of using the biopsy technique with members of the Canadian Wheelchair International Team. The results demonstrate that these athletes possess muscles with larger fibre areas than seen in Olympic athletes.

A W Taylor; E McDonnell; D Royer; R Loiselle; N Lush; R Steadward



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:; 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)



Skeletal Muscle Activity and the Fate of Myonuclei  

PubMed Central

Abstract Adult skeletal muscle fiber is a symplast multinuclear structure developed in ontogenesis by the fusion of the myoblasts (muscle progenitor cells). The nuclei of a muscle fiber (myonuclei) are those located at the periphery of fiber in the space between myofibrils and sarcolemma. In theory, a mass change in skeletal muscle during exercise or unloading may be associated with the altered myonuclear number, ratio of the transcription, and translation and proteolysis rates. Here we review the literature data related to the phenomenology and hypothetical mechanisms of the myonuclear number alterations during enhanced or reduced muscle contractile activity. In many cases (during severe muscle and systemic diseases and gravitational unloading), muscle atrophy is accompanied by a reduction in the amount of myonuclei. Such reduction is usually explained by the development of myonuclear apoptosis. A myonuclear number increase may be provided only by the satellite cell nuclei incorporation via cell fusion with the adjacent myofiber. It is believed that it is these cells which supply fiber with additional nuclei, providing postnatal growth, work hypertrophy, and repair processes. Here we discuss the possible mechanisms controlling satellite cell proliferation during exercise, functional unloading, and passive stretch.

Turtikova, O.V.; Nemirovskaya, T.L.; Grigoriev, A.I.



Neuropeptide Y and neurovascular control in skeletal muscle and skin.  


Neuropeptide Y (NPY) is a ubiquitous peptide with multiple effects on energy metabolism, reproduction, neurogenesis, and emotion. In addition, NPY is an important sympathetic neurotransmitter involved in neurovascular regulation. Although early studies suggested that the vasoactive effects of NPY were limited to periods of high stress, there is growing evidence for the involvement of NPY on baseline vasomotor tone and sympathetically evoked vasoconstriction in vivo in both skeletal muscle and the cutaneous circulation. In Sprague-Dawley rat skeletal muscle, Y(1)-receptor activation appears to play an important role in the regulation of basal vascular conductance, and this effect is similar in magnitude to the alpha(1)-receptor contribution. Furthermore, under baseline conditions, agonist and receptor-based mechanisms for Y(1)-receptor-dependent control of vascular conductance in skeletal muscle are greater in male than female rats. In skin, there is Y(1)-receptor-mediated vasoconstriction during whole body, but not local, cooling. As with the NPY system in muscle, this neural effect in skin differs between males and females and in addition, declines with aging. Intriguingly, skin vasodilation to local heating also requires NPY and is currently thought to be acting via a nitric oxide pathway. These studies are establishing further interest in the role of NPY as an important vasoactive agent in muscle and skin, adding to the complexity of neurovascular regulation in these tissues. In this review, we focus on the role of NPY on baseline vasomotor tone in skeletal muscle and skin and how NPY modulates vasomotor tone in response to stress, with the aim of compiling what is currently known, while highlighting some of the more pertinent questions yet to be answered. PMID:19571208

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



Purification of desmin from adult mammalian skeletal muscle.  

PubMed Central

A method has been developed for preparation of purified desmin from mature mammalian (porcine) skeletal muscle. A crude desmin-containing fraction was prepared by modification of procedures used for isolation of smooth-muscle intermediate-filament protein [Small & Sobieszek (1977) J. Cell Sci. 23, 243-268]. The desmin was extracted in 1 M-acetic acid/20 mM-NaCl at 4 degrees C for 15h from the residue remaining after actomyosin extraction from washed myofibrils. Successive chromatography on hydroxyapatite and DEAE-Sepharose CL-6B in 6M-urea yielded desmin that was routinely more than 97% 55 000-dalton protein and that had no detectable actin contamination. Removal of urea by dialysis against 10mM-Tris/acetate (pH 8.5)/1 mM dithioerythritol and subsequent clarification at 134 000 g (rav. 5.9 cm) for 1 h results in a clear desmin solution. Dialysis of purified desmin against 100 mM-NaCl/1 mM-MgCl2/10 mM-imidazole/HCl, pH 7.0, at 2 degrees C resulted in the formation of synthetic desmin filaments have an average diameter of 9-11.5 nm. The present studies demonstrate that the relatively small amount of desmin in mature skeletal muscle can be isolated in sufficient quantity and purity to permit detailed studies of its properties and function. Although 10nm filaments have not been unequivocally demonstrated in mature muscle in vivo, that the purified skeletal-muscle desmin will form 10 nm filaments in vitro lends support to their possible existence and cytoskeletal function in mature skeletal-muscle cells. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PLATE 1 Fig. 5.

O'Shea, J M; Robson, R M; Hartzer, M K; Huiatt, T W; Rathbun, W E; Stromer, M H



Autophagic response to exercise training in skeletal muscle with age.  


Autophagy, a highly conserved quality control mechanism, is essential for the maintenance of cellular homeostasis and for the orchestration of an efficient cellular response to stress. During aging, the efficiency of autophagic degradation declines, and intracellular waste products accumulate. Therefore, in this study, we tested the hypothesis that skeletal muscle from old mice would have decreased autophagosome formation when compared to the muscle from young mice. We also examined whether autophagic regulatory events differ between muscle fiber types and in response to exercise in aged male mice. The extensor digitorum longus (EDL) and gastrocnemius muscles were studied in young and old ICR mice. Exercise was performed by allowing the mice to run on a treadmill with a 5° incline at 16.4 m/min for 40 min/day, 5 days/week for 8 weeks after a 1-week adaptation period. Our results indicated that the levels of microtubule-associated protein 1b light chain 3, a marker of autophagosome formation, were lower in both the EDL and the gastrocnemius muscle of old mice compared to those young mice. To identify the factors related to the changes observed, the expression of autophagy regulatory proteins was examined in the EDL and gastrocnemius muscles. Beclin-1, autophagy-related gene 7 (ATG7), and lysosome-associated membrane protein were found to be lower in the EDL and gastrocnemius muscles of old mice compared to those in the young mice, then Beclin-1, ATG7, and muscle-specific RING finger protein-1 upregulated after regular exercise. Moreover, the muscle weight/body weight was significantly increased only in the gastrocnemius muscle of the old trained mice. These data suggest that autophagy regulatory events are attenuated in old skeletal muscle. However, this effect is upregulated when animals are subjected to exercise training. PMID:23471597

Kim, Yong An; Kim, Young Sang; Oh, Seung Lyul; Kim, Hee-Jae; Song, Wook



Needle Biopsy of Skeletal Muscle in Dogs: Light and Electron Microscopy of Resting Muscle.  

National Technical Information Service (NTIS)

A technique for needle biopsy of skeletal muscle in dogs was utilized in an experiment on the effects of ration on induced fatigue in a group of 15 military German Shepherd Dogs. Specimens of resting muscle were processed both for light and electron micro...

B. V. Sanders G. S. Trevino R. S. Demaree T. A. O'Donnell



Task-specific design of skeletal muscle: balancing muscle structural composition  

Microsoft Academic Search

Skeletal muscle fibers are composed of three structural elements, each contributing a unique aspect of muscle function, yet each ‘competing’ in a sense for space inside the cell. The volume occupied by myofibrils determines the force of contraction, the volume of sarcoplasmic reticulum sets the rate of onset and relaxation of a fiber’s contraction and hence contraction frequency, and the

Stan L. Lindstedt; Travis McGlothlin; Eric Percy; Judah Pifer



Calciseptine, a Ca 2+ Channel Blocker, Has Agonist Actions on L-type Ca 2+ Currents of Frog and Mammalian Skeletal Muscle  

Microsoft Academic Search

.   Calciseptine is a natural peptide consisting of 60 amino acids with four disulfide bonds. The peptide is a natural L-type\\u000a Ca2+-channel blocker in heart and other systems, but its actions in skeletal muscle have not been previously described. The aim\\u000a of this study is to characterize the effects of calciseptine on L-type Ca2+ channels of skeletal muscle and on

M. C. García; Z. Hernández-Gallegos; J. Escamilla; J. A. Sánchez



Evidence for fusion between cardiac and skeletal muscle cells.  


