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1

Regulation of skeletal muscle proteolysis by amino acids.  

PubMed

Skeletal muscle is the major reservoir of body protein that can be mobilized in a number of muscle wasting conditions, that include kidney failure. Increased proteolysis in such conditions provides free amino acids that are used for acute-phase protein synthesis or that are degraded for energy purposes. Amino acids act as signals to regulate both protein synthesis and protein breakdown. We review the current but limited information available on the regulation of proteolytic systems in muscle cells. In particular, recent data have shown that amino acid deprivation in C2C12 myotubes stimulates autophagic sequestration by mechanisms that implicate the Apg system through a class III phosphoinositide-3'-kinase (PI3K III ) signaling cascade. PMID:15648001

Béchet, Daniel; Tassa, Amina; Combaret, Lydie; Taillandier, Daniel; Attaix, Didier

2005-01-01

2

Amino Acid Transporters in the Regulation of Human Skeletal Muscle Protein Metabolism  

PubMed Central

Purpose of the Review To highlight recent research on amino acid sensing and signaling and the role of amino acid transporters in the regulation of human skeletal muscle protein metabolism. Recent Findings The mechanisms that sense amino acid availability and activate mechanistic target of rapamycin complex 1 (mTORC1) signaling and protein synthesis are emerging, with multiple new proteins and intracellular amino acid sensors recently identified. Amino acid transporters have a role in the delivery of amino acids to these intracellular sensors and new findings provide further support for amino acid transporters as possible extracellular amino acid sensors. There is growing evidence in human skeletal muscle that amino acid transporter expression is dynamic and responsive to various stimuli, indicating amino acid transporters may have a unique role in the regulation of human skeletal muscle adaptation. Summary There is a clear need to further examine the role of amino acid transporters in human skeletal muscle and their link to cellular amino acid sensing and signaling in the control of protein metabolism. A better understanding of amino acid transport and transporters will allow us to optimize nutritional strategies to accelerate muscle health and improve outcomes for clinical populations. PMID:24100668

Dickinson, Jared M.; Rasmussen, Blake B.

2014-01-01

3

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

4

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...

5

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

PubMed

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. PMID:24016666

Murakami, Taro; Yoshinaga, Mariko

2013-10-01

6

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

PubMed

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

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

2014-01-01

7

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...

8

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

PubMed Central

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

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

1993-01-01

9

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...

10

Enhanced skeletal muscle protein synthesis rates in pigs treated with somatotropin requires fed amino acids levels  

Technology Transfer Automated Retrieval System (TEKTRAN)

Chronic somatotropin (pST) treatment in pigs increases skeletal muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin alone could not account for the pST-induced increase in protein synthesis. This study...

11

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

12

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

PubMed Central

Regardless of age or gender, resistance training or provision of adequate amounts of dietary protein (PRO) or essential amino acids (EAA) can increase muscle protein synthesis (MPS) in healthy adults. Combined PRO or EAA ingestion proximal to resistance training, however, can augment the post-exercise MPS response and has been shown to elicit a greater anabolic effect than exercise plus carbohydrate. Unfortunately, chronic/adaptive response data comparing the effects of different protein sources is limited. A growing body of evidence does, however, suggest that dairy PRO, and whey in particular may: 1) stimulate the greatest rise in MPS, 2) result in greater muscle cross-sectional area when combined with chronic resistance training, and 3) at least in younger individuals, enhance exercise recovery. Therefore, this review will focus on whey protein supplementation and its effects on skeletal muscle mass when combined with heavy resistance training. PMID:20565767

2010-01-01

13

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

14

Structure of Skeletal Muscle  

MedlinePLUS

... Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Muscular System » Structure of Skeletal Muscle Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

15

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...

16

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

PubMed

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

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

2014-06-01

17

Amino acid residues 4425-4621 localized on the three-dimensional structure of the skeletal muscle ryanodine receptor.  

PubMed Central

We have localized a region contained within the sequence of amino acid residues 4425-4621 on the three-dimensional structure of the skeletal muscle ryanodine receptor (RyR). Mouse monoclonal antibodies raised against a peptide comprising these residues have been complexed with ryanodine receptors and imaged in the frozen-hydrated state by cryoelectron microscopy. These images, along with images of antibody-free ryanodine receptor, were used to compute two-dimensional averaged images and three-dimensional reconstructions. Two-dimensional averages of immunocomplexes in which the ryanodine receptor was in the fourfold symmetrical orientation disclosed four symmetrical regions of density located on the edges of the receptor's cytoplasmic assembly that were absent from control averages of receptor without added antibody. Three-dimensional reconstructions revealed the antibody-binding sites to be on the so-called handle domains of the ryanodine receptor's cytoplasmic assembly, near their junction with the transmembrane assembly. This study is the first to demonstrate epitope mapping on the three-dimensional structure of the ryanodine receptor. PMID:10692321

Benacquista, B L; Sharma, M R; Samsó, M; Zorzato, F; Treves, S; Wagenknecht, T

2000-01-01

18

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

19

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

PubMed

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

Hamdi, M M; Mutungi, G

2011-07-15

20

Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats.  

PubMed

Background: Enhanced glutamine (GLN) intake may affect the catabolism of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), which play a regulatory role in protein turnover. We examined the effects of enhanced GLN availability on leucine oxidation, amino acid concentrations, and protein metabolism in muscles from healthy and septic rats. Methods: Cecal ligation and puncture were used as a model of sepsis. Twenty-four hours after surgery, the soleus (SOL, red muscle) and the extensor digitorum longus (EDL, white muscle) were incubated in medium containing 0.5 or 2.0 mM GLN. Protein breakdown, protein synthesis, and leucine oxidation were determined via 3-methylhistidine release, muscle L-[1-(14)C]leucine radioactivity, and the radioactivity of released (14)CO2, respectively. Results: In muscles from septic animals, increased proteolysis and leucine oxidation and decreased protein synthesis were detected. These effects were more pronounced in the EDL. In septic muscles, the addition of GLN decreased leucine oxidation in both muscles and increased protein synthesis in the EDL. In muscles from untreated animals, decreased leucine oxidation after the addition of GLN to the medium was associated with decreased protein synthesis in the SOL and decreased concentrations of serine, glycine, histidine, alanine, arginine, proline, and lysine in both muscles. Conclusions: White muscle fibers are more sensitive to septic stimuli than red fibers are. In sepsis, enhanced GLN intake may ameliorate GLN deficiency, inhibit BCAA catabolism, and stimulate protein synthesis. In the healthy state, surplus of GLN may lead to severe alterations in the intramuscular concentration of several amino acids and impair protein synthesis. PMID:24906686

Holecek, Milan; Sispera, Ludek; Skalska, Hana

2014-06-01

21

Mechanotransduction in skeletal muscle  

PubMed Central

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

Burkholder, Thomas J.

2007-01-01

22

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

Microsoft Academic Search

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

Juha J Hulmi; Christopher M Lockwood; Jeffrey R Stout

2010-01-01

23

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  

Microsoft Academic Search

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

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

2010-01-01

24

Lysosomal proteolysis in skeletal muscle.  

PubMed

Lysosomal proteases are abundantly expressed in fetal muscles, but poorly represented in the adult skeletal muscles. The lysosomal proteolytic system is nonetheless stimulated in adult muscles in a variety of pathological conditions. Furthermore, recent investigations describe autophagosomes in muscle fibers in vitro and in vivo, and report myopathies with excessive autophagy. This review presents our current knowledge about the lysosomal proteolytic system and summarizes the evidences pertaining to the role of lysosomes and autophagosomes in muscle physiology and pathology. PMID:16125113

Bechet, Daniel; Tassa, Amina; Taillandier, Daniel; Combaret, Lydie; Attaix, Didier

2005-10-01

25

Adult skeletal muscle stem cells.  

PubMed

Skeletal muscles in vertebrates have a phenomenal regenerative capacity. A muscle that has been crushed can regenerate fully both structurally and functionally within a month. Remarkably, efficient regeneration continues to occur following repeated injuries. Thousands of muscle precursor cells are needed to accomplish regeneration following acute injury. The differentiated muscle cells, the multinucleated contractile myofibers, are terminally withdrawn from mitosis. The source of the regenerative precursors is the skeletal muscle stem cells-the mononucleated cells closely associated with myofibers, which are known as satellite cells. Satellite cells are mitotically quiescent or slow-cycling, committed to myogenesis, but undifferentiated. Disruption of the niche after muscle damage results in their exit from quiescence and progression towards commitment. They eventually arrest proliferation, differentiate, and fuse to damaged myofibers or make de novo myofibers. Satellite cells are one of the well-studied adult tissue-specific stem cells and have served as an excellent model for investigating adult stem cells. They have also emerged as an important standard in the field of ageing and stem cells. Several recent reviews have highlighted the importance of these cells as a model to understand stem cell biology. This chapter begins with the discovery of satellite cells as skeletal muscle stem cells and their developmental origin. We discuss transcription factors and signalling cues governing stem cell function of satellite cells and heterogeneity in the satellite cell pool. Apart from satellite cells, a number of other stem cells have been shown to make muscle and are being considered as candidate stem cells for amelioration of muscle degenerative diseases. We discuss these "offbeat" muscle stem cells and their status as adult skeletal muscle stem cells vis-a-vis satellite cells. The ageing context is highlighted in the concluding section. PMID:25344672

Sambasivan, Ramkumar; Tajbakhsh, Shahragim

2015-01-01

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

The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signalling in mouse skeletal muscle.  

PubMed

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

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

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

30

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

31

Satellite cells: the architects of skeletal muscle.  

PubMed

The outstanding regenerative capacity of skeletal muscle is attributed to the resident muscle stem cell termed satellite cell. Satellite cells are essential for skeletal muscle regeneration as they ultimately provide the myogenic precursors that rebuild damaged muscle tissue. Satellite cells characteristically are a heterogeneous population of stem cells and committed progenitor cells. Delineation of cellular hierarchy and understanding how lineage fate choices are determined within the satellite cell population will be invaluable for the advancement of muscle regenerative therapies. PMID:24439806

Chang, Natasha C; Rudnicki, Michael A

2014-01-01

32

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

33

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

34

Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement  

PubMed Central

Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement. Using l-[1,2-13C]leucine as a tracer, we measured the fractional synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins in 18 participants during sustained (7-h) insulin or saline infusion (n = 9 each). We also measured muscle ATP production, mitochondrial enzyme activities, mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins regulating protein synthesis. The concentration of circulating essential AA decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle PS rates were also lower during insulin (2–7 h) than during saline infusions despite increased mRNA levels of selected mitochondrial genes. Under these conditions, insulin did not alter mitochondrial enzyme activities and ATP production. These effects were associated with enhanced phosphorylation of Akt but not of protein synthesis activators mTOR, p70S6K, and 4EBP1. In conclusion, sustained physiological hyperinsulinemia without AA replacement did not stimulate PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial ATP production in healthy humans. These results support that insulin and AA act in conjunction to stimulate muscle mitochondrial function and mitochondrial protein synthesis. PMID:22967500

Barazzoni, Rocco; Short, Kevin R.; Asmann, Yan; Coenen-Schimke, Jill M.; Robinson, Matthew M.

2012-01-01

35

Amino acid sequence and distribution of mRNA encoding a major skeletal muscle laminin binding protein: an extracellular matrix-associated protein with an unusual COOH-terminal polyaspartate domain  

PubMed Central

Two cDNAs encoding an abundant chicken muscle extracellular matrix (ECM)-associated laminin-binding protein (LBP) have been isolated and sequenced. The predicted primary amino acid sequence includes a probable signal peptide and a site for N-linked glycosylation, but lacks a hydrophobic segment long enough to span the membrane. The COOH terminus consists of an unusual repeat of 33 consecutive aspartate residues. Comparison with other sequences indicates that this protein is different from previously described LBPs and ECM receptors. RNA blot analysis of LBP gene expression showed that LBP mRNA was abundant in skeletal and heart muscle, but barely detectable in other tissues. Blots of chicken genomic DNA suggest that a single gene encodes this LBP. The amino acid sequence and mRNA distribution are consistent with the biochemical characterization described by Hall and co-workers (Hall, D. E., K. A. Frazer, B. C. Hahn, and L. F. Reichardt. 1988. J. Cell Biol. 107:687-697). These analyses indicate that LBP is an abundant ECM-associated muscle protein with an unusually high negative charge that interacts with both membranes and laminin, and has properties of a peripheral, not integral membrane protein. Taken together, our studies show that muscle LBP is a secreted, peripheral membrane protein with an unusual polyaspartate domain. Its laminin and membrane binding properties suggest that it may help mediate muscle cell interactions with the extracellular matrix. We propose the name "aspartactin" for this LBP. PMID:3417769

1988-01-01

36

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

37

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

38

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

39

Regrowth of skeletal muscle atrophied from inactivity.  

PubMed

The current state of knowledge regarding regrowth of skeletal muscle after inactivity-induced atrophy is reviewed. Muscle regrowth is incomplete after hindlimb suspension in juvenile rats and after limb immobilization in old animals. The process of regrowth from immobilization-induced atrophy likely involves the reversal of directional changes in molecules producing muscle loss while initiating anabolic processes for regrowth of muscle mass. Unfortunately, the molecular mechanisms responsible for successful, or failed, muscle regrowth are not well understood. The purpose of the review is to provide current knowledge about the biology of muscle regrowth from inactivity-induced atrophy. PMID:14707768

Machida, Shuichi; Booth, Frank W

2004-01-01

40

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

41

Denervation and reinnervation of skeletal muscle  

NASA Technical Reports Server (NTRS)

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

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

1983-01-01

42

Myoglobin Function in Exercising Skeletal Muscle  

NASA Astrophysics Data System (ADS)

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

Cole, Randolph P.

1982-04-01

43

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

44

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

45

Stereoencephalotomy and control of skeletal muscle tone.  

PubMed

Following therapeutic stereotactic lesions in the ventrolateral subthalamus and adjacent nuclei there are two phenomena concerning muscle tone: decreased muscle stiffness and failure in load compensation. In order to clarify whether hypotonia is due to decreased reflex activity and/or reduced nonreflex muscle stiffness, torque-induced stretch responses in the forearm flexor muscles and muscle spindle afferent discharge were investigated. In hypotonia following these lesions, the immediate compensation of abrupt external perturbations was diminished prior to reflex onset. A special feedback system is presented which originates in skeletal muscles and which continuously controls the muscle stiffness during movements. This afferent fiber system probably has a greater representation at the thalamic level as compared to the peripheral nerve. It is assumed that the decrease in muscle stiffness as well as the failure in load compensation are due to diminished static gamma-drive. This lack in somatosensory feedback can be compensated voluntarily by changing the mode of innervation. PMID:2657944

Struppler, A

1989-01-01

46

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

47

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

48

Transmission of polarized light in skeletal muscle.  

PubMed

Experiments were conducted to study polarized light transmission in fresh bovine skeletal muscle of varying thicknesses. Two-dimensional polarization-sensitive transmission images were acquired and analyzed using a numerical parametric fitting algorithm. The total transmittance intensity and degree-of-polarization were calculated for both central ballistic and surrounding scattering regions. Full Mueller matrix images were derived from the raw polarization images and the polar decomposition algorithm was applied to extract polarization parameters. The results suggest that polarized light propagation through skeletal muscle is affected by strong birefringence, diattenuation, multiple scattering induced depolarization and the sarcomere diffraction effect. PMID:21361681

Shuaib, Ali; Li, Xin; Yao, Gang

2011-02-01

49

Transmission of polarized light in skeletal muscle  

NASA Astrophysics Data System (ADS)

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

Shuaib, Ali; Li, Xin; Yao, Gang

2011-02-01

50

Tissue engineering for skeletal muscle regeneration  

PubMed Central

Summary Stem cells and regenerative medicine have obtained a remarkable consent from the scientific community for their promising ability to recover aged, injured and diseased tissue. However, despite the noteworthy potential, hurdles currently hinder their use and clinical application: cell survival, immune response, tissue engraftment and efficient differentiation. Hence a new interdisciplinary scientific approach, such as tissue engineering, is going deep attempts to mimic neo-tissue-genesis as well as stem cell engraftment amelioration. Skeletal muscle tissue engineering represents a great potentiality in medicine for muscle regeneration exploiting new generation injectable hydrogel as scaffold supporting progenitor/stem cells for muscle differentiation reconstructing the natural skeletal muscle tissue architecture influenced by matrix mechanical and physical property and by a dynamic environment. PMID:23738301

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

2012-01-01

51

RESEARCH Open Access A human skeletal muscle interactome centered  

E-print Network

RESEARCH Open Access A human skeletal muscle interactome centered on proteins involved in muscular skeletal-muscle cDNA library to establish a proteome-scale map of protein-protein interactions centered , Marc Bartoli1,2 and Isabelle Richard1* Abstract Background: The complexity of the skeletal muscle

Paris-Sud XI, Université de

52

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

53

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

54

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

55

Skeletal muscle fibre types in the dog.  

PubMed Central

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

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

1993-01-01

56

Skeletal muscle metabolism in hypokinetic rats  

NASA Technical Reports Server (NTRS)

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

Tischler, M. E.

1984-01-01

57

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

58

Domain Characterization of Rabbit Skeletal Muscle Myosin Light Chain Kinase  

PubMed Central

Myosin light chain kinase can be divided into three distinct structural domains, an amino-terminal “tail,” of unknown function, a central catalytic core and a carboxy-terminal calmodulin-binding regulatory region. We have used a combination of deletion mutagenesis and monoclonal antibody epitope mapping to define these domains more closely. A 2.95-kilobase cDNA has been isolated that includes the entire coding sequence of rabbit skeletal muscle myosin light chain kinase (607 amino acids). This cDNA, expressed in COS cells encoded a Ca2+/calmodulin-dependent myosin light chain kinase with a specific activity similar to that of the enzyme purified from rabbit skeletal muscle. Serial carboxy-terminal deletions of the regulatory and catalytic domains were constructed and expressed in COS cells. The truncated kinases had no detectable myosin light chain kinase activity. Monoclonal antibodies which inhibit the activity of the enzyme competitively with respect to myosin light chain were found to bind between residues 235–319 and 165–173, amino-terminal of the previously defined catalytic core. Thus, residues that are either involved in substrate binding or in close proximity to a light chain binding site may be located more amino-terminal than the previously defined catalytic core. PMID:1688558

Herring, B. Paul; Stull, James T.; Gallagher, Patricia J.

2010-01-01

59

Insulin Increases Ceramide Synthesis in Skeletal Muscle  

PubMed Central

Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG) were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects. PMID:24949486

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

2014-01-01

60

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

61

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...

62

Pannexin 1 channels in skeletal muscles  

PubMed Central

Normal myotubes and adult innervated skeletal myofibers express the glycoprotein pannexin1 (Panx1). Six of them form a “gap junction hemichannel-like” structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules. So far little is known about the role of Panx1 channels in muscles but skeletal muscles of Panx1?/? mice do not show an evident phenotype. Innervated adult fast and slow skeletal myofibers show Panx1 reactivity in close proximity to dihydropyridine receptors in the sarcolemma of T-tubules. These Panx1 channels are activated by electrical stimulation and extracellular ATP. Panx1 channels play a relevant role in potentiation of muscle contraction because they allow release of ATP and uptake of glucose, two molecules required for this response. In support of this notion, the absence of Panx1 abrogates the potentiation of muscle contraction elicited by repetitive electrical stimulation, which is reversed by exogenously applied ATP. Phosphorylation of Panx1 Thr and Ser residues might be involved in Panx1 channel activation since it is enhanced during potentiation of muscle contraction. Under denervation, Panx1 levels are upregulated and this partially explains the reduction in electrochemical gradient, however its absence does not prevent denervation-induced atrophy but prevents the higher oxidative state. Panx1 also forms functional channels at the cell surface of myotubes and their functional state has been associated with intracellular Ca2+ signals and regulation of myotube plasticity evoked by electrical stimulation. We proposed that Panx1 channels participate as ATP channels and help to keep a normal oxidative state in skeletal muscles. PMID:24782784

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

2014-01-01

63

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

PubMed

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

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

2014-10-01

64

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

65

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

66

Sexually dimorphic effect of aging on skeletal muscle protein synthesis  

PubMed Central

Background Although there appear to be no differences in muscle protein turnover in young and middle aged men and women, we have reported significant differences in the rate of muscle protein synthesis between older adult men and women. This suggests that aging may affect muscle protein turnover differently in men and women. Methods We measured the skeletal muscle protein fractional synthesis rate (FSR) by using stable isotope-labeled tracer methods during basal postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic-euglycemic clamp in eight young men (25–45 y), ten young women (25–45 y), ten old men (65–85 y) and ten old women (65–85 y). Results The basal muscle protein FSR was not different in young and old men (0.040?±?0.004 and 0.043?±?0.005%·h-1, respectively) and combined insulin, glucose and amino acid infusion significantly increased the muscle protein FSR both in young (to 0.063?±?0.006%·h-1) and old (to 0.051?±?0.008%·h-1) men but the increase (0.023?±?0.004 vs. 0.009?±?0.004%·h-1, respectively) was ~60% less in the old men (P?=?0.03). In contrast, the basal muscle protein FSR was ~30% greater in old than young women (0.060?±?0.003 vs. 0.046?±?0.004%·h-1, respectively; P?amino acid infusion significantly increased the muscle protein FSR in young (P?muscle protein synthesis and thus the metabolic processes responsible for the age-related decline in muscle mass. PMID:22620287

2012-01-01

67

Interstitial space of mouse skeletal muscle  

PubMed Central

1. A new preparation of mouse skeletal muscle, prepared from pectoral muscles, is described. 2. The sorbitol space of this muscle, both in vivo and in vitro, has been measured with dynamic loading of the muscle in vitro as an experimental variable. 3. The Na+ and K+ contents of the muscle have been determined and the apparent intracellular concentration for these ions calculated both in vivo and after incubation in vitro. 4. Histological studies on the incubated muscle have been made so as to permit comparison of the changes in the chemical measurements with changes in the ultrastructure of the muscle. 5. The results of these experiments show that there is an increase in the apparent extracellular space of the muscle following incubation. This increase is constant, and independent of the load, with the important exception that unloaded muscles do not reach an equilibrium during the period of incubation and have a much greater apparent extracellular space. 6. Intracellular Na+ and K+ concentrations are consistent with the sorbitol being restricted to an extracellular phase in the loaded muscle; but the evidence implies that sorbitol in the unloaded muscle penetrates into a space from which Na+ is excluded. 7. The total water content of the muscle per unit weight is unchanged by incubation, indicating that the apparent change in sorbitol space is in the ratio of intracellular space to extracellular space rather than by addition of water to the extracellular space. The significance of these results is discussed with reference to the use of such preparations for in vitro studies. ImagesPlate 1 PMID:7131323

Sheff, Michael F.; Zacks, Sumner I.

1982-01-01

68

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

69

Transmission of polarized light in skeletal muscle  

Microsoft Academic Search

Experiments were conducted to study polarized light transmission in fresh bovine skeletal muscle of varying thicknesses. Two-dimensional polarization-sensitive transmission images were acquired and analyzed using a numerical parametric fitting algorithm. The total transmittance intensity and degree-of-polarization were calculated for both central ballistic and surrounding scattering regions. Full Mueller matrix images were derived from the raw polarization images and the polar

Ali Shuaib; Xin Li; Gang Yao

2011-01-01

70

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

71

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

72

Are antioxidants useful for treating skeletal muscle atrophy?  

Microsoft Academic Search

Changes in the skeletal muscle protein mass frequently occur in both physiological and pathological states. Muscle hypotrophy, in particular, is commonly observed during aging and is characteristic of several pathological conditions such as neurological diseases, cancer, diabetes, and sepsis. The skeletal muscle protein content depends on the relative rates of synthesis and degradation, which must be coordinately regulated to maintain

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

2009-01-01

73

Genetic determinism of fiber type proportion in human skeletal muscle  

Microsoft Academic Search

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

JEAN-AIME SIMONEAU; CLAUDE BOUCHARD

74

Ubiquitin-proteasome-dependent proteolysis in skeletal muscle  

E-print Network

pathway has recently been reported to be of major importance in the breakdown of skeletal muscle proteins be used to manipulate muscle protein mass. Such concepts are essential for the devel- opment of anti-cachectic therapies for many clinical situations. @ Inra/Elsevier, Paris skeletal muscle / protein breakdown

Paris-Sud XI, Université de

75

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

76

GLUT-3 expression in human skeletal muscle  

NASA Technical Reports Server (NTRS)

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

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

2000-01-01

77

Role of microRNAs in skeletal muscle hypertrophy  

PubMed Central

Skeletal muscle comprises approximately 40% of body weight, and is important for locomotion, as well as for metabolic homeostasis. Adult skeletal muscle mass is maintained by a fine balance between muscle protein synthesis and degradation. In response to cytokines, nutrients, and mechanical stimuli, skeletal muscle mass is increased (hypertrophy), whereas skeletal muscle mass is decreased (atrophy) in a variety of conditions, including cancer cachexia, starvation, immobilization, aging, and neuromuscular disorders. Recent studies have determined two important signaling pathways involved in skeletal muscle mass. The insulin-like growth factor-1 (IGF-1)/Akt pathway increases skeletal muscle mass via stimulation of protein synthesis and inhibition of protein degradation. By contrast, myostatin signaling negatively regulates skeletal muscle mass by reducing protein synthesis. In addition, the discovery of microRNAs as novel regulators of gene expression has provided new insights into a multitude of biological processes, especially in skeletal muscle physiology. We summarize here the current knowledge of microRNAs in the regulation of skeletal muscle hypertrophy, focusing on the IGF-1/Akt pathway and myostatin signaling. PMID:24474938

Hitachi, Keisuke; Tsuchida, Kunihiro

2014-01-01

78

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

79

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

80

Increased Excitability of Acidified Skeletal Muscle  

PubMed Central

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

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

2005-01-01

81

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

82

Osmoregulatory processes and skeletal muscle metabolism  

NASA Astrophysics Data System (ADS)

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

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

83

Interactive Classroom Demonstration of Skeletal Muscle Contraction  

NSDL National Science Digital Library

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

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

2002-12-01

84

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

PubMed Central

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

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

2014-01-01

85

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...

