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1

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

SciTech Connect

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

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

2013-10-04

2

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...

3

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

PubMed Central

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

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

2014-01-01

4

REGULATION OF CARDIAC AND SKELETAL MUSCLE PROTEIN SYNTHESIS BY INDIVIDUAL BRANCHED-CHAIN AMINO ACIDS IN NEONATAL PIGS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Skeletal muscle grows at a very rapid rate in the neonatal pig, due in part to an enhanced sensitivity of protein synthesis to the postprandial rise in amino acids. An increase in leucine alone stimulates protein synthesis in skeletal muscle of the neonatal pig; however, the effect of isoleucine and...

5

Effect of exercise and obesity on skeletal muscle amino acid uptake  

SciTech Connect

To determine if amino acid uptake by muscle of the obese Zucker rat is impaired, epitrochlearis (EPI) and soleus strip (SOL) muscles from 32 pairs of female lean (Fa/-) and obese (fa/fa) Zucker rats were incubated using ({sup 14}C){alpha}-aminoisobutyric acid (AIB). Because contractile activity also influences amino acid uptake, the effect of acute endurance exercise on amino acid uptake by skeletal muscle from lean and obese rats was also studied. Muscle wet and dry weights were similar in lean and obese rats. However, both muscle protein content and concentration from obese rats were significantly reduced. In preliminary studies, pinning EPI at resting length during incubation significantly increased AIB uptake and reduced muscle water accumulation. AIB uptake was similar in stripped and intact SOL. Lean and obese rats were studied at rest or following a 1 hr treadmill run at 8% grade Muscles were pinned, and preincubated for 30 min at 37{degree}C in Krebs Ringer bicarbonate buffer (KRB) containing 5mM glucose under 95:5 O{sub 2}/CO{sub 2}, followed by 30, 60, 120, or 180 min of incubation in KRB with 0.5 mM AIB, ({sup 14}C)-AIB to measure amino acid, and ({sup 3}H)-inulin to determine extracellular water.

Friedman, J.E.

1988-01-01

6

Effects of Parathyroid Hormone on Skeletal Muscle Protein and Amino Acid Metabolism in the Rat  

PubMed Central

Because prominent skeletal muscle dysfunction and muscle wasting are seen in both chronic uremia and in primary hyperparathyroidism, and because markedly elevated parathyroid hormone levels occur in both disorders, potential effects of parathyroid hormone on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism were studied in vitro using isolated intact rat epitrochlearis skeletal muscle preparations. Intact bovine parathyroid hormone and the synthetic 1-34 fragment of this hormone stimulated the release of alanine and glutamine from muscle of control but not from chronically uremic animals. This stimulation was dependent upon the concentration of parathyroid hormone added: At 105 ng/ml parathyroid hormone increased alanine release 84% and glutamine release 75%. Intracellular levels of alanine and glutamine were not altered by parathyroid hormone. Increasing concentrations of the 1-34 polypeptide decreased [3H]leucine incorporation into protein of muscles from both control and uremic animals. Using muscles from animals given a pulse-chase label of [guanido-14C]arginine in vivo, parathyroid hormone increased the rate of loss of 14C label from acid-precipitable protein during incubation and correspondingly increased the rate of appearance of this label in the incubation media. Parathyroid hormone increased muscle cAMP levels by 140% and cGMP levels by 185%, but had no effect on skeletal muscle cyclic nucleotide phosphodiesterase activities as assayed in vitro. Adenylyl cyclase activity in membrane preparations from control but not uremic rats was stimulated by parathyroid hormone in a concentration-dependent fashion. However, no stimulation of guanylyl cyclase activity was noted by parathyroid hormone, although stimulation by sodium azide was present. Incubation of muscles with added parathyroid hormone produced a diminished responsiveness towards epinephrine or serotonin regulation of amino acid release and cAMP formation in the presence compared to the absence of parathyroid hormone. In the absence of parathyroid hormone, detectable inhibition of alanine and glutamine release was produced by 10?9 M epinephrine, whereas in the presence of parathyroid hormone (1,000 ng/ml) inhibition of alanine and glutamine release required 10?6 M or greater epinephrine. Resistance to cyclic AMP action as well as inhibition of cyclic AMP formation by parathyroid hormone was found. Preincubation of rat sarcolemma with 1-34 parathyroid hormone produced a decreased activity of the isoproterenol-stimulable adenylyl cyclase activity but there was no apparent change in the concentration of isoproterenol required for one-half maximal and maximal stimulation of the enzyme. These findings suggest that high levels of parathyroid hormone have direct effects on skeletal muscle protein, amino acid, and cyclic nucleotide metabolism in muscle of normal but not uremic animals. Treatment with these high levels of parathyroid hormone in vitro appears to reproduce in normal muscle, the metabolic deficits and loss of hormone responsiveness observed in muscle of chronically uremic animals. It is therefore possible that direct effects of parathyroid hormone on skeletal muscle may account in part for the muscle dysfunction and wasting of primary hyperparathyroidism and chronic uremia. PMID:6306055

Garber, Alan J.

1983-01-01

7

Effect of amino acids and glucose on exercise-induced gut and skeletal muscle proteolysis in dogs  

Microsoft Academic Search

The effect of amino acid and\\/or glucose administration before and during exercise on protein metabolism in visceral tissues and skeletal muscle was examined in mongrel dogs. The dogs were subjected to treadmill running (150 minutes at 10 km\\/h and 12% incline) and intravenously infused with a solution containing amino acids and glucose (AAG), amino acids (AA), glucose (G) or saline

Koichiro Hamada; Keitaro Matsumoto; Koji Okamura; Tatsuya Doi; Kaori Minehira; Seiichi Shimizu

1999-01-01

8

Stimulation of skeletal muscle protein synthesis in neonatal pigs by long-term infusion of leucine is amino acid dependent  

Technology Transfer Automated Retrieval System (TEKTRAN)

Infusing leucine for 1 hr increases skeletal muscle protein synthesis in neonatal pigs, but this is not sustained for 2 h unless the leucine-induced fall in amino acids is prevented. We aimed to determine whether continuous leucine infusion can stimulate protein synthesis for a prolonged period whe...

9

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. PMID:24149876

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

2011-01-01

10

Free amino acids in brain, liver, and skeletal muscle tissue of voles infected with Trypanosoma brucei gambiense.  

PubMed

The concentrations of several acidic and neutral amino acids of brain, liver, and skeletal muscle were determined in field voles, Microtus montanus, and compared to values obtained from voles harboring a chronic infection of Trypanosoma brucei gambiense. All of the amino acids examined were found at comparable levels in brain tissue from both groups of animals with the exception of tyrosine, which was reduced by approximately 45% in the infected voles. Similarly, the only difference noted in liver tissue was 32% decrease of free tyrosine in the infected animals. With respect to muscle tissue, in addition to a 45% reduction of free tyrosine in the infected voles, decreases of a smaller magnitude were also noted for threonine, glutamate, and valine. The relatively specific alteration of free tyrosine concentrations in the investigated tissues of trypanosome-infected animals suggests an alteration in host metabolism of this amino acid and/or parasite utilization. PMID:338875

Newport, G R; Page, C R

1977-12-01

11

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. PMID:22338078

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

2012-01-01

12

Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle.  

PubMed Central

We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers, using stable isotopic tracers of amino acids. Calculations of muscle protein synthesis, breakdown, and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy. Insulin was infused (0.15 mU/min per 100 ml leg) into the femoral artery to increase femoral venous insulin concentration (from 10 +/- 2 to 77 +/- 9 microU/ml) with minimal systemic perturbations. Tissue concentrations of free essential amino acids decreased (P < 0.05) after insulin. The fractional synthesis rate of muscle protein (precursor-product approach) increased (P < 0.01) after insulin from 0.0401 +/- 0.0072 to 0.0677 +/- 0.0101%/h. Consistent with this observation, rates of utilization for protein synthesis of intracellular phenylalanine and lysine (arteriovenous balance approach) also increased from 40 +/- 8 to 59 +/- 8 (P < 0.05) and from 219 +/- 21 to 298 +/- 37 (P < 0.08) nmol/min per 100 ml leg, respectively. Release from protein breakdown of phenylalanine, leucine, and lysine was not significantly modified by insulin. Local hyperinsulinemia increased (P < 0.05) the rates of inward transport of leucine, lysine, and alanine, from 164 +/- 22 to 200 +/- 25, from 126 +/- 11 to 221 +/- 30, and from 403 +/- 64 to 595 +/- 106 nmol/min per 100 ml leg, respectively. Transport of phenylalanine did not change significantly. We conclude that insulin promoted muscle anabolism, primarily by stimulating protein synthesis independently of any effect on transmembrane transport. Images PMID:7860765

Biolo, G; Declan Fleming, R Y; Wolfe, R R

1995-01-01

13

Skeletal muscle stem cells.  

PubMed

Skeletal muscle satellite cells (myoblasts) are the primary stem cells of skeletal muscle which contribute to growth, maintenance, and repair of the muscles. Satellite cells are the first stem cells used for cellular cardiomyoplasty more than 20 years ago. The isolation, culture, labeling, and identification of satellite cells are described in detail here. The implantation and outcomes of cellular cardiomyoplasty using satellite cells have been summarized in the previous chapter (Chapter 1). PMID:23807783

Kao, Grace W; Lamb, Elizabeth K; Kao, Race L

2013-01-01

14

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

2003-01-01

15

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

PubMed

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

2013-01-01

16

Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated  

Technology Transfer Automated Retrieval System (TEKTRAN)

Insulin and amino acids act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the separate effects of fed levels of INS and AA on the activation of signaling components leading to tr...

17

Amino acid infusion fails to stimulate skeletal muscle protein synthesis up to one year post injury in children with severe burns  

PubMed Central

Background Burn injury results in increased skeletal muscle protein turnover, where the magnitude of protein breakdown outweighs synthesis resulting in muscle wasting. The impact of increased amino acid (AA) provision on skeletal muscle fractional synthesis rate (FSR) in severely burned patients during their convalescence after discharge from hospital is not known. Subsequently, the purpose of this study was to determine skeletal muscle FSR in response to AA infusion in severely burned pediatric patients at discharge from hospital, and at six and twelve months post injury. Methods Stable isotope infusion studies were performed in the postprandial state and during intravenous AA infusion. Skeletal muscle biopsies were obtained and isotope enrichment determined in order to calculate skeletal muscle FSR. Patients were studied at discharge from hospital (n=11), and at six (n=15), and twelve months (n=14) post injury. Results The cohorts of patients studied at each time point post injury were not different with regards to age, body mass or burn size. AA infusion failed to stimulate FSR above basal values at discharge from hospital (0.27±0.04 vs. 0.26±0.06 %·hr?1), six months post injury (0.20±0.04 vs. 0.22±0.03 %·hr?1), and twelve months post injury (0.16±0.03 vs. 0.15±0.05 %·hr?1). Daily FSR was numerically lower at six months post burn (5.51±0.79 %·day?1) and significantly (P<0.05) lower at 12 months post burn (3.67±0.65 %·day?1) relative to discharge group (6.32±1.02 %·day?1). Discussion The findings of the current study suggest that the deleterious impact of burn injury on skeletal muscle AA metabolism persists for up to one year post injury. In light of these findings, nutritional and pharmacological strategies aimed at attenuating muscle protein breakdown post burn may be a more efficacious approach to maintaining muscle mass in severely burned patients. PMID:23694875

Cotter, Matthew; Diaz, Eva C; Jennings, Kristofer; Herndon, David N; Børsheim, Elisabet

2013-01-01

18

Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs.  

PubMed

The increase in fractional rate of protein synthesis (Ks) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs also exhibit an increase in Ks with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 micromol leucine, 0.640 micromol isoleucine and 0.693 micromol valine/min.kg); (3) 18.7 micromol glucose/min.kg (to induce endogenous insulin secretion); (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine (Phe) as follows: (1) L-[1-13C]Phe; (2) L-phenyl-[ring 2H5]-alanine; (3) L-[15N]Phe; (4) L-[ring 2,6-3H]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine Ks in m. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, Ks was increased by an average of 40% at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on Ks compared with control sheep. Ks was approximately 60% greater for vastus muscle than for m. longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in Ks in muscle of growing ruminant animals. PMID:15469643

Wester, T J; Lobley, G E; Birnie, L M; Crompton, L A; Brown, S; Buchan, V; Calder, A G; Milne, E; Lomax, M A

2004-09-01

19

Expression of heat shock protein (Hsp90) paralogues is regulated by amino acids in skeletal muscle of Atlantic salmon.  

PubMed

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. PMID:24040223

Garcia de la Serrana, Daniel; Johnston, Ian A

2013-01-01

20

Skeletal muscle Ras-related GTP binding B mRNA and protein expression is increased after essential amino acid ingestion in healthy humans.  

PubMed

Essential amino acids (EAAs) are potent stimulators of mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis. However, regulators upstream of mTORC1 that are responsive to EAA availability are not well described, especially in human skeletal muscle. The purpose of this study was to determine changes in leucyl-tRNA synthetase (LARS/LARS) and Ras-related GTP binding B (RAGB/RAGB) mRNA and protein expression in healthy human skeletal muscle after acute EAA ingestion. Muscle biopsies sampled from the vastus lateralis were obtained from 13 young adults (7 males, 6 females; aged 22.9 ± 0.9 y; body mass index 21.7 ± 0.9 kg/m(2)) in the fasting state (baseline) and 1 and 3 h after EAA (13 g; 2.4 g of Leu) ingestion. Real-time quantitative polymerase chain reaction and Western blotting were used to determine changes in LARS/LARS and RAGB/RAGB mRNA and protein expression, respectively. Stable isotope tracers and gas chromatography mass spectrometry were used to determine Leu intracellular concentrations and muscle protein synthesis. EAA ingestion increased RAGB/RAGB mRNA (?60%) and protein (?100%) abundance in adult skeletal muscle (P ? 0.05). EAAs also increased muscle Leu concentrations (?130%), mTOR phosphorylation (?30%), and muscle protein synthesis (?50%; P ? 0.05) but did not alter muscle LARS/LARS abundance (P > 0.05). We conclude that acute EAA ingestion is capable of increasing RAGB expression in human skeletal muscle. Future work is needed to determine whether this adaptive response is important to promote muscle protein anabolism in humans. This trial was registered at clinicaltrials.gov as NCT01669590. PMID:25056691

Carlin, Matthew B; Tanner, Ruth E; Agergaard, Jakob; Jalili, Thunder; McClain, Donald A; Drummond, Micah J

2014-09-01

21

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

PubMed Central

Background This study was designed to evaluate the effects of hydrolyzed protein supplementation upon skeletal muscle total protein and peroxidation in rats following exhaustive swimming exercise. Methods Twenty-four rats were randomized to 4 experimental groups (n?=?6 per group): control group fed standard diet without exercise (SD), exercise (EX), exercise plus standard diet for 72 hours (EX?+?SD), and exercise plus standard diet supplemented with hydrolyzed protein (2 g/kg/d) for 72 hours (EX?+?HP). Immediately following exercise, the EX group was euthanized for collecting plasma and skeletal muscle samples. The EX?+?SD and EX?+?HP groups were fed their respective diets for 72 hour still plasma and skeletal muscle collection. Skeletal muscle samples were used to measure levels of total protein (TP), malondialdehyde (MDA), and protein carbonyl (PC). Plasma samples were used to analyze the amino acids spectrum. Results Compared with the EX?+?SD, EX?+?HP presented the significantly increased TP (P?=?0.02) and decreased MDA and PC levels (P?=?0.035). MDA was negatively correlated with the methionine levels. Moreover, EX?+?HP maintained higher levels of plasmaleucine, isoleucine, and methionine than EX?+?SD, which may be associated with the increased skeletal muscle TP levels observed (P?skeletal muscle TP and ameliorate peroxidation damage in rats subjected to exhaustive exercise stress, which may be, at least in part, related with the maintenance of plasma leucine, isoleucine, and methionine levels. PMID:24565110

2014-01-01

22

Prions in skeletal muscle.  

PubMed

Considerable evidence argues that consumption of beef products from cattle infected with bovine spongiform encephalopathy (BSE) prions causes new variant Creutzfeldt-Jakob disease. In an effort to prevent new variant Creutzfeldt-Jakob disease, certain "specified offals," including neural and lymphatic tissues, thought to contain high titers of prions have been excluded from foods destined for human consumption [Phillips, N. A., Bridgeman, J. & Ferguson-Smith, M. (2000) in The BSE Inquiry (Stationery Office, London), Vol. 6, pp. 413-451]. Here we report that mouse skeletal muscle can propagate prions and accumulate substantial titers of these pathogens. We found both high prion titers and the disease-causing isoform of the prion protein (PrP(Sc)) in the skeletal muscle of wild-type mice inoculated with either the Me7 or Rocky Mountain Laboratory strain of murine prions. Particular muscles accumulated distinct levels of PrP(Sc), with the highest levels observed in muscle from the hind limb. To determine whether prions are produced or merely accumulate intramuscularly, we established transgenic mice expressing either mouse or Syrian hamster PrP exclusively in muscle. Inoculating these mice intramuscularly with prions resulted in the formation of high titers of nascent prions in muscle. In contrast, inoculating mice in which PrP expression was targeted to hepatocytes resulted in low prion titers. Our data demonstrate that factors in addition to the amount of PrP expressed determine the tropism of prions for certain tissues. That some muscles are intrinsically capable of accumulating substantial titers of prions is of particular concern. Because significant dietary exposure to prions might occur through the consumption of meat, even if it is largely free of neural and lymphatic tissue, a comprehensive effort to map the distribution of prions in the muscle of infected livestock is needed. Furthermore, muscle may provide a readily biopsied tissue from which to diagnose prion disease in asymptomatic animals and even humans. PMID:11904434

Bosque, Patrick J; Ryou, Chongsuk; Telling, Glenn; Peretz, David; Legname, Giuseppe; DeArmond, Stephen J; Prusiner, Stanley B

2002-03-19

23

Calcium Channels from Cyprinus Carpio Skeletal Muscle  

Microsoft Academic Search

The complete amino acid sequence of the L-type calcium channel alpha_1 subunit from the carp (Cyprinus carpio) white skeletal muscle was deduced by cDNA cloning and sequence analysis. The open reading frame encodes 1852 amino acids (M_r 210,060). A 155-amino acid COOH-terminal sequence (after the fourth internal repeat) is evolutionarily preserved (90% homology) and may represent an important functional domain

Manfred Grabner; Klaus Friedrich; Hans-Gunther Knaus; Jorg Striessnig; Fritz Scheffauer; Robert Staudinger; Walter J. Koch; Arnold Schwartz; Hartmut Glossman

1991-01-01

24

Skeletal muscle relaxant ingestion.  

PubMed

We retrospectively analyzed 56 consecutive cases involving acute skeletal muscle relaxant exposure that were reported to the Poison Control Center over a 1-year period. The age range was 9 mo to 56 years (mean 18.9 +/- 13.1) with the site of exposure being the primary residence in 54 cases (96.4%). The reasons for inquiry to the Poison Center were reported to be intentional suicide in 26 cases (46.4%), accidental in 21 cases (37.5%), with intentional misuses in 5 cases (8.9%). No deaths were reported. Eighteen cases (32.1%) were reported with co-ingestants (average number of substances taken was 2.7 +/- 0.8). Of these cases 3 patients (16.7%) had major effects with life-threatening symptoms with 6 (33.3%) patients having no symptoms. Of the remaining 38 cases, 17 (44.7%) wer cyclobenzaprine, 6 (15.8%) were methocarbamol, 5 (13.2%) were carisoprodol, 5 (13.2%) were chlorzoxazone, 3 (7.89%) were Baclofen and the remainder were either life-threatening symptoms (2.6%), while 29 (74.3%) had no or minor effects with symptoms that subsided. We conclude that morbidity and mortality are low in pure skeletal muscle relaxant ingestion, however it may be increased in multiple ingestions. PMID:2327059

Lebby, T I; Dugger, K; Lipscomb, J W; Leikin, J B

1990-04-01

25

Skeletal Muscle Alpha-Actin Diseases  

Microsoft Academic Search

Skeletal muscle ?-actin is the principal protein component of the adult skeletal muscle thin filament. The interaction between\\u000a skeletal, muscle ?-actin and the various myosin heavy chain proteins in the different muscle fibre types generates the force\\u000a of muscle contraction. Skeletal muscle ?-alpha actin is thus of fundamental importance to normal muscle contraction. To date\\u000a over 140 different disease-causing mutations

Kathryn N. North; Nigel G. Laing

26

The Catalytic Subunit of the System L1 Amino Acid Transporter (Slc7a5) Facilitates Nutrient Signalling in Mouse Skeletal Muscle  

PubMed Central

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/?) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ?40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass. PMID:24586861

Poncet, Nadège; Mitchell, Fiona E.; Ibrahim, Adel F. M.; McGuire, Victoria A.; English, Grant; Arthur, J. Simon C; Shi, Yun-Bo; Taylor, Peter M.

2014-01-01

27

Skeletal muscle involvement in cardiomyopathies.  

PubMed

The link between heart and skeletal muscle disorders is based on similar molecular, anatomical and clinical features, which are shared by the 'primary' cardiomyopathies and 'primary' neuromuscular disorders. There are, however, some peculiarities that are typical of cardiac and skeletal muscle disorders. Skeletal muscle weakness presenting at any age may indicate a primary neuromuscular disorder (associated with creatine kinase elevation as in dystrophinopathies), a mitochondrial disease (particularly if encephalopathy, ocular myopathy, retinitis, neurosensorineural deafness, lactic acidosis are present), a storage disorder (progressive exercise intolerance, cognitive impairment and retinitis pigmentosa, as in Danon disease), or metabolic disorders (hypoglycaemia, metabolic acidosis, hyperammonaemia or other specific biochemical abnormalities). In such patients, skeletal muscle weakness usually precedes the cardiomyopathy and dominates the clinical picture. Nevertheless, skeletal involvement may be subtle, and the first clinical manifestation of a neuromuscular disorder may be the occurrence of heart failure, conduction disorders or ventricular arrhythmias due to cardiomyopathy. ECG and echocardiogram, and eventually, a more detailed cardiovascular evaluation may be required to identify early cardiac involvement. Paediatric and adult cardiologists should be proactive in screening for neuromuscular and related disorders to enable diagnosis in probands and evaluation of families with a focus on the identification of those at risk of cardiac arrhythmia and emboli who may require specific prophylactic treatments, for example, pacemaker, implantable cardioverter-defibrillator and anticoagulation. PMID:24149064

Limongelli, Giuseppe; D'Alessandro, Raffaella; Maddaloni, Valeria; Rea, Alessandra; Sarkozy, Anna; McKenna, William J

2013-12-01

28

Current Topics for Teaching Skeletal Muscle Physiology  

NSDL National Science Digital Library

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

Susan V. Brooks (University of Michigan)

2003-12-01

29

Tropomyosins in Skeletal Muscle Diseases  

Microsoft Academic Search

A number of congenital muscle diseases and disorders are caused by mutations in genes that encode the proteins present in\\u000a or associated with the thin filaments of the muscle sarcomere.1 These genes include ?-skeletal actin (ACTA1), ?-tropomyosin (TPM2), ?-tropomyosin slow (TPM3), nebulin (NEB), troponin I fast (TNNI2), troponin T slow (TNNT1), troponin T fast (TNNT3) and cofilin (CFL2). Mutations in

Anthony J. Kee; Edna C. Hardeman

30

Skeletal muscle cellularity and expression of myogenic regulatory factors and myosin heavy chains in rainbow trout (Oncorhynchus mykiss): effects of changes in dietary plant protein sources and amino acid profiles.  

PubMed

The nutritional regulation of skeletal muscle growth is very little documented in fish. The aim of the study presented here was to determine how changes in dietary plant protein sources and amino acid profiles affect the muscle growth processes of fish. Juvenile rainbow trout (Oncorhynchys mykiss) were fed two diets containing fish meal and a mixture of plant protein sources either low (control diet) or rich in soybean meal (diet S). Both diets were supplemented with crystalline indispensable amino acids (IAA) to match the rainbow trout muscle IAA profile. Diet S was also supplemented with glutamic acid, an AA present in high quantities in trout muscle. Rainbow trout fed diets C and S were not significantly different in terms of overall somatic growth or daily nitrogen gain, although their parameters of dietary protein utilisation differed. Distribution of skeletal white muscle fibre diameter and expression of certain selected muscle genes were also affected by dietary changes. In the white muscle, diet S led to a significant decrease (x0.9) in the mean and median diameters of muscle fibres, to a significant decrease (x0.6) in the expression of MyoD and to a significant increase (x1.7) in the expression of fast-MHC, with no significant changes in myogenin expression. There was no change in the expression of the genes analysed in lateral red muscle (MyoD, MyoD2, myogenin and slow-MHC). These results demonstrated that changes occurred in skeletal white muscle cellularity and expression of MyoD and fast-MHC, although overall growth and protein accretion were not modified, when a diet rich in soybean meal and glutamic acid was ingested. Present findings also indicated that the white and red muscles of rainbow trout are differently affected by nutritional changes. PMID:20434580

Alami-Durante, H; Wrutniak-Cabello, C; Kaushik, S J; Médale, F

2010-08-01

31

Tropomyosins in skeletal muscle diseases.  

PubMed

A number of congenital muscle diseases and disorders are caused by mutations in genes that encode the proteins present in or associated with the thin filaments of the muscle sarcomere. These genes include alpha-skeletal actin (ACTA1), beta-tropomyosin (TPM2), alpha-tropomyosin slow (TPM3), nebulin (NEB), troponin I fast (TNNI2), troponin T slow (TNNT1), troponin T fast (TNNT3) and cofilin (CFL2). Mutations in two of the four tropomyosin (Tm) genes, TPM2 and TPM3, result in at least three different skeletal muscle diseases and one disorder as distinguished by the presence of specific clinical features and/or structural abnormalities--nemaline myopathy (TPM2 and TPM3), distal arthrogryposis (TPM2), cap disease (TPM2) and congenital fiber type disproportion (TPM3). These diseases have overlapping clinical features and pathologies and there are cases of family members who have the same mutation, but different diseases (Table 1). The relatively recent discovery of nonmuscle or cytoskeletal Tms in skeletal muscle adds to this complexity since it is now possible that a disease-causing mutation could be in a striated isoform and a cytoskeletal isoform both present in muscle. PMID:19209820

Kee, Anthony J; Hardeman, Edna C

2008-01-01

32

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”. PMID:23858303

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

2013-01-01

33

Skeletal muscle satellite cells  

NASA Technical Reports Server (NTRS)

Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form of control is to determine which of the many growth factors that can alter satellite cell behavior in vitro are at work in vivo. Little work has been done to determine what controls are at work after a regeneration response has been initiated. It seems likely that, after injury, growth factors are liberated through proteolytic activity and initiate an activation process whereby cells enter into a proliferative phase. After myofibers are formed, it also seems likely that satellite cell behavior is regulated through diffusible factors arising from the fibers rather than continuous control by circulating factors.(ABSTRACT TRUNCATED AT 400 WORDS).

Schultz, E.; McCormick, K. M.

1994-01-01

34

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

PubMed

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

2009-03-01

35

Signaling pathways controlling skeletal muscle mass  

PubMed Central

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

Egerman, Marc A.

2014-01-01

36

STRUCTURE OF SKELETAL MUSCLE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46 Structure of an Individual Muscle Fiber . . . . . . . . . . . . . . . . . . . . .  

E-print Network

STRUCTURE OF SKELETAL MUSCLE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46 Structure of an Individual Muscle Fiber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46 The Connective Tissue System within the Muscle Belly

Cooper, Robin L.

37

Skeletal muscle: microcirculatory adaptation to metabolic demand  

Microsoft Academic Search

HEPPLE, R. T. Skeletal muscle: microcirculatory adaptation to metabolic demand. Med. Sci. Sports Exerc., Vol. 32, No. 1, pp. 117-123, 2000. The issue of whether skeletal muscle is master or slave of the cardiovascular system depends on frame of reference. Acute manipulations of convective O2 delivery clearly show that O2 supply sets the upper limit of muscle VO2max. However, studies

RUSSELL T. HEPPLE

2000-01-01

38

Effects on skeletal muscle amino acids and whole body nitrogen metabolism of total parenteral nutrition following laparoscopic cholecystectomy and given to healthy volunteers.  

PubMed

In this descriptive study total parenteral nutrition (TPN) without glutamine was administered over 2 days to patients undergoing laparoscopic cholecystectomy (n = 8) and to volunteers (n = 8). Effects on muscle amino acids and nitrogen economy were studied. Muscle protein synthesis, determined by ribosome and polyribosome concentrations were measured in the patients. In both patients and volunteers the muscle amino acid patterns indicated muscle protein catabolism. Decreases in glutamine were seen in both groups (21.8 +/- 4.6% in patients and 17.5 +/- 5.4% in the volunteers). In both groups a negative nitrogen balance was seen (-4.1 +/- 1.2 gram and -10.3 +/- 2.4 gram respectively). The patients also showed decreased ribosome (by 13.7 +/- 4.5%) and polyribosome concentration (by 17.4 +/- 4.6%), indicating a decrease in muscle protein synthesis. No comparisons are made between the two groups since they are not comparable. However, it is concluded in these two descriptive studies, that during these conditions, TPN does not prevent muscle protein catabolism either during basal conditions or after a minor surgical trauma such as laparoscopic cholecystectomy. PMID:10205340

Hammarqvist, F; Jacks, J; Wernerman, J

1998-10-01

39

Increased skeletal muscle capillarization enhances insulin sensitivity.  

PubMed

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the ?1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats (n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ?40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ?24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ?30% concomitant with an ?20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes. PMID:25352432

Akerstrom, Thorbjorn; Laub, Lasse; Vedel, Kenneth; Brand, Christian Lehn; Pedersen, Bente Klarlund; Lindqvist, Anna Kaufmann; Wojtaszewski, Jørgen F P; Hellsten, Ylva

2014-12-15

40

Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice  

Microsoft Academic Search

Taurine, a sulfur-containing ?-amino acid, is highly contained in heart and skeletal muscle. Taurine has a variety of biological actions, such as ion movement, calcium handling and cytoprotection in the cardiac and skeletal muscles. Meanwhile, taurine deficiency leads various pathologies, including dilated cardiomyopathy, in cat and fox. However, the essential role of taurine depletion on pathogenesis has not been fully

Takashi Ito; Shohei Oishi; Mika Takai; Yasushi Kimura; Yoriko Uozumi; Yasushi Fujio; Stephen W Schaffer; Junichi Azuma

2010-01-01

41

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. PMID:21194022

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

2011-01-01

42

Regulation of skeletal muscle perfusion during exercise  

NASA Technical Reports Server (NTRS)

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

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

1998-01-01

43

Skeletal Muscle Autophagy: A New Metabolic Regulator  

PubMed Central

Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Proper autophagic flux is vital for both functional skeletal muscle, which controls support and movement of the skeleton, and muscle metabolism. The role of autophagy as a metabolic regulator in muscle has been previously studied; however, the underlying molecular mechanisms that control autophagy in skeletal muscle have only just begun to emerge. Here, we review recent literature on the molecular pathways controlling skeletal muscle autophagy, and discuss how they connect autophagy to metabolic regulation. We also focus on the implications these studies hold for understanding metabolic and muscle wasting diseases. PMID:24182456

Neel, Brian A.; Lin, Yuxi; Pessin, Jeffrey E.

2013-01-01

44

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. PMID:23386981

Porter, Craig; Hurren, Nicholas M; Herndon, David N; Børsheim, Elisabet

2013-01-01

45

Skeletal muscle mitochondria: the aerobic gate?  

PubMed

At an animal's maximum aerobic capacity (VO2max), the O2 flowing through the respiratory system is consumed by a functionally exclusive sink, skeletal muscle mitochondria. Thus, O2 consumption will never exceed the muscles O2 demand. If the system is ideally designed, structures upstream to the skeletal muscle O2 sink must be built to insure adequate O2 delivery to the working muscle. There are a number of structure-function solutions available to supply the demanded O2 to the muscle; these have been found to vary, often ontogenetically, with hypoxia, training, etc. But there is one relationship that is invariant: Total O2 uptake can be predicted by the total (active) skeletal muscle mitochondrial volume. In aerobic and sedentary animals, across a range of body sizes, maximum (in vivo) mitochondrial O2 consumption is constant among mammals (at approximately 2000 O2 molecules per square micron of inner mitochondrial membrane per second). Because the volume of mitochondria is one of the most plastic of all respiratory structures, we interpret this relationship as suggesting that skeletal muscle mitochondria alone sets the demand for O2 and, thus, the volume of skeletal muscle mitochondria dictates an animal's maximum aerobic capacity. PMID:3289318

Lindstedt, S L; Wells, D J

1988-01-01

46

Space travel directly induces skeletal muscle atrophy  

NASA Technical Reports Server (NTRS)

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

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

1999-01-01

47

Cardiac assistance from skeletal muscle: a reappraisal.  