Cardiomyoplasty with skeletal myoblasts may benefit cardiac function after infarction. Recent reports indicate that adult stem cells can fuse with other cell types. Because myoblasts are "fusigenic" cells by nature, we hypothesized they might be particularly likely to fuse with cardiomyocytes. To test this, neonatal rat cardiomyocytes labeled with LacZ and green fluorescent protein (GFP) were cocultured with unlabeled C2C12 myoblasts. After 3 days, we observed a small population of skeletal myotubes that expressed LacZ and GFP, indicating cell fusion. To test whether such fusion occurred in vivo, LacZ-expressing C2C12 myoblasts were grafted into normal nude mouse hearts. At 2 weeks after grafting, cells at the graft-host interface expressed both LacZ and cardiac-specific myosin light chain 2v (MLC2v). To test more definitively whether fusion between skeletal and cardiac muscle could occur, we used a Cre/lox reporter system that activated LacZ only upon cell fusion. When neonatal cardiomyocytes from -myosin heavy chain promoter (-MHC)-Cre mice were cocultured with myoblasts from floxed-lacZ reporter mice, LacZ was activated in a subset of cells, indicating cell fusion occurred in vitro. Finally, we grafted the floxed-lacZ myoblasts into normal hearts of -MHC-Cre+ and -MHC-Cre- mice (n=5 each). Hearts analyzed at 4 days and 1 week after transplantation demonstrated activation of LacZ when the skeletal muscle cells were implanted into hearts of -MHC-Cre+ mice, but not after implantation into -MHC-Cre- mice. These data indicate that skeletal muscle cell grafting gives rise to a subpopulation of skeletal-cardiac hybrid cells with a currently unknown phenotype. The full text of this article is available online at PMID:15001531

Reinecke, Hans; Minami, Elina; Poppa, Veronica; Murry, Charles E



Stem cells in the hood: the skeletal muscle niche.  


It is generally accepted that the principal resident progenitor underlying regenerative capacity in skeletal muscle is the satellite cell. Satellite cells are present throughout life even though regenerative capacity declines with age and disease. Recently, other stem cell populations have been identified that can participate in muscle growth and regeneration. These cells may provide therapeutically useful sources of muscle stem cells as an alternative to satellite cells; however, the roles of these nonsatellite cell populations during muscle homeostasis, regeneration, and aging are unclear. Here, we discuss how the stem cell neighborhood influences satellite cell behavior and bring together recent discoveries pertaining to a wide variety of adult stem cells, including muscle stem cells and their niche. PMID:22877884

Pannérec, Alice; Marazzi, Giovanna; Sassoon, David



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



S1P2 receptor promotes mouse skeletal muscle regeneration.  


Sphingosine 1-phosphate is a bioactive lipid that modulates skeletal muscle growth through its interaction with specific receptors localized in the cell membrane of muscle fibers and satellite cells. This study analyzes the role of S1P(2) receptor during in vivo regeneration of soleus muscle in two models of S1P(2) deficiency: the S1P(2)-null mouse and wild-type mice systemically treated with the S1P(2) receptor antagonist JTE-013. To stimulate regeneration, muscle degeneration was induced by injecting into soleus muscle the myotoxic drug notexin. Both ablation of S1P(2) receptor and its functional inactivation delayed regeneration of soleus muscle. The exogenous supplementation of S1P or its removal, by a specific antibody, two conditions known to stimulate or inhibit, respectively, soleus muscle regeneration, were without effects when the S1P(2) receptor was absent or inactive. The delayed regeneration was associated with a lower level of myogenin, a muscle differentiation marker, and reduced phosphorylation of Akt, a key marker of muscle growth. Consistently, silencing of S1P(2) receptor abrogated the pro-myogenic action of S1P in satellite cells, paralleled by low levels of the myogenic transcription factor myogenin. The study indicates that S1P(2) receptor plays a key role in the early phases of muscle regeneration by sustaining differentiation and growth of new-forming myofibers. PMID:22744969

Germinario, Elena; Peron, Samantha; Toniolo, Luana; Betto, Romeo; Cencetti, Francesca; Donati, Chiara; Bruni, Paola; Danieli-Betto, Daniela




Microsoft Academic Search

It is now generally accepted that hybrid skeletal muscle fibres are not experimental artefacts, but complex molecular systems that expand the functional repertoire of the muscle to which they belong. The purpose of this review is to highlight the cognitive value of hybrid fibres by discussing several insights into skeletal muscle biology produced by studies using hybrid fibres and\\/or muscles

Gabriela M. M. Stephenson


Skeletal Muscle Metabolism Limits Exercise Capacity in Patients With Chronic Heart Failure  

Microsoft Academic Search

Background—Several studies have indicated that skeletal muscle is important in determining the exercise capacity of patients with chronic heart failure (CHF). However, this theory has been investigated only in experiments based on local exercise involving a small muscle mass. We investigated skeletal muscle metabolism during maximal systemic exercise to determine whether muscle metabolism limits exercise capacity in patients with CHF.

Koichi Okita; Kazuya Yonezawa; Hirotaka Nishijima; Akiko Hanada; Mitsunori Ohtsubo; Tetsuro Kohya; Takeshi Murakami; Akira Kitabatake


The localization of VAMP5 in skeletal and cardiac muscle.  


Vesicle-associated membrane protein 5 (VAMP5) is a member of the SNARE protein family, which is generally thought to regulate the docking and fusion of vesicles with their target membranes. This study investigated the expression and localization of the VAMP5 protein. Immunoblotting analyses detected the VAMP5 protein in skeletal muscle, heart, spleen, lung, liver, and kidney tissue, but not in brain or small intestine tissue. Through the immunofluorescence microscopy of skeletal muscle, we found that the expression level of VAMP5 varies among fibers. Most of the fibers with high expression levels of VAMP5 were categorized as type IIa fibers on the basis of their myosin heavy chain subtypes. In addition, the expression patterns of VAMP5 and glucose transporter 4 (GLUT4) were similar. In cardiac muscle, we determined that VAMP5 was localized to the vicinity of intercalated discs. These results suggest that VAMP5 plays local roles in membrane trafficking in skeletal and cardiac muscle. PMID:23180306

Takahashi, Maiko; Tajika, Yuki; Khairani, Astrid Feinisa; Ueno, Hitoshi; Murakami, Tohru; Yorifuji, Hiroshi



The cardiac isoform of ?-actin in regenerating and atrophic skeletal muscle, myopathies and rhabdomyomatous tumors: an immunohistochemical study using monoclonal antibodies  

Microsoft Academic Search

The two sarcomeric isoforms of actins, cardiac and skeletal muscle ?-actin, are highly homologous so that their immunohistochemical distinction is extremely difficult. Taking advantage of monoclonal antibodies distinguishing the two conservative amino acid exchanges near the aminoterminus, we have performed an extended immunohistochemical analysis of the cardiac ?-actin (CAA) isoform in normal, regenerating, diseased and neoplastic human muscle tissues. Intense

Roland Moll; Hans-Jürgen Holzhausen; Hans-Dieter Mennel; Caecilia Kuhn; Renate Baumann; Christiane Taege; Werner W. Franke



Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration.  


Sphingosine 1-phosphate (S1P) is a bioactive lipid known to control cell growth that was recently shown to act as a trophic factor for skeletal muscle, reducing the progress of denervation atrophy. The aim of this work was to investigate whether S1P is involved in skeletal muscle fiber recovery (regeneration) after myotoxic injury induced by bupivacaine. The postnatal ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. Immunofluorescence analysis demonstrated that S1P-specific receptors S1P(1) and S1P(3) are expressed by quiescent satellite cells. Soleus muscles undergoing regeneration following injury induced by intramuscular injection of bupivacaine exhibited enhanced expression of S1P(1) receptor, while S1P(3) expression progressively decreased to adult levels. S1P(2) receptor was absent in quiescent cells but was transiently expressed in the early regenerating phases only. Administration of S1P (50 microM) at the moment of myotoxic injury caused a significant increase of the mean cross-sectional area of regenerating fibers in both rat and mouse. In separate experiments designed to test the trophic effects of S1P, neutralization of endogenous circulating S1P by intraperitoneal administration of anti-S1P antibody attenuated fiber growth. Use of selective modulators of S1P receptors indicated that S1P(1) receptor negatively and S1P(3) receptor positively modulate the early phases of regeneration, whereas S1P(2) receptor appears to be less important. The present results show that S1P signaling participates in the regenerative processes of skeletal muscle. PMID:20042733

Danieli-Betto, Daniela; Peron, Samantha; Germinario, Elena; Zanin, Marika; Sorci, Guglielmo; Franzoso, Susanna; Sandonà, Dorianna; Betto, Romeo



Imaging two-dimensional mechanical waves of skeletal muscle contraction.  