86

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...

87

INTRODUCTION Vertebrate skeletal muscle fibers can be subdivided into  

E-print Network

, mutants with disrupted notochord development have a loss of muscle pioneers, and muscle pioneer loss of Engrailed-expressing muscle pioneers. In addition, mutant embryos have partial cyclopiaINTRODUCTION Vertebrate skeletal muscle fibers can be subdivided into multiple fiber types based

Devoto, Stephen H.

88

Influence of Temperature on Isometric Contractions of Rat Skeletal Muscles  

Microsoft Academic Search

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

R. Close; J. F. Y. Hoh

1968-01-01

89

Growth factor involvement in tension-induced skeletal muscle growth  

NASA Technical Reports Server (NTRS)

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

Vandenburgh, Herman W.

1987-01-01

90

Role of Calpain in Skeletal-Muscle Protein Degradation  

Microsoft Academic Search

Although protein degradation is enhanced in muscle-wasting conditions and limits the rate of muscle growth in domestic animals, the proteolytic system responsible for degrading myofibrillar proteins in skeletal muscle is not well defined. The goals of this study were to evaluate the roles of the calpains (calcium-activated cysteine proteases) in mediating muscle protein degradation and the extent to which these

Jing Huang; Neil E. Forsberg

1998-01-01

91

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

92

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

PubMed

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

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

2008-10-01

93

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...

94

Growth factor involvement in tension-induced skeletal muscle growth  

NASA Technical Reports Server (NTRS)

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

Vandenburgh, H. H.

1987-01-01

95

Skeletal muscle protein synthesis and degradation in patients with chronic renal failure  

Microsoft Academic Search

Skeletal muscle protein synthesis and degradation in patients with chronic renal failure. Muscle protein turnover and amino acid (AA) exchange across the forearm were studied in nine postabsorptive patients with chronic renal failure (CRF) under unrestricted calorie-protein diets and eight controls by using the arterio-venous difference technique associated with the 3H-phenylalanine kinetics. In patients with CRF: (1) the rate of

Giacomo Garibotto; Rodolfo Russo; Antonella Sofia; Maria Rita Sala; Cristina Robaudo; Paolo Moscatelli; Giacomo Deferrari; Alberto Tizianello

1994-01-01

96

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

97

Tuberculous infection of skeletal muscle in a case of dermatomyositis.  

PubMed

A patient with dermatomyositis associated with carcinoma was treated with steroids and antibiotics for possible tuberculosis. Autopsy showed an overwhelming diffuse nongranulomatous infection of Mycobacterium tuberculosis involving only the skeletal muscles and one inguinal lymph node. The rare localization of tuberculosis to skeletal muscle in this case is possibly due to steroid immunosuppression and the humoral immune attack on muscle blood vessels that is a part of dermatomyositis. PMID:8007998

Davidson, G S; Voorneveld, C R; Krishnan, N

1994-07-01

98

Molecular cloning of two fast myosin heavy chain cDNAs from chicken embryo skeletal muscle.  

PubMed Central

Recombinant DNA clones containing sequences for two different types of myosin heavy chain (HC) genes from chicken embryonic skeletal muscle were constructed and analyzed. Specificity of the clones for myosin HC was demonstrated by hybrid-arrested translation, by hybridization to a 7.0-kb mRNA, and by comparison of DNA sequences with known amino acid sequences of rabbit skeletal muscle myosin HC. Restriction enzyme and electron-microscopic heteroduplex analysis showed the presence of two distinct but homologous cDNA sequences. Hybrid melting curves indicated that both types of sequences represent fast myosin HC sequences. Images PMID:6265916

Umeda, P K; Sinha, A M; Jakovcic, S; Merten, S; Hsu, H J; Subramanian, K N; Zak, R; Rabinowitz, M

1981-01-01

99

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

100

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

PubMed

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

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

2005-02-01

101

Inhibition of skeletal muscle development: less differentiation gives more muscle.  

PubMed

The fact that stem cells have to be protected from premature differentiation is true for many organs in the developing embryo and the adult organism. However, there are several arguments that this is particularly important for (skeletal) muscle. There are some evolutionary arguments that muscle is a "default" pathway for mesodermal cells, which has to be actively prevented in order to allow cells to differentiate into other tissues. Myogenic cells originate from very small areas of the embryo where only a minor portion of these cells is supposed to differentiate. Differentiated muscle fibres are unconditionally post-mitotic, leaving undifferentiated stem cells as the only source of regeneration. The mechanical usage of muscle and its superficial location in the vertebrate body makes regeneration a frequently used mechanism. Looking at the different inhibitory mechanisms that have been found within the past 10 or so years, it appears as if evolution has taken this issue very serious. At all possible levels we find regulatory mechanisms that help to fine tune the differentiation of myogenic cells. Secreted molecules specifying different populations of somitic cells, diffusing or membrane-bound signals among fellow myoblasts, modulating molecules within the extracellular matrix and last, but not least, a changing set of activating and repressing cofactors. We have come a long way from the simple model of MyoD just to be turned on at the right time in the right cell. PMID:12132393

Füchtbauer, Ernst-Martin

2002-01-01

102

Skeletal muscle metabolism in hypokinetic rats  

NASA Technical Reports Server (NTRS)

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

Tischler, Marc E.

1993-01-01

103

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

104

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

105

Imaging of skeletal muscle in vitamin D deficiency  

PubMed Central

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

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

2014-01-01

106

Imaging of skeletal muscle in vitamin D deficiency.  

PubMed

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

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

2014-04-28

107

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

108

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...

109

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...

110

Skeletal Muscle Stem Cells from Animals I. Basic Cell Biology  

PubMed Central

Skeletal muscle stem cells from food-producing animals are 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 of muscle stem cell biology and function is essential for developing technologies and strategies to augment the metabolic efficiency and muscle hypertrophy of growing animals potentially leading to greater efficiency and reduced environmental impacts of animal production, while concomitantly improving product uniformity and consumer acceptance and enjoyment of muscle foods. PMID:20827399

Dodson, Michael V.; Hausman, Gary J.; Guan, LeLuo; Du, Min; Rasmussen, Theodore P.; Poulos, Sylvia P.; Mir, Priya; Bergen, Werner G.; Fernyhough, Melinda E.; McFarland, Douglas C.; Rhoads, Robert P.; Soret, Beatrice; Reecy, James M.; Velleman, Sandra G.; Jiang, Zhihua

2010-01-01

111

Excitability of skeletal muscle during development, denervation, and tissue culture.  

PubMed

A quantitative understanding of the bulk excitability of skeletal muscle tissues is important for the design of muscle tissue bioreactor systems, implantable muscle stimulators, and other systems where electrical pulses are employed to elicit contractions in muscle tissue both in vitro and in vivo. The purpose of the present study is to systematically compare the excitability of mammalian (rat) skeletal muscle under a range of conditions (including neonatal development, denervation, and chronic in vivo stimulation of denervated muscle) and of self-organized muscle tissue constructs engineered in vitro from both primary cells and cell lines. Excitability is represented by rheobase (R(50), units = V/mm) and chronaxie (C(50), units = microseconds) values, with lower values for each indicating greater excitability. Adult skeletal muscle is the most excitable (R(50) ~ 0.29, C(50) ~ 100); chronically denervated whole muscles (R(50) ~ 2.54, C(50) ~ 690) and muscle engineered in vitro from cell lines (C2C12 + 10T1/2) (R(50) ~ 1.93, C(50) ~ 416) have exceptionally low excitability; muscle engineered in vitro from primary myocytes (R(50) ~ 0.99, C(50) ~ 496) has excitability similar to that of day 14 neonatal rat muscle (R(50) ~ 0.65, C(50) ~ 435); stimulated-denervated muscles retain excellent excitability when chronically electrically stimulated (R(50) ~ 0.40, C(50) ~ 100); and neonatal rat muscle excitability improves during the first 6 weeks of development, steadily approaching that of adult muscle. PMID:17867927

Dennis, Robert G; Dow, Douglas E

2007-10-01

112

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

PubMed Central

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

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

2013-01-01

113

Postnatal ontogeny of skeletal muscle protein synthesis in pigs  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

114

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

115

Original article Microstructure of skeletal muscles of growing  

E-print Network

grass silage or hay ad lib and a restricted amount of concentrate from 2 weeks of age onwards. Muscle). It is well established in cattle that the proportions between muscle fibre types change with age and bodyOriginal article Microstructure of skeletal muscles of growing calves fed silage-based vs hay

Paris-Sud XI, Université de

116

Postnatal ontogeny of skeletal muscle protein synthesis in pigs  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

117

Insulin action on skeletal muscle protein metabolism during catabolic states  

E-print Network

of muscle protein. Evidence of the ability of insulin to stimulate muscle protein synthesis in vivo was also-induced cytokines, resulted in a decrease in insulin action on protein synthesis or degradation. The effect; Inra/ Elsevier, Paris. insulin / skeletal muscle / protein synthesis / protein breakdown / catabolic

Paris-Sud XI, Université de

118

Finite element modelling of contracting skeletal muscle.  

PubMed Central

To describe the mechanical behaviour of biological tissues and transport processes in biological tissues, conservation laws such as conservation of mass, momentum and energy play a central role. Mathematically these are cast into the form of partial differential equations. Because of nonlinear material behaviour, inhomogeneous properties and usually a complex geometry, it is impossible to find closed-form analytical solutions for these sets of equations. The objective of the finite element method is to find approximate solutions for these problems. The concepts of the finite element method are explained on a finite element continuum model of skeletal muscle. In this case, the momentum equations have to be solved with an extra constraint, because the material behaves as nearly incompressible. The material behaviour consists of a highly nonlinear passive part and an active part. The latter is described with a two-state Huxley model. This means that an extra nonlinear partial differential equation has to be solved. The problems and solutions involved with this procedure are explained. The model is used to describe the mechanical behaviour of a tibialis anterior of a rat. The results have been compared with experimentally determined strains at the surface of the muscle. Qualitatively there is good agreement between measured and calculated strains, but the measured strains were higher. PMID:14561336

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

2003-01-01

119

Single actomyosin motor interactions in skeletal muscle.  

PubMed

We present a study of intramuscular motion during contraction of skeletal muscle myofibrils. Myofibrillar actin was labeled with fluorescent dye so that the ratio of fluorescently labeled to unlabeled protein was 1:10(5). Such sparse labeling assured that there was on average only one actin-marker present in the focus at a given time. From the intensity signal in the two orthogonal detection channels, significant fluctuations, similar to fluorescent burst in diffusion-based single-molecule detection schemes, were identified via a threshold algorithm and analyzed with respect to their intensity and polarization. When only rigor complexes were formed, the fluctuations of polarized intensity were characterized by unimodal Gaussian photon distributions. During contraction, in contrast, bimodal Gaussian photon distributions were observed above the rigor background threshold. This suggests that the bimodal Gaussian photon distributions represent pre- and post-power stroke conformations. Clusters of polarized photons indicated an anisotropy decay of single actomyosin motors of ~9s during muscle contraction. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. PMID:21315775

Földes-Papp, Zeno; Liao, Shih-Chu Jeff; Barbieri, Ben; Gryczynski, Karol; Luchowski, Rafal; Gryczynski, Zygmunt; Gryczynski, Ignacy; Borejdo, Julian; You, Tiefeng

2011-05-01

120

Single actomyosin motor interactions in skeletal muscle  

PubMed Central

We present a study of intramuscular motion during contraction of skeletal muscle myofibrils. Myofibrillar actin was labeled with fluorescent dye so that the ratio of fluorescently labeled to unlabeled protein was 1:105. Such sparse labeling assured that there was on average only one actin-marker present in the focus at a given time. From the intensity signal in the two orthogonal detection channels, significant fluctuations, similar to fluorescent burst in diffusion-based single-molecule detection schemes, were identified via a threshold algorithm and analyzed with respect to their intensity and polarization. When only rigor complexes were formed, the fluctuations of polarized intensity were characterized by unimodal Gaussian photon distributions. During contraction, in contrast, bimodal Gaussian photon distributions were observed above the rigor background threshold. This suggests that the bimodal Gaussian photon distributions represent pre- and post-power stroke conformations. Clusters of polarized photons indicated an anisotropy decay of single actomyosin motors of ~ 9 s during muscle contraction. PMID:21315775

Földes-Papp, Zeno; Liao, Shih-Chu Jeff; Barbieri, Ben; Gryczynski, Karol; Luchowski, Rafal; Gryczynski, Zygmunt; Gryczynski, Ignacy; Borejdo, Julian; You, Tiefeng

2011-01-01

121

Centrally acting oral skeletal muscle relaxants.  

PubMed

A critical examination of the literature on centrally acting, orally administered skeletal muscle relaxants (SMRs) is presented. The available comparative clinical studies are reviewed, and the pharmacology, metabolism and adverse effects of the oral SMRs are discussed briefly. The drugs covered are carisoprodol, chlorphenesin carbamate, chlorzoxazone, cyclobenzaprine hydrochloride, diazepam, metaxalone, methocarbamol, and orphenadrine citrate. The mechanism of action of these agents is not well defined, and their effects are measured mainly by subjective responses. Thus, acceptable evidence of efficacy is difficult to obtain, especially if clinical studies continue to be designed inadequately. There are inadequate data to support the superiority of any one drug. Further, unique clinical efficacy of any oral SMR in comparison to nonspecific sedation has not been established. Based on subjective responses, all agents, except diazepam, have been shown to be superior to placebo in acute disorders; cyclobenzaprine has not been evaluated in acute conditions. SMRs are less effective in chronic disorders. Combination muscle relaxant-analgesic products appear to be superior to their individual components, but the relative efficacy of these combination products in comparison to combined use of individual sedative and analgesic agents is unknown. PMID:6999895

Elenbaas, J K

1980-10-01

122

Expression of androgen receptor target genes in skeletal muscle  

PubMed Central

We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR)-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (AR?ZF2) versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR?ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, Igf2 and calcineurin Aa, was increased in AR?ZF2 muscle, and the expression of all but p57Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle. PMID:24713826

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

2014-01-01

123

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

PubMed

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

2014-10-01

124

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

125

Na+-K+ Pump Regulation and Skeletal Muscle Contractility  

NSDL National Science Digital Library

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

MD Torben Clausen (University of Aarhus Department of Physiology)

2003-10-01

126

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

127

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

128

Impaired skeletal muscle perfusion in obese Zucker rats.  

PubMed

Skeletal muscle arterioles from obese Zucker rats (OZR) exhibit oxidant stress-based alterations in reactivity, enhanced alpha-adrenergic constriction, and reduced distensibility vs. microvessels of lean Zucker rats (LZR). The present study determined the impact of these alterations for perfusion and performance of in situ skeletal muscle during periods of elevated metabolic demand. During bouts of isometric tetanic contractions, fatigue of in situ gastrocnemius muscle of OZR was increased vs. LZR; this was associated with impaired active hyperemia. In OZR, vasoactive responses of skeletal muscle arterioles from the contralateral gracilis muscle were impaired, due in part to elevated oxidant tone; reactivity was improved after treatment with polyethylene glycol-superoxide dismutase (PEGSOD). Arterioles of OZR also exhibited increased alpha-adrenergic sensitivity, which was abolished by treatment with phentolamine (10-5 M). Intravenous infusion of phentolamine (10 mg/kg) or PEG-SOD (2,000 U/kg) in OZR altered neither fatigue rates nor active hyperemia from untreated levels; however, combined infusion improved performance and hyperemia, although not to levels in LZR. Microvessel density in the contralateral gastrocnemius muscle, determined via histological analyses, was reduced by approximately 25% in OZR vs. LZR, while individual arterioles from the contralateral gracilis muscle demonstrated reduced distensibility. These data suggest that altered arteriolar reactivity contributes to reduced muscle performance and active hyperemia in OZR. Further, despite pharmacological improvements in arteriolar reactivity, reduced skeletal muscle microvessel density and arteriolar distensibility also contribute substantially to reduced active hyperemia and potentially to impaired muscle performance. PMID:12855417

Frisbee, Jefferson C

2003-11-01

129

Alterations in Mitochondria and Their Impact in Aging Skeletal Muscle  

Microsoft Academic Search

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

Russell T. Hepple

130

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

131

Molecular Basis of AMP Deaminase Deficiency in Skeletal Muscle  

Microsoft Academic Search

AMP deaminase (AMPD; EC 3.5.4.6) is encoded by a multigene family in mammals. The AMPD1 gene is expressed at high levels in skeletal muscle, where this enzyme is thought to play an important role in energy metabolism. Deficiency of AMPD activity in skeletal muscle is associated with symptoms of a metabolic myopathy. Eleven unrelated individuals with AMPD deficiency were studied,

Takayuki Morisaki; Manfred Gross; Hiroko Morisaki; Dieter Pongratz; Nepomuk Zollner; Edward W. Holmes

1992-01-01

132

ACTIVATION OF CASPASE-3 IN THE SKELETAL MUSCLE DURING HEMODIALYSIS  

PubMed Central

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

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

2010-01-01

133

Systems analysis of biological networks in skeletal muscle function  

PubMed Central

Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation–contraction coupling enabling Ca2+ release. Ca2+ then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. PMID:23188744

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

2014-01-01

134

Macrophage Plasticity in Skeletal Muscle Repair  

PubMed Central

Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle. PMID:24860823

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

2014-01-01

135

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...

136

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

137

Mitochondrial energetics is impaired in vivo in aged skeletal muscle  

PubMed Central

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

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

2014-01-01

138

Mitochondrial energetics is impaired in vivo in aged skeletal muscle.  

PubMed

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

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

2014-02-01

139

Mueller matrix decomposition of diffuse reflectance imaging in skeletal muscle.  

PubMed

Propagation of polarized light in skeletal muscle is significantly affected by anisotropic muscle structures. To completely characterize muscle polarization properties, we acquired the whole Mueller matrix images of the diffuse reflectance. A polar decomposition algorithm was applied to extract the individual diattenuation, retardance, and depolarization images from the measured Mueller matrix. The decomposed polarization properties in muscle show distinctly different patterns from those obtained in isotropic scattering media. Stretching the prerigor muscle sample induced clear changes in the raw polarization reflectance images. However, muscle stretching induced minimal changes in the decomposed Mueller matrix images. PMID:19424381

Li, Xin; Yao, Gang

2009-05-10

140

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

PubMed

Chronic metabolic diseases develop from the complex interaction of environmental and genetic factors, although the extent to which each contributes to these disorders is unknown. Here, we test the hypothesis that artificial selection for low intrinsic aerobic running capacity is associated with reduced skeletal muscle metabolism and impaired metabolic health. Rat models for low- (LCR) and high- (HCR) intrinsic running capacity were derived from genetically heterogeneous N:NIH stock for 20 generations. Artificial selection produced a 530% difference in running capacity between LCR/HCR, which was associated with significant functional differences in glucose and lipid handling by skeletal muscle, as assessed by hindlimb perfusion. LCR had reduced rates of skeletal muscle glucose uptake (?30%; P = 0.04), glucose oxidation (?50%; P = 0.04), and lipid oxidation (?40%; P = 0.02). Artificial selection for low aerobic capacity was also linked with reduced molecular signaling, decreased muscle glycogen, and triglyceride storage, and a lower mitochondrial content in skeletal muscle, with the most profound changes to these parameters evident in white rather than red muscle. We show that a low intrinsic aerobic running capacity confers reduced insulin sensitivity in skeletal muscle and is associated with impaired markers of metabolic health compared with high intrinsic running capacity. Furthermore, selection for high running capacity, in the absence of exercise training, endows increased skeletal muscle insulin sensitivity and oxidative capacity in specifically white muscle rather than red muscle. These data provide evidence that differences in white muscle may have a role in the divergent aerobic capacity observed in this generation of LCR/HCR. PMID:21270346

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

2011-04-01

141

Original article Microstructure of skeletal muscles of growing calves  

E-print Network

- stricted amount of concentrate from 2 weeks of age onwards. Muscle fibres were differentiated ac- cordingOriginal article Microstructure of skeletal muscles of growing calves fed silage-based vs hay of age. From the 2nd week to the 3rd month, growth was observed virtually only in the FTG fibres

Paris-Sud XI, Université de

142

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...

143

An improved vaseline gap voltage clamp for skeletal muscle fibers  

Microsoft Academic Search

A Vaseline gap potentiometric recording and voltage clamp method is developed for frog skeletal muscle fibers. The method is based on the Franken- haeuser-Dodge voltage clamp for myelinated nerve with modifications to improve the frequency response, to compensate for external series resistance, and to com- pensate for the complex impedance of the current-passing pathway. Fragments of single muscle fibers are

BERTIL HILLE; DONALD T. CAMPBELL

1976-01-01

144

Neural Regulation of -Dystroglycan Biosynthesis and Glycosylation in Skeletal Muscle  

E-print Network

--Dystrophin- associated proteins--Denervation--Glycosylation--Lami- nin--Muscle development. J. Neurochem. 74, 70­80 (2000Neural Regulation of -Dystroglycan Biosynthesis and Glycosylation in Skeletal Muscle *Andres.S.A. Abstract: -Dystroglycan ( -DG) is part of a complex of cell surface proteins linked to dystrophin

Campbell, Kevin P.

145

Obesity, insulin resistance, and skeletal muscle nitric oxide synthase  

PubMed Central

The molecular mechanisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means ± SE: nonobese, body mass index = 25.5 ± 0.3 kg/m2, n = 13; obese, body mass index = 36.6 ± 0.4 kg/m2, n = 14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensitivity index (SI). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. SI was significantly lower in the obese compared with the nonobese group (?43%; P < 0.05), yet skeletal muscle iNOS protein expression was not different between nonobese and obese groups. Skeletal muscle eNOS protein was significantly higher in the nonobese than the obese group, and skeletal muscle nNOS protein tended to be higher (P = 0.054) in the obese compared with the nonobese group. Alternative analysis based on SI (high and low tertile) indicated that the most insulin-resistant group did not have significantly more skeletal muscle iNOS protein than the most insulin-sensitive group. In conclusion, human insulin resistance does not appear to be associated with an elevation in skeletal muscle iNOS protein in middle-aged individuals under fasting conditions. PMID:22797309

Kraus, Raymond M.; Houmard, Joseph A.; Kraus, William E.; Tanner, Charles J.; Pierce, Joseph R.; Choi, Myung Dong

2012-01-01

146

Perlecan and synaptophysin changes in denervated skeletal muscle?  

PubMed Central

The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix component, which is located at the skeletal muscle cell surface as acetylcholine esterase, as well as synaptophysin, a synaptic marker. Results showed degeneration and inflammation following transection of the sciatic nerve. In addition, the sciatic nerve-dominated skeletal muscle degenerated with mild inflammation, indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances. With prolonged injury time (1-4 weeks post-injury), perlecan expression gradually decreased and reached the lowest level at 4 weeks, but synaptophysin expression remained unchanged after denervation. Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.

Ma, Kai; Huang, Zhifeng; Ma, Jianfeng; Shao, Longquan; Wang, Huiming; Wang, Yanliang

2012-01-01

147

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

148

High skeletal muscle adenylate cyclase in malignant hyperthermia.  

PubMed Central

Malignant hyperthermia occurs in humans with several congenital myopathies, usually in response to general anesthesia. Commonly, individuals who develop this syndrome lack symptoms of muscle disease, and their muscle lacks specific pathological changes. A biochemical marker for this myopathy has not previously been available; we found activity of adenylate cyclase and content of cyclic AMP to be abnormally high in skeletal muscle. Secondary modification of protein phosphorylation could explain observed abnormalities of phosphorylase activation and sarcoplasmic reticulum function. PMID:6271806

Willner, J H; Cerri, C G; Wood, D S

1981-01-01

149

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

150

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...

151

Developmental regulation of interstitial cell density in bullfrog skeletal muscle.  

PubMed

Denervation of skeletal muscle results in striking connective tissue remodelling in junctional areas of muscle. Since extracellular matrix molecules mediate axonal growth and synaptic differentiation, it is likely that the interstitial cells and matrix molecules that accumulate near synaptic sites after denervation influence the regrowth and regeneration of synaptic connections. The experiments presented here addressed the question of whether the junctional connective tissue in developing bullfrog skeletal muscle was also specialized in its cellular and molecular composition. Denervation responses of muscle, such as extrajunctional sensitivity to acetylcholine, often reproduce the characteristics of developing muscle during synaptogenesis. In developing muscle, the distribution of interstitial cells was nonuniform during the period of muscle fibre birth and synaptogenesis. Interstitial cells were concentrated near synaptic sites as in denervated adult muscle. Unlike denervated adult muscle, there were no junctional accumulations of fibronectin or tenascin, matrix molecules produced by interstitial cells, in developing muscles. These results demonstrate that the junctional connective tissue in developing muscle is identified by a high density of interstitial cells that may play a role in the identification and formation of synaptic sites. Further, the junctional matrix environment of developing muscle is distinct from the matrix remodelling that occurs in response to denervation, suggesting that the matrix production by interstitial cells during development is regulated differently from that after denervation of the neuromuscular junction. PMID:9154526

Connor, E A

1997-01-01

152

In vivo calcium regulation in diabetic skeletal muscle.  

