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Sample records for age-related skeletal muscle

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

    PubMed

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

    2016-07-17

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

  2. Age-related loss of muscle fibres is highly variable amongst mouse skeletal muscles.

    PubMed

    Sheard, Philip W; Anderson, Ross D

    2012-04-01

    Sarcopenia is the age-related loss of skeletal muscle mass and strength, attributable in part to muscle fibre loss. We are currently unable to prevent fibre loss because we do not know what causes it. To provide a platform from which to better understand the causes of muscle fibre death we have quantified fibre loss in several muscles of aged C57Bl/6J mice. Comparison of muscle fibre numbers on dystrophin-immunostained transverse tissue sections at 6 months of age with those at 24 months shows a significant fibre loss in extensor digitorum longus and soleus, but not in sternomastoid or cleidomastoid muscles. The muscles of the elderly mice were mostly lighter than their younger counterparts, but fibres in the elderly muscles were of about the same cross-sectional area. This study shows that the contribution of fibre death to sarcopenia is highly variable and that there is no consistent pattern of age-related fibre loss between skeletal muscles.

  3. Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.

    PubMed

    Chalil, Sreeda; Pierre, Nicolas; Bakker, Astrid D; Manders, Ralph J; Pletsers, Annelies; Francaux, Marc; Klein-Nulend, Jenneke; Jaspers, Richard T; Deldicque, Louise

    2015-12-25

    Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging.

  4. Stuck in gear: age-related loss of variable gearing in skeletal muscle.

    PubMed

    Holt, Natalie C; Danos, Nicole; Roberts, Thomas J; Azizi, Emanuel

    2016-04-01

    Skeletal muscles power a broad diversity of animal movements, despite only being able to produce high forces over a limited range of velocities. Pennate muscles use a range of gear ratios, the ratio of muscle shortening velocity to fiber shortening velocity, to partially circumvent these force-velocity constraints. Muscles operate with a high gear ratio at low forces; fibers rotate to greater angles of pennation, enhancing velocity but compromising force. At higher forces, muscles operate with a lower gear ratio; fibers rotate little so limiting muscle shortening velocity, but helping to preserve force. This ability to shift gears is thought to be due to the interplay of contractile force and connective tissue constraints. In order to test this hypothesis, gear ratios were determined in the medial gastrocnemius muscles of both healthy young rats, and old rats where the interaction between contractile and connective tissue properties was assumed to be disrupted. Muscle fiber and aponeurosis stiffness increased with age (P<0.05) from 19.1±5.0 kPa and 188.5±24.2 MPa, respectively, in young rats to 39.1±4.2 kPa and 328.0±48.3 MPa in old rats, indicating a mechanical change in the interaction between contractile and connective tissues. Gear ratio decreased with increasing force in young (P<0.001) but not old (P=0.72) muscles, indicating that variable gearing is lost in old muscle. These findings support the hypothesis that variable gearing results from the interaction between contractile and connective tissues and suggest novel explanations for the decline in muscle performance with age.

  5. Stuck in gear: age-related loss of variable gearing in skeletal muscle.

    PubMed

    Holt, Natalie C; Danos, Nicole; Roberts, Thomas J; Azizi, Emanuel

    2016-04-01

    Skeletal muscles power a broad diversity of animal movements, despite only being able to produce high forces over a limited range of velocities. Pennate muscles use a range of gear ratios, the ratio of muscle shortening velocity to fiber shortening velocity, to partially circumvent these force-velocity constraints. Muscles operate with a high gear ratio at low forces; fibers rotate to greater angles of pennation, enhancing velocity but compromising force. At higher forces, muscles operate with a lower gear ratio; fibers rotate little so limiting muscle shortening velocity, but helping to preserve force. This ability to shift gears is thought to be due to the interplay of contractile force and connective tissue constraints. In order to test this hypothesis, gear ratios were determined in the medial gastrocnemius muscles of both healthy young rats, and old rats where the interaction between contractile and connective tissue properties was assumed to be disrupted. Muscle fiber and aponeurosis stiffness increased with age (P<0.05) from 19.1±5.0 kPa and 188.5±24.2 MPa, respectively, in young rats to 39.1±4.2 kPa and 328.0±48.3 MPa in old rats, indicating a mechanical change in the interaction between contractile and connective tissues. Gear ratio decreased with increasing force in young (P<0.001) but not old (P=0.72) muscles, indicating that variable gearing is lost in old muscle. These findings support the hypothesis that variable gearing results from the interaction between contractile and connective tissues and suggest novel explanations for the decline in muscle performance with age. PMID:27030778

  6. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy*

    PubMed Central

    Ebert, Scott M.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.; Murry, Daryl J.; Fox, Daniel K.; Bongers, Kale S.; Lira, Vitor A.; Meyerholz, David K.; Talley, John J.; Adams, Christopher M.

    2015-01-01

    Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality, and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle. PMID:26338703

  7. An analysis of age-related loss of skeletal muscle mass and its significance on osteoarthritis in a Korean population

    PubMed Central

    Kim, Hun-Tae; Kim, Hyun-Je; Ahn, Hee-Yun; Hong, Young-Hoon

    2016-01-01

    Background/Aims: This study was conducted in order to analyze the effects of sarcopenia on age-related osteoarthritis (OA) of the knee in a Korean population. Methods: All the Korean subjects who visited the Yeungnam University Medical Center Health Promotion Center between 2008 and 2012 in order to undergo a routine medical examination were enrolled. A total of 5,723 young, healthy people (2,959 males, 2,764 females) enrolled as normal subjects and 23,473 subjects (13,006 males and 10,467 females) were included for evaluation of the effects of sarcopenia on OA. There were 266 subjects who followed-up bioelectrical impedance analysis at a 4-year interval. Of 327 subjects enrolled in this study, knees with anteroposterior X-rays were assessed according to the Kellgren-Lawrence (K/L) grade. Results: Skeletal muscle mass index (SMI) and basal metabolic rate (BMR) showed a steady decrease with the advance of age (p < 0.01), but SMI showed strong positive correlation with BMR (r = 0.72, β = 30.96, p < 0.01). During the 4-year interval, BMR showed a significant decrease with aging (p < 0.01), consistently with the decrease of SMI. Knees with normal SMI were prone to be designated as K/L grade 0 or 1; however, subjects with sarcopenia showed a trend toward the higher K/L grade, classified as knee radiological osteoarthritis (ROA) (p < 0.01). Conclusions: The results of this study may indicate that sarcopenia as age-related loss of skeletal muscle mass is interactively correlated with the presence and severity of age-related OA. PMID:26976151

  8. Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training.

    PubMed

    Consitt, Leslie A; Saxena, Gunjan; Saneda, Alicson; Houmard, Joseph A

    2016-07-01

    The purpose of this study was to determine whether plasma lactate and skeletal muscle glucose regulatory pathways, specifically PDH dephosphorylation, are impaired during hyperinsulinemic conditions in middle- to older-aged individuals and determine whether exercise training could improve key variables responsible for skeletal muscle PDH regulation. Eighteen young (19-29 yr; n = 9 males and 9 females) and 20 middle- to older-aged (57-82 yr; n = 10 males and 10 females) individuals underwent a 2-h euglycemic hyperinsulinemic clamp. Plasma samples were obtained at baseline and at 30, 50, 90, and 120 min for analysis of lactate, and skeletal muscle biopsies were performed at 60 min for analysis of protein associated with glucose metabolism. In response to insulin, plasma lactate was elevated in aged individuals when normalized to insulin action. Insulin-stimulated phosphorylation of skeletal muscle PDH on serine sites 232, 293, and 300 decreased in young individuals only. Changes in insulin-stimulated PDH phosphorylation were positively related to changes in plasma lactate. No age-related differences were observed in skeletal muscle phosphorylation of LDH, GSK-3α, or GSK-3β in response to insulin or PDP1, PDP2, PDK2, PDK4, or MPC1 total protein. Twelve weeks of endurance- or strength-oriented exercise training improved insulin-stimulated PDH dephosphorylation, which was related to a reduced lactate response. These findings suggest that impairments in insulin-induced PDH regulation in a sedentary aging population contribute to impaired glucose metabolism and that exercise training is an effective intervention for treating metabolic inflexibility. PMID:27221120

  9. 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...

  10. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Griffiths, Richard D.; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.—Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  11. Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle: a comparative study of newborn, adult and aged rats.

    PubMed Central

    Andersson, A M; Olsen, M; Zhernosekov, D; Gaardsvoll, H; Krog, L; Linnemann, D; Bock, E

    1993-01-01

    Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM concentration in aged muscle was sixfold higher than in young adult muscle. In contrast with previous reports, NCAM polypeptides of 200, 145, 125 and 120 kDa were observed by immunoblotting throughout postnatal development and aging, the relative proportions of the individual NCAM polypeptides remaining virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2.9 kb were present in perinatal and young adult skeletal muscle, whereas only the 5.2 and 2.9 kb mRNA classes could be demonstrated in aged muscle. This indicates that metabolism of the various NCAM polypeptides is individually regulated during aging. Alternative splicing of NCAM mRNA in skeletal muscle was studied by Northern blotting using DNA oligonucleotide probes specifically hybridizing to selected exons or exon combinations. Exon VASE, which has previously been shown to be present in both brain and heart NCAM mRNA, was virtually absent from skeletal muscle at all ages studied. In contrast, the majority of NCAM mRNA in postnatal skeletal muscle was shown to contain extra exons inserted between exons 12 and 13. Of the various possible exon combinations at this splice site

  12. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

    PubMed Central

    Baehr, Leslie M.; West, Daniel W.D.; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID:26826670

  13. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.

    PubMed

    Baehr, Leslie M; West, Daniel W D; Marcotte, George; Marshall, Andrea G; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength.

  14. Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

    PubMed

    Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob; Barrows, Katherine M; Briggs, Robert A; Kwon, Oh Sung; Young, Laura M; Hopkins, Paul N; Volpi, Elena; Marcus, Robin L; LaStayo, Paul C; Drummond, Micah J

    2015-09-15

    Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults.

  15. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  16. Structure of Skeletal Muscle

    MedlinePlus

    ... Cells, Tissues, & Membranes Cell Structure & Function Cell Structure Cell Function Body Tissues Epithelial Tissue Connective Tissue Muscle Tissue ... nerves. This is directly related to the primary function of skeletal muscle, ... an impulse from a nerve cell. Generally, an artery and at least one vein ...

  17. Glucocorticoids and Skeletal Muscle.

    PubMed

    Bodine, Sue C; Furlow, J David

    2015-01-01

    Glucocorticoids are known to regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite that of insulin. In many catabolic diseases, such as sepsis, starvation, and cancer cachexia, endogenous glucocorticoids are elevated contributing to the loss of muscle mass and function. Further, exogenous glucocorticoids are often given acutely and chronically to treat inflammatory conditions such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, resulting in muscle atrophy. This chapter will detail the nature of glucocorticoid-induced muscle atrophy and discuss the mechanisms thought to be responsible for the catabolic effects of glucocorticoids on muscle. PMID:26215994

  18. Skeletal muscle: an endocrine organ.

    PubMed

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

    2013-01-01

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

  19. Aging related changes in determinants of muscle force generating capacity: a comparison of muscle aging in men and male rodents.

    PubMed

    Ballak, Sam B; Degens, Hans; de Haan, Arnold; Jaspers, Richard T

    2014-03-01

    Human aging is associated with a progressive decline in skeletal muscle mass and force generating capacity, however the exact mechanisms underlying these changes are not fully understood. Rodents models have often been used to enhance our understanding of mechanisms of age-related changes in human skeletal muscle. However, to what extent age-related alterations in determinants of muscle force generating capacity observed in rodents resemble those in humans has not been considered thoroughly. This review compares the effect of aging on muscle force generating determinants (muscle mass, fiber size, fiber number, fiber type distribution and muscle specific tension), in men and male rodents at similar relative age. It appears that muscle aging in male F344*BN rat resembles that in men most; 32-35-month-old rats exhibit similar signs of muscle weakness to those of 70-80-yr-old men, and the decline in 36-38-month-old rats is similar to that in men aged over 80 yrs. For male C57BL/6 mice, age-related decline in muscle force generating capacity seems to occur only at higher relative age than in men. We conclude that the effects on determinants of muscle force differ between species as well as within species, but qualitatively show the same pattern as that observed in men.

  20. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.

    PubMed

    Buford, Thomas W; Anton, Stephen D; Judge, Andrew R; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M

    2010-10-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

  1. Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

    PubMed

    Chabi, B; Pauly, M; Carillon, J; Carnac, G; Favier, F B; Fouret, G; Bonafos, B; Vanterpool, F; Vernus, B; Coudray, C; Feillet-Coudray, C; Bonnieu, A; Lacan, D; Koechlin-Ramonatxo, C

    2016-06-01

    While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling.

  2. Age-Related Loss of Muscle Mass and Strength

    PubMed Central

    Goldspink, Geoffrey

    2012-01-01

    Age-related muscle wasting and increased frailty are major socioeconomic as well as medical problems. In the quest to extend quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and to prevent them falling and breaking bones that are brittle due to osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues, and a vicious circle is established as muscle loss results in bone loss and weakening of tendons. Molecular and proteomic approaches now provide strategies for preventing age-related muscle wasting. Here, attention is paid to the role of the GH/IGF-1 axis and the special role of the IGFI-Ec (mechano growth factor/MGF) which is derived from the IGF-I gene by alternative splicing. During aging MGF levels decline but when administered MGF activates the muscle satellite (stem) cells that “kick start” local muscle repair and induces hypertrophy. PMID:22506111

  3. Mechanotransduction in skeletal muscle

    PubMed Central

    Burkholder, Thomas J.