PubMed

Cardiac assistance from skeletal muscle offers an attractive surgical solution to the problem of end-stage heart failure, yet it is widely regarded as a failed approach. I argue here that this is an outdated assessment. Systematic progress has been made over the last 25 years in understanding the relevant basic science. In the light of these advances we should be reconsidering the place of skeletal muscle assist in the surgical armamentarium. PMID:18954996

Salmons, Stanley

2009-02-01

48

RESEARCH Open Access Dystrophin deficiency exacerbates skeletal muscle  

E-print Network

RESEARCH Open Access Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin globular domains. The absence of dystrophin disrupts this link, leading to compromised muscle sarcolemmal of damaged sarcolemma in skeletal muscle. Because dysferlin and dystrophin play different roles

Campbell, Kevin P.

49

How sex hormones promote skeletal muscle regeneration.  

PubMed

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

Velders, Martina; Diel, Patrick

2013-11-01

50

Aspects of skeletal muscle modelling.  

PubMed Central

The modelling of skeletal muscle raises a number of philosophical questions, particularly in the realm of the relationship between different possible levels of representation and explanation. After a brief incursion into this area, a list of desiderata is proposed as a guiding principle for the construction of a viable model, including: comprehensiveness, soundness, experimental consistency, predictive ability and refinability. Each of these principles is illustrated by means of simple examples. The presence of internal constraints, such as incompressibility, may lead to counterintuitive results. A one-panel example is exploited to advocate the use of the principle of virtual work as the ideal tool to deal with these situations. The question of stability in the descending limb of the force-length relation is addressed and a purely mechanical analogue is suggested. New experimental results confirm the assumption that fibre stiffness is positive even in the descending limb. The indeterminacy of the force-sharing problem is traditionally resolved by optimizing a, presumably, physically meaningful target function. After presenting some new results in this area, based on a separation theorem, it is suggested that a more fundamental approach to the problem is the abandoning of optimization criteria in favour of an explicit implementation of activation criteria. PMID:14561335

Epstein, Marcelo; Herzog, Walter

2003-01-01

51

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

PubMed Central

Cultured embryonic and adult skeletal muscle cells have a number of different uses. The micro-dissected explants technique described in this chapter is a robust and reliable method for isolating relatively large numbers of proliferative skeletal muscle cells from juvenile, adult or embryonic muscles as a source of skeletal muscle stem cells. The authors have used micro-dissected explant cultures to analyse the growth characteristics of skeletal muscle cells in wild-type and dystrophic muscles. Each of the components of tissue growth, namely cell survival, proliferation, senescence and differentiation can be analysed separately using the methods described here. The net effect of all components of growth can be established by means of measuring explant outgrowth rates. The micro-explant method can be used to establish primary cultures from a wide range of different muscle types and ages and, as described here, has been adapted by the authors to enable the isolation of embryonic skeletal muscle precursors. Uniquely, micro-explant cultures have been used to derive clonal (single cell origin) skeletal muscle stem cell (SMSc) lines which can be expanded and used for in vivo transplantation. In vivo transplanted SMSc behave as functional, tissue-specific, satellite cells which contribute to skeletal muscle fibre regeneration but which are also retained (in the satellite cell niche) as a small pool of undifferentiated stem cells which can be re-isolated into culture using the micro-explant method. PMID:20972391

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

2010-01-01

52

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

53

Space travel directly induces skeletal muscle atrophy  

Microsoft Academic Search

Space travel causes rapid and pro- nounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To de- velop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and\\/or by a direct effect on

HERMAN VANDENBURGH; JOSEPH CHROMIAK; JANET SHANSKY; MICHAEL DEL TATTO; JULIE LEMAIRE

54

Sex hormones and skeletal muscle weakness.  

PubMed

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

2013-06-01

55

Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation*  

PubMed Central

During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics of protein secretion. We identified and quantitatively analyzed 635 secreted proteins, including 35 growth factors, 40 cytokines, and 36 metallopeptidases. The extensive presence of these proteins that can act as potent signaling mediators to other cells and tissues strongly highlights the important role of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188 of these secreted proteins to be significantly regulated during the process of myogenesis. Comparative analyses of selected secreted proteins revealed little correlation between their mRNA and protein levels, indicating pronounced regulation by posttranscriptional mechanisms. Furthermore, analyses of the intracellular levels of members of the semaphorin family and their corresponding secretion dynamics demonstrated that the release of secreted proteins is tightly regulated by the secretory pathway, the stability of the protein, and/or the processing of secreted proteins. Finally, we provide 299 unique hydroxyproline sites mapping to 48 distinct secreted proteins and have discovered a novel hydroxyproline motif. PMID:20631206

Henningsen, Jeanette; Rigbolt, Kristoffer T. G.; Blagoev, Blagoy; Pedersen, Bente Klarlund; Kratchmarova, Irina

2010-01-01

56

Leucine stimulation of skeletal muscle protein synthesis  

SciTech Connect

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

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

1986-03-01

57

Skeletal muscle pathology in Huntington's disease  

PubMed Central

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a polyglutamine stretch within the huntingtin protein (HTT). The neurological symptoms, that involve motor, cognitive and psychiatric disturbances, are caused by neurodegeneration that is particularly widespread in the basal ganglia and cereberal cortex. HTT is ubiquitously expressed and in recent years it has become apparent that HD patients experience a wide array of peripheral organ dysfunction including severe metabolic phenotype, weight loss, HD-related cardiomyopathy and skeletal muscle wasting. Although skeletal muscles pathology became a hallmark of HD, the mechanisms underlying muscular atrophy in this disorder are unknown. Skeletal muscles account for approximately 40% of body mass and are highly adaptive to physiological and pathological conditions that may result in muscle hypertrophy (due to increased mechanical load) or atrophy (inactivity, chronic disease states). The atrophy is caused by degeneration of myofibers and their replacement by fibrotic tissue is the major pathological feature in many genetic muscle disorders. Under normal physiological conditions the muscle function is orchestrated by a network of intrinsic hypertrophic and atrophic signals linked to the functional properties of the motor units that are likely to be imbalanced in HD. In this article, we highlight the emerging field of research with particular focus on the recent studies of the skeletal muscle pathology and the identification of new disease-modifying treatments. PMID:25339908

Zielonka, Daniel; Piotrowska, Izabela; Marcinkowski, Jerzy T.; Mielcarek, Michal

2014-01-01

58

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

2012-07-01

59

Multiple Sclerosis Affects Skeletal Muscle Characteristics  

PubMed Central

Background The impact of multiple sclerosis (MS) on skeletal muscle characteristics, such as muscle fiber cross sectional area (CSA), fiber type proportion, muscle strength and whole muscle mass, remains conflicting. Methods In this cross sectional study, body composition and muscle strength of the quadriceps were assessed in 34 MS (EDSS: 2.5±0.19) patients and 18 matched healthy controls (HC). Hereafter a muscle biopsy (m.vastus lateralis) was taken. Results Compared to HC, mean muscle fiber CSA of all fibers, as well as CSA of type I, II and IIa fibers were smaller and muscle strength of the quadriceps was lower in MS patients. Whole body composition was comparable between groups. However, compared to HC, the biopsied leg tended to have a higher fat percentage (p?=?0.1) and a lower lean mass (p?=?0.06) in MS patients. Conclusion MS seems to negatively influence skeletal muscle fiber CSA, muscle strength and muscle mass of the lower limbs of mildly affected MS patients. This emphasises the need for rehabilitation programs focusing on muscle preservation of the lower limb. Trial Registration ClinicalTrials.gov NCT01845896 PMID:25264868

Wens, Inez; Dalgas, Ulrik; Vandenabeele, Frank; Krekels, Maartje; Grevendonk, Lotte; Eijnde, Bert O.

2014-01-01

60

Identification of amino acids associated with skeletal muscle growth in late gestation and at weaning in lambs of well-nourished sheep.  

PubMed

The objective of this study was to determine the association between intracellular free AA (FAA) profiles in skeletal muscle with muscle growth in twin and singleton fetuses in late pregnancy and at weaning, under an ad libitum feeding regime of the dam. Plasma from singleton- (n = 9) and twin-bearing (n = 10) ewes at d 140 of pregnancy and FAA in the semitendinosus muscle (STM) from the corresponding fetuses were studied. At weaning, intracellular STM FAA concentrations were compared between twins at the same age as singletons (Twin(age); n = 17) and at the same weight as singletons (Twin(wt); n = 17) to that of singletons (n = 20). Twin fetuses were 15% lighter (P = 0.03) with a 20% lighter STM (P = 0.02) compared to singletons. Maternal plasma FAA were similar (P ? 0.17) between singleton- and twin-bearing ewes. Twin fetuses had greater (P < 0.05) plasma concentrations of glutamine, histidine, and methionine and lower (P < 0.05) concentrations of aspartate, citrulline, glutamate, and ornithine compared with singletons. In fetal STM, twins had lower (P < 0.05) concentrations of aspartate and valine and greater (P < 0.01) concentration of methionine. Correlations were found between fetal STM weight and intracellular concentrations of arginine (r = 0.66, P < 0.01) and glutamine (r = 0.49, P < 0.01). Compared to singletons at weaning, Twin(age) were 16% lighter (P < 0.01) and the STM weight was proportionately 16% lighter (P < 0.01). For Twin(wt), the magnitude of the difference for STM weight was reduced to 8% lighter (P = 0.02). Compared to singletons, Twin(age) lambs had greater (P < 0.05) intracellular concentrations of glutamine, histidine, threonine, asparagine, alanine, serine, and glutamate but reduced taurine. The differences in FAA concentrations were less between Twin(wt) and singletons than between Twin(age) and singletons. Positive correlations were found between leucine, lysine, methionine, phenylalanine, proline, threonine, and tyrosine muscle concentration and STM weight at weaning. Males differed from females in intracellular FAA both in late pregnancy and at weaning. Twins had reduced RNA content during pregnancy and at weaning, suggesting a lower capacity for protein accretion. These data suggest that specific FAA concentrations are associated with differences in muscle growth during late pregnancy, notably arginine and glutamine, and reduced protein synthesis capacity. However, the relevance of specific FAA varies according to stage of development and sex of the lamb. PMID:25349352

Sales, F A; Pacheco, D; Blair, H T; Kenyon, P R; Nicholas, G; Senna Salerno, M; McCoard, S A

2014-11-01

61

Gene Regions Responding to Skeletal Muscle Atrophy  

NASA Technical Reports Server (NTRS)

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

Booth, Frank W.

1997-01-01

62

Role of skeletal muscle in lung development.  

PubMed

Skeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia. We employed various genetically engineered mice lacking different groups of respiratory muscles or lacking all the skeletal muscle and established the criteria for pulmonary hypoplasia in mice, and therefore established a mouse model for this disease. We followed up this discovery with systematic subtractive microarray analysis approach and revealed novel functions in lung development and disease for several molecules. We believe that our approach combines elements of both in vivo and in vitro approaches and allows us to study the function of a series of molecules in the context of lung development and disease and, simultaneously, in the context of lung's dependence on skeletal muscle-executed FBMs. PMID:22648538

Baguma-Nibasheka, Mark; Gugic, Dijana; Saraga-Babic, Mirna; Kablar, Boris

2012-07-01

63

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))

1990-10-01

64

Ultrastructural Localization of Calsequestrin in Rat Skeletal Muscle by  

E-print Network

Ultrastructural Localization of Calsequestrin in Rat Skeletal Muscle by Immunoferritin Labeling. ABSTRACT The ultrastructural localization of calsequestrin in rat skeletal muscle (gracilis) was determined. The sarcoplasmic reticulum is the intracellular membrane system that, together with the transverse tubular system

Campbell, Kevin P.

65

Structural and functional roles of nebulin in skeletal muscle  

E-print Network

giant actin-binding template protein in skeletal muscle sarcomere. Interaction of actin and cloned humangiant actin-binding template protein in skeletal muscle sarcomere. Interaction of actin and cloned human

Gokhin, David Samuel

2009-01-01

66

Biofunctional hydrogels for skeletal muscle constructs.  

PubMed

Hydrogel scaffolds encapsulating C2C12 mouse skeletal muscle cells have been engineered as in vitro constructs towards regenerative medicine therapies for the enhancement and inducement of functional skeletal muscle formation. Previous work has largely involved two-dimensional (2D) muscle strips, naturally occurring hydrogels and incomplete examination of the effects of the scaffold and/or biological functionalization on myogenic differentiation in a controllable manner. The goal of this study was to identify key properties in functionalized poly(ethylene glycol) (PEG)-maleimide (MAL) synthetic hydrogels that promote cell attachment, proliferation and differentiation for the formation of multinucleated myotubes and functional skeletal muscle tissue constructs. Significant differences in myoblast viability were observed as a function of cell seeding density, polymer weight percentage and bioadhesive ligands. The identified optimized conditions for cell survival, required for myotube development, were carried over for differentiation assays. PEG hydrogels (5% weight/volume), functionalized with 2.0?mm RGD adhesive peptide and crosslinked with protease-cleavable peptides, incubated for 3?days before supplementation with 2% horse serum, significantly increased expression of differentiated skeletal muscle markers by 50%; 17% more multinucleated cells and a 40% increase in the number of nuclei/differentiated cell compared to other conditions. Functionality of cell-laden hydrogels was demonstrated by a 20% decrease in the extruded length of the hydrogel when stimulated with a contractile agent, compared to 7% for a saline control. This study provided strategies to engineer a three-dimensional (3D) microenvironment, using synthetic hydrogels to promote the development of differentiated muscle tissue from skeletal muscle progenitor cells to form contractile units. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24616405

Salimath, Apoorva S; García, Andrés J

2014-02-26

67

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

Microsoft Academic Search

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

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

2002-01-01

68

Peripheral endocannabinoids regulate skeletal muscle development and maintenance  

Microsoft Academic Search

As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interests, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of

Dongjiao Zhao

2010-01-01

69

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

PubMed Central

Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX) is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear. PMID:24936977

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

2014-01-01

70

Tissue engineering skeletal muscle for orthopaedic applications  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

71

Development of Sensory Receptors in Skeletal Muscle  

NASA Technical Reports Server (NTRS)

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

DeSantis, Mark

2000-01-01

72

[Skeletal muscle dysfunction in COPD].  

PubMed

Muscle function is frequently affected in patients with chronic obstructive pulmonary disease (COPD), influencing the symptoms and prognosis of this disease. The distribution and severity of this dysfunction are heterogeneous and therefore the main causes seem, in part, to be specific to the muscular group examined, which is the case of the overactivity and unfavorable geometry characteristic of respiratory muscles, compared with the relative inactivity of the muscles of the limbs. There are also factors that are common to all the muscles in the body. Notable among these factors are systemic inflammation, nutritional alterations, the use of certain drugs, hypoxia and the presence of comorbidity and/or advanced age. However, while the respiratory muscles show a phenotype adapted to their unfavorable situation and manage to partially compensate for this situation, the muscles of the limbs show involutive changes, which contribute to dysfunction. Therefore, although functional loss can develop in distinct muscular territories, the causes - and consequently the therapeutic approaches - differ, including nutritional support, muscle training and/or rest, depending on the muscle. PMID:20116748

Gea, Joaquim; Martínez-Llorens, Juana; Ausín, Pilar

2009-01-01

73

Gender difference of androgen actions on skeletal muscle transcriptome.  

PubMed

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), OVX+dihydrotestosterone (DHT) injection 1, 3, or 24 h before kill in mice. The 438 transcript species differentially expressed between gender showed that females had higher expression levels of mRNA related to cytoskeleton/contractile apparatus and mitochondrial processes as well as protein, lipid, and amino acid metabolisms. In females, OVX and DHT modulated 109 and 128 transcript species respectively. OVX repressed transcripts of fast/glycolytic fiber, glycolysis, and glucose transport, whereas all these effects were reversed 3 h after the DHT injection. Moreover, DHT treatment induced transcripts which reduce intracellular Ca(2+) level at early time points. These results may suggest that DHT treatment in OVX mice increases muscle contractility by affecting fiber distribution and intracellular Ca(2+) concentration as well as improving glucose metabolism. On the other hand, transcripts of fast/oxidative fiber, oxidative phosphorylation, and ATP production were repressed 24 h after DHT administration. In our previous study using male mice, transcripts in oxidative phosphorylation and ATP production were induced 24 h after DHT injection (Yoshioka M, Boivin A, Ye P, Labrie F & St-Amand J 2006 Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression. Journal of Molecular Endocrinology 36 247-259 ). These results demonstrate gender differences in DHT actions on skeletal muscle, and contribute to a precise understanding of the molecular mechanisms of androgen actions in the female skeletal muscle. PMID:17693611

Yoshioka, Mayumi; Boivin, André; Bolduc, Carl; St-Amand, Jonny

2007-08-01

74

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

Microsoft Academic Search

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

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

1987-01-01

75

Cellular Players in Skeletal Muscle Regeneration  

PubMed Central

Skeletal muscle, a tissue endowed with remarkable endogenous regeneration potential, is still under focused experimental investigation mainly due to treatment potential for muscle trauma and muscular dystrophies. Resident satellite cells with stem cell features were enthusiastically described quite a long time ago, but activation of these cells is not yet controlled by any medical interventions. However, after thorough reports of their existence, survival, activation, and differentiation there are still many questions to be answered regarding the intimate mechanism of tissue regeneration. This review delivers an up-to-date inventory of the main known key players in skeletal muscle repair, revealed by various models of tissue injuries in mechanical trauma, toxic lesions, and muscular dystrophy. A better understanding of the spatial and temporal relationships between various cell populations, with different physical or paracrine interactions and phenotype changes induced by local or systemic signalling, might lead to a more efficient approach for future therapies. PMID:24779022

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

2014-01-01

76

Skeletal muscle development in the mouse embryo.  

PubMed

In this review we discuss the recent findings concerning the mechanisms that restrict somitic cells to the skeletal muscle fate, the myogenic regulatory factors controlling skeletal muscle differentiation and specification of myogenic cell lineages, the nature of inductive signals and the role of secreted proteins in embryonic patterning of the myotome. More specifically, we review data which strongly support the hypothesis that Myf-5 plays a unique role in development of epaxial muscle, that MyoD plays a unique role in development of hypaxial muscles derived from migratory myogenic precursor cells, and that both genes are responsible for development of intercostal and abdominal muscles (hypaxial muscles that develop from the dermatomal epithelia). In addition, while discussing upstream and post-translational regulation of myogenic regulatory factors (MRFs), we suggest that correct formation of the myotome requires a complex cooperation of DNA binding proteins and cofactors, as well as inhibitory function of non-muscle cells of the forming somite, whose proteins would sequester and suppress the transcription of MRFs. Moreover, in the third part of our review, we discuss embryonic structures, secreted proteins and myogenic induction. However, although different signaling molecules with activity in the process of somite patterning have been identified, not many of them are found to be necessary during in vivo embryonic development. To understand their functions, generation of multiple mutants or conditional/tissue-specific mutants will be necessary. PMID:10809386

Kablar, B; Rudnicki, M A

2000-04-01

77

Nutritional regulation of mTOR signaling in skeletal muscle of neonates in vivo  

Technology Transfer Automated Retrieval System (TEKTRAN)

The post-prandial rise in both amino acids and insulin independently stimulate protein synthesis in the rapidly growing skeletal muscle of the neonate. Leucine, in particular, is important in mediating the response to amino acids. We have shown that a physiological rise in leucine, but not isoleuc...

78

AMINO ACIDS AUGMENT MUSCLE PROTEIN SYNTHESIS IN NEONATAL PIGS DURING ENDOTOXEMIA BY MODULATING TRANSLATION INITIATION  

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 ...

79

Role of skeletal muscle in mandible development.  

PubMed

As a continuation of the previous study on palate development (Rot and Kablar, 2013), here we explore the relationship between the secondary cartilage mandibular condyles (parts of the temporomandibular joint) and the contributions (mechanical and secretory) from the adjacent skeletal musculature. Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Among abnormal skeletal features, micrognathia (mandibular hypoplasia) was detected: small, bent and posteriorly displaced mandible. As an example of Waddingtonian epigenetics, we suggest that muscle, in addition to acting via mechanochemical signal transduction pathways, networks and promoters, also exerts secretory stimuli on skeleton. Our goal is to identify candidate molecules at that muscle-mandible interface. By employing Systematic Subtractive Microarray Analysis approach, we compared gene expression between mandibles of amyogenic and wild type mouse fetuses and we identified up- and down-regulated genes. This step was followed by a bioinformatics approach and consultation of web-accessible mouse databases. We searched for individual tissue-specific gene expression and distribution, and for the functional effects of mutations in a particular gene. The database search tools allowed us to generate a set of candidate genes with involvement in mandibular development: Cacna1s, Ckm, Des, Mir300, Myog and Tnnc1. We also performed mouse-to-human translational experiments and found analogies. In the light of our findings we discuss various players in mandibular morphogenesis and make an argument for the need to consider mandibular development as a consequence of reciprocal epigenetic interactions of both skeletal and non-skeletal compartments. PMID:24867377

Rot, Irena; Mardesic-Brakus, Snjezana; Costain, Willard J; Saraga-Babic, Mirna; Kablar, Boris

2014-11-01

80

Amino acid residues 489-503 of dihydropyridine receptor (DHPR) ?1a subunit are critical for structural communication between the skeletal muscle DHPR complex and type 1 ryanodine receptor.  

PubMed

The ?1a subunit is a cytoplasmic component of the dihydropyridine receptor (DHPR) complex that plays an essential role in skeletal muscle excitation-contraction (EC) coupling. Here we investigate the role of the C-terminal end of this auxiliary subunit in the functional and structural communication between the DHPR and the Ca(2+) release channel (RyR1). Progressive truncation of the ?1a C terminus showed that deletion of amino acid residues Gln(489) to Trp(503) resulted in a loss of depolarization-induced Ca(2+) release, a severe reduction of L-type Ca(2+) currents, and a lack of tetrad formation as evaluated by freeze-fracture analysis. However, deletion of this domain did not affect expression/targeting or density (Qmax) of the DHPR-?1S subunit to the plasma membrane. Within this motif, triple alanine substitution of residues Leu(496), Leu(500), and Trp(503), which are thought to mediate direct ?1a-RyR1 interactions, weakened EC coupling but did not replicate the truncated phenotype. Therefore, these data demonstrate that an amino acid segment encompassing sequence (489)QVQVLTSLRRNLSFW(503) of ?1a contains critical determinant(s) for the physical link of DHPR and RyR1, further confirming a direct correspondence between DHPR positioning and DHPR/RyR functional interactions. In addition, our data strongly suggest that the motif Leu(496)-Leu(500)-Trp(503) within the ?1a C-terminal tail plays a nonessential role in the bidirectional DHPR/RyR1 signaling that supports skeletal-type EC coupling. PMID:25384984

Eltit, Jose M; Franzini-Armstrong, Clara; Perez, Claudio F

2014-12-26

81

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. PMID:22175016

Barbieri, Elena; Sestili, Piero

2012-01-01

82

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. PMID:19807897

Hamilton, B

2010-01-01

83

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. PMID:23049683

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

2012-01-01

84

Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet.  

PubMed

Increased levels of plasma free amino acids (pFAAs) can disturb the blood glucose levels in patients with obesity, diabetes mellitus and metabolic syndrome (MS) and are associated with enhanced protein oxidation. Oxidation of proteins, especially in the muscles, can promote protein degradation and elevate the levels of pFAAs. Gamma-aminobutyric acid (GABA), a food additive, can reduce high-fat diet (HFD)-induced hyperglycaemia; however, the mechanisms remain unclear. The aim of this study was to evaluate the effects of GABA on protein oxidation and pFAAs changes. One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation. While medium and low doses of GABA mitigated HFD-induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders. Medium dose of GABA increased the levels of GABA, but high dose of GABA reduced the levels of plasma GABA and increased the activity of succinic semialdehyde dehydrogenase in the liver. Therefore, treatment with GABA mitigated HFD-induced hyperglycaemia probably by repairing HFD-induced muscular oxidative stress and pFAA disorders in mice. Our data also suggest that an optimal dose of GABA is crucial for the prevention of excess GABA-related decrease in the levels of pFAA and GABA as well as obesity. PMID:25266692

Xie, Z X; Xia, S F; Qiao, Y; Shi, Y H; Le, G W

2015-06-01

85

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. PMID:25098362

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

2012-01-01

86

Skeletal muscle disease: patterns of MRI appearances  

PubMed Central

Although the presumptive diagnosis of skeletal muscle disease (myopathy) may be made on the basis of clinical–radiological correlation in many cases, muscle biopsy remains the cornerstone of diagnosis. Myopathy is suspected when patients complain that the involved muscle is painful and tender, when they experience difficulty performing tasks that require muscle strength or when they develop various systemic manifestations. Because the cause of musculoskeletal pain may be difficult to determine clinically in many cases, MRI is increasingly utilised to assess the anatomical location, extent and severity of several pathological conditions affecting muscle. Infectious, inflammatory, traumatic, neurological, neoplastic and iatrogenic conditions can cause abnormal signal intensity on MRI. Although diverse, some diseases have similar MRI appearances, whereas others present distinct patterns of signal intensity abnormality. In general, alterations in muscle signal intensity fall into one of three cardinal patterns: muscle oedema, fatty infiltration and mass lesion. Because some of the muscular disorders may require medical or surgical treatment, correct diagnosis is essential. In this regard, MRI features, when correlated with clinical and laboratory findings as well as findings from other methods such as electromyography, may facilitate correct diagnosis. This article will review and illustrate the spectrum of MRI appearances in several primary and systemic disorders affecting muscle, both common and uncommon. The aim of this article is to provide radiologists and clinicians with a collective, yet succinct and useful, guide to a wide array of myopathies. PMID:22960244

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

2012-01-01

87

Effect of limb immobilization on skeletal muscle  

NASA Technical Reports Server (NTRS)

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

Booth, F. W.

1982-01-01

88

Development of Sensory Receptors in Skeletal Muscle  

NASA Technical Reports Server (NTRS)

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

DeSantis, Mark

2000-01-01

89

Role of skeletal muscle in palate development.  

PubMed

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

Rot, I; Kablar, B

2013-01-01

90

Extrarenal potassium adaptation: role of skeletal muscle  

SciTech Connect

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

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

1986-08-01

91

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

PubMed

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

2012-04-24

92

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. 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.

2012-01-01

93

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.

1986-03-01

94

Skeletal Muscle Deregulation of the ubiquitin-proteasome system  

E-print Network

Skeletal Muscle Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients Anvar et al. Anvar et al. Skeletal Muscle 2011, 1:15 http-onset progressive muscle disorder caused by a poly-alanine expansion mutation in the Poly(A) Binding Protein Nuclear

Paris-Sud XI, Université de

95

Skeletal Muscle Basement Membrane-Sarcolemma-Cytoskeleton Interaction Minireview Series*  

E-print Network

Skeletal Muscle Basement Membrane-Sarcolemma-Cytoskeleton Interaction Minireview Series* Published Center, Dallas, Texas 75390 The sarcolemma (muscle plasma membrane) plays a central role in skeletal muscle structure and function (1). In addition to the housekeeping functions of a cell plasma membrane

Campbell, Kevin P.

96

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

2012-01-01

97

Trichinella spiralis: Subversion of differentiated mammalian skeletal muscle cells  

Microsoft Academic Search

Infection by Trichinella spiralis initiates changes in terminally differentiated mammalian skeletal muscle cells that lead to host cell cycle re-entry, cell cycle arrest in apparent G2\\/M phase, the repression of differentiated skeletal muscle characteristics and the expression of a phenotype unlike other stages in the muscle lineage. Although the parasite must be involved in initiating these changes, its precise role

D. P. Jasmer

1995-01-01

98

Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension  

PubMed Central

Background Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH. Methods The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls. Results PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO2 max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output. Conclusion Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH. PMID:25460348

Breda, Ana Paula; Pereira de Albuquerque, Andre Luis; Jardim, Carlos; Morinaga, Luciana Kato; Suesada, Milena Mako; Fernandes, Caio Julio Cesar; Dias, Bruno; Lourenço, Rafael Burgomeister; Salge, Joao Marcos; Souza, Rogerio

2014-01-01

99

Estrogen receptor in bovine skeletal muscle.  

PubMed

In connection with investigations of the anabolic action of estrogens, we examined skeletal muscle of veal calves for estradiol receptors. The high speed supernatant of muscle homogenate was incubated with .5 nM 3H-estradiol and for the determination of nonspecific binding with .5 nM 3H-estradiol plus 13 nM estradiol at 0 C overnight. After treatment with charcoal two times, the supernatant was analyzed by agar gel electrophoresis. Specific binding was found in the typical position of cytosolic estradiol receptor. Ninety percent of 3H-estradiol binding was suppressed by estradiol-17 beta, zeranol, estrone or diethylstilbestrol, but was not affected by testosterone, dihydrotestosterone, trenbolone or progesterone. The specific binding activity varied between .3 and 2.0 fmol/mg protein and the dissociation constant of the receptor was Kd = 60 pM. After an enrichment up to 42 fmol/mg cytosolic protein using heparin sepharose, the receptor remained unchanged as determined by agar gel electrophoresis. Although uterine tissue generally contains 1,000 times more estradiol receptors, these results clearly demonstrate that skeletal muscle also contains estradiol receptors with identical properties. This indicates that one possible component of the anabolic action of estrogens may be the direct stimulation of the muscle via the estradiol receptor. PMID:3972749

Meyer, H H; Rapp, M

1985-01-01

100

Regenerating skeletal muscle in the face of aging and disease.  

PubMed

Skeletal muscle is a fundamental organ in the generation of force and movement, the regulation of whole-body metabolism, and the provision of resiliency. Indeed, physical medicine and rehabilitation is recognized for optimizing skeletal muscle health in the context of aging (sarcopenia) and disease (cachexia). Exercise is, and will remain, the cornerstone of therapies to improve skeletal muscle health. However, there are now a number of promising biologic and small molecule interventions currently under development to rejuvenate skeletal muscle, including myostatin inhibitors, selective androgen receptor modulators, and an activator of the fast skeletal muscle troponin complex. The opportunities for skeletal muscle-based regenerative therapies and a selection of emerging pharmacologic interventions are discussed in this review. PMID:24879554

Jasuja, Ravi; LeBrasseur, Nathan K

2014-11-01

101

Effects of regular exercise training on skeletal muscle contractile function  

NASA Technical Reports Server (NTRS)

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

Fitts, Robert H.

2003-01-01

102

Metabolic and structural impairment of skeletal muscle in heart failure  

PubMed Central

Physiologic endurance exercise performance is primarily limited by cardiac function. In patients with heart failure, there is dissociation between cardiac performance and exercise capacity, suggesting a distinct role of abnormal peripheral organ function, including skeletal muscle function. The impact of heart failure upon skeletal muscle and exercise performance will be discussed with a focus on molecular, structural, and functional derangements in skeletal muscle of patients with heart failure. PMID:23065040

Zizola, Cynthia; Schulze, P. Christian

2013-01-01

103

Skeletal Muscle Gender Dimorphism from Proteomics  

PubMed Central

Gross contraction in skeletal muscle is primarily determined by a relatively small number of contractile proteins, however this tissue is also remarkably adaptable to environmental factors1 such as hypertrophy by resistance exercise and atrophy by disuse. It thereby exhibits remodeling and adaptations to stressors (heat, ischemia, heavy metals, etc.)2,3. Damage can occur to muscle by a muscle exerting force while lengthening, the so-called eccentric contraction4. The contractile proteins can be damaged in such exertions and need to be repaired, degraded and/or resynthesized; these functions are not part of the contractile proteins, but of other much less abundant proteins in the cell. To determine what subset of proteins is involved in the amelioration of this type of damage, a global proteome must be established prior to exercise5 and then followed subsequent to the exercise to determine the differential protein expression and thereby highlight candidate proteins in the adaptations to damage and its repair. Furthermore, most studies of skeletal muscle have been conducted on the male of the species and hence may not be representative of female muscle. In this article we present a method for extracting proteins reproducibly from male and female muscles, and separating them by two-dimensional gel electrophoresis followed by high resolution digital imaging6. This provides a protocol for spots (and subsequently identified proteins) that show a statistically significant (p < 0.05) two-fold increase or decrease, appear or disappear from the control state. These are then excised, digested with trypsin and separated by high-pressure liquid chromatography coupled to a mass spectrometer (LC/MS) for protein identification (LC/MS/MS)5. This methodology (Figure 1) can be used on many tissues with little to no modification (liver, brain, heart etc.). PMID:22215112

Dimova, Kalina; Metskas, Lauren Ann; Kulp, Mohini; Scordilis, Stylianos P.