PubMed

In skeletal muscle, dysfunctional contractile activity has been linked to impaired intracellular Ca(2+) concentration ([Ca(2+)]i) regulation. Muscle force production is impaired and fatigability and muscle fragility deteriorate with diabetes. Use of a novel in vivo model permits investigation of [Ca(2+)]i homeostasis in diabetic skeletal muscle. Within this in vivo environment we have shown that diabetes perturbs the Ca(2+) regulatory system such that resting [Ca(2+)]i homeostasis following muscle contractions is compromised and elevations of [Ca(2+)]i are exacerbated. This review considers the impact of diabetes on the capacity of skeletal muscle to regulate [Ca(2+)]i, following muscle contractions and, in particular, the relationship between muscle fatigue and elevated [Ca(2+)]i in a highly ecologically relevant circulation-intact environment. Importantly, the role of mitochondria in calcium sequestration and the possibility that diabetes impacts this process is explored. Given the profound microcirculatory dysfunction in diabetes this preparation offers the unique opportunity to study the interrelationships among microvascular function, blood-myocyte oxygen flux and [Ca(2+)]i as they relate to enhanced muscle fatigability and exercise intolerance. PMID:25224503

Eshima, Hiroaki; Poole, David C; Kano, Yutaka

2014-11-01

153

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

154

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

155

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

156

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

157

Optimizing the measurement of mitochondrial protein synthesis in human skeletal muscle.  

PubMed

The measurement of mitochondrial protein synthesis after food ingestion, contractile activity, and/or disease is often used to provide insight into skeletal muscle adaptations that occur in the longer term. Studies have shown that protein ingestion stimulates mitochondrial protein synthesis in human skeletal muscle. Minor differences in the stimulation of mitochondrial protein synthesis occur after a single bout of resistance or endurance exercise. There appear to be no measurable differences in mitochondrial protein synthesis between critically ill patients and aged-matched controls. However, the mitochondrial protein synthetic response is reduced at a more advanced age. In this paper, we discuss the challenges involved in the measurement of human skeletal muscle mitochondrial protein synthesis rates based on stable isotope amino acid tracer methods. Practical guidelines are discussed to improve the reliability of the measurement of mitochondrial protein synthesis rates. The value of the measurement of mitochondrial protein synthesis after a single meal or exercise bout on the prediction of the longer term skeletal muscle mass and performance outcomes in both the healthy and disease populations requires more work, but we emphasize that the measurements need to be reliable to be of any value to the field. PMID:25494678

Burd, Nicholas A; Tardif, Nicolas; Rooyackers, Olav; van Loon, Luc J C

2015-01-01

158

Are antioxidants useful for treating skeletal muscle atrophy?  

PubMed

Changes in the skeletal muscle protein mass frequently occur in both physiological and pathological states. Muscle hypotrophy, in particular, is commonly observed during aging and is characteristic of several pathological conditions such as neurological diseases, cancer, diabetes, and sepsis. The skeletal muscle protein content depends on the relative rates of synthesis and degradation, which must be coordinately regulated to maintain the equilibrium. Pathological muscle depletion is characterized by a negative nitrogen balance, which results from disruption of this equilibrium due to reduced synthesis, increased breakdown, or both. The current view, mainly based on experimental data, considers hypercatabolism as the major cause of muscle protein depletion. Several signaling pathways that probably contribute to muscle atrophy have been identified, and there is increasing evidence that oxidative stress, due to reactive oxygen species production overwhelming the intracellular antioxidant systems, plays a role in causing muscle depletion both during aging and in chronic pathological states. In particular, oxidative stress has been proposed to enhance protein breakdown, directly or by interacting with other factors. This review focuses on the possibility of using antioxidant treatments to target molecular pathways involved in the pathogenesis of skeletal muscle wasting. PMID:19591922

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

2009-10-01

159

Localisation of AMPK ? subunits in cardiac and skeletal muscles.  

PubMed

The trimeric protein AMP-activated protein kinase (AMPK) is an important sensor of energetic status and cellular stress, and mutations in genes encoding two of the regulatory ? subunits cause inherited disorders of either cardiac or skeletal muscle. AMPK?2 mutations cause hypertrophic cardiomyopathy with glycogen deposition and conduction abnormalities; mutations in AMPK?3 result in increased skeletal muscle glycogen. In order to gain further insight into the roles of the different ? subunits in muscle and into possible disease mechanisms, we localised the ?2 and ?3 subunits, along with the more abundant ?1 subunit, by immunofluorescence in cardiomyocytes and skeletal muscle fibres. The predominant cardiac ?2 variant, ?2-3B, gave a striated pattern in cardiomyocytes, aligning with the Z-disk but with punctate staining similar to T-tubule (L-type Ca(2+) channel) and sarcoplasmic reticulum (SERCA2) markers. In skeletal muscle fibres AMPK?3 localises to the I band, presenting a uniform staining that flanks the Z-disk, also coinciding with the position of Ca(2+) influx in these muscles. The localisation of ?2-3B- and ?3-containing AMPK suggests that these trimers may have similar functions in the different muscles. AMPK containing ?2-3B was detected in oxidative skeletal muscles which had low expression of ?3, confirming that these two regulatory subunits may be co-ordinately regulated in response to metabolic requirements. Compartmentalisation of AMPK complexes is most likely dependent on the regulatory ? subunit and this differential localisation may direct substrate selection and specify particular functional roles. PMID:24037260

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

2013-12-01

160

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

161

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

162

Eccentric Exercise Facilitates Mesenchymal Stem Cell Appearance in Skeletal Muscle  

PubMed Central

Eccentric, or lengthening, contractions result in injury and subsequently stimulate the activation and proliferation of satellite stem cells which are important for skeletal muscle regeneration. The discovery of alternative myogenic progenitors in skeletal muscle raises the question as to whether stem cells other than satellite cells accumulate in muscle in response to exercise and contribute to post-exercise repair and/or growth. In this study, stem cell antigen-1 (Sca-1) positive, non-hematopoetic (CD45-) cells were evaluated in wild type (WT) and ?7 integrin transgenic (?7Tg) mouse muscle, which is resistant to injury yet liable to strain, 24 hr following a single bout of eccentric exercise. Sca-1+CD45? stem cells were increased 2-fold in WT muscle post-exercise. The ?7 integrin regulated the presence of Sca-1+ cells, with expansion occurring in ?7Tg muscle and minimal cells present in muscle lacking the ?7 integrin. Sca-1+CD45? cells isolated from ?7Tg muscle following exercise were characterized as mesenchymal-like stem cells (mMSCs), predominantly pericytes. In vitro multiaxial strain upregulated mMSC stem cells markers in the presence of laminin, but not gelatin, identifying a potential mechanistic basis for the accumulation of these cells in muscle following exercise. Transplantation of DiI-labeled mMSCs into WT muscle increased Pax7+ cells and facilitated formation of eMHC+DiI? fibers. This study provides the first demonstration that mMSCs rapidly appear in skeletal muscle in an ?7 integrin dependent manner post-exercise, revealing an early event that may be necessary for effective repair and/or growth following exercise. The results from this study also support a role for the ?7 integrin and/or mMSCs in molecular- and cellular-based therapeutic strategies that can effectively combat disuse muscle atrophy. PMID:22253772

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

2012-01-01

163

Collagen quantification across human skeletal muscles  

E-print Network

physiological cross- sectional area (PCSA), pennation angle, muscle5-10 . PCSA=physiological cross sectional area. Muscle fibermuscles…..34 Figure 6: Scatter plot of average collagen content versus physiological cross-sectional

Lin, Evie Ya Hui

2011-01-01

164

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

165

A comparative histochemical and morphometric study of canine skeletal muscle.  

PubMed Central

The purpose of this study was to determine whether there were differences in skeletal muscle properties in the hindlimb muscles of different types of dogs. Muscle samples were obtained from the gracilis, sartorius cranial head, sartorius caudal head and tibialis anterior muscles of mixed-breed and hound-type dogs and Beagles. Fiber type, fiber size and capillary morphometry determinations of each muscle from each dog were made from sections stained for myofibrillar ATPase activity. Individual animals were bilaterally symmetric for all measured variables. Fiber type, fiber size and capillary geometry varied between dogs of a given type and muscles within a given dog. There were no differences between dog types for fiber type or fiber size; significant variation in log(muscle)/log(body) mass ratios between dog types was observed for all muscles. The results indicate that for a given muscle, significant variation can occur in skeletal muscle characteristics between different types of dogs and that these differences can be independent of differences in exercise history. Images Fig. 1. PMID:2523755

Kuzon, W M; Rosenblatt, J D; Pynn, B R; Marchetti, P J; Plyley, M J; McKee, N H

1989-01-01

166

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

167

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, Ivy Tech Community College, 2 Department of Physical Therapy, Indiana University School of Health promotes right ventricular (RV) and skeletal muscle dysfunction that contributes to reduced exercise

Zhou, Yaoqi

168

Prions in skeletal muscles of deer with chronic wasting disease.  

PubMed

The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly wide geographic area, as well as the interspecies transmission of bovine spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob disease, have raised concerns about the zoonotic potential of CWD. Because meat consumption is the most likely means of exposure, it is important to determine whether skeletal muscle of diseased cervids contains prion infectivity. Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure. PMID:16439622

Angers, Rachel C; Browning, Shawn R; Seward, Tanya S; Sigurdson, Christina J; Miller, Michael W; Hoover, Edward A; Telling, Glenn C

2006-02-24

169

Monocarboxylate transporter expression at the onset of skeletal muscle regeneration  

PubMed Central

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

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

2013-01-01

170

Burn injury causes mitochondrial dysfunction in skeletal muscle  

PubMed Central

Severe burn trauma is generally followed by a catabolic response that leads to muscle wasting and weakness affecting skeletal musculature. Here, we perform whole-genome expression and in vivo NMR spectroscopy studies to define respectively the full set of burn-induced changes in skeletal muscle gene expression and the role of mitochondria in the altered energy expenditure exhibited by burn patients. Our results show 1,136 genes differentially expressed in a mouse hind limb burn model and identify expression pattern changes of genes involved in muscle development, protein degradation and biosynthesis, inflammation, and mitochondrial energy and metabolism. To assess further the role of mitochondria in burn injury, we performed in vivo 31P NMR spectroscopy on hind limb skeletal muscle, to noninvasively measure high-energy phosphates and the effect of magnetization transfer on inorganic phosphate (Pi) and phosphocreatine (PCr) resonances during saturation of ?ATP resonance, mediated by the ATP synthesis reactions. Although local burn injury does not alter high-energy phosphates or pH, apart from PCr reduction, it does significantly reduce the rate of ATP synthesis, to further implicate a role for mitochondria in burn trauma. These results, in conjunction with our genomic results showing down-regulation of mitochondrial oxidative phosphorylation and related functions, strongly suggest alterations in mitochondrial-directed energy expenditure reactions, advancing our understanding of skeletal muscle dysfunction suffered by burn injury patients. PMID:15809440

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

2005-01-01

171

Prospective heterotopic ossification progenitors in adult human skeletal muscle.  

PubMed

Skeletal muscle has strong regenerative capabilities. However, failed regeneration can lead to complications where aberrant tissue forms as is the case with heterotopic ossification (HO), in which chondrocytes, osteoblasts and white and brown adipocytes can arise following severe trauma. In humans, the various HO cell types likely originate from multipotent mesenchymal stromal cells (MSCs) in skeletal muscle, which have not been identified in humans until now. In the present study, adherent cells from freshly digested skeletal muscle tissue were expanded in defined culture medium and were FACS-enriched for the CD73(+)CD105(+)CD90(-) population, which displayed robust multilineage potential. Clonal differentiation assays confirmed that all three lineages originated from a single multipotent progenitor. In addition to differentiating into typical HO lineages, human muscle resident MSCs (hmrMSCs) also differentiated into brown adipocytes expressing uncoupling protein 1 (UCP1). Characterizing this novel multipotent hmrMSC population with a brown adipocyte differentiation capacity has enhanced our understanding of the contribution of non-myogenic progenitor cells to regeneration and aberrant tissue formation in human skeletal muscle. PMID:25445454

Downey, Jennifer; Lauzier, Dominique; Kloen, Peter; Klarskov, Klaus; Richter, Martin; Hamdy, Reggie; Faucheux, Nathalie; Scimè, Anthony; Balg, Frédéric; Grenier, Guillaume

2015-02-01

172

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

173

Human skeletal muscle responses to spaceflight and possible countermeasures  

NASA Technical Reports Server (NTRS)

The current status of knowledge concerning the effects of unweighting skeletal muscle is summarized. The results of both ground-based and space-based animal studies are reviewed which show that there is rapid loss in muscle mass, primarily in slow-twitch muscle, of the rat during unweighting of muscle. There is also a shift in the myosin isoforms with muscles such that slow-twitch muscles take on many of the characteristics of fast-twitch muscles. Ground-based studies in human suggest that programs of electrical stimulation can be developed to simulate normal muscular contractions. Attempts to develop countermeasures to the adverse effects of space travel on muscular functions in humans have not been successful to date.

Gollnick, Philip D.; Edgerton, V. Reggie; Saltin, Bengt

1990-01-01

174

Electrical stimulation prevents apoptosis in denervated skeletal muscle.  

PubMed

The purpose of this study was to investigate the hypothesis that electrical stimulation regulates the levels of gene expression related to apoptosis in denervated muscle and prevents muscle atrophy after denervation.Nineteen rats were used in this study. To denervate soleus muscle, sciatic nerve was resected under aseptic condition. Electrical stimulation with 4 mA rectangular pulses of 0.5 ms duration at 2 Hz lasting for 1 hour was delivered to lower limb including the soleus muscle using two surface electrodes. After the stimulation periods of 4 weeks, the levels of gene expression related to apoptosis were evaluated. Electrical stimulation increased valosin-containing protein (VCP) expression and decreased cleaved caspase-12 expression in denervated muscles. These results indicated that electrical stimulation to denervated muscle suppresses ER-specific apoptosis by enhancing VCP expression. We proposed that electrical stimulation would be a potential treatment for preventing atrophy of denervated skeletal muscles. PMID:20871144

Arakawa, Takuya; Katada, Akihiro; Shigyo, Hiroshi; Kishibe, Kan; Adachi, Masaaki; Nonaka, Satoshi; Harabuchi, Yasuaki

2010-01-01

175

Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension.  

PubMed

Despite improvements in survival with disease-targeted therapies, the majority of patients with pulmonary arterial hypertension (PAH) have persistent exercise intolerance that results from impaired cardiac function and skeletal muscle dysfunction. Our intent was to understand the molecular mechanisms mediating skeletal muscle dysfunction in PAH. A total of 12 patients with PAH and 10 matched control subjects were assessed. Patients with PAH demonstrated diminished exercise capacity (lower oxygen uptake max, lower anaerobic threshold and higher minute ventilation/CO2) compared with control subjects. Quadriceps muscle cross-sectional area was significantly smaller in patients with PAH. The vastus lateralis muscle was biopsied to enable muscle fiber morphometric assessment and to determine expression levels/activation of proteins regulating (1) muscle mass, (2) mitochondria biogenesis and shaping machinery, and (3) excitation-contraction coupling. Patients with PAH demonstrated a decreased type I/type II muscle fiber ratio, with a smaller cross-sectional area in the type I fibers. Diminished AKT and p70S6 kinase phosphorylation, with increased atrogin-1 and muscle RING-finger protein-1 transcript levels, were evident in the PAH muscle, suggesting engagement of cellular signaling networks stimulating ubiquitin-proteasome-mediated proteolysis of muscle, with concurrent depression of networks mediating muscle hypertrophy. Although there were no differences in expression/activation of proteins associated with mitochondrial biogenesis or fission (MTCO2 [cytochrome C oxidase subunit II]/succinate dehydrogenase flavoprotein subunit A, mitochondrial transcription factor A, nuclear respiratory factor-1/dynamin-related protein 1 phosphorylation), protein levels of a positive regulator of mitochondrial fusion, Mitofusin2, were significantly lower in patients with PAH. Patients with PAH demonstrated increased phosphorylation of ryanodine receptor 1 receptors, suggesting that altered sarcoplasmic reticulum Ca(++) sequestration may impair excitation-contraction coupling in the PAH muscle. These data suggest that muscle dysfunction in PAH results from a combination of muscle atrophy and intrinsically impaired contractility. PMID:23972212

Batt, Jane; Ahmed, Samar Shadly; Correa, Judy; Bain, Alexandra; Granton, John

2014-01-01

176

The influence of skeletal muscle on systemic aging and lifespan  

PubMed Central

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

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

2013-01-01

177

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

178

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

179

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

180

Electron paramagnetic resonance reveals age-related myosin structural changes in rat skeletal muscle fibers  

E-print Network

. Electron paramagnetic resonance reveals age-related myosin structural changes in rat skeletal muscle fibers (force/cross-sectional area) in skeletal muscle from aged an- imals results from structural changes-related decline in skeletal muscle force generation. spectroscopy; specific tension; force; weakness; aging

Thomas, David D.

181

EXCITABILITY OF ENGINEERED MUSCLE CONSTRUCTS, DENERVATED AND STIMULATED-DENERVATED MUSCLES OF RATS, AND CONTROL SKELETAL  

E-print Network

.32±0.02 & 0.04±0.00; and old (28 months of age) 0.56±0.11 & 0.40±0.03 rodents; and (3) EDL muscles of ratsEXCITABILITY OF ENGINEERED MUSCLE CONSTRUCTS, DENERVATED AND STIMULATED-DENERVATED MUSCLES OF RATS, AND CONTROL SKELETAL MUSCLES IN NEONATAL, YOUNG, ADULT AND OLD MICE AND RATS. Robert G. Dennis, Douglas E. Dow

Dennis, Robert G.

182

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

183

Regulation of Skeletal Muscle Mitochondrial Content During Aging  

Microsoft Academic Search

Mitochondrial content of skeletal muscle varies among fiber types, and changes in complex ways during aging. We evaluated the regulatory origins of differences in mitochondrial content among muscles of varied fiber type in F3443BNF1 rats, and how these regulatory patterns are altered with aging. In adult (12 month) animals we found that units citrate synthase (CS)\\/g tissue, a marker for

Carrie N. Lyons; Odile Mathieu-Costello; Christopher D. Moyes

2006-01-01

184

Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation  

PubMed Central

Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (“pain-sensing” nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2– 4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain. PMID:21957236

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

2012-01-01

185

Emphysema-induced reductions in locomotory skeletal muscle contractile function.  

PubMed

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

Mattson, John P; Martin, James C

2005-07-01

186

Validation of shear wave elastography in skeletal muscle.  

PubMed

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

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

2013-09-27

187

ORIGINAL ARTICLE The influence of skeletal muscle anisotropy on electroporation  

E-print Network

ORIGINAL ARTICLE The influence of skeletal muscle anisotropy on electroporation: in vivo study.com Abstract The aim of this study was to theoretically and experimentally investigate electroporation of mouse tibialis cranialis and to determine the reversible electroporation threshold values needed for parallel

Ljubljana, University of

188

Characterization of human carbonic anhydrase III from skeletal muscle  

Microsoft Academic Search

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

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

1979-01-01

189

ADAPTIVE RESPONSES OF HUMAN SKELETAL MUSCLE TO VIBRATION EXPOSURE  

Microsoft Academic Search

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

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

1999-01-01

190

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,...

191

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...

192

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

193

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

194

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

195

Elevated nuclear Foxo1 suppresses excitability of skeletal muscle fibers  

PubMed Central

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

Hernández-Ochoa, Erick O.; Schachter, Tova Neustadt

2013-01-01

196

Elevated nuclear Foxo1 suppresses excitability of skeletal muscle fibers.  

PubMed

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

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

2013-09-15

197

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

198

Vitamin D and its role in skeletal muscle.  

PubMed

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

Ceglia, Lisa; Harris, Susan S

2013-02-01

199

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

200

Exercise induces interleukin-8 expression in human skeletal muscle  

PubMed Central

Skeletal muscle has been recognized as an endocrine organ, and muscle cell cultures express several cytokines with potential hormonal effects. Interleukin-8 (IL-8), a chemokine, which induces angiogenesis, is expressed in working muscles; however, the cell source of origin has not been identified. We aimed to elucidate if IL-8 protein is: (1) expressed in contracting muscle fibres and (2) whether there is a release of IL-8 from exercising muscle. Seventeen healthy male volunteers were included in two independent protocols: 3 h of ergometer bicycle exercise at 60% of (n = 6) or rest (n = 5), and 3 h of two-legged knee-extensor exercise at 60% of maximal workload (n = 6). Repetitive muscle biopsy samples were obtained from the vastus lateralis in all experiments. A marked increase in IL-8 mRNA was found in muscle biopsy samples obtained after exercise. A marked IL-8 protein expression was demonstrated within the cytoplasm of muscle fibres in biopsy samples obtained in the recovery phase following 3 h of bicycle exercise, and the peak occurred 3–6 h postexercise. A small transient net release of IL-8 from working muscle was found at 1.5 h of knee-extensor exercise. However, the small release of IL-8 from muscle did not result in an increase in the systemic plasma concentration of IL-8, suggesting that muscle-derived IL-8 may play a local role, e.g. in angiogenesis. PMID:15618276

Akerstrom, Thorbjorn; Steensberg, Adam; Keller, Pernille; Keller, Charlotte; Penkowa, Milena; Pedersen, Bente Klarlund

2005-01-01

201

Physiological characteristics of skeletal muscles of dogs and cats.  

PubMed

Our purpose was to determine if physiological characteristics of skeletal muscles of dogs and cats are related to their histochemical and biochemical characteristics. Maximum oxygen consumption (VO2max) and blood flow (Q) at VO2max were determined for in situ muscles of dogs and cats. Compared to cat muscles, dog muscles per unit mass had higher succinate oxidase activities, VO2max's, and Q's at VO2max's. There are positive relationships between Q at VO2max and VO2max and between VO2max and succinate oxidase activity. The higher VO2max's and succinate oxidase activities of dog muscles are consistent with the presence in these muscles of only slow-twitch fatique-resistant fibers and fast-twitch fatique-resistant fibers, whereas up to 50% of the fibers found in cat muscles are fast-twitch fatiqable. Capillary-to-fiber ratios are 2.40-2.97 for dog muscles compared to 2.17-2.84 for cat muscles. Thus the two- to threefold higher Q at VO2max for dog muscles compared to cat muscles is not due to a greater number of capillaries. PMID:879310

Maxwell, L C; Barclay, J K; Mohrman, D E; Faulkner, J A

1977-07-01

202

Tomographic elastography of contracting skeletal muscles from their natural vibrations  

NASA Astrophysics Data System (ADS)

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

Sabra, Karim G.; Archer, Akibi

2009-11-01

203

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

204

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

205

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

206

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

207

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

PubMed

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

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

2014-03-01

208

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.

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

2015-01-01

209

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

210

Stem cells in the hood: the skeletal muscle niche.  

PubMed

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

Pannérec, Alice; Marazzi, Giovanna; Sassoon, David

2012-10-01

211

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

212

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

213

Three-Dimensional Reconstruction of the Normal and Fibrotic Skeletal Muscle Extracellular Collagen Network  

E-print Network

myogenic potency of aging skeletal muscle. Dev Biol 294, 50-muscle fibrosis occurs in muscular dystrophies, diabetes, immobilization, and aging (muscle fibrosis commonly develops in muscular dystrophies, myopathy (24), and with aging (

Gillies, Allison R.

214

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

215

Skeletal Muscle Metastases as Initial Presentation of Gastric Carcinoma  

PubMed Central

Patient: Male, 67 Final Diagnosis: Metastatic gastric carcinoma Symptoms: Painful swelling of soft tissue Medication: Folinic acid • fluouracil • irinotecan Clinical Procedure: Radiological-pathological work-up Specialty: Oncology Objective: Rare disease Background: Gastric carcinoma is one of the most common malignancies in the world. Skeletal muscle metastases from gastric carcinoma are rare. Case Report: We report a case of a 67-year-old man patient with skeletal muscle metastasis developing from gastric carcinoma. He had a painful swelling of the left thigh. A chest computed tomography (CT) scan with enhancement showed pulmonary thromboembolism. Despite heparin therapy, edema and pain of the lower limbs increased bilaterally, so the patient underwent pelvic magnetic resonance imaging (MRI), which documented an altered signal intensity in the upper third of his thighs bilaterally. Furthermore, the examination of the ultrasound (US)-guided biopsy specimen of the left gluteal muscle showed signet ring cell adenocarcinoma metastasis. An upper gastrointestinal tract endoscopy confirmed a gastric ulceration, with a biopsy positive for signet ring cell adenocarcinoma. Because of the advanced stage of disease, the patient underwent only supportive care and died 74 days after admission. Conclusions: Skeletal muscle metastasis may be the initial presentation of gastric carcinoma and diagnosis could be difficult. Biopsy is mandatory for diagnosis. PMID:25544018

Pergolini, Ilaria; Crippa, Stefano; Santinelli, Alfredo; Marmorale, Cristina

2014-01-01

216

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

217

Myostatin gene inactivation prevents skeletal muscle wasting in cancer.  