    2007-01-01

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

  4. Age-related changes in neuromuscular function of the quadriceps muscle in physically active adults.

    PubMed

    Mau-Moeller, Anett; Behrens, Martin; Lindner, Tobias; Bader, Rainer; Bruhn, Sven

    2013-06-01

    Substantial evidence exists for the age-related decline in maximal strength and strength development. Despite the importance of knee extensor strength for physical function and mobility in the elderly, studies focusing on the underlying neuromuscular mechanisms of the quadriceps muscle weakness are limited. The aim of this study was to investigate the contributions of age-related neural and muscular changes in the quadriceps muscle to decreases in isometric maximal voluntary torque (iMVT) and explosive voluntary strength. The interpolated twitch technique and normalized surface electromyography (EMG) signal during iMVT were analyzed to assess changes in neural drive to the muscles of 15 young and 15 elderly volunteers. The maximal rate of torque development as well as rate of torque development, impulse and neuromuscular activation in the early phase of contraction were determined. Spinal excitability was estimated using the H reflex technique. Changes at the muscle level were evaluated by analyzing the contractile properties and lean mass. The age-related decrease in iMVT was accompanied by a decline in voluntary activation and normalized surface EMG amplitude. Mechanical parameters of explosive voluntary strength were reduced while the corresponding muscle activation remained primarily unchanged. The spinal excitability of the vastus medialis was not different while M wave latency was longer. Contractile properties and lean mass were reduced. In conclusion, the age-related decline in iMVT of the quadriceps muscle might be due to a reduced neural drive and changes in skeletal muscle properties. The decrease in explosive voluntary strength seemed to be more affected by muscular than by neural changes. PMID:23453325

  5. Age-related structural and functional changes of low back muscles.

    PubMed

    Hiepe, Patrick; Gussew, Alexander; Rzanny, Reinhard; Kurz, Eduard; Anders, Christoph; Walther, Mario; Scholle, Hans-Christoph; Reichenbach, Jürgen R

    2015-05-01

    During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and muscle functional MRI (mfMRI) parameters, including proton transverse relaxation time (T2), diffusion (D) and vascular volume fraction (f), were investigated in moderately exercised low back muscles of young and late-middle-aged healthy subjects with (31)P-MR spectroscopy, T2- and diffusion-weighted MRI at 3T. In addition, T1-weighted MRI data were acquired to determine muscle cross-sectional areas (CSA) and to assess fat infiltration into muscle tissue. Except for pH, both age groups showed similar load-induced MR changes and rates of perceived exertion (RPE), which indicates comparable behavior of muscle activation at moderate loads. Changes of mfMRI parameters were significantly associated with RPE in both cohorts. Age-related differences were observed, with lower pH and higher Pi/ATP ratios as well as lower D and f values in the late-middle-aged subjects. These findings are ascribed to age-related changes of fiber type composition, fiber size and vascularity. Interestingly, post exercise f was negatively associated with fat infiltration with the latter being significantly higher in late-middle-aged subjects. CSA of low back muscles remained unchanged, while CSA of inner back muscle as well as mean T2 at rest were associated with maximum force capacity. Overall, applying the proposed MR approach provides evidence of age-related changes in several muscle tissue characteristics and gives new insights into the physiological processes that take place during aging.

  6. Detection of age-related duplications in mtDNA from human muscles and bones.

    PubMed

    Lacan, Marie; Thèves, Catherine; Keyser, Christine; Farrugia, Audrey; Baraybar, Jose-Pablo; Crubézy, Eric; Ludes, Bertrand

    2011-03-01

    Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

  7. Skeletal Muscle Hypertrophy after Aerobic Exercise Training

    PubMed Central

    Konopka, Adam R.; Harber, Matthew P.

    2014-01-01

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

  8. Skeletal muscle involvement in cardiomyopathies.

    PubMed

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

    2013-12-01

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

  9. Skeletal muscle cramps during exercise.

    PubMed

    Schwellnus, M P

    1999-11-01

    Cramps are painful, involuntary contractions of skeletal muscle that occur during or immediately after exercise and are common in endurance athletes. Although cramps can occur in many rare medical conditions, most athletes who have exercise-associated muscle cramping do not have congenital or acquired medical disorders. The cause of cramping is not well understood but may have to do with abnormal spinal control of motor neuron activity, particularly when a muscle contracts in a shortened position. Important risk factors include muscle fatigue and poor stretching habits. Treatment consists mainly of passive stretching, with supportive measures as needed. Special diagnostic studies and conditioning programs may be necessary for recurrent episodes.

  10. Phosphoproteomic analysis of aged skeletal muscle.

    PubMed

    Gannon, Joan; Staunton, Lisa; O'Connell, Kathleen; Doran, Philip; Ohlendieck, Kay

    2008-07-01

    One of the most important post-translational modifications is represented by phosphorylation on tyrosine, threonine and serine residues. Since abnormal phosphorylation is associated with various pathologies, it was of interest to perform a phosphoproteomic profiling of age-related skeletal muscle degeneration. We used the fluorescent phospho-specific Pro-Q Diamond dye to determine whether changes in the overall phosphorylation of the soluble skeletal muscle proteome differs significantly between young adult and senescent fibres. As an established model system of sarcopenia, we employed 30-month-old rat gastrocnemius fibres. Following the mass spectrometric identification of 59 major 2-D phosphoprotein landmark spots, the fluorescent dye staining survey revealed that 22 muscle proteins showed a differential expression pattern between 3-month- and 30-month-old muscle. Increased phosphorylation levels were shown for myosin light chain 2, tropomyosin alpha, lactate dehydrogenase, desmin, actin, albumin and aconitase. In contrast, decreased phospho-specific dye binding was observed for cytochrome c oxidase, creatine kinase and enolase. Thus, aging-induced alterations in phosphoproteins appear to involve the contractile machinery and the cytoskeleton, as well as the cytosolic and mitochondrial metabolism. This confirms that sarcopenia of old age is a complex neuromuscular pathology that is associated with drastic changes in the abundance and structure of key muscle proteins. PMID:18575773

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

    PubMed

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

    2014-02-01

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

  12. Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

    PubMed

    Nishida, Naoya; Taguchi, Aki; Motoyoshi, Kazumi; Hyodo, Masamitsu; Gyo, Kiyofumi; Desaki, Junzo

    2013-03-01

    We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing.

  13. Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism.

    PubMed

    Akasaki, Yuichi; Ouchi, Noriyuki; Izumiya, Yasuhiro; Bernardo, Barbara L; Lebrasseur, Nathan K; Walsh, Kenneth

    2014-02-01

    Aging is associated with the development of insulin resistance, increased adiposity, and accumulation of ectopic lipid deposits in tissues and organs. Starting in mid-life there is a progressive decline in lean muscle mass associated with the preferential loss of glycolytic, fast-twitch myofibers. However, it is not known to what extent muscle loss and metabolic dysfunction are causally related or whether they are independent epiphenomena of the aging process. Here, we utilized a skeletal-muscle-specific, conditional transgenic mouse expressing a constitutively active form of Akt1 to examine the consequences of glycolytic, fast-twitch muscle growth in young vs. middle-aged animals fed standard low-fat chow diets. Activation of the Akt1 transgene led to selective skeletal muscle hypertrophy, reversing the loss of lean muscle mass observed upon aging. The Akt1-mediated increase in muscle mass led to reductions in fat mass and hepatic steatosis in older animals, and corrected age-associated impairments in glucose metabolism. These results indicate that the loss of lean muscle mass is a significant contributor to the development of age-related metabolic dysfunction and that interventions that preserve or restore fast/glycolytic muscle may delay the onset of metabolic disease.

  14. Skeletal muscle satellite cells

    NASA Technical Reports Server (NTRS)

    Schultz, E.; McCormick, K. M.

    1994-01-01

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

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

    SciTech Connect

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

    2010-09-24

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

  16. Age-related changes in miR-143-3p:Igfbp5 interactions affect muscle regeneration.

    PubMed

    Soriano-Arroquia, Ana; McCormick, Rachel; Molloy, Andrew P; McArdle, Anne; Goljanek-Whysall, Katarzyna

    2016-04-01

    A common characteristic of aging is defective regeneration of skeletal muscle. The molecular pathways underlying age-related decline in muscle regenerative potential remain elusive. microRNAs are novel gene regulators controlling development and homeostasis and the regeneration of most tissues, including skeletal muscle. Here, we use satellite cells and primary myoblasts from mice and humans and an in vitro regeneration model, to show that disrupted expression of microRNA-143-3p and its target gene, Igfbp5, plays an important role in muscle regeneration in vitro. We identified miR-143 as a regulator of the insulin growth factor-binding protein 5 (Igfbp5) in primary myoblasts and show that the expression of miR-143 and its target gene is disrupted in satellite cells from old mice. Moreover, we show that downregulation of miR-143 during aging may act as a compensatory mechanism aiming at improving myogenesis efficiency; however, concomitant upregulation of miR-143 target gene, Igfbp5, is associated with increased cell senescence, thus affecting myogenesis. Our data demonstrate that dysregulation of miR-143-3p:Igfbp5 interactions in satellite cells with age may be responsible for age-related changes in satellite cell function. PMID:26762731

  17. [Regeneration capacity of skeletal muscle].

    PubMed

    Wernig, A

    2003-07-01

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

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

    PubMed

    Chatterjee, Somik; Ma, Ke

    2016-01-01

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

  19. Circadian clock regulation of skeletal muscle growth and repair

    PubMed Central

    Chatterjee, Somik; Ma, Ke

    2016-01-01

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

  20. Skeletal Muscle Abnormalities in Heart Failure.

    PubMed

    Kinugawa, Shintaro; Takada, Shingo; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

    2015-01-01

    Exercise capacity is lowered in patients with heart failure, which limits their daily activities and also reduces their quality of life. Furthermore, lowered exercise capacity has been well demonstrated to be closely related to the severity and prognosis of heart failure. Skeletal muscle abnormalities including abnormal energy metabolism, transition of myofibers from type I to type II, mitochondrial dysfunction, reduction in muscular strength, and muscle atrophy have been shown to play a central role in lowered exercise capacity. The skeletal muscle abnormalities can be classified into the following main types: 1) low endurance due to mitochondrial dysfunction; and 2) low muscle mass and muscle strength due to imbalance of protein synthesis and degradation. The molecular mechanisms of these skeletal muscle abnormalities have been studied mainly using animal models. The current review including our recent study will focus upon the skeletal muscle abnormalities in heart failure. PMID:26346520

  1. Regulation of NADPH oxidases in skeletal muscle.

    PubMed

    Ferreira, Leonardo F; Laitano, Orlando

    2016-09-01

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

  2. Age-Related Differences in Muscle Shear Moduli in the Lower Extremity.

    PubMed

    Akagi, Ryota; Yamashita, Yota; Ueyasu, Yuta

    2015-11-01

    This study investigated the age-related differences in shear moduli of the rectus femoris muscle (RF), the lateral head of the gastrocnemius muscle (LG) and the soleus muscle (SOL) using shear wave ultrasound elastography. Thirty-one young individuals and 49 elderly individuals volunteered for this study. The shear modulus of RF was determined at 50% of the thigh length, and those of LG and SOL were determined at 30% of the lower leg length. RF and LG shear moduli were significantly higher in young individuals than in elderly individuals, but there was no age-related difference in SOL shear modulus. From the standpoint of an index reflecting muscle mechanical properties, it is suggested that the lower muscle shear moduli of RF and LG are the reason for the decreased explosive muscle strength in the lower extremity and the increased risk of falls for elderly individuals.

  3. Angiotensin II: role in skeletal muscle atrophy.

    PubMed

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

    2012-09-01

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

  4. Channelopathies of skeletal muscle excitability

    PubMed Central

    Cannon, Stephen C.

    2016-01-01

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

  5. Redox control of skeletal muscle atrophy.

    PubMed

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

    2016-09-01

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

  6. Skeletal muscle is an endocrine organ.

    PubMed

    Iizuka, Kenji; Machida, Takuji; Hirafuji, Masahiko

    2014-01-01

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

  7. Satellite cells in human skeletal muscle plasticity.

    PubMed

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  8. Inflammation induced loss of skeletal muscle.

    PubMed

    Londhe, Priya; Guttridge, Denis C

    2015-11-01

    Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".

  9. Monitoring Murine Skeletal Muscle Function for Muscle Gene Therapy

    PubMed Central

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

    2011-01-01

    The primary function of skeletal muscle is to generate force. Muscle force production is compromised in various forms of acquired and/or inherited muscle diseases. An important goal of muscle gene therapy is to recover muscle strength. Genetically engineered mice and spontaneous mouse mutants are readily available for preclinical muscle gene therapy studies. In this chapter, we outlined the methods commonly used for measuring murine skeletal muscle function. These include ex vivo and in situ analysis of the contractile profile of a single intact limb muscle (the extensor digitorium longus for ex vivo assay and the tibialis anterior muscle for in situ assay), grip force analysis, and downhill treadmill exercise. Force measurement in a single muscle is extremely useful for pilot testing of new gene therapy protocols by local gene transfer. Grip force and treadmill assessments offer body-wide evaluation following systemic muscle gene therapy. PMID:21194022

  10. Regulation of skeletal muscle perfusion during exercise

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  11. Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

    DOE PAGES

    Alwood, Joshua S.; Kumar, Akhilesh; Tran, Luan H.; Wang, Angela; Limoli, Charles L.; Globus, Ruth K.