2011-01-01

104

The molecular basis for load-induced skeletal muscle hypertrophy.  

PubMed

In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Last, new mechanisms are highlighted for how ?2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise. PMID:25359125

Marcotte, George R; West, Daniel W D; Baar, Keith

2015-03-01

105

REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE  

PubMed Central

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

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

2014-01-01

106

Nuclear Factor-kappa B Signaling in Skeletal Muscle Atrophy  

PubMed Central

Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-?B) is one of most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-?B in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-?B can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-?B in skeletal muscle with particular reference to different models of muscle-wasting and the development of novel therapy. PMID:18574572

Li, Hong; Malhotra, Shweta; Kumar, Ashok

2008-01-01

107

Skeletal muscle biomechanics drives intramuscular transport of locally delivered drugs  

E-print Network

Introduction: Effective local drug delivery to contractile tissues such as skeletal muscle requires a thorough understanding of the impact of mechanical loads on intramuscular pharmacokinetics. Current preparations for ...

Wu, Peter I-Kung

2007-01-01

108

The impact of severe burn injury on skeletal muscle mitochondrial function  

PubMed Central

Severe burn injury induces a pathophysiological response that affects almost every physiological system within the body. Inflammation, hypermetabolism, muscle wasting, and insulin resistance are all hallmarks of the pathophysiological response to burn injury, with perturbations in metabolism known to persist for several years post injury. Skeletal muscle is the main depot of lean tissue within the body and as the primary site of peripheral glucose disposal, plays an important role in metabolic regulation. Following a large burn, skeletal muscle functions as and endogenous amino acid store, providing substrates for more pressing functions post burn, such as the synthesis of acute phase proteins and the deposition of new skin. Subsequently, burn patients become cachexic, which is associated with poor outcomes in terms of metabolic health and functional capacity. While a loss of skeletal muscle contractile proteins per se will no doubt negatively impact functional capacity, detriments in skeletal muscle quality, i.e. a loss in mitochondrial number and/or function may be quantitatively just as important. The goal of this review article is to summarize the current understanding of the impact of burn injury on skeletal muscle mitochondrial content and function, to offer direction for future research concerning skeletal muscle mitochondrial function in patients with severe burns, and to renew interest in the role of these organelles in metabolic dysfunction following burn injury. PMID:23664225

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

2013-01-01

109

Prolonged stimulation of muscle protein synthesis by leucine in neonates is dependent on amino acid availability  

Technology Transfer Automated Retrieval System (TEKTRAN)

The rise in amino acids and insulin after a meal independently stimulate protein synthesis in skeletal muscle of neonates by activating the intracellular signalling pathways that regulate mRNA translation. Leucine, in particular, is important in mediating the response to amino acids. Previously, w...

110

Regulation of protein synthesis by amino acids in muscle of neonates  

Technology Transfer Automated Retrieval System (TEKTRAN)

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 bee...

111

Interactive Classroom Demonstration of Skeletal Muscle Contraction  

NSDL National Science Digital Library

Students in a traditional lecture-style course often struggle to visualize the sequence of events in the molecular mechanism of skeletal muscle contraction as represented in anatomy and physiology textbooks (e.g., Ref. 1). The author of this article has successfully used the following interactive method with first-year nursing students. If the students are able to state the functions of calcium, troponin, tropomyosin, and cross-bridges, the demonstration requires only 15Â?20 minutes of class time. The size of the actin and myosin filaments can be varied according to the class size.

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

2002-12-01

112

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

NASA Astrophysics Data System (ADS)

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

Gao, Yingxin; Zhang, Chi

2015-03-01

113

Skeletal muscle responses to unloading in humans  

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

114

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

PubMed

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

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

2014-01-01

115

Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication  

Microsoft Academic Search

Summary  Femoral arterio-venous (A-V) differences of blood free amino acids and plasma ammonia (NH3) were simultaneously determined after an overnight fast in 16 patients with decompensated liver cirrhosis in the absence\\u000a and presence of encephalopathy, as compared with those in 8 control subjects. In spite of increased releases of phenylalanine\\u000a (Phe) and tyrosine (Tyr) from the peripheral tissue, releases of isoleucine

Masanori Hayashi; Hiroo Ohnishi; Yasuhiko Kawade; Yasutoshi Muto; Yoshiyata Takahashi

1981-01-01

116

Prospective identification of myogenic endothelial cells in human skeletal muscle  

Microsoft Academic Search

We document anatomic, molecular and developmental relationships between endothelial and myogenic cells within human skeletal muscle. Cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry. These myoendothelial cells regenerate myofibers in the injured skeletal muscle of severe combined immunodeficiency mice more effectively than CD56+ myogenic progenitors. They proliferate long term, retain a

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

2007-01-01

117

Skeletal muscle stem cells from animals I. Basic cell biology  

Technology Transfer Automated Retrieval System (TEKTRAN)

Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

118

INTRAMUSCULAR ADIPOCYTES- POTENTIAL TO PREVENT LIPOTOXICITY IN SKELETAL MUSCLE  

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...

119

Satellite cell proliferation in adult skeletal muscle  

NASA Technical Reports Server (NTRS)

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

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

1995-01-01

120

Modelling skeletal muscle fibre orientation arrangement.  

PubMed

Skeletal muscle tissues have complex geometries. In addition, the complex fibre orientation arrangement makes it quite difficult to create an accurate finite element muscle model. There are many possible ways to specify the complex fibre orientations in a finite element model, for example defining a local element coordinate system. In this paper, an alternative method using ABAQUS, which is combination of the finite element method and the non-uniform rational B-spline solid representation, is proposed to calculate the initial fibre orientations. The initial direction of each muscle fibre is specified as the tangent direction of the NURBS curve which the fibre lies on, and the directions of the deformed fibres are calculated from the initial fibre directions, the deformation gradients and the fibre stretch ratios. Several examples are presented to demonstrate the ability of the proposed method. Results show that the proposed method is able to characterise both the muscle complex fibre orientation arrangement and its complex mechanical response. PMID:20924862

Lu, Y T; Zhu, H X; Richmond, S; Middleton, J

2011-12-01

121

BIOLOGICAL FRAMEWORKS FOR ENGINEERS Laboratory Experience #3 [Skeletal Muscle Biomechanics  

E-print Network

, is found to describe nearly all muscle thus far examined, include cardiac and smooth muscle as wellME498/599 BIOLOGICAL FRAMEWORKS FOR ENGINEERS Laboratory Experience #3 [Skeletal Muscle physiologic range of muscle lengths and arm positions. Study inverse relationship between load and velocity

Sniadecki, Nathan J.

122

BIOLOGICAL FRAMEWORKS FOR ENGINEERS Laboratory Experience #3 [Skeletal Muscle Biomechanics  

E-print Network

, is found to describe nearly all muscle thus far examined, include cardiac and smooth muscle as wellME411/511 BIOLOGICAL FRAMEWORKS FOR ENGINEERS Laboratory Experience #3 [Skeletal Muscle physiologic range of muscle lengths and arm positions. Study inverse relationship between load and velocity

Sniadecki, Nathan J.

123

Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor  

Microsoft Academic Search

The sequence of 5,037 amino acids composing the ryanodine receptor from rabbit skeletal muscle sarcoplasmic reticulum has been deduced by cloning and sequencing the complementary DNA. The predicted structure suggests that the calcium release channel activity resides in the C-terminal region of the receptor molecule, whereas the remaining portion constitutes the 'foot' structure spanning the junctional gap between the sarcoplasmic

Hiroshi Takeshima; Seiichiro Nishimura; Takeshi Matsumoto; Hiroyuki Ishida; Kenji Kangawa; Naoto Minamino; Hisayuki Matsuo; Masamichi Ueda; Masao Hanaoka; Tadaaki Hirose; Shosaku Numa

1989-01-01

124

TLR2 deficiency attenuates skeletal muscle atrophy in mice.  

PubMed

Oxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice. Immobilization for 2 weeks increased the expression of cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle weight loss and a reduction in treadmill running times induced by immobilization were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization-associated increases in ubiquitinated protein levels were lower in the TLR2 KO mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and increased the levels of ubiquitinated proteins, although these levels were increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a potential target for preventing skeletal muscle atrophy. PMID:25749338

Kim, Dae-Sung; Cha, Hye-Na; Jo, Hye Jun; Song, In-Hwan; Baek, Suk-Hwan; Dan, Jin-Myoung; Kim, Yong-Woon; Kim, Jong-Yeon; Lee, In-Kyu; Seo, Jae-Sung; Park, So-Young

2015-04-10

125

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation  

Technology Transfer Automated Retrieval System (TEKTRAN)

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study...

126

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

1987-01-01

127

Physiology and metabolism of tissue-engineered skeletal muscle.  

PubMed

Skeletal muscle is a major target for tissue engineering, given its relative size in the body, fraction of cardiac output that passes through muscle beds, as well as its key role in energy metabolism and diabetes, and the need for therapies for muscle diseases such as muscular dystrophy and sarcopenia. To date, most studies with tissue-engineered skeletal muscle have utilized murine and rat cell sources. On the other hand, successful engineering of functional human muscle would enable different applications including improved methods for preclinical testing of drugs and therapies. Some of the requirements for engineering functional skeletal muscle include expression of adult forms of muscle proteins, comparable contractile forces to those produced by native muscle, and physiological force-length and force-frequency relations. This review discusses the various strategies and challenges associated with these requirements, specific applications with cultured human myoblasts, and future directions. PMID:24912506

Cheng, Cindy S; Davis, Brittany N J; Madden, Lauran; Bursac, Nenad; Truskey, George A

2014-09-01

128

Tissue triage and freezing for models of skeletal muscle disease.  

PubMed

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

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

2014-01-01

129

Tissue Triage and Freezing for Models of Skeletal Muscle Disease  

PubMed Central

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

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

2014-01-01

130

Cloning of cDNAs for fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase from frog skeletal muscle and liver, and their expression in skeletal muscle.  

PubMed

Frog (Rana catesbeiana) skeletal muscle (M-type) and liver (L-type) cDNAs of fructose 6-phosphate 2-kinase/fructose 2,6-bisphosphatase were isolated from lambda gt10 phage cDNA library. The full-length L-type cDNA (1829 bp) encodes a 469 amino acids subunit (M(r) 54,800), while the M-type cDNA (1792 bp) encodes 455 amino acids (M(r) 52,901). The amino acid sequence of the M-type isozyme is identical to that of the L-type isozyme except for the N-terminus. The N-terminal 30 amino acids of the L-type isozyme are replaced by an unique sequence of 16 amino acids in the M-type isozyme. Both L- and M-type cDNAs were detected also in a lambda gt10 phage library of skeletal muscle. Relative amount of the M- and L-type mRNAs is skeletal muscle was determined by the reverse transcription-polymerase chain reaction method. The M/L mRNA ratio in frog skeletal muscle shows seasonal variations, being 0.56/1 in early summer and 5.3/1 in winter. These results suggest that there is a seasonal change in the isozyme composition and that the glycolysis in frog skeletal muscle may be regulated by type of the isozyme synthesized. PMID:7509597

Sakai, A; Watanabe, F; Furuya, E

1994-02-15

131

Calprotectin is released from human skeletal muscle tissue during exercise  

PubMed Central

Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at ?60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of ?50% of peak power output and arterial–femoral venous differences were obtained. Arterial plasma concentrations for calprotectin increased 2-fold compared to rest and there was a net release of calprotectin from the working muscle. In conclusion, IL-6 infusion and muscle contractions induce expression of S100A8 and S100A9 in skeletal muscle. However, IL-6 alone is not a sufficient stimulus to facilitate release of calprotectin from skeletal muscle. PMID:18511485

Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian; Nielsen, Anders Rinnov; Nielsen, Søren; Åkerström, Thorbjörn; Aastrøm, Maj-brit; Borup, Rehannah; Pedersen, Bente Klarlund

2008-01-01

132

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...

133

A metabolic link to skeletal muscle wasting and regeneration  

PubMed Central

Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed “metabolic reprogramming.” PMID:24567722

Koopman, René; Ly, C. Hai; Ryall, James G.

2014-01-01

134

Microfluidic devices for construction of contractile skeletal muscle microtissues.  

PubMed

Cell-culture microchips mimicking tissue/organ-specific functions are required as alternatives to animal testing for drug discovery and disease models. Although three-dimensional (3D) cell culture microfluidic devices can create more biologically relevant cellular microenvironments and higher throughput analysis platforms of cell behavior than conventional techniques, devices for skeletal muscle cells have not been developed. In the present study, we aimed to develop microfluidic devices for 3D cultures of skeletal muscle cells. Skeletal muscle cells mixed with a collagen type-I solution was introduced into the microchannel for cells (MC-C) and was gelated. Then, the medium was introduced into the microchannel for medium (MC-M). During this process, connecting microchannels (Con-MCs) prevented leakage of the collagen solution mixed with cells from MC-C to MC-M and supplied the nutrients from the medium in MC-M to the cells in MC-C. Skeletal muscle microtissues cultured in the microchannel for a week consisted of myotubes were confirmed by histological analysis and immunofluorescence staining. The skeletal muscle microtissues in the microchannel contracted in response to externally applied electrical stimulation (1 and 50 Hz). These results indicate that the functional skeletal muscle microtissues were constructed in the microchannel. Thus, the microfluidic device for culturing 3D skeletal muscle microtissues presented in this study has a potential to be used for drug discovery and toxicological tests. PMID:25085533

Shimizu, Kazunori; Araki, Hiroyuki; Sakata, Kohei; Tonomura, Wataru; Hashida, Mitsuru; Konishi, Satoshi

2015-02-01

135

Time course of gene expression during mouse skeletal muscle hypertrophy.  

PubMed

The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ?2-fold increase or ?50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy. PMID:23869057

Chaillou, Thomas; Lee, Jonah D; England, Jonathan H; Esser, Karyn A; McCarthy, John J

2013-10-01

136

Time course of gene expression during mouse skeletal muscle hypertrophy  

PubMed Central

The purpose of this study was to perform a comprehensive transcriptome analysis during skeletal muscle hypertrophy to identify signaling pathways that are operative throughout the hypertrophic response. Global gene expression patterns were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during plantaris muscle hypertrophy induced by synergist ablation in adult mice. Principal component analysis and the number of differentially expressed genes (cutoffs ?2-fold increase or ?50% decrease compared with control muscle) revealed three gene expression patterns during overload-induced hypertrophy: early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days) patterns. Based on the robust changes in total RNA content and in the number of differentially expressed genes, we focused our attention on the intermediate gene expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes encoding components of the branched-chain amino acid degradation pathway during hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis or previously shown to be regulated by the transcription factor Kruppel-like factor-15, which was also downregulated during hypertrophy. Moreover, the integrin-linked kinase signaling pathway was activated during hypertrophy, and the downregulation of muscle-specific micro-RNA-1 correlated with the upregulation of five predicted targets associated with the integrin-linked kinase pathway. In conclusion, we identified two novel pathways that may be involved in muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15 and micro-RNA-1) that provide targets for future studies investigating the importance of these pathways in muscle hypertrophy. PMID:23869057

Lee, Jonah D.; England, Jonathan H.; Esser, Karyn A.; McCarthy, John J.

2013-01-01

137

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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 tr...

138

Rapamycin blocks leucine-induced protein synthesis by suppressing mTORC1 activation in skeletal muscle of neonatal pigs  

Technology Transfer Automated Retrieval System (TEKTRAN)

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 (Leu). To elucidate the molecular mechanism by which Leu stimulates protein synthesis in neonatal muscle, overnight fasted 7-day-old piglets were...

139

Leucine and alpha-Ketoisocaproic acid, but not norleucine, stimulate skeletal muscle protein synthesis in neonatal pigs  

Technology Transfer Automated Retrieval System (TEKTRAN)

The branched-chain amino acid, leucine, acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of young pigs. However, the chemical structure responsible for this effect has not been identified. We have shown that the other branched-chain amino acids, isoleucine and valine, are ...

140

Applications of skeletal muscle progenitor cells for neuromuscular diseases  

PubMed Central

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

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

2012-01-01

141

Smoking-induced Skeletal Muscle Dysfunction. From Evidence to Mechanisms.  

PubMed

Smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from skeletal muscle dysfunction, and it has been suggested that cigarette smoke exposure contributes to the development of skeletal muscle dysfunction even before overt pulmonary pathology. This review summarizes the evidence that muscles of nonsymptomatic smokers are weaker and less fatigue resistant than those of nonsmokers. Although physical inactivity of many smokers contributes to some alterations observed in skeletal muscle, exposure to cigarette smoke per se can also induce skeletal muscle dysfunction. Cigarette smoke constituents and systemic inflammatory mediators enhance proteolysis and inhibit protein synthesis, leading to loss of muscle mass. Reduced skeletal muscle contractile endurance in smokers may result from impaired oxygen delivery to the mitochondria and ability of the mitochondria to generate ATP due to interaction of carbon monoxide with hemoglobin, myoglobin, and components of the respiratory chain. Besides hampering contractile function, smoking may have immediate beneficial effects on motor skills, which are attributable to nicotine. In contrast to pulmonary pathology, many of the effects of smoking on skeletal muscle are most likely reversible by smoking cessation. PMID:25581779

Degens, Hans; Gayan-Ramirez, Ghislaine; van Hees, Hieronymus W H

2015-03-15

142

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)

2010-10-01

143

Molecular forms of acetylcholinesterase and pseudocholinesterase in chicken skeletal muscles  

E-print Network

Molecular forms of acetylcholinesterase and pseudocholinesterase in chicken skeletal muscles of Histo%gy and Embryo%gy Academy of Medicine, Warsaw, Poland. Summary. Chicken muscles offer several of molecular forms of chicken muscle acetylcholinesterase (AChE), and likewise of pseudocholinesterase (1/t

Paris-Sud XI, Université de

144

A second MNGIE patient without typical mitochondrial skeletal muscle involvement.  

PubMed

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease caused by mutations in the gene encoding thymidine phosphorylase (TYMP). Clinically, MNGIE is characterized by gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Most MNGIE patients have signs of mitochondrial dysfunction in skeletal muscle at morphological and enzyme level, as well as mitochondrial DNA depletion, multiple deletions and point mutations. A case without mitochondrial skeletal muscle involvement and with a TYMP splice-acceptor site mutation (c. 215-1 G>C) has been reported. Here, we describe an Italian patient with the same mutation and without mitochondrial skeletal muscle involvement, suggesting a possible genotype-phenotype correlation. PMID:20232099

Cardaioli, Elena; Da Pozzo, Paola; Malfatti, Edoardo; Battisti, Carla; Gallus, Gian Nicola; Gaudiano, Carmen; Macucci, Marco; Malandrini, Alessandro; Margollicci, Maria; Rubegni, Anna; Dotti, Maria Teresa; Federico, Antonio

2010-08-01

145

Skeletal muscle: a brief review of structure and function.  

PubMed

Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40 % of total body weight and contains 50-75 % of all body proteins. In general, muscle mass depends on the balance between protein synthesis and degradation and both processes are sensitive to factors such as nutritional status, hormonal balance, physical activity/exercise, and injury or disease, among others. In this review, we discuss the various domains of muscle structure and function including its cytoskeletal architecture, excitation-contraction coupling, energy metabolism, and force and power generation. We will limit the discussion to human skeletal muscle and emphasize recent scientific literature on single muscle fibers. PMID:25294644

Frontera, Walter R; Ochala, Julien

2015-03-01

146

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.

1986-03-05

147

Dysregulation of SIRT-1 in aging mice increases skeletal muscle fatigue by a PARP-1-dependent mechanism  

PubMed Central

Accumulation of reactive oxygen species (ROS) in skeletal muscles and the resulting decline in muscle performance are hallmarks of sarcopenia. However, the precise mechanism by which ROS results in a decline in muscle performance is unclear. We demonstrate that isometric-exercise concomitantly increases the activities of Silent information regulator 1 (SIRT-1) and Poly [ADP-ribose] polymerase (PARP-1), and that activated SIRT-1 physically binds with and inhibits PARP-1 activity by a deacetylation dependent mechanism in skeletal muscle from young mice. In contrast, skeletal muscle from aged mice displays higher PARP-1 activity and lower SIRT-1 activity due to decreased intracellular NAD+ content, and as a result reduced muscle performance in response to exercise. Interestingly, injection of PJ34, a PARP-1 inhibitor, in aged mice increased SIRT-1 activity by preserving intracellular NAD+ content, which resulted in higher skeletal muscle mitochondrial biogenesis and performance. We found that the higher activity of PARP-1 in H2O2-treated myotubes or in exercised-skeletal muscles from aged mice is due to an elevated level of PARP-1 acetylation by the histone acetyltransferase General control of amino acid synthesis protein 5-like 2 (GCN-5). These results suggest that activation of SIRT-1 and/or inhibition of PARP-1 may ameliorate skeletal muscle performance in pathophysiological conditions such as sarcopenia and disuse-induced atrophy in aging. PMID:25361036

Mohamed, Junaith S.; Wilson, Joseph C.; Myers, Matthew J.; Sisson, Kayla J.; Alway, Stephen E.

2014-01-01

148

Angiopoietin-1 enhances skeletal muscle regeneration in mice.  

PubMed

Activation of muscle progenitor cell myogenesis and endothelial cell angiogenesis is critical for the recovery of skeletal muscle from injury. Angiopoietin-1 (Ang-1), a ligand of Tie-2 receptors, enhances angiogenesis and skeletal muscle satellite cell survival; however, its role in skeletal muscle regeneration after injury is unknown. We assessed the effects of Ang-1 on fiber regeneration, myogenesis, and angiogenesis in injured skeletal muscle (tibialis anterior, TA) in mice. We also assessed endogenous Ang-1 levels and localization in intact and injured TA muscles. TA fiber injury was triggered by cardiotoxin injection. Endogenous Ang-1 mRNA levels immediately decreased in response to cardiotoxin then increased during the 2 wk. Ang-1 protein was expressed in satellite cells, both in noninjured and recovering TA muscles. Positive Ang-1 staining was present in blood vessels but not in nerve fibers. Four days after the initiation of injury, injection of adenoviral Ang-1 into injured muscles resulted in significant increases in in situ TA muscle contractility, muscle fiber regeneration, and capillary density. In cultured human skeletal myoblasts, recombinant Ang-1 protein increased survival, proliferation, migration, and differentiation into myotubes. The latter effect was associated with significant upregulation of the expression of the myogenic regulatory factors MyoD and Myogenin and certain genes involved in cell cycle regulation. We conclude that Ang-1 strongly enhances skeletal muscle regeneration in response to fiber injury and that this effect is mediated through induction of the myogenesis program in muscle progenitor cells and the angiogenesis program in endothelial cells. PMID:25608750

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

2015-04-01

149

The lateral plate mesoderm: a novel source of skeletal muscle.  

PubMed

It has been established in the last century that the skeletal muscle cells of vertebrates originate from the paraxial mesoderm. However, recently the lateral plate mesoderm has been identified as a novel source of the skeletal muscle. The branchiomeric muscles, such as masticatory and facial muscles, receive muscle progenitor cells from both the cranial paraxial mesoderm and lateral plate mesoderm. At the occipital level, the lateral plate mesoderm is the sole source of the muscle progenitors of the dorsolateral neck muscle, such as trapezius and sternocleidomastoideus in mammals and cucullaris in birds. The lateral plate mesoderm requires a longer time for generating skeletal muscle cells than the somites. The myogenesis of the lateral plate is determined early, but not cell autonomously and requires local signals. Lateral plate myogenesis is regulated by mechanisms controlling the cranial myogenesis. The connective tissue of the lateral plate-derived muscle is formed by the cranial neural crest. Although the cranial neural crest cells do not control the early myogenesis, they regulate the patterning of the branchiomeric muscles and the cucullaris muscle. Although satellite cells derived from the cranial lateral plate show distinct properties from those of the trunk, they can respond to local signals and generate myofibers for injured muscles in the limbs. In this review, we key feature in detail the muscle forming properties of the lateral plate mesoderm and propose models of how the myogenic fate may have arisen. PMID:25344670

Pu, Qin; Patel, Ketan; Huang, Ruijin

2015-01-01

150

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)

2005-08-01

151

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

2011-01-01

152

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. PMID:21949456

Gillies, Allison R.; Lieber, Richard L.

2011-01-01

153

The effects of obesity on skeletal muscle regeneration  

PubMed Central

Obesity and metabolic disorders such as type 2 diabetes mellitus are accompanied by increased lipid deposition in adipose and non-adipose tissues including liver, pancreas, heart and skeletal muscle. Recent publications report impaired regenerative capacity of skeletal muscle following injury in obese mice. Although muscle regeneration has not been thoroughly studied in obese and type 2 diabetic humans and mechanisms leading to decreased muscle regeneration in obesity remain elusive, the initial findings point to the possibility that muscle satellite cell function is compromised under conditions of lipid overload. Elevated toxic lipid metabolites and increased pro-inflammatory cytokines as well as insulin and leptin resistance that occur in obese animals may contribute to decreased regenerative capacity of skeletal muscle. In addition, obesity-associated alterations in the metabolic state of skeletal muscle fibers and satellite cells may directly impair the potential for satellite cell-mediated repair. Here we discuss recent studies that expand our understanding of how obesity negatively impacts skeletal muscle maintenance and regeneration. PMID:24381559

Akhmedov, Dmitry; Berdeaux, Rebecca

2013-01-01

154

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. PMID:21798084

2011-01-01

155

Maintaining skeletal muscle mass: lessons learned from hibernation.  

PubMed

Muscle disuse and starvation are often associated with a catabolic response leading to a dramatic loss of skeletal muscle mass. Hibernating animals represent a unique situation where muscle mass is maintained despite prolonged periods of immobilization and lack of nutrition. We analysed the molecular pathways upregulated during hibernation in an obligate hibernator, the 13-lined ground squirrel (Ictidomys tridecemlineatus). Although Akt has an established role in skeletal muscle maintenance, we found that activated Akt was decreased in skeletal muscle of hibernating squirrels. Another serine-threonine kinase, serum- and glucocorticoid-regulated kinase 1 (SGK1), was upregulated during hibernation and contributed to protection from loss of muscle mass via downregulation of proteolysis and autophagy and via an increase in protein synthesis. We extended our observations to non-hibernating animals and demonstrated that SGK1-null mice developed muscle atrophy. These mice displayed an exaggerated response to immobilization and starvation. Furthermore, SGK1 overexpression prevented immobilization-induced muscle atrophy. Taken together, our results identify SGK1 as a novel therapeutic target to combat skeletal muscle loss in acquired and inherited forms of muscle atrophy. PMID:24443348

Ivakine, Evgueni A; Cohn, Ronald D

2014-04-01

156

Skeletal muscle and bone: effect of sex steroids and aging  

NSDL National Science Digital Library

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

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

2008-02-14

157

Bex1 knock out mice show altered skeletal muscle regeneration  

SciTech Connect

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

Koo, Jae Hyung [Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States)], E-mail: jkoo001@umaryland.edu; Smiley, Mark A. [Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States); Lovering, Richard M. [Department of Physiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States); Margolis, Frank L. [Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States)

2007-11-16

158

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...

159

Estimation of skeletal muscle mass from body creatine content  

NASA Technical Reports Server (NTRS)

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

Pace, N.; Rahlmann, D. F.

1982-01-01

160

Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders  

PubMed Central

Needle biopsy samples were taken from vastus lateralis muscle (VL) of five male body builders (BB, age 27.4 ± 0.93 years; mean ±s.e.m.), who had being performing hypertrophic heavy resistance exercise (HHRE) for at least 2 years, and from five male active, but untrained control subjects (CTRL, age 29.9 ± 2.01 years). The following determinations were performed: anatomical cross-sectional area and volume of the quadriceps and VL muscles in vivo by magnetic resonance imaging (MRI); myosin heavy chain isoform (MHC) distribution of the whole biopsy samples by SDS-PAGE; cross-sectional area (CSA), force (Po), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n= 524) of single skinned muscle fibres classified on the basis of MHC isoform composition by SDS-PAGE; actin sliding velocity (Vf) on pure myosin isoforms by in vitro motility assays. In BB a preferential hypertrophy of fast and especially type 2X fibres was observed. The very large hypertrophy of VL in vivo could not be fully accounted for by single muscle fibre hypertrophy. CSA of VL in vivo was, in fact, 54% larger in BB than in CTRL, whereas mean fibre area was only 14% larger in BB than in CTRL. MHC isoform distribution was shifted towards 2X fibres in BB. Po/CSA was significantly lower in type 1 fibres from BB than in type 1 fibres from CTRL whereas both type 2A and type 2X fibres were significantly stronger in BB than in CTRL. Vo of type 1 fibres and Vf of myosin 1 were significantly lower in BB than in CTRL, whereas no difference was observed among fast fibres and myosin 2A. The findings indicate that skeletal muscle of BB was markedly adapted to HHRE through extreme hypertrophy, a shift towards the stronger and more powerful fibre types and an increase in specific force of muscle fibres. Such adaptations could not be fully accounted for by well known mechanisms of muscle plasticity, i.e. by the hypertrophy of single muscle fibre (quantitative mechanism) and by a regulation of contractile properties of muscle fibres based on MHC isoform content (qualitative mechanism). Two BB subjects took anabolic steroids and three BB subjects did not. The former BB differed from the latter BB mostly for the size of their muscles and muscle fibres. PMID:16339176

D'Antona, Giuseppe; Lanfranconi, Francesca; Pellegrino, Maria Antonietta; Brocca, Lorenza; Adami, Raffaella; Rossi, Rosetta; Moro, Giorgio; Miotti, Danilo; Canepari, Monica; Bottinelli, Roberto

2006-01-01

161

Skeletal Muscle as a Peripheral Modifier of Behavior  

ERIC Educational Resources Information Center

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

Jenkins, Robert R.

1978-01-01

162

Acylcarnitines: potential implications for skeletal muscle insulin resistance  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

163

INTRODUCTION In mammalian skeletal muscle, increases in exercise intensity are  

E-print Network

238 INTRODUCTION In mammalian skeletal muscle, increases in exercise intensity are sustained by a concomitant increase in the proportion of glucose oxidation relative to fatty acids (Brooks, 1998; Hargreaves, including increased rates of glucose transport into muscle cells, increased activation of pyruvate

Garland Jr., Theodore

164

Thin filament proteins mutations associated with skeletal myopathies: Defective regulation of muscle contraction  

Microsoft Academic Search

In humans, more than 140 different mutations within seven genes (ACTA1, TPM2, TPM3, TNNI2, TNNT1, TNNT3, and NEB) that encode\\u000a thin filament proteins (skeletal ?-actin, ?-tropomyosin, ?-tropomyosin, fast skeletal muscle troponin I, slow skeletal muscle\\u000a troponin T, fast skeletal muscle troponin T, and nebulin, respectively) have been identified. These mutations have been linked\\u000a to muscle weakness and various congenital skeletal

Julien Ochala

2008-01-01

165

Method for Decellularizing Skeletal Muscle Without Detergents or Proteolytic Enzymes  

PubMed Central

Decellularized skeletal muscle is a promising model that can be used to study cell–matrix interactions and changes that occur in muscle extracellular matrix (ECM) in myopathies and muscle wasting diseases. The goal of this study is to develop a novel method to decellularize skeletal muscle that maintains the native biochemical composition and structure of the ECM. This method consists of sequential incubation of mouse tibialis anterior muscles in latrunculin B, high ionic strength salt solution, and DNase I and avoids use of proteases or detergents that degrade the ECM. Characterization of the decellularized muscles using hematoxylin and eosin staining along with DNA quantification suggested complete removal of DNA, whereas biochemical analyses indicated no loss of collagens and only a slight reduction in glycosaminoglycans. Western blot analysis of decellularized tissues showed removal of the vast majority of the contractile proteins actin and myosin, and morphological analysis using scanning electron microscopy suggested removal of myofibers from decellularized muscle tissues. Passive mechanical testing of decellularized muscle bundles revealed the typical nonlinear behavior, similar to that of intact muscle. Together, these results suggest that the protocol developed successfully decellularizes skeletal muscle without altering its composition and mechanical function. PMID:20973753

Gillies, Allison R.; Smith, Lucas R.; Lieber, Richard L.