PubMed

Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice. Myostatin gene inactivation prevented the severe loss of skeletal muscle mass induced in mice engrafted with Lewis lung carcinoma (LLC) cells or in Apc(Min) (/+) mice, an established model of colorectal cancer and cachexia. Mechanistically, myostatin loss attenuated the activation of muscle fiber proteolytic pathways by inhibiting the expression of atrophy-related genes, MuRF1 and MAFbx/Atrogin-1, along with autophagy-related genes. Notably, myostatin loss also impeded the growth of LLC tumors, the number and the size of intestinal polyps in Apc(Min) (/+) mice, thus strongly increasing survival in both models. Gene expression analysis in the LLC model showed this phenotype to be associated with reduced expression of genes involved in tumor metabolism, activin signaling, and apoptosis. Taken together, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and link this condition to tumor growth, with implications for furthering understanding of cancer as a systemic disease. PMID:25336187

Gallot, Yann S; Durieux, Anne-Cécile; Castells, Josiane; Desgeorges, Marine M; Vernus, Barbara; Plantureux, Léa; Rémond, Didier; Jahnke, Vanessa E; Lefai, Etienne; Dardevet, Dominique; Nemoz, Georges; Schaeffer, Laurent; Bonnieu, Anne; Freyssenet, Damien G

2014-12-15

218

Engineered skeletal muscle tissue networks with controllable architecture  

PubMed Central

The engineering of functional skeletal muscle tissue substitutes holds promise for the treatment of various muscular diseases and injuries. However, no tissue fabrication technology currently exists for the generation of a relatively large and thick bioartificial muscle made of densely packed, uniformly aligned, and differentiated myofibers. In this study, we describe a versatile cell/hydrogel micromolding approach where polydimethylsiloxane (PDMS) molds containing an array of elongated posts were used to fabricate relatively large neonatal rat skeletal muscle tissue networks with reproducible and controllable architecture. By combining cell-mediated fibrin gel compaction and precise microfabrication of mold dimensions including the length and height of the PDMS posts, we were able to simultaneously support high cell viability, guide cell alignment along the microfabricated tissue pores, and reproducibly control the overall tissue porosity, size, and thickness. The interconnected muscle bundles within the porous tissue networks were composed of densely packed, aligned, and highly differentiated myofibers. The formed myofibers expressed myogenin, developed abundant cross-striations, and generated spontaneous tissue contractions at the macroscopic spatial scale. The proliferation of non-muscle cells was significantly reduced compared to monolayer cultures. The more complex muscle tissue architectures were fabricated by controlling the spatial distribution and direction of the PDMS posts. PMID:19070360

Bian, Weining; Bursac, Nenad

2009-01-01

219

Regeneration of injured skeletal muscle after the injury  

PubMed Central

Summary Muscle injuries are one of the most common traumas occurring in sports. Despite their clinical importance, few clinical studies exist on the treatment of these traumas. Thus, the current treatment recommendations for muscle injuries have either been derived from experimental studies or been tested only empirically. Although non operative treatment should almost always be the 1st choice as it results in good functional outcomes in the majority of athletes with muscle injuries, the consequences of failed treatment can be very dramatic, possibly postponing an athlete’s return to sports for weeks or even months. Moreover, the recognition of some basic principles of skeletal muscle regeneration and healing processes can considerably help in both avoiding the imminent dangers and accelerating the return to competition. Accordingly, in this review, the authors have summarized the prevailing understanding on the biology of muscle regeneration in hopes of extending these findings to clinical practice in an attempt to propose an evidence-based approach for the diagnosis and optimal treatment of skeletal muscle injuries. PMID:24596699

Järvinen, Tero AH; Järvinen, Markku; Kalimo, Hannu

2013-01-01

220

Neurofibromin (Nf1) is required for skeletal muscle development  

PubMed Central

Neurofibromatosis type 1 (NF1) is a multi-system disease caused by mutations in the NF1 gene encoding a Ras-GAP protein, neurofibromin, which negatively regulates Ras signaling. Besides neuroectodermal malformations and tumors, the skeletal system is often affected (e.g. scoliosis and long bone dysplasia) demonstrating the importance of neurofibromin for development and maintenance of the musculoskeletal system. Here, we focus on the role of neurofibromin in skeletal muscle development. Nf1 gene inactivation in the early limb bud mesenchyme using Prx1-cre (Nf1Prx1) resulted in muscle dystrophy characterized by fibrosis, reduced number of muscle fibers and reduced muscle force. This was caused by an early defect in myogenesis affecting the terminal differentiation of myoblasts between E12.5 and E14.5. In parallel, the muscle connective tissue cells exhibited increased proliferation at E14.5 and an increase in the amount of connective tissue as early as E16.5. These changes were accompanied by excessive mitogen-activated protein kinase pathway activation. Satellite cells isolated from Nf1Prx1 mice showed normal self-renewal, but their differentiation was impaired as indicated by diminished myotube formation. Our results demonstrate a requirement of neurofibromin for muscle formation and maintenance. This previously unrecognized function of neurofibromin may contribute to the musculoskeletal problems in NF1 patients. PMID:21478499

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

2011-01-01

221

Defining skeletal muscle resident progenitors and their cell fate potentials.  

PubMed

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

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

2013-07-01

222

Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita.  

PubMed

The periodic paralyses are a group of autosomal dominant muscle diseases sharing a common feature of episodic paralysis. In one form, paramyotonia congenita (PC), the paralysis usually occurs with muscle cooling. Electrophysiologic studies of muscle from PC patients have revealed temperature-dependent alterations in sodium channel (NaCh) function. This observation led to demonstration of genetic linkage of a skeletal muscle NaCh gene to a PC disease allele. We now report the use of the single-strand conformation polymorphism technique to define alleles specific to PC patients from three families. Sequencing of these alleles defined base pair changes within the same codon, which resulted in two distinct amino acid substitutions for a highly conserved arginine residue in the S4 helix of domain 4 in the adult skeletal muscle NaCh. These data establish the chromosome 17q NaCh locus as the PC gene and represent two mutations causing the distinctive, temperature-sensitive PC phenotype. PMID:1316765

Ptácek, L J; George, A L; Barchi, R L; Griggs, R C; Riggs, J E; Robertson, M; Leppert, M F

1992-05-01

223

Leucine Supplementation Improves Skeletal Muscle Regeneration after Cryolesion in Rats  

PubMed Central

This study was undertaken in order to provide further insight into the role of leucine supplementation in the skeletal muscle regeneration process, focusing on myofiber size and strength recovery. Young (2-month-old) rats were subjected or not to leucine supplementation (1.35 g/kg per day) started 3 days prior to cryolesion. Then, soleus muscles were cryolesioned and continued receiving leucine supplementation until 1, 3 and 10 days later. Soleus muscles from leucine-supplemented animals displayed an increase in myofiber size and a reduction in collagen type III expression on post-cryolesion day 10. Leucine was also effective in reducing FOXO3a activation and ubiquitinated protein accumulation in muscles at post-cryolesion days 3 and 10. In addition, leucine supplementation minimized the cryolesion-induced decrease in tetanic strength and increase in fatigue in regenerating muscles at post-cryolesion day 10. These beneficial effects of leucine were not accompanied by activation of any elements of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin signalling pathway in the regenerating muscles. Our results show that leucine improves myofiber size gain and strength recovery in regenerating soleus muscles through attenuation of protein ubiquitination. In addition, leucine might have therapeutic effects for muscle recovery following injury and in some muscle diseases. PMID:24416379

Pereira, Marcelo G.; Baptista, Igor L.; Carlassara, Eduardo O. C.; Moriscot, Anselmo S.; Aoki, Marcelo S.; Miyabara, Elen H.

2014-01-01

224

Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK  

Microsoft Academic Search

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

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

2002-01-01

225

Skeletal Muscle Type Comparison of Subsarcolemmal Mitochondrial Membrane Phospholipid Fatty Acid Composition in Rat  

Microsoft Academic Search

The phospholipid composition of membranes can influence the physiological functioning of the cell or subcellular organelle.\\u000a This association has been previously demonstrated in skeletal muscle, where cellular or subcellular membrane, specifically\\u000a mitochondria, phospholipid composition is linked to muscle function. However, these observations are based on whole mixed\\u000a skeletal muscle analysis, with little information on skeletal muscles of differing fiber-type compositions.

Leslie E. Stefanyk; Nicole Coverdale; Brian D. Roy; Sandra J. Peters; Paul J. LeBlanc

2010-01-01

226

Adaptations of mouse skeletal muscle to low intensity vibration training  

PubMed Central

Purpose We tested the hypothesis that low intensity vibration training in mice improves contractile function of hindlimb skeletal muscles and promotes exercise-related cellular adaptations. Methods We subjected C57BL/6J mice to 6 wk, 5 d·wk?1, 15 min·d?1 of sham or low intensity vibration (45 Hz, 1.0 g) while housed in traditional cages (Sham-Active, n=8; Vibrated-Active, n=10) or in small cages to restrict physical activity (Sham-Restricted, n=8; Vibrated-Restricted, n=8). Contractile function and resistance to fatigue were tested in vivo (anterior and posterior crural muscles) and ex vivo on the soleus muscle. Tibialis anterior and soleus muscles were evaluated histologically for alterations in oxidative metabolism, capillarity, and fiber types. Epididymal fat pad and hindlimb muscle masses were measured. Two-way ANOVAs were used to determine effects of vibration and physical inactivity. Results Vibration training resulted in a 10% increase in maximal isometric torque (P=0.038) and 16% faster maximal rate of relaxation (P=0.030) of the anterior crural muscles. Posterior crural muscles were unaffected by vibration, with the exception of greater rates of contraction in Vibrated-Restricted mice compared to Vibrated-Active and Sham-Restricted mice (P=0.022). Soleus muscle maximal isometric tetanic force tended to be greater (P=0.057) and maximal relaxation was 20% faster (P=0.005) in Vibrated compared to Sham mice. Restriction of physical activity induced muscle weakness but was not required for vibration to be effective in improving strength or relaxation. Vibration training did not impact muscle fatigability or any indicator of cellular adaptation investigated (P?0.431). Fat pad but not hindlimb muscle masses were affected by vibration training. Conclusion Vibration training in mice improved muscle contractility, specifically strength and relaxation rates, with no indication of adverse effects to muscle function or cellular adaptations. PMID:23274599

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

2013-01-01

227

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

228

Stromal interaction molecule 1 (STIM1) regulates sarcoplasmic/endoplasmic reticulum Ca²?-ATPase 1a (SERCA1a) in skeletal muscle.  

PubMed

Stromal interaction molecule 1 (STIM1) mediates Ca2+ movements from the extracellular space to the cytosol through a store-operated Ca2+ entry (SOCE) mechanism in various cells including skeletal muscle cells. In the present study, to reveal the unidentified functional role of the STIM1 C terminus from 449 to 671 amino acids in skeletal muscle, binding assays and quadrupole time-of-flight mass spectrometry were used to identify proteins binding in this region along with proteins that mediate skeletal muscle contraction and relaxation. STIM1 binds to sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1a (SERCA1a) via this region (called STIM1-SBR). The binding was confirmed in endogenous full-length STIM1 in rabbit skeletal muscle and mouse primary skeletal myotubes via co-immunoprecipitation assay and immunocytochemistry. STIM1 knockdown in mouse primary skeletal myotubes decreased Ca2+ uptake from the cytosol to the sarcoplasmic reticulum (SR) through SERCA1a only at micromolar cytosolic Ca2+ concentrations, suggesting that STIM1 could be required for the full activity of SERCA1a possibly during the relaxation of skeletal muscle. Various Ca2+ imaging experiments using myotubes expressing STIM1-SBR suggest that STIM1 is involved in intracellular Ca2+ distributions between the SR and the cytosol via regulating SERCA1a activity without affecting SOCE. Therefore, in skeletal muscle, STIM1 could play an important role in regulating Ca2+ movements between the SR and the cytosol. PMID:24077737

Lee, Keon Jin; Hyun, Changdo; Woo, Jin Seok; Park, Chang Sik; Kim, Do Han; Lee, Eun Hui

2014-05-01

229

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

230

Skeletal Muscle Catabolism in TNBS-Induced Murine Colitis  

PubMed Central

The present study determined whether the muscle atrophy produced by colitis is associated with altered rates of muscle protein synthesis or degradation, as well as the potential role of the local (e.g., muscle) insulin-like growth factor (IGF) system and muscle-specific ubiquitin E3 ligases atrogin-1 and MuRF1 in mediating altered muscle protein balance. Colitis was induced in C57BL/6 mice by intra-rectal administration of trinitrobenzne sulfonic acid (TNBS), and blood and tissues collected on day 10. Mice with inflammatory bowel disease (IBD) demonstrated reduced skeletal muscle mass and protein content, whereas colonic segment weight and gross damage score were both increased in mice with colitis, compared to time-matched control values. There was no change in muscle protein synthesis in mice with IBD, but there was an increased protein breakdown (45%), proteasome activity (85%), and mRNA expression for atrogin-1 and MuRF1 (200–300%) in muscle. These changes were associated with a reduction in liver (but not muscle) IGF-I mRNA as well as a reduction in both total and free IGF-I in the blood. Colitis decreased the hepatic content of IGF binding protein (IGFBP)-3 mRNA by 40% and increased IGFBP-1 mRNA by 100%. In contrast, colitis did alter IGFBP mRNAs in muscle. The TNF?, IL-6 and NOS2 mRNA content of both liver and skeletal muscle was increased in TNBS-treated mice, and plasma TNF? and IL-6 concentrations were also elevated. These data suggest TNBS-induced colitis is independent of a change in muscle protein synthesis but dependent on stimulation of protein degradation via increased expression of muscle-specific atrogenes, which may be mediated in part by the reduction in circulating concentration of IGF-I and the concomitant increase in inflammatory mediators observed in the blood and muscle per se. PMID:20546811

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

2010-01-01

231

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

PubMed Central

The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n= 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n= 8) not involved in any kind of resistance exercise underwent a heavy resistance exercise protocol that stimulated the vastus lateralis muscle and biopsies were obtained from this muscle pre-exercise as well as 6, 24 and 48 h post-exercise. IL-15 mRNA levels were twofold higher in the triceps (type 2 fibre dominance) compared with the soleus muscle (type 1 fibre dominance), but Western blotting and immunohistochemistry revealed that muscle IL-15 protein content did not differ between triceps brachii, quadriceps and soleus muscles. Following resistance exercise, IL-15 mRNA levels were up-regulated twofold at 24 h of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal muscle were not paralleled by similar changes in muscular IL-15 protein expression suggesting that muscle IL-15 may exist in a translationally inactive pool. PMID:17690139

Nielsen, Anders Rinnov; Mounier, Remi; Plomgaard, Peter; Mortensen, Ole Hartvig; Penkowa, Milena; Speerschneider, Tobias; Pilegaard, Henriette; Pedersen, Bente Klarlund

2007-01-01

232

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

233

Different cytokines modulate ubiquitin gene expression in rat skeletal muscle.  

PubMed

Intravenous administration of different cytokines caused important changes in the expression of ubiquitin genes in skeletal muscle. Tumour necrosis factor-alpha caused a 2.2- and 1.9-fold increase in the expression of the 2.4 and 1.2 kb transcripts, respectively. Administration of interferon-gamma also caused a 2.2- and 1.8-fold increase in the 2.4 and 1.2 kb transcripts, respectively. While administration of leukaemia inhibitory factor and interleukin-6 resulted in no changes in ubiquitin gene expression, interleukin-1 administration also caused an increase in both ubiquitin gene transcripts (2.8- and 1.9-fold for the 2.4 and 1.2 kb transcripts, respectively). The results suggest that some of the cytokine effects on the ubiquitin system gene expression could be related to the enhanced skeletal muscle proteolysis found during cancer cachexia and other pathological states. PMID:9929164

Llovera, M; Carbó, N; López-Soriano, J; García-Martínez, C; Busquets, S; Alvarez, B; Agell, N; Costelli, P; López-Soriano, F J; Celada, A; Argilés, J M

1998-11-13

234

Regulation of glucose transport in skeletal muscle  

Microsoft Academic Search

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

R. JAMES BARNARD; JACX F. YOUNGREN

235

Skeletal muscle lipid flux: running water carries no poison.  

PubMed

Lipids are the most abundant organic constituents in many humans. The rise in obesity prevalence has prompted a need for a more refined understanding of the effects of lipid molecules on cell physiology. In skeletal muscle, deposition of lipids can be associated with insulin resistance that contributes to the development of diabetes. Here, we review the evidence that muscle cells are equipped with the molecular machinery to convert and sequester lipid molecules, thus rendering them harmless. Induction of mitochondrial and lipogenic flux in the setting of elevated lipid deposition can protect muscle from lipid-induced "poisoning" of the cellular machinery. Lipid flux may also be directed toward the synthesis of ligands for nuclear receptors, further enhancing the capacity of muscle for lipid metabolism to promote favorable physiology. Exploiting these mechanisms may have implications for the treatment of obesity-related diseases. PMID:21558546

Funai, Katsuhiko; Semenkovich, Clay F

2011-08-01

236

Skeletal muscle lipid flux: running water carries no poison  

PubMed Central

Lipids are the most abundant organic constituents in many humans. The rise in obesity prevalence has prompted a need for a more refined understanding of the effects of lipid molecules on cell physiology. In skeletal muscle, deposition of lipids can be associated with insulin resistance that contributes to the development of diabetes. Here, we review the evidence that muscle cells are equipped with the molecular machinery to convert and sequester lipid molecules, thus rendering them harmless. Induction of mitochondrial and lipogenic flux in the setting of elevated lipid deposition can protect muscle from lipid-induced “poisoning” of the cellular machinery. Lipid flux may also be directed toward the synthesis of ligands for nuclear receptors, further enhancing the capacity of muscle for lipid metabolism to promote favorable physiology. Exploiting these mechanisms may have implications for the treatment of obesity-related diseases. PMID:21558546

Funai, Katsuhiko

2011-01-01

237

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

238

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

239

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

240

Skeletal muscle architectural adaptations to marathon run training.  

PubMed

We assessed lateral gastrocnemius (LG) and vastus lateralis (VL) architecture in 16 recreational runners before and after 12 weeks of marathon training. LG fascicle length decreased 10% while pennation angle increased 17% (p < 0.05). There was a significant correlation between diminished blood lactate levels and LG pennation angle change (r = 0.90). No changes were observed in VL. This is the first evidence that run training can modify skeletal muscle architectural features. PMID:25494870

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

2015-01-01

241

Different cytokines modulate ubiquitin gene expression in rat skeletal muscle  

Microsoft Academic Search

Intravenous administration of different cytokines caused important changes in the expression of ubiquitin genes in skeletal muscle. Tumour necrosis factor-? caused a 2.2- and 1.9-fold increase in the expression of the 2.4 and 1.2 kb transcripts, respectively. Administration of interferon-? also caused a 2.2- and 1.8-fold increase in the 2.4 and 1.2 kb transcripts, respectively. While administration of leukaemia inhibitory

Marta Llovera; Neus Carbó; Joaqu??n López-Soriano; Cèlia Garc??a-Mart??nez; S??lvia Busquets; Belén Alvarez; Neus Agell; Paola Costelli; Francisco J. López-Soriano; Antonio Celada; Josep M. Argilés

1998-01-01

242

Skeletal muscle pathology in ovine congenital progressive muscular dystrophy  

Microsoft Academic Search

Fiber-type proportions were determined in 12 skeletal muscles (peronaeus tertius, tibialis cranialis, tensor fascia lata, psoas major, extensor digitorum lateralis, tensor fascia antibrachii, vastus intermedius, soleus, anconaeus, and flexor digitorum superficialis of fore and hind limb) from infantile (20 weeks), juvenile (16 months) and adult (2.5 and 3.5 years) Merino sheep with ovine congenital progressive muscular dystrophy and in age-matched

R. B. Richards; I. K. Passmore; E. F. Dempsey

1988-01-01

243

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

244

Compartment calcium model of frog skeletal muscle during activation.  

PubMed

Skeletal muscle contraction is triggered by a rise in calcium (Ca(2+)) concentration in the myofibrillar space. The objective of this study was to develop a voltage dependent compartment model of Ca(2+) dynamics in frog skeletal muscle fibers. The compartment model corresponds to the myofibrillar space (MS) and a calcium store, the sarcoplasmic reticulum (SR). Ca(2+) is released from the SR to the MS based on the voltage and is able to bind to several proteins in the MS. We use a detailed model to account for voltage dependent Ca(2+) release and inactivation. With this model, we are able to match previous experimental data for Ca(2+) release and binding to proteins for an applied (fixed) voltage. We explore the sensitivity of parameters in the model and illustrate the importance of inactivation of the SR; during a long depolarization, the SR must be inactivated in order to achieve realistic Ca(2+) concentrations in the MS. A Hodgkin Huxley type model was also developed to describe voltage at the surface membrane using electrophysiological data from previous experiments. This voltage model was then used as the time dependent voltage to determine Ca(2+) release from the SR. With this fully coupled model, we were able to match previous experimental results for Ca(2+) concentrations for a given applied current. Additionally, we examined simulated Ca(2+) concentrations in the case of twitch and tetanus, corresponding to different applied currents. The developed model is robust and reproduces many aspects of voltage dependent calcium signaling in frog skeletal muscle fibers. This modeling framework provides a platform for future studies of excitation contraction coupling in skeletal muscle fibers. PMID:25234233

Liu, Weifan; Olson, Sarah D

2015-01-01

245

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 remodeling must accommodate extended inactivity during winter torpor, the motor requirements of transient winter active periods, and sustained activity following spring emergence. Muscle volume in 13-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-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 remodeling 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 end of winter. Muscle protein synthesis was 66% depressed in early but not late winter compared to 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

2014-12-01

246

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

PubMed Central

Repetitive stimulation potentiates contractile tension of fast-twitch skeletal muscle. We examined the role of myosin regulatory light chain (RLC) phosphorylation in this physiological response by ablating Ca2+/calmodulin-dependent skeletal muscle myosin light chain kinase (MLCK) gene expression. Western blot and quantitative-PCR showed that MLCK is expressed predominantly in fast-twitch skeletal muscle fibers with insignificant amounts in heart and smooth muscle. In contrast, smooth muscle MLCK had a more ubiquitous tissue distribution, with the greatest expression observed in smooth muscle tissue. Ablation of the MYLK2 gene in mice resulted in loss of skeletal muscle MLCK expression, with no change in smooth muscle MLCK expression. In isolated fast-twitch skeletal muscles from these knockout mice, there was no significant increase in RLC phosphorylation in response to repetitive electrical stimulation. Furthermore, isometric twitch-tension potentiation after a brief tetanus (posttetanic twitch potentiation) or low-frequency twitch potentiation (staircase) was attenuated relative to responses in muscles from wild-type mice. Interestingly, the site of phosphorylation of the small amount of monophosphorylated RLC in the knockout mice was the same site phosphorylated by MLCK, indicating a potential alternative signaling pathway affecting contractile potentiation. Loss of skeletal muscle MLCK expression had no effect on cardiac RLC phosphorylation. These results identify myosin light chain phosphorylation by the dedicated skeletal muscle Ca2+/calmodulin-dependent MLCK as a primary biochemical mechanism for tension potentiation due to repetitive stimulation in fast-twitch skeletal muscle. PMID:16299103

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

2005-01-01

247

A ribonuclease from human skeletal muscle  

PubMed Central

1. A ribonuclease has been prepared from human muscle by ammonium sulphate fractionation, heat treatment and ion-exchange chromatography. 2. The enzyme degrades polycytidylic acid and polyuridylic acid to the nucleoside 3?-phosphates, with nucleoside 2?:3?-cyclic phosphates as intermediates. Polyadenylic acid and polyguanylic acid are not attacked. 3. The enzyme has maximal activity at pH8.5. The molecular weight (by gel filtration) is between 11000 and 12000. It is relatively heat-stable. It exhibits optimum activity in a medium of high ionic strength, and is inhibited by several bivalent cations, particularly Zn2+. PMID:5472160

Goldspink, D. F.; Pennington, R. J.

1970-01-01

248

The Role of Six1 in the Genesis of Muscle Cell and Skeletal Muscle Development  

PubMed Central

The sine oculis homeobox 1 (Six1) gene encodes an evolutionarily conserved transcription factor. In the past two decades, much research has indicated that Six1 is a powerful regulator participating in skeletal muscle development. In this review, we summarized the discovery and structural characteristics of Six1 gene, and discussed the functional roles and molecular mechanisms of Six1 in myogenesis and in the formation of skeletal muscle fibers. Finally, we proposed areas of future interest for understanding Six1 gene function. PMID:25210496

Wu, Wangjun; Huang, Ruihua; Wu, Qinghua; Li, Pinghua; Chen, Jie; Li, Bojiang; Liu, Honglin

2014-01-01

249

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

250

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

251

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

PubMed Central

Abstract 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

2014-01-01

252

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.

253

Viscoelastic properties of passive skeletal muscle in compression: Stress-relaxation behaviour and constitutive modelling  

Microsoft Academic Search

The compressive properties of skeletal muscle are important in impact biomechanics, rehabilitation engineering and surgical simulation. However, the mechanical behaviour of muscle tissue in compression remains poorly characterised. In this paper, the time-dependent properties of passive skeletal muscle were investigated using a combined experimental and theoretical approach. Uniaxial ramp and hold compression tests were performed in vitro on fresh porcine

M. Van Loocke; C. G. Lyons; C. K. Simms

2008-01-01

254

Modulations of the calcineurin\\/NF-AT pathway in skeletal muscle atrophy  

Microsoft Academic Search

Calcineurin has been proposed to regulate skeletal muscle hypertrophy, while its relevance to the pathogenesis of muscle atrophy is unknown. The present study was aimed to investigate if perturbations of the calcineurin pathway may be involved in causing skeletal muscle atrophy in two different experimental conditions: cancer cachexia (rats bearing the AH-130 hepatoma), and hyperglycemia (rats treated with streptozotocin). Calcineurin

Paola Costelli; Vanessa Almendro; Maria Teresa Figueras; Patrizia Reffo; Fabio Penna; Manuela Aragno; Raffaella Mastrocola; Giuseppe Boccuzzi; Silvia Busquets; Gabriella Bonelli; Francisco J. Lopez Soriano; Josep M. Argilés; Francesco M. Baccino

2007-01-01

255

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

Microsoft Academic Search

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

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

2003-01-01

256

Dynamics of Myosin-Driven Skeletal Muscle Contraction: I. Steady-State Force Generation  

E-print Network

- generating element in the muscle is the motor protein myosin II (Huxley and Niedergerke, 1954; Huxley-dependent ADP release step can explain the dynamics of skeletal muscle contraction. Proteins of the myosinDynamics of Myosin-Driven Skeletal Muscle Contraction: I. Steady-State Force Generation Ganhui Lan

Sun, Sean

257

Acylcarnitines: potential implications for skeletal muscle insulin resistance.  