    2012-01-01

    Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy). We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male) were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137 Cs) and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evidentmore » at longer times in controls (4 months). Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy) exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis.« less

  12. Myostatin in the Pathophysiology of Skeletal Muscle

    PubMed Central

    Carnac, Gilles; Vernus, Barbara; Bonnieu, Anne

    2007-01-01

    Myostatin is an endogenous, negative regulator of muscle growth determining both muscle fiber number and size. The myostatin pathway is conserved across diverse species ranging from zebrafish to humans. Experimental models of muscle growth and regeneration have implicated myostatin as an important mediator of catabolic pathways in muscle cells. Inhibition of this pathway has emerged as a promising therapy for muscle wasting. Here we discuss the recent developments and the controversies in myostatin research, focusing on the molecular and cellular mechanisms underlying the actions of myostatin on skeletal muscle and the potential therapeutic role of myostatin on muscle-related disorders. PMID:19412331

  13. Cardiac assistance from skeletal muscle: a reappraisal.

    PubMed

    Salmons, Stanley

    2009-02-01

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

  14. Space travel directly induces skeletal muscle atrophy

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  15. Space travel directly induces skeletal muscle atrophy.

    PubMed

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

    1999-06-01

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

  16. Changes in skeletal muscle with aging: effects of exercise training.

    PubMed

    Rogers, M A; Evans, W J

    1993-01-01

    There is an approximate 30% decline in muscle strength and a 40% reduction in muscle area between the second and seventh decades of life. Thus, the loss of muscle mass with aging appears to be the major factor in the age-related loss of muscle strength. The loss of muscle mass is partially due to a significant decline in the numbers of both Type I and Type II muscle fibers plus a decrease in the size of the muscle cells, with the Type II fibers showing a preferential atrophy. There appears to be no loss of glycolytic capacity in senescent skeletal muscle whereas muscle oxidative enzyme activity and muscle capillarization decrease by about 25%. Vigorous endurance exercise training in older people, where the stimulus is progressively increased, elicits a proliferation of muscle capillaries, an increase in oxidative enzyme activity, and a significant improvement in VO2max. Likewise, progressive resistive training in older individuals results in muscle hypertrophy and increased strength, if the training stimulus is of a sufficient intensity and duration. Since older individuals adapt to resistive and endurance exercise training in a similar fashion to young people, the decline in the muscle's metabolic and force-producing capacity can no longer be considered as an inevitable consequence of the aging process. Rather, the adaptations in aging skeletal muscle to exercise training may prevent sarcopenia, enhance the ease of carrying out the activities of daily living, and exert a beneficial effect on such age-associated diseases as Type II diabetes, coronary artery disease, hypertension, osteoporosis, and obesity. PMID:8504850

  17. Aspects of skeletal muscle modelling.

    PubMed Central

    Epstein, Marcelo; Herzog, Walter

    2003-01-01

    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

  18. Do inflammatory cells influence skeletal muscle hypertrophy?

    PubMed

    Koh, Timothy J; Pizza, Francis X

    2009-06-01

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

  19. Skeletal muscle weakness in osteogeneis imperfecta mice

    PubMed Central

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

    2010-01-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (Po, Po/mg and Po/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased Po and an inability to sustain Po for the 300 ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. PMID:20619344

  20. How sex hormones promote skeletal muscle regeneration.

    PubMed

    Velders, Martina; Diel, Patrick

    2013-11-01

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

  1. Ovarian function in mice results in abrogated skeletal muscle PPARdelta and FoxO1-mediated gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause, the age-related loss of ovarian hormone production, promotes increased adiposity and associated metabolic pathology, but molecular mechanisms remain unclear. We previously reported that estrogen increases skeletal muscle PPARDelta expression in vivo, and transgenic mice overexpressing mus...

  2. Connexins in skeletal muscle development and disease.

    PubMed

    Merrifield, Peter A; Laird, Dale W

    2016-02-01

    Gap junctions consist of clusters of intercellular channels composed of connexins that connect adjacent cells and allow the exchange of small molecules. While the 21 member multi-gene family of connexins are ubiquitously found in humans, only Cx39, Cx40, Cx43 and Cx45 have been documented in developing myoblasts and injured adult skeletal muscle while healthy adult skeletal muscle is devoid of connexins. The use of gap junctional blockers and cultured myoblast cell lines have suggested that these connexins play a critical role in myotube formation and muscle regeneration. More recent genetically-modified mouse models where Cx43 function is greatly compromized or ablated have further supported a role for Cx43 in regulating skeletal muscle development. In the last decade, we have become aware of a cohort of patients that have a development disorder known as oculodentodigital dysplasia (ODDD). These patients harbor either gain or loss of Cx43 function gene mutations that result in many organ anomalies raising questions as to whether they suffer from defects in skeletal muscle formation or regeneration upon injury. Interesting, some ODDD patients report muscle weakness and loss of limb control but it is not clear if this is neurogenic or myogenic in origin. This review will focus on the role connexins play in muscle development and repair and discuss the impact of Cx43 mutants on muscle function. PMID:26688333

  3. Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype.

    PubMed

    Hénique, Carole; Mansouri, Abdelhak; Vavrova, Eliska; Lenoir, Véronique; Ferry, Arnaud; Esnous, Catherine; Ramond, Elodie; Girard, Jean; Bouillaud, Frédéric; Prip-Buus, Carina; Cohen, Isabelle

    2015-06-01

    Adult skeletal muscle is a dynamic, remarkably plastic tissue, which allows myofibers to switch from fast/glycolytic to slow/oxidative types and to increase mitochondrial fatty acid oxidation (mFAO) capacity and vascularization in response to exercise training. mFAO is the main muscle energy source during endurance exercise, with carnitine palmitoyltransferase 1 (CPT1) being the key regulatory enzyme. Whether increasing muscle mFAO affects skeletal muscle physiology in adulthood actually remains unknown. To investigate this, we used in vivo electrotransfer technology to express in mouse tibialis anterior (TA), a fast/glycolytic muscle, a mutated CPT1 form (CPT1mt) that is active but insensitive to malonyl-CoA, its physiologic inhibitor. In young (2-mo-old) adult mice, muscle CPT1mt expression enhanced mFAO (+40%), but also increased the percentage of oxidative fibers (+28%), glycogen content, and capillary-to-fiber density (+45%). This CPT1mt-induced muscle remodeling, which mimicked exercise-induced oxidative phenotype, led to a greater resistance to muscle fatigue. In the context of aging, characterized by sarcopenia and reduced oxidative capacity, CPT1mt expression in TAs from aged (20-mo-old) mice partially reversed aging-associated sarcopenia and fiber-type transition, and increased muscle capillarity. These findings provide evidence that mFAO regulates muscle phenotype and may be a potential target to combat age-related decline in muscle function. PMID:25713059

  4. Myoglobinuria and Skeletal Muscle Phosphorylase Deficiency

    PubMed Central

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

    1966-01-01

    Investigation of a patient complaining of exercise-induced dark urine, pain, stiffness and tenderness of skeletal muscle revealed findings characteristic of McArdle's disease. The dark urine was attributable to the excretion of myoglobin, and an ischemic exercise test failed to demonstrate the usual rise and fall in blood lactate and pyruvate. Enzyme assays of skeletal muscle showed an absence of phosphorylase, a slight increase in phosphorylase b kinase and a slight decrease in phosphoglucomutase. Chemical and histochemical analyses demonstrated an increase in the skeletal muscle glycogen content and an enlargement of the muscle cells. No abnormality of liver glycogen metabolism was found. In the absence of specific therapy, an effective and practical form of treatment is reduction of exercise below the threshold of symptoms. ImagesFig. 1Fig. 2Fig. 6Fig. 7Fig. 8 PMID:4952390

  5. Optimizing skeletal muscle reinnervation with nerve transfer.

    PubMed

    Lien, Samuel C; Cederna, Paul S; Kuzon, William M

    2008-11-01

    Denervation as a consequence of nerve injury causes profound structural and functional changes within skeletal muscle and can lead to a marked impairment in function of the affected limb. Prompt reinnervation of a muscle with a sufficient number of motion-specific motor axons generally results in good structural and functional recovery, whereas long-term denervation or insufficient or improper axonal recruitment uniformly results in poor functional recovery. Only nerve transfer has been highly efficacious in changing the clinical outcomes of patients with skeletal muscle denervation, especially in the case of proximal limb nerve injuries. Rapid reinnervation with an abundant number of motor axons remains the only clinically effective means to restore function to denervated skeletal muscles. PMID:18928892

  6. The benefits of coffee on skeletal muscle.

    PubMed

    Dirks-Naylor, Amie J

    2015-12-15

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

  7. Epigenetic regulation of skeletal muscle metabolism.

    PubMed

    Howlett, Kirsten F; McGee, Sean L

    2016-07-01

    Normal skeletal muscle metabolism is essential for whole body metabolic homoeostasis and disruptions in muscle metabolism are associated with a number of chronic diseases. Transcriptional control of metabolic enzyme expression is a major regulatory mechanism for muscle metabolic processes. Substantial evidence is emerging that highlights the importance of epigenetic mechanisms in this process. This review will examine the importance of epigenetics in the regulation of muscle metabolism, with a particular emphasis on DNA methylation and histone acetylation as epigenetic control points. The emerging cross-talk between metabolism and epigenetics in the context of health and disease will also be examined. The concept of inheritance of skeletal muscle metabolic phenotypes will be discussed, in addition to emerging epigenetic therapies that could be used to alter muscle metabolism in chronic disease states. PMID:27215678

  8. Denervation and reinnervation of skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

  9. Human Skeletal Muscle Health with Spaceflight

    NASA Astrophysics Data System (ADS)

    Trappe, Scott

    2012-07-01

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

  10. Therapies for sarcopenia and regeneration of old skeletal muscles

    PubMed Central

    Grounds, Miranda D

    2014-01-01

    Age related loss of skeletal muscle mass and function (sarcopenia) reduces independence and the quality of life for individuals, and leads to falls and fractures with escalating health costs for the rapidly aging human population. Thus there is much interest in developing interventions to reduce sarcopenia. One area that has attracted recent attention is the proposed use of myogenic stem cells to improve regeneration of old muscles. This mini-review challenges the fundamental need for myogenic stem cell therapy for sarcopenia. It presents evidence that demonstrates the excellent capacity of myogenic stem cells from very old rodent and human muscles to form new muscles after experimental myofiber necrosis. The many factors required for successful muscle regeneration are considered with a strong focus on integration of components of old muscle bioarchitecture. The fundamental role of satellite cells in homeostasis of normal aging muscles and the incidence of endogenous regeneration in old muscles is questioned. These issues, combined with problems for clinical myogenic stem cell therapies for severe muscle diseases, raise fundamental concerns about the justification for myogenic stem cell therapy for sarcopenia. PMID:25101758

  11. Gene Regions Responding to Skeletal Muscle Atrophy

    NASA Technical Reports Server (NTRS)

    Booth, Frank W.

    1997-01-01

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

  12. Satellite cells in human skeletal muscle plasticity

    PubMed Central

    Snijders, Tim; Nederveen, Joshua P.; McKay, Bryon R.; Joanisse, Sophie; Verdijk, Lex B.; van Loon, Luc J. C.; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models. PMID:26557092

  13. Mechanotransduction pathways in skeletal muscle hypertrophy.

    PubMed

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

    2012-02-01

    In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process. PMID:22171534

  14. Mechanotransduction pathways in skeletal muscle hypertrophy.

    PubMed

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

    2012-02-01

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

  15. Age-related differences in Achilles tendon properties and triceps surae muscle architecture in vivo.

    PubMed

    Stenroth, Lauri; Peltonen, Jussi; Cronin, Neil J; Sipilä, Sarianna; Finni, Taija

    2012-11-01

    This study examined the concurrent age-related differences in muscle and tendon structure and properties. Achilles tendon morphology and mechanical properties and triceps surae muscle architecture were measured from 100 subjects [33 young (24 ± 2 yr) and 67 old (75 ± 3 yr)]. Motion analysis-assisted ultrasonography was used to determine tendon stiffness, Young's modulus, and hysteresis during isometric ramp contractions. Ultrasonography was used to measure muscle architectural features and size and tendon cross-sectional area. Older participants had 17% lower (P < 0.01) Achilles tendon stiffness and 32% lower (P < 0.001) Young's modulus than young participants. Tendon cross-sectional area was also 16% larger (P < 0.001) in older participants. Triceps surae muscle size was smaller (P < 0.05) and gastrocnemius medialis muscle fascicle length shorter (P < 0.05) in old compared with young. Maximal plantarflexion force was associated with tendon stiffness and Young's modulus (r = 0.580, P < 0.001 and r = 0.561, P < 0.001, respectively). Comparison between old and young subjects with similar strengths did not reveal a difference in tendon stiffness. The results suggest that regardless of age, Achilles tendon mechanical properties adapt to match the level of muscle performance. Old people may compensate for lower tendon material properties by increasing tendon cross-sectional area. Lower tendon stiffness in older subjects might be beneficial for movement economy in low-intensity locomotion and thus optimized for their daily activities.