Skeletal muscle contraction is related to rapid mechanical shortening and thickening. Recently, specialized ultrasound systems have been applied to demonstrate and quantify transient tissue velocities and one-dimensional (1-D) propagation of mechanical waves during muscle contraction. Such waves could potentially provide novel information on musculoskeletal characteristics, function and disorders. In this work, we demonstrate two-dimensional (2-D) mechanical wave imaging following the skeletal muscle contraction. B-mode image acquisition during multiple consecutive electrostimulations, speckle-tracking and a time-stamp sorting protocol were used to obtain 1.4 kHz frame rate 2-D tissue velocity imaging of the biceps brachii muscle contraction. The results present novel information on tissue velocity profiles and mechanical wave propagation. In particular, counter-propagating compressional and shear waves in the longitudinal direction were observed in the contracting tissue (speed 2.8-4.4 m/s) and a compressional wave in the transverse direction of the non-contracting muscle tissue (1.2-1.9 m/s). In conclusion, analysing transient 2-D tissue velocity allows simultaneous assessment of both active and passive muscle tissue properties. PMID:23219037

Grönlund, Christer; Claesson, Kenji; Holtermann, Andreas



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



Defining skeletal muscle resident progenitors and their cell fate potentials.  


The satellite cell is the major tissue-resident stem cell underlying muscle regeneration; however, multiple non-satellite myogenic progenitors as well as non-myogenic populations that support the muscle regenerative process have been identified. PW1 is expressed in satellite cells as well as in a subset of interstitial cells with myogenic potential termed PICs (PW1+ interstitial cells). Microarray profiling revealed that PICs express a broad range of genes common to mesenchymal stem cells, whereas satellite cells express genes consistent with a committed myogenic progenitor. Isolated PICs from both young and adult muscles can differentiate into smooth and skeletal muscle and fat whereas satellite cells are restricted to a skeletal muscle fate. We demonstrate that the adipogenic potential of PICs corresponds to a subpopulation that expresses platelet derived growth factor receptor alpha (PDGFR?) and overlaps with the recently described interstitial adipogenic progenitors. By contrast, PICs with myogenic potential do not express PDGFR?. Moreover, we observe a discrete and transient population of juvenile PICs based upon SCA1 expression that disappears by 3 weeks of postnatal development coincident with a switch in the cellular and genetic mechanisms underlying postnatal muscle growth. PMID:23739133

Pannérec, Alice; Formicola, Luigi; Besson, Vanessa; Marazzi, Giovanna; Sassoon, David A



Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation  

Technology Transfer Automated Retrieval System (TEKTRAN)

Protein synthesis and eukaryotic initiation factor (eIF) activation are increased in skeletal muscle of neonatal pigs parenterally infused with amino acids. Leucine appears to be the most effective single amino acid to trigger these effects. To examine the response to enteral leucine supplementation...


Indices of skeletal muscle damage and connective tissue breakdown following eccentric muscle contractions  

Microsoft Academic Search

Indirect indices of exercise-induced human skeletal muscle damage and connective tissue breakdown were studied following\\u000a a single bout of voluntary eccentric muscle contractions. Subjects (six female, two male), mean (SD) age 22 (2) years performed\\u000a a bout of 50 maximum voluntary eccentric contractions of the knee extensors of a single leg. The eccentric exercise protocol\\u000a induced muscle soreness (P?

S. J. Brown; R. B. Child; S. H. Day; A. E. Donnelly



PI3 kinase regulation of skeletal muscle hypertrophy and atrophy.  


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



Abcg2 labels multiple cell types in skeletal muscle and participates in muscle regeneration  

PubMed Central

Skeletal muscle contains progenitor cells (satellite cells) that maintain and repair muscle. It also contains muscle side population (SP) cells, which express Abcg2 and may participate in muscle regeneration or may represent a source of satellite cell replenishment. In Abcg2-null mice, the SP fraction is lost in skeletal muscle, although the significance of this loss was previously unknown. We show that cells expressing Abcg2 increased upon injury and that muscle regeneration was impaired in Abcg2-null mice, resulting in fewer centrally nucleated myofibers, reduced myofiber size, and fewer satellite cells. Additionally, using genetic lineage tracing, we demonstrate that the progeny of Abcg2-expressing cells contributed to multiple cell types within the muscle interstitium, primarily endothelial cells. After injury, Abcg2 progeny made a minor contribution to regenerated myofibers. Furthermore, Abcg2-labeled cells increased significantly upon injury and appeared to traffic to muscle from peripheral blood. Together, these data suggest an important role for Abcg2 in positively regulating skeletal muscle regeneration.

Doyle, Michelle J.; Zhou, Sheng; Tanaka, Kathleen Kelly; Pisconti, Addolorata; Farina, Nicholas H.; Sorrentino, Brian P.



Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy.  


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. PMID:11247852

Spangenburg, E E; Williams, J H; Roy, R R; Talmadge, R J



Exercise, GLUT4, and skeletal muscle glucose uptake.  


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



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


Optical NIR monitoring of skeletal muscle contraction  

NASA Astrophysics Data System (ADS)

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

Lago, Paolo; Gelmetti, Andrea; Pavesi, Roberta; Zambarbieri, D.



Characteristics of impala (Aepyceros melampus) skeletal muscles.  


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



Myosin light chain kinase and myosin phosphorylation effect frequency-dependent potentiation of skeletal muscle contraction  

Microsoft Academic Search

Repetitive stimulation potentiates contractile tension of fast-twitch skeletal muscle. We examined the role of myosin regulatory light chain (RLC) phosphorylation in this physiological response by ablating Ca2+\\/calmodulin-dependent skeletal muscle myosin light chain kinase (MLCK) gene expression. Western blot and quantitative-PCR showed that MLCK is expressed predominantly in fast-twitch skeletal muscle fibers with insignificant amounts in heart and smooth muscle. In

Gang Zhi; Jeffrey W. Ryder; Jian Huang; Peiguo Ding; Yue Chen; Yingming Zhao; Kristine E. Kamm; James T. Stull



Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK  

Microsoft Academic Search

Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium\\/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis,

Hai Wu; Shane B. Kanatous; Frederick A. Thurmond; Teresa Gallardo; Eiji Isotani; Rhonda Bassel-Duby; R. Sanders Williams



Insulin action in denervated skeletal muscle  

SciTech Connect

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

Smith, R.L.



Beating is necessary for transdifferentiation of skeletal muscle-derived cells into cardiomyocytes  

Microsoft Academic Search

Cell transplantation could be a potential therapy for heart damage. Skeletal myoblasts have been expected to be a good cell source for autologous transplantation; however, the safety and efficacy of their transplantation are still controversial. Recent studies have revealed that skeletal muscle possesses the stem cell population that is distinct from myoblasts. To elucidate whether skeletal muscle stem cells can

Yoshihiro Iijima; Toshio Nagai; Miho Mizukami; Katsuhisa Matsuura; Takehiko Ogura; Hiroshi Wada; Haruhiko Toko; Hiroshi Akazawa; Hiroyuki Takano; Haruaki Nakaya; Issei Komuro



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.



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

PubMed Central

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

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



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


Sustained periods of negative energy balance decrease body mass due to losses of both fat and skeletal muscle mass. Decreases in skeletal muscle mass are associated with a myriad of negative consequences, including suppressed basal metabolic rate, decreased protein turnover, decreased physical performance, and increased risk of injury. Decreases in skeletal muscle mass in response to negative energy balance are due to imbalanced rates of muscle protein synthesis and degradation. However, the underlying physiological mechanisms contributing to the loss of skeletal muscle during energy deprivation are not well described. Recent studies have demonstrated that consuming dietary protein at levels above the current recommended dietary allowance (0.8 g · kg(-1) · d(-1)) may attenuate the loss of skeletal muscle mass by affecting the intracellular regulation of muscle anabolism and proteolysis. However, the specific mechanism by which increased dietary protein spares skeletal muscle through enhanced molecular control of muscle protein metabolism has not been elucidated. This article reviews the available literature related to the effects of negative energy balance on skeletal muscle mass, highlighting investigations that assessed the influence of varying levels of dietary protein on skeletal muscle protein metabolism. Further, the molecular mechanisms that may contribute to the regulation of skeletal muscle mass in response to negative energy balance and alterations in dietary protein level are described. PMID:22516719

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



Calsequestrin expression and calcium binding is increased in streptozotocin-induced diabetic rat skeletal muscle though not in cardiac muscle  

Microsoft Academic Search

Altered mechanisms of Ca2+ transport may underlie the contractile dysfunctions that have been frequently reported to occur in diabetic cardiac and skeletal muscle tissues. Calsequestrin, a high-capacity Ca2+-binding protein, is involved in the regulation of the excitation-contraction-relaxation cycle of both skeletal and cardiac muscle fibres. We have investigated the expression of calsequestrin and Ca2+ binding in cardiac and skeletal muscle

F. Howarth; L. Glover; K. Culligan; M. Qureshi; K. Ohlendieck



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.