PubMed

Insulin resistance may be linked to incomplete fatty acid ?-oxidation and the subsequent increase in acylcarnitine species in different tissues including skeletal muscle. It is not known if acylcarnitines participate in muscle insulin resistance or simply reflect dysregulated metabolism. The aims of this study were to determine whether acylcarnitines can elicit muscle insulin resistance and to better understand the link between incomplete muscle fatty acid ?-oxidation, oxidative stress, inflammation, and insulin-resistance development. Differentiated C2C12, primary mouse, and human myotubes were treated with acylcarnitines (C4:0, C14:0, C16:0) or with palmitate with or without carnitine acyltransferase inhibition by mildronate. Treatment with C4:0, C14:0, and C16:0 acylcarnitines resulted in 20-30% decrease in insulin response at the level of Akt phosphorylation and/or glucose uptake. Mildronate reversed palmitate-induced insulin resistance concomitant with an ?25% decrease in short-chain acylcarnitine and acetylcarnitine secretion. Although proinflammatory cytokines were not affected under these conditions, oxidative stress was increased by 2-3 times by short- or long-chain acylcarnitines. Acylcarnitine-induced oxidative stress and insulin resistance were reversed by treatment with antioxidants. Results are consistent with the conclusion that incomplete muscle fatty acid ?-oxidation causes acylcarnitine accumulation and associated oxidative stress, raising the possibility that these metabolites play a role in muscle insulin resistance.-Aguer, C., McCoin, C. S., Knotts, T. A., Thrush, A. B., Ono-Moore, K., McPherson, R., Dent, R., Hwang, D. H., Adams, S. H., Harper, M.-E. Acylcarnitines: potential implications for skeletal muscle insulin resistance. PMID:25342132

Aguer, Céline; McCoin, Colin S; Knotts, Trina A; Thrush, A Brianne; Ono-Moore, Kikumi; McPherson, Ruth; Dent, Robert; Hwang, Daniel H; Adams, Sean H; Harper, Mary-Ellen

2015-01-01

258

MicroRNA transcriptome profiles during swine skeletal muscle development  

PubMed Central

Background MicroRNA (miR) are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells, three stages of fetal growth, day-old neonate, and the adult. Results Twelve potential novel miR were detected that did not match previously reported sequences. In addition, a number of miR previously reported to be expressed in mammalian muscle were detected, having a variety of abundance patterns through muscle development. Muscle-specific miR-206 was nearly absent in proliferating satellite cells in culture, but was the highest abundant miR at other time points evaluated. In addition, miR-1 was moderately abundant throughout developmental stages with highest abundance in the adult. In contrast, miR-133 was moderately abundant in adult muscle and either not detectable or lowly abundant throughout fetal and neonate development. Changes in abundance of ubiquitously expressed miR were also observed. MiR-432 abundance was highest at the earliest stage of fetal development tested (60 day-old fetus) and decreased throughout development to the adult. Conversely, miR-24 and miR-27 exhibited greatest abundance in proliferating satellite cells and the adult, while abundance of miR-368, miR-376, and miR-423-5p was greatest in the neonate. Conclusion These data present a complete set of transcriptome profiles to evaluate miR abundance at specific stages of skeletal muscle growth in swine. Identification of these miR provides an initial group of miR that may play a vital role in muscle development and growth. PMID:19208255

McDaneld, Tara G; Smith, Timothy PL; Doumit, Matthew E; Miles, Jeremy R; Coutinho, Luiz L; Sonstegard, Tad S; Matukumalli, Lakshmi K; Nonneman, Dan J; Wiedmann, Ralph T

2009-01-01

259

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

260

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

Microsoft Academic Search

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

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

2006-01-01

261

Skeletal muscle hydatid cysts presenting as soft tissue masses  

PubMed Central

Muscle hydatidosis is rare, accounting only for 3–5% of all cases. We present a case series of 9 patients (8 male, one female, mean age 59.3 years, range 48-75 years) with primary echinococcosis of skeletal muscles. The cysts presented as soft tissue masses in 8 patients, whereas in one, the cyst was an incidental finding on a CT scan performed for investigation of a lung problem. All hydatid cysts were confined into muscles, without affecting the bone. The location was the thigh region in 6 patients (quadriceps in 4, biceps in 2), the popliteal fossa (gastrocnemius) in one, the humerus (triceps branchii) in one and the shoulder (infraspinatus) in one patient. MRI showed multi-vesicular cysts in all patients. Indirect hemagglutination serological test was positive in 6 out of 9 cases. En block surgical excision of the cysts was undertaken in all patients. Two patients received antihelminthic chemotherapy preoperatively. Histopathologic findings confirmed the diagnosis. No recurrence occurred during the follow-up period (1-8 years). Skeletal muscle echinococcosis should be considered in the differential diagnosis of limb masses, especially in endemic countries. A meticulous history taking and MRI imaging are essential, while pericystectomy is an effective method of treatment. PMID:20596270

Gougoulias, N E; Varitimidis, S E; Bargiotas, K A; Dovas, T N; Karydakis, G; Dailiana, Z H

2010-01-01

262

TNF-? is involved in activating DNA fragmentation in skeletal muscle  

PubMed Central

Intraperitoneal administration of 100??g kg?1 (body weight) of tumour necrosis factor-? to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-?-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-?-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-? receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-? partly mediates DNA fragmentation during experimental cancer-associated cachexia. British Journal of Cancer (2002) 86, 1012–1016. DOI: 10.1038/sj/bjc/6600167 www.bjcancer.com © 2002 Cancer Research UK PMID:11953838

Carbó, N; Busquets, S; van Royen, M; Alvarez, B; López-Soriano, F J; Argilés, J M

2002-01-01

263

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

264

Vitamin D and skeletal muscle tissue and function.  

PubMed

This review aims to summarize current knowledge on the role of vitamin D in skeletal muscle tissue and function. Vitamin D deficiency can cause a myopathy of varying severity. Clinical studies have indicated that vitamin D status is positively associated with muscle strength and physical performance and inversely associated with risk of falling. Vitamin D supplementation has shown to improve tests of muscle function, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults. Molecular mechanisms of vitamin D action on muscle tissue include genomic and non-genomic effects via a receptor present in muscle cells. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] to its nuclear receptor, which results in changes in gene transcription of mRNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a cell surface receptor. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Recently, VDR polymorphisms have been described to affect muscle function. Parathyroid hormone which is strongly linked with vitamin D status also may play a role in muscle function; however, distinguishing its role from that of vitamin D has yet to be fully clarified. Despite the enormous advances in recent decades, further research is needed to fully characterize the exact underlying mechanisms of vitamin D action on muscle tissue and to understand how these cellular changes translate into clinical improvements in physical performance. PMID:18727936

Ceglia, Lisa

2008-12-01

265

Free Radical Formation after Intensive Exercise in Thoroughbred Skeletal Muscles  

PubMed Central

Although high oxygen consumption in skeletal muscle may result in severe oxidative stress, there are no direct studies that have documented free radical production in horse muscles after intensive exercise. To find a new parameter indicating the muscle adaptation state for the training of Thoroughbred horses, we examined free radical formation in the muscle by using electron paramagnetic resonance (EPR). Ten male Thoroughbred horses received conventional training for 18 weeks. Before and after the training period, all horses performed an exhaustive incremental load exercise on a 6% incline treadmill. Muscle samples of the middle gluteal muscle were taken pre-exercise and 1 min, 1 hr, and 1 day after exercise. Muscle fiber type composition was also determined in the pre-exercise samples by immunohistochemical staining with monoclonal antibody to myosin heavy chain. We measured the free radical in the muscle homogenate using EPR at room temperature, and the amount was expressed as relative EPR signal intensity. There was a significant increase in Type IIA muscle fiber composition and a decrease in Type IIX fiber composition after the training period. Before the training period, the mean value of the relative EPR signal intensity showed a significant increase over the pre-exercise value at 1 min after the exercise and an incomplete recovery at 24 hr after the exercise. While no significant changes were found in the relative EPR signal intensity after the training period. There was a significant relationship between percentages of Type IIA fiber and change rates in EPR signal intensity at 1 min after exercise. The measurement of free radicals may be useful for determining the muscle adaptation state in the training of Thoroughbred horses. PMID:24833984

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

2011-01-01

266

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

PubMed

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

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

2014-06-01

267

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

268

Role of hydrogen sulfide in skeletal muscle biology and metabolism.  

PubMed

Hydrogen sulfide (H2S) is a novel endogenous gaseous signal transducer (gasotransmitter). Its emerging role in multiple facets of inter- and intra-cellular signaling as a metabolic, inflammatory, neuro and vascular modulator has been increasingly realized. Although H2S is known for its effects as an anti-hypertensive, anti-inflammatory and anti-oxidant molecule, the relevance of these effects in skeletal muscle biology during health and during metabolic syndromes is unclear. H2S has been implicated in vascular relaxation and vessel tone enhancement, which might lead to mitigation of vascular complications caused by the metabolic syndromes. Metabolic complications may also lead to mitochondrial remodeling by interfering with fusion and fission, therefore, leading to mitochondrial mitophagy and skeletal muscle myopathy. Mitochondrial protection by H2S enhancing treatments may mitigate deterioration of muscle function during metabolic syndromes. In addition, H2S might upregulate uncoupling proteins and might also cause browning of white fat, resulting in suppression of imbalanced cytokine signaling caused by abnormal fat accumulation. Likewise, as a source for H(+) ions, it has the potential to augment anaerobic ATP synthesis. However, there is a need for studies to test these putative H2S benefits in different patho-physiological scenarios before its full-fledged usage as a therapeutic molecule. The present review highlights current knowledge with regard to exogenous and endogenous H2S roles in skeletal muscle biology, metabolism, exercise physiology and related metabolic disorders, such as diabetes and obesity, and also provides future directions. PMID:25461301

Veeranki, Sudhakar; Tyagi, Suresh C

2014-11-25

269

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

270

Ca2+-Dependent Regulations and Signaling in Skeletal Muscle: From Electro-Mechanical Coupling to Adaptation  

PubMed Central

Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca2+ is critically involved in the innervation of skeletal muscle fibers that results in the exertion of an action potential along the muscle fiber membrane, the prerequisite for skeletal muscle contraction. Furthermore and among others, Ca2+ regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca2+-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca2+ ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca2+ ions in adult muscle but also highlight recent findings of critical Ca2+-dependent mechanisms essential for skeletal muscle-regulation and maintenance. PMID:25569087

Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

2015-01-01

271

The effects of growth factors on skeletal muscle lesions  

PubMed Central

Skeletal muscle injuries are common causes of severe long-term pain and physical disability, accounting for up to 55% of all sports injuries. The phases of the healing process after direct or indirect muscle injury are complex but clearly defined processes comprising well-coordinated steps: degeneration, inflammation, regeneration, and fibrosis. Despite this frequent occurrence and the presence of a body of data on the pathophysiology of muscle injuries, none of the treatment strategies adopted to date have been shown to be really effective in strictly controlled trials. Most current muscle injury treatments are based on limited experimental and clinical data and/or were only empirically tested. Platelet-rich plasma (PRP) is a promising alternative approach based on the ability of autologous growth factors (GFs) to accelerate tissue healing, improve muscular regeneration, increase neovascularization and reduce fibrosis, allowing rapid recovery after muscle lesions. Thus, further experimental studies that include the quantification of specific GFs released by PRP, as well as additional data on angiogenesis, myogenesis and functional recovery are needed to ultimately validate the hypothesis of PRP efficacy in the treatment of muscle lesions and open the way for its wide clinical application.

GIGANTE, ANTONIO; CIANFORLINI, MARCO; MANZOTTI, SANDRA; ULISSE, SERENA

2013-01-01

272

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

273

Exercise differentially regulates renalase expression in skeletal muscle and kidney.  

PubMed

Renalase is a newly discovered amine oxidase and may lower blood pressure by metabolizing catecholamines. We have hypothesized that exercise and training may regulate renalase expression to control blood pressure. In this study, we investigated changes in renalase expression after exercise and training in white and red portion of the gastrocnemius muscle, kidney, and serum in rats. Rats were either untrained or subjected to six weeks of endurance training, which predominantly recruits red fibers. Rats from each group were sacrificed before (n = 10), immediately after (n = 10), or three hours (n = 10) following exercise. Renalase mRNA and protein levels were measured by RT-PCR and ELISA, respectively. There were no significant changes in renalase expression after prolonged training or acute exercise in the serum or red muscle of rats. However, in white muscle, renalase mRNA and protein levels decreased after acute exercise in untrained rats, whereas, in trained rats, its protein level remained unchanged, despite a decrease in mRNA. Thus, exercise influenced renalase expression only in white muscle fibers that are not predominantly recruited during exercise. The reduction of renalase protein in white muscle suggests that renalase may contribute to blood redistribution between contracting and non-contracting fibers during exercise. In the kidney, renalase protein levels decreased after training, while mRNA levels increased. The reduction in renalase protein levels may contribute to functional kidney hypoperfusion, which has been observed after training. In conclusion, exercise differentially regulates renalase expression in skeletal muscle and kidney. PMID:24366404

Czarkowska-Paczek, Bozena; Zendzian-Piotrowska, Malgorzata; Gala, Kamila; Sobol, Maria; Paczek, Leszek

2013-01-01

274

Autophagy Signaling in Skeletal Muscle of Infarcted Rats  

PubMed Central

Background Heart failure (HF)-induced skeletal muscle atrophy is often associated to exercise intolerance and poor prognosis. Better understanding of the molecular mechanisms underlying HF-induced muscle atrophy may contribute to the development of pharmacological strategies to prevent or treat such condition. It has been shown that autophagy-lysosome system is an important mechanism for maintenance of muscle mass. However, its role in HF-induced myopathy has not been addressed yet. Therefore, the aim of the present study was to evaluate autophagy signaling in myocardial infarction (MI)-induced muscle atrophy in rats. Methods/Principal Findings Wistar rats underwent MI or Sham surgeries, and after 12 weeks were submitted to echocardiography, exercise tolerance and histology evaluations. Cathepsin L activity and expression of autophagy-related genes and proteins were assessed in soleus and plantaris muscles by fluorimetric assay, qRT-PCR and immunoblotting, respectively. MI rats displayed exercise intolerance, left ventricular dysfunction and dilation, thereby suggesting the presence of HF. The key findings of the present study were: a) upregulation of autophagy-related genes (GABARAPL1, ATG7, BNIP3, CTSL1 and LAMP2) was observed only in plantaris while muscle atrophy was observed in both soleus and plantaris muscles, and b) Cathepsin L activity, Bnip3 and Fis1 protein levels, and levels of lipid hydroperoxides were increased specifically in plantaris muscle of MI rats. Conclusions Altogether our results provide evidence for autophagy signaling regulation in HF-induced plantaris atrophy but not soleus atrophy. Therefore, autophagy-lysosome system is differentially regulated in atrophic muscles comprising different fiber-types and metabolic characteristics. PMID:24427319

Jannig, Paulo R.; Moreira, Jose B. N.; Bechara, Luiz R. G.; Bozi, Luiz H. M.; Bacurau, Aline V.; Monteiro, Alex W. A.; Dourado, Paulo M.; Wisløff, Ulrik; Brum, Patricia C.

2014-01-01

275

Collagen crosslinking does not dictate stiffness in a transgenic mouse model of skeletal muscle fibrosis.  

PubMed

Skeletal muscle fibrosis is characterized by increases in tissue stiffness and collagen content. However, a very weak correlation exists between collagen content and stiffness in skeletal muscle. Recently, it has been hypothesized that collagen crosslinking explains tissue stiffness in fibrotic skeletal muscle. Therefore, we addressed this hypothesis by correlating tissue stiffness with lysyl-pyridinoline, hydroxylysyl-pyridinoline, and pentosidine collagen crosslinks. Stepwise regression revealed that, separate or together, collagen crosslinks did not correlate with tissue stiffness. Our result demonstrates that increased tissue stiffness in skeletal muscle fibrosis is not simply explained by increased collagen crosslinks and/or collagen crosslink density. We suggest that collagen organization may affect tissue stiffness. PMID:25529136

Chapman, Mark A; Pichika, Rajeswari; Lieber, Richard L

2015-01-21

276

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

277

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

278

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

279

Thyroid hormones regulate skeletal muscle regeneration after acute injury.  

PubMed

We evaluated the effects of hypo- and hyperthyroid statuses during the initial phase of skeletal muscle regeneration in rats. To induce hypo- or hyperthyroidism, adult male Wistar rats were treated with methimazole (0.03 %) or T4 (10 ?g/100 g), respectively, for 10 days. Three days before sacrifice, a crush injury was produced in the solear muscles of one half of the animals, while the other half remained intact. T3, T4, TSH, and leptin serum levels were not affected by the injury. Serum T3 and T4 levels were significantly increased in hyperthyroid and hyper-injury animals. Hypothyroidism was confirmed by the significant increase in serum TSH levels in hypothyroid and hypo-injury animals. Injury increased cell infiltration and macrophage accumulation especially in hyperthyroid animals. Both type 2 and type 3 deiodinases were induced by lesion, and the opposite occurred with the type 1 isoform, at least in the control and hyperthyroid groups. Injury increased both MyoD and myogenin expression in all the studied groups, but only MyoD expression was increased by thyroidal status only at the protein level. We conclude that thyroid hormones modulate skeletal muscle regeneration possibly by regulating the inflammatory process, as well as MyoD and myogenin expression in the injured tissue. PMID:24798447

Leal, Anna Lúcia R C; Albuquerque, João Paulo C; Matos, Marina S; Fortunato, Rodrigo S; Carvalho, Denise P; Rosenthal, Doris; da Costa, Vânia Maria Corrêa

2014-05-01

280

Determination of MiRNA Targets in Skeletal Muscle Cells  

PubMed Central

MicroRNAs (miRNAs) are a class of small ?22 nucleotide noncoding RNAs which regulate gene expression at the posttranscriptional level by either destabilizing and consequently degrading their targeted mRNAs or by repressing their translation. Emerging evidence has demonstrated that miRNAs are essential for normal mammalian development, homeostasis, and many other functions. In addition, deleterious changes in miRNA expression were associated with human diseases. Several muscle-specific miRNAs, including miR-1, miR-133, miR-206, and miR-208, have been shown to be important for normal myo-blast differentiation, proliferation, and muscle remodeling in response to stress. They have also been implicated in various cardiac and skeletal muscular diseases. miRNA-based gene therapies hold great potential for the treatment of cardiac and skeletal muscle diseases. Herein, we describe methods commonly applied to study the biological role of miRNAs, as well as techniques utilized to manipulate miRNA expression and to investigate their target regulation. PMID:22130855

Huang, Zhan-Peng; Espinoza-Lewis, Ramón; Wang, Da-Zhi

2014-01-01

281

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

282

Apoptosis in capillary endothelial cells in ageing skeletal muscle  

PubMed Central

The age-related loss of skeletal muscle mass and function (sarcopenia) is a consistent hallmark of ageing. Apoptosis plays an important role in muscle atrophy, and the intent of this study was to specify whether apoptosis is restricted to myofibre nuclei (myonuclei) or occurs in satellite cells or stromal cells of extracellular matrix (ECM). Sarcopenia in mouse gastrocnemius muscle was characterized by myofibre atrophy, oxidative type grouping, delocalization of myonuclei and ECM fibrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) indicated a sharp rise in apoptosis during ageing. TUNEL coupled with immunostaining for dystrophin, paired box protein-7 (Pax7) or laminin-2?, respectively, was used to identify apoptosis in myonuclei, satellite cells and stromal cells. In adult muscle, apoptosis was not detected in myofibres, but was restricted to stromal cells. Moreover, the age-related rise in apoptotic nuclei was essentially due to stromal cells. Myofibre-associated apoptosis nevertheless occurred in old muscle, but represented < 20% of the total muscle apoptosis. Specifically, apoptosis in old muscle affected a small proportion (0.8%) of the myonuclei, but a large part (46%) of the Pax7+ satellite cells. TUNEL coupled with CD31 immunostaining further attributed stromal apoptosis to capillary endothelial cells. Age-dependent rise in apoptotic capillary endothelial cells was concomitant with altered levels of key angiogenic regulators, perlecan and a perlecan domain V (endorepellin) proteolytic product. Collectively, our results indicate that sarcopenia is associated with apoptosis of satellite cells and impairment of capillary functions, which is likely to contribute to the decline in muscle mass and functionality during ageing. PMID:24245531

Wang, Huijuan; Listrat, Anne; Meunier, Bruno; Gueugneau, Marine; Coudy-Gandilhon, Cécile; Combaret, Lydie; Taillandier, Daniel; Polge, Cécile; Attaix, Didier; Lethias, Claire; Lee, Kijoon; Goh, Kheng Lim; Béchet, Daniel

2014-01-01

283

Developmental programming of skeletal muscle phenotype/metabolism.  

PubMed

Skeletal muscle is a highly dynamic and malleable tissue that is able to adapt to different stimuli placed upon it, both during gestation and after birth, ultimately resulting in anatomical changes to muscle fibre composition. Variation in nutrient supply throughout gestation is common, whether in livestock or in the human. The specific effects of maternal nutrition on foetal development are at the forefront of scientific research. However, results describing how different maternal feeding strategies affect skeletal muscle fibre development in the offspring are not fully consistent, even where the same time windows during gestation have been examined. The aim of this study is to determine the effects of increased maternal nutrition (above the recommended levels) on the Musculus semitendinosus phenotype of progeny. In all, 24 pregnant sows were assigned to one of four feeding regimes during gestation; T1 (control group): 30 MJ digestible energy per day (MJ DE/day) throughout gestation, T2: same as that for T1 but increased to 60 MJ DE/day from 25 to 50 days of gestation (dg), T3: same as that for T1 but increased to 60 MJ DE/day from 50 to 80 dg, T4: same as that for T1 but increased nutrition to 60 MJ DE/day from 25 to 80 dg. Light- and heavy-weight littermate pairs of the same sex were selected at birth and individually fed to slaughter (c. 158 days). Histochemical and immunohistochemical staining were used to identify the predominantly oxidative (deep) and less oxidative (superficial) regions of the M. semitendinosus, and to determine total fibre number and proportions of fibre types. The results demonstrate that increased maternal nutrition alters skeletal muscle phenotype in the offspring by changing fibre-type proportions, leading to an increased oxidative capacity due to an increase in Type IIA fibres. No change in total muscle area, total muscle fibre number, or fibre cross-sectional area is observed. The precise molecular mechanism(s) by which these findings occur is being investigated. PMID:22444819

Markham, T C W; Latorre, R M; Lawlor, P G; Ashton, C J; McNamara, L B; Natter, R; Rowlerson, A; Stickland, N C

2009-07-01

284

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...

285

The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre size.  

PubMed

The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which regulates proliferation and apoptosis in organ development. YAP function has been extensively characterized in epithelial cells and tissues, but its function in adult skeletal muscle remains poorly defined. Here we show that YAP positively regulates basal skeletal muscle mass and protein synthesis. Mechanistically, we show that YAP regulates muscle mass via interaction with TEAD transcription factors. Furthermore, YAP abundance and activity in muscles is increased following injury or degeneration of motor nerves, as a process to mitigate neurogenic muscle atrophy. Our findings highlight an essential role for YAP as a positive regulator of skeletal muscle size. Further investigation of interventions that promote YAP activity in skeletal muscle might aid the development of therapeutics to combat muscle wasting and neuromuscular disorders. PMID:25581281

Watt, K I; Turner, B J; Hagg, A; Zhang, X; Davey, J R; Qian, H; Beyer, C; Winbanks, C E; Harvey, K F; Gregorevic, P

2015-01-01

286

Novel tissue culture method: skeletal muscle implantation under gizzard serous membrane of a chick.  

PubMed

A novel method for a long-term culture of skeletal muscle is described. Skeletal muscle pieces from young chicks were implanted under the gizzard serous membrane of the same chicks. Following muscle degeneration, new well-grouped muscle fibers were formed by the fusion of myocytes that differentiated from surviving satellite cells, and the regenerated muscle tissues were maintained in position for longer than 60 days. The implants were in the vital circulatory system, receiving trophic and oxygen supplies, and are completely free from motor nerve innervation and cell contamination with exogenous muscle cells, not as in intra-muscular implantation. Therefore, this tissue culture method should be useful for studying skeletal muscle regeneration and maturation over a long period. Furthermore, osteogenesis and feather development were also found in the implants of embryonic limbs by using the same method. These observations showed that not only skeletal muscle tissues but also other tissues could be cultured under the gizzard serous membrane. PMID:10766970

Nakada, K; Mishima, T; Miyazaki, J I; Hirabayashi, T

2000-05-01

287

Formation and optogenetic control of engineered 3D skeletal muscle bioactuators{  

E-print Network

Formation and optogenetic control of engineered 3D skeletal muscle bioactuators{ Mahmut Selman of mature, functional 3D muscle microtissues have been formed from the optogenetically encoded myoblasts manner. Our studies integrate tools from optogenetics and microelectromechanical systems (MEMS

Chen, Christopher S.

288

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); Dr. Peter D. Brodfuehrer (Bryn Mawr College Dept. of Biology); Dr. Beth L. Raughley (Bryn Mawr College Department of Biology)

2004-03-01

289

Skeletal muscle changes after hemiparetic stroke and potential beneficial effects of exercise intervention strategies.  