2011-01-01

166

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))

1991-07-01

167

Mechanically induced alterations in cultured skeletal muscle growth  

NASA Technical Reports Server (NTRS)

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

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

1991-01-01

168

Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle.  

PubMed

Irisin converts white adipose tissue (WAT) into brown adipose tissue (BAT), as regulated by energy expenditure. The relationship between irisin concentrations after exercise in rats compared humans after exercise remains controversial. We therefore: (1) measured irisin expression in cardiac and skeletal muscle, liver, kidney, peripheral nerve sheath and skin tissues, as also serum irisin level in 10 week-old rats without exercise, and (2) measured tissue supernatant irisin levels in cardiac and skeletal muscle, and in response to exercise in young and old rats to establishing which tissues produced most irisin. Young (12 months) and old rats (24 months) with or without 10min exercise (water floating) and healthy 10 week-old Sprague-Dawley rats without exercise were used. Irisin was absent from sections of skeletal muscle of unexercised rats, the only part being stained being the perimysium. In contrast, cardiac muscle tissue, peripheral myelin sheath, liver, kidneys, and skin dermis and hypodermis were strongly immunoreactivity. No irisin was seen in skeletal muscle of unexercised young and old rats, but a slight amount was detected after exercise. Strong immunoreactivity occurred in cardiac muscle of young and old rats with or without exercise, notably in pericardial connective tissue. Serum irisin increased after exercise, being higher in younger than older rats. Irisin in tissue supernatants (cardiac and skeletal muscle) was high with or without exercise. High supernatant irisin could come from connective tissues around skeletal muscle, especially nerve sheaths located within it. Skeletal muscle is probably not a main irisin source. PMID:24345335

Aydin, Suna; Kuloglu, Tuncay; Aydin, Suleyman; Eren, Mehmet Nesimi; Celik, Ahmet; Yilmaz, Musa; Kalayci, Mehmet; Sahin, ?brahim; Gungor, Orhan; Gurel, Ali; Ogeturk, Murat; Dabak, Ozlem

2014-02-01

169

In vitro stimulation of skeletal muscle protein synthesis by leucine and insulin  

SciTech Connect

The objective of this study was to determine the potential of leu to stimulate skeletal muscle protein synthesis in the presence or absence of insulin or insulin plus a mixture of the other plasma amino acids. Male Sprague-Dawley rats weighing 75 g were fasted for 24 hrs, sacrificed, and the soleus muscle isolated from the hind limb. Protein synthesis was determined in isolated muscles incubated for 2 hrs at 37/sup 0/C in a Krebs-Ringer bicarbonate buffer containing 0.5 ..mu..Ci of /sup 14/C-tyrosine and supplemented with either 10 mM glucose (G), glucose plus 0.1 IU/m. insulin (I), or glucose, insulin and plasma levels of amino acids (IAA). Contralateral muscles were incubated in the respective media with the addition of 0.5 mM L-leucine. Insulin stimulated protein synthesis by 51% above the G group, and IAA produced a 110% stimulation. Leu stimulated protein synthesis by an additional 15-20% in each of the medias. These results confirm the ability of leu to stimulate skeletal muscle protein synthesis in vitro and establish that the effect is additive with stimulations by insulin and other amino acids.

Hatlestad, C.L.; Layman, D.K.

1986-03-01

170

Systemic Gene Transfer to Skeletal Muscle Using Reengineered AAV Vectors  

PubMed Central

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

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

2011-01-01

171

Trophic regulation of acetylcholinesterase isoenzymes in adult mammalian skeletal muscles  

Microsoft Academic Search

This work addresses the physiological regulation of skeletal muscle acetylcholinesterase (AChE) isoforms by examining endplate-enriched samples from adult rat gracilis muscles 48 h after: lowintensity treadmill exercise; obturator nerve transection; nerve impulse conduction blockade by tetrodotoxin; acetylcholine (ACh) receptor (AChR) inactivation by a-bungarotoxin; and, addition of obturator nerve extracts to muscles in organ culture. Results document the important role(s) of

Hugo L. Fernandez; Cheryl A. Hodges-Savola

1992-01-01

172

Structural and functional changes in skeletal muscle in anorexia nervosa  

Microsoft Academic Search

Protein-energy malnutrition in anorexia nervosa is an under-recognised cause of muscle dysfunction. To characterise the skeletal\\u000a myopathy that occurs in patients with severe anorexia nervosa, muscle function and structure were comprehensively examined\\u000a in eight young adult female patients with severe (40%) self-induced weight loss. All of the patients showed impaired muscle\\u000a function on strength and exercise measurement. The maximum voluntary

Declan M. McLoughlin; Edward Spargo; Wassif S. Wassif; Diane J. Newham; Timothy J. Peters; Peter L. Lantos; Gerald F. M. Russell

1998-01-01

173

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND: The effects of essential amino acid (EAA) supplementation during moderate steady state (ie, endurance) exercise on postexercise skeletal muscle metabolism are not well described, and the potential role of supplemental leucine on muscle protein synthesis (MPS) and associated molecular re...

174

Dystrophin-associated Proteins Are Greatly Reduced in Skeletal Muscle from mdx Mice  

E-print Network

accompanied by skeletal muscle necrosis makes the mdx mouse an excellent model system to study how muscleDystrophin-associated Proteins Are Greatly Reduced in Skeletal Muscle from mdx Mice Kay- man Duchenne muscular dystrophy gene, exists in skeletal muscle as a large oligomeric complex

Campbell, Kevin P.

175

Thyroid hormones and skeletal muscle — new insights and potential implications  

PubMed Central

Thyroid hormone signalling regulates crucial biological functions, including energy expenditure, thermogenesis, development and growth. The skeletal muscle is a major target of thyroid hormone signalling. The type two (DIO2) and three (DIO3) iodothyronine deiodinases have been identified in skeletal muscle. DIO2 expression is tightly regulated and catalyzes outer ring monodeiodination of the secreted prohormone tetraiodothyronine (T4) to generate the active hormone triiodothyronine (T3). T3 may remain in the myocyte to signal through nuclear receptors or exit the cell to mix with the extracellular pool. By contrast, DIO3 inactivates T3 through removal of an inner ring iodine. Regulation of the expression and activity of deiodinases constitutes a cell-autonomous, pre-receptor mechanism for controlling the intracellular concentration of T3. This local control of T3 activity is crucial during the various phases of myogenesis. Here, we review the roles of T3 in skeletal muscle development and homeostasis, with a focus on the emerging local deiodinase-mediated control of T3 signalling. Moreover, we discuss these novel findings in the context of both muscle homeostasis and pathology, and examine how they can be therapeutically harnessed to improve satellite cell-mediated muscle repair in patients with skeletal muscle disorders, muscle atrophy or injury. PMID:24322650

Salvatore, Domenico; Simonides, Warner S.; Dentice, Monica; Zavacki, Ann Marie; Larsen, P. Reed

2014-01-01

176

Forces generated by both skeletal and cardiac muscle depend strongly upon muscle length. The in vivo range of lengths is  

E-print Network

2455 Forces generated by both skeletal and cardiac muscle depend strongly upon muscle length for cardiac and skeletal muscles (Allen and Kentish, 1985; Layland et al., 1995). Despite the importance into muscle design. Cardiac muscle is one case where the functional consequences of operating length are well

Daniel, Tom

177

Quantitative force comparison of polyacrylonitrile fibers with skeletal muscle  

NASA Astrophysics Data System (ADS)

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

Gonzalez, Roger V.; Lee, Christopher Y.

1998-07-01

178

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.

1977-01-01

179

Regulation of the skeletal muscle blood flow in humans.  

PubMed

In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators, including NO and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and, very importantly, can offset local sympathetic vasoconstriction. Adenosine triphosphate is released into plasma from erythrocytes and endothelial cells, and the plasma concentration increases in both the feed artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine concentration does not increase during exercise. In the skeletal muscle interstitium, there is a marked increase in the concentration of ATP and adenosine, and this increase is tightly coupled to the increase in blood flow. The sources of interstitial ATP and adenosine are thought to be skeletal muscle cells and endothelial cells. In the interstitium, both ATP and adenosine stimulate the formation of NO and prostaglandins, but ATP has also been suggested to induce vasoconstriction and stimulate afferent nerves that signal to increase sympathetic nerve activity. Adenosine has been shown to contribute to exercise hyperaemia, whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation. PMID:25192730

Mortensen, Stefan P; Saltin, Bengt

2014-12-01

180

Redox proteins are constitutively secreted by skeletal muscle.  

PubMed

Myokines are skeletal muscle-derived hormones. In this study, using a C2C12 myotube contraction system, we sought to determine whether the skeletal muscle secreted thioredoxin (TRX) and related redox proteins. Redox proteins such as TRXs, peroxiredoxins, and glutaredoxins were detected in the C2C12 myotube culture medium in the absence of any stimulation. The amounts of TRXs, peroxiredoxins, and glutaredoxins secreted by the C2C12 myotubes were not affected by the contraction, unless the myotubes were injured. Because TRX-1 was known to be a secreted protein that lacks a signal peptide, we examined whether this protein was secreted via exosome vesicles. The results indicated that TRX-1 was not secreted via exosome vesicles. We concluded that TRX-1 and related redox proteins are myokines that are constitutively secreted by the skeletal muscle cells. Although the mechanism of TRX-1 secretion remains unclear, our findings suggest that the skeletal muscle is an endocrine organ and the redox proteins that are constitutively secreted from the skeletal muscle may exert antioxidant and systemic health-promoting effects. PMID:25205643

Manabe, Yasuko; Takagi, Mayumi; Nakamura-Yamada, Mio; Goto-Inoue, Naoko; Taoka, Masato; Isobe, Toshiaki; Fujii, Nobuharu L

2014-11-01

181

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

SciTech Connect

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

Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States) [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States) [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States) [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States) [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States) [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States) [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

2010-09-24

182

Growth Factors and Tension-Induced Skeletal Muscle Growth  

NASA Technical Reports Server (NTRS)

The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we have performed experiments to determine whether mechanical stimulation of cultured avian muscle cells alters their response to anabolic steroids or glucocorticoids. In static cultures, testosterone had no effect on muscle cell growth, but 5alpha-dihydrotestosterone and the synthetic steroid stanozolol increased cell growth by up to 18% and 30%, respectively, after a three day exposure. We completed development of a new IBM-based mechanical cell stimulator system to provide greater flexibility in operating and monitoring our experiments. Our previous long term studies on myofiber growth were designed around a perfusion system of our own design. We have recently changed to performing these studies using a modified CELLCO cartridge bioreactor system Z since it has been certified as the ground-based model for the Shuttle's Space Tissue Loss (STL) F= Cell Culture Module. The current goals of this aspect of the project are three fold: 1) to design a Z cell culture system for studying avian skeletal myofiber atrophy on the Shuttle and Space Station; 0 2) to expand the use of bioreactors to cells which do not grow in either suspension or attached to the hollow fibers; and 3) to combine the bioreactor system with our computerized mechanical cell stimulator to have a better in vitro model to study tension/gravity/stretch regulation of skeletal muscle size. Preliminary studies also reported on involved : (1) how release of tension can induce rapid atrophy of tissues cultured avian skeletal muscle cells, and (2) a mechanism to transfer and maintain avian skeletal muscle organoids in modified cartridges in the Space Tissue Loss Module.

Vandenburgh, Herman H.

1994-01-01

183

Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

184

Trichinella spiralis infected skeletal muscle cells arrest in G 2/M and cease muscle gene expression  

E-print Network

Abstract. 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

Douglas E Jasmer

1993-01-01

185

?-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells  

Microsoft Academic Search

Nemaline myopathy is a neuromuscular disorder, characterized by muscle weakness and hypotonia and is, in 20% of the cases, caused by mutations in the gene encoding ?-skeletal muscle actin, ACTA1. It is a heterogeneous disease with various clinical phenotypes and severities. In patients the ultrastructure of muscle cells is often disturbed by nemaline rods and it is thought this is

Drieke Vandamme; Ellen Lambert; Davy Waterschoot; Christian Cognard; Joël Vandekerckhove; Christophe Ampe; Bruno Constantin; Heidi Rommelaere

2009-01-01

186

Kelch proteins: emerging roles in skeletal muscle development and diseases  

PubMed Central

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

2014-01-01

187

Growth factor involvement in tension-induced skeletal muscle growth  

NASA Technical Reports Server (NTRS)

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

Vandenburgh, Herman H.

1993-01-01

188

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

PubMed Central

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

2012-01-01

189

Fast Skeletal Muscle Troponin Activation Increases Force of Mouse Fast Skeletal Muscle and Ameliorates Weakness Due to Nebulin-Deficiency  

PubMed Central

The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT) and nebulin deficient (NEB KO) mice. Nebulin is a sarcomeric protein that when absent (NEB KO mouse) or present at low levels (nemaline myopathy (NM) patients with NEB mutations) causes muscle weakness. We studied the effect of fast skeletal troponin activation on WT muscle and tested whether it might be a therapeutic mechanism to increase muscle strength in nebulin deficient muscle. We measured tension–pCa relations with and without added CK-2066260. Maximal active tension in NEB KO tibialis cranialis fibers in the absence of CK-2066260 was ?60% less than in WT fibers, consistent with earlier work. CK-2066260 shifted the tension-calcium relationship leftwards, with the largest relative increase (up to 8-fold) at low to intermediate calcium levels. This was a general effect that was present in both WT and NEB KO fiber bundles. At pCa levels above ?6.0 (i.e., calcium concentrations <1 µM), CK-2066260 increased tension of NEB KO fibers to beyond that of WT fibers. Crossbridge cycling kinetics were studied by measuring ktr (rate constant of force redevelopment following a rapid shortening/restretch). CK-2066260 greatly increased ktr at submaximal activation levels in both WT and NEB KO fiber bundles. We also studied the sarcomere length (SL) dependence of the CK-2066260 effect (SL 2.1 µm and 2.6 µm) and found that in the NEB KO fibers, CK-2066260 had a larger effect on calcium sensitivity at the long SL. We conclude that fast skeletal muscle troponin activation increases force at submaximal activation in both wildtype and NEB KO fiber bundles and, importantly, that this troponin activation is a potential therapeutic mechanism for increasing force in NM and other skeletal muscle diseases with loss of muscle strength. PMID:23437068

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

2013-01-01

190

Exercise-Induced Skeletal Muscle Damage.  

ERIC Educational Resources Information Center

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

Evans, William J.

1987-01-01

191

Functional heterogeneity of side population cells in skeletal muscle  

SciTech Connect

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

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

2006-03-17

192

Exercise Training Improves Cardiac and Skeletal Muscle Metabolism in Rats with Pulmonary Arterial Hypertension  

E-print Network

Exercise Training Improves Cardiac and Skeletal Muscle Metabolism in Rats with Pulmonary Arterial In patients with pulmonary arterial hypertension (PAH), a shift from oxidative to glycolytic metabolism promotes right ventricular (RV) and skeletal muscle dysfunction that contributes to reduced exercise

Zhou, Yaoqi

193

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

PubMed Central

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

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

2014-01-01

194

Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension  

E-print Network

Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent and morphogenesis. While progress has been made in deciphering the molecular mechanism that underlies this process perspective on the regulatory interaction between muscle contraction and skeletal morphogenesis by uncovering

195

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

PubMed

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

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

2014-05-23

196

A micromechanical model of skeletal muscle to explore the effects of fiber and fascicle geometry  

E-print Network

A micromechanical model of skeletal muscle to explore the effects of fiber and fascicle geometry Keywords: Muscle mechanics Micromechanical modeling Homogenization Muscle microstructure Transverse. The goal of this work was to develop micromechanical models of muscle to determine the effects

Blemker, Silvia Salinas

197

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

Technology Transfer Automated Retrieval System (TEKTRAN)

Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

198

Exercise and sex steroid hormones in skeletal muscle.  

PubMed

Sex steroid hormones are secreted mainly by the ovary and testis and regulate diverse physiological processes in target tissues. Recent studies have shown that sex steroidogenesis-related mRNA and protein expressions, such as for 17?-hydroxysteroid dehydrogenase (HSD), 3?-HSD, 5?-reductase and aromatase cytochrome P-450 (P450arom) enzymes, are detected in the skeletal muscle, while testosterone, estradiol, and 5?-dihydrotestosterone (DHT) were locally synthesized in skeletal muscle from dehydroepiandrosterone (DHEA). Moreover, in animal and human studies, the sex steroidogenesis enzymes and sex steroid hormone levels in skeletal muscle are upregulated by acute and chronic exercise stimulation. The enhanced muscle sex steroidgenesis is associated with glycemic control via upregulation of muscle glucose transporter-4 (GLUT-4) signaling in obese and diabetic rats and with muscle mass and strength in older men. Thus, an exercise-induced increase of sex steroid hormone in muscle may positively impact age-related concerns such as life-related diseases and sarcopenia. PMID:24704257

Sato, Koji; Iemitsu, Motoyuki

2015-01-01

199

Mitochondrial biogenesis and angiogenesis in skeletal muscle of the elderly.  

PubMed

The aim of this study was to test the hypotheses that 1) skeletal muscles of elderly subjects can adapt to a single endurance exercise bout and 2) endurance trained elderly subjects have higher expression/activity of oxidative and angiogenic proteins in skeletal muscle than untrained elderly people. To investigate this, lifelong endurance trained elderly (ET; n = 8) aged 71.3 ± 3.4 years and untrained elderly subjects (UT; n = 7) aged 71.3 ± 4 years, performed a cycling exercise bout at 75% VO(2max) with vastus lateralis muscle biopsies obtained before (Pre), immediately after exercise (0 h) and at 2 h of recovery. Capillarization was detected histochemically and oxidative enzyme activities were determined on isolated mitochondria. GLUT4, HKII, Cyt c and VEGF protein expression was measured on muscle lysates from Pre-biopsies, phosphorylation of AMPK and P38 on lysates from Pre and 0 h biopsies, while PGC-1?, VEGF, HKII and TFAM mRNA content was determined at all time points. ET had ~40% higher PDH, CS, SDH, ?-KG-DH and ATP synthase activities and 27% higher capillarization than UT, reflecting increased skeletal muscle oxidative capacity with lifelong endurance exercise training. In addition, acute exercise increased in UT PGC-1? mRNA 11-fold and VEGF mRNA 4-fold at 2 h of recovery, and AMPK phosphorylation ~5-fold immediately after exercise, relative to Pre, indicating an ability to adapt metabolically and angiogenically to endurance exercise. However, in ET PGC-1? mRNA only increased 5 fold and AMPK phosphorylation ~2-fold, while VEGF mRNA remained unchanged after the acute exercise bout. P38 increased similarly in ET and UT after exercise. In conclusion, the present findings suggest that lifelong endurance exercise training ensures an improved oxidative capacity of skeletal muscle, and that skeletal muscle of elderly subjects maintains the ability to respond to acute endurance exercise. PMID:21504786

Iversen, Ninna; Krustrup, Peter; Rasmussen, Hans N; Rasmussen, Ulla F; Saltin, Bengt; Pilegaard, Henriette

2011-08-01

200

Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells  

PubMed Central

During development, cardiac and skeletal muscle share major transcription factors and sarcomere proteins which were generally regarded as specific to either cardiac or skeletal muscle but not both in terminally differentiated adult cardiac or skeletal muscle. Here, we investigated whether artificial muscle constructed from human skeletal muscle derived stem cells (MDSCs) recapitulates developmental similarities between cardiac and skeletal muscle. We constructed 3-dimensional collagen-based engineered muscle tissue (EMT) using MDSCs (MDSC-EMT) and compared the biochemical and contractile properties with EMT using induced pluripotent stem (iPS) cell-derived cardiac cells (iPS-EMT). Both MDSC-EMT and iPS-EMT expressed cardiac specific troponins, fast skeletal muscle myosin heavy chain, and connexin-43 mimicking developing cardiac or skeletal muscle. At the transcriptional level, MDSC-EMT and iPS-EMT upregulated both cardiac and skeletal muscle-specific genes and expressed Nkx2.5 and Myo-D proteins. MDSC-EMT displayed intracellular calcium ion transients and responses to isoproterenol. Contractile force measurements of MDSC-EMT demonstrated functional properties of immature cardiac and skeletal muscle in both tissues. Results suggest that the EMT from MDSCs mimics developing cardiac and skeletal muscle and can serve as a useful in vitro functioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair. PMID:24734224

Tchao, Jason; Kim, Jong Jin; Lin, Bo; Salama, Guy; Lo, Cecilia W.; Yang, Lei; Tobita, Kimimasa

2014-01-01

201

Road to Exercise Mimetics: Targeting Nuclear Receptors in Skeletal Muscle  

PubMed Central

Skeletal muscle comprises the largest organ in the human body and is the major site for energy expenditure. It exhibits remarkable plasticity in response to physiological stimuli such as exercise. Physical exercise remodels skeletal muscle and enhances its capability to burn calories, which has been shown to be beneficial for many clinical conditions including metabolic syndrome and cancer. Nuclear receptors (NRs) comprise a class of transcription factors found only in metazoans that regulate major biological processes such as reproduction, development, and metabolism. Recent studies have demonstrated crucial roles for NRs and their co-regulators in regulating skeletal muscle energy metabolism and exercise-induced muscle remodeling. While nothing can fully replace exercise, development of exercise mimetics that enhance or even substitute for the beneficial effects of physical exercise would be of great benefit. The unique property of NRs that allows modulation by endogenous or synthetic ligands makes them bona fide therapeutic targets. In this review, we present an overview of the current understanding of NRs and their co-regulators in skeletal muscle oxidative metabolism and summarize recent progress in the development of exercise mimetics that target NRs and their co-regulators. PMID:24280961

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

2014-01-01

202

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

PubMed Central

In our preceding companion paper (Wang Y, Winters J, Subramaniam S. J Appl Physiol. doi: 10.1152/japplphysiol.01514.2011), we used extensive expression profile data on normal human subjects, in combination with legacy knowledge to classify skeletal muscle function into four models, namely excitation-activation, mechanical, metabolic, and signaling-production model families. In this paper, we demonstrate how this classification can be applied to study two well-characterized myopathies: amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Using skeletal muscle profile data from ALS and DMD patients compared with that from normal subjects, normal young in the case of DMD, we delineate molecular mechanisms that are causative and consequential to skeletal muscle dysfunction. In ALS, our analysis establishes the metabolic role and specifically identifies the mechanisms of calcium dysregulation and defects in mitochondrial transport of materials as important for muscle dysfunction. In DMD, we illustrate how impaired mechanical function is strongly coordinated with other three functional networks, resulting in transformation of the skeletal muscle into hybrid forms as a compensatory mechanism. Our functional models also provide, in exquisite detail, the mechanistic role of myriad proteins in these four families in normal and disease function. PMID:23085957

Wang, Yu; Winters, Jack

2012-01-01

203

Altered cross-bridge properties in skeletal muscle dystrophies  

PubMed Central

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

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

2014-01-01

204

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

PubMed Central

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

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

2005-01-01

205

Compartmentalized acyl-CoA metabolism in skeletal muscle regulates systemic glucose homeostasis.  

PubMed

The impaired capacity of skeletal muscle to switch between the oxidation of fatty acid (FA) and glucose is linked to disordered metabolic homeostasis. To understand how muscle FA oxidation affects systemic glucose, we studied mice with a skeletal muscle-specific deficiency of long-chain acyl-CoA synthetase (ACSL)1. ACSL1 deficiency caused a 91% loss of ACSL-specific activity and a 60-85% decrease in muscle FA oxidation. Acsl1(M-/-) mice were more insulin sensitive, and, during an overnight fast, their respiratory exchange ratio was higher, indicating greater glucose use. During endurance exercise, Acsl1(M-/-) mice ran only 48% as far as controls. At the time that Acsl1(M-/-) mice were exhausted but control mice continued to run, liver and muscle glycogen and triacylglycerol stores were similar in both genotypes; however, plasma glucose concentrations in Acsl1(M-/-) mice were ?40 mg/dL, whereas glucose concentrations in controls were ?90 mg/dL. Excess use of glucose and the likely use of amino acids for fuel within muscle depleted glucose reserves and diminished substrate availability for hepatic gluconeogenesis. Surprisingly, the content of muscle acyl-CoA at exhaustion was markedly elevated, indicating that acyl-CoAs synthesized by other ACSL isoforms were not available for ?-oxidation. This compartmentalization of acyl-CoAs resulted in both an excessive glucose requirement and severely compromised systemic glucose homeostasis. PMID:25071025

Li, Lei O; Grevengoed, Trisha J; Paul, David S; Ilkayeva, Olga; Koves, Timothy R; Pascual, Florencia; Newgard, Christopher B; Muoio, Deborah M; Coleman, Rosalind A

2015-01-01

206

Neural regulation of parvalbumin expression in mammalian skeletal muscle.  

PubMed Central

Parvalbumin was purified from rabbit fast skeletal muscle and used to raise antibodies in sheep. Subsequently, a sensitive 'sandwich' enzyme-linked immunoadsorbent assay permitted quantification of parvalbumin in homogenates of embryonic, maturing, innervated, denervated and chronically stimulated skeletal muscles of the rabbit. High concentrations of parvalbumin were detected in various adult fast-twitch muscles of the rabbit (700-1200 micrograms/g of muscle), whereas slow-twitch muscles contained negligible concentrations (3-5 micrograms/g of muscle). Parvalbumin was not detectable in embryonic-rabbit muscles (21, 25, 28 days of gestation), either presumptive fast- or slow-twitch. However, parvalbumin concentrations did increase during postnatal development in presumptive fast-twitch muscles. Thus the onset of parvalbumin synthesis appears to be correlated with the neonatal-to-adult transition of motor-neuron activity [Navarrete & Vrbová (1983) Dev. Brain Res. 8, 11-19]. The increase of parvalbumin in maturing, presumptive fast-twitch muscle was suppressed by denervation. In the adult rabbit, denervation of the tibialis anterior muscle caused a reduction of parvalbumin to a level normally found in slow-twitch muscles. In contrast, the already low levels of parvalbumin in maturing and adult slow-twitch soleus muscle were unaffected by denervation. Chronic low-frequency stimulation of adult fast-twitch muscle resulted in a rapid reduction of parvalbumin to a level normally found in slow-twitch muscle. These data support the hypothesis that the expression of parvalbumin is under positive control of fast-type motor-neuron activity. Images Fig. 1. PMID:3741391

Leberer, E; Pette, D

1986-01-01

207

Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading  

NASA Technical Reports Server (NTRS)

The regulatory role of transcriptional alterations in unloaded skeletal muscles was investigated by determining levels of total muscle RNA and mRNA fractions in soleus, gastrocnemius, and extensor digitorum longus (EDL) of rats subjected to whole-body suspension for up to 7 days. After 7 days, total RNA and mRNA contents were lower in soleus and gastrocnemius, compared with controls, but the concentrations of both RNAs per g muscle were unaltered. Alpha-actin mRNA (assessed by dot hybridization) was significantly reduced in soleus after 1, 3, and 7 days of suspension and in gastrocnemius after 3 and 7 days, but was unchanged in EDL. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked alteration in mRNAs coding for several small proteins. Results suggest that altered transcription and availability of specific mRNAs contribute significantly to the regulation of protein synthesis during skeletal muscle unloading.

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

1989-01-01

208

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

PubMed

Muscle wasting impairs physical performance, increases mortality and reduces medical intervention efficacy in chronic diseases and cancer. Developing proficient intervention strategies requires improved understanding of the molecular mechanisms governing muscle mass wasting and recovery. Involvement of muscle protein- and myonuclear turnover during recovery from muscle atrophy has received limited attention. The insulin-like growth factor (IGF)-I signaling pathway has been implicated in muscle mass regulation. As glycogen synthase kinase 3 (GSK-3) is inhibited by IGF-I signaling, we hypothesized that muscle-specific GSK-3? deletion facilitates the recovery of disuse-atrophied skeletal muscle. Wild-type mice and mice lacking muscle GSK-3? (MGSK-3? KO) were subjected to a hindlimb suspension model of reversible disuse-induced muscle atrophy and followed during recovery. Indices of muscle mass, protein synthesis and proteolysis, and post-natal myogenesis which contribute to myonuclear accretion, were monitored during the reloading of atrophied muscle. Early muscle mass recovery occurred more rapidly in MGSK-3? KO muscle. Reloading-associated changes in muscle protein turnover were not affected by GSK-3? ablation. However, coherent effects were observed in the extent and kinetics of satellite cell activation, proliferation and myogenic differentiation observed during reloading, suggestive of increased myonuclear accretion in regenerating skeletal muscle lacking GSK-3?. This study demonstrates that muscle mass recovery and post-natal myogenesis from disuse-atrophy are accelerated in the absence of GSK-3?. PMID:25496993

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

2015-03-01

209

Metformin Protects Skeletal Muscle from Cardiotoxin Induced Degeneration  

PubMed Central

The skeletal muscle tissue has a remarkable capacity to regenerate upon injury. Recent studies have suggested that this regenerative process is improved when AMPK is activated. In the muscle of young and old mice a low calorie diet, which activates AMPK, markedly enhances muscle regeneration. Remarkably, intraperitoneal injection of AICAR, an AMPK agonist, improves the structural integrity of muscles of dystrophin-deficient mdx mice. Building on these observations we asked whether metformin, a powerful anti-hyperglycemic drug, which indirectly activates AMPK, affects the response of skeletal muscle to damage. In our conditions, metformin treatment did not significantly influence muscle regeneration. On the other hand we observed that the muscles of metformin treated mice are more resilient to cardiotoxin injury displaying lesser muscle damage. Accordingly myotubes, originated in vitro from differentiated C2C12 myoblast cell line, become more resistant to cardiotoxin damage after pre-incubation with metformin. Our results indicate that metformin limits cardiotoxin damage by protecting myotubes from necrosis. Although the details of the molecular mechanisms underlying the protective effect remain to be elucidated, we report a correlation between the ability of metformin to promote resistance to damage and its capacity to counteract the increment of intracellular calcium levels induced by cardiotoxin treatment. Since increased cytoplasmic calcium concentrations characterize additional muscle pathological conditions, including dystrophies, metformin treatment could prove a valuable strategy to ameliorate the conditions of patients affected by dystrophies. PMID:25461598

Langone, Francesca; Cannata, Stefano; Fuoco, Claudia; Lettieri Barbato, Daniele; Testa, Stefano; Nardozza, Aurelio Pio; Ciriolo, Maria Rosa; Castagnoli, Luisa; Gargioli, Cesare; Cesareni, Gianni

2014-01-01

210

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

2009-01-01

211

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

2000-01-01

212

Skeletal Muscle ColVI myopathies: where do we stand, where do  

E-print Network

. In particular, mitochondrial dysfunction and a defect in the autophagic clearance system of skeletal muscle haveSkeletal Muscle 7 1 ColVI myopathies: where do we stand, where do we go? Allamand et al. Allamand et al. Skeletal Muscle 2011, 1:30 http://www.skeletalmusclejournal.com/content/1/1/30 (23

Paris-Sud XI, Université de

213

The influence of skeletal muscle on systemic aging and lifespan Fabio Demontis,1,2  

E-print Network

REVIEW The influence of skeletal muscle on systemic aging and lifespan Fabio Demontis,1,2 Rosanna: exercise; intertissue communication during aging; myokine signaling; skeletal muscle aging; systemic aging, we review recent studies highlighting the interconnection of skeletal muscle and systemic aging

Perrimon, Norbert

214

Nitric oxide synthase in human skeletal muscles related to defined fibre types  

Microsoft Academic Search

Skeletal muscle functions regulated by NO are now firmly established. However, the knowledge about the NO synthase (NOS) expression related to a defined fibre type in human skeletal muscles necessitates further clarification. To address this issue, we examined localization of NOS isoforms I, II and III, in human skeletal muscles employing immunocytochemical labeling with tyramide signal amplification complemented with enzyme

Karla Punkt; Matthias Fritzsche; Christoph Stockmar; Pierre Hepp; Christoph Josten; Maren Wellner; Stefan Schering; Igor B. Buchwalow

2006-01-01

215

Ultrastructural alterations in skeletal muscle fibers of rats after exercise  

NASA Technical Reports Server (NTRS)

Ultrastructural alterations in skeletal muscle fibers were electron microscopically studied in rats forced to run on the treadmill until all-out. When they were mild and limited to relatively small areas, the reconstruction of filaments ensued within 10 days without infiltration of cells. When they were severe and extensive, phagocytes infiltrated in the lesions and removed degenerative sacroplasmic debris from muscle fibers. A little later, myoblasts appeared and regeneration was accomplished in 30 days in much the same manner as in myogenesis.