  16. Age-related relationships between muscle fat content and metabolic traits in growing rabbits.

    PubMed

    Gondret, Florence; Hocquette, Jean-François; Herpin, Patrick

    2004-01-01

    This study was aimed at ascribing muscle fat accretion in growing rabbits to changes in several extra-muscular and intra-muscular metabolic pathways. At 10 wk or 20 wk of age (n = 8 per group), tissue lipid content and metabolic indicators of nutrient anabolic or catabolic pathways were simultaneously assessed in the liver, perirenal fat, the heart and the Longissimus lumborum (LL) muscle, together with plasma concentrations in energy-yielding metabolites. Lipid content significantly increased with age (P < or = 0.01) in the glycolytic LL muscle (+67%) and the oxidative heart (+30%). In the former muscle, it was statistically correlated (r2 = 0.68; P < 0.01) to the changes in the orientation of muscle metabolism towards an enhanced lipogenic capacity and a depressed capacity for fatty acid transport and nutrient oxidation, and to indications of lower availability in plasma glucose and triglycerides. In the heart, age-related fat accretion was positively associated (r2 = 0.48, P < 0.01) to intrinsic metabolic changes towards an enhanced lipogenic capacity, together with a lower availability in plasma glucose. Variables representative of cardiac catabolic capacity tended to be negatively correlated to fat content in the heart (r2 = 0.15, P = 0.07). In growing rabbits, muscle fat content variation was proven to result from a reciprocal balance between catabolic and anabolic fatty acid fluxes, rather than to be assigned to one specific energy metabolic pathway.

  17. Cytokine Signaling in Skeletal Muscle Wasting.

    PubMed

    Zhou, Jin; Liu, Bin; Liang, Chun; Li, Yangxin; Song, Yao-Hua

    2016-05-01

    Skeletal muscle wasting occurs in a variety of diseases including diabetes, cancer, Crohn's disease, chronic obstructive pulmonary disease (COPD), disuse, and denervation. Tumor necrosis factor α (TNF-α) is involved in mediating the wasting effect. To date, a causal relationship between TNF-α signaling and muscle wasting has been established in animal models. However, results from clinical trials are conflicting. This is partly due to the fact that other factors such as TNF-like weak inducer of apoptosis (TWEAK) and interleukin 6 (IL-6) are also involved in skeletal muscle wasting. Because muscle wasting is often associated with physical inactivity and reduced food intake, therapeutic interventions will be most effective when multiple approaches are used in conjunction with nutritional support and exercise. PMID:27025788

  18. Laminin-211 in skeletal muscle function

    PubMed Central

    Holmberg, Johan; Durbeej, Madeleine

    2013-01-01

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

  19. YAP-Mediated Mechanotransduction in Skeletal Muscle

    PubMed Central

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

    2016-01-01

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

  20. Aging-Related Geniohyoid Muscle Atrophy Is Related to Aspiration Status in Healthy Older Adults

    PubMed Central

    2013-01-01

    Background. Age-related muscle weakness due to atrophy and fatty infiltration in orofacial muscles may be related to swallowing deficits in older adults. An important component of safe swallowing is the geniohyoid (GH) muscle, which helps elevate and stabilize the hyoid bone, thus protecting the airway. This study aimed to explore whether aging and aspiration in older adults were related to GH muscle atrophy and fatty infiltration. Method. Eighty computed tomography scans of the head and neck from 40 healthy older (average age 78 years) and 40 younger adults (average age 32 years) were analyzed. Twenty aspirators and 20 nonaspirators from the 40 older adults had been identified previously. Two-dimensional views in the sagittal and coronal planes were used to measure the GH cross-sectional area and fatty infiltration. Results. GH cross-sectional area was larger in men than in women (p < .05). Decreased cross-sectional area was associated with aging (p < .05), and cross-sectional area was significantly smaller in aspirators compared with nonaspirators, but only among the older men (p < .01). Increasing fatty infiltration was associated with aging in the middle (p < .05) and posterior (p < .01) portions of the GH muscle. There was no significant difference in fatty infiltration of the GH muscle among aspirators and nonaspirators. Conclusion. GH muscle atrophy was associated with aging and aspiration. Fatty infiltration in the GH muscle was increased with aging but not related to aspiration status. These findings suggest that GH muscle atrophy may be a component of decreased swallowing safety and aspiration in older adults and warrants further investigation. PMID:23112114

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

    PubMed

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

    2013-02-01

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

  2. Isolation, Cryosection and Immunostaining of Skeletal Muscle.

    PubMed

    Ortuste Quiroga, Huascar P; Goto, Katsumasa; Zammit, Peter S

    2016-01-01

    Adult skeletal muscle is maintained and repaired by resident stem cells called satellite cells, located between the plasmalemma of a muscle fiber, and the surrounding basal lamina. When needed, satellite cells are activated to form proliferative myoblasts, that then differentiate and fuse to existing muscle fibers, or fuse together to form replacement myofibers. In parallel, a proportion of satellite cells self-renew, to maintain the stem cell pool. To date, Pax7 is the marker of choice for identifying quiescent satellite cells. Co-immunostaining of skeletal muscle with Pax7 and laminin allows both identification of satellite cells, and the myofiber that they are associated with. Furthermore, satellite cells can be followed through the early stages of the myogenic program by co-immunostaining with myogenic regulatory factors such as MyoD. To test genetically modified mice for satellite cell expression, co-immunostaining can be performed for Pax7 and reporter genes such as eGFP. Here, we describe a method for identification of satellite cells in skeletal muscle sections, including muscle isolation, cryosectioning and co-immunostaining for Pax7 and laminin. PMID:27492168

  3. Redox Characterization of Functioning Skeletal Muscle

    PubMed Central

    Zuo, Li; Pannell, Benjamin K.

    2015-01-01

    Skeletal muscle physiology is influenced by the presence of chemically reactive molecules such as reactive oxygen species (ROS). These molecules regulate multiple redox-sensitive signaling pathways that play a critical role in cellular processes including gene expression and protein modification. While ROS have gained much attention for their harmful effects in muscle fatigue and dysfunction, research has also shown ROS to facilitate muscle adaptation after stressors such as physical exercise. This manuscript aims to provide a comprehensive review of the current understanding of redox signaling in skeletal muscle. ROS-induced oxidative stress and its role in the aging process are discussed. Mitochondria have been shown to generate large amounts of ROS during muscular contractions, and thus are susceptible to oxidative stress. ROS can modify proteins located in the mitochondrial membrane leading to cell death and osmotic swelling. ROS also contribute to the necrosis and inflammation of muscle fibers that is associated with muscular diseases including Duchenne muscular dystrophy. It is imperative that future research continues to investigate the exact role of ROS in normal skeletal muscle function as well as muscular dysfunction and disease. PMID:26635624

  4. Human skeletal muscle biochemical diversity

    PubMed Central

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

    2012-01-01

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

  5. Skeletal muscle fibre types in the dog.

    PubMed Central

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

    1993-01-01

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

  6. Advances and challenges in skeletal muscle angiogenesis

    PubMed Central

    Baum, Oliver; Hellsten, Ylva; Egginton, Stuart

    2015-01-01

    The role of capillaries is to serve as the interface for delivery of oxygen and removal of metabolites to/from tissues. During the past decade there has been a proliferation of studies that have advanced our understanding of angiogenesis, demonstrating that tissue capillary supply is under strict control during health but poorly controlled in disease, resulting in either excessive capillary growth (pathological angiogenesis) or losses in capillarity (rarefaction). Given that skeletal muscle comprises nearly 40% of body mass in humans, skeletal muscle capillary density has a significant impact on metabolism, endocrine function, and locomotion and is tightly regulated at many different levels. Skeletal muscle is also high adaptable and thus one of the few organ systems that can be experimentally manipulated (e.g., by exercise) to study physiological regulation of angiogenesis. This review will focus on the methodological concerns that have arisen in determining skeletal muscle capillarity and highlight the concepts that are reshaping our understanding of the angio-adaptation process. We also summarize selected new findings (physical influences, molecular changes, and ultrastructural rearrangement of capillaries) that identify areas of future research with the greatest potential to expand our understanding of how angiogenesis is normally regulated, and that may also help to better understand conditions of uncontrolled (pathological) angiogenesis. PMID:26608338

  7. Tissue engineering skeletal muscle for orthopaedic applications

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  8. Development of Sensory Receptors in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    DeSantis, Mark

    2000-01-01

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

  9. Apoptosis in capillary endothelial cells in ageing skeletal muscle

    PubMed Central

    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

    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-2α, 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

  10. Age-related changes of muscle and plasma amino acids in healthy children.

    PubMed

    Hammarqvist, Folke; Angsten, Gertrud; Meurling, Staffan; Andersson, Kerstin; Wernerman, Jan

    2010-07-01

    The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1-4 years, n = 13 and group 3: 5-15 years, n = 15). A reference group of healthy adults (21-38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.

  11. Skeletal muscle metastasis from uterine leiomyosarcoma.

    PubMed

    O'Brien, J M; Brennan, D D; Taylor, D H; Holloway, D P; Hurson, B; O'Keane, J C; Eustace, S J

    2004-11-01

    A case of a 68-year-old woman who presented with a rapidly enlarging painful right thigh mass is presented. She had a known diagnosis of uterine leiomyosarcoma following a hysterectomy for dysfunctional uterine bleeding. She subsequently developed a single hepatic metastatic deposit that responded well to radiofrequency ablation. Whole-body MRI and MRA revealed a vascular mass in the sartorius muscle and a smaller adjacent mass in the gracilis muscle, proven to represent metastatic leiomyosarcoma of uterine origin. To our knowledge, metastatic uterine leiomyosarcoma to the skeletal muscle has not been described previously in the English medical literature.

  12. Insulin Increases Ceramide Synthesis in Skeletal Muscle

    PubMed Central

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

    2014-01-01

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

  13. Cellular Players in Skeletal Muscle Regeneration

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2005-07-01

    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

  15. Age-related weakness of proximal muscle studied with motor cortical mapping: a TMS study.

    PubMed

    Plow, Ela B; Varnerin, Nicole; Cunningham, David A; Janini, Daniel; Bonnett, Corin; Wyant, Alexandria; Hou, Juliet; Siemionow, Vlodek; Wang, Xiao-Feng; Machado, Andre G; Yue, Guang H

    2014-01-01

    Aging-related weakness is due in part to degeneration within the central nervous system. However, it is unknown how changes to the representation of corticospinal output in the primary motor cortex (M1) relate to such weakness. Transcranial magnetic stimulation (TMS) is a noninvasive method of cortical stimulation that can map representation of corticospinal output devoted to a muscle. Using TMS, we examined age-related alterations in maps devoted to biceps brachii muscle to determine whether they predicted its age-induced weakness. Forty-seven right-handed subjects participated: 20 young (22.6 ± 0.90 years) and 27 old (74.96 ± 1.35 years). We measured strength as force of elbow flexion and electromyographic activation of biceps brachii during maximum voluntary contraction. Mapping variables included: 1) center of gravity or weighted mean location of corticospinal output, 2) size of map, 3) volume or excitation of corticospinal output, and 4) response density or corticospinal excitation per unit area. Center of gravity was more anterior in old than in young (p<0.001), though there was no significant difference in strength between the age groups. Map size, volume, and response density showed no significant difference between groups. Regardless of age, center of gravity significantly predicted strength (β = -0.34, p = 0.005), while volume adjacent to the core of map predicted voluntary activation of biceps (β = 0.32, p = 0.008). Overall, the anterior shift of the map in older adults may reflect an adaptive change that allowed for the maintenance of strength. Laterally located center of gravity and higher excitation in the region adjacent to the core in weaker individuals could reflect compensatory recruitment of synergistic muscles. Thus, our study substantiates the role of M1 in adapting to aging-related weakness and subtending strength and muscle activation across age groups. Mapping from M1 may offer foundation for an examination of mechanisms that preserve

  16. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats

    PubMed Central

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E.; Hernandez, Jessica Soto; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-01-01

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle. PMID:26415224

  17. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.

    PubMed

    Javadov, Sabzali; Jang, Sehwan; Rodriguez-Reyes, Natividad; Rodriguez-Zayas, Ana E; Soto Hernandez, Jessica; Krainz, Tanja; Wipf, Peter; Frontera, Walter

    2015-11-24

    Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.

  18. Reactive Oxygen Species in Skeletal Muscle Signaling

    PubMed Central

    Barbieri, Elena; Sestili, Piero

    2012-01-01

    Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also—within certain concentrations—useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS hold a particular relevance. According to their hormetic nature, in muscles ROS may trigger different signaling pathways leading to diverging responses, from adaptation to cell death. Whether a “positive” or “negative” response will prevail depends on many variables such as, among others, the site of ROS production, the persistence of ROS flow or target cells' antioxidant status. In this light, a specific threshold of physiological ROS concentrations above which ROS exert negative, toxic effects is hard to determine, and the concept of “physiologically compatible” levels of ROS would better fit with such a dynamic scenario. In this review these concepts will be discussed along with the most relevant signaling pathways triggered and/or affected by ROS in skeletal muscle. PMID:22175016

  19. Age-related structural changes in upper extremity muscle tissue in a non-human primate model

    PubMed Central

    Santago, Anthony C.; Plate, Johannes F.; Shively, Carol A.; Register, Thomas C.; Smith, Thomas L.; Saul, Katherine R.