PubMed

Stroke is the leading cause of disability in the United States. New evidence reveals significant structural and metabolic changes in skeletal muscle after stroke. Muscle alterations include gross atrophy and shift to fast myosin heavy chain in the hemiparetic (contralateral) leg muscle; both are related to gait deficit severity. The underlying molecular mechanisms of this atrophy and muscle phenotype shift are not known. Inflammatory markers are also present in contralateral leg muscle after stroke. Individuals with stroke have a high prevalence of insulin resistance and diabetes. Skeletal muscle is a major site for insulin-glucose metabolism. Increasing evidence suggests that inflammatory pathway activation and oxidative injury could lead to wasting, altered function, and impaired insulin action in skeletal muscle. The health benefits of exercise in disabled populations have now been recognized. Aerobic exercise improves fitness, strength, and ambulatory performance in subjects with chronic stroke. Therapeutic exercise may modify or reverse skeletal muscle abnormalities. PMID:18566944

Hafer-Macko, Charlene E; Ryan, Alice S; Ivey, Frederick M; Macko, Richard F

2008-01-01

290

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

E-print Network

Anisotropy of ultrasonic propagation and scattering properties in fresh rat skeletal muscle frequency dependent information in the 4­14 MHz range. The attenuation coefficient in each muscle anisotropy. Anisotropy in ultrasonic parameters characterizing biological tissue has been reported

Illinois at Urbana-Champaign, University of

291

Chemokine-like receptor 1 regulates skeletal muscle cell myogenesis.  

PubMed

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

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

2012-06-01

292

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

293

Procedures for Rat in situ Skeletal Muscle Contractile Properties  

PubMed Central

There are many circumstances where it is desirable to obtain the contractile response of skeletal muscle under physiological circumstances: normal circulation, intact whole muscle, at body temperature. This includes the study of contractile responses like posttetanic potentiation, staircase and fatigue. Furthermore, the consequences of disease, disuse, injury, training and drug treatment can be of interest. This video demonstrates appropriate procedures to set up and use this valuable muscle preparation. To set up this preparation, the animal must be anesthetized, and the medial gastrocnemius muscle is surgically isolated, with the origin intact. Care must be taken to maintain the blood and nerve supplies. A long section of the sciatic nerve is cleared of connective tissue, and severed proximally. All branches of the distal stump that do not innervate the medial gastrocnemius muscle are severed. The distal nerve stump is inserted into a cuff lined with stainless steel stimulating wires. The calcaneus is severed, leaving a small piece of bone still attached to the Achilles tendon. Sonometric crystals and/or electrodes for electromyography can be inserted. Immobilization by metal probes in the femur and tibia prevents movement of the muscle origin. The Achilles tendon is attached to the force transducer and the loosened skin is pulled up at the sides to form a container that is filled with warmed paraffin oil. The oil distributes heat evenly and minimizes evaporative heat loss. A heat lamp is directed on the muscle, and the muscle and rat are allowed to warm up to 37°C. While it is warming, maximal voltage and optimal length can be determined. These are important initial conditions for any experiment on intact whole muscle. The experiment may include determination of standard contractile properties, like the force-frequency relationship, force-length relationship, and force-velocity relationship. With care in surgical isolation, immobilization of the origin of the muscle and alignment of the muscle-tendon unit with the force transducer, and proper data analysis, high quality measurements can be obtained with this muscle preparation. PMID:22025076

MacIntosh, Brian R.; Esau, Shane P.; Holash, R. John; Fletcher, Jared R.

2011-01-01

294

Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy?  

PubMed

Exercise-induced muscle damage (EIMD) occurs primarily from the performance of unaccustomed exercise, and its severity is modulated by the type, intensity, and duration of training. Although concentric and isometric actions contribute to EIMD, the greatest damage to muscle tissue is seen with eccentric exercise, where muscles are forcibly lengthened. Damage can be specific to just a few macromolecules of tissue or result in large tears in the sarcolemma, basal lamina, and supportive connective tissue, and inducing injury to contractile elements and the cytoskeleton. Although EIMD can have detrimental short-term effects on markers of performance and pain, it has been hypothesized that the associated skeletal muscle inflammation and increased protein turnover are necessary for long-term hypertrophic adaptations. A theoretical basis for this belief has been proposed, whereby the structural changes associated with EIMD influence gene expression, resulting in a strengthening of the tissue and thus protection of the muscle against further injury. Other researchers, however, have questioned this hypothesis, noting that hypertrophy can occur in the relative absence of muscle damage. Therefore, the purpose of this article will be twofold: (a) to extensively review the literature and attempt to determine what, if any, role EIMD plays in promoting skeletal muscle hypertrophy and (b) to make applicable recommendations for resistance training program design. PMID:22344059

Schoenfeld, Brad J

2012-05-01

295

Soleus muscles of SAMP8 mice provide an accelerated model of skeletal muscle senescence.  

PubMed

Animal models are valuable research tools towards effective prevention of sarcopenia and towards a better understanding of the mechanisms underlying skeletal muscle aging. We investigated whether senescence-accelerated mouse (SAM) strains provide valid models for skeletal muscle aging studies. Male senescence-prone mice SAMP6 and SAMP8 were studied at age 10, 25 and 60 weeks and compared with senescence-resistant strain, SAMR1. Soleus and EDL muscles were tested for in vitro contractile properties, phosphocreatine content, muscle mass and fiber-type distribution. Declined muscle mass and contractility were observed at 60 weeks, the differences being more pronounced in SAMP8 than SAMP6 and more pronounced in soleus than EDL. Likewise, age-related decreases in muscle phosphocreatine content and type-II fiber size were most pronounced in SAMP8 soleus. In conclusion, typical features of muscular senescence occur at relatively young age in SAMP8 and nearly twice as fast as compared with other models. We suggest that soleus muscles of SAMP8 mice provide a cost-effective model for muscular aging studies. PMID:16023814

Derave, Wim; Eijnde, Bert O; Ramaekers, Monique; Hespel, Peter

2005-07-01

296

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

297

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

298

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

299

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

300

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

301

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

302

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

303

Further considerations on in vitro skeletal muscle cell death  

PubMed Central

Summary 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

2013-01-01

304

Regulatory circuitry of TWEAK-Fn14 system and PGC-1? in skeletal muscle atrophy program.  

PubMed

Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1? preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1? and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1? and mitochondrial content (?50%) in skeletal muscle. Levels of PGC-1? are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1? inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1? inhibited the TWEAK-induced activation of NF-?B (?50%) and dramatically reduced (?90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1? also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1?. Overexpression of PGC-1? not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle. PMID:24327607

Hindi, Sajedah M; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M; Ogura, Yuji; Yan, Zhen; Burkly, Linda C; Zheng, Timothy S; Kumar, Ashok

2014-03-01

305

Journal of Biomechanics 35 (2002) 657663 Skeletal muscle is sensitive to the tensiontime integral but not to the  

E-print Network

Journal of Biomechanics 35 (2002) 657­663 Skeletal muscle is sensitive to the tension­time integral. In skeletal muscle, mechanical forces have a major impact on the regulation of cellular volume, yet the nature

Manitoba, University of

306

Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4 dependent pathway  

E-print Network

Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber.108 #12;2 Abstract Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved cell mobilization and skeletal muscle fiber regeneration via a paracrine Wnt dependent mechanism

Paris-Sud XI, Université de

307

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

308

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

309

Nutritional and hormonal regulation of energy metabolism in skeletal muscles of meat-producing animals  

Microsoft Academic Search

In meat-producing animals, skeletal muscle is a tissue of major economic importance. Energy metabolism of skeletal muscle should be assessed in relation to its main physiological functions which are growth as well as posture, physical activity and thermogenesis. These functions have specific energy requirements which may entail competition in the utilization of energy-yielding nutrients, and modify the efficiency of ATP

J. F Hocquette; I Ortigues-Marty; D Pethick; P Herpin; X Fernandez

1998-01-01

310

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

Microsoft Academic Search

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

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

2007-01-01

311

Skeletal muscle apoptosis is not increased in gastric cancer patients with mild–moderate weight loss  

Microsoft Academic Search

Numerous experimental and clinical studies have shown that skeletal muscle apoptotis may increase in wasting conditions and suggest that apoptosis might contribute to the loss of lean body mass. Data in cancer patients are still lacking.The present study aimed at verifying whether apoptosis was enhanced in the skeletal muscle of 16 patients with gastric cancer with respect to controls. A

Maurizio Bossola; Massimiliano Mirabella; Enzo Ricci; Paola Costelli; Fabio Pacelli; Antonio Pio Tortorelli; Maurizio Muscaritoli; Filippo Rossi Fanelli; Francesco Maria Baccino; Pietro Attilio Tonali; Giovan Battista Doglietto

2006-01-01

312

ADIPOCYTE DIFFERENTIATION-RELATED PROTEIN IN HUMAN SKELETAL MUSCLE: RELATIONSHIP TO INSULIN SENSITIVITY  

Technology Transfer Automated Retrieval System (TEKTRAN)

To determine whether adipocyte differentiation-related protein (ADRP), a lipid droplet-associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non-diabetic (OND) a...

313

Hormonal regulation of skeletal muscle hypertrophy in rats: the testosterone to cortisol ratio  

Microsoft Academic Search

This study determined the influence that the catabolic hormone, corticosterone (C), and the anabolic hormone, testosterone (T), had in regulating skeletal muscle hypertrophy using the rat hind limb ablation model. Specifically, the ratio of T : C (TCR) was manipulated via hormone implants and injections and concentrations measured to evaluate the relative contribution of each hormone to skeletal muscle protein

Michael A. Crowley; Kathleen S. Matt

1996-01-01

314

Advanced Glycation End Product in Diabetic Rat Skeletal Muscle in vivo  

Microsoft Academic Search

Background: Advanced glycation end products (AGEs) are implicated in the etiology of diabetic complications in the kidney, nerve and eye. Skeletal muscle contractile parameters have also been found to be altered in diabetes. Glycation has not been extensively studied in skeletal muscle, but AGE-modified proteins may influence contractility. Objective and Methods: The aim of this study was to use immunohistochemistry

LeAnn M. Snow; Christa B. Lynner; Erin M. Nielsen; Hillari S. Neu; LaDora V. Thompson

2006-01-01

315

Adenosine A3 receptor stimulation induces protection of skeletal muscle from eccentric exercise-mediated injury  

E-print Network

Adenosine A3 receptor stimulation induces protection of skeletal muscle from eccentric exercise of skeletal muscle from eccentric exercise-mediated injury. Am J Physiol Regul Integr Comp Physiol 299: R259­R267, 2010. First published April 28, 2010; doi:10.1152/ajpregu.00060.2010.--Effective therapy

Campbell, Kevin P.

316

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

E-print Network

Cloning and characterization of fiber type-specific ryanodine receptor isoforms in skeletal muscles. Block. Cloning and characterization of fiber type-specific ryanodine receptor isoforms in skeletal muscles of fish. Am. J. Physiol. 275 (Cell Physiol. 44): C401­C415, 1998.--We have cloned a group of c

Block, Barbara A.

317

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

318

Postnatal changes in insulin binding in slow and fast-twitch rabbit skeletal muscles  

E-print Network

muscles and did not change with age. The numbers of receptors were similar in both muscles at birth). The high affinity constant (Kd) was about 0.15 10-9 M in both muscles and dit not change with #12;agePostnatal changes in insulin binding in slow and fast-twitch rabbit skeletal muscles L. LEFAUCHEUR

Boyer, Edmond

319

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...

320

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

321

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

322

Chitinase-3-like protein 1 protects skeletal muscle from TNF?-induced inflammation and insulin resistance.  

PubMed

CHI3L1 (chitinase-3-like protein 1) is a glycoprotein consisting of 383 amino acids with a molecular mass of 40 kDa, and its serum level is elevated in inflammatory diseases. Although CHI3L1 is described as a biomarker of inflammation, the function of this protein is not completely understood. In the present study, we examined the regulation of CHI3L1 in primary human skeletal muscle cells. Moreover, we analysed potential autocrine effects of CHI3L1. We show that myotubes express CHI3L1 in a differentiation-dependent manner. Furthermore, pro-inflammatory cytokines up-regulate CHI3L1 expression (6-fold) and release (3-fold). Importantly, CHI3L1 treatment blocked TNF? (tumour necrosis factor ?)-induced inflammation by inhibiting NF-?B (nuclear factor ?B) activation in skeletal muscle cells. We show that this effect is mediated via PAR2 (protease-activated receptor 2). In addition, CHI3L1 treatment diminished the TNF?-induced expression and secretion of IL (interleukin)-8, MCP1 (monocyte chemoattractant protein 1) and IL-6. In addition, impaired insulin action at the level of Akt and GSK3?/? (glycogen synthase kinase 3?/?) phosphoryl-ation and insulin-stimulated glucose uptake was normalized by CHI3L1. In conclusion, the novel myokine CHI3L1, which is induced by pro-inflammatory cytokines, can counteract TNF?-mediated inflammation and insulin resistance in human skeletal muscle cells, potentially involving an auto- and/or para-crine mechanism. PMID:24512683

Görgens, Sven W; Eckardt, Kristin; Elsen, Manuela; Tennagels, Norbert; Eckel, Jürgen

2014-05-01

323

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

324

Functional and histological characteristics of skeletal muscle and the effects of leptin in the genetically obese (ob\\/ob) mouse  

Microsoft Academic Search

BACKGROUND: Skeletal muscle mass in genetically obese (ob\\/ob) mice displays a reduced mass compared with their normal lean counterpart mice. However, the functional capacity of the available skeletal muscle mass in these animals has not yet been determined.OBJECTIVE: To investigate the properties of skeletal muscle in ob\\/ob mice and determine the effects of leptin administration on skeletal muscle in these

SA Warmington; R Tolan; S McBennett

2000-01-01

325

Deletion of Skeletal Muscle SOCS3 Prevents Insulin Resistance in Obesity  

PubMed Central

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance. PMID:22961088

Jorgensen, Sebastian Beck; O’Neill, Hayley M.; Sylow, Lykke; Honeyman, Jane; Hewitt, Kimberly A.; Palanivel, Rengasamy; Fullerton, Morgan D.; Öberg, Lisa; Balendran, Anudharan; Galic, Sandra; van der Poel, Chris; Trounce, Ian A.; Lynch, Gordon S.; Schertzer, Jonathan D.; Steinberg, Gregory R.

2013-01-01

326

Caffeine-induced Release of Intracellular Ca2+ from Chinese Hamster Ovary Cells Expressing Skeletal Muscle Ryanodine Receptor  

PubMed Central

The ryanodine receptor (RyR)/Ca2+ release channel is an essential component of excitation–contraction coupling in striated muscle cells. To study the function and regulation of the Ca2+ release channel, we tested the effect of caffeine on the full-length and carboxyl-terminal portion of skeletal muscle RyR expressed in a Chinese hamster ovary (CHO) cell line. Caffeine induced openings of the full length RyR channels in a concentration-dependent manner, but it had no effect on the carboxyl-terminal RyR channels. CHO cells expressing the carboxyl-terminal RyR proteins displayed spontaneous changes of intracellular [Ca2+]. Unlike the native RyR channels in muscle cells, which display localized Ca2+ release events (i.e., “Ca2+ sparks” in cardiac muscle and “local release events” in skeletal muscle), CHO cells expressing the full length RyR proteins did not exhibit detectable spontaneous or caffeine-induced local Ca2+ release events. Our data suggest that the binding site for caffeine is likely to reside within the amino-terminal portion of RyR, and the localized Ca2+ release events observed in muscle cells may involve gating of a group of Ca2+ release channels and/or interaction of RyR with muscle-specific proteins. PMID:9382901

Bhat, Manjunatha B.; Zhao, Jiying; Zang, Weijin; Balke, C. William; Takeshima, Hiroshi; Wier, W. Gil; Ma, Jianjie

1997-01-01

327

FOXO1 activates glutamine synthetase gene in mouse skeletal muscles through a region downstream of 3'-UTR: possible contribution to ammonia detoxification.  

PubMed

Skeletal muscle is a reservoir of energy in the form of protein, which is degraded under catabolic conditions, resulting in the formation of amino acids and ammonia as a byproduct. The expression of FOXO1, a forkhead-type transcription factor, increases during starvation and exercise. In agreement, transgenic FOXO1-Tg mice that overexpress FOXO1 in skeletal muscle exhibit muscle atrophy. The aim of this study was to examine the role of FOXO1 in amino acid metabolism. The mRNA and protein expressions of glutamine synthetase (GS) were increased in skeletal muscle of FOXO1-Tg mice. Fasting induced FOXO1 and GS expression in wild-type mice but hardly increased GS expression in muscle-specific FOXO1 knockout (FOXO1-KO) mice. Activation of FOXO1 also increased GS mRNA and protein expression in C2C12 myoblasts. Using a transient transfection reporter assay, we observed that FOXO1 activated the GS reporter construct. Mutation of a putative FOXO1-binding consensus sequence in the downstream genomic region of GS decreased basal and FOXO1-dependent reporter activity significantly. A chromatin immunoprecipitation assay showed that FOXO1 was recruited to the 3' region of GS in C2C12 myoblasts. These results suggest that FOXO1 directly upregulates GS expression. GS is considered to mediate ammonia clearance in skeletal muscle. In agreement, an intravenous ammonia challenge increased blood ammonia concentrations to a twofold higher level in FOXO1-KO than in wild-type mice, demonstrating that the capacity for ammonia disposal correlated inversely with the expression of GS in muscle. These data indicate that FOXO1 plays a role in amino acid metabolism during protein degradation in skeletal muscle. PMID:25074987

Kamei, Yasutomi; Hattori, Maki; Hatazawa, Yukino; Kasahara, Tomomi; Kanou, Masanobu; Kanai, Sayaka; Yuan, Xunmei; Suganami, Takayoshi; Lamers, Wouter H; Kitamura, Tadahiro; Ogawa, Yoshihiro

2014-09-15

328

Exercise restores skeletal muscle glucose delivery but not insulin-mediated glucose transport and phosphorylation in obese subjects  

E-print Network

/Objective: Insulin resistance in obese subjects results in the impaired disposal of glucose by skeletal muscle]FDG) in resting and isometrically exercising skeletal muscle during normoglycemic hyperinsulinemia. Data were resistance in obese subjects results in an impaired use of glucose by skeletal muscle [1,2]; it is a strong

Paris-Sud XI, Université de

329

Roles of nonmyogenic mesenchymal progenitors in pathogenesis and regeneration of skeletal muscle  

PubMed Central

Adult skeletal muscle possesses a remarkable regenerative ability that is dependent on satellite cells. However, skeletal muscle is replaced by fatty and fibrous connective tissue in several pathological conditions. Fatty and fibrous connective tissue becomes a major cause of muscle weakness and leads to further impairment of muscle function. Because the occurrence of fatty and fibrous connective tissue is usually associated with severe destruction of muscle, the idea that dysregulation of the fate switch in satellite cells may underlie this pathological change has emerged. However, recent studies identified nonmyogenic mesenchymal progenitors in skeletal muscle and revealed that fatty and fibrous connective tissue originates from these progenitors. Later, these progenitors were also demonstrated to be the major contributor to heterotopic ossification in skeletal muscle. Because nonmyogenic mesenchymal progenitors represent a distinct cell population from satellite cells, targeting these progenitors could be an ideal therapeutic strategy that specifically prevents pathological changes of skeletal muscle, while preserving satellite cell-dependent regeneration. In addition to their roles in pathogenesis of skeletal muscle, nonmyogenic mesenchymal progenitors may play a vital role in muscle regeneration by regulating satellite cell behavior. Conversely, muscle cells appear to regulate behavior of nonmyogenic mesenchymal progenitors. Thus, these cells regulate each other reciprocally and a proper balance between them is a key determinant of muscle integrity. Furthermore, nonmyogenic mesenchymal progenitors have been shown to maintain muscle mass in a steady homeostatic condition. Understanding the nature of nonmyogenic mesenchymal progenitors will provide valuable insight into the pathophysiology of skeletal muscle. In this review, we focus on nonmyogenic mesenchymal progenitors and discuss their roles in muscle pathogenesis, regeneration, and homeostasis. PMID:24605102

Uezumi, Akiyoshi; Ikemoto-Uezumi, Madoka; Tsuchida, Kunihiro

2014-01-01

330

Evidence for a Role of the Lumenal M3-M4 Loop in Skeletal Muscle Ca 2+ Release Channel (Ryanodine Receptor) Activity and Conductance  

Microsoft Academic Search

We tested the hypothesis that part of the lumenal amino acid segment between the two most C-terminal membrane segments of the skeletal muscle ryanodine receptor (RyR1) is important for channel activity and conductance. Eleven mutants were generated and expressed in HEK293 cells focusing on amino acid residue I4897 homologous to the selectivity filter of K+ channels and six other residues

Ling Gao; David Balshaw; Le Xu; Ashutosh Tripathy; Chunlin Xin; Gerhard Meissner

2000-01-01

331

Responses of skeletal muscle to unloading, a review  

NASA Technical Reports Server (NTRS)

Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.

Tischler, M. E.; Jaspers, S. R.; Henriksen, E. J.; Jacob, S.

1985-01-01

332

Responses of skeletal muscle to unloading - A review  

NASA Technical Reports Server (NTRS)

Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.

Tischler, M. E.; Jaspers, S. R.; Henriksen, E. J.; Jacob, S.

1985-01-01

333

Short-term starvation decreases skeletal muscle protein synthesis rate in man.  

PubMed

The rate of protein synthesis in skeletal muscle was determined in the post-absorptive state and after 3 days of starvation in healthy volunteers. The flooding dose technique employing intravenous injection of (1-13C)leucine (0.05 g kg-1) was used and incorporation of isotope into muscle protein was measured by taking percutaneous biopsies at 0 and 90 min. Blood samples were taken during the incorporation period for assessment of the enrichment of the free amino acid precursor of protein synthesis. The median (25,75 quartiles) rate of muscle protein synthesis after an overnight fast was 2.03 (2.00,2.23) % days-1 when the precursor enrichment was obtained by measurement of the plasma alpha-ketoisocaproate, taken to be representative of muscle free leucine. Repeat measurements in the same subjects after 3 days of total starvation showed a decrease to 1.82 (1.57,2.05) % days-1. Rates calculated on the basis of the plasma leucine as precursor were 5% lower at both times. An interindividual variation in response to starvation was observed, but the median decrease of 13% in the rate of protein synthesis was statistically significant (P less than 0.01). PMID:1606811

Essén, P; McNurlan, M A; Wernerman, J; Milne, E; Vinnars, E; Garlick, P J

1992-05-01

334

De novo prion aggregates trigger autophagy in skeletal muscle.  

PubMed

In certain sporadic, familial, and infectious prion diseases, the prion protein misfolds and aggregates in skeletal muscle in addition to the brain and spinal cord. In myocytes, prion aggregates accumulate intracellularly, yet little is known about clearance pathways. Here we investigated the clearance of prion aggregates in muscle of transgenic mice that develop prion disease de novo. In addition to neurodegeneration, aged mice developed a degenerative myopathy, with scattered myocytes containing ubiquitinated, intracellular prion inclusions that were adjacent to myocytes lacking inclusions. Myocytes also showed elevated levels of the endoplasmic reticulum chaperone Grp78/BiP, suggestive of impaired protein degradation and endoplasmic reticulum stress. Additionally, autophagy was induced, as indicated by increased levels of beclin-1 and LC3-II. In C2C12 myoblasts, inhibition of autophagosome maturation or lysosomal degradation led to enhanced prion aggregation, consistent with a role for autophagy in prion aggregate clearance. Taken together, these findings suggest that the induction of autophagy may be a central strategy for prion aggregate clearance in myocytes. IMPORTANCE In prion diseases, the prion protein misfolds and aggregates in the central nervous system and sometimes in other organs, including muscle, yet the cellular pathways of prion aggregate clearance are unclear. Here we investigated the clearance of prion aggregates in the muscle of a transgenic mouse model that develops profound muscle degeneration. We found that endoplasmic reticulum stress pathways were activated and that autophagy was induced. Blocking of autophagic degradation in cell culture models led to an accumulation of aggregated prion protein. Collectively, these findings suggest that autophagy has an instrumental role in prion protein clearance. PMID:24307586

Joshi-Barr, Shivanjali; Bett, Cyrus; Chiang, Wei-Chieh; Trejo, Margarita; Goebel, Hans H; Sikorska, Beata; Liberski, Pawel; Raeber, Alex; Lin, Jonathan H; Masliah, Eliezer; Sigurdson, Christina J

2014-02-01

335

Phosphorescence quenching microrespirometry of skeletal muscle in situ  

PubMed Central

We have developed an optical method for the evaluation of the oxygen consumption (V?o2) in microscopic volumes of spinotrapezius muscle. Using phosphorescence quenching microscopy (PQM) for the measurement of interstitial Po2, together with rapid pneumatic compression of the organ, we recorded the oxygen disappearance curve (ODC) in the muscle of the anesthetized rats. A 0.6-mm diameter area in the tissue, preloaded with the phosphorescent oxygen probe, was excited once a second by a 532-nm Q-switched laser with pulse duration of 15 ns. Each of the evoked phosphorescence decays was analyzed to obtain a sequence of Po2 values that constituted the ODC. Following flow arrest and tissue compression, the interstitial Po2 decreased rapidly and the initial slope of the ODC was used to calculate the V?o2. Special analysis of instrumental factors affecting the ODC was performed, and the resulting model was used for evaluation of V?o2. The calculation was based on the observation of only a small amount of residual blood in the tissue after compression. The contribution of oxygen photoconsumption by PQM and oxygen inflow from external sources was evaluated in specially designed tests. The average oxygen consumption of the rat spinotrapezius muscle was V?o2 = 123.4 ± 13.4 (SE) nl O2/cm3·s (N = 38, within 6 muscles) at a baseline interstitial Po2 of 50.8 ± 2.9 mmHg. This technique has opened the opportunity for monitoring respiration rates in microscopic volumes of functioning skeletal muscle. PMID:20971766

Golub, Aleksander S.; Tevald, Michael A.

2011-01-01

336

Can changes in microcirculation explain capillary growth in skeletal muscle?  