Prior knowledge, random walks and human skeletal muscle segmentation.  


In this paper, we propose a novel approach for segmenting the skeletal muscles in MRI automatically. In order to deal with the absence of contrast between the different muscle classes, we proposed a principled mathematical formulation that integrates prior knowledge with a random walks graph-based formulation. Prior knowledge is represented using a statistical shape atlas that once coupled with the random walks segmentation leads to an efficient iterative linear optimization system. We reveal the potential of our approach on a challenging set of real clinical data. PMID:23285597

Baudin, P Y; Azzabou, N; Carlier, P G; Paragios, Nikos



Numerical Simulation of Ca 2+ “Sparks” in Skeletal Muscle  

Microsoft Academic Search

A three dimensional (3D) model of Ca2+ diffusion and binding within a sarcomere of a myofibril, including Ca2+ binding sites troponin, parvalbumin, sarcoplasmic reticulum Ca2+ pump, and fluorescent Ca2+-indicator dye (fluo-3), was developed to numerically simulate laser scanning confocal microscope images of Ca2+ “sparks” in skeletal muscle. Diffusion of free dye (D), calcium dye (CaD), and Ca2+ were included in

Yu-Hua Jiang; Michael G. Klein; Martin F. Schneider



Cellular and Molecular Mechanisms of Skeletal Muscle Plasticity  

Microsoft Academic Search

Skeletal muscles are used for a wide variety of motor tasks ranging from maintaining posture to whistling, from jumping to\\u000a breathing, from running at ?40Km\\/h for 10s (100 meters) to running at half the speed for ?2h (i.e., the marathon, 42,195Km).\\u000a The capacity to accomplish such variable motor tasks relies on the very fine motor control performed by the nervous

Monica Canepari; Roberto Bottinelli


Expression of laminin subunits in human fetal skeletal muscle  

Microsoft Academic Search

Summary  The laminin variant of adult skeletal muscle fibres and Schwann cells is known as merosin, and is composed of M-B1-B2 chains. Blood vessels and immature fibres express the A chain in association with B1 or S, and B2. The importance of merosin has recently been shown by its absence in one form of congenital muscular dystrophy and in the mutant

C. A. Sewry; M. Chevallay; F. M. S. Tomé



Expression of laminin subunits in human fetal skeletal muscle  

Microsoft Academic Search

Summary  The laminin variant of adult skeletal muscle fibres and Schwann cells is known as merosin, and is composed of M-B1-B2 chains.\\u000a Blood vessels and immature fibres express the A chain in association with B1 or S, and B2. The importance of merosin has recently\\u000a been shown by its absence in one form of congenital muscular dystrophy and in the mutantdy\\/dy

C. A. Sewry; M. Chevallay; F. M. S. Tomé



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



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



DHPR ?1S subunit controls skeletal muscle mass and morphogenesis  

PubMed Central

The ?1S subunit has a dual function in skeletal muscle: it forms the L-type Ca2+ channel in T-tubules and is the voltage sensor of excitation–contraction coupling at the level of triads. It has been proposed that L-type Ca2+ channels might also be voltage-gated sensors linked to transcriptional activity controlling differentiation. By using the U7-exon skipping strategy, we have achieved long-lasting downregulation of ?1S in adult skeletal muscle. Treated muscles underwent massive atrophy while still displaying significant amounts of ?1S in the tubular system and being not paralysed. This atrophy implicated the autophagy pathway, which was triggered by neuronal nitric oxide synthase redistribution, activation of FoxO3A, upregulation of autophagy-related genes and autophagosome formation. Subcellular investigations showed that this atrophy was correlated with the disappearance of a minor fraction of ?1S located throughout the sarcolemma. Our results reveal for the first time that this sarcolemmal fraction could have a role in a signalling pathway determining muscle anabolic or catabolic state and might act as a molecular sensor of muscle activity.

Pietri-Rouxel, France; Gentil, Christel; Vassilopoulos, Stephane; Baas, Dominique; Mouisel, Etienne; Ferry, Arnaud; Vignaud, Alban; Hourde, Christophe; Marty, Isabelle; Schaeffer, Laurent; Voit, Thomas; Garcia, Luis



A Mathematical Analysis of Obstructed Diffusion within Skeletal Muscle  

PubMed Central

Abstract Molecules are transported through the myofilament lattice of skeletal muscle fibers during muscle activation. The myofilaments, along with the myosin heads, sarcoplasmic reticulum, t-tubules, and mitochondria, obstruct the diffusion of molecules through the muscle fiber. In this work, we studied the process of obstructed diffusion within the myofilament lattice using Monte Carlo simulation, level-set and homogenization theory. We found that these intracellular obstacles significantly reduce the diffusion of material through skeletal muscle and generate diffusion anisotropy that is consistent with experimentally observed slower diffusion in the radial than the longitudinal direction. Our model also predicts that protein size has a significant effect on the diffusion of material through muscle, which is consistent with experimental measurements. Protein diffusion on the myofilament lattice is also anomalous (i.e., it does not obey Brownian motion) for proteins that are close in size to the myofilament spacing. The obstructed transport of Ca2+ and ATP-bound Ca2+ through the myofilament lattice also generates smaller Ca2+ transients. In addition, we used homogenization theory to discover that the nonhomogeneous distribution in the troponin binding sites has no effect on the macroscopic Ca2+ dynamics. The nonuniform sarcoplasmic reticulum Ca2+-ATPase pump distribution also introduces small asymmetries in the myoplasmic Ca2+ transients.

Shorten, P.R.; Sneyd, J.



An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes.  


An X-linked recessive disease is reported in a large pedigree. The disease is characterised by a triad of dilated cardiomyopathy, neutropenia and skeletal myopathy. The untreated patients, all boys, died in infancy or early childhood from septicemia or cardiac decompensation. Ultrastructural abnormalities were observed in mitochondria in cardiac muscle cells, neutrophil bone marrow cells and to a lesser extent (0-9%) in skeletal muscle cells. Membrane-bound vacuoles were seen in neutrophil bone marrow cells. Intramuscular fat droplets were increased in type I skeletal muscle fibres. An affected patient had intermittent lactic acidemia, borderline low plasma carnitine, the latter decreasing during periods of illness, and low muscle carnitine (27% pretreatment; 35-40% posttreatment). While on treatment with oral carnitine he had less weakness and no cardiac complaints, but his neutropenia was not affected. Respiratory chain abnormalities were observed in this patient's isolated skeletal muscle mitochondria. These were: (1) diminished concentrations of cytochromes c1 + c, b and aa3 to 29, 47 and 64% of the averaged controls, and (2) a lowered P:0 ratio for oxidation of ascorbate + TMPD, with diminished uncoupler stimulated Mg2+-ATPase activity. Muscle AMP deaminase was deficient (5 resp. 17%). Only one previous report (Neustein et al. 1979) on X-linked mitochondrial cardiomyopathy exists, which probably refers to the same entity. Biochemical studies and haematological abnormalities (neutropenia) are reported for the first time. PMID:6142097

Barth, P G; Scholte, H R; Berden, J A; Van der Klei-Van Moorsel, J M; Luyt-Houwen, I E; Van 't Veer-Korthof, E T; Van der Harten, J J; Sobotka-Plojhar, M A



Glutamine preserves skeletal muscle force during an inflammatory insult.  