    2015-01-01

    Background Longitudinal studies of upper extremity aging in humans include logistical concerns that animal models can overcome. The vervet is a promising species with which to study aging related processes. However, age-related changes in upper extremity muscle structure have not been quantified in this species. This study measured age-related changes to muscle structure, examined relationships between muscle structure and measures of physical performance, and evaluated the presence of rotator cuff tears. Methods Muscle structure: volume, optimal fiber length, physiological cross-sectional area (PCSA), of 10 upper extremity muscles was quantified from the right upper limb of 5 middle aged and 6 older adult female vervets. Results Total measured PCSA was smaller (p=0.001) in the older adult vervets than the middle aged vervets. Muscle volume reduction predominate the age-related reductions in PCSA. Total measured PCSA was not correlated to any measures of physical performance. No rotator cuff tears were observed. Supraspinatus volume was relatively larger and deltoid volume relatively smaller in the vervet compared to a human. Conclusion The vervet is an appropriate translational model for age-related upper extremity muscle volume loss. Functional measures were not correlated to PCSA, suggesting the vervets may have enough strength for normal function despite loss of muscle tissue. Reduced relative demand on the supraspinatus may be responsible for the lack of naturally occurring rotator cuff tears. PMID:25963066

  20. Wave biomechanics of the skeletal muscle

    NASA Astrophysics Data System (ADS)

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

    2006-12-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. TWEAK promotes exercise intolerance by decreasing skeletal muscle oxidative phosphorylation capacity

    PubMed Central

    2013-01-01

    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 γ coactivator 1α (PGC-1α) 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-1α 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

  3. Skeletal muscle mitochondrial energetic efficiency and aging.

    PubMed

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Liverini, Giovanna; Iossa, Susanna

    2015-01-01

    Aging is associated with a progressive loss of maximal cell functionality, and mitochondria are considered a key factor in aging process, since they determine the ATP availability in the cells. Mitochondrial performance during aging in skeletal muscle is reported to be either decreased or unchanged. This heterogeneity of results could partly be due to the method used to assess mitochondrial performance. In addition, in skeletal muscle the mitochondrial population is heterogeneous, composed of subsarcolemmal and intermyofibrillar mitochondria. Therefore, the purpose of the present review is to summarize the results obtained on the functionality of the above mitochondrial populations during aging, taking into account that the mitochondrial performance depends on organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP from the oxidation of fuels. PMID:25970752

  4. Tissue Engineered Strategies for Skeletal Muscle Injury

    PubMed Central

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

    2012-01-01

    Skeletal muscle injuries are common in athletes, occurring with direct and indirect mechanisms and marked residual effects, such as severe long-term pain and physical disability. Current therapy consists of conservative management including RICE protocol (rest, ice, compression and elevation), nonsteroidal anti-inflammatory drugs, and intramuscular corticosteroids. However, current management of muscle injuries often does not provide optimal restoration to preinjury status. New biological therapies, such as injection of platelet-rich plasma and stem-cell-based therapy, are appealing. Although some studies support PRP application in muscle-injury management, reasons for concern persist, and further research is required for a standardized and safe use of PRP in clinical practice. The role of stem cells needs to be confirmed, as studies are still limited and inconsistent. Further research is needed to identify mechanisms involved in muscle regeneration and in survival, proliferation, and differentiation of stem cells. PMID:25098362

  5. Leptin receptors in human skeletal muscle.

    PubMed

    Guerra, Borja; Santana, Alfredo; Fuentes, Teresa; Delgado-Guerra, Safira; Cabrera-Socorro, Alfredo; Dorado, Cecilia; Calbet, Jose A L

    2007-05-01

    Human skeletal muscle expresses leptin receptor mRNA; however, it remains unknown whether leptin receptors (OB-R) are also expressed at the protein level. Fourteen healthy men (age = 33.1 +/- 2.0 yr, height = 175.9 +/- 1.7 cm, body mass = 81.2 +/- 3.8 kg, body fat = 22.5 +/- 1.9%; means +/- SE) participated in this investigation. The expression of OB-R protein was determined in skeletal muscle, subcutaneous adipose tissue, and hypothalamus using a polyclonal rabbit anti-human leptin receptor. Three bands with a molecular mass close to 170, 128, and 98 kDa were identified by Western blot with the anti-OB-R antibody. All three bands were identified in skeletal muscle: the 98-kDa and 170-kDa bands were detected in hypothalamus, and the 98-kDa and 128-kDa bands were detected in thigh subcutaneous adipose tissue. The 128-kDa isoform was not detected in four subjects, whereas in the rest its occurrence was fully explained by the presence of intermuscular adipose tissue, as demonstrated using an anti-perilipin A antibody. No relationship was observed between the basal concentration of leptin in serum and the 170-kDa band density. In conclusion, a long isoform of the leptin receptor with a molecular mass close to 170 kDa is expressed at the protein level in human skeletal muscle. The amount of 170-kDa protein appears to be independent of the basal concentration of leptin in serum.

  6. Development of Sensory Receptors in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    DeSantis, Mark

    2000-01-01

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

  7. Effect of limb immobilization on skeletal muscle

    NASA Technical Reports Server (NTRS)

    Booth, F. W.

    1982-01-01

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

  8. Extrarenal potassium adaptation: role of skeletal muscle

    SciTech Connect

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

    1986-08-01

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

  9. Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle.

    PubMed

    Cho, Yoshitake; Hazen, Bethany C; Gandra, Paulo G; Ward, Samuel R; Schenk, Simon; Russell, Aaron P; Kralli, Anastasia

    2016-02-01

    Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age-related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1- and ESRR-induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno-associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4-wk-old mice. Compared to control vector, AAV1-Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40-80%). Moreover, AAV1-Perm1-transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31%, respectively), without prominent changes in fiber-type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise. PMID:26481306

  10. Satellite Cells and Skeletal Muscle Regeneration.

    PubMed

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

    2015-07-01

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

  11. Phosphorylation of human skeletal muscle myosin

    SciTech Connect

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

    1986-03-01

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

  12. GLUT-3 expression in human skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  13. Physiological mechanisms of action of incretin and insulin in regulating skeletal muscle metabolism.

    PubMed

    Abdulla, Haitham; Phillips, Bethan; Smith, Kenneth; Wilkinson, Daniel; Atherton, Philip J; Idris, Iskandar

    2014-01-01

    Type II diabetes (T2D) is a progressive condition affecting approximately 350 million adults worldwide. Whilst skeletal muscle insulin resistance and beta-cell dysfunction are recognised causes of T2D, progressive loss of lean muscle mass (reducing surface area for glucose disposal area) in tandem with ageing-related adiposity (i.e. sarcopenic obesity) also plays an important role in driving hyperglycaemia progression. The anabolic effects of nutrition on the muscle are driven by the uptake of amino acids, into skeletal muscle protein, and insulin plays a crucial role in regulating this. Meanwhile glucagon-like peptide (GLP-1) and glucose- dependent insulinotropic peptide (GIP) are incretin hormones released from the gut into the bloodstream in response to macronutrients, and have an established role in enhancing insulin secretion. Intriguingly, endocrine functions of incretins were recently shown to extend beyond classical insulinotropic effects, with GLP-1/GIP receptors being found in extra-pancreatic cells i.e., skeletal muscle and peripheral (muscle) microvasculature. Since, incretins have been shown to modulate blood flow and muscle glucose uptake in an insulin-independent manner, incretins may play a role in regulating nutrient-mediated modulation of muscle metabolism and microvascular tone, independently of their insulinotropic effects. In this review we will discuss the role of skeletal muscle in glucose homeostasis, disturbances related to insulin resistance, regulation of skeletal muscle metabolism, muscle microvascular abnormalities and disturbances of protein (PRO) metabolism seen in old age and T2D. We will also discuss the emerging non-insulinotropic role of GLP-1 in modulating skeletal muscle metabolism and microvascular blood flow. PMID:25323297

  14. Endoplasmic Reticulum Stress in Skeletal Muscle Homeostasis and Disease

    PubMed Central

    Rayavarapu, Sree; Coley, William

    2013-01-01

    Our appreciation of the role of endoplasmic reticulum(ER) stress pathways in both skeletal muscle homeostasis and the progression of muscle diseases is gaining momentum. This review provides insight into ER stress mechanisms during physiologic and pathological disturbances in skeletal muscle. The role of ER stress in the response to dietary alterations and acute stressors, including its role in autoimmune and genetic muscle disorders, has been described. Recent studies identifying ER stress markers in diseased skeletal muscle are noted. The emerging evidence for ER–mitochondrial interplay in skeletal muscle and its importance during chronic ER stress in activation of both inflammatory and cell death pathways (autophagy, necrosis, and apoptosis) have been discussed. Thus, understanding the ER stress–related molecular pathways underlying physiologic and pathological phenotypes in healthy and diseased skeletal muscle should lead to novel therapeutic targets for muscle disease. PMID:22410828

  15. Circadian Rhythms, skeletal muscle molecular clocks and exercise

    PubMed Central

    Schroder, Elizabeth A.; Esser, Karyn A.

    2013-01-01

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

  16. Murine models of atrophy, cachexia, and sarcopenia in skeletal muscle

    PubMed Central

    Romanick, Mark; Brown-Borg, Holly M.

    2013-01-01

    With the extension of life span over the past several decades, the age-related loss of muscle mass and strength that characterizes sarcopenia is becoming more evident and thus, has a more significant impact on society. To determine ways to intervene and delay, or even arrest the physical frailty and dependence that accompany sarcopenia, it is necessary to identify those biochemical pathways that define this process. Animal models that mimic one or more of the physiological pathways involved with this phenomenon are very beneficial in providing an understanding of the cellular processes at work in sarcopenia. The ability to influence pathways through genetic manipulation gives insight into cellular responses and their impact on the physical expression of sarcopenia. This review evaluates several murine models that have the potential to elucidate biochemical processes integral to sarcopenia. Identifying animal models that reflect sarcopenia or its component pathways will enable researchers to better understand those pathways that contribute to age-related skeletal muscle mass loss, and in turn, develop interventions that will prevent, retard, arrest, or reverse this phenomenon. PMID:23523469

  17. Skeletal Muscle Gender Dimorphism from Proteomics

    PubMed Central

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

    2011-01-01

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

  18. Skeletal muscle gender dimorphism from proteomics.

    PubMed

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

    2011-01-01

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

  19. REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE

    PubMed Central

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

    2014-01-01

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

  20. Highly extensible skeletal muscle in snakes.

    PubMed

    Close, Matthew; Perni, Stefano; Franzini-Armstrong, Clara; Cundall, David

    2014-07-15

    Many snakes swallow large prey whole, and this process requires large displacements of the unfused tips of the mandibles and passive stretching of the soft tissues connecting them. Under these conditions, the intermandibular muscles are highly stretched but subsequently recover normal function. In the highly stretched condition we observed in snakes, sarcomere length (SL) increased 210% its resting value (SL0), and actin and myosin filaments no longer overlapped. Myofibrils fell out of register and triad alignment was disrupted. Following passive recovery, SLs returned to 82% SL0, creating a region of double-overlapping actin filaments. Recovery required recoil of intracellular titin filaments, elastic cytoskeletal components for realigning myofibrils, and muscle activation. Stretch of whole muscles exceeded that of sarcomeres as a result of extension of folded terminal tendon fibrils, stretching of extracellular elastin and independent slippage of muscle fibers. Snake intermandibular muscles thus provide a unique model of how basic components of vertebrate skeletal muscle can be modified to permit extreme extensibility.

  1. Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

    PubMed Central

    Vu, Lisa; Haygood, Tamara Miner

    2015-01-01

    Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus. PMID:27190554

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

    NASA Technical Reports Server (NTRS)

    Fitts, Robert H.

    2003-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-04-01

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

  6. Modeling of the Skeletal Muscle Microcirculation

    NASA Astrophysics Data System (ADS)

    Jacobitz, Frank; Beth, Christophe; Salado, Jerome

    2004-11-01

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

  7. Effects of Use and Disuse on Non-paralyzed and Paralyzed Skeletal Muscles

    PubMed Central

    Dolbow, David R.; Gorgey, Ashraf S.