PubMed Central

Capillary growth (increase in capillary/fibre (C/F) ratio by 20%) was elicited in skeletal muscles either by long-term increase in blood flow (5 weeks administration of prazosin in drinking water, 50 mg/l) or 7 days electrical stimulation (8 h/day at 10 Hz). Mechanisms that could explain it ((a) increased interaction of blood components with endothelial cells (due to increased haematocrit or decreased intermittency of flow); (b) increased velocity of flow and thus shear stress; (c) increased capillary diameters and thus wall tension) were studied in vivo. Red blood cell velocity (Vrbc), vessel diameters and intermittency of capillary flow were measured in superficially located capillaries in rat tibialis anterior muscles about 18 hours after the last treatment, in prazosin treated and chronically stimulated animals, and also in animals where red blood cell interaction with capillary endothelium was increased by elevating haematocrit from 43.2 +/- 1.7% to 60.9 +/- 0.72% by 11 weeks administration of CoCl2. Animals of comparable size and sex were used as controls. Capillaries in chronically stimulated muscles had increased Vrbc at rest (0.42 +/- 0.06 mm/s vs 0.27 +/- 0.04 in control muscles) and somewhat wider diameters, although the intermittency of flow was not different from control muscles. Capillaries in prazosin treated rats had a lower intermittency of flow, similar diameters and considerably higher Vrbc (0.53 +/- 0.06 mm/s) than control animals. CoCl2 treatment resulted in a similar intermittency of flow, did not alter capillary diameters or Vrbc and did not result in an increase in C/F ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8471536

Dawson, J. M.; Hudlicka, O.

1993-01-01

337

Uncoupled skeletal muscle mitochondria contribute to hypermetabolism in severely burned adults.  

PubMed

Elevated metabolic rate is a hallmark of the stress response to severe burn injury. This response is mediated in part by adrenergic stress and is responsive to changes in ambient temperature. We hypothesize that uncoupling of oxidative phosphorylation in skeletal muscle mitochondria contributes to increased metabolic rate in burn survivors. Here, we determined skeletal muscle mitochondrial function in healthy and severely burned adults. Indirect calorimetry was used to estimate metabolic rate in burn patients. Quadriceps muscle biopsies were collected on two separate occasions (11 ± 5 and 21 ± 8 days postinjury) from six severely burned adults (68 ± 19% of total body surface area burned) and 12 healthy adults. Leak, coupled, and uncoupled mitochondrial respiration was determined in permeabilized myofiber bundles. Metabolic rate was significantly greater than predicted values for burn patients at both time points (P < 0.05). Skeletal muscle oxidative capacity, citrate synthase activity, a marker of mitochondrial abundance, and mitochondrial sensitivity to oligomycin were all lower in burn patients vs. controls at both time points (P < 0.05). A greater proportion of maximal mitochondrial respiration was linked to thermogenesis in burn patients compared with controls (P < 0.05). Increased metabolic rate in severely burned adults is accompanied by derangements in skeletal muscle mitochondrial function. Skeletal muscle mitochondria from burn victims are more uncoupled, indicating greater heat production within skeletal muscle. Our findings suggest that skeletal muscle mitochondrial dysfunction contributes to increased metabolic rate in burn victims. PMID:25074988

Porter, Craig; Herndon, David N; Børsheim, Elisabet; Chao, Tony; Reidy, Paul T; Borack, Michael S; Rasmussen, Blake B; Chondronikola, Maria; Saraf, Manish K; Sidossis, Labros S

2014-09-01

338

CYTOLOGICAL STUDIES OF FIBER TYPES IN SKELETAL MUSCLE  

PubMed Central

A comparative investigation of the mammalian diaphragm has revealed a correlation between certain cytological aspects of red and white muscle fibers and functional activity. This skeletal muscle presents the advantage of a similar and constant function among the mammals, but its functional activity varies in a quantitative manner. Both the rate of breathing (and hence the rate of contraction of the diaphragm) and metabolic activity are known to be inversely related to body size; and this study has demonstrated a relationship between cytological characteristics of the diaphragm and body size of the animal. Small fibers rich in mitochondria (red fibers) are characteristic of small mammals, which have high metabolic activity and fast breathing rates; and large fibers with relatively low mitochondrial content predominate in large mammals, which have lower metabolic activity and slower breathing rates. In mammals with body size intermediate between these two groups (including the laboratory rat), the diaphragm consists of varying mixtures of fiber types. In general, the mitochondrial content of diaphragm fibers is inversely related to body size. It appears, then, that the red fiber reflects a high degree of metabolic activity or a relatively high rate of contraction within the range exhibited by this muscle. PMID:5950272

Gauthier, Geraldine F.; Padykula, Helen A.

1966-01-01

339

Systemic immunological effects of cytokine genes injected into skeletal muscle.  

PubMed Central

Somatic gene therapy is an interesting approach for the delivery of cytokines for prolonged periods. The present experiments show that direct injections into mouse skeletal muscle of cDNA expression vectors encoding interleukin 2 (IL-2), IL-4, or type beta 1 transforming growth factor (TGF-beta 1) induce biological effects characteristic of these cytokines in vivo. Mice injected intramuscularly with a vector encoding IL-2 had enhanced humoral and cellular immune responses to an exogenous antigen, transferrin, that was delivered at a separate site. These IL-2 effects were abolished by coadministration of a vector directing synthesis of TGF-beta 1. The TGF-beta 1 vector by itself depressed the anti-transferrin antibody response and caused an 8-fold increase in plasma TGF-beta 1 activity. The TGF-beta 1 plasmid injection did not cause muscle infiltration with monocytes or neutrophils and there was no evidence for fibrotic changes. Muscle injection with a cDNA encoding IL-4 selectively increased IgG1 levels but did not alter the cellular immune response to transferrin. In lupus-prone mice (MRL/lpr/lpr), injection with IL-2 expression vectors increased and TGF-beta 1 vectors decreased auto-antibodies to chromatin. These results demonstrate that intramuscular injection of cytokine genes, in the absence of infectious viral vectors, can regulate humoral and cellular immune responses in vivo. PMID:8506293

Raz, E; Watanabe, A; Baird, S M; Eisenberg, R A; Parr, T B; Lotz, M; Kipps, T J; Carson, D A

1993-01-01

340

Metabolic and structural changes in skeletal muscle during hypocaloricdieting1'2  

Microsoft Academic Search

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal\\/day) followed by a repeat biopsy after 2 wk of a 400-kcal\\/day carbohydrate diet. Hypocaloric

David McR; MBBS Russell; Paul M Walker; Lawrence A Leiter; Anders AF Sima; Wayne K Tanner; Donald AG Mickle; Jocelyn Whitwell; Errol B Marliss; Khursheed N Jeejeebhoy

341

Systems biology of skeletal muscle: fiber type as an organizing principle.  

PubMed

Skeletal muscle force generation and contraction are fundamental to countless aspects of human life. The complexity of skeletal muscle physiology is simplified by fiber type classification where differences are observed from neuromuscular transmission to release of intracellular Ca(2+) from the sarcoplasmic reticulum and the resulting recruitment and cycling of cross-bridges. This review uses fiber type classification as an organizing and simplifying principle to explore the complex interactions between the major proteins involved in muscle force generation and contraction. PMID:22811254

Greising, Sarah M; Gransee, Heather M; Mantilla, Carlos B; Sieck, Gary C

2012-01-01

342

Systems Biology of Skeletal Muscle: Fiber Type as an Organizing Principle  

PubMed Central

Skeletal muscle force generation and contraction are fundamental to countless aspects of human life. The complexity of skeletal muscle physiology is simplified by fiber type classification where differences are observed from neuromuscular transmission to release of intracellular Ca2+ from the sarcoplasmic reticulum and the resulting recruitment and cycling of cross-bridges. This review uses fiber type classification as an organizing and simplifying principle to explore the complex interactions between the major proteins involved in muscle force generation and contraction. PMID:22811254

Greising, Sarah M; Gransee, Heather M; Mantilla, Carlos B; Sieck, Gary C

2012-01-01

343

Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis  

Microsoft Academic Search

In skeletal muscle homogenates of 14 patients with sporadic amyotrophic lateral sclerosis, an approximately twofold lower specific activity of NADH:CoQ oxidoreductase in comparison to an age matched control group (n=28) was detected. This finding was confirmed by a detailed analysis of mitochondrial oxidative phosphorylation in skeletal muscle using saponin-permeabilized muscle fibers. (i) A significantly lowered maximal glutamate+malate and pyruvate+malate supported

Falk R Wiedemann; Kirstin Winkler; Andrey V Kuznetsov; Claudius Bartels; Stefan Vielhaber; Helmut Feistner; Wolfram S Kunz

1998-01-01

344

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.  

PubMed

Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals. PMID:24166991

Jiang, H; Ge, X

2014-01-01

345

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.  

PubMed

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function. PMID:23488938

Grant, R W; Vester Boler, B M; Ridge, T K; Graves, T K; Swanson, K S

2013-08-01

346

Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle.  

PubMed Central

Previous studies provided evidence that sepsis-induced muscle proteolysis in experimental animals is caused by increased ubiquitin-proteasome-dependent protein breakdown. It is not known if a similar mechanism accounts for muscle proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and the 20 S proteasome subunit HC3 by Northern blot analysis in muscle tissue from septic (n = 7) and non-septic (n = 11) patients. Plasma and muscle amino acid concentrations and concentrations in urine of 3-methylhistidine (3-MH), creatinine, and cortisol were measured at the time of surgery to assess the catabolic state of the patients. A three- to fourfold increase in mRNA levels for ubiquitin and HC3 was noted in muscle tissue from the septic patients concomitant with increased muscle levels of phenylalanine and 3-MH and reduced levels of glutamine. Total plasma amino acids were decreased by approximately 30% in the septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic patients. The cortisol levels in urine were higher in septic than in control patients but this difference did not reach statistical significance. The results suggest that sepsis is associated with increased mRNAs of the ubiquitin-proteasome pathway in human skeletal muscle. PMID:9005983

Tiao, G; Hobler, S; Wang, J J; Meyer, T A; Luchette, F A; Fischer, J E; Hasselgren, P O

1997-01-01

347

Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.  

PubMed

Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs. PMID:24319010

Duffy, Rebecca M; Feinberg, Adam W

2014-01-01

348

Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells  

PubMed Central

Cumulative evidence indicates that Wnt pathways play crucial and diverse roles to assemble the neuromuscular junction (NMJ), a peripheral synapse characterized by the clustering of acetylcholine receptors (AChR) on postsynaptic densities. The molecular determinants of Wnt effects at the NMJ are still to be fully elucidated. We report here that the Wnt receptor Frizzled-9 (Fzd9) is expressed in developing skeletal muscles during NMJ synaptogenesis. In cultured myotubes, gain- and loss-of-function experiments revealed that Fzd9-mediated signaling impairs the AChR-clustering activity of agrin, an organizer of postsynaptic differentiation. Overexpression of Fzd9 induced the cytosolic accumulation of ?-catenin, a key regulator of Wnt signaling. Consistently, Fzd9 and ?-catenin localize in the postsynaptic domain of embryonic NMJs in vivo. Our findings represent the first evidence pointing to a crucial role of a Fzd-mediated, ?-catenin-dependent signaling on the assembly of the vertebrate NMJ. PMID:24860427

Avilés, Evelyn C.; Pinto, Cristina; Hanna, Patricia; Ojeda, Jorge; Pérez, Viviana; De Ferrari, Giancarlo V.; Zamorano, Pedro; Albistur, Miguel; Sandoval, Daniel; Henríquez, Juan P.

2014-01-01

349

Bench to Bedside Primer: Skeletal Muscle and Sarcopenia  

NSDL National Science Digital Library

This bench-to-bedside is a four-page ÃÂprimerÃÂ (a booklet of basic principles) that highlights skeletal muscle physiology. This primer should be readable by your students or the general public to help inform them about the organ system, diseases that affect it, and basic and clinical research being done on it. It could also be used as a teaching model your students could follow in creating their own bench-to-beside primer.This teaching resource was developed by a K-12 science teacher in the American Physiological SocietyÃÂs 2011 Frontiers Online in Physiology Program. For more information on this program, please visit www.frontiersinphys.org.

Daniel Bartsch (Billings Senior High School)

2011-10-07

350

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats.  

PubMed

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand. PMID:12649071

Frisbee, Jefferson C

2003-07-01

351

The determinants of transverse tubular volume in resting skeletal muscle  

PubMed Central

The transverse tubular (t)-system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis and disruption of excitation–contraction coupling. However, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF?t-system?sarcoplasm?ECF that ultimately depends on Na+/K+-ATPase activity. Membrane properties that maximize this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na+/K+-ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume. PMID:25384782

Sim, Jingwei; Fraser, James A

2014-01-01

352

The determinants of transverse tubular volume in resting skeletal muscle.  

PubMed

The transverse tubular (t)-system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis and disruption of excitation-contraction coupling. However, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF?t-system?sarcoplasm?ECF that ultimately depends on Na(+)/K(+)-ATPase activity. Membrane properties that maximize this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na(+)/K(+)-ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume. PMID:25384782

Sim, Jingwei; Fraser, James A

2014-12-15

353

Integration of signals generated by nutrients, hormones, and exercise in skeletal muscle1234  

PubMed Central

This review focuses on anabolic signaling pathways through which insulin, amino acids, and resistance exercise act to regulate the protein kinase complex referred to as mechanistic target of rapamycin complex (mTORC) 1. Initially, individual pathways through which the 3 anabolic signals act to modulate mTORC1 signaling will be discussed, followed by a summation of evidence showing an additive effect of the regulators. The emphasis will be on mTORC1 signaling in skeletal muscle and its contribution to modulation of rates of protein synthesis. In addition, results from studies using cells in culture will be used to provide a more complete picture of the molecular details of the individual pathways. PMID:24284445

Kimball, Scot R

2014-01-01

354

Extracting skeletal muscle fiber fields from noisy diffusion tensor data.  

PubMed

Diffusion Tensor Imaging (DTI) allows the non-invasive study of muscle fiber architecture but musculoskeletal DTI suffers from low signal-to-noise ratio. Noise in the computed tensor fields can lead to poorly reconstructed muscle fiber fields. This paper describes an algorithm for producing denoised muscle fiber fields from noisy diffusion tensor data as well as its preliminary validation. The algorithm computes a denoised vector field by finding the components of its Helmholtz-Hodge decomposition that optimally match the diffusion tensor field. A key feature of the algorithm is that it performs denoising of the vector field simultaneously with its extraction from the noisy tensor field. This allows the vector field reconstruction to be constrained by the architectural properties of skeletal muscles. When compared to primary eigenvector fields extracted from noisy synthetic data, the denoised vector fields show greater similarity to the ground truth for signal-to-noise ratios ranging from 20 to 5. Similarity greater than 0.9 (in terms of fiber direction) is observed for all signal-to-noise ratios, for smoothing parameter values greater than or equal to 10 (larger values yield more smoothing). Fiber architectures were computed from human forearm diffusion tensor data using extracted primary eigenvectors and the denoised data. Qualitative comparison of the fiber fields showed that the denoised fields were anatomically more plausible than the noisy fields. From the results of experiments using both synthetic and real MR datasets we conclude that the denoising algorithm produces anatomically plausible fiber architectures from diffusion tensor images with a wide range of signal-to-noise ratios. PMID:21345716

Levin, David I W; Gilles, Benjamin; Mädler, Burkhard; Pai, Dinesh K

2011-06-01

355

Skeletal Muscle Function during Exercise—Fine-Tuning of Diverse Subsystems by Nitric Oxide  

PubMed Central

Skeletal muscle is responsible for altered acute and chronic workload as induced by exercise. Skeletal muscle adaptations range from immediate change of contractility to structural adaptation to adjust the demanded performance capacities. These processes are regulated by mechanically and metabolically induced signaling pathways, which are more or less involved in all of these regulations. Nitric oxide is one of the central signaling molecules involved in functional and structural adaption in different cell types. It is mainly produced by nitric oxide synthases (NOS) and by non-enzymatic pathways also in skeletal muscle. The relevance of a NOS-dependent NO signaling in skeletal muscle is underlined by the differential subcellular expression of NOS1, NOS2, and NOS3, and the alteration of NO production provoked by changes of workload. In skeletal muscle, a variety of highly relevant tasks to maintain skeletal muscle integrity and proper signaling mechanisms during adaptation processes towards mechanical and metabolic stimulations are taken over by NO signaling. The NO signaling can be mediated by cGMP-dependent and -independent signaling, such as S-nitrosylation-dependent modulation of effector molecules involved in contractile and metabolic adaptation to exercise. In this review, we describe the most recent findings of NO signaling in skeletal muscle with a special emphasis on exercise conditions. However, to gain a more detailed understanding of the complex role of NO signaling for functional adaptation of skeletal muscle (during exercise), additional sophisticated studies are needed to provide deeper insights into NO-mediated signaling and the role of non-enzymatic-derived NO in skeletal muscle physiology. PMID:23538841

Suhr, Frank; Gehlert, Sebastian; Grau, Marijke; Bloch, Wilhelm

2013-01-01

356

Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease.  

PubMed

Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease. PMID:18054318

Gates, Allison C; Bernal-Mizrachi, Carlos; Chinault, Sharon L; Feng, Chu; Schneider, Jochen G; Coleman, Trey; Malone, James P; Townsend, R Reid; Chakravarthy, Manu V; Semenkovich, Clay F

2007-12-01

357

In vivo assessment of catechol O-methyltransferase activity in rabbit skeletal muscle.  

PubMed

With the use of microdialysis technique in the anesthetized rabbit, we examined the catechol O-methyltransferase (COMT) activity at the skeletal muscle interstitium. We implanted a dialysis probe into the adductor muscle, and monitored dialysate catecholamines and their metabolites with chromatogram-electrochemical detection. Administration of COMT inhibitor (entacapone) decreased dialysate 3-methoxy 4-hydroxyphenylglycol (MHPG) levels. Local administration of dihydroxyphenylglycol induced increases in dialysate MHPG levels. These increases in dialysate MHPG levels were suppressed by the addition of entacapone. The concentration of MHPG in the skeletal muscle dialysate corresponded to the COMT activity in the skeletal muscle. Furthermore, local administration of norepinephrine or epinephrine increased normetanephrine or metanephrine levels in dialysate but not MHPG levels. Skeletal muscle microdialysis with local administration of catecholamine offers a new method for in vivo assessment of regional COMT activity. PMID:15182744

Fujii, Takafumi; Yamazaki, Toji; Akiyama, Tsuyoshi; Sano, Shunji; Mori, Hidezo

2004-04-30

358

Impaired Skeletal Muscle Regeneration in the Absence of Fibrosis during Hibernation in 13-Lined Ground Squirrels  

PubMed Central

Skeletal muscle atrophy can occur as a consequence of immobilization and/or starvation in the majority of vertebrates studied. In contrast, hibernating mammals are protected against the loss of muscle mass despite long periods of inactivity and lack of food intake. Resident muscle-specific stem cells (satellite cells) are known to be activated by muscle injury and their activation contributes to the regeneration of muscle, but whether satellite cells play a role in hibernation is unknown. In the hibernating 13-lined ground squirrel we show that muscles ablated of satellite cells were still protected against atrophy, demonstrating that satellite cells are not involved in the maintenance of skeletal muscle during hibernation. Additionally, hibernating skeletal muscle showed extremely slow regeneration in response to injury, due to repression of satellite cell activation and myoblast differentiation caused by a fine-tuned interplay of p21, myostatin, MAPK, and Wnt signaling pathways. Interestingly, despite long periods of inflammation and lack of efficient regeneration, injured skeletal muscle from hibernating animals did not develop fibrosis and was capable of complete recovery when animals emerged naturally from hibernation. We propose that hibernating squirrels represent a new model system that permits evaluation of impaired skeletal muscle remodeling in the absence of formation of tissue fibrosis. PMID:23155423

Soleimani, Arshia; Lin, Brian M.; Burks, Tyesha N.; Marx, Ruth; Lin, Benjamin; Zellars, Richard C.; Zhang, Yonggang; Huso, David L.; Marr, Tom G.; Leinwand, Leslie A.; Merriman, Dana K.; Cohn, Ronald D.

2012-01-01

359

Tuning Passive Mechanics through Differential Splicing of Titin during Skeletal Muscle Development  

PubMed Central

Abstract During postnatal development, major changes in mechanical properties of skeletal muscle occur. We investigated passive properties of skeletal muscle in mice and rabbits that varied in age from 1 day to ?1 year. Neonatal skeletal muscle expressed large titin isoforms directly after birth, followed by a gradual switch toward progressively smaller isoforms that required weeks-to-months to be completed. This suggests an extremely high plasticity of titin splicing during skeletal muscle development. Titin exon microarray analysis showed increased expression of a large group of exons in neonatal muscle, when compared to adult muscle transcripts, with the majority of upregulated exons coding for the elastic proline-glutamate-valine-lysine (PEVK) region of titin. Protein analysis supported expression of a significantly larger PEVK segment in neonatal muscle. In line with these findings, we found >50% lower titin-based passive stiffness of neonatal muscle when compared to adult muscle. Inhibiting 3,5,3?-tri-iodo-L-thyronine and 3,5,3?,5?-tetra-iodo-L-thyronine secretion did not alter isoform switching, suggesting no major role for thyroid hormones in regulating differential titin splicing during postnatal development. In summary, our work shows that stiffening of skeletal muscle during postnatal development occurs through a decrease in titin isoform size, due mainly to a marked restructuring of the PEVK region of titin. PMID:19843460

Ottenheijm, Coen A.C.; Knottnerus, Anna M.; Buck, Danielle; Luo, Xiuju; Greer, Kevin; Hoying, Adam; Labeit, Siegfried; Granzier, Henk

2009-01-01

360

Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD  

PubMed Central

Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population. In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190– -30 HU; skeletal muscle -29–150 HU. Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72–0.95). Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes. PMID:24993908

Maddocks, Matthew; Shrikrishna, Dinesh; Vitoriano, Simone; Natanek, Samantha A.; Tanner, Rebecca J.; Hart, Nicholas; Kemp, Paul R.; Moxham, John; Polkey, Michael I.; Hopkinson, Nicholas S.

2014-01-01

361

Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD.  

PubMed

Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population. In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190- -30 HU; skeletal muscle -29-150 HU. Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72-0.95). Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes. PMID:24993908

Maddocks, Matthew; Shrikrishna, Dinesh; Vitoriano, Simone; Natanek, Samantha A; Tanner, Rebecca J; Hart, Nicholas; Kemp, Paul R; Moxham, John; Polkey, Michael I; Hopkinson, Nicholas S

2014-11-01

362

Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.  

PubMed Central

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity > 10% of maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC), contraction-induced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia. We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia. PMID:8755671

Hansen, J; Thomas, G D; Harris, S A; Parsons, W J; Victor, R G

1996-01-01

363

Tubular aggregates are from whole sarcoplasmic reticulum origin: alterations in calcium binding protein expression in mouse skeletal muscle during aging  

Microsoft Academic Search

Tubular aggregates are observed in various muscle disorders and appear as densely packed tubules believed to arise from sarcoplasmic reticulum of striated muscle. They are found both in human skeletal muscle, especially from patients suffering from ‘tubular aggregate myopathy’ and in fast twitch skeletal muscle of the male inbred mouse during aging. In this work, we studied tubular aggregates present

F Chevessier; I Marty; M Paturneau-Jouas; M Verdière-Sahuqué

2004-01-01

364

A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice.  

PubMed

It has been well established that a starvation-induced decrease in insulin/IGF-I and serum amino acids effectively suppresses the mammalian target of rapamycin (mTor) signaling to induce autophagy, which is a major degradative cellular pathway in skeletal muscles. In this study, we investigated the systematic effects of exercise on the mTor signaling of skeletal muscles. Wild type C57BL/6J mice were starved for 24h under synchronous autophagy induction conditions. Under these conditions, endogenous LC3-II increased, while both S6-kinse and S6 ribosomal protein were dephosphorylated in the skeletal muscles, which indicated mTor inactivation. Using GFP-LC3 transgenic mice, it was also confirmed that fluorescent GFP-LC3 dots in the skeletal muscles increased, including soleus, plantaris, and gastrocnemius, which clearly showed autophagosomal induction. These starved mice were then subjected to a single bout of running on a treadmill (12m/min, 2h, with a lean of 10 degrees). Surprisingly, biochemical analyses revealed that the exercise elicited a decrease in the LC3-II/LC3-I ratio as well as an inversion from the dephosphorylated state to the rephosphorylated state of S6-kinase and ribosomal S6 in these skeletal muscles. Consistently, the GFP-LC3 dots of the skeletal muscles were diminished immediately after the exercise. These results indicated that exercise suppressed starvation-induced autophagy through a reactivation of mTor signaling in the skeletal muscles of these starved mice. PMID:25485704

Zheng, Dong-Mei; Bian, Zehua; Furuya, Norihiko; Oliva Trejo, Juan Alejandro; Takeda-Ezaki, Mitsue; Takahashi, Katsuyuki; Hiraoka, Yuka; Mineki, Reiko; Taka, Hikari; Ikeda, Shin-Ichi; Komatsu, Masaaki; Fujimura, Tsutomu; Ueno, Takashi; Ezaki, Junji

2015-01-01

365

Integration of carbohydrate and lipid metabolism in skeletal muscle during postnatal development  

E-print Network

Integration of carbohydrate and lipid metabolism in skeletal muscle during postnatal development R, muscle metabolism represents a large drain of energetic substrates. The newborn has to provide additional utilisation by muscle is of upmost importance for postnatal metabolic homeo- tasis. In the human, fibre types

Paris-Sud XI, Université de

366

TRIADIN DELETION INDUCES IMPAIRED SKELETAL MUSCLE Sarah Oddoux1,2  

E-print Network

title: Triadin KO mouse Triadin is a multiple proteins family, some isoforms being involved in muscle1 TRIADIN DELETION INDUCES IMPAIRED SKELETAL MUSCLE FUNCTION Sarah Oddoux1,2 , Julie Brocard1,2, § From : 1 INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, F

Boyer, Edmond

367

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

PubMed Central

While much work has previously been done in the modeling of skeletal muscle, no model has, to date, been developed that describes the mechanical behavior with an explicit strain-energy function associated with the active response of skeletal muscle tissue. A model is presented herein that has been developed to accommodate this design consideration using a robust dynamical approach. The model shows excellent agreement with a previously published model of both the active and passive length-tension properties of skeletal muscle. PMID:19045546

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

2010-01-01

368

Detection of 3-methoxy-4-hydroxyphenylglycol in rabbit skeletal muscle microdialysate.  