The purpose of this study was to test the hypothesis that acute glutamine (GLN) supplementation can counteract skeletal muscle contractile dysfunction occurring in response to inflammation by elevating muscle heat shock protein (Hsp) expression and reducing inflammatory cytokines. Mice received 5 mg/kg lipopolysaccharide (LPS) concurrently with 1 g/kg GLN or vehicle treatments. Plantarflexor isometric force production was measured at 2 hours post-injection. Blood and gastrocnemius muscles were collected, and serum and muscle tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and muscle Hsp70 and Hsp25 were quantified. Saline/LPS treatment was associated with a 33% reduction in maximal force and elevated serum TNF-alpha and IL-6. GLN completely prevented this force decrement with LPS. GLN was found to reduce muscle Hsp70 and IL-6, but only in the presence of LPS. GLN supplementation provides an effective, novel, clinically applicable means of preserving muscle force during acute inflammation. These data indicate that force preservation is not dependent on reductions in serum cytokines or muscle TNF-alpha, or elevated Hsp levels. PMID:19705479

Meador, Benjamin M; Huey, Kimberly A



Skeletal muscle metabolism during exercise is influenced by heat acclimation.  


The influence of heat acclimation on skeletal muscle metabolism during submaximal exercise was studied in 13 healthy men. The subjects performed 30 min of cycle exercise (70% of individual maximal O2 uptake) in a cool [21 degrees C, 30% relative humidity (rh)] and a hot (49 degrees C, 20% rh) environment before and again after they were heat acclimated. Aerobic metabolic rate was lower (0.1 l X min-1; P less than 0.01) during exercise in the heat compared with the cool both before and after heat acclimation. Muscle and plasma lactate accumulation with exercise was greater (P less than 0.01) in the hot relative to the cool environment both before and after acclimation. Acclimation lowered (P less than 0.01) aerobic metabolic rate as well as muscle and plasma lactate accumulation in both environments. The amount of muscle glycogen utilized during exercise in the hot environment did not differ from that in the cool either before or after acclimation. These findings indicate that accumulation of muscle lactate is increased and aerobic metabolic rate is decreased during exercise in the heat before and after heat acclimation; increased muscle glycogen utilization does not account for the increased muscle lactate accumulation during exercise under extreme heat stress; and heat acclimation lowers the aerobic metabolic rate and muscle and blood lactate accumulation during exercise in a cool as well as a hot environment. PMID:4077800

Young, A J; Sawka, M N; Levine, L; Cadarette, B S; Pandolf, K B




PubMed Central

Work-induced growth of rat soleus muscle is accompanied by an early increase in new RNA synthesis. To determine the cell type(s) responsible for the increased RNA synthesis, we compared light autoradiographs of control and hypertrophying muscles from rats injected with tritiated uridine 12, 24, and 48 h after inducing hypertrophy. There was an increased number of silver grains over autoradiographs of hypertrophied muscle. This increase occurred over connective tissue cells; there was no increase in the number of silver grains over the muscle fibers. Quantitative studies demonstrated that between 70 and 80% of the radioactivity in the muscle that survived fixation and washing was in RNA. Pretreatment of the animals with actinomycin D reduced in parallel both the radioactivity in RNA and the number of silver grains over autoradiographs. Proliferation of the connective tissue in hypertrophying muscle was evident in light micrographs, and electron micrographs identified the proliferating cells as enlarged fibroblasts and macrophages; the connective tissue cells remained after hypertrophy was completed. Thus, proliferating connective tissue cells are the major site of the increase in new RNA synthesis during acute work-induced growth of skeletal muscle. It is suggested that in the analysis of physiological adaptations of muscle, the connective tissue cells deserve consideration as a site of significant molecular activity.

Jablecki, Charles K.; Heuser, John E.; Kaufman, Seymour



?-Adrenergic Inhibition of Contractility in L6 Skeletal Muscle Cells  

PubMed Central

The ?-adrenoceptors (?-ARs) control many cellular processes. Here, we show that ?-ARs inhibit calcium depletion-induced cell contractility and subsequent cell detachment of L6 skeletal muscle cells. The mechanism underlying the cell detachment inhibition was studied by using a quantitative cell detachment assay. We demonstrate that cell detachment induced by depletion of extracellular calcium is due to myosin- and ROCK-dependent contractility. The ?-AR inhibition of L6 skeletal muscle cell detachment was shown to be mediated by the ?2-AR and increased cAMP but was surprisingly not dependent on the classical downstream effectors PKA or Epac, nor was it dependent on PKG, PI3K or PKC. However, inhibition of potassium channels blocks the ?2-AR mediated effects. Furthermore, activation of potassium channels fully mimicked the results of ?2-AR activation. In conclusion, we present a novel finding that ?2-AR signaling inhibits contractility and thus cell detachment in L6 skeletal muscle cells by a cAMP and potassium channel dependent mechanism.

Oberg, Anette I.; Dehvari, Nodi; Bengtsson, Tore



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



Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts  

NASA Astrophysics Data System (ADS)

Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP production. Although insulin is a major regulator of fuel metabolism, its effect on mitochondrial ATP production is not known. Here we report increases in vastus lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans (P < 0.01) i.v. infused with insulin (1.5 milliunits/kg of fat-free mass per min) while clamping glucose, amino acids, glucagon, and growth hormone. Increased ATP production occurred in association with increased mRNA levels from both mitochondrial (NADH dehydrogenase subunit IV) and nuclear [cytochrome c oxidase (COX) subunit IV] genes (164-180%) encoding mitochondrial proteins (P < 0.05). In addition, muscle mitochondrial protein synthesis, and COX and citrate synthase enzyme activities were increased by insulin (P < 0.05). Further studies demonstrated no effect of low to high insulin levels on muscle mitochondrial ATP production for people with type 2 diabetes mellitus, whereas matched nondiabetic controls increased 16-26% (P < 0.02) when four different substrate combinations were used. In conclusion, insulin stimulates mitochondrial oxidative phosphorylation in skeletal muscle along with synthesis of gene transcripts and mitochondrial protein in human subjects. Skeletal muscle of type 2 diabetic patients has a reduced capacity to increase ATP production with high insulin levels. cytochrome c oxidase | NADH dehydrogenase subunit IV | amino acids | citrate synthase

Stump, Craig S.; Short, Kevin R.; Bigelow, Maureen L.; Schimke, Jill M.; Sreekumaran Nair, K.



Bridging the myoplasmic gap: recent developments in skeletal muscle excitation–contraction coupling  

Microsoft Academic Search

Conformational coupling between the L-type voltage-gated Ca2+ channel (or 1,4–dihydropyridine receptor; DHPR) and the ryanodine-sensitive Ca2+ release channel of the sarcoplasmic reticulum (RyR1) is the mechanistic basis for excitation–contraction (EC) coupling in\\u000a skeletal muscle. In this article, recent findings regarding the roles of the individual cytoplasmic domains (the amino- and\\u000a carboxyl-termini, cytoplasmic loops I–II, II–III, and III–IV) of the DHPR

Roger A. Bannister



Skeletal muscle volume following dehydration induced by exercise in heat  

PubMed Central

Background Intracellular skeletal muscle water is redistributed into the extracellular compartment during periods of dehydration, suggesting an associated decline in muscle volume. The purpose of this study was to evaluate skeletal muscle volume in active (knee extensors (KE)) and less active (biceps/triceps brachii, deltoid) musculature following dehydration induced by exercise in heat. Methods Twelve participants (seven men, five women) cycled in the heat under two conditions: (1) dehydration (DHYD) resulting in 3% and 5% losses of estimated total body water (ETBW), which was assessed by changes in body mass, and (2) fluid replacement (FR) where 3% and 5% losses of ETBW were counteracted by intermittent (20 to 30 min) fluid ingestion via a carbohydrate-electrolyte beverage. During both conditions, serum osmolality and skeletal muscle volume (assessed by magnetic resonance imaging) were measured at baseline and at the 3% and 5% ETBW loss measurement points. Results In DHYD, serum osmolality increased at 3% (p?=?0.005) and 5% (p?muscle volume declined from 1,464?±?446 ml to 1,406?±?425 ml (3.9%, p?muscles. There were no changes in volume for the biceps/triceps (p?=?0.35) or deltoid (p?=?0.92) during DHYD. FR prevented the loss of KE muscle volume at 3% (1,430?±?435 ml, p?=?0.074) and 5% (1,431?±?439 ml, p?=?0.156) ETBW loss time points compared to baseline (1,445?±?436 ml). Conclusions Following exercise in the heat, the actively contracting muscles lost volume, while replacing lost fluids intermittently during exercise in heat prevented this decline. These results support the use of muscle volume as a marker of water loss.