Akuzawa, M.; Hataya, M.

1982-01-01

216

The Emerging Biomolecular Role of Vitamin D in Skeletal Muscle  

PubMed Central

In this review, we summarize current evidence for a direct effect of vitamin D on skeletal muscle. A number of studies identify the receptor for 1,25-dihydroxyvitamin-D3 (vitamin D receptor (VDR)) and the enzyme CYP27B1 (1-?-hydroxylase) in muscle. We hypothesize that vitamin D acts on myocytes via the VDR, and we examine proposed effects on myocyte proliferation, differentiation, growth, and inflammation. PMID:24508736

Pojednic, Rachele M.; Ceglia, Lisa

2015-01-01

217

Myopathic changes in murine skeletal muscle lacking synemin.  

PubMed

Diseases of striated muscle linked to intermediate filament (IF) proteins are associated with defects in the organization of the contractile apparatus and its links to costameres, which connect the sarcomeres to the cell membrane. Here we study the role in skeletal muscle of synemin, a type IV IF protein, by examining mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean fiber diameter, a decrease in twitch and tetanic force, and an increase in susceptibility to injury caused by lengthening contractions. Organization of proteins associated with the contractile apparatus and costameres is not significantly altered in the synm-null. Elastimetry of the sarcolemma and associated contractile apparatus in extensor digitorum longus myofibers reveals a reduction in tension consistent with an increase in sarcolemmal deformability. Although fatigue after repeated isometric contractions is more marked in TA muscles of synm-null mice, the ability of the mice to run uphill on a treadmill is similar to controls. Our results suggest that synemin contributes to linkage between costameres and the contractile apparatus and that the absence of synemin results in decreased fiber size and increased sarcolemmal deformability and susceptibility to injury. Thus synemin plays a moderate but distinct role in fast twitch skeletal muscle. PMID:25567810

García-Pelagio, Karla P; Muriel, Joaquin; O'Neill, Andrea; Desmond, Patrick F; Lovering, Richard M; Lund, Linda; Bond, Meredith; Bloch, Robert J

2015-03-15

218

Characterization of a 6K oligonucleotide turkey skeletal muscle microarray.  

PubMed

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

2011-02-01

219

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.

1989-01-01

220

Acute exercise activates local bioactive androgen metabolism in skeletal muscle.  

PubMed

Androgens, such as testosterone, play important roles in regulation of diverse physiological process of target tissues. Recently, we reported that steroidogenic enzymes exist in skeletal muscle and regulate local production of testosterone in response to exercise. Testosterone is transformed into a bioactive androgen metabolite, dihydrotestosterone (DHT) by 5alpha-reductase. However, it is unclear whether exercise stimulates local bioactive androgen metabolism in the skeletal muscle in both sexes. In the present study, we examined sex differences in the levels of dehydroepiandrosterone (DHEA), free testosterone, DHT, and steroidogenesis-related enzymes 5alpha-reductase and androgen receptor (AR) in rat's skeletal muscle before and after a single bout of exercise. Basal muscular free testosterone and DHT levels were higher in males than females, whereas the levels of DHEA did not differ between the sexes. Muscular DHEA, free testosterone, and DHT levels were increased in both sexes after the exercise. There were no differences of 5alpha-reductase and AR transcripts and proteins between the sexes, and the expression of 5alpha-reductase was significantly increased in both sexes after the exercise. Finally, the expression of AR was significantly higher in female rats, but not in males after the exercise. These data suggest that acute exercise enhances the local bioactive androgen metabolism in the skeletal muscle of both sexes. PMID:20045012

Aizawa, Katsuji; Iemitsu, Motoyuki; Maeda, Seiji; Otsuki, Takeshi; Sato, Koji; Ushida, Takashi; Mesaki, Noboru; Akimoto, Takayuki

2010-03-01

221

MicroRNA Transcriptome Profiles During Swine Skeletal Muscle Development  

Technology Transfer Automated Retrieval System (TEKTRAN)

MicroRNA (miR) are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells,...

222

Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice  

Technology Transfer Automated Retrieval System (TEKTRAN)

Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

223

Quantitation of “autophagic flux” in mature skeletal muscle  

PubMed Central

Reliable and quantitative assays to measure in vivo autophagy are essential. Currently, there are varied methods for monitoring autophagy; however, it is a challenge to measure “autophagic flux” in an in vivo model system. Conversion and subsequent degradation of the microtubule-associated protein 1 light chain 3 (MAP1-LC3/LC3) to the autophagosome associated LC3-II isoform can be evaluated by immunoblot. However, static levels of endogenous LC3-II protein may render possible misinterpretations since LC3-II levels can increase, decrease or remain unchanged in the setting of autophagic induction. Therefore, it is necessary to measure LC3-II protein levels in the presence and absence of lysomotropic agents that block the degradation of LC3-II, a technique aptly named the “autophagometer.” In order to measure autophagic flux in mouse skeletal muscle, we treated animals with the microtubule depolarizing agent colchicine. Two days of 0.4 mg/kg/day intraperitoneal colchicine blocked autophagosome maturation to autolysosomes and increased LC3-II protein levels in mouse skeletal muscle by >100%. the addition of an autophagic stimulus such as dietary restriction or rapamycin led to an additional increase in LC3-II above that seen with colchicine alone. Moreover, this increase was not apparent in the absence of a “colchicine block.” Using this assay, we evaluated the autophagic response in skeletal muscle upon denervation induced atrophy. Our studies highlight the feasibility of performing an “in vivo autophagometer” study using colchicine in skeletal muscle. PMID:20657169

Ju, Jeong-Sun; Varadhachary, Arun S; Miller, Sara E

2010-01-01

224

Distant cis-regulatory elements in human skeletal muscle differentiation  

Microsoft Academic Search

Identifying gene regulatory elements and their target genes in human cells remains a significant challenge. Despite increasing evidence of physical interactions between distant regulatory elements and gene promoters in mammalian cells, many studies consider only promoter-proximal regulatory regions. We identify putative cis-regulatory modules (CRMs) in human skeletal muscle differentiation by combining myogenic TF binding data before and after differentiation with

Rachel Patton McCord; Vicky W. Zhou; Tiffany Yuh; Martha L. Bulyk

225

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.

1986-01-01

226

Lifelong physical exercise delays age-associated skeletal muscle decline.  

PubMed

Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977). PMID:24550352

Zampieri, S; Pietrangelo, L; Loefler, S; Fruhmann, H; Vogelauer, M; Burggraf, S; Pond, A; Grim-Stieger, M; Cvecka, J; Sedliak, M; Tirpáková, V; Mayr, W; Sarabon, N; Rossini, K; Barberi, L; De Rossi, M; Romanello, V; Boncompagni, S; Musarò, A; Sandri, M; Protasi, F; Carraro, U; Kern, H

2015-02-01

227

Advancements in stem cells treatment of skeletal muscle wasting  

PubMed Central

Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders, in which progressive muscle wasting and weakness is often associated with exhaustion of muscle regeneration potential. Although physiological properties of skeletal muscle tissue are now well known, no treatments are effective for these diseases. Muscle regeneration was attempted by means transplantation of myogenic cells (from myoblast to embryonic stem cells) and also by interfering with the malignant processes that originate in pathological tissues, such as uncontrolled fibrosis and inflammation. Taking into account the advances in the isolation of new subpopulation of stem cells and in the creation of artificial stem cell niches, we discuss how these emerging technologies offer great promises for therapeutic approaches to muscle diseases and muscle wasting associated with aging. PMID:24575052

Meregalli, Mirella; Farini, Andrea; Sitzia, Clementina; Torrente, Yvan

2014-01-01

228

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. PMID:23284699

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

2012-01-01

229

Functional classification of skeletal muscle networks. I. Normal physiology  

PubMed Central

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+ fluxes to bind Ca2+ to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling. PMID:23085959

Wang, Yu; Winters, Jack

2012-01-01

230

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

NSDL National Science Digital Library

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

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

2011-04-01

231

Mitochondrial Involvement and Impact in Aging Skeletal Muscle  

PubMed Central

Atrophy is a defining feature of aging skeletal muscle that contributes to progressive weakness and an increased risk of mobility impairment, falls, and physical frailty in very advanced age. Amongst the most frequently implicated mechanisms of aging muscle atrophy is mitochondrial dysfunction. Recent studies employing methods that are well-suited to interrogating intrinsic mitochondrial function find that mitochondrial respiration and reactive oxygen species emission changes are inconsistent between aging rat muscles undergoing atrophy and appear normal in human skeletal muscle from septuagenarian physically active subjects. On the other hand, a sensitization to permeability transition seems to be a general property of atrophying muscle with aging and this effect is even seen in atrophying muscle from physically active septuagenarian subjects. In addition to this intrinsic alteration in mitochondrial function, factors extrinsic to the mitochondria may also modulate mitochondrial function in aging muscle. In particular, recent evidence implicates oxidative stress in the aging milieu as a factor that depresses respiratory function in vivo (an effect that is not present ex vivo). Furthermore, in very advanced age, not only does muscle atrophy become more severe and clinically relevant in terms of its impact, but also there is evidence that this is driven by an accumulation of severely atrophied denervated myofibers. As denervation can itself modulate mitochondrial function and recruit mitochondrial-mediated atrophy pathways, future investigations need to address the degree to which skeletal muscle mitochondrial alterations in very advanced age are a consequence of denervation, rather than a primary organelle defect, to refine our understanding of the relevance of mitochondria as a therapeutic target at this more advanced age. PMID:25309422

Hepple, Russell T.

2014-01-01

232

Plasticity of skeletal muscle mitochondria: structure and function.  

PubMed

Mitochondria in skeletal muscle tissue can undergo rapid and characteristic changes as a consequence of manipulations of muscle use and environmental conditions. Endurance exercise training leads to increases of mitochondrial volume of up to 50% in training interventions of a few weeks in previously untrained subjects. Additionally, a shift of substrate metabolism toward a higher reliance on lipids is observed, structurally reflected as a doubling of the intramyocellular lipid content. A similar increase in intramyocellular lipids without an increase in mitochondrial volume is observed as a consequence of a high-fat diet. Strength training has a major impact on muscle myofibrillar volume, however the mitochondrial compartment appears relatively unchanged. Bedrest and microgravity conditions lead to losses of both myofibrillar and mitochondrial volume, likely as a consequence of the decrease in metabolic and mechanical stress on muscle tissue. Permanent severe hypoxia leads to a loss of muscle mass and muscle oxidative capacity; however, hypoxia signaling events are triggered, which lead to distinct reprogramming phenomena of the transcriptome of the muscle cells. The molecular mechanisms that orchestrate the plasticity of skeletal muscle mitochondria are just beginning to unfold. The present data indicate that transcriptional events largely contribute to increases in mitochondrial mass in human skeletal muscle with endurance training. Expression of mitochondrial proteins from the nuclear and mitochondrial genomes is coordinated and involves the nuclear-encoded transcription factors NRF-1 and TFAM. Transcription of genes encoding the mitochondrial proteins involved in beta oxidation can be regulated separately from the genes of the Krebs cycle and the respiratory chain. Transcription factors AP-1 and PPARalpha/gamma and the protein kinase AMPK are signaling molecules that transduce the metabolic and mechanical factors sensed during endurance training into the complex transcriptional adaptations of mitochondrial proteins. PMID:12544642

Hoppeler, Hans; Fluck, Martin

2003-01-01

233

Stem Cells for Skeletal Muscle Regeneration: Therapeutic Potential and Roadblocks  

PubMed Central

Conditions involving muscle wasting, such as muscular dystrophies, cachexia, and sarcopenia, would benefit from approaches that promote skeletal muscle regeneration. Stem cells are particularly attractive since they are able to differentiate into specialized cell types while retaining the ability to self-renew, and thus provide a long-term response. This review will discuss recent advancements on different types of stem cells that have been attributed to be endowed with muscle regenerative potential. We will discuss the nature of these cells and their advantages and disadvantages in regards to therapy for muscular dystrophies. PMID:24299739

Rinaldi, Fabrizio; Perlingeiro, Rita C. R.

2014-01-01

234

Passive in vivo elastography from skeletal muscle noise  

SciTech Connect

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

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

2007-05-07

235

Cadmium-induced arteriolar constriction in skeletal muscle microcirculation.  

PubMed

Cadmium, an environmental pollutant, is known to induce hypertension in animal models, in part via an increase in peripheral vascular resistance. Since prior studies have investigated the vascular effects of cadmium using large, nonresistance arteries, we directly assessed cadmium's action on resistance size arterioles in skeletal muscle using the intact rat cremaster muscle preparation. Cadmium evoked a concentration-dependent constriction of the large arterioles (120 to 50 microns in diameter) but elicited no change in the diameter of smaller arterioles (30 to 15 microns). Blockade of alpha-adrenergic receptors did not diminish the constrictor response of the larger arterioles to cadmium, but bathing the cremaster muscles with a solution containing low calcium attenuated the arteriolar constriction to cadmium. Calcium repletion caused the arterioles to constrict further. These observations provide the first direct evidence that cadmium constricts resistance arterioles in skeletal muscle. The cadmium constriction: (1) is selective for the large arterioles, (2) is not mediated by alpha-adrenergic receptors, and (3) is influenced by the extracellular level of calcium. We conclude that arteriolar constriction in skeletal muscle tissue may play a role in the hypertensive actions of cadmium. PMID:8507453

Zhang, C; Thind, G S; Joshua, I G; Fleming, J T

1993-04-01

236

Expression of sialic acids in human adult skeletal muscle tissue.  

PubMed

Investigations mostly in animal models have shown a role of sialic acid in the morphology and functionality of skeletal muscle during development and adult life. Several studies in humans have been performed regarding changes in sialic acid expression in a particular pathology, hereditary inclusion body myopathy, leading to muscular weakness and atrophy, with a similar phenomenon appearing also in sarcopenia of aging. In this study the expression of monomeric and polymeric sialic acids was evaluated in human skeletal muscle during adult life. Surgical biopsies of the Quadriceps femoris muscle from men aged 18-25 years (young group; n=8) and men aged 72-78 (elderly group; n=10) were collected for analysis. Expression of sialic acids was evaluated using lectin histochemistry, associated with enzymatic and chemical treatments to characterize monomeric and polymeric sialic acids. The polysialic acid expression was also evaluated by immunohistochemistry. Various types of sialic acid in the muscle tissue, in different amounts in the study groups, were detected. Monomeric sialic acids decreased in the elderly group compared with the young group, whereas polysialic acid increased. Sialic acid acetylation was present only in the young group. These findings demonstrated that changes in the expression of sialic acids in skeletal muscle tissue may be related to morphofunctional modifications occurring during aging. PMID:24703356

Marini, Mirca; Ambrosini, Stefano; Sarchielli, Erica; Thyrion, Giorgia Donata Zappoli; Bonaccini, Laura; Vannelli, Gabriella Barbara; Sgambati, Eleonora

2014-06-01

237

Immunomodulatory effects of massage on nonperturbed skeletal muscle in rats  

PubMed Central

Massage is an ancient manual therapy widely utilized by individuals seeking relief from various musculoskeletal maladies. Despite its popularity, the majority of evidence associated with massage benefits is anecdotal. Recent investigations have uncovered physiological evidence supporting its beneficial use following muscle injury; however, the effects of massage on healthy, unperturbed skeletal muscle are unknown. Utilizing a custom-fabricated massage mimetic device, the purpose of this investigation was to elucidate the effects of various loading magnitudes on healthy skeletal muscle with particular interest in the gene expression profile and modulation of key immune cells involved in the inflammatory response. Twenty-four male Wistar rats (200 g) were subjected to cyclic compressive loading (CCL) over the right tibialis anterior muscle for 30 min, once a day, for 4 consecutive days using four loading conditions: control (0N), low load (1.4N), moderate load (4.5N), and high load (11N). Microarray analysis showed that genes involved with the immune response were the most significantly affected by application of CCL. Load-dependent changes in cellular abundance were seen in the CCL limb for CD68+ cells, CD163+ cells, and CD43+cells. Surprisingly, load-independent changes were also discovered in the non-CCL contralateral limb, suggesting a systemic response. These results show that massage in the form of CCL exerts an immunomodulatory response to uninjured skeletal muscle, which is dependent upon the applied load. PMID:24201707

Waters-Banker, Christine; Dupont-Versteegden, Esther E.

2013-01-01

238

Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models  

NASA Technical Reports Server (NTRS)

An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

Marquette, Michele L.; Sognier, Marguerite A.

2013-01-01

239

Compartmentalization of NO signaling cascade in skeletal muscles  

SciTech Connect

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

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

2005-05-06

240

Influence of spaceflight on rat skeletal muscle  

NASA Technical Reports Server (NTRS)

The effect of a 7-day spaceflight (aboard NASA's SL-3) on the size and the metabolism of single fibers from several rat muscles was investigated along with the specificity of these responses as related to the muscle type and the size of fibers. It was found that the loss of mass after flight was varied from 36 percent in the soleus to 15 percent in the extensor digitorum longus. Results of histochemical analyses showed that the succinate dehydrogenase (SDH) activity in muscles of flight-exposed rats was maintained at the control levels, whereas the alpha-glycerol phosphate dehydrogenase (GPD) activity was either maintained or increased. The analyses of the metabolic profiles of ATPase, SDH, and GPD indicated that, in some muscles, there was an increase in the poportion of fast oxidative-glycolytic fibers.

Martin, Thomas P.; Edgerton, V. Reggie; Grindeland, Richard E.

1988-01-01

241

Direct Central Nervous System Effect of Alcohol Alters Synthesis and Degradation of Skeletal Muscle Protein  

PubMed Central

Aims: Alcohol can directly impair protein synthesis in cultured myocytes as well as in in situ perfused skeletal muscle. However, alcohol in the general circulation diffuses rapidly into the central nervous system (CNS). Therefore, this study determined whether localized elevation of alcohol within the CNS is capable of decreasing muscle protein synthesis. Methods: Conscious unstrained male rats received a continuous intracerebroventricular (ICV) infusion of ethanol and skeletal muscle protein synthesis and degradation were assessed. Results: ICV alcohol decreased protein synthesis in the gastrocnemius after 6 and 24 h, compared with the time-matched controls. The reduction was equivalent for both sarcoplasmic and myofibrillar proteins and was reversible. The inhibitory effect of alcohol was not prevented by the catalase inhibitor 3-amino-1,2,4-triazole and was mimicked by ICV-administered t-butanol. The alcohol-induced decrease in muscle protein synthesis was associated with a concomitant reduction in phosphorylation of 4E-binding protein and ribosomal S6 kinase-1, suggesting impaired mammalian target of rapamycin kinase activity. ICV alcohol also impaired the ability of leucine to stimulate protein synthesis. Conversely, ICV alcohol increased muscle proteasome activity and muscle RING-finger protein-1 mRNA content. Altered muscle protein metabolism was not associated with changes in muscle mRNA content for tumor necrosis factor ?, interleukin-6 or insulin-like growth factor (IGF)-I or circulating insulin or IGF-I. Conclusion: Selective elevation of alcohol within the CNS is capable of decreasing protein synthesis and increasing protein degradation in muscle in the absence of alcohol in the general circulation, thus revealing a previously unrecognized central neural mechanism, which may account for part of the inhibitory effect of ingested alcohol on muscle protein homeostasis. PMID:23079499

Pruznak, Anne M.; Nystrom, Jay; Lang, Charles H.

2013-01-01

242

Skeletal muscle metastasis from breast cancer: management and literature review.  

PubMed

Skeletal muscle metastasis from breast cancer is a very rare clinical entity. We describe an extremely rare case of breast cancer metastasis to the rectus abdominis muscle. Our patient, who had undergone a left modified radical mastectomy for breast cancer four years ago, presented with a painful abdominal mass. Computed tomography scans showed a rim-enhancing mass with central hypoatennuation within the sheath of the rectus abdominis muscle. A Fine needle aspiration biopsy was initially performed and the findings were suggestive of malignancy. The muscle lesion was then resected and the histopathological analysis showed metastasis of breast cancer. Through our review of the literature, we found that only two cases of rectus abdominis muscle metastasis from breast cancer have been reported so far. This case highlights the need to rule out muscle metastatic lesions in patients with history of breast cancer presenting with these clinical and imaging characteristics. Differentiation from primary sarcoma is of paramount importance. Skeletal muscle metastases usually indicate an advanced disease associated with poor prognosis. Treatment should be individualized depending on the patient's clinical condition. PMID:25159186

Salemis, Nikolaos S

2015-01-01

243

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...

244

The formation of skeletal muscle: from somite to limb  

PubMed Central

During embryogenesis, skeletal muscle forms in the vertebrate limb from progenitor cells originating in the somites. These cells delaminate from the hypaxial edge of the dorsal part of the somite, the dermomyotome, and migrate into the limb bud, where they proliferate, express myogenic determination factors and subsequently differentiate into skeletal muscle. A number of regulatory factors involved in these different steps have been identified. These include Pax3 with its target c-met, Lbx1 and Mox2 as well as the myogenic determination factors Myf5 and MyoD and factors required for differentiation such as Myogenin, Mrf4 and Mef2 isoforms. Mutants for genes such as Lbx1 and Mox2, expressed uniformly in limb muscle progenitors, reveal unexpected differences between fore and hind limb muscles, also indicated by the differential expression of Tbx genes. As development proceeds, a secondary wave of myogenesis takes place, and, postnatally, satellite cells become located under the basal lamina of adult muscle fibres. Satellite cells are thought to be the progenitor cells for adult muscle regeneration, during which similar genes to those which regulate myogenesis in the embryo also play a role. In particular, Pax3 as well as its orthologue Pax7 are important. The origin of secondary/fetal myoblasts and of adult satellite cells is unclear, as is the relation of the latter to so-called SP or stem cell populations, or indeed to potential mesangioblast progenitors, present in blood vessels. The oligoclonal origin of postnatal muscles points to a small number of founder cells, whether or not these have additional origins to the progenitor cells of the somite which form the first skeletal muscles, as discussed here for the embryonic limb. PMID:12587921

Buckingham, Margaret; Bajard, Lola; Chang, Ted; Daubas, Philippe; Hadchouel, Juliette; Meilhac, Sigolène; Montarras, Didier; Rocancourt, Didier; Relaix, Frédéric

2003-01-01

245

Atomoxetine prevents dexamethasone-induced skeletal muscle atrophy in mice.  

PubMed

Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. ?2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator-activated receptor-? coactivator-1 ? (PGC-1?) isoforms, ATP synthase ?, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 ? subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1?-4-IGF1-Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1? expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. PMID:25292181

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

2014-12-01

246

Enhanced Myogenesis in adult skeletal muscle by transgenic expression of Myostatin Propeptide  

Technology Transfer Automated Retrieval System (TEKTRAN)

Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-ß, plays a dominant role in the genetic control of muscle mass. Transgenic expression of myostatin propeptide in skeletal muscle showed ...

247

Electrospun degradable polyesterurethane membranes: potential scaffolds for skeletal muscle tissue engineering  

Microsoft Academic Search

Skeletal muscle tissue engineering represents an attractive approach to overcome problems associated with autologous transfer of muscle tissue and provides a valid alternative in muscle regeneration enhancement. The aim of this study was to investigate the suitability, as scaffold for skeletal muscle tissue engineering, of a known biodegradable block copolymer (DegraPol®) processed by electrospinning in the novel form of microfibrous

Stefania A. Riboldi; Maurilio Sampaolesi; Peter Neuenschwander; Giulio Cossu; Sara Mantero

2005-01-01

248

Anisotropy of ultrasonic propagation and scattering properties in fresh rat skeletal muscle in vitro  

E-print Network

in fresh rat skeletal muscle within 5 h post-mortem. Excised rat semimembranosus and soleus muscles- fresh anisotropy studies. Results are presented for ten rat soleus muscles, and ten rat semimembranosusAnisotropy of ultrasonic propagation and scattering properties in fresh rat skeletal muscle

Illinois at Urbana-Champaign, University of

249

Functional morphology of serially linked skeletal muscle fibers.  

PubMed

In the skeletal muscle fiber organization of many vertebrate muscles, serial arrangements or linkages of muscle fibers along the muscle or fascicle are commonly found. These serially linked muscle fibers employ distinct junctional morphologies from muscle to muscle. Notable are the end-to-end linkages of muscle fibers through tendinous intersections (TIs), where many fibers end onto a continuous connective tissue plate with folded terminations similar to myotendinous junctions. Besides this end-to-end linkage, overlapping linkages or arrangements occur among nonspanning fibers terminating intrafascicularly. These nonspanning fibers bear tapering terminations with direct cell-cell (myomuscular) junctions or without any specialized junctions. Despite their overlapping linkages or tapering profiles, nonspanning fibers maintain a uniform sarcomere length along the linked fibers, suggesting that the overlapping-linked nonspanning fibers are equivalent to the end-to-end linked fibers in their mechanical capacity. However, the junctional compliance could differ in their extracellular elastic components and their organization at junctional sites, e.g., direct mechanical (myomuscular) junctions vs. indirect linkages through connective tissue. Increasing evidence suggests that the elastic components, including muscle fibers as well as connective tissues, are more critical than previously thought for the mode and/or the efficiency of tension transmission among serially arranged fibers and thus for the mechanical properties of the muscle. PMID:9575360

Hijikata, T; Ishikawa, H

1997-01-01

250

The genetics of skeletal muscle disorders in horses.  

PubMed

Horses are remarkable athletes and a fascinating species in which to study the genetic bases of athletic performance, skeletal muscle biology, and neuromuscular disease. Genetic selection in horses has resulted in many breeds that possess anatomical, physiological, and metabolic variations linked to speed, power, and endurance that are beginning to be defined at the molecular level. Along with the concentration of positive traits, equine breeding programs have also inadvertently concentrated heritable muscle diseases for which mutations impacting electrical conduction, muscle contraction, and energy metabolism within and across breeds have been characterized. The study of heritable muscle diseases in horses has provided exciting insights into the normal structure and function of muscle and important diagnostic tools for veterinarians. Results empower breeders and breed associations to make difficult decisions about how to use this information to improve the overall health and well-being of horses. PMID:25387114

Mickelson, James R; Valberg, Stephanie J

2015-02-16

251

Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma.  

PubMed

We present a rare case of intrahepatic cholangiocarcinoma (ICC) with multiple skeletal muscle metastases. The patient was a 55-year-old Asian woman presenting with abdominal pain; abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area. After 3 mo of treatment with palliative radiotherapy and chemotherapy, magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases. We performed an ultrasound-guided percutaneous fine-needle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma. The patient treated with palliative chemotherapy and achieved 10 mo of survival. Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment, compare to the other cases reported muscle metastases at diagnosis. PMID:25684968

Lee, Jiyoung; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Kim, Su Young; Rhyou, Hyo In

2015-02-14

252

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. PMID:23509749

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

2013-01-01

253

Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma  

PubMed Central

We present a rare case of intrahepatic cholangiocarcinoma (ICC) with multiple skeletal muscle metastases. The patient was a 55-year-old Asian woman presenting with abdominal pain; abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area. After 3 mo of treatment with palliative radiotherapy and chemotherapy, magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases. We performed an ultrasound-guided percutaneous fine-needle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma. The patient treated with palliative chemotherapy and achieved 10 mo of survival. Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment, compare to the other cases reported muscle metastases at diagnosis. PMID:25684968

Lee, Jiyoung; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Kim, Su Young; Rhyou, Hyo In

2015-01-01

254

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

1997-01-01

255

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

Microsoft Academic Search

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 syn- chronized muscle infections, (3H)thymidine was incor- porated into infected cell nuclei from 2-5 days post infection. Labeled nuclei were stably integrated into the infected

Douglas E Jasmer

1993-01-01

256

Metabolic adaptations in skeletal muscle overexpressing GLUT4: effects on muscle and physical activity  

Microsoft Academic Search

To understand the long-term metabolic and functional consequences of increased GLUT4 con- tent, intracellular substrate utilization was investigated in isolated muscles of transgenic mice overexpressing GLUT4 selectively in fast-twitch skeletal muscles. Rates of glycolysis, glycogen synthesis, glucose oxidation, and free fatty acid (FFA) oxidation as well as glycogen content were assessed in isolated EDL (fast-twitch) and soleus (slow-twitch) muscles from

TSU-SHUEN TSAO; JING LI; KENNETH S. CHANG; ANTINE E. STENBIT; DANA GALUSKA; JUDY E. ANDERSON; JULEEN R. ZIERATH; ROGER J. MCCARTER; MAUREEN J. CHARRON

2001-01-01

257

Mitosis and intermediate-sized filaments in developing skeletal muscle  

Microsoft Academic Search

ABSTRACT A new,class of filaments intermediate,in diameter,between,actin and,myosin,filaments has been demonstrated in skeletal muscle cells cultured from chick embryos. These filaments, which account for the majorarrested in metaphase,by mitotic inhibitors. Definitive thick (about 150 A) or thin (about 60 A) myofilaments,are not found in skeletal myogenic,cells arrested in metaphase. Myogenic,cells arrested in metaphase,do not bind fluorescein-labeled,antibody,directed against myosin or actin.

H Ishikawa; R. Bischoff; H. Holtzer

1969-01-01

258

Skeletal muscle responses to unweighting in humans  

NASA Technical Reports Server (NTRS)

An overview of earth-based studies is presented emphasizing the data on muscular strength and size derived from experiments under simulated microgravity. The studies involve the elimination of weight-bearing responsibility of lower-limb human musculature to simulate the unweighting effects of space travel in the absence of exercise. Reference is given to bedrest and unilateral lower-limb suspension, both of which provide data that demonstrate the decreased strength of the knee extensors of 20-25 percent. The response is related to the decrease in cross-sectional area of the knee extensors which is a direct indication of muscle-fiber atrophy. Most of the effects of unweighting are associated with extensor muscles in the lower limbs and not with postural muscles. Unweighting is concluded to cause significant adaptations in the human neuromuscular system that require further investigation.

Dudley, Gary A.

1991-01-01

259

Neuromuscular Electrical Stimulation for Skeletal Muscle Function  

PubMed Central

Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

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

2012-01-01

260

Diaphragmatic lymphatic vessel behavior during local skeletal muscle contraction.  

PubMed

The mechanism through which the stresses developed in the diaphragmatic tissue during skeletal muscle contraction sustain local lymphatic function was studied in 10 deeply anesthetized, tracheotomized adult Wistar rats whose diaphragm was exposed after thoracotomy. To evaluate the direct effect of skeletal muscle contraction on the hydraulic intraluminal lymphatic pressures (Plymph) and lymphatic vessel geometry, the maximal contraction of diaphragmatic fibers adjacent to a lymphatic vessel was elicited by injection of 9.2 nl of 1 M KCl solution among diaphragmatic fibers while Plymph was recorded through micropuncture and vessel geometry via stereomicroscopy video recording. In lymphatics oriented perpendicularly to the longitudinal axis of muscle fibers and located at <300 ?m from KCl injection, vessel diameter at maximal skeletal muscle contraction (Dmc) decreased to 61.3 ± 1.4% of the precontraction value [resting diameter (Drest)]; however, if injection was at >900 ?m from the vessel, Dmc enlarged to 131.1 ± 2.3% of Drest. In vessels parallel to muscle fibers, Dmc increased to 122.8 ± 2.9% of Drest. During contraction, Plymph decreased as much as 22.5 ± 2.6 cmH2O in all submesothelial superficial vessels, whereas it increased by 10.7 ± 5.1 cmH2O in deeper vessels running perpendicular to contracting muscle fibers. Hence, the three-dimensional arrangement of the diaphragmatic lymphatic network seems to be finalized to efficiently exploit the stresses exerted by muscle fibers during the contracting inspiratory phase to promote lymph formation in superficial submesothelial lymphatics and its further propulsion in deeper intramuscular vessels. PMID:25485903

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

2015-02-01

261

Roles of ADAM8 in elimination of injured muscle fibers prior to skeletal muscle regeneration.  