    2016-01-01

    Skeletal muscle is an integral part of the somatic nervous system and plays a primary role in the performance of physical activities. Because physical activity is vital to countering the effects of aging and age related diseases and is a key component in the maintenance of healthy body composition it is important to understand the effects of use and disuse on skeletal muscle. While voluntary muscle activity provides optimal benefits to muscle and the maintenance of healthy body composition, neuromuscular electrical stimulation may be a viable alternative activity for individuals with paralysis. Body composition with a healthy muscle to fat ratio has been associated with healthy blood lipid and glucose profiles that may decrease the risk of cardiovascular and metabolic diseases. PMID:26816665

  8. Effect of vitamin D on skeletal muscle.

    PubMed

    Walrand, Stéphane

    2016-06-01

    Beyond its traditional biological roles on bone health, extra-skeletal effects of vitamin D are currently under extensive research. The expression of the vitamin D receptor in most tissues has also strengthened the argument for its multiple functions. Among these, the effect of vitamin D on the mass and muscle performance has long been discussed. In ancient Greece, Herodotus recommended the sun as a cure for the "weak and soft muscles" and former Olympians exposed to sunlight to improve their physical performance. In 1952, Dr Spellerberg, a sports physiologist, has conducted an extensive study on the effects of UV irradiation on the performance of elite athletes. Following the significant results of this investigation, the scientist has informed the Olympic Committee that UV irradiation had a "persuasive" effect on physical performance and motor skills. These data are consistent with many subsequent studies reporting an improvement in physical activity, speed and endurance in young subjects treated with UV or with supplements containing vitamin D. Additional observation indicates a significant effect on muscle strength, particularly in the lower limbs. Concerning the mechanisms involved, some recent fundamental studies have shown that vitamin D exerts some molecular effects within the muscle cell. Specifically, a regulatory effect of vitamin D on calcium flux, mineral homeostasis and signaling pathways controlling protein anabolism has been reported in muscle tissue. Several epidemiological studies show that low vitamin D status is always associated with a decrease in muscle mass, strength and contractile capacity in older people. Vitamin D deficiency accelerates muscle loss with age (sarcopenia), and therefore leads to a reduction in physical capacity and to an increased risk of falls and fractures. In contrast, an additional intake of vitamin D in older people significantly improves muscle function and physical performance. PMID:27100224

  9. Osmoregulatory processes and skeletal muscle metabolism

    NASA Astrophysics Data System (ADS)

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

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

  10. Proteomic profiling reveals a severely perturbed protein expression pattern in aged skeletal muscle.

    PubMed

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

    2007-08-01

    Extended longevity is often accompanied by frailty and increased susceptibility to a variety of crippling disorders. One of the most striking features of human aging is sarcopenia, which is defined as the age-related decline in skeletal muscle mass and strength. Although various metabolic and functional defects in aging muscle fibres have been described over the last decade, it is not known whether a pathophysiological hierarchy exists within degenerative pathways leading to muscle wasting. Hence, in order to identify novel biomarkers of age-dependent skeletal muscle degeneration, we have here applied mass spectrometry-based proteomics for studying global muscle protein expression patterns. As a model system of sarcopenia, we have employed crude extracts from senescent rat gastrocnemius muscle, as compared to young adult tissue preparations. Using the highly sensitive protein dye Deep Purple for the analysis of the 2-D separated muscle proteome and peptide mass fingerprinting for the identification of individual protein spots, a differential expression pattern was observed for contractile proteins, metabolic factors, regulatory components and heat shock elements. A drastic increase was shown for alpha B-crystallin, myosin light chain MLC-1, phosphoglycerate kinase, adenylate kinase, triosephosphate isomerase, albumin, aconitase and nucleoside-diphosphate kinase in aged fibres. In contrast, the expression of pyruvate kinase, aldolase, creatine kinase, transferrin, alpha-tropomyosin and myosin light chain MLC-3 was decreased in old skeletal muscle. Comparative 2-D immunoblotting of selected candidate proteins has confirmed the effect of aging on the skeletal muscle proteome. These findings demonstrate a severely perturbed protein expression pattern in aged skeletal muscle, which reflects the underlying molecular alterations causing a drastic decline of muscle strength in the senescent organism. In the long-term, the systematic deduction of abnormal protein expression

  11. Dairy in Adulthood: From Foods to Nutrient Interactions on Bone and Skeletal Muscle Health

    PubMed Central

    Bonjour, Jean-Philippe; Kraenzlin, Marius; Levasseur, Régis; Warren, Michelle; Whiting, Susan

    2013-01-01

    The risk of fragility fractures exponentially increases with aging. Reduced mass and strength of both bone in osteoporosis and skeletal muscle in sarcopenia play a key role in the age-related incidence of fragility fractures. Undernutrition is often observed in the elderly, particularly in those subjects experiencing osteoporotic fractures, more likely as a cause than a consequence. Calcium (Ca), inorganic phosphate (Pi), vitamin D, and protein are nutrients that impact bone and skeletal muscle integrity. Deficiency in the supply of these nutrients increases with aging. Dairy foods are rich in Ca, Pi, and proteins and in many countries are fortified with vitamin D. Dairy foods are important souces of these nutrients and go a long way to meeting the recommendations, which increase with aging. This review emphaszes the interactions between these 4 nutrients, which, along with physical activity, act through cellular and physiological pathways favoring the maintenance of both bone and skeletal muscle structure and function. PMID:24024770

  12. Skeletal muscle responses to unloading in humans

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  13. Regulation of exercise-stimulated glucose uptake in skeletal muscle

    PubMed Central

    2016-01-01

    AMP-activated protein kinase (AMPK) is a Ser/Thr kinase that has been thought to be an important mediator for exercise-stimulated glucose uptake in skeletal muscle. Liver kinase B1 (LKB1) is an upstream kinase for AMPK and AMPK-related protein kinases, of which the function in skeletal muscle has not been well documented. Our group and others have generated mice lacking AMPK activity in skeletal muscle, as well as muscle-specific LKB1 knockout mice. In this review, we discuss the potential role of AMPK and LKB1 in regulating exercise-stimulated glucose uptake in skeletal muscle. We also discuss our recent study, demonstrating the molecular mechanism of obesity-induced development of skeletal muscle insulin resistance. PMID:27462580

  14. Life-Long Wheel Running Attenuates Age-Related Fiber Loss in the Plantaris Muscle of Mice: a Pilot Study.

    PubMed

    Suwa, M; Ishioka, T; Kato, J; Komaita, J; Imoto, T; Kida, A; Yokochi, T

    2016-06-01

    The purpose of this study was to investigate whether long-term wheel running would attenuate age-related loss of muscle fiber. Male ICR mice were divided into young (Y, n=12, aged 3 months), old-sedentary (OS, n=5, aged 24 months), and old-exercise (OE, n=6, aged 24 months) groups. The OE group started spontaneous wheel running at 3 months and continued until 24 months of age. Soleus and plantaris muscles were fixed in 4% paraformaldehyde buffer. The fixed muscle was digested in a 50% NaOH solution to isolate single fiber and then fiber number was quantified. The masses of the soleus and plantaris muscles were significantly lower at 24 months than at 3 months of age, and this age-related difference was attenuated by wheel running (P<0.05). Soleus muscle fiber number did not differ among the groups. In the plantaris muscle, the fiber number in the OS group (1 288±92 fibers) was significantly lower than in the Y group (1 874±93 fibers), and this decrease was attenuated in the OE group (1 591±80 fibers) (P<0.05). These results suggest that age-related fiber loss occurs only in the fast-twitch fiber-rich muscle of mice, and that life-long wheel running exercise can prevent this fiber loss.

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

    NASA Astrophysics Data System (ADS)

    Gao, Yingxin; Zhang, Chi

    2015-03-01

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

  16. Inferring the Skeletal Muscle Developmental Changes of Grazing and Barn-Fed Goats from Gene Expression Data.

    PubMed

    Huang, Jinyu; Jiao, Jinzhen; Tan, Zhi-Liang; He, Zhixiong; Beauchemin, Karen A; Forster, Robert; Han, Xue-Feng; Tang, Shao-Xun; Kang, Jinghe; Zhou, Chuanshe

    2016-09-14

    Thirty-six Xiangdong black goats were used to investigate age-related mRNA and protein expression levels of some genes related to skeletal muscle structural proteins, MRFs and MEF2 family, and skeletal muscle fiber type and composition during skeletal muscle growth under grazing (G) and barn-fed (BF) feeding systems. Goats were slaughtered at six time points selected to reflect developmental changes of skeletal muscle during nonrumination (days 0, 7, and 14), transition (day 42), and rumination phases (days 56 and 70). It was observed that the number of type IIx in the longissimus dorsi was increased quickly while numbers of type IIa and IIb decreased slightly, indicating that these genes were coordinated during the rapid growth and development stages of skeletal muscle. No gene expression was affected (P > 0.05) by feeding system except Myf5 and Myf6. Protein expressions of MYOZ3 and MEF2C were affected (P < 0.05) by age, whereas PGC-1α was linearly decreased in the G group, and only MYOZ3 protein was affected (P < 0.001) by feeding system. Moreover, it was found that PGC-1α and MEF2C proteins may interact with each other in promoting muscle growth. The current results indicate that (1) skeletal muscle growth during days 0-70 after birth is mainly myofiber hypertrophy and differentiation, (2) weaning affects the expression of relevant genes of skeletal muscle structural proteins, skeletal muscle growth, and skeletal muscle fiber type and composition, and (3) nutrition or feeding regimen mainly influences the expression of skeletal muscle growth genes. PMID:27561543

  17. Satellite cell proliferation in adult skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  18. 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...

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

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman W.

    1987-01-01

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

  20. Slow myosin in developing rat skeletal muscle

    PubMed Central

    1987-01-01

    Through S1 nuclease mapping using a specific cDNA probe, we demonstrate that the slow myosin heavy-chain (MHC) gene, characteristic of adult soleus, is expressed in bulk hind limb muscle obtained from the 18-d rat fetus. We support these results by use of a monoclonal antibody (mAb) which is highly specific to the adult slow MHC. Immunoblots of MHC peptide maps show the same peptides, uniquely recognized by this antibody in adult soleus, are also identified in 18-d fetal limb muscle. Thus synthesis of slow myosin is an early event in skeletal myogenesis and is expressed concurrently with embryonic myosin. By immunofluorescence we demonstrate that in the 16-d fetus all primary myotubes in future fast and future slow muscles homogeneously express slow as well as embryonic myosin. Fiber heterogeneity arises owing to a developmentally regulated inhibition of slow MHC accumulation as muscles are progressively assembled from successive orders of cells. Assembly involves addition of new, superficial areas of the anterior tibial muscle (AT) and extensor digitorum longus muscle (EDL) in which primary cells initially stain weakly or are unstained with the slow mAb. In the developing AT and EDL, expression of slow myosin is unstable and is progressively restricted as these muscles specialize more and more towards the fast phenotype. Slow fibers persisting in deep portions of the adult EDL and AT are interpreted as vestiges of the original muscle primordium. A comparable inhibition of slow MHC accumulation occurs in the developing soleus but involves secondary, not primary, cells. Our results show that the fate of secondary cells is flexible and is spatially determined. By RIA we show that the relative proportions of slow MHC are fivefold greater in the soleus than in the EDL or AT at birth. After neonatal denervation, concentrations of slow MHC in the soleus rapidly decline, and we hypothesize that, in this muscle, the nerve protects and amplifies initial programs of slow MHC

  1. Aging alters contractile properties and fiber morphology in pigeon skeletal muscle.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E; Hollander, John M; Wimsatt, Jeffrey H

    2014-12-01

    In this study, we tested the hypothesis that skeletal muscle from pigeons would display age-related alterations in isometric force and contractile parameters as well as a shift of the single muscle fiber cross-sectional area (CSA) distribution toward smaller fiber sizes. Maximal force output, twitch contraction durations and the force-frequency relationship were determined in tensor propatagialis pars biceps muscle from young 3-year-old pigeons, middle-aged 18-year-old pigeons, and aged 30-year-old pigeons. The fiber CSA distribution was determined by planimetry from muscle sections stained with hematoxylin and eosin. Maximal force output of twitch and tetanic contractions was greatest in muscles from young pigeons, while the time to peak force of twitch contractions was longest in muscles from aged pigeons. There were no changes in the force-frequency relationship between the age groups. Interestingly, the fiber CSA distribution in aged muscles revealed a greater number of larger sized muscle fibers, which was verified visually in histological images. Middle-aged and aged muscles also displayed a greater amount of slow myosin containing muscle fibers. These data demonstrate that muscles from middle-aged and aged pigeons are susceptible to alterations in contractile properties that are consistent with aging, including lower force production and longer contraction durations. These functional changes were supported by the appearance of slow myosin containing muscle fibers in muscles from middle-aged and aged pigeons. Therefore, the pigeon may represent an appropriate animal model for the study of aging-related alterations in skeletal muscle function and structure.

  2. Omega-3 Fatty Acids and Skeletal Muscle Health

    PubMed Central

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

    2015-01-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527

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

    PubMed

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

    2015-11-01

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527

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

    PubMed

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

    2015-11-19

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

  5. Age-related differences in muscle control of the lower extremity for support and propulsion during walking

    PubMed Central

    Toda, Haruki; Nagano, Akinori; Luo, Zhiwei

    2016-01-01

    [Purpose] This study examined age-related differences in muscle control for support and propulsion during walking in both males and females in order to develop optimal exercise regimens for muscle control. [Subjects and Methods] Twenty elderly people and 20 young people participated in this study. Coordinates of anatomical landmarks and ground reaction force during walking were obtained using a 3D motion analysis system and force plates. Muscle forces during walking were estimated using OpenSim. Muscle modules were obtained by using non-negative matrix factorization analysis. A two-way analysis of covariance was performed to examine the difference between the elderly and the young in muscle weightings using walking speed as a covariate. The similarities in activation timing profiles between the elderly and the young were analyzed by cross-correlation analysis in males and females. [Results] In the elderly, there was a change in the coordination of muscles around the ankle, and muscles of the lower extremity exhibited co-contraction in late stance. Timing and shape of these modules were similar between elderly and young people. [Conclusion] Our results suggested that age-related alteration of muscle control was associated with support and propulsion during walking. PMID:27134360

  6. Age-related differences in muscle control of the lower extremity for support and propulsion during walking.

    PubMed

    Toda, Haruki; Nagano, Akinori; Luo, Zhiwei

    2016-03-01

    [Purpose] This study examined age-related differences in muscle control for support and propulsion during walking in both males and females in order to develop optimal exercise regimens for muscle control. [Subjects and Methods] Twenty elderly people and 20 young people participated in this study. Coordinates of anatomical landmarks and ground reaction force during walking were obtained using a 3D motion analysis system and force plates. Muscle forces during walking were estimated using OpenSim. Muscle modules were obtained by using non-negative matrix factorization analysis. A two-way analysis of covariance was performed to examine the difference between the elderly and the young in muscle weightings using walking speed as a covariate. The similarities in activation timing profiles between the elderly and the young were analyzed by cross-correlation analysis in males and females. [Results] In the elderly, there was a change in the coordination of muscles around the ankle, and muscles of the lower extremity exhibited co-contraction in late stance. Timing and shape of these modules were similar between elderly and young people. [Conclusion] Our results suggested that age-related alteration of muscle control was associated with support and propulsion during walking.