PubMed

A high-performance liquid chromatography with electrochemical detection (HPLC-ED) method is described for determination of 3-methoxy-4-hydroxyphenylglycol (MHPG) in microdialysate from the skeletal muscle interstitial space. Using a microdialysis technique, we sampled 30 microl dialysate from the skeletal muscle interstitial space and injected dialysate directly into HPLC-ED system. The control MHPG concentration of dialysate was 213+/-18 pg/ml. The MHPG concentrations were reduced by entacapone (catechol-O-methyltransferase inhibitor, COMT), augmented by local infusion of dihydroxyphenylglycol. This system offers a new possibility for simple, rapid monitoring of MHPG as an index of COMT activity in skeletal muscle. PMID:14630372

Tokunaga, Noriyuki; Yamazaki, Toji; Akiyama, Tsuyoshi; Mori, Hidezo

2003-12-01

369

TWEAK promotes exercise intolerance by decreasing skeletal muscle oxidative phosphorylation capacity  

PubMed Central

Background Proinflammatory cytokine tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 are the major regulators of skeletal muscle mass in many catabolic conditions. However, their role in muscle metabolism remains largely unknown. In the present study, we investigated the role of TWEAK on exercise capacity and skeletal muscle mitochondrial content and oxidative metabolism. Methods We employed wild-type and TWEAK-knockout (KO) mice and primary myotube cultures and performed biochemical, bioenergetics, and morphometric assays to evaluate the effects of TWEAK on exercise tolerance and muscle mitochondrial function and angiogenesis. Results TWEAK-KO mice showed improved exercise tolerance compared to wild-type mice. Electron microscopy analysis showed that the abundance of subsarcolemmal and intermyofibrillar mitochondria is significantly increased in skeletal muscle of TWEAK-KO mice compared to wild-type mice. Furthermore, age-related loss in skeletal muscle oxidative capacity was rescued in TWEAK-KO mice. Expression of a key transcriptional regulator peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?) and several other molecules involved in oxidative metabolism were significantly higher in skeletal muscle of TWEAK-KO mice. Moreover, treatment of primary myotubes with soluble TWEAK inhibited the expression of PGC-1? and mitochondrial genes and decreased mitochondrial respiratory capacity. Deletion of TWEAK also improved angiogenesis and transcript levels of vascular endothelial growth factor in skeletal muscle of mice. Conclusions These results demonstrate that TWEAK decreases mitochondrial content and oxidative phosphorylation and inhibits angiogenesis in skeletal muscle. Neutralization of TWEAK is a potential approach for improving exercise capacity and oxidative metabolism in skeletal muscle. PMID:23835416

2013-01-01

370

In vivo expression of G-protein 12 dimer in adult mouse skeletal muscle alters L-type calcium current and excitation-contraction coupling  

E-print Network

1 In vivo expression of G-protein 12 dimer in adult mouse skeletal muscle alters L-type calcium, Grenoble, France. Running title: G-proteins in skeletal muscle Key words: skeletal muscle, G-protein)). In skeletal muscle, no less than 43 GPCRs were found to be expressed at the protein or mRNA level. Signaling

Paris-Sud XI, Université de

371

De Novo Prion Aggregates Trigger Autophagy in Skeletal Muscle  

PubMed Central

ABSTRACT In certain sporadic, familial, and infectious prion diseases, the prion protein misfolds and aggregates in skeletal muscle in addition to the brain and spinal cord. In myocytes, prion aggregates accumulate intracellularly, yet little is known about clearance pathways. Here we investigated the clearance of prion aggregates in muscle of transgenic mice that develop prion disease de novo. In addition to neurodegeneration, aged mice developed a degenerative myopathy, with scattered myocytes containing ubiquitinated, intracellular prion inclusions that were adjacent to myocytes lacking inclusions. Myocytes also showed elevated levels of the endoplasmic reticulum chaperone Grp78/BiP, suggestive of impaired protein degradation and endoplasmic reticulum stress. Additionally, autophagy was induced, as indicated by increased levels of beclin-1 and LC3-II. In C2C12 myoblasts, inhibition of autophagosome maturation or lysosomal degradation led to enhanced prion aggregation, consistent with a role for autophagy in prion aggregate clearance. Taken together, these findings suggest that the induction of autophagy may be a central strategy for prion aggregate clearance in myocytes. IMPORTANCE PMID:24307586

Joshi-Barr, Shivanjali; Bett, Cyrus; Chiang, Wei-Chieh; Trejo, Margarita; Goebel, Hans H.; Sikorska, Beata; Liberski, Pawel; Raeber, Alex; Lin, Jonathan H.; Masliah, Eliezer

2014-01-01

372

Increased myogenic responsiveness of skeletal muscle arterioles with juvenile growth.  

PubMed

Previous studies from this laboratory suggest that during juvenile growth, structural changes in the arteriolar network are accompanied by changes in some of the mechanisms responsible for regulation of tissue blood flow. To test the hypothesis that arteriolar myogenic behavior is altered with growth, we studied gracilis muscle arterioles isolated from Sprague-Dawley rats at two ages: 21-28 and 42-49 days. When studied at their respective in vivo pressures, the myogenic index (instantaneous slope of the active pressure-diameter curve) of arterioles from 42-49-day-old rats was more negative than that of arterioles from 21-28-day-old rats, indicating greater myogenic responsiveness. Endothelial denudation, or prostaglandin H(2) (PGH(2))/thromboxane A(2) (TxA(2)) receptor antagonism without denudation, significantly reduced the myogenic responsiveness of arterioles from the older rats over a wide range of pressures but had no consistent effects on the myogenic responsiveness of arterioles from the younger rats. The heme oxygenase inhibitor chromium (III) mesoporphyrin IX chloride had no effect on the myogenic activity of arterioles from either age group. These findings indicate that microvascular growth in young animals is accompanied by an increase in the myogenic behavior of arterioles, possibly because PGH(2) or TxA(2) assumes a role in reinforcing myogenic activity over this period. As a result, the relative contribution of myogenic activity to blood flow regulation in skeletal muscle may increase during rapid juvenile growth. PMID:18375725

Samora, Julie Balch; Frisbee, Jefferson C; Boegehold, Matthew A

2008-05-01

373

Endothelial cell uptake of adenosine in canine skeletal muscle  

PubMed Central

The vascularly isolated muscles in the hindlimbs of five dogs were perfused with an oxygenated physiological salt solution. The extractions of adenosine and of a nontransported analogue of adenosine, 9-?-d-arabinofuranosyl hypoxanthine (AraH), were determined by the single-pass indicator-dilution technique. A bolus containing [125I]albumin (reference tracer), [14C]adenosine, and [3H]AraH was injected into the artery while samples of venous effluent were collected over the next minute. This injection was repeated with dipyridamole (10–5 M) in the perfusate. Early extractions of AraH (EAra) and adenosine (EAdo) under control conditions were 48 ± 4 and 80 ± 4%, respectively. In the presence of dipyridamole, EAra was unchanged (47 ± 5) while EAdo decreased to 45 ± 7%. Since early extraction reflects primarily the barrier posed by endothelial cells, these results demonstrate significant endothelial uptake of adenosine. Analysis of these data using a mathematical model of blood-tissue exchange indicates that, under the conditions of these experiments, at least 78% of the adenosine taken up by skeletal muscle entered endothelial cells. PMID:3513628

GORMAN, MARK W.; BASSINGTHWAIGHTE, JAMES B.; OLSSON, RAY A.; SPARKS, HARVEY V.

2010-01-01

374

Skeletal muscle tissue engineering: which cell to use?  

PubMed

Tissue-engineered skeletal muscle is urgently required to treat a wide array of devastating congenital and acquired conditions. Selection of the appropriate cell type requires consideration of several factors which amongst others include, accessibility of the cell source, in vitro myogenicity at high efficiency with the ability to maintain differentiation over extended periods of time, susceptibility to genetic manipulation, a suitable mode of delivery and finally in vivo differentiation giving rise to restoration of structural morphology and function. Potential stem-progenitor cell sources include and are not limited to satellite cells, myoblasts, mesoangioblasts, pericytes, muscle side-population cells, CD133(+) cells, in addition to embryonic stem cells, mesenchymal stem cells, amniotic fluid stem cells and induced pluripotent stem (iPS) cells. The relative merits and inherent limitations of these cell types within the field of tissue-engineering are discussed in the light of current research. Recent advances in the field of iPS cells should bear the fruits for some exciting developments within the field in the forthcoming years. PMID:23679017

Fishman, Jonathan Mark; Tyraskis, Athanasios; Maghsoudlou, Panagiotis; Urbani, Luca; Totonelli, Giorgia; Birchall, Martin A; De Coppi, Paolo

2013-12-01

375

Isolation and characterization of a novel gene sfig in rat skeletal muscle up-regulated by spaceflight (STS-90)  

NASA Technical Reports Server (NTRS)

We obtained the skeletal muscle of rats exposed to weightless conditions during a 16-day-spaceflight (STS-90). By using a differential display technique, we identified 6 up-regulated and 3 down-regulated genes in the gastrocnemius muscle of the spaceflight rats, as compared to the ground control. The up-regulated genes included those coding Casitas B-lineage lymphoma-b, insulin growth factor binding protein-1, titin and mitochondrial gene 16 S rRNA and two novel genes (function unknown). The down-regulated genes included those encoding RNA polymerase II elongation factor-like protein, NADH dehydrogenase and one novel gene (function unknown). In the present study, we isolated and characterized one of two novel muscle genes that were remarkably up-regulated by spaceflight. The deduced amino acid sequence of the spaceflight-induced gene (sfig) comprises 86 amino acid residues and is well conserved from Drosophila to Homo sapiens. A putative leucine-zipper structure located at the N-terminal region of sfig suggests that this gene may encode a transcription factor. The up-regulated expression of this gene, confirmed by Northern blot analysis, was observed not only in the muscles of spaceflight rats but also in the muscles of tail-suspended rats, especially in the early stage of tail-suspension when gastrocnemius muscle atrophy initiated. The gene was predominantly expressed in the kidney, liver, small intestine and heart. When rat myoblastic L6 cells were grown to 100% confluence in the cell culture system, the expression of sfig was detected regardless of the cell differentiation state. These results suggest that spaceflight has many genetic effects on rat skeletal muscle.

Kano, Mihoko; Kitano, Takako; Ikemoto, Madoka; Hirasaka, Katsuya; Asanoma, Yuki; Ogawa, Takayuki; Takeda, Shinichi; Nonaka, Ikuya; Adams, Gregory R.; Baldwin, Kenneth M.; Oarada, Motoko; Kishi, Kyoichi; Nikawa, Takeshi

2003-01-01

376

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

SciTech Connect

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 cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal {beta} III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders.

Arsic, Nikola; Mamaeva, Daria; Lamb, Ned J. [Cell Biology Unit, Institute for Human Genetics, CNRS, 141 rue de la Cardonille, Montpellier (France); Fernandez, Anne [Cell Biology Unit, Institute for Human Genetics, CNRS, 141 rue de la Cardonille, Montpellier (France)], E-mail: af@acrux.igh.cnrs.fr

2008-04-01

377

Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent  

NASA Technical Reports Server (NTRS)

This investigation examined the effect of mechanical loading state on focal adhesion kinase (FAK), paxillin, and serum response factor (SRF) in rat skeletal muscle. We found that FAK concentration and tyrosine phosphorylation, paxillin concentration, and SRF concentration are all lower in the lesser load-bearing fast-twitch plantaris and gastrocnemius muscles compared with the greater load-bearing slow-twitch soleus muscle. Of these three muscles, 7 days of mechanical unloading via tail suspension elicited a decrease in FAK tyrosine phosphorylation only in the soleus muscle and decreases in FAK and paxillin concentrations only in the plantaris and gastrocnemius muscles. Unloading decreased SRF concentration in all three muscles. Mechanical overloading (via bilateral gastrocnemius ablation) for 1 or 8 days increased FAK and paxillin concentrations in the soleus and plantaris muscles. Additionally, whereas FAK tyrosine phosphorylation and SRF concentration were increased by < or =1 day of overloading in the soleus muscle, these increases did not occur until somewhere between 1 and 8 days of overloading in the plantaris muscle. These data indicate that, in the skeletal muscles of rats, the focal adhesion complex proteins FAK and paxillin and the transcription factor SRF are generally modulated in association with the mechanical loading state of the muscle. However, the somewhat different patterns of adaptation of these proteins to altered loading in slow- vs. fast-twitch skeletal muscles indicate that the mechanisms and time course of adaptation may partly depend on the prior loading state of the muscle.

Gordon, S. E.; Fluck, M.; Booth, F. W.

2001-01-01

378

Skeletal Muscle Expression of the Adhesion-GPCR CD97: CD97 Deletion Induces an Abnormal Structure of the Sarcoplasmatic Reticulum but Does Not Impair Skeletal Muscle Function  

PubMed Central

CD97 is a widely expressed adhesion class G-protein-coupled receptor (aGPCR). Here, we investigated the presence of CD97 in normal and malignant human skeletal muscle as well as the ultrastructural and functional consequences of CD97 deficiency in mice. In normal human skeletal muscle, CD97 was expressed at the peripheral sarcolemma of all myofibers, as revealed by immunostaining of tissue sections and surface labeling of single myocytes using flow cytometry. In muscle cross-sections, an intracellular polygonal, honeycomb-like CD97-staining pattern, typical for molecules located in the T-tubule or sarcoplasmatic reticulum (SR), was additionally found. CD97 co-localized with SR Ca2+-ATPase (SERCA), a constituent of the longitudinal SR, but not with the receptors for dihydropyridine (DHPR) or ryanodine (RYR), located in the T-tubule and terminal SR, respectively. Intracellular expression of CD97 was higher in slow-twitch compared to most fast-twitch myofibers. In rhabdomyosarcomas, CD97 was strongly upregulated and in part more N-glycosylated compared to normal skeletal muscle. All tumors were strongly CD97-positive, independent of the underlying histological subtype, suggesting high sensitivity of CD97 for this tumor. Ultrastructural analysis of murine skeletal myofibers confirmed the location of CD97 in the SR. CD97 knock-out mice had a dilated SR, resulting in a partial increase in triad diameter yet not affecting the T-tubule, sarcomeric, and mitochondrial structure. Despite these obvious ultrastructural changes, intracellular Ca2+ release from single myofibers, force generation and fatigability of isolated soleus muscles, and wheel-running capacity of mice were not affected by the lack of CD97. We conclude that CD97 is located in the SR and at the peripheral sarcolemma of human and murine skeletal muscle, where its absence affects the structure of the SR without impairing skeletal muscle function. PMID:24949957

Zyryanova, Tatiana; Schneider, Rick; Adams, Volker; Sittig, Doreen; Kerner, Christiane; Gebhardt, Claudia; Ruffert, Henrik; Glasmacher, Stefan; Hepp, Pierre; Punkt, Karla; Neuhaus, Jochen; Hamann, Jörg; Aust, Gabriela

2014-01-01

379

A Physiologically Based, Multi-Scale Model of Skeletal Muscle Structure and Function  

PubMed Central

Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle’s response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle’s response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue. PMID:22993509

Röhrle, O.; Davidson, J. B.; Pullan, A. J.

2012-01-01

380

Skeletal muscle-endothelial cell cross talk through angiotensin II.  

PubMed

The role of angiotensin II (ANG II) in postnatal vasculogenesis and angiogenesis during skeletal muscle (SKM) regeneration is unknown. We examined the capacity of ANG II to stimulate capillary formation and growth during cardiotoxin-induced muscle regeneration in ACE inhibitor-treated ANG II type 1a receptor knockout (AT1a(-/-)) and C57Bl/6 control mice. Analysis of tibialis anterior (TA) cross-sections revealed 17% and 23% reductions in capillarization in AT1a(-/-) and captopril treated mice, respectively, when compared with controls, 21 days postinjury. Conversely, no differences in capillarization were detected at early time points (7 and 10 days). These results identify ANG II as a regulator of angiogenesis but not vasculogenesis in vivo. In vitro angiogenesis assays of human umbilical vein endothelial cells (HUVECs) further confirmed ANG II as proangiogeneic as 71% and 124% increases in tube length and branch point number were observed following ANG II treatment. Importantly, treatment of HUVECs with conditioned media from differentiated muscle cells resulted in an 84% and 203% increase in tube length and branch point number compared with controls, which was abolished following pretreatment of the cells with an angiotensin-converting enzyme inhibitor. The pro-angiogenic effect of ANG II can be attributed to an enhanced endothelial cell migration because both transwell and under agarose migration assays revealed a 37% and 101% increase in cell motility, respectively. Collectively, these data highlight ANG II as a proangiogenic regulator during SKM regeneration in vivo and more importantly demonstrates that ANG II released from SKM can signal endothelial cells and regulate angiogenesis through the induction of endothelial cell migration. PMID:20861465

Bellamy, Leeann M; Johnston, Adam P W; De Lisio, Michael; Parise, Gianni

2010-12-01

381

Myostatin levels in skeletal muscle of hibernating ground squirrels  

PubMed Central

SUMMARY Myostatin, a negative regulator of muscle mass, is elevated during disuse and starvation. Mammalian hibernation presents a unique scenario, where animals are hypocaloric and in torpor, but the extent of muscle protein loss is minimized. We hypothesized that myostatin expression, which is usually increased early in disuse and under hypocaloric conditions, could be suppressed in this unique model. Skeletal muscle was collected from thirteen-lined ground squirrels, Spermophilus tridecemlineatus, at six time points during hibernation: control euthermic (CON); entrance into hibernation (ENT), body temperature (Tb) falling; early hibernation (EHib), stable Tb in torpor for 24 h; late hibernation (LHib), stable Tb in torpor for 3 days; early arousal (EAr), Tb rising; and arousal (AR), Tb restored to 34–37°C for about 18 h. There was no significant increase of myostatin during ENT, EHib or LHib. Unexpectedly, there were approximately sixfold increases in myostatin protein levels as squirrels arose from torpor. The elevation during EAr remained high in AR, which represented an interbout time period. Mechanisms that could release the suppression or promote increased levels of myostatin were assessed. SMAD2 and phosphorylated SMAD2 were increased during EHib, but only the phosphorylated SMAD2 during AR mirrored increases in myostatin. Follistatin, a negative regulator of myostatin, did not follow the same time course as myostatin or its signaling pathway, indicating more control of myostatin at the signaling level. However, SMAD7, an inhibitory SMAD, did not appear to play a significant role during deep hibernation. Hibernation is an excellent natural model to study factors involved in the endogenous intracellular mechanisms controlling myostatin. PMID:21753045

Brooks, Naomi E.; Myburgh, Kathryn H.; Storey, Kenneth B.

2011-01-01

382

Measuring quality of life impairment in skeletal muscle channelopathies  

PubMed Central

Background and purpose Fatigue and pain have been previously shown to be important determinants for decreasing quality of life (QoL) in one report in patients with non-dystrophic myotonia. The aims of our study were to assess QoL in skeletal muscle channelopathies (SMC) using INQoL (individualized QoL) and SF-36 questionnaires. Methods We administered INQoL and SF-36 to 66 Italian patients with SMC (26: periodic paralysis, 36: myotonia congenita and 4: Andersen-Tawil) and compared the results in 422 patients with myotonic dystrophies (DM1: 382; and DM2: 40). Results (i) INQoL index in SMC is similar to that in DMs (P = 0.79). (ii) Patients with myotonia congenita have the worst perception of QoL. (iii) Myotonia has the most detrimental effect on patients with myotonia congenita, followed by patients with DM2 and then by patients with DM1 and hyperkalemic periodic paralysis. (iv) Pain is a significant complaint in patients with myotonia congenita, hypokalemic periodic paralysis and DM2 but not in DM1. (v) Fatigue has a similar detrimental effect on all patient groups except for patients with hyperkalemic periodic paralysis in whom muscle weakness and myotonia more than fatigue affect QoL perception. (vi) Muscle symptoms considered in INQoL correlate with physical symptoms assessed by SF-36 (R from ?0.34 to ?0.76). Conclusions QoL perception in patients with SMC is similar to that of patients with DMs, chronic multisystem disabling conditions. Our results provide information to target treatment and health care of these patients. The sensitivity of INQoL to changes in QoL in the SMC needs to be further explored in longitudinal studies. PMID:22607270

Sansone, V A; Ricci, C; Montanari, M; Apolone, G; Rose, M; Meola, G

2012-01-01

383

The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle  

PubMed Central

We use a highly specific and sensitive antibody to further characterize the distribution of dystrophin in skeletal, cardiac, and smooth muscle. No evidence for localization other than at the cell surface is apparent in skeletal muscle and no 427-kD dystrophin labeling was detected in sciatic nerve. An elevated concentration of dystrophin appears at the myotendinous junction and the neuromuscular junction, labeling in the latter being more intense specifically in the troughs of the synaptic folds. In cardiac muscle the distribution of dystrophin is limited to the surface plasma membrane but is notably absent from the membrane that overlays adherens junctions of the intercalated disks. In smooth muscle, the plasma membrane labeling is considerably less abundant than in cardiac or skeletal muscle and is found in areas of membrane underlain by membranous vesicles. As in cardiac muscle, smooth muscle dystrophin seems to be excluded from membrane above densities that mark adherens junctions. Dystrophin appears as a doublet on Western blots of skeletal and cardiac muscle, and as a single band of lower abundance in smooth muscle that corresponds most closely in molecular weight to the upper band of the striated muscle doublet. The lower band of the doublet in striated muscle appears to lack a portion of the carboxyl terminus and may represent a dystrophin isoform. Isoform differences and the presence of dystrophin on different specialized membrane surfaces imply multiple functional roles for the dystrophin protein. PMID:1918148

1991-01-01

384

Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: A multifactorial process  

SciTech Connect

Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the robustness of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow to muscle conversion. We transplanted GFP transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopietic markers. Irradiation was essential to conversion although whether by injury or induction of chimerism is not clear. Cardiotoxin and to a lesser extent PBS injected muscles showed significant number of GFP+ muscle fibers while uninjected muscles showed only rare GFP+ cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent with G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57 BL/6 and GFP to Rosa26 mice showed fusion of donor cells to recipient muscle. High numbers of donor derived muscle colonies and up to12 percent GFP positive muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels which could be clinically significant in developing strategies for the treatment of muscular dystrophies. In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.

Abedi, Mehrdad; Greer, Deborah A.; Colvin, Gerald A.; Demers, Delia A.; Dooner, Mark S.; Harpel, Jasha A.; Weier, Heinz-Ulrich G.; Lambert, Jean-Francois; Quesenberry, Peter J.

2004-01-10

385

Prolonged erythropoietin treatment does not impact gene expression in human skeletal muscle.  

PubMed

Introduction: We assessed the presence of erythropoietin receptor (Epo-R) in human skeletal muscle and alterations in gene expression after prolonged erythropoiesis-stimulating agent (ESA). Methods: Nine healthy men were treated with ESA for 10 weeks (Darbepoietin-?). Muscle biopsies were collected before and after treatment. Alterations in gene expression were evaluated by gene array. Western blotting and PCR analysis evaluated Epo-R presence in human skeletal muscle. Results: Very low Epo-R mRNA levels were found, but a new and sensitive antibody did not identify Epo-R protein in human skeletal muscle. The between-subject variation in skeletal muscle gene expression was larger than the changes observed in response to prolonged ESA treatment. Conclusion: Erythropoietin is unlikely to exert direct effects in human skeletal muscle due to a lack of Epo-R protein. Furthermore, prolonged ESA treatment does not seem to exert either direct or indirect effects on skeletal muscle gene expression. © 2014 Wiley Periodicals, Inc. PMID:25088500

Christensen, Britt; Nellemann, Birgitte; Thorsen, Kasper; Nielsen, Morten Muhlig; Pedersen, Steen B; Ornstrup, Marie Juul; Jørgensen, Jens Otto L; Jessen, Niels

2014-08-01

386

Role of nitric oxide in skeletal muscle glucose uptake during exercise.  

PubMed

Nitric oxide is produced within skeletal muscle fibres and has various functions in skeletal muscle. There is evidence that NO may be essential for normal increases in skeletal muscle glucose uptake during contraction/exercise. Although there have been some discrepant results, it has been consistently demonstrated that inhibition of NO synthase (NOS) attenuates the increase in skeletal muscle glucose uptake during contraction in mouse and rat muscle ex vivo, during in situ contraction in rats and during exercise in humans. The NO-mediated increase in skeletal muscle glucose uptake during contraction/exercise is probably due to the modulation of intramuscular signalling that ultimately increases glucose transporter 4 (GLUT4) translocation and is, surprisingly, independent of blood flow. In this review, we discuss the evidence for and against a role of NO in regulating skeletal muscle glucose uptake during contraction/exercise and outline the possible mechanism(s) involved. Emerging findings regarding the role of neuronal NOS mu (nNOS?) in this process are also discussed. PMID:25192731

Hong, Yet Hoi; Betik, Andrew C; McConell, Glenn K

2014-12-01

387

New fiber formation in the interstitial spaces of rat skeletal muscle during postnatal growth.  

PubMed

The purpose of this study was to determine whether fiber hyperplasia occurs in the rat plantaris muscle during postnatal weeks 3-20. Total