PubMed

Skeletal muscle regeneration requires processes different from developmental myogenesis. One important difference is a requirement of inflammatory reactions prior to regenerative myogenesis, by which injured muscle fibers must be eliminated to make new myotubes. In this study, we show that efficient elimination of injured muscle fibers during regeneration requires ADAM8, a member of a disintegrin and metalloprotease (ADAM) family. Skeletal muscle of dystrophin-null mice, an animal model for Duchenne Muscular Dystrophy, deteriorates by the lack of ADAM8, which is characterized by increased area of muscle degeneration and increased number of necrotic and calcified muscle fibers. Adam8 is highly expressed in neutrophils. Upon cardiotoxin-induced skeletal muscle injury, neutrophils invade into muscle fibers through the basement membrane and form large clusters in wild type, but not in ADAM8-deficient mice, although neutrophils of the latter infiltrate into interstitial tissues similarly to those of wild type mice. Neutrophils lose their adhesiveness to blood vessels after infiltration, which includes an ectodomain shedding of P-Selectin Glycoprotein Ligand-1 (PSGL-1) on their surface. Expression of PSGL-1 on the surface of neutrophils remains higher in ADAM8-deficient than in wild type mice. These results suggest that ADAM8 mediates an enhanced invasiveness of neutrophils into injured muscle fibers by the removal of their adhesiveness to blood vessels after infiltration into interstitial tissues. PMID:25511460

Nishimura, Daigo; Sakai, Hiroshi; Sato, Takahiko; Sato, Fuminori; Nishimura, Satoshi; Toyama-Sorimachi, Noriko; Bartsch, Jörg W; Sehara-Fujisawa, Atsuko

2015-02-01

262

Cardiovascular regulation by skeletal muscle reflexes in health and disease  

PubMed Central

Heart rate and blood pressure are elevated at the onset and throughout the duration of dynamic or static exercise. These neurally mediated cardiovascular adjustments to physical activity are regulated, in part, by a peripheral reflex originating in contracting skeletal muscle termed the exercise pressor reflex. Mechanically sensitive and metabolically sensitive receptors activating the exercise pressor reflex are located on the unencapsulated nerve terminals of group III and group IV afferent sensory neurons, respectively. Mechanoreceptors are stimulated by the physical distortion of their receptive fields during muscle contraction and can be sensitized by the production of metabolites generated by working skeletal myocytes. The chemical by-products of muscle contraction also stimulate metaboreceptors. Once activated, group III and IV sensory impulses are transmitted to cardiovascular control centers within the brain stem where they are integrated and processed. Activation of the reflex results in an increase in efferent sympathetic nerve activity and a withdrawal of parasympathetic nerve activity. These actions result in the precise alterations in cardiovascular hemodynamics requisite to meet the metabolic demands of working skeletal muscle. Coordinated activity by this reflex is altered after the development of cardiovascular disease, generating exaggerated increases in sympathetic nerve activity, blood pressure, heart rate, and vascular resistance. The basic components and operational characteristics of the reflex, the techniques used in human and animals to study the reflex, and the emerging evidence describing the dysfunction of the reflex with the advent of cardiovascular disease are highlighted in this review. PMID:21841019

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

2011-01-01

263

Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.  

PubMed Central

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting. PMID:9202072

Tawa, N E; Odessey, R; Goldberg, A L

1997-01-01

264

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis  

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

265

Activity Dependent Signal Transduction in Skeletal Muscle  

NASA Technical Reports Server (NTRS)

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

Hamilton, Susan L.

1999-01-01

266

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy  

NASA Technical Reports Server (NTRS)

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

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

2001-01-01

267

Oxidative stress impairs skeletal muscle repair in diabetic rats.  

PubMed

Alongside increased proteolysis, the inability to repair damaged skeletal muscle is a characteristic feature of uncontrolled diabetes. This study evaluates the role of oxidative stress in muscle-specific gene regulatory regions and myosin chain synthesis in streptozotocin (STZ)-induced diabetic and ZDF rats. In the gastrocnemius muscle of diabetic rats, prooxidant compounds were seen to increase while antioxidant levels fell. Myogenic regulatory factors--Myo, myogenin, and Jun D--were also reduced, and muscle enhancer factor (MEF)-1 DNA binding activity was impaired. Moreover, synthesis of muscle creatine kinase and both heavy and light chains of myosin were impaired, suggesting that oxidative stress triggers the cascade of events that leads to impaired muscle repair. Dehydroepiandrosterone has been reported to possess antioxidant properties. When it was administered to diabetic rats, in addition to an improved oxidative imbalance there was a recovery of myogenic factors, MEF-1 DNA binding activity, synthesis of muscle creatine kinase, and myosin light and heavy chains. Vitamin E administration to STZ-induced diabetic rats reverses oxidative imbalance and improves muscle gene transcription, reinforcing the suggestion that oxidative stress may play a role in diabetes-related impaired muscle repair. PMID:15047625

Aragno, Manuela; Mastrocola, Raffaella; Catalano, Maria Graziella; Brignardello, Enrico; Danni, Oliviero; Boccuzzi, Giuseppe

2004-04-01

268

Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy.  

PubMed

Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy. PMID:25406264

Bongers, Kale S; Fox, Daniel K; Kunkel, Steven D; Stebounova, Larissa V; Murry, Daryl J; Pufall, Miles A; Ebert, Scott M; Dyle, Michael C; Bullard, Steven A; Dierdorff, Jason M; Adams, Christopher M

2015-01-15

269

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

PubMed

The ryanodine receptor, a Ca(2+)-releasing channel in sarcoplasmic reticulum (SR), plays an important role in the excitation-contraction coupling of skeletal muscle. In a previous study [Hirata, Nakahata and Ohizumi (2000) Mol. Pharmacol. 57, 1235-1242], we reported that mastoparan caused Ca(2+) release through ryanodine receptor from the heavy fraction of SR (HSR) isolated from rabbit skeletal muscle, and that it specifically bound to a 97 kDa protein which was distinct from Ca(2+)-pump or triadin. The present study was undertaken to identify and characterize the 97 kDa mastoparan-binding protein. The 97 kDa protein was purified from solubilized HSR by DEAE-Sepharose column chromatography and preparative SDS/PAGE. The partial amino acid sequence of the purified 97 kDa protein was matched with that of glycogen phosphorylase (GP). The proteolytic cleavage pattern of the 97 kDa protein was identical with that of GP. Furthermore, [(125)I-Tyr(3)]mastoparan specifically bound to GP. Interestingly, mastoparan-induced Ca(2+) release was inhibited by exogenous addition of GP-a, and mastoparan dissociated GP from HSR. These results indicate that the 97 kDa mastoparan-binding protein is GP, which negatively regulates Ca(2+) release from HSR. There may be a functional cross-talk between Ca(2+) release from HSR and glycogenolysis for energy supply mediated through GP in skeletal muscles. PMID:12519071

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

2003-04-01

270

Analysis of muscle gene transcription in cultured skeletal muscle cells.  

PubMed

The mechanisms by which muscle gene expression is initiated and maintained are not fully understood. Muscle genes are regulated by combinatorial interactions between numerous transcription factors bound to enhancers and promoters, and their associated protein complexes. Among the most important are the MyoD and MEF2 transcription factor families, but dozens of other factors play important regulatory roles, and many additional transcription factors are certain to be involved. Expression of muscle-specific genes varies among different anatomical muscles and in fast- vs. slow-twitch fiber types, suggesting different mechanisms of regulation in response to diverse physiological cues. Thus, identifying novel transcriptional regulators and interactions is key to understanding how different cells establish the muscle phenotype; it is also critical for developing methods to combat diseases such as muscular dystrophy. Using Muscle creatine kinase as a model, we outline the key steps involved in identifying muscle gene control elements, their binding factors, and mechanisms of transcriptional activation and repression. The basic principles described here can also be applied to the transcriptional analysis of other cell-type specific genes. PMID:22130852

Himeda, Charis L; Tai, Phillip W L; Hauschka, Stephen D

2012-01-01

271

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.

2003-06-01

272

Mutations in the skeletal muscle ?-actin gene in patients with actin myopathy and nemaline myopathy  

Microsoft Academic Search

Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin

Kristen J. Nowak; Duangrurdee Wattanasirichaigoon; Hans H. Goebel; Matthew Wilce; Katarina Pelin; Kati Donner; Rebecca L. Jacob; Christoph Hübner; Konrad Oexle; Janice R. Anderson; Christopher M. Verity; Kathryn N. North; Susan T. Iannaccone; Clemens R. Müller; Peter Nürnberg; Francesco Muntoni; Caroline Sewry; Imelda Hughes; Rebecca Sutphen; Atilano G. Lacson; Kathryn J. Swoboda; Jaqueline Vigneron; Carina Wallgren-Pettersson; Alan H. Beggs; Nigel G. Laing

1999-01-01

273

Textbook Reading Assignment: Sadava Ch. 48 Skeletal Muscular System General: This is an important chapter muscles make up most of your body and are  

E-print Network

Textbook Reading Assignment: Sadava Ch. 48 ­ Skeletal Muscular System: Skeletal, cardiac and smooth muscle, myoblast Striated vs. smooth muscle Muscle fiber Tropomyosin Actin Myosin Twitch Tetanus (tetany) Slow twitch, oxidative skeletal muscle

Prestwich, Ken

274

Bone marrow-derived cell regulation of skeletal muscle regeneration  

PubMed Central

Limb regeneration requires the coordination of multiple stem cell populations to recapitulate the process of tissue formation. Therefore, bone marrow (BM) -derived cell regulation of skeletal muscle regeneration was examined in mice lacking the CC chemokine receptor 2 (CCR2). Myofiber size, numbers of myogenic progenitor cells (MPCs), and recruitment of BM-derived cells and macrophages were assessed after cardiotoxin-induced injury of chimeric mice produced by transplanting BM from wild-type (WT) or CCR2?/? mice into irradiated WT or CCR2?/? host mice. Regardless of the host genotype, muscle regeneration and recruitment of BM-derived cells and macrophages were similar in mice replenished with WT BM, whereas BM-derived cells and macrophage accumulation were decreased and muscle regeneration was impaired in all animals receiving CCR2?/? BM. Furthermore, numbers of MPCs (CD34+/Sca-1?/CD45? cells) were significantly increased in mice receiving CCR2?/? BM despite the decreased size of regenerated myofibers. Thus, the expression of CCR2 on BM-derived cells regulated macrophage recruitment into injured muscle, numbers of MPC, and the extent of regenerated myofiber size, all of which were independent of CCR2 expression on host-derived cells. Future studies in regenerative medicine must include consideration of the role of BM-derived cells, possibly macrophages, in CCR2-dependent events that regulate effective skeletal muscle regeneration.—Sun, D., Martinez, C. O., Ochoa, O., Ruiz-Willhite, L., Bonilla, J. R., Centonze, V. E., Waite, L. L., Michalek, J. E., McManus, L. M., Shireman, P. K. Bone marrow-derived cell regulation of skeletal muscle regeneration. PMID:18827026

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

2009-01-01

275

Skeletal muscle ?-actin diseases (actinopathies): pathology and mechanisms.  

PubMed

Mutations in the skeletal muscle ?-actin gene (ACTA1) cause a range of congenital myopathies characterised by muscle weakness and specific skeletal muscle structural lesions. Actin accumulations, nemaline and intranuclear bodies, fibre-type disproportion, cores, caps, dystrophic features and zebra bodies have all been seen in biopsies from patients with ACTA1 disease, with patients frequently presenting with multiple pathologies. Therefore increasingly it is considered that these entities may represent a continuum of structural abnormalities arising due to ACTA1 mutations. Recently an ACTA1 mutation has also been associated with a hypertonic clinical presentation with nemaline bodies. Whilst multiple genes are known to cause many of the pathologies associated with ACTA1 mutations, to date actin aggregates, intranuclear rods and zebra bodies have solely been attributed to ACTA1 mutations. Approximately 200 different ACTA1 mutations have been identified, with 90 % resulting in dominant disease and 10 % resulting in recessive disease. Despite extensive research into normal actin function and the functional consequences of ACTA1 mutations in cell culture, animal models and patient tissue, the mechanisms underlying muscle weakness and the formation of structural lesions remains largely unknown. Whilst precise mechanisms are being grappled with, headway is being made in terms of developing therapeutics for ACTA1 disease, with gene therapy (specifically reducing the proportion of mutant skeletal muscle ?-actin protein) and pharmacological agents showing promising results in animal models and patient muscle. The use of small molecules to sensitise the contractile apparatus to Ca(2+) is a promising therapeutic for patients with various neuromuscular disorders, including ACTA1 disease. PMID:22825594

Nowak, Kristen J; Ravenscroft, Gianina; Laing, Nigel G

2013-01-01

276

Muscle Atrophy in Response to Cytotoxic Chemotherapy Is Dependent on Intact Glucocorticoid Signaling in Skeletal Muscle  

PubMed Central

Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia. PMID:25254959

Braun, Theodore P.; Szumowski, Marek; Levasseur, Peter R.; Grossberg, Aaron J.; Zhu, XinXia; Agarwal, Anupriya; Marks, Daniel L.

2014-01-01

277

cap alpha. -skeletal and. cap alpha. -cardiac actin genes are coexpressed in adult human skeletal muscle and heart  

SciTech Connect

The authors determined the actin isotypes encoded by 30 actin cDNA clones previously isolated from an adult human muscle cDNA library. Using 3' untranslated region probes, derived from ..cap alpha.. skeletal, ..beta..- and ..gamma..-actin cDNAs and from an ..cap alpha..-cardiac actin genomic clone, they showed that 28 of the cDNAs correspond to ..cap alpha..-skeletal actin transcripts. Unexpectedly, however, the remaining two cDNA clones proved to derive from ..cap alpha..-cardiac actin mRNA. Sequence analysis confirmed that the two skeletal muscle ..cap alpha..-cardiac actin cDNAs are derived from transcripts of the cloned ..cap alpha..-cardiac actin gene. Comparison of total actin mRNA levels in adult skeletal muscle and adult heart revealed that the steady-state levels in skeletal muscle are about twofold greater, per microgram of total cellular RNA, than those in heart. Thus, in skeletal muscle and in heart, both of the sarcomeric actin mRNA isotypes are quite abundant transcripts. They conclude that ..cap alpha..-skeletal and ..cap alpha..-cardiac actin genes are coexpressed as an actin pair in human adult striated muscles. Since the smooth-muscle actins (aortic and stomach) and the cytoplasmic actins (..beta.. and ..gamma..) are known to be coexpressed in smooth muscle and nonmuscle cells, respectively, they postulate that coexpression of actin pairs may be a common feature of mammalian actin gene expression in all tissues.

Gunning, P.; Ponte, P.; Blau, H.; Kedes, L.

1983-11-01

278

Effect of hindlimb immobilization on the fatigability of skeletal muscle  

NASA Technical Reports Server (NTRS)

The effect of 6 weeks of disuse atrophy produced by hindlimb immobilization was studied in situ (33.5 C) in the soleus and extensor digitorum longus muscles of rats. The results indicate that disuse causes preferential alterations in the isometric contractile properties of slow-twitch, as opposed to fast-twitch, skeletal muscles. During continuous contractile activity, atrophied muscles were found to have lower ATP levels and an apparent increase in their dependence on anaerobic metabolism, as reflected by the more extensive depletion of glycogen and enhanced lactate formation. Although the atrophied muscles were determined to have fewer cross bridges and thus generated lower tension, the pattern of decline in active cross-bridge formation and tetanic tension during contractile activity was found to proceed in a manner similar to controls.

Witzmann, F. A.; Kim, D. H.; Fitts, R. H.

1983-01-01

279

NOTE: Anisotropic photon migration in human skeletal muscle  

NASA Astrophysics Data System (ADS)

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

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

2006-03-01

280

Methods for the Organogenesis of Skeletal Muscle in Tissue Culture  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

281

Vasodilator interactions in skeletal muscle blood flow regulation.  

PubMed

During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or on the extraluminal side of the blood vessels. A number of vasodilators have been shown to bring about this increase in blood flow and, importantly, interactions between these compounds seem to be essential for the precise regulation of blood flow. Two compounds stand out as central in these vasodilator interactions: nitric oxide (NO) and prostacyclin. These two vasodilators are both stimulated by several compounds, e.g. adenosine, ATP, acetylcholine and bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperaemic response remains unexplained. It is plausible that this remaining hyperaemia may be explained by cAMP- and cGMP-independent smooth muscle relaxation, such as effects of endothelial derived hyperpolarization factors (EDHFs) or through metabolic modulation of sympathetic effects. The nature and role of EDHF as well as potential novel mechanisms in muscle blood flow regulation remain to be further explored to fully elucidate the regulation of exercise hyperaemia. PMID:22988140

Hellsten, Y; Nyberg, M; Jensen, L G; Mortensen, S P

2012-12-15

282

Dysferlin overexpression in skeletal muscle produces a progressive myopathy  

PubMed Central

Objective The dose-response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy. Methods We have generated three lines of transgenic mice, expressing low, mid and high levels of full-length human dysferlin from a muscle-specific promoter. Transgenic skeletal muscle was analyzed and scored for morphological and functional deficits. Results Overexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait and reduced muscle mass and strength. Moreover, protein dosage correlated with phenotype severity. In contrast to dysferlin-null skeletal muscle, no evidence of sarcolemmal impairment was revealed. Rather, increased levels of Ca2+-regulated, dysferlin-binding proteins and ER stress chaperone proteins were observed in muscle lysates from transgenic mice as compared to controls. Interpretation Expression levels of dysferlin are important for appropriate function without deleterious or cytotoxic effects. As a corollary, we propose that future endeavors in gene replacement for correction of dysferlinopathy should be tailored to take account of this. PMID:20373350

Glover, Louise E.; Newton, Kimberly; Krishnan, Gomathi; Bronson, Roderick; Boyle, Alexandra; Krivickas, Lisa S.; Brown, Robert H.

2013-01-01

283

Receptor Expression in Rat Skeletal Muscle Cell Cultures  

NASA Technical Reports Server (NTRS)

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

Young, Ronald B.

1996-01-01

284

Mechanical stimulation improves tissue-engineered human skeletal muscle  

NASA Technical Reports Server (NTRS)

Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

2002-01-01

285

Effect of microwave electromagnetic field on skeletal muscle fibre activity.  

PubMed

The aim of the present study was to investigate the influence of microwave irradiation on fatiguing activity of isolated frog skeletal muscle fibres. The changes in the electrical and mechanical activity were used as criteria for the exposure effects. Repetitive suprathreshold stimulation with interstimulus interval of 200 ms for 3 min was applied. Intracellular (ICAP) and extracellular (ECAP) action potentials and twitch contractions (Tw) of muscle fibres after 1 hour microwave exposure (2.45 GHz, 20 mW/cm( 2) power density) were compared with those recorded after one hour sham exposure (control). The duration of uninterrupted activity in the trial (endurance time; ET) was not significantly affected by microwave field exposure. After microwave irradiation, the ICAP amplitude was higher, the rising time was shorter, and the resting membrane potential was more negative compared to controls. There was a slower rate of parameters changes during ET in potentials obtained from irradiated fibres. Microwave exposure increased the propagation velocity of excitation, the ECAP and Tw amplitudes, as well as shortened their time parameters. We concluded that a 2.45 GHz microwave field possesses a stimulating effect on muscle fibre activity, which is in part due to its specific, non-thermal properties. The microwave induced-changes in muscle fibre activity may reduce development of skeletal muscle fatigue. PMID:12221521

Radicheva, N; Mileva, K; Vukova, T; Georgieva, B; Kristev, I

2002-07-01

286

A second MNGIE patient without typical mitochondrial skeletal muscle involvement  

Microsoft Academic Search

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease caused by mutations in the\\u000a gene encoding thymidine phosphorylase (TYMP). Clinically, MNGIE is characterized by gastrointestinal dysmotility, cachexia,\\u000a ptosis, ophthalmoparesis, peripheral neuropathy and leukoencephalopathy. Most MNGIE patients have signs of mitochondrial dysfunction\\u000a in skeletal muscle at morphological and enzyme level, as well as mitochondrial DNA depletion, multiple deletions and point\\u000a mutations.

Elena Cardaioli; Paola Da Pozzo; Edoardo Malfatti; Carla Battisti; Gian Nicola Gallus; Carmen Gaudiano; Marco Macucci; Alessandro Malandrini; Maria Margollicci; Anna Rubegni; Maria Teresa Dotti; Antonio Federico

2010-01-01

287

Chicken skeletal muscle tropomodulin: novel localization and characterization  

Microsoft Academic Search

Tropomodulin is a 40.6-kDa isoform-specific tropomyosin-binding protein which inhibits actin filament elongation from the slow-growing (pointed) end and localizes at or near the pointed ends of thin filaments in rat skeletal muscle. Immunofluorescent localization using affinity-purified anti-tropomodulin antibodies in avian myofibril preparations demonstrates novel immunoreactivity at the Z-disc in addition to the previously reported localization at the periphery of I-Z-I

Mark A. Sussman; Masamichi Ito; Mathew P. Daniels; Bernhard Flucher; Sara Buranen; Larry Kedes

1996-01-01

288

The role of mitochondria in aging of skeletal muscle  

Microsoft Academic Search

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

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

2008-01-01

289

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

Microsoft Academic Search

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

SHIGEHIRO NAKAJIMA; SHIZUKO IWASAKI; KUNIHIKO OBATA

2009-01-01

290

Exercise-induced phospho-proteins in skeletal muscle  

Microsoft Academic Search

Efforts to identify exercise-induced signaling events in skeletal muscle have been influenced by ground-breaking discoveries in the insulin action field. Initial discoveries demonstrating that exercise enhances insulin sensitivity raised the possibility that contraction directly modulates insulin receptor signaling events. Although the acute effects of exercise on glucose metabolism are clearly insulin-independent, the canonical insulin signaling cascade has been used as

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

2008-01-01

291

Protein Kinase (AMPK) and PGC1? in Skeletal Muscle  

Microsoft Academic Search

Skeletal muscle is the major site of insulin-stimulated glucose uptake and oxidation processes which are controlled, in part, by activation of the cellular energy-sensor, AMP-activated protein kinase (AMPK). In addition, the transcription coactivator, peroxisome- proliferator activated receptor ? coactivator-1? (PGC-1?), has been considered to be a master regulator of cellular metabolism. Recently, nitric oxide (NO) was shown to be involved

Karla Davila; Vitor A. Lira; David S. Criswell

2009-01-01

292

Prioritization of skeletal muscle growth for emergence from hibernation.  

PubMed

Mammalian hibernators provide an extreme example of naturally occurring challenges to muscle homeostasis. The annual hibernation cycle is characterized by shifts between summer euthermy with tissue anabolism and accumulation of body fat reserves, and winter heterothermy with fasting and tissue catabolism. The circannual patterns of skeletal muscle remodelling must accommodate extended inactivity during winter torpor, the motor requirements of transient winter active periods, and sustained activity following spring emergence. Muscle volume in thirteen-lined ground squirrels (Ictidomys tridecemlineatus) calculated from MRI upper hindlimb images (n=6 squirrels, n=10 serial scans) declined from hibernation onset, reaching a nadir in early February. Paradoxically, mean muscle volume rose sharply after February despite ongoing hibernation, and continued total body mass decline until April. Correspondingly, the ratio of muscle volume to body mass was steady during winter atrophy (October-February) but increased (+70%) from February to May, which significantly outpaced changes in liver or kidney examined by the same method. Generally stable myocyte cross-sectional area and density indicated that muscle remodelling is well regulated in this hibernator, despite vastly altered seasonal fuel and activity levels. Body composition analysis by echo MRI showed lean tissue preservation throughout hibernation amid declining fat mass by the end of winter. Muscle protein synthesis was 66% depressed in early but not late winter compared with a summer fasted baseline, while no significant changes were observed in the heart, liver or intestine, providing evidence that could support a transition in skeletal muscle regulation between early and late winter, prior to spring emergence and re-feeding. PMID:25452506

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

2015-01-15

293

Signalling and the control of skeletal muscle size  

SciTech Connect

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

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

2010-11-01

294

Fast skeletal muscle troponin T increases the cooperativity of transgenic mouse cardiac muscle contraction  

PubMed Central

To investigate the functional significance of different troponin T (TnT) isoforms in the Ca2+ activation of muscle contraction, transgenic mice have been constructed with a chicken fast skeletal muscle TnT transgene driven by a cardiac ?-myosin heavy chain gene promoter. Cardiac muscle-specific expression of the fast skeletal muscle TnT has been obtained with significant myofibril incorporation. Expression of the endogenous cardiac muscle thin filament regulatory proteins, such as troponin I and tropomyosin, was not altered in the transgenic mouse heart, providing an authentic system for the functional characterization of TnT isoforms. Cardiac muscle contractility was analysed for the force vs. Ca2+ relationship in skinned ventricular trabeculae of transgenic mice in comparison with wild-type litter-mates. The results showed unchanged pCa50 values (5.1 ± 0.04 and 5.1 ± 0.1, respectively) but significantly steeper slopes (the Hill coefficient was 2.0 ± 0.2 vs. 1.0 ± 0.2, P < 0.05). The results demonstrate that the structural and functional variation of different TnT isoforms may contribute to the difference in responsiveness and overall cooperativity of the thin filament-based Ca2+ regulation between cardiac and skeletal muscles. PMID:10517814

Huang, Qi-Quan; Brozovich, Frank V; Jin, Jian-Ping

1999-01-01

295

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.

296

Formation and optogenetic control of engineered 3D skeletal muscle bioactuators  

E-print Network

Densely arrayed skeletal myotubes are activated individually and as a group using precise optical stimulation with high spatiotemporal resolution. Skeletal muscle myoblasts are genetically encoded to express a light-activated ...

Sakar, Mahmut Selman

297

Dietary nitrate reduces skeletal muscle oxygenation response to physical exercise: a quantitative muscle functional MRI study.  

PubMed

Dietary inorganic nitrate supplementation (probably via conversion to nitrite) increases skeletal muscle metabolic efficiency. In addition, it may also cause hypoxia-dependent vasodilation and this has the potential to augment oxygen delivery to exercising skeletal muscle. However, direct evidence for the latter with spatial localization to exercising muscle groups does not exist. We employed quantitative functional MRI (fMRI) to characterize skeletal muscle oxygen utilization and replenishment by assessment of tissue oxygenation maximal change and recovery change, respectively. Eleven healthy subjects were enrolled, of whom 9 (age 33.3 ± 4.4 years, five males) completed the study. Each subject took part in three MRI visits, with dietary nitrate (7cl concentrated beetroot juice) consumed before the third visit. During each visit fMRIs were conducted concurrently with plantar flexion exercise at workloads of 15% and 25% maximum voluntary contraction (MVC). No significant changes were found between visits 1 and 2 in the fMRI measures. A decrease in maximal change was found at 15% MVC in soleus between visits 2 and 3 (5.12 ± 2.36 to 2.55 ± 1.42, P = 0.004) and between visits 1 and 3 (4.43 ± 2.12 to 2.55 ± 1.42, P = 0.043), but not at 25% MVC or within gastrocnemius. There was no difference in recovery change between visits. We found that dietary nitrate supplementation reduces tissue oxygenation alterations during physical exercise in skeletal muscle. This effect is more prominent in muscles with predominantly type 1 fibers and at lower workloads. This indicates that in healthy subjects dietary nitrate predominantly affects skeletal muscle energy efficiency with no change in oxygen delivery. PMID:25052493

Bentley, Rachel; Gray, Stuart R; Schwarzbauer, Christian; Dawson, Dana; Frenneaux, Michael; He, Jiabao

2014-07-01

298

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. PMID:23849266

2012-01-01

299

Laser-inflicted injury of zebrafish embryonic skeletal muscle.  

PubMed

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

Otten, Cécile; Abdelilah-Seyfried, Salim

2013-01-01

300

Fatty acid-binding protein in bovine skeletal muscle  

E-print Network

contaminant. Sequencing initially yielded the amino acid sequence of bovine myoglobin; after treatment with CNBr, alignment of amino acids in sFABP(s) with murine adipocyte 422 FABP and rat heart FABP were made with 14 out of 16 and eight out of 11... hydrolysates, revealed composition data with similarities intermediate among bovine heart myoglobin, rat heart muscle FABP, and mouse 3T3-adipocyte FABP. Similarkies in amino acid composition between sFABP and myoglobin suggested that myoglobin was a major...

Moore, Kimberly Kirby

1989-01-01

301

Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle.  

PubMed

Nitric oxide (NO) functions as a molecular mediator in numerous processes in cellular development and physiology. Differential expression and regulation of a family of three NO synthase (NOS) gene products help achieve this diversity of action. Previous studies identify post-translational modification and interaction of NOS with specific protein targets as tissue-specific modes of regulation. Here, we show that alternative splicing specifically regulates neuronal NOS (nNOS, type I) in striated muscle. nNOS in skeletal muscle is slightly more massive than nNOS from brain owing to a 102-base pair (34-amino acid) alternatively spliced segment between exons 16 and 17. Following purification, this novel nNOS mu isoform has similar catalytic activity to that of nNOS expressed in cerebellum. nNOS mu appears to function exclusively in differentiated muscle as its expression occurs coincidentally with myotube fusion in culture. An isoform-specific antibody detects nNOS mu protein only in skeletal muscle and heart. This study identifies alternative splicing as a means for tissue-specific regulation of nNOS and reports the first additional protein sequence for a mammalian NOS since the original cloning of the gene family. PMID:8626668

Silvagno, F; Xia, H; Bredt, D S

1996-05-10

302

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

PubMed Central

Described here is a method to measure contractility of isolated skeletal muscles. Parameters such as muscle force, muscle power, contractile kinetics, fatigability, and recovery after fatigue can be obtained to assess specific aspects of the excitation-contraction coupling (ECC) process such as excitability, contractile machinery and Ca2+ handling ability. This method removes the nerve and blood supply and focuses on the isolated skeletal muscle itself. We routinely use this method to identify genetic components that alter the contractile property of skeletal muscle though modulating Ca2+ signaling pathways. Here, we describe a newly identified skeletal muscle phenotype, i.e., mechanic alternans, as an example of the various and rich information that can be obtained using the in vitro muscle contractility assay. Combination of this assay with single cell assays, genetic approaches and biochemistry assays can provide important insights into the mechanisms of ECC in skeletal muscle. PMID:23149471

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

2012-01-01

303

Role of microRNAs in skeletal muscle development and rhabdomyosarcoma (Review).  