  7. Proliferative effect of Hachimijiogan, a Japanese herbal medicine, in C2C12 skeletal muscle cells

    PubMed Central

    Takeda, Takashi; Tsuiji, Kenji; Li, Bin; Tadakawa, Mari; Yaegashi, Nobuo

    2015-01-01

    Background Hachimijiogan (HJG), Ba-Wei-Di-Huang-Wan in Chinese, is one of the most popular herbal medicines in Japanese Kampo. HJG is often prescribed for the prevention and treatment of age-related diseases. Muscle atrophy plays an important role in aging-related disabilities such as sarcopenia. The purpose of this study was to investigate the possible beneficial effect of HJG on skeletal muscle. Methods Cells of murine skeletal muscle myoblast cell line C2C12 were used as an in vitro model of muscle cell proliferation and differentiation. The effect of HJG on C2C12 cell proliferation and differentiation was assessed. We counted the number of myotubes morphologically to assess the degree of differentiation. Results HJG treatment (200 μg/mL) for 3 days significantly increased C2C12 cell number by 1.23-fold compared with that of the control. HJG promoted the proliferation of C2C12 cells through activation of the ERK1/2 signaling pathway without affecting the Akt signaling pathway. HJG did not affect the differentiation of C2C12 cells. Conclusion HJG had beneficial effects on skeletal muscle myoblast proliferation. These findings may provide a useful intervention for the prevention and treatment of sarcopenia. PMID:25709418

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

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.

    1987-01-01

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

  9. Expanding roles for AMPK in skeletal muscle plasticity.

    PubMed

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

    2015-06-01

    Skeletal muscle possesses a remarkable plasticity and responds to environmental and physiological challenges by changing its phenotype in terms of size, composition, and metabolic properties. Muscle fibers rapidly adapt to drastic changes in energy demands during exercise through fine-tuning of the balance between catabolic and anabolic processes. One major sensor of energy demand in exercising muscle is AMP-activated protein kinase (AMPK). Recent advances have shed new light on the relevance of AMPK both as a multitask gatekeeper and as an energy regulator in skeletal muscle. Here we summarize recent findings on the function of AMPK in skeletal muscle adaptation to contraction and highlight its role in the regulation of energy metabolism and the control of skeletal muscle regeneration post-injury. PMID:25818360

  10. Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis.

    PubMed

    Tierney, Matthew T; Sacco, Alessandra

    2016-06-01

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

  11. Compartmentalized ATP synthesis in skeletal muscle triads.

    PubMed

    Han, J W; Thieleczek, R; Varsányi, M; Heilmeyer, L M

    1992-01-21

    Isolated skeletal muscle triads contain a compartmentalized glycolytic reaction sequence catalyzed by aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase. These enzymes express activity in the structure-associated state leading to synthesis of ATP in the triadic junction upon supply of glyceraldehyde 3-phosphate or fructose 1,6-bisphosphate. ATP formation occurs transiently and appears to be kinetically compartmentalized, i.e., the synthesized ATP is not in equilibrium with the bulk ATP. The apparent rate constants of the aldolase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reaction are significantly increased when fructose 1,6-bisphosphate instead of glyceraldehyde 3-phosphate is employed as substrate. The observations suggest that fructose 1,6-bisphosphate is especially effectively channelled into the junctional gap. The amplitude of the ATP transient is decreasing with increasing free [Ca2+] in the range of 1 nM to 30 microM. In the presence of fluoride, the ATP transient is significantly enhanced and its declining phase is substantially retarded. This observation suggests utilization of endogenously synthesized ATP in part by structure associated protein kinases and phosphatases which is confirmed by the detection of phosphorylated triadic proteins after gel electrophoresis and autoradiography. Endogenous protein kinases phosphorylate proteins of apparent Mr 450,000, 180,000, 160,000, 145,000, 135,000, 90,000, 54,000, 51,000, and 20,000, respectively. Some of these phosphorylated polypeptides are in the Mr range of known phosphoproteins involved in excitation-contraction coupling of skeletal muscle, which might give a first hint at the functional importance of the sequential glycolytic reactions compartmentalized in triads. PMID:1731894

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

    PubMed Central

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

    2014-01-01

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

  13. Calprotectin is released from human skeletal muscle tissue during exercise

    PubMed Central

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

    2008-01-01

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

  14. Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

    PubMed Central

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

    2015-01-01

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

  15. Molecular events in skeletal muscle during disuse atrophy

    NASA Technical Reports Server (NTRS)

    Kandarian, Susan C.; Stevenson, Eric J.

    2002-01-01

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

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

    PubMed

    Ottenheijm, Coen A C; Granzier, Henk

    2010-10-01

    Nebulin is a giant protein and a constituent of the skeletal muscle sarcomere. The name of this protein refers to its unknown (i.e., nebulous) function. However, recent rapid advances reveal that nebulin plays important roles in the regulation of muscle contraction. When these functions of nebulin are compromised, muscle weakness ensues, as is the case in patients with nemaline myopathy. PMID:20940435

  17. Glucose transporter expression in human skeletal muscle fibers.

    PubMed

    Gaster, M; Handberg, A; Beck-Nielsen, H; Schroder, H D

    2000-09-01

    The present study was initiated to investigate GLUT-1 through -5 expression in developing and mature human skeletal muscle. To bypass the problems inherent in techniques using tissue homogenates, we applied an immunocytochemical approach, employing the sensitive enhanced tyramide signal amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle fibers, only GLUT-4 was expressed at significant levels. GLUT-1 immunoreactivity was below the detection limit in muscle fibers, indicating that this glucose transporter is of minor importance for muscle glucose supply. Thus we hypothesize that GLUT-4 also mediates basal glucose transport in muscle fibers, possibly through constant exposure to tonal contraction and basal insulin levels. PMID:10950819

  18. Expression of elongation factor-1 alpha and S1 in young and old human skeletal muscle.

    PubMed

    Welle, S; Thornton, C; Bhatt, K; Krym, M

    1997-09-01

    Previous research has indicated that reduced expression of elongation factor-1 alpha (EF-1 alpha) may be an important determinant of the reduced rate of protein synthesis in senescent animals and cultured cells. The present study examined whether expression of EF-1 alpha or S1, a homologous protein found exclusively in postmitotic tissues, is reduced in senescent human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis muscles of healthy young (22-31 yr old) and old (61-74 yr old) subjects. As reported previously, myofibrillar protein synthesis was approximately 40% slower in the older muscle (p < .001) as determined by incorporation of a stable isotope. Immunoblotting revealed no difference in the concentration of EF-1 alpha + S1 between younger and older muscle. RT-PCR assays indicated that S1 mRNA was much more abundant than EF-1 alpha mRNA in muscles of both age groups, with no reduction in either EF-1 alpha or S1 mRNA abundance in older muscles. We conclude that expression of EF-1 alpha and S1 is not diminished in older muscles and does not explain the age-related slowing of protein synthesis in human skeletal muscle. However, we cannot exclude the possibility that the activity of these proteins declines during senescence due to post-translational modifications. PMID:9310071

  19. Age-related differences in muscle recruitment and reaction-time performance.

    PubMed

    Arnold, Pauline; Vantieghem, Stijn; Gorus, Ellen; Lauwers, Elien; Fierens, Yves; Pool-Goudzwaard, Annelies; Bautmans, Ivan

    2015-10-01

    Previously, we showed that prolonged reaction-time (RT) in older persons is related to increased antagonist muscle co-activation, occurring already before movement onset. Here, we studied whether a difference in temporal agonist and antagonist muscle activation exists between young and older persons during an RT-test. We studied Mm. Biceps (antagonist muscle) & Triceps (agonist muscle) Brachii activation time by sEMG in 60 young (26 ± 3 years) and 64 older (80 ± 6 years) community-dwelling subjects during a simple point-to-point RT-test (moving a finger using standardized elbow-extension from one pushbutton to another following a visual stimulus). RT was divided in pre-movement-time (PMT, time for stimulus processing) and movement-time (MT, time for motor response completion). Muscle activation time 1) following stimulus onset (PMAT) and 2) before movement onset (MAT) was calculated. PMAT for both muscles was significantly longer for the older subjects compared to the young (258 ± 53 ms versus 224 ± 37 ms, p=0.042 for Biceps and 280 ± 70 ms versus 218 ± 43 ms for Triceps, p<0.01). Longer agonist muscle PMAT was significantly related to worse PMT and RT in young (respectively r=0.76 & r=0.68, p<0.001) and elderly (respectively r=0.42 & r=0.40, p=0.001). In the older subjects we also found that the antagonist muscle activated significantly earlier than the agonist muscle (-22 ± 55 ms, p=0.003). We conclude that in older persons, besides the previously reported increased antagonist muscle co-activation, the muscle firing sequence is also profoundly altered. This is characterized by a delayed muscle activation following stimulus onset, and a significantly earlier recruitment of the antagonist muscle before movement onset.

  20. The extracellular compartments of frog skeletal muscle.

    PubMed Central

    Neville, M C; Mathias, R T

    1979-01-01

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

  1. Skeletal muscle pathology in endurance athletes with acquired training intolerance

    PubMed Central

    Grobler, L; Collins, M; Lambert, M; Sinclair-Smith, C; Derman, W; St, C; Noakes, T

    2004-01-01

    Background: It is well established that prolonged, exhaustive endurance exercise is capable of inducing skeletal muscle damage and temporary impairment of muscle function. Although skeletal muscle has a remarkable capacity for repair and adaptation, this may be limited, ultimately resulting in an accumulation of chronic skeletal muscle pathology. Case studies have alluded to an association between long term, high volume endurance training and racing, acquired training intolerance, and chronic skeletal muscle pathology. Objective: To systematically compare the skeletal muscle structural and ultrastructural status of endurance athletes with acquired training intolerance (ATI group) with asymptomatic endurance athletes matched for age and years of endurance training (CON group). Methods: Histological and electron microscopic analyses were carried out on a biopsy sample of the vastus lateralis from 18 ATI and 17 CON endurance athletes. The presence of structural and ultrastructural disruptions was compared between the two groups of athletes. Results: Significantly more athletes in the ATI group than in the CON group presented with fibre size variation (15 v 6; p = 0.006), internal nuclei (9 v 2; p = 0.03), and z disc streaming (6 v 0; p = 0.02). Conclusions: There is an association between increased skeletal muscle disruptions and acquired training intolerance in endurance athletes. Further studies are required to determine the nature of this association and the possible mechanisms involved. PMID:15562162

  2. Type 2 diabetes mellitus and skeletal muscle metabolic function.

    PubMed

    Phielix, Esther; Mensink, Marco

    2008-05-23

    Type 2 diabetic patients are characterized by a decreased fat oxidative capacity and high levels of circulating free fatty acids (FFAs). The latter is known to cause insulin resistance, in particularly in skeletal muscle, by reducing insulin stimulated glucose uptake, most likely via accumulation of lipid inside the muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this. Furthermore, type 2 diabetes is associated with impaired metabolic flexibility, i.e. an impaired switching from fatty acid to glucose oxidation in response to insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are important components of skeletal muscle insulin resistance. The cause of these derangements in skeletal muscle of type 2 diabetic patients remains to be elucidated. An impaired mitochondrial function is a likely candidate. Evidence from both in vivo and ex vivo studies supports the idea that an impaired skeletal muscle mitochondrial function is related to the development of insulin resistance and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of mitochondrial function using ex vivo high-resolution respirometry revealed opposite results. Future (human) studies should challenge this concept of impaired mitochondrial function underlying metabolic defects and prove if mitochondria are truly functional impaired in insulin resistance, or low in number, and whether it represents the primary starting point of pathogenesis of insulin resistance, or is just an other feature of the insulin resistant state. PMID:18342897

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

    SciTech Connect

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

    1986-03-05

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

  4. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice.

    PubMed

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

    2013-02-01

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.

  5. Angiopoietin-1 enhances skeletal muscle regeneration in mice

    PubMed Central

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

    2015-01-01

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

  6. Underestimation of urinary biomarker-to-creatinine ratio resulting from age-related gain in muscle mass in rats.

    PubMed

    Tonomura, Yutaka; Morikawa, Yuji; Takagi, Shingo; Torii, Mikinori; Matsubara, Mitsunobu

    2013-01-01

    Recent efforts have been made to identify useful urinary biomarkers of nephrotoxicity. Furthermore, the application of urine to the other toxicities as new biomarker source has been recently expanded. Meanwhile, correction of urinary biomarker concentrations according to fluctuations in urine flow rate is required for adequate interpretation of the alteration. The urinary biomarker-to-creatinine ratio (UBCR) is widely used because of the convenience, while the urinary biomarker-excretion rate is regarded as the gold standard corrective method. Because creatinine is a catabolite in energy production in muscles, we hypothesized that altered muscle mass could affect creatinine kinetics, ultimately affecting UBCR. However, no study has examined this hypothesis. In this study, we examined the influence of muscle mass gain on UBCR, using male Sprague-Dawley rats during the growth phase, 6-12-week old. Both plasma creatinine and excretion of urinary creatinine (Ucr excretion) showed increases with muscle mass gain in rats, in which the alterations of UBCR were lowered. The renal mRNA level of the organic cation transporter-2 (Oct2), a creatinine transporter, showed an age-related increase, whereas the mRNA level of multidrug and toxin extrusions-1 (Mate1) remained constant. Multiple regression analysis showed that the increase in creatinine clearance highly contributed to the age-related increase in Ucr excretion compared to the mRNA levels of Oct2 and Mate1. This suggested that the age-related increase in Ucr excretion may be attributable to the increased transglomerular passage of creatinine. In conclusion, the results suggest that muscle mass gain can affect creatinine kinetics, leading to underestimation of UBCR. Therefore, it is important to understand the characteristics of the corrective method when using urinary biomarker, the failure of which can result in an incorrect diagnosis.