Optical reflectance in fibrous tissues and skeletal muscles  

NASA Astrophysics Data System (ADS)

We studied two biological tissues with optically anisotropic structures: high moisture soy protein extrudates and skeletal muscles. High moisture extrusion has been used to produce vegetable meat analogs that resemble real animal meat and have significant health benefits. Since visual and textural properties are key factors for consumer acceptance, assessing fiber formation in the extruded soy protein product is important for quality control purpose. A non-destructive method based on photon migration was developed to measure fiber formation in extruded soy proteins. The measured fiber formation index in intact samples showed good agreement with that obtained from image analysis on peeled samples. By implementing this new method in a fast laser scanning system, we have acquired two dimensional mappings of fiber formation and orientation in the entire sample in real time. In addition to fibrous structures, skeletal muscles have a unique periodic sarcomere structure which produces strong light diffractions. However, inconsistent experimental results have been reported in single fiber diffraction studies. By applying the three-dimensional coupled wave theory in a physical sarcomere model, we found that a variety of experimental observations can be explained if inhomogeneous muscle morphological profiles are considered. We also discovered that the sarcomere structure produced a unique optical reflectance pattern in whole muscle. None of the existing light propagation theories are able to describe this pattern. We developed a Monte Carlo model incorporating the sarcomere diffraction effect. The simulated results quantitatively resemble the unique patterns observed in experiments. We used a set of parameters to quantify the optical reflectance profiles produced by a point incident light in whole muscle. Two parameters, q and B, were obtained by numerically fitting the equi-intensity contours of the reflectance pattern. Two spatial gradients were calculated along the directions parallel and perpendicular to muscle fibers. The mean diffuse intensity was obtained by excluding the specular reflectance. These five parameters provide a comprehensive and complete description of the diffuse reflectance in muscle. In a study of 336 muscle samples, we found these optical parameters were subject to the effects of different muscle physical and biochemical factors. Different types of muscle have significantly different diffuse intensities. Aging shows different effects on the q parameter in different muscles. In addition, the mean diffuse intensity is significantly different (p<0.05) in different animal breeds. Optical parameters showed good correlations with Warner-Bratzler shear force. Further studies on a large sample group are necessary to develop a statistical model to predict muscle physical and chemical properties using these non-destructive optical measurements.

Ranasinghesagara, Janaka C.


Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype.  


Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. Given that the aif hypomorphic harlequin (Hq) mutant mouse model displays severe sarcopenia, we examined skeletal muscle from the aif hypomorphic mice in more detail. Adult AIF-deficient skeletal myofibers display oxidative stress and a severe form of atrophy, associated with a loss of myonuclei and a fast to slow fiber type switch, both in "slow" muscles such as soleus, as well as in "fast" muscles such as extensor digitorum longus, most likely resulting from an increase of MEF2 activity. This fiber type switch was conserved in regenerated soleus and EDL muscles of Hq mice subjected to cardiotoxin injection. In addition, muscle regeneration in soleus and EDL muscles of Hq mice was severely delayed. Freshly cultured myofibers, soleus and EDL muscle sections from Hq mice displayed a decreased satellite cell pool, which could be rescued by pretreating aif hypomorphic mice with the manganese-salen free radical scavenger EUK-8. Satellite cell activation seems to be abnormally long in Hq primary culture compared to controls. However, AIF deficiency did not affect myoblast cell proliferation and differentiation. Thus, AIF protects skeletal muscles against oxidative stress-induced damage probably by protecting satellite cells against oxidative stress and maintaining skeletal muscle stem cell number and activation. PMID:22076146

Armand, Anne-Sophie; Laziz, Iman; Djeghloul, Dounia; Lécolle, Sylvie; Bertrand, Anne T; Biondi, Olivier; De Windt, Leon J; Chanoine, Christophe



Estrogen replacement and skeletal muscle: mechanisms and population health.  


There is a growing body of information supporting the beneficial effects of estrogen and estrogen-based hormone therapy (HT) on maintenance and enhancement of muscle mass, strength, and connective tissue. These effects are also evident in enhanced recovery from muscle atrophy or damage and have significant implications particularly for the muscular health of postmenopausal women. Evidence suggests that HT will also help maintain or increase muscle mass, improve postatrophy muscle recovery, and enhance muscle strength in aged females. This is important because this population, in particular, is at risk for a rapid onset of frailty. The potential benefits of estrogen and HT relative to skeletal muscle function and composition combined with other health-related enhancements associated with reduced risk of cardiovascular events, overall mortality, and metabolic dysfunction, as well as enhanced cognition and bone health cumulate in a strong argument for more widespread and prolonged consideration of HT if started proximal to menopausal onset in most women. Earlier reports of increased health risks with HT use in postmenopausal women has led to a decline in HT use. However, recent reevaluation regarding the health effects of HT indicates a general lack of risks and a number of significant health benefits of HT use when initiated at the onset of menopause. Although further research is still needed to fully delineate its mechanisms of action, the general use of HT by postmenopausal women, to enhance muscle mass and strength, as well as overall health, with initiation soon after the onset of menopause should be considered. PMID:23869062

Tiidus, Peter M; Lowe, Dawn A; Brown, Marybeth



Epigenetic drugs in the treatment of skeletal muscle atrophy  

PubMed Central

Purpose of review A dynamic network of anabolic and catabolic pathways regulates skeletal muscle mass in adult organisms. Muscle atrophy is the detrimental outcome of an imbalance of this network. The purpose of this review is to provide a critical evaluation of different forms of muscle atrophy from a mechanistic and therapeutic point of view. Recent findings The identification and molecular characterization of distinct pathways implicated in the pathogenesis of muscle atrophy have revealed potential targets for therapeutic interventions. However, an effective application of these therapies requires a better understanding of the relative contribution of these pathways to the development of muscle atrophy in distinct pathological conditions. Summary We propose that the decline in anabolic signals (‘passive atrophy’) and activation of catabolic pathways (‘active atrophy’) contribute differently to the pathogenesis of muscle atrophy associated with distinct diseases or unfavorable conditions. Interestingly, these pathways might converge on common transcriptional effectors, suggesting that an optimal intervention should be directed to targets at the chromatin level. We provide the rationale for the use of epigenetic drugs such as deacetylase inhibitors, which target multiple signaling pathways implicated in the pathogenesis of muscle atrophy.

Guasconi, Valentina; Puri, Pier Lorenzo



Fuel economy in food-deprived skeletal muscle: signaling pathways and regulatory mechanisms  

Microsoft Academic Search

Energy deprivation poses a tremendous challenge to skeletal muscle. Glucose (ATP) depletion causes muscle fibers to undergo rapid adaptive changes toward the use of fatty acids (instead of glucose) as fuel. Physiological situations involving energy depriva- tion in skeletal muscle include exercise and fasting. A vast body of evidence is available on the signaling pathways that lead to structural\\/metabolic changes

Pieter de Lange; Maria Moreno; Elena Silvestri; Assunta Lombardi; Fernando Goglia; Antonia Lanni



Skeletal Muscle Stem Cells Do Not Transdifferentiate Into Cardiomyocytes After Cardiac Grafting  

Microsoft Academic Search

Skeletal muscle cell-derived grafts in the heart may benefit myocardial performance after infarction. Several studies have suggested that skeletal muscle stem cells (satellite cells) from adult muscle undergo transdifferentiation into cardiomyocytes after grafting into the heart, but expression of cardiac markers in graft cells has not been rigorously confirmed. To determine the fate of satellite cell-derived grafts in the heart,

Hans Reinecke; Veronica Poppa; Charles E. Murry



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



Skeletal Muscle Resting Membrane Potential in Potassium Deficiency  

PubMed Central

The resting transmembrane potential of skeletal muscle (Em) is thought to be a function of the ratio of intracellular to extracellular potassium concentration ([Ki]/[Ko]). In potassium deficiency, the fall of [Ki] is proportionately less than the fall of [Ko], thus theoretically predicting a rise of Em. To examine this theory and to characterize Em in kaliopenic myopathy, muscle composition and Em were measured during moderate (n = 5) and severe (n = 11) K deficiency in the dog and compared with measurements in the severely K-deficient rat (n = 10). Mean measured Em rose during moderate K deficiency in four of five dogs (-85.4 to -94.6 mV) and during severe K deficiency in the rat (-89.1 to -94.9 mV). Both values closely approximated the increase in Em predicted by the Goldman equation. In contrast, during severe K deficiency in the dog, a significant decline (P < 0.001) of mean Em to -55 mV was observed. Since skeletal myopathy and paralysis do not occur in the rat as a consequence of K deficiency, the observation that Em falls as paralysis occurs in the unexercised dog suggests that alteration of muscle membrane function may play a role in kaliopenic myopathy. Such an event could explain the ease with which frank muscle necrosis may be induced by exercise in the K-deficient dog.