PubMed

Skeletal muscle accounts for ~40% of total body mass. The principle functions of skeletal muscle include supporting the body structure, controlling motor movements and storing energy. Rhabdomyosarcoma (RMS) is a skeletal muscle?derived soft tissue tumor widely occurring in the pediatric population. In previous years, microRNAs (miRNAs) have been demonstrated to be important in skeletal muscle development, function and the pathogenesis of various diseases, including RMS. The present review provided an overview of current knowledge on the muscle?specific and ubiquitously?expressed miRNAs involved in skeletal muscle differentiation and their dysregulation in RMS. Additionally, the potential use and challenges of miRNAs as therapeutic targets in this soft?tissue sarcoma were examined and the future prospects for miRNAs in muscle biology and muscle disorders were discussed. PMID:25633282

Ju, Huiming; Yang, Yuefei; Sheng, Anzhi; Jiang, Xing

2015-06-01

304

Fetal Stem Cells and Skeletal Muscle Regeneration: A Therapeutic Approach  

PubMed Central

More than 40% of the body mass is represented by muscle tissue, which possesses the innate ability to regenerate after damage through the activation of muscle-specific stem cells, namely satellite cells. Muscle diseases, in particular chronic degenerative states of skeletal muscle such as dystrophies, lead to a perturbation of the regenerative process, which causes the premature exhaustion of satellite cell reservoir due to continuous cycles of degeneration/regeneration. Nowadays, the research is focused on different therapeutic approaches, ranging from gene and cell to pharmacological therapy, but still there is no definitive cure in particular for genetic muscle disease. Keeping this in mind, in this article, we will give special consideration to muscle diseases and the use of fetal derived stem cells as a new approach for therapy. Cells of fetal origin, from cord blood to placenta and amniotic fluid, can be easily obtained without ethical concern, expanded and differentiated in culture, and possess immune-modulatory properties. The in vivo approach in animal models can be helpful to study the mechanism underneath the operating principle of the stem cell reservoir, namely the niche, which holds great potential to understand the onset of muscle pathologies. PMID:25221507

Pozzobon, Michela; Franzin, Chiara; Piccoli, Martina; De Coppi, Paolo

2014-01-01

305

Protein Diffusion in Living Skeletal Muscle Fibers: Dependence on Protein Size, Fiber Type, and Contraction  

E-print Network

. Proteins were injected into single, intact skeletal muscle fibers taken from either soleus or extensorProtein Diffusion in Living Skeletal Muscle Fibers: Dependence on Protein Size, Fiber Type digitorum longus (edl) muscle of adult rats. No correlation was found between sarcomere spacing

Voigt, Chris

306

AUTOMATIC SKELETAL MUSCLE SEGMENTATION THROUGH RANDOM WALKS AND GRAPH-BASED SEED PLACEMENT  

E-print Network

AUTOMATIC SKELETAL MUSCLE SEGMENTATION THROUGH RANDOM WALKS AND GRAPH-BASED SEED PLACEMENT P University Paris 06, Paris, FR. ABSTRACT In this paper we propose a novel skeletal muscle segmentation method appropriate seed posi- tions with respect to the different muscle classes. This is achieved by taking

Boyer, Edmond

307

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

Microsoft Academic Search

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

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

2011-01-01

308

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

2007-01-01

309

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

PubMed

Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1(-/-) mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. PMID:25218946

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

2015-02-01

310

A role of tensin in skeletal-muscle regeneration.  

PubMed Central

Regeneration of skeletal muscle requires the activation, proliferation, differentiation and fusion of satellite cells to generate new muscle fibres. This study was designed to determine the role of tensin in this process. Cardiotoxin was used to induce regeneration in the anterior tibial muscles of tensin-knockout and wild-type mice. From histological analysis, we found that the regeneration process lasted longer in knockout than in wild-type mice. To investigate the mechanism involved in this delay, we examined each regeneration step in animals and cultured primary cells. We found fewer proliferating myogenic cells identified by bromodeoxyuridine and desmin double labelling in knockout mice on the first 2 days after injury. Expression of myosin, paxillin, dystrophin and dystrophin-associated proteins were delayed in knockout mice. Withdrawal from the cell cycle was less efficient in isolated knockout myoblasts, and the fusion capacity was reduced in these cells as well. These defects in regeneration most likely contributed to the 9-fold increase of centrally nucleated fibres occurring in the non-injected knockout mice. Our results demonstrated clearly that tensin plays a role in skeletal-muscle regeneration. PMID:11389681

Ishii, A; Lo, S H

2001-01-01

311

Sphingolipid Metabolism, Oxidant Signaling, and Contractile Function of Skeletal Muscle  

PubMed Central

Abstract Significance Sphingolipids are a class of bioactive lipids that regulate diverse cell functions. Ceramide, sphingosine, and sphingosine-1-phosphate accumulate in tissues such as liver, brain, and lung under conditions of cellular stress, including oxidative stress. The activity of some sphingolipid metabolizing enzymes, chiefly the sphingomyelinases, is stimulated during inflammation and in response to oxidative stress. Ceramide, the sphingomyelinase product, as well as the ceramide metabolite, sphingosine-1-phosphate, can induce the generation of more reactive oxygen species, propagating further inflammation. Recent Advances This review article summarizes information on sphingolipid biochemistry and signaling pertinent to skeletal muscle and describes the potential influence of sphingolipids on contractile function. Critical Issues It encompasses topics related to (1) the pathways for complex sphingolipid biosynthesis and degradation, emphasizing sphingolipid regulation in various muscle fiber types and subcellular compartments; (2) the emerging evidence that implicates ceramide, sphingosine, and sphingosine-1-phosphate as regulators of muscle oxidant activity, and (3) sphingolipid effects on contractile function and fatigue. Future Directions We propose that prolonged inflammatory conditions alter ceramide, sphingosine, and sphingosine-1-phosphate levels in skeletal muscle and that these changes promote the weakness, premature fatigue, and cachexia that plague individuals with heart failure, cancer, diabetes, and other chronic inflammatory diseases. Antioxid. Redox Signal. 15, 2501–2517. PMID:21453197

Nikolova-Karakashian, Mariana N.

2011-01-01

312

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

PubMed Central

Background Elevated fatty acids contribute to the development of type 2 diabetes and affect skeletal muscle insulin sensitivity. Since elevated intramuscular lipids and insulin resistance is strongly correlated, aberrant lipid storage or lipid intermediates may be involved in diabetes pathogenesis. The aim of this study was to develop a method to determine the dynamic metabolic fate of lipids in primary human skeletal muscle cells and in intact mouse skeletal muscle. We report a simple and fast method to characterize lipid profiles in skeletal muscle using thin layer chromatography. Findings The described method was specifically developed to assess lipid utilization in cultured and intact skeletal muscle. We determined the effect of a pan-diacylglycerol kinase (DGK) class I inhibitor (R59949) on lipid metabolism to validate the method. In human skeletal muscle cells, DGK inhibition impaired diacylglycerol (DAG) conversion to phosphatidic acid and increased triglyceride synthesis. In intact glycolytic mouse skeletal muscle, DGK inhibition triggered the accumulation of DAG species. Conversely, the DGK inhibitor did not affect DAG content in oxidative muscle. Conclusion This simple assay detects rapid changes in the lipid species composition of skeletal muscle with high sensitivity and specificity. Determination of lipid metabolism in skeletal muscle may further elucidate the mechanisms contributing to the pathogenesis of insulin resistance in type 2 diabetes or obesity. PMID:24962347

2014-01-01

313

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 distinct, and/or additional mechanism(s) to Leu. PMID:23551944

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

2013-01-01

314

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

2011-01-01

315

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. PMID:23936073

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

2013-01-01

316

[Transdisciplinary Approach for Sarcopenia. The effects of exercise on skeletal muscle hypertrophy and satellite cells].  

PubMed

Skeletal muscle has a high degree of plasticity. The mass of skeletal muscle maintains owing to muscle protein synthesis and the regeneration by satellite cells. Skeletal muscle atrophy with aging (sarcopenia) is developed by decline of muscle protein synthesis and dysfunction of satellite cells. It is urgently necessary for today's highly aged society to elucidate the mechanism of sarcopenia and to establish prevention measure. This review shows that the positive effects of "exercise" on muscle protein synthesis and satellite cell function including their main molecular mechanism. PMID:25266091

Fujimaki, Shin; Takemasa, Tohru; Kuwabara, Tomoko

2014-10-01

317

Cloning, characterization, and expression of a novel GDP dissociation inhibitor isoform from skeletal muscle.  

PubMed

Cellular mechanisms for controlling membrane trafficking appear to involve small GTP-binding proteins such as the Rab proteins. Rab function is regulated by GDP dissociation inhibitor (GDI), which releases Rab proteins from membranes and inhibits GDP dissociation. Here we report the isolation of a full-length cDNA encoding a novel GDI isoform of 445 amino acids (GDI-2) with a deduced molecular weight of 50,649 from mouse skeletal muscle. Full-length and partial cDNA clones encoding a previously reported GDI protein (GDI-1) were also isolated from cDNA libraries prepared from rat brain and mouse skeletal muscle, respectively. The degree of deduced amino acid sequence identity between mouse GDI-2 and our mouse GDI-1 cDNA clone is 86%. Northern (RNA blot) analysis revealed that in human tissues, both GDI-1 and GDI-2 transcripts were abundant in brain, skeletal muscle, and pancreas but were weakly expressed in heart and liver. GDI-1 mRNA was expressed in kidney, whereas GDI-2 was almost absent, while in lung the relative amounts of these mRNA species were reversed. Specific antibodies against mouse GDI-1 and GDI-2 based on unique peptide sequences in the proteins were raised. Differentiation of 3T3-L1 fibroblasts into highly insulin-responsive adipocytes was accompanied by large increases in both mRNA and protein levels of GDI-1 and GDI-2. GDI-1 and GDI-2 expressed as glutathione S-transferase fusion proteins were both able to solubilize the membrane-bound forms of Rab4 and Rab5 in a GDP/GTP-dependent manner. Taken together, these data demonstrate that the protein products of at least two genes regulate the membrane dynamics of Rab proteins in mice. PMID:7513052

Shisheva, A; Südhof, T C; Czech, M P

1994-05-01

318

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

1999-01-01

319

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

PubMed Central

Abstract Skeletal muscle interstitium is crucial for regulation of blood flow, passage of substances from capillaries to myocytes and muscle regeneration. We show here, probably, for the first time, the presence of telocytes (TCs), a peculiar type of interstitial (stromal) cells, in rat, mouse and human skeletal muscle. TC features include (as already described in other tissues) a small cell body and very long and thin cell prolongations—telopodes (Tps) with moniliform appearance, dichotomous branching and 3D-network distribution. Transmission electron microscopy (TEM) revealed close vicinity of Tps with nerve endings, capillaries, satellite cells and myocytes, suggesting a TC role in intercellular signalling (via shed vesicles or exosomes). In situ immunolabelling showed that skeletal muscle TCs express c-kit, caveolin-1 and secrete VEGF. The same phenotypic profile was demonstrated in cell cultures. These markers and TEM data differentiate TCs from both satellite cells (e.g. TCs are Pax7 negative) and fibroblasts (which are c-kit negative). We also described non-satellite (resident) progenitor cell niche. In culture, TCs (but not satellite cells) emerge from muscle explants and form networks suggesting a key role in muscle regeneration and repair, at least after trauma. PMID:21609392

Popescu, L M; Manole, Emilia; ?erboiu, Crengu?a S; Manole, C G; Suciu, Laura C; Gherghiceanu, Mihaela; Popescu, B O

2011-01-01

320

Three-dimensionally printed biological machines powered by skeletal muscle.  

PubMed

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

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

2014-07-15

321

Three-dimensionally printed biological machines powered by skeletal muscle  

PubMed Central

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

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

2014-01-01

322

The peculiar apoptotic behavior of skeletal muscle cells.  

PubMed

Apoptosis plays an active role in maintaining skeletal muscle homeostasis. Its deregulation is involved in several skeletal muscle disorders such as dystrophies, myopathies, disuse and sarcopenia. The aim of this work was to study in vitro the apoptotic behavior induced by etoposide, staurosporine and hydrogen peroxide in the C2C12 skeletal muscle cell line, comparing myoblast vs myotube sensitivity, investigated by means of morphological and cytofluorimetric analyses. Myotubes appeared more resistant than myoblasts to apoptotic induction. In myoblasts treated with etoposide, nuclei with chromatin condensation were observed, in the presence of a diffuse DNA fragmentation, as shown by confocal microscopy. The latter also appeared in myotubes, where apoptotic and normal nuclei coexisted inside the same syncytium. After staurosporine treatment, myobalsts evidenced late apoptotic features and a high number of TUNEL-positive nuclei. Secondary necrosis appeared in myotubes, where myonuclei with cleaved DNA again coexisted with normal myonuclei. After H?O? exposure, myotubes, differently from myoblasts, showed a poor sensitivity to cell death. Intriguingly, autophagic granules appeared abundantly in myotubes after each treatment. In myotubes, mitochondria were better preserved than in myoblasts since those which were damaged were probably degraded through autophagic processes. These findings demonstrate a scarce sensitivity of myotubes to apoptotic stimuli due to acquisition of an apoptosis-resistant phenotype during differentiation. The presence of nuclear-dependent "territorial" death domains in the syncytium could explain a slower death of myotubes compared to mononucleated cells. In addition, autophagy could preserve and protect muscle cell integrity against chemical stimuli, making C2C12 cells, in particular myotubes, more resistant to apoptosis induction. PMID:23400589

Salucci, Sara; Burattini, Sabrina; Baldassarri, Valentina; Battistelli, Michela; Canonico, Barbara; Valmori, Aurelio; Papa, Stefano; Falcieri, Elisabetta

2013-08-01

323

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

PubMed

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 a numerical algorithm based on the concept of the Hill's three-element muscle model. The proposed numerical algorithm could be used to predict concentric, eccentric, isometric and isotonic contraction behaviours of the muscle. The proposed numerical algorithm and constitutive model for the muscle were derived and implemented into a non-linear large deformation finite element programme ABAQUS by using user-defined material subroutines. A number of scenarios have been used to demonstrate capability of the model for simulating both quasi-static and dynamic response of the muscle. Validation of the proposed model has been performed by comparing the simulated results with the experimental ones of frog gastrocenemius muscle deformation. The effects of the fusiform muscle geometry and fibre orientation on the stress and fibre stretch distributions of frog muscle during isotonic contraction have also been investigated by using the proposed model. The predictability of the present model for dynamic response of the muscle has been demonstrated by simulating the extension of a squid tentacle during a strike to catch prey. PMID:19264310

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

2009-05-11

324

Leucine incorporation into mixed skeletal muscle protein in humans  

SciTech Connect

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

Nair, K.S.; Halliday, D.; Griggs, R.C. (Univ. of Rochester School of Medicine and Dentistry, NY (USA) Clinical Research Centre, Harrow (England))

1988-02-01

325

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles  

NASA Technical Reports Server (NTRS)

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

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

1986-01-01

326

A Small Volatile Bacterial Molecule Triggers Mitochondrial Dysfunction in Murine Skeletal Muscle  

PubMed Central

Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tissues, including in the lungs of cystic fibrosis (CF) patients, acts as an interkingdom immunomodulatory signal that facilitates pathogen persistence, and host tolerance to infection. Transcriptome results have led to the hypothesis that 2-AA causes further harm to the host by triggering mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function is essential to survival, and is compromised in many chronic illnesses, including infections and CF-associated muscle wasting, we here determine the global effects of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS), proton (1H) nuclear magnetic resonance (NMR) metabolomics, in vivo 31P NMR, whole-genome expression analysis and functional studies. Our results show that 2-AA when injected into mice, induced a biological signature of insulin resistance as determined by 1H NMR analysis-, and dramatically altered insulin signaling, glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR-?, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up-regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not alter high-energy phosphates or pH by in vivo 31P NMR analysis, it significantly reduced the rate of ATP synthesis. This affect was corroborated by results demonstrating down-regulation of the expression of genes involved in energy production and muscle function, and was further validated by muscle function studies. Together, these results further demonstrate that 2-AA, acts as a mediator of interkingdom modulation, and likely effects insulin resistance associated with a molecular signature of mitochondrial dysfunction in skeletal muscle. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections. PMID:24098655

Tzika, A. Aria; Constantinou, Caterina; Bandyopadhaya, Arunava; Psychogios, Nikolaos; Lee, Sangseok; Mindrinos, Michael; Martyn, J. A. Jeevendra; Tompkins, Ronald G.; Rahme, Laurence G.

2013-01-01

327

Human skeletal muscle protein breakdown during spaceflight  

NASA Technical Reports Server (NTRS)

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

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

1997-01-01

328

Muscle-specific Drp1 overexpression impairs skeletal muscle growth via translational attenuation.  

PubMed

Mitochondrial fission and fusion are essential processes in the maintenance of the skeletal muscle function. The contribution of these processes to muscle development has not been properly investigated in vivo because of the early lethality of the models generated so far. To define the role of mitochondrial fission in muscle development and repair, we have generated a transgenic mouse line that overexpresses the fission-inducing protein Drp1 specifically in skeletal muscle. These mice displayed a drastic impairment in postnatal muscle growth, with reorganisation of the mitochondrial network and reduction of mtDNA quantity, without the deficiency of mitochondrial bioenergetics. Importantly we found that Drp1 overexpression activates the stress-induced PKR/eIF2?/Fgf21 pathway thus leading to an attenuated protein synthesis and downregulation of the growth hormone pathway. These results reveal for the first time how mitochondrial network dynamics influence muscle growth and shed light on aspects of muscle physiology relevant in human muscle pathologies. PMID:25719247

Touvier, T; De Palma, C; Rigamonti, E; Scagliola, A; Incerti, E; Mazelin, L; Thomas, J-L; D'Antonio, M; Politi, L; Schaeffer, L; Clementi, E; Brunelli, S

2015-01-01

329

Bioelectrical impedance can predict skeletal muscle and fat-free skeletal muscle of beef cows and their carcasses.  

PubMed

Multiple linear regression equations predicting total skeletal muscle (TM) and total skeletal fat-free muscle (TFFM) weight were developed from data of 33 beef cows. Animals varied in weight (385 to 749 kg), age (3 to 10 yr), and fatness (.13 to 2.54 cm). A four-terminal impedance meter/plethysmograph measured resistance and reactance on the live animals, exsanguinated (bled) animals, and on the subsequent hot and cold carcasses. Stainless steel, sterile needles (20-gauge) were used as electrodes. They were inserted to depths of 12.7 mm for measurements made before and after exsanguination and to 25.4 mm for carcass measurements. Cold carcass resistance and reactance were measured a second time using 13-gauge needles inserted to depth of 76.2 mm. Distance between detector electrodes was measured. Carcass sides were physically separated into muscle, fat, and bone. Chemical composition (moisture, protein, and fat) was determined on the muscle portion. Equations predicting TM weight from live, bled, hot carcass, and cold carcass data had adjusted R2 values of .90, .96, .94, and .92, respectively. Analogous adjusted R2 values for TFFM weight were .87, .93, .90, and .87. Resistance was a predictor variable in all equations. The use of larger needles resulted in higher adjusted R2 values and inclusion of reactance as a predictor variable. Mallows Cp values were close to the ideal value of the number of independent variables in the prediction equations plus one (1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7759360

Marchello, M J; Slanger, W D

1994-12-01

330

Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages  

Microsoft Academic Search

Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these

Nikola Arsic; Daria Mamaeva; Ned J. Lamb; Anne Fernandez

2008-01-01

331

Severe nemaline myopathy caused by mutations of the stop codon of the skeletal muscle alpha actin gene ( ACTA1)  

Microsoft Academic Search

Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle ?-actin (ACTA1) genes. Here we report for the first time three patients with severe nemaline myopathy and mutations of the ACTA1 stop codon: TAG>TAT (tyrosine), TAG>CAG (glutamine) and TAG>TGG (tryptophan). All three mutations will cause inclusion of an additional 47 amino acids, translated from the 3? UTR

William Wallefeld; Sabine Krause; Kristen J. Nowak; Danielle Dye; Rita Horváth; Zoltán Molnár; Miklós Szabó; Kazuhiro Hashimoto; Cristina Reina; Jose De Carlos; Jordi Rosell; Ana Cabello; Carmen Navarro; Ichizo Nishino; Hanns Lochmüller; Nigel G. Laing

2006-01-01

332

Hyperinsulinemia and skeletal muscle fatty acid trafficking  

PubMed Central

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

2013-01-01

333

Genetic architecture of gene expression in ovine skeletal muscle  

PubMed Central

Background In livestock populations the genetic contribution to muscling is intensively monitored in the progeny of industry sires and used as a tool in selective breeding programs. The genes and pathways conferring this genetic merit are largely undefined. Genetic variation within a population has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle. Results The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing and expressed as an Estimated Breeding Value by comparison with contemporary sires. Microarray gene expression data were obtained for longissimus lumborum samples taken from forty progeny of the six sires (4-8 progeny/sire). Initial unsupervised hierarchical clustering analysis revealed strong genetic architecture to the gene expression data, which also discriminated the sire-based Estimated Breeding Value for the trait. An integrated systems biology approach was then used to identify the major functional pathways contributing to the genetics of enhanced muscling by using both Estimated Breeding Value weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome), RNA processing, mitochondrial function and transcriptional regulation. Conclusions This study has revealed strong genetic structure in the gene expression program within ovine longissimus lumborum muscle. The balance between muscle protein synthesis, at the levels of both transcription and translation control, and protein catabolism mediated by regulated proteolysis is likely to be the primary determinant of the genetic merit for the muscling trait in this sheep population. There is also evidence that high genetic merit for muscling is associated with a fibre type shift toward fast glycolytic fibres. This study provides insight into mechanisms, presumably subject to strong artificial selection, that underpin enhanced muscling in sheep populations. PMID:22171619

2011-01-01

334

Fetal programming of fat and collagen in porcine skeletal muscles  

PubMed Central

Connective tissue plays a key role in the scaffolding and development of skeletal muscle. Pilot studies carried out in our laboratory have shown that the smallest porcine littermate has a higher content of connective tissue within skeletal muscle compared with its largest littermate. The present study investigated the prenatal development of intralitter variation in terms of collagen content within connective tissue and intramuscular fat of the M. semitendinosus. Twenty-three pairs of porcine fetuses from a Large White–Landrace origin were used aged from 36 to 86 days of gestation. The largest and smallest littermates were chosen by weight and the M. semitendinosus was removed from each. Complete transverse muscle sections were stained with Oil Red O (detection of lipids) and immunocytochemistry was performed using an antibody to collagen I. Slides were analysed and paired t-Tests revealed the smallest littermate contained a significantly higher proportion of fat deposits and collagen I content compared with the largest littermate. Recent postnatal studies showing elevated levels of intramuscular lipids and low scores for meat tenderness in the smallest littermate corroborate our investigations. It can be concluded that the differences seen in connective tissue elements have a fetal origin that may continue postnatally. PMID:16367803

Karunaratne, JF; Ashton, CJ; Stickland, NC

2005-01-01

335

Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting  

PubMed Central

Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration. PMID:24406502

Al-Sawaf, Othman; Fragoulis, Athanassios; Rosen, Christian; Kan, Yuet Wai; Sönmez, Tolga Taha; Pufe, Thomas; Wruck, Christoph Jan

2014-01-01

336

Nrf2 Protects Against TWEAK-mediated Skeletal Muscle Wasting  

NASA Astrophysics Data System (ADS)

Skeletal muscle (SM) regeneration after injury is impaired by excessive inflammation. Particularly, the inflammatory cytokine tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent inducer of skeletal muscle wasting and fibrosis. In this study we investigated the role of Nrf2, a major regulator of oxidative stress defence, in SM ischemia/reperfusion (I/R) injury and TWEAK induced atrophy. We explored the time-dependent expression of TWEAK after I/R in SM of Nrf2-wildtype (WT) and knockout (KO) mice. Nrf2-KO mice expressed significant higher levels of TWEAK as compared to WT mice. Consequently, Nrf2-KO mice present an insufficient regeneration as compared to Nrf2-WT mice. Moreover, TWEAK stimulation activates Nrf2 in the mouse myoblast cell line C2C12. This Nrf2 activation inhibits TWEAK induced atrophy in C2C12 differentiated myotubes. In summary, we show that Nrf2 protects SM from TWEAK-induced cell death in vitro and that Nrf2-deficient mice therefore have poorer muscle regeneration.

Al-Sawaf, Othman; Fragoulis, Athanassios; Rosen, Christian; Kan, Yuet Wai; Sönmez, Tolga Taha; Pufe, Thomas; Wruck, Christoph Jan

2014-01-01

337

Regulation of Skeletal Muscle Oxidative Capacity and Muscle Mass by SIRT3  

PubMed Central

We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3). Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER), indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPAR? expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction. PMID:24454908

Khalek, Waed Abdel; Ward, Jack Lee; Yang, Henry; Chabi, Béatrice; Wrutniak-Cabello, Chantal; Tong, Qiang

2014-01-01

338

Altered Macrophage Phenotype Transition Impairs Skeletal Muscle Regeneration  

PubMed Central

Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b+(CD90/B220/CD49b/NK1.1/Ly6G)?(F4/80/I-Ab/CD11c)?Ly6C+/?] accumulation occurred; interestingly, Ly6C+ and Ly6C? monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C+ macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b+F4/80+ cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b+F4/80+Ly6C?CD301? macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C? macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration. PMID:24525152

Wang, Hanzhou; Melton, David W.; Porter, Laurel; Sarwar, Zaheer U.; McManus, Linda M.; Shireman, Paula K.

2015-01-01

339

Altered macrophage phenotype transition impairs skeletal muscle regeneration.  

PubMed

Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b(+)(CD90/B220/CD49b/NK1.1/Ly6G)(-)(F4/80/I-Ab/CD11c)(-)Ly6C(+/-)] accumulation occurred; interestingly, Ly6C(+) and Ly6C(-) monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C(+) macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b(+)F4/80(+) cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b(+)F4/80(+)Ly6C(-)CD301(-) macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C(-) macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration. PMID:24525152

Wang, Hanzhou; Melton, David W; Porter, Laurel; Sarwar, Zaheer U; McManus, Linda M; Shireman, Paula K

2014-04-01

340

Hyperthermia increases interleukin-6 in mouse skeletal muscle.  

PubMed

Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42°C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37°C recovery; whereas exposure to 41°C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41°C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4°C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-? gene expression was routinely suppressed at all levels of hyperthermia (40.5-42°C) in the isolated models, but TNF-? was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a "heat stress sensor" at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6. PMID:22673618

Welc, Steven S; Phillips, Neil A; Oca-Cossio, Jose; Wallet, Shannon M; Chen, Daniel L; Clanton, Thomas L

2012-08-15

341

Skeletal Muscle Lipid Deposition and Insulin Resistance: Impact of Dietary Fatty Acids and Exercise  

Technology Transfer Automated Retrieval System (TEKTRAN)

Evidence has mounted indicating that elevated intramuscular triacylglycerol levels are associated with diminished insulin sensitivity in skeletal muscle. This lipid accumulation is most likely due to enhanced fatty acid uptake into the muscle coupled with diminished mitochondrial lipid oxidation. Th...

342

An Introductory Biology Lab That Uses Enzyme Histochemistry to Teach Students About Skeletal Muscle Fiber Types  

NSDL National Science Digital Library

Journal article discussing new lab that utilizes enzyme histochemistry and morphological observations to draw conclusions about the composition of functionally different types of muscle fibers present in skeletal muscle

Dr. Lauren J. Sweeney (Bryn Mawr College Department of Biology)

2004-03-01

343

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

PubMed Central

The 5?-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We furthermore discuss the possible role of AMPK as a master switch in skeletal muscle metabolism with the main focus on AMPK in metabolic regulation during muscle work. Finally, AMPK has a well established role in regulating expression of genes encoding various enzymes in muscle, and this issue is discussed in relation to adaptation of skeletal muscle to exercise training. PMID:16690705

Jørgensen, Sebastian B; Richter, Erik A; Wojtaszewski, Jørgen F P

2006-01-01

344

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

NASA Technical Reports Server (NTRS)

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

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

1994-01-01

345

Adaptations of human skeletal muscle fibers to spaceflight  

NASA Technical Reports Server (NTRS)

Human skeletal muscle fibers seem to share most of the same interrelationships among myosin ATPase activity, myosin heavy chain (MHC) phenotype, mitochondrial enzyme activities, glycolytic enzyme activities, and cross-sectional area (CSA) as found in rat, cat, and other species. One difference seems to be that fast fibers with high mitochrondrial content occur less frequently in humans than in the rat or cat. Recently, we have reported that the type of MHC expressed and the size of the muscle fibers in humans that have spent 11 days in space change significantly. Specifically, about 8% more fibers express fast MHCs and all phenotypes atrophy in the vastus lateralis (VL) post compared to preflight. In the present paper we examine the relationships among the population of myonuclei, MHC type, and CSA of single human muscle fibers before and after spaceflight. These are the first data that define the relationship among the types of MHC expressed, myonuclei number, and myonuclei domain of single fibers in human muscle. We then compare these data to similar measures in the cat. In addition, the maximal torque that can be generated by the knee extensors and their fatigability before and after spaceflight are examined. These data provide some indication of the potential physiologica consequences of the muscle adaptations that occur in humans in response to spaceflight.

Day, M. Kathleen; Allen, David L.; Mohajerani, Laleh; Greenisen, Michael C.; Roy, Roland R.; Edgerton, V. Reggie

1995-01-01

346

Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice  

PubMed Central

Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP-activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30–50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight. The ability to ambulate is compromised with an often complete loss of hindlimb function. Skeletal muscle atrophy is associated with a 50–75% reduction in mammalian target of rapamycin pathway phosphorylation, as well as lower peroxisome proliferator-activated receptor-? coactivator-1 content and cAMP response element binding protein phosphorylation (43 and 40% lower in mLKB1-KO mice, respectively). Maximum in situ specific force production is not affected, but fatigue is exaggerated, and relaxation kinetics are slowed in the myopathic mice. The increased fatigue is associated with a 30–78% decrease in mitochondrial protein content, a shift away from type IIA/D toward type IIB muscle fibers, and a tendency (P = 0.07) for decreased capillarity in mLKB1-KO muscles. Hearts from myopathic mLKB1-KO mice exhibit grossly dilated atria, suggesting cardiac insufficiency and heart failure, which likely contributes to the phenotype. These findings indicate that LKB1 plays a critical role in the maintenance of both skeletal and cardiac function. PMID:20360428

Hancock, Chad R.; Evanson, Bradley G.; Kenney, Steven G.; Malan, Brandon B.; Mongillo, Anthony D.; Brown, Jacob D.; Hepworth, Squire; Fillmore, Natasha; Parcell, Allen C.; Kooyman, David L.; Winder, William W.

2010-01-01

347

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy  

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

348

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy  

NASA Technical Reports Server (NTRS)

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

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

1996-01-01

349

Roles of Two Ryanodine Receptor Isoforms Coexisting in Skeletal Muscle  

Microsoft Academic Search

Ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum and plays an important role in excitation–contraction coupling in skeletal muscle. The Ca2+ release through the RyR channel can be gated by two distinct modes: depolarization-induced Ca2+ release (DICR) and Ca2+-induced Ca2+ release (CICR). Two different RyR isoforms, RyR1 (or ?-RyR) and RyR3 (or ?-RyR), have been found

Takashi Murayama; Yasuo Ogawa

2002-01-01

350

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

NASA Technical Reports Server (NTRS)

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

Adams, Gregory R.

2002-01-01

351

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

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

352

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

NASA Technical Reports Server (NTRS)

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

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

1991-01-01

353

Skeletal muscle satellite cells cultured in simulated microgravity  

NASA Technical Reports Server (NTRS)

Satellite cells are postnatal myoblasts responsible for providing additional nuclei to growing or regenerating muscle cells. Satellite cells retain the capacity to proliferate and differentiate in vitro and therefore provide a useful model to study postnatal muscle development. Most culture systems used to study postnatal muscle development are limited by the two-dimensional (2-D) confines of the culture dish. Limiting proliferation and differentiation of satellite cells in 2-D could potentially limit cell-cell contacts important for developing the level of organization in skeletal muscle obtained in vivo. Culturing satellite cells on microcarrier beads suspended in the High-Aspect-Ratio-Vessel (HARV) designed by NASA provides a low shear, three-dimensional (3-D) environment to study muscle development. Primary cultures established from anterior tibialis muscles of growing rats (approximately 200 gm) were used for all studies and were composed of greater than 75 % satellite cells. Different inoculation densities did not affect the proliferative potential of satellite cells in the HARV. Plating efficiency, proliferation, and glucose utilization were compared between 2-D flat culture and 3-D HARV culture. Plating efficiency (cells attached - cells plated x 100) was similar between the two culture systems. Proliferation was reduced in HARV cultures and this reduction was apparent for both satellite cells and non-satellite cells. Furthermore, reduction in proliferation within the HARV could not be attributed to reduced substrate availability since glucose levels in media from HARV and 2-D cell culture were similar. Morphologically, microcarrier beads within the HARVS were joined together by cells into three-dimensional aggregates composed of greater than 10 beads/aggregate. Aggregation of beads did not occur in the absence of cells. Myotubes were often seen on individual beads or spanning the surface of two beads. In summary, proliferation and differentiation of satellite cells on microcarrier beads within the HARV bioreactor results in a three dimensional level of organization that could provide a more suitable model to study postnatal muscle development.