  7. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  8. Maintaining skeletal muscle mass: lessons learned from hibernation.

    PubMed

    Ivakine, Evgueni A; Cohn, Ronald D

    2014-04-01

    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.

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

    PubMed Central

    2011-01-01

    Background Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential changes in protein clusters during physiological adaptations or pathological processes. Results Skeletal muscle proteomics attempts to establish the global identification and biochemical characterisation of all members of the muscle-associated protein complement. A considerable number of proteomic studies have employed large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography, and combined them with mass spectrometry as the method of choice for high-throughput protein identification. Muscle proteomics has been applied to the comprehensive biochemical profiling of developing, maturing and aging muscle, as well as the analysis of contractile tissues undergoing physiological adaptations seen in disuse atrophy, physical exercise and chronic muscle transformation. Biomedical investigations into proteome-wide alterations in skeletal muscle tissues were also used to establish novel biomarker signatures of neuromuscular disorders. Importantly, mass spectrometric studies have confirmed the enormous complexity of posttranslational modifications in skeletal muscle proteins. Conclusions This review critically examines the scientific impact of modern muscle proteomics and discusses its successful application for a better understanding of muscle biology, but also outlines its technical limitations and emerging techniques to establish new biomarker candidates. PMID:21798084

  10. Adipokines in Healthy Skeletal Muscle and Metabolic Disease.

    PubMed

    Coles, C A

    2016-01-01

    Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross-talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease. PMID:27003399

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

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1992-01-01

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

  12. Quantitative studies of skeletal muscle lactate metabolism

    SciTech Connect

    Pagliassotti, M.J.

    1988-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1(-/-) and Clock(Δ19) mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle.

  15. Systems analysis of biological networks in skeletal muscle function

    PubMed Central

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

    2014-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation–contraction coupling enabling 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

  16. Markers of Human Skeletal Muscle Mitochondrial Biogenesis and Quality Control: Effects of Age and Aerobic Exercise Training

    PubMed Central

    2014-01-01

    Perturbations in mitochondrial health may foster age-related losses of aerobic capacity (VO2peak) and skeletal muscle size. However, limited data exist regarding mitochondrial dynamics in aging human skeletal muscle and the influence of exercise. The purpose of this study was to examine proteins regulating mitochondrial biogenesis and dynamics, VO2peak, and skeletal muscle size before and after aerobic exercise training in young men (20 ± 1 y) and older men (74 ± 3 y). Exercise-induced skeletal muscle hypertrophy occurred independent of age, whereas the improvement in VO2peak was more pronounced in young men. Aerobic exercise training increased proteins involved with mitochondrial biogenesis, fusion, and fission, independent of age. This is the first study to examine pathways of mitochondrial quality control in aging human skeletal muscle with aerobic exercise training. These data indicate normal aging does not influence proteins associated with mitochondrial health or the ability to respond to aerobic exercise training at the mitochondrial and skeletal muscle levels. PMID:23873965

  17. Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training.

    PubMed

    Konopka, Adam R; Suer, Miranda K; Wolff, Christopher A; Harber, Matthew P

    2014-04-01

    Perturbations in mitochondrial health may foster age-related losses of aerobic capacity (VO2peak) and skeletal muscle size. However, limited data exist regarding mitochondrial dynamics in aging human skeletal muscle and the influence of exercise. The purpose of this study was to examine proteins regulating mitochondrial biogenesis and dynamics, VO2peak, and skeletal muscle size before and after aerobic exercise training in young men (20 ± 1 y) and older men (74 ± 3 y). Exercise-induced skeletal muscle hypertrophy occurred independent of age, whereas the improvement in VO2peak was more pronounced in young men. Aerobic exercise training increased proteins involved with mitochondrial biogenesis, fusion, and fission, independent of age. This is the first study to examine pathways of mitochondrial quality control in aging human skeletal muscle with aerobic exercise training. These data indicate normal aging does not influence proteins associated with mitochondrial health or the ability to respond to aerobic exercise training at the mitochondrial and skeletal muscle levels.

  18. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

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

    2007-11-16

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

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

    PubMed Central

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

    2006-01-01

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

  20. Functional Skeletal Muscle Formation with a Biologic Scaffold

    PubMed Central

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

    2010-01-01

    Biologic scaffolds composed of extracellular matrix (ECM) have been used to reinforce or replace damaged or missing musculotendinous tissues in both preclinical studies and in human clinical applications. However, most studies have focused upon morphologic endpoints and few studies have assessed the in-situ functionality of newly formed tissue; especially new skeletal muscle tissue. The objective of the present study was to determine both the in-situ tetanic contractile response and histomorphologic characteristics of skeletal muscle tissue reconstructed using one of four test articles in a rodent abdominal wall model: 1) porcine small intestinal submucosa (SIS)-ECM; 2) carbodiimide-crosslinked porcine SIS-ECM; 3) autologous tissue; or 4) polypropylene mesh. Six months after surgery, the remodeled SIS-ECM showed almost complete replacement by islands and sheets of skeletal muscle, which generated a similar maximal contractile force to native tissue but with greater resistance to fatigue. The autologous tissue graft was replaced by a mixture of collagenous connective tissue, adipose tissue with fewer islands of skeletal muscle compared to SIS-ECM and a similar fatigue resistance to native muscle. Carbodiimide-crosslinked SIS-ECM and polypropylene mesh were characterized by a chronic inflammatory response and produced little or no measureable tetanic force. The findings of this study show that non-crosslinked xenogeneic SIS scaffolds and autologous tissue are associated with the restoration of functional skeletal muscle with histomorphologic characteristics that resemble native muscle. PMID:20638716

  1. Nuclear factor-kappa B signaling in skeletal muscle atrophy.

    PubMed

    Li, Hong; Malhotra, Shweta; Kumar, Ashok

    2008-10-01

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

  2. Skeletal muscle mitochondrial health and spinal cord injury

    PubMed Central

    O’Brien, Laura C; Gorgey, Ashraf S

    2016-01-01

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

  3. Estimation of skeletal muscle mass from body creatine content

    NASA Technical Reports Server (NTRS)

    Pace, N.; Rahlmann, D. F.

    1982-01-01

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

  4. The Mitochondrial Calcium Uniporter controls skeletal muscle trophism in vivo

    PubMed Central

    Mammucari, Cristina; Gherardi, Gaia; Zamparo, Ilaria; Raffaello, Anna; Boncompagni, Simona; Chemello, Francesco; Cagnin, Stefano; Braga, Alessandra; Zanin, Sofia; Pallafacchina, Giorgia; Zentilin, Lorena; Sandri, Marco; De Stefani, Diego; Protasi, Feliciano; Lanfranchi, Gerolamo; Rizzuto, Rosario

    2015-01-01

    Summary Muscle atrophy contributes to the poor prognosis of many pathophysiological conditions, but pharmacological therapies are still limited. Muscle activity leads to major swings in mitochondrial [Ca2+] which control aerobic metabolism, cell death and survival pathways. We have investigated in vivo the effects of mitochondrial Ca2+ homeostasis in skeletal muscle function and trophism, by overexpressing or silencing the Mitochondrial Calcium Uniporter (MCU). The results demonstrate that both in developing and in adult muscles MCU-dependent mitochondrial Ca2+ uptake has a marked trophic effect that does not depend on aerobic control, but impinges on two major hypertrophic pathways of skeletal muscle, PGC-1α4 and IGF1-AKT/PKB. In addition, MCU overexpression protects from denervation-induced atrophy. These data reveal a novel Ca2+-dependent organelle-to-nucleus signaling route, which links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss. PMID:25732818

  5. Challenges to acellular biological scaffold mediated skeletal muscle tissue regeneration.

    PubMed

    Corona, Benjamin T; Greising, Sarah M

    2016-10-01

    Volumetric muscle loss (VML) injuries present a complex and heterogeneous clinical problem that results in a chronic loss of muscle tissue and strength. The primary limitation to muscle tissue regeneration after VML injury is the frank loss of all native muscle constituents in the defect, especially satellite cells and the basal lamina. Recent advancements in regenerative medicine have set forth encouraging and emerging translational and therapeutic options for these devastating injuries including the surgical implantation of acellular biological scaffolds. While these biomaterials can modulate the wound environment, the existing data do not support their capacity to promote appreciable muscle fiber regeneration that can contribute to skeletal muscle tissue functional improvements. An apparent restriction of endogenous satellite cell (i.e., pax7(+)) migration to acellular biological scaffolds likely underlies this deficiency. This work critically evaluates the role of an acellular biological scaffold in orchestrating skeletal muscle tissue regeneration, specifically when used as a regenerative medicine approach for VML injury. PMID:27472161

  6. Challenges to acellular biological scaffold mediated skeletal muscle tissue regeneration.

    PubMed

    Corona, Benjamin T; Greising, Sarah M

    2016-10-01

    Volumetric muscle loss (VML) injuries present a complex and heterogeneous clinical problem that results in a chronic loss of muscle tissue and strength. The primary limitation to muscle tissue regeneration after VML injury is the frank loss of all native muscle constituents in the defect, especially satellite cells and the basal lamina. Recent advancements in regenerative medicine have set forth encouraging and emerging translational and therapeutic options for these devastating injuries including the surgical implantation of acellular biological scaffolds. While these biomaterials can modulate the wound environment, the existing data do not support their capacity to promote appreciable muscle fiber regeneration that can contribute to skeletal muscle tissue functional improvements. An apparent restriction of endogenous satellite cell (i.e., pax7(+)) migration to acellular biological scaffolds likely underlies this deficiency. This work critically evaluates the role of an acellular biological scaffold in orchestrating skeletal muscle tissue regeneration, specifically when used as a regenerative medicine approach for VML injury.

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

    PubMed

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

    2015-04-01

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

  8. No-dependent signaling pathways in unloaded skeletal muscle

    PubMed Central

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

    2015-01-01

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

  9. Premature Aging in Skeletal Muscle Lacking Serum Response Factor

    PubMed Central

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

    2008-01-01

    Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor) is a crucial transcription factor for muscle-specific gene expression and for post-natal skeletal muscle growth. To assess its role in adult skeletal muscle physiology, we developed a post-mitotic myofiber-specific and tamoxifen-inducible SRF knockout model. Five months after SRF loss, no obvious muscle phenotype was observed suggesting that SRF is not crucial for myofiber maintenance. However, mutant mice progressively developed IIB myofiber-specific atrophy accompanied by a metabolic switch towards a more oxidative phenotype, muscular lipid accumulation, sarcomere disorganization and fibrosis. After injury, mutant muscles exhibited an altered regeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalities encountered in aging skeletal muscle. Interestingly, we also observed an important age associated decrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process. PMID:19079548

  10. Chemokine receptor CCR2 involvement in skeletal muscle regeneration.

    PubMed

    Warren, Gordon L; Hulderman, Tracy; Mishra, Dawn; Gao, Xin; Millecchia, Lyndell; O'Farrell, Laura; Kuziel, William A; Simeonova, Petia P

    2005-03-01

    Chemokines, signaling through the CCR2 receptor, are highly expressed in injured skeletal muscle. Their target specificity depends on the cellular expression of the specific receptors. Here we demonstrate that, in freeze-injured muscle, CCR2 co-localized with Mac-3, a marker of activated macrophages as well as with myogenin, a marker of activated muscle precursor cells. The degeneration/regeneration process in skeletal muscle of CCR2-/- and wild-type mice was not significantly different at day 3. However in contrast to the regenerated muscle of the wild-type mice, the muscle from CCR2-/- mice was characterized by impaired regeneration, inflammation, and fibrotic response at day 14, increased fat infiltration, fibrosis, and calcification at day 21, and impaired strength recovery until at least 28 days post-injury. Consistently, the increased expression of Mac-1 and TNF-alpha was prolonged in the injured muscle of CCR2-/- mice. The expression pattern of the myogenic factors MyoD and myogenin was similar for both types of mice, while NCAM, which is associated with the initiation of fusion of muscle precursor cells, was more increased in the injured muscle of CCR2-/- mice. In conclusion, the study delineates that signaling through CCR2 is involved in muscle precursor cell activities necessary for complete and rapid regeneration of injured skeletal muscle. PMID:15601671

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

    PubMed Central

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

    2015-01-01

    The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge of regulatory signals that control the myogenic process. The obestatin/GPR39 system operates as an autocrine signal in the regulation of skeletal myogenesis. Using a mouse model of skeletal muscle regeneration after injury and several cellular strategies, we explored the potential use of obestatin as a therapeutic agent for the treatment of trauma-induced muscle injuries. Our results evidenced that the overexpression of the preproghrelin, and thus obestatin, and GPR39 in skeletal muscle increased regeneration after muscle injury. More importantly, the