Bilbrey, Gordon L.; Herbin, Luis; Carter, Norman W.; Knochel, James P.



Diffusional anisotropy is induced by subcellular barriers in skeletal muscle.  


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 have regions of very homogeneous fiber type. Fish were cold-acclimated (5 degrees C) to amplify the contrast between red and white fibers. Apparent diffusion coefficients, D, were measured axially, D(axially) and radially, D(radially), in small muscle strips over a time course ranging from 12 to 700 ms. Radial diffusion was strongly time dependent in both fiber types, and D decreased with time until a steady-state value was reached at a diffusion time approximately 100 ms. Diffusion was also highly anisotropic, with D(axially) being higher than D(radially) for all time points. The time scale over which changes in D(radially) occurred indicated that the observed anisotropy was not a result of interactions with the thick and thin filament lattice of actin and myosin or restriction within the cylindrical sarcolemma, as has been previously suggested. Rather, the sarcoplasmic reticulum (SR) and mitochondria appear to be the principal intracellular structures that inhibit mobility in an orientation-dependent manner. This work is the first example of diffusional anisotropy induced by readily identifiable intracellular structures. PMID:10195323

Kinsey, S T; Locke, B R; Penke, B; Moerland, T S



Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise.  


High-performance physical activity and postexercise recovery lead to significant changes in amino acid and protein metabolism in skeletal muscle. Central to these changes is an increase in the metabolism of the BCAA leucine. During exercise, muscle protein synthesis decreases together with a net increase in protein degradation and stimulation of BCAA oxidation. The decrease in protein synthesis is associated with inhibition of translation initiation factors 4E and 4G and ribosomal protein S6 under regulatory controls of intracellular insulin signaling and leucine concentrations. BCAA oxidation increases through activation of the branched-chain alpha-keto acid dehydrogenase (BCKDH). BCKDH activity increases with exercise, reducing plasma and intracellular leucine concentrations. After exercise, recovery of muscle protein synthesis requires dietary protein or BCAA to increase tissue levels of leucine in order to release the inhibition of the initiation factor 4 complex through activation of the protein kinase mammalian target of rapamycin (mTOR). Leucine's effect on mTOR is synergistic with insulin via the phosphoinositol 3-kinase signaling pathway. Together, insulin and leucine allow skeletal muscle to coordinate protein synthesis with physiological state and dietary intake. PMID:16424142

Norton, Layne E; Layman, Donald K



Membrane glycoproteins of differentiating skeletal muscle cells  

SciTech Connect

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

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



Real-time measurement of nitric oxide in single mature mouse skeletal muscle fibres during contractions  

PubMed Central

Nitric oxide (NO) is thought to play multiple roles in skeletal muscle including regulation of some adaptations to contractile activity, but appropriate methods for the analysis of intracellular NO activity are lacking. In this study we have examined the intracellular generation of NO in isolated single mature mouse skeletal muscle fibres at rest and following a period of contractile activity. Muscle fibres were isolated from the flexor digitorum brevis muscle of mice and intracellular NO production was visualized in real-time using the fluorescent NO probe 4-amino-5-methylamino-2?;,7?;-difluorofluorescein diacetate (DAF-FM DA). Some leakage of DAF-FM was apparent from fibres loaded with the probe, but they retained sufficient probe to respond to changes in intracellular NO following addition of the NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC-7) up to 30 min after loading. Electrically stimulated contractions in isolated fibres increased the rate of change in DAF-FM fluorescence by ?48% compared to non-stimulated fibres (P < 0.05) and the rate of change in DAF-FM fluorescence in the stimulated fibres returned to control values by 5 min after contractions. Treatment of isolated fibres with the NO synthase inhibitors NG-nitro-l-arginine methyl ester hydrochloride (l-NAME) or NG-monomethyl-l-arginine (l-NMMA) reduced the increase in DAF-FM fluorescence observed in response to contractions of untreated fibres. Treatment of fibres with the cell-permeable superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulphonic acid (Tiron) also reduced the increase in fluorescence observed during contractions suggesting that superoxide, or more probably peroxynitrite, contributes to the fluorescence observed. Thus this technique can be used to examine NO generation in quiescent and contracting skeletal muscle fibres in real time, although peroxynitrite and other reactive nitrogen species may potentially contribute to the fluorescence values observed.

Pye, Deborah; Palomero, Jesus; Kabayo, Tabitha; Jackson, Malcolm J



Rapid induction of REDD1 expression by endurance exercise in rat skeletal muscle.  


An acute bout of exercise induces repression of protein synthesis in skeletal muscle due in part to reduced signaling through the mammalian target of rapamycin complex 1 (mTORC1). Previous studies have shown that upregulated expression of regulated in DNA damage and development (REDD) 1 and 2 is an important mechanism in the regulation of mTORC1 activity in response to a variety of stresses. This study investigated whether induction of REDD1/2 expression occurs in rat skeletal muscle in response to a burst of endurance exercise. In addition, we determined if ingestion of glucose or branched chain amino acids (BCAA) before exercise changes the expression of REDD1/2 in muscle. Rats ran on a motor-driven treadmill at a speed of 28 mmin(-1) for 90 min, and then the gastrocnemius muscle was removed and analyzed for phosphorylation of the eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1) and expression of REDD1/2. Exercise repressed the mTORC1-signaling pathway regardless of the ingestion of nutrients before the exercise, as shown by dephosphorylation of 4E-BP1. In addition, exercise induced the expression of REDD1 mRNA (?8-fold) and protein (?3-fold). Exercise-induced expression of REDD1 was not affected by the ingestion of glucose or BCAA. Expression of REDD2 mRNA was not altered by either exercise or nutrients. These findings indicated that enhanced expression of REDD1 may be an important mechanism that could partially explain the downregulation of mTORC1 signaling, and subsequent inhibition of protein synthesis in skeletal muscle during exercise. PMID:21272563

Murakami, Taro; Hasegawa, Kazuya; Yoshinaga, Mariko



Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes  

Microsoft Academic Search

BACKGROUND: Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. METHODS: Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx5cv); (H1) biopsied human quadriceps from controls

Alvin T Kho; Peter B Kang; Isaac S Kohane; Louis M Kunkel



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



Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression  

PubMed Central

Infection by Trichinella spiralis causes a variety of changes in skeletal muscle cells including the hypertrophy of nuclei and decreased expression of muscle specific proteins. Potential cellular processes leading to these changes were investigated. In synchronized muscle infections, [3H]thymidine was incorporated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected cell up to 60 days post infection and appear to originate from differentiated skeletal muscle nuclei present at the time of infection. These nuclei were further shown to contain a mean DNA content of approximately 4N, indicating that the [3H]thymidine uptake reflects DNA synthesis and subsequent long-term suspension of the infected cell in the cell cycle at G2/M. Associated with these changes, muscle specific gene transcripts were reduced to < 1- < 0.1% in the infected cell compared to normal muscle. Transcript levels of the muscle transcriptional regulatory factors myogenin, MyoD1, and Id were reduced to < 10, < 1, and increased approximately 250%, respectively, in the infected cell compared to normal muscle, indicating transcriptional inactivation of muscle genes. DNA synthesis in the infected cell may represent the initiation event which leads to expression of this infected cell phenotype.



Detection of enterovirus in human skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects  

Microsoft Academic Search

Enterovirus RNA has been found previously in specimens of muscle biopsy from patients with idiopathic dilated cardiomyopathy, chronic in- flammatory muscle diseases, and fibromyalgia or chronic fatigue syndrome (fibromyalgia\\/chronic fatigue syndrome). These results suggest that skeletal muscle may host enteroviral persistent infection.Totestthishypothesis,weinvestigated by reverse transcription-polymerase chain reac- tion (RT-PCR) assay the presence of enterovirus in skeletal muscle of patients with

Fatima Douche-Aourik; Willy Berlier; Thomas Bourlet; Rafik Harrath; Shabir Omar; Florence Grattard; Christian Denis; Bruno Pozzetto



Differential gene expression in skeletal muscle cells after membrane depolarization.  