Molnar, Greg; Hartzell, Charles R.; Schroedl, Nancy A.; Gonda, Steve R.

1993-01-01

354

Structural dynamics of troponin during activation of skeletal muscle  

PubMed Central

Time-resolved changes in the conformation of troponin in the thin filaments of skeletal muscle were followed during activation in situ by photolysis of caged calcium using bifunctional fluorescent probes in the regulatory and the coiled-coil (IT arm) domains of troponin. Three sequential steps in the activation mechanism were identified. The fastest step (1,100 s?1) matches the rate of Ca2+ binding to the regulatory domain but also dominates the motion of the IT arm. The second step (120 s?1) coincides with the azimuthal motion of tropomyosin around the thin filament. The third step (15 s?1) was shown by three independent approaches to track myosin head binding to the thin filament, but is absent in the regulatory head. The results lead to a four-state structural kinetic model that describes the molecular mechanism of muscle activation in the thin filament–myosin head complex under physiological conditions. PMID:24616505

Fusi, Luca; Brunello, Elisabetta; Sevrieva, Ivanka R.; Sun, Yin-Biao; Irving, Malcolm

2014-01-01

355

Further considerations on in vitro skeletal muscle cell death.  

PubMed

The present review discusses the apoptotic behavior induced by chemical and physical triggers in C2C12 skeletal muscle cells, comparing myoblast to myotube sensitivity, and investigating it by means of morphological, biochemical and cytofluorimetric analyses. After all treatments, myotubes, differently from myoblasts, showed a poor sensitivity to cell death. Intriguingly, in cells exposed to staurosporine, etoposide and UVB radiation, apoptotic and normal nuclei within the same fibercould be revealed. The presence of nuclear-dependent "territorial" death domains in the syncytium could explain a delayed cell death of myotubes compared to mononucleated cells. Moreover, autophagic granules abundantly appeared in myotubes after each treatment. Autophagy could protect muscle cell integrity against chemical and physical stimuli, making C2C12 myotubes, more resistant to cell death induction. PMID:24596689

Battistelli, Michela; Salucci, Sara; Burattini, Sabrina; Falcieri, Elisabetta

2013-10-01

356

Distant cis-regulatory elements in human skeletal muscle differentiation.  

PubMed

Identifying gene regulatory elements and their target genes in human cells remains a significant challenge. Despite increasing evidence of physical interactions between distant regulatory elements and gene promoters in mammalian cells, many studies consider only promoter-proximal regulatory regions. We identify putative cis-regulatory modules (CRMs) in human skeletal muscle differentiation by combining myogenic TF binding data before and after differentiation with histone modification data in myoblasts. CRMs that are distant (>20 kb) from muscle gene promoters are common and are more likely than proximal promoter regions to show differentiation-specific changes in myogenic TF binding. We find that two of these distant CRMs, known to activate transcription in differentiating myoblasts, interact physically with gene promoters (PDLIM3 and ACTA1) during differentiation. Our results highlight the importance of considering distal CRMs in investigations of mammalian gene regulation and support the hypothesis that distant CRM-promoter looping contacts are a general mechanism of gene regulation. PMID:21907276

McCord, Rachel Patton; Zhou, Vicky W; Yuh, Tiffany; Bulyk, Martha L

2011-12-01

357

Receptor tyrosine kinase specific for the skeletal muscle lineage: Expression in embryonic muscle, at the neuromuscular junction, and after injury  

Microsoft Academic Search

While a number of growth factors have been described that are highly specific for particular cell lineages, neither a factor nor a receptor uniquely specific to the skeletal muscle lineage has previously been described. Here we identify a receptor tyrosine kinase (RTK) specific to skeletal muscle, which we term “MuSK” for muscle-specific kinase. MuSK is expressed at low levels in

David M. Valenzuela; Trevor N. Stitt; Peter S. DiStefano; Eduardo Rojas; Karen Mattsson; Debra L. Compton; Lorna Nunez; John S. Park; Jennifer L. Stark; David R. Gies; Susan Thomas; Michelle M. Le Beau; Anthony A. Fernald; Neal G. Copeland; Nancy A. Jenkins; Steven J. Burden; David J. Glass; George D. Yancopoulos

1995-01-01

358

Studies on neurotrophic regulation of murine skeletal muscle  

PubMed Central

1. A quantitative comparison was made of the effects of the paralysis caused by botulinum toxin (BoTx) type A with those of surgical denervation on the development of tetrodotoxin (TTX) resistant action potentials and of extrajunctional acetylcholine (ACh) receptors in rat and mouse skeletal muscle. 2. After surgical denervation, TTX resistant action potentials were present in all fibres on the third day and their rate of rise and amount of overshoot reached peak values at the fifth day. BoTx poisoning failed, despite causing complete paralysis, to induce TTX resistant action potentials in all fibres and their average rate of rise was at all times (4-12 days) only about half that in denervated fibres. Similarly BoTx poisoning induced a smaller increase than surgical denervation in the number of extrajunctional ACh receptors, measured as 3H-labelled Naja naja siamensis ?-neurotoxin binding sites. 3. Surgical denervation of BoTx poisoned muscles induced TTX resistant action potentials in all fibres and their rate of rise and amount of overshoot were 2-3 times those in BoTx poisoned muscles only. Denervation also significantly increased the binding of labelled ?-neurotoxin. These effects of denervation were prevented by the administration of actinomycin D, a blocker of protein synthesis. 4. Administration of the ?-neurotoxin to BoTx poisoned animals resulted in the appearance of TTX resistant action potentials in all fibres and in a significant increase in their rate of rise and overshoot. 5. The results show that, despite causing complete paralysis, BoTx is less effective than surgical denervation in inducing denervatory changes in skeletal muscle. This suggests that the BoTx poisoned nerve has an influence which suppresses the appearance of denervation signs. Since the ?-neurotoxin blocked this influence remaining release of ACh, quantal or non-quantal, may be responsible for this neurotrophic action. PMID:722508

Mathers, D. A.; Thesleff, S.

1978-01-01

359

Insulinotropic and Muscle Protein Synthetic Effects of Branched-Chain Amino Acids: Potential Therapy for Type 2 Diabetes and Sarcopenia  

PubMed Central

The loss of muscle mass and strength with aging (i.e., sarcopenia) has a negative effect on functional independence and overall quality of life. One main contributing factor to sarcopenia is the reduced ability to increase skeletal muscle protein synthesis in response to habitual feeding, possibly due to a reduction in postprandial insulin release and an increase in insulin resistance. Branched-chain amino acids (BCAA), primarily leucine, increases the activation of pathways involved in muscle protein synthesis through insulin-dependent and independent mechanisms, which may help counteract the “anabolic resistance” to feeding in older adults. Leucine exhibits strong insulinotropic characteristics, which may increase amino acid availability for muscle protein synthesis, reduce muscle protein breakdown, and enhance glucose disposal to help maintain blood glucose homeostasis. PMID:23201839

Manders, Ralph J.; Little, Jonathan P.; Forbes, Scott C.; Candow, Darren G.

2012-01-01

360

Potassium initiates vasodilatation induced by a single skeletal muscle contraction in hamster cremaster muscle  

PubMed Central

The rapid onset of vasodilatation within seconds of a single contraction suggests that the vasodilators involved may be products of skeletal muscle activation, such as potassium (K+). To test the hypothesis that K+ was in part responsible for the rapid dilatation produced by muscle contraction we stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction stimulated over a range of stimulus frequencies (4, 10, 20, 30, 40, 60 and 80 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of an inhibitor of a source of K+, the voltage dependent K+ channel inhibitor 3,4-diaminopyridine (DAP, 3 × 10?4m) and inhibitors of the K+ dilatory signal transduction pathway, either a Na+ K+-ATPase inhibitor (ouabain; 10?4m) or an inward rectifying K+ channel inhibitor (barium chloride, BaCl2; 5 × 10?5m). We observed significant inhibitions of the rapid dilatation at all stimulus frequencies with each inhibitor. The dilatory event at 4 s was significantly inhibited at all stimulus frequencies by an average of 65.7 ± 3.6%, 58.8 ± 6.1% and 64.4 ± 2.1% in the presence DAP, ouabain and BaCl2, respectively. These levels of inhibition did not correlate with non-specific changes in force generation by skeletal muscle measured in vitro. Therefore, our data support that K+ is involved in the rapid dilatation in response to a single muscle contraction across a wide range of stimulus frequencies. PMID:17363384

Armstrong, Marika L; Dua, Ashok K; Murrant, Coral L

2007-01-01

361

Role of the occult insulin receptors in the regulation of atrophy and hypertrophy of skeletal muscles  

SciTech Connect

Insulin levels in the plasma are variable, as are insulin receptor numbers on the surface of skeletal muscles. Increased blood supply to the muscle during exercise delivers more insulin to the muscles even though insulin levels are suppressed by epinephrine. Increasing muscle temperatures result in an increased insulin effect, if enough receptors are available for binding. In exhaustive exercise, insulin levels are minimal but the movement of glucose across the cell membrane increases. Since insulin-receptor affinity decreases at high temperature, the only way this increased movement of glucose can be accomplished is by increased insulin binding. Thus more receptors must be available to capture the insulin. Epinephrine levels drop drastically after exercise. Insulin levels increase and the cell can import glucose, amino acids, and nucleotides. As the cell temperature decreases after exercise, insulin binding increases but the total effect decreases because the many surface receptors disappear again over a period of time. If the muscle is immobilized, the number of surface receptors decreases. There is less insulin effect and as a result the muscle atrophies. Acetylcholine (ACh) causes the proper arrangement of the myofibrils in the foetus, and has some effect on the rate of atrophy in an immobilized muscle. It also appears to maintain the cell membrane organization. Disuse atrophy is caused by a decrease in cell size, while exercise hypertrophy is caused by an increase in cell size. Growth hormone (STH) is therefore ruled out as the exercise hypertrophy controlling factor, since STH causes cell division and not hypertrophy. Testosterone can also be ruled out as the controlling factor in the development of hypertrophy and atrophy of muscles. Estrogen can likewise be ruled out. (ERB)

McLeod, M.J.

1980-10-01

362

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

PubMed

In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue. We show that this technique can resolve features of muscle tissue including fibers, fascicles and tendon, and can also detect necrotic lesions in skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy. In many instances, OCME provides better or additional contrast complementary to that provided by OCT. These results suggest that OCME could provide new understanding and opportunity for assessment of skeletal muscle pathologies. PMID:25401023

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

2014-09-01

363

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

PubMed Central

In many muscle pathologies, impairment of skeletal muscle function is closely linked to changes in the mechanical properties of the muscle constituents. Optical coherence micro-elastography (OCME) uses optical coherence tomography (OCT) imaging of tissue under a quasi-static, compressive mechanical load to map variations in tissue mechanical properties on the micro-scale. We present the first study of OCME on skeletal muscle tissue. We show that this technique can resolve features of muscle tissue including fibers, fascicles and tendon, and can also detect necrotic lesions in skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy. In many instances, OCME provides better or additional contrast complementary to that provided by OCT. These results suggest that OCME could provide new understanding and opportunity for assessment of skeletal muscle pathologies. PMID:25401023

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

2014-01-01

364

Module-based multiscale simulation of angiogenesis in skeletal muscle  

PubMed Central

Background Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem. Results We present an object-oriented module-based computational integration strategy to build a multiscale model of angiogenesis that links currently available models. As an example case, we use this approach to integrate modules representing microvascular blood flow, oxygen transport, vascular endothelial growth factor transport and endothelial cell behavior (sensing, migration and proliferation). Modeling methodologies in these modules include algebraic equations, partial differential equations and agent-based models with complex logical rules. We apply this integrated model to simulate exercise-induced angiogenesis in skeletal muscle. The simulation results compare capillary growth patterns between different exercise conditions for a single bout of exercise. Results demonstrate how the computational infrastructure can effectively integrate multiple modules by coordinating their connectivity and data exchange. Model parameterization offers simulation flexibility and a platform for performing sensitivity analysis. Conclusions This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions. PMID:21463529

2011-01-01

365

Effects of ethanol on rat heart and skeletal muscles  

SciTech Connect

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

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

1991-03-11

366

Large fiber size in skeletal muscle is metabolically advantageous  

PubMed Central

Skeletal muscle fiber size is highly variable, and while diffusion appears to limit maximal fiber size, there is no paradigm for the control of minimal size. The optimal fiber size hypothesis posits that the reduced surface area to volume (SA:V) in larger fibers reduces the metabolic cost of maintaining the membrane potential, and so fibers attain an optimal size that minimizes metabolic cost while avoiding diffusion limitation. Here we examine changes during hypertrophic fiber growth in metabolic cost and activity of the Na+-K+-ATPase in white skeletal muscle from crustaceans and fishes. We provide evidence for a major tenet of the optimal fiber size hypothesis by demonstrating that larger fibers are metabolically cheaper to maintain, and the cost of maintaining the membrane potential is proportional to fiber SA:V. The influence of SA:V on metabolic cost is apparent during growth in 16 species spanning a 20-fold range in fiber size, suggesting that this principle may apply widely. PMID:23851638

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

2013-01-01

367

Oriented surfaces of adsorbed cellulose nanowhiskers promote skeletal muscle myogenesis.  

PubMed

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

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

2013-01-01

368

MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation  

Microsoft Academic Search

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder caused by thymidine phosphorylase (TP) deficiency, resulting in severe gastrointestinal dysmotility and skeletal muscle abnormalities. A patient is reported with a classical MNGIE clinical presentation but without skeletal muscle involvement at morphological, enzymatic, or mitochondrial DNA level, though gastrointestinal myopathy was present. MNGIE was diagnosed by markedly raised plasma thymidine

K Szigeti; L-J C Wong; C-L Perng; G M Saifi; K Eldin; A M Adesina; D L Cass; M Hirano; J R Lupski; F Scaglia

2004-01-01

369

Is Visfatin an Adipokine or Myokine? Evidence for Greater Visfatin Expression in Skeletal Muscle than  

E-print Network

Is Visfatin an Adipokine or Myokine? Evidence for Greater Visfatin Expression in Skeletal Muscle- ceral adipose tissue in mammals, has been implicated in the immune system, cellular aging, and glucose real-time quantitative PCR and Western blotting, chicken skeletal muscle was found to contain 5- and 3

Ramachandran, Ramesh

370

Classification: Biological Sciences, Developmental Biology;1 CRIPTO REGULATES SKELETAL MUSCLE REGENERATION AND MODULATES SATELLITE3  

E-print Network

1 Classification: Biological Sciences, Developmental Biology;1 2 CRIPTO REGULATES SKELETAL MUSCLE.U.Leuven, Leuven 3000, Belgium14 5. INSERM, U955, team 10 "Cell interactions in the neuromuscular system, University College London. WC1E1 6DE, United Kingdom2 3 4 Running Title: Role of Cripto in skeletal muscle

Boyer, Edmond

371

Nuclear genetic control of mitochondrial translation in skeletal muscle revealed in patients  

E-print Network

Nuclear genetic control of mitochondrial translation in skeletal muscle revealed in patients in a developmentally regulated nuclear factor important for mitochondrial translation in skeletal muscle. INTRODUCTION The enzymatic system responsible for the generation of ATP by oxidative phosphorylation of ADP, located

Shoubridge, Eric

372

Chronic leptin treatment stimulates lipid oxidation in immortalized and primary mouse skeletal muscle cells  

Microsoft Academic Search

Leptin administration enhances lipid oxidation in skeletal muscle. Nevertheless, direct and chronic effect of leptin has not been well characterized. Here, we measured the effect of leptin on skeletal muscles and their signaling pathways using differentiated C2C12 myotubes and primary myotube cultures. Differentiated myotubes expressed both the short and long forms of leptin receptors. Leptin increased lipid oxidation in myotubes

Yunike Akasaka; Masaki Tsunoda; Tomohiro Ide; Koji Murakami

2009-01-01

373

Acclimation temperature affects the metabolic response of amphibian skeletal muscle to insulin  

Microsoft Academic Search

Frog skeletal muscle mainly utilizes the substrates glucose and lactate for energy metabolism. The goal of this study was to determine the effect of insulin on the uptake and metabolic fate of lactate and glucose at rest in skeletal muscle of the American bullfrog, Lithobates catesbeiana, under varying temperature regimens. We hypothesize that lactate and glucose metabolic pathways will respond

Ann M. Petersen; Todd T. Gleeson

2011-01-01

374

Exercise and Type 2 Diabetes: Molecular Mechanisms Regulating Glucose Uptake in Skeletal Muscle  

ERIC Educational Resources Information Center

Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial…

Stanford, Kristin I.; Goodyear, Laurie J.

2014-01-01

375

Modeling Cellular Metabolism and Energetics in Skeletal Muscle: Large-Scale Parameter Estimation and Sensitivity Analysis  

Microsoft Academic Search

Skeletal muscle plays a major role in the regulation of whole-body energy metabolism during physiological stresses such as ischemia, hypoxia, and exercise. Current experimental techniques provide relatively little in vivo data on dynamic responses of metabolite concentrations and metabolic fluxes in skeletal muscle to such physiological stimuli. As a complementary approach to experimental measurements and as a framework for quantitatively

Ranjan K. Dash; Yanjun Li; Jaeyeon Kim; Gerald M. Saidel; Marco E. Cabrera

2008-01-01

376

Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells  

E-print Network

Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells , Vincent Mouly6 and Shahragim Tajbakhsh1,§ 1 Stem Cells and Development, Department of Developmental by The Company of Biologists Ltd doi: 10.1242/jcs.097006 Summary Skeletal muscle stem cell fate in adult mice

Boyer, Edmond

377

Lower physical activity is associated with fat infiltration within skeletal muscle in young girls  

Technology Transfer Automated Retrieval System (TEKTRAN)

Fat infiltration within skeletal muscle is strongly associated with obesity, type 2 diabetes mellitus, and metabolic syndrome. Lower physical activity may be a risk factor for greater fat infiltration within skeletal muscle, although whether lower physical activity is associated with fat infiltrati...

378

THE EXPRESSION OF NEUREGULIN AND ERBB RECEPTORS IN HUMAN SKELETAL MUSCLE: EFFECTS OF PROGRESSIVE RESISTANCE TRAINING  

Technology Transfer Automated Retrieval System (TEKTRAN)

The neuregulin/erbB-signaling axis contributes to the development and growth of multiple mammalian tissues including skeletal muscle. In this study, we sought to characterize the native expression of this system in human skeletal muscle and test the hypothesis that a program of progressive resistanc...

379

Organization of Calcium Channel 1a Subunits in Triad Junctions in Skeletal Muscle*  

E-print Network

Organization of Calcium Channel 1a Subunits in Triad Junctions in Skeletal Muscle* Received-1617 and § Physiologie, Medizinische Hochschule, 30625 Hannover, Germany In skeletal muscle, dihydropyridine receptors and highly mobile as indicated by flu- orescence recovery after photobleaching. Thus, 1a does not appear

Betz, William J.

380

Telocytes within human skeletal muscle stem cell niche  

PubMed Central

Human skeletal muscle tissue displays specific cellular architecture easily damaged during individual existence, requiring multiple resources for regeneration. Congruent with local prerequisites, heterogeneous muscle stem cells (MuSCs) are present in the muscle interstitium. In this study, we aimed to characterize the properties of human muscle interstitial cells that had the characteristic morphology of telocytes (TCs). Immunocytochemistry and immunofluorescence showed that cells with TC morphology stained positive for c-kit/CD117 and VEGF. C-kit positive TCs were separated with magnetic-activated cell sorting, cultured in vitro and expanded for study. These cells exhibited high proliferation capacity (60% expressed endoglin/CD105 and 80% expressed nuclear Ki67). They also exhibited pluripotent capacity limited to Oct4 nuclear staining. In addition, 90% of c-kit positive TCs expressed VEGF. C-kit negative cells in the MuSCs population exhibited fibroblast-like morphology, low trilineage differential potential and negative VEGF staining. These results suggested that c-kit/CD117 positive TCs represented a unique cell type within the MuSC niche. PMID:21781275

Bojin, Florina M; Gavriliuc, Oana I; Cristea, Mirabela I; Tanasie, Gabriela; Tatu, Carmen S; Panaitescu, Carmen; Paunescu, Virgil

2011-01-01

381

CYTOCHEMICAL LOCALIZATION OF LACTIC DEHYDROGENASE IN WHITE SKELETAL MUSCLE  

PubMed Central

The limitations of the conventional histochemical methods for localization of lactic dehydrogenase (LDH) in white skeletal muscle have been analyzed quantitatively. It is demonstrated that more than 80 per cent of LDH diffuses into the incubation medium within the first 10 minutes of incubation. Furthermore, it is confirmed that the addition of phenazine methosulfate (PMS) to the ingredients of the histochemical reaction for LDH increases substantially the capacity of the white muscle extract to reduce Nitro-BT. Based on these observations, a modified method of cytochemical localization of LDH has been developed. This method prevents the leakage of LDH from tissue sections by the application of all the ingredients of the histochemical reaction to tissue sections in a thin gelatin film. The incubation mixture contains PMS so that the staining system is independent of tissue diaphorase. The application of this method to the adductor magnus muscle of the rabbit revealed a fine reticulum in the sarcoplasm of all muscle fibers, in addition to the staining of mitochondria. The distribution of the staining suggests that LDH is localized in the sarcoplasmic reticulum. PMID:14195619

Fahimi, H. Dariush; Amarasingham, Chandra Raj

1964-01-01

382

Temporal analysis of PI3kinase and MAPK signal transduction during skeletal muscle overload  

Microsoft Academic Search

Skeletal muscles can adapt to increased mechanical forces (or loading) by increasing the size and strength of the muscle. Knowledge of the molecular mechanisms by which muscle responds to increased loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. The objective of this research was to examine the temporal associations between the activation of

Christian Joseph Carlson

2001-01-01

383

Sphingosine 1-phosphate axis: a new leader actor in skeletal muscle biology  

PubMed Central

Sphingosine 1-phosphate (S1P) is a bioactive lipid involved in the regulation of biological processes such as proliferation, differentiation, motility, and survival. Here we review the role of S1P in the biology and homeostasis of skeletal muscle. S1P derives from the catabolism of sphingomyelin and is produced by sphingosine phosphorylation catalyzed by sphingosine kinase (SK). S1P can act either intracellularly or extracellularly through specific ligation to its five G protein-coupled receptors (GPCR) named S1P receptors (S1PR). Many experimental findings obtained in the last 20 years demonstrate that S1P and its metabolism play a multifaceted role in the regulation of skeletal muscle regeneration. Indeed, this lipid is known to activate muscle-resident satellite cells, regulating their proliferation and differentiation, as well as mesenchymal progenitors such as mesoangioblasts that originate outside skeletal muscle, both involved in tissue repair following an injury or disease. The molecular mechanism of action of S1P in skeletal muscle cell precursors is highly complex, especially because S1P axis is under the control of a number of growth factors and cytokines, canonical regulators of skeletal muscle biology. Moreover, this lipid is crucially involved in the regulation of skeletal muscle contractile properties, responsiveness to insulin, fatigue resistance and tropism. Overall, on the basis of these findings S1P signaling appears to be an appealing pharmacological target for improving skeletal muscle repair. Nevertheless, further understanding is required on the regulation of S1P downstream signaling pathways and the expression of S1PR. This article will resume our current knowledge on S1P signaling in skeletal muscle, hopefully stimulating further investigation in the field, aimed at individuating novel molecular targets for ameliorating skeletal muscle regeneration and reducing fibrosis of the tissue after a trauma or due to skeletal muscle diseases. PMID:24324439

Donati, Chiara; Cencetti, Francesca; Bruni, Paola

2013-01-01

384

Chronic enteral leucine supplementation of a low protein diet increases skeletal muscle protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation  

Technology Transfer Automated Retrieval System (TEKTRAN)

Leucine appears to be the key amino acid that positively regulates mTOR signalling. We hypothesized that prolonged feeding (24 hours) of a Leu supplemented low protein (LP) diet in neonatal pigs will increase protein synthesis in skeletal muscle to a rate similar to that of a high protein diet (HP)....

385

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

Technology Transfer Automated Retrieval System (TEKTRAN)

Insulin (INS) and amino acids (AA) act independently to stimulate protein synthesis in skeletal muscle of neonatal pigs, and the responses decrease with development. The purpose of this study was to compare the effect of INS and AA on the activation of signaling components leading to translation in...

386

Coupling of skeletal muscle to a prosthesis for circulatory support.  

PubMed

A durable bond between the end of skeletal muscles and prosthetic structures could, with appropriate linkage, allow circulatory support power by synchronous and/or sequential contraction of several in situ conditioned muscles. Potential advantages relative to a myoplasty wrap involve 1) less traumatic dissection, 2) efficient linear force development, 3) selectable contraction rate, 4) greater stroke work, 5) independent control of muscle pre-load and end diastolic pressure, and 6) independent control of duration of muscle tension and ejection time. However, no existing means of tissue-prosthetic bonding appears adequate. Practicality would demand that full tension bearing capacity by the bond take no longer than muscle conditioning. A prosthesis was developed to achieve those goals. As scaled for this study, it is made of 7,200-7,800 unspun, unplaited, 22 to 26 microns diameter polyester fibers swaged into four taper needles for weaving through distal muscle. The other end is formed into a polyurethane sheathed kernmantel cord for distal fixation. Devices were implanted in six 3 to 4 kg rabbits (unilateral posterior tibial tendon replacement, random side selection with contralateral dissection/closure controls), and their tensile strength was tested at 30 days. All healed well; leg movements were normal after 1 week. Limbs were frozen at -70 degrees C between death and testing. Control failure occurred at 243 +/- 94 N and experimental at 163 +/- 44 N (p = 0.065, t-test); highest estimated requirement was 17.2 N. Interface strength was adequate by 30 days. Continued investigations, addressing other questions, are warranted. PMID:9360078

Melvin, D B; Glos, D L; Abiog, M C; Litsky, A S

1997-01-01

387

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

PubMed Central

Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength. PMID:23977392

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

2013-01-01

388

Leucine and ?-Ketoisocaproic Acid, but Not Norleucine, Stimulate Skeletal Muscle Protein Synthesis in Neonatal Pigs1–3  

PubMed Central

The branched-chain amino acid, leucine, acts as a nutrient signal to stimulate protein synthesis in skeletal muscle of young pigs. However, the chemical structure responsible for this effect has not been identified. We have shown that the other branched-chain amino acids, isoleucine and valine, are not able to stimulate protein synthesis when raised in plasma to levels within the postprandial range. In this study, we evaluated the effect of leucine, ?-ketoisocaproic acid (KIC), and norleucine infusion (0 or 400 ?mol·kg?1·h?1 for 60 min) on protein synthesis and activation of translation initiation factors in piglets. Infusion of leucine, KIC, and norleucine raised plasma levels of each compound compared with controls. KIC also increased (P < 0.01) and norleucine reduced (P < 0.02) plasma levels of leucine compared with controls. Administration of leucine and KIC resulted in greater (P < 0.006) phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) and eIF4G, lower (P < 0.04) abundance of the inactive 4E-BP1·eIF4E complex, and greater (P < 0.05) active eIF4G·eIF4E complex formation in skeletal muscle compared with controls. Protein synthesis in skeletal muscle was greater (P < 0.02) in leucine- and KIC-infused pigs than in those in the control group. Norleucine infusion did not affect muscle protein synthesis or translation initiation factor activation. In liver, neither protein synthesis nor activation of translation initiation factors was affected by treatment. These results suggest that the ability of leucine to act as a nutrient signal to stimulate skeletal muscle protein synthesis is specific for leucine and/or its metabolite, KIC. PMID:20534881

Escobar, Jeffery; Frank, Jason W.; Suryawan, Agus; Nguyen, Hanh V.; Van Horn, Cynthia G.; Hutson, Susan M.; Davis, Teresa A.

2010-01-01

389

Endogenous erythropoietin signaling facilitates skeletal muscle repair and recovery following pharmacologically induced damage  

PubMed Central

Erythropoietin acts by binding to its cell surface receptor on erythroid progenitor cells to stimulate erythrocyte production. Erythropoietin receptor expression in nonhematopoietic tissue, including skeletal muscle progenitor cells, raises the possibility of a role for erythropoietin beyond erythropoiesis. Mice with erythropoietin receptor restricted to hematopoietic tissue were used to assess contributions of endogenous erythropoietin to promote skeletal myoblast proliferation and survival and wound healing in a mouse model of cardiotoxin induced muscle injury. Compared with wild-type controls, these mice had fewer skeletal muscle Pax-7+ satellite cells and myoblasts that do not proliferate in culture, were more susceptible to skeletal muscle injury and reduced maximum load tolerated by isolated muscle. In contrast, mice with chronic elevated circulating erythropoietin had more Pax-7+ satellite cells and myoblasts with increased proliferation and survival in culture, decreased muscle injury, and accelerated recovery of maximum load tolerated by isolated muscle. Skeletal muscle myoblasts also produced endogenous erythropoietin that increased at low O2. Erythropoietin promoted proliferation, survival, and wound recovery in myoblasts via the phosphoinositide 3-kinase/AKT pathway. Therefore, endogenous and exogenous erythropoietin contribute to increasing satellite cell number following muscle injury, improve myoblast proliferation and survival, and promote repair and regeneration in this mouse induced muscle injury model independent of its effect on erythrocyte production.—Jia, Y., Suzuki, N., Yamamoto, M., Gassmann, M., Noguchi, C. T. Endogenous erythropoietin signaling facilitates skeletal muscle repair and recovery following pharmacologically induced damage. PMID:22490927

Jia, Yi; Suzuki, Norio; Yamamoto, Masayuki; Gassmann, Max; Noguchi, Constance Tom

2012-01-01

390

Skeletal Muscle Fascicle Arrangements Can Be Reconstructed Using a Laplacian Vector Field Simulation  

PubMed Central

Skeletal muscles are characterized by a large diversity in anatomical architecture and function. Muscle force and contraction are generated by contractile fiber cells grouped in fascicle bundles, which transmit the mechanical action between origin and insertion attachments of the muscle. Therefore, an adequate representation of fascicle arrangements in computational models of skeletal muscles is important, especially when investigating three-dimensional muscle deformations in finite element models. However, obtaining high resolution in vivo measurements of fascicle arrangements in skeletal muscles is currently still challenging. This motivated the development of methods in previous studies to generate numerical representations of fascicle trajectories using interpolation templates. Here, we present an alternative approach based on the hypothesis of a rotation and divergence free (Laplacian) vector field behavior which reflects observed physical characteristics of fascicle trajectories. To obtain this representation, the Laplace equation was solved in anatomical reconstructions of skeletal muscle shapes based on medical images using a uniform flux boundary condition on the attachment areas. Fascicle tracts were generated through a robust flux based tracing algorithm. The concept of this approach was demonstrated in two-dimensional synthetic examples of typical skeletal muscle architectures. A detailed evaluation was performed in an example of the anatomical human tibialis anterior muscle which showed an overall agreement with measurements from the literature. The utility and capability of the proposed method was further demonstrated in other anatomical examples of human skeletal muscles with a wide range of muscle shapes and attachment morphologies. PMID:24204878

Choi, Hon Fai; Blemker, Silvia S.

2013-01-01

391

Induction of functional tissue-engineered skeletal muscle constructs by defined electrical stimulation  

PubMed Central

Electrical impulses are necessary for proper in vivo skeletal muscle development. To fabricate functional skeletal muscle tissues in vitro, recapitulation of the in vivo niche, including physical stimuli, is crucial. Here, we report a technique to engineer skeletal muscle tissues in vitro by electrical pulse stimulation (EPS). Electrically excitable tissue-engineered skeletal muscle constructs were stimulated with continuous electrical pulses of 0.3?V/mm amplitude, 4?ms width, and 1?Hz frequency, resulting in a 4.5-fold increase in force at day 14. In myogenic differentiation culture, the percentage of peak twitch force (%Pt) was determined as the load on the tissue constructs during the artificial exercise induced by continuous EPS. We optimized the stimulation protocol, wherein the tissues were first subjected to 24.5%Pt, which was increased to 50–60%Pt as the tissues developed. This technique may be a useful approach to fabricate tissue-engineered functional skeletal muscle constructs. PMID:24759171

Ito, Akira; Yamamoto, Yasunori; Sato, Masanori; Ikeda, Kazushi; Yamamoto, Masahiro; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

2014-01-01