Skeletal muscle is a highly plastic tissue with a remarkable capacity to adapt itself to challenges imposed by contractile activity. Adaptive response, that include hypertrophy and activation of oxidative mechanisms have been associated with transient changes in transcriptional activity of specific genes. To define the set of genes regulated by a depolarizing stimulus, we used 22 K mouse oligonucleotide microarrays. Total RNA from C2C12 myotubes was obtained at 2, 4, 18, and 24 h after high K+ stimulation. cDNA from control and depolarized samples was labeled with cyanine 3 or 5 dyes prior to microarray hybridization. Loess normalization followed by statistical analysis resulted in 423 differentially expressed genes using an unadjusted P-value < or = 0.01 as cut off. Depolarization affects transcriptional activity of a limited number of genes, mainly associated with metabolism, cell communication and response to stress. A number of genes related to Ca2+ signaling pathways are induced at 4 h, reinforcing the potential role of Ca2+ in early steps of signal transduction that leads to gene expression. Significant changes in the expression of molecules involved in muscle cell structure were observed; K+-depolarization increased Tnni1 and Acta1 mRNA levels in both differentiated C2C12 and rat skeletal muscle cells in primary culture. Of these two, depolarization induced slow Ca2+ transients appear to have a role only in the regulation of Tnni1 transcriptional activity. We suggest that depolarization induced expression of a small set of genes may underlie Ca2+ dependent plasticity of skeletal muscle cells. PMID:17146758

Jureti?, Nevenka; Urzúa, Ulises; Munroe, David J; Jaimovich, Enrique; Riveros, Nora



Hyperinsulinemia and skeletal muscle fatty acid trafficking.  


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

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



Changes in human skeletal muscle length during stimulated eccentric muscle actions  

Microsoft Academic Search

Following eccentric exercise, increases in muscle length alter the length-tension relation of skeletal muscle. However, its\\u000a unclear if this change occurs during eccentric exercise. Therefore, 70 eccentric actions of the knee extensors of one leg\\u000a (with superimposed electrical stimulation) were performed at 100°\\/s, from full extension to full flexion. Angle-specific eccentric\\u000a force was recorded throughout. Force decreased at all angles

Stephen J. Brown; Alan Donnelly



Smooth muscle and skeletal muscle myosins produce similar unitary forces and displacements in the laser trap.  

PubMed Central

Purified smooth muscle myosin in the in vitro motility assay propels actin filaments at 1/10 the velocity, yet produces 3-4 times more force than skeletal muscle myosin. At the level of a single myosin molecule, these differences in force and actin filament velocity may be reflected in the size and duration of single motion and force-generating events, or in the kinetics of the cross-bridge cycle. Specifically, an increase in either unitary force or duty cycle may explain the enhanced force-generating capacity of smooth muscle myosin. Similarly, an increase in attached time or decrease in unitary displacement may explain the reduced actin filament velocity of smooth muscle myosin. To discriminate between these possibilities, we used a laser trap to measure unitary forces and displacements from single smooth and skeletal muscle myosin molecules. We analyzed our data using mean-variance analysis, which does not rely on scoring individual events by eye, and emphasizes periods in the data with constant properties. Both myosins demonstrated multiple but similar event populations with discrete peaks at approximately +11 and -11 nm in displacement, and 1.5 and 3.5 pN in force. Mean attached times for smooth muscle myosin were longer than for skeletal-muscle myosin. These results explain much of the difference in actin filament velocity between these myosins, and suggest that an increased duty cycle is responsible for the enhanced force-generating capacity of smooth over skeletal-muscle myosin. Images FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8

Guilford, W H; Dupuis, D E; Kennedy, G; Wu, J; Patlak, J B; Warshaw, D M



Distinct troponin C isoform requirements in cardiac and skeletal muscle.  


The zebrafish mutant silent partner is characterized by a dysmorphic, non-contractile ventricle resulting in an inability to generate normal blood flow. We have identified the genetic lesion in the zebrafish homolog of the slow twitch skeletal/cardiac troponin C gene. Although human troponin C1 (TNNC1) is expressed in both cardiac and skeletal muscle, duplication of this gene in zebrafish has resulted in tissue-specific partitioning of troponin C expression and function. Mutation of the zebrafish paralog tnnc1a, which is expressed predominantly in the heart, results in a loss of contractility and myofibrillar organization within ventricular cardiomyocytes, while skeletal muscle remains functional and intact. We further show that defective contractility in the developing heart results in abnormal atrial and ventricular chamber morphology. Together, our results suggest that tnnc1a is required both for the function and structural integrity of the contractile machinery in cardiomyocytes, helping to clarify potential mechanisms of troponin C-mediated cardiomyopathy. PMID:20925115

Sogah, Vanessa M; Serluca, Fabrizio C; Fishman, Mark C; Yelon, Deborah L; Macrae, Calum A; Mably, John D



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



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



Constitutive Modeling of Skeletal Muscle Tissue with an Explicit Strain-Energy Function  

PubMed Central

While much work has previously been done in the modeling of skeletal muscle, no model has, to date, been developed that describes the mechanical behavior with an explicit strain-energy function associated with the active response of skeletal muscle tissue. A model is presented herein that has been developed to accommodate this design consideration using a robust dynamical approach. The model shows excellent agreement with a previously published model of both the active and passive length-tension properties of skeletal muscle.

Odegard, G.M.; Donahue, T.L. Haut; Morrow, D.A.; Kaufman, K.R.



Comparison of properties of Ca2+ release channels between rabbit and frog skeletal muscles  

Microsoft Academic Search

Biochemical investigation of Ca2+ release channel proteins has been carried out mainly with rabbit skeletal muscles, while frog skeletal muscles have been preferentially used for physiological investigation of Ca2+ release. In this review, we compared the properties of ryanodine receptors (RyR), Ca2+ release channel protein, in skeletal muscles between rabbit and frog. While the Ryr1 isoform is the main RyR

Yasuo Ogawa; Takashi Murayama; Nagomi Kurebayashi



Activation of PPAR-? in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids  

Microsoft Academic Search

Aims\\/hypothesis  GW501516, an agonist of peroxisome proliferator-activated receptor-? (PPAR-?), increases lipid combustion and exerts antidiabetic action in animals, effects which are attributed mainly to direct effects on skeletal muscle. We explored such actions further in isolated rat skeletal muscle.Materials and methods  Specimens of rat skeletal muscle were pretreated with GW501516 (0.01–30 ?mol\\/l) for 0.5, 4 or 24 h and rates of fuel metabolism were

B. Brunmair; K. Staniek; J. Dörig; Z. Szöcs; K. Stadlbauer; V. Marian; F. Gras; C. Anderwald; H. Nohl; W. Waldhäusl; C. Fürnsinn



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



Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.  


Citrulline malate (CM; CAS 54940-97-5, Stimol®) is known to limit the deleterious effect of asthenic state on muscle function, but its effect under healthy condition remains poorly documented. The aim of this longitudinal double-blind study was to investigate the effect of oral ingestion of CM on muscle mechanical performance and bioenergetics in normal rat. Gastrocnemius muscle function was investigated strictly non-invasively using nuclear magnetic resonance techniques. A standardized rest-stimulation- (5.7 min of repeated isometric contractions electrically induced by transcutaneous stimulation at a frequency of 3.3 Hz) recovery-protocol was performed twice, i.e., before (t(0)-24 h) and after (t(0)+48 h) CM (3 g/kg/day) or vehicle treatment. CM supplementation did not affect PCr/ATP ratio, [PCr], [Pi], [ATP] and intracellular pH at rest. During the stimulation period, it lead to a 23% enhancement of specific force production that was associated to significant decrease in both PCr (28%) and oxidative (32%) costs of contraction, but had no effect on the time-courses of phosphorylated compounds and intracellular pH. Furthermore, both the rate of PCr resynthesis during the post-stimulation period (VPCr(rec)) and the oxidative ATP synthesis capacity (Q(max)) remained unaffected by CM treatment. These data demonstrate that CM supplementation under healthy condition has an ergogenic effect associated to an improvement of muscular contraction efficiency. PMID:21664351

Giannesini, Benoît; Le Fur, Yann; Cozzone, Patrick J; Verleye, Marc; Le Guern, Marie-Emmanuelle; Bendahan, David



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

PubMed Central

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 [1,2-13C2]Leu and [2H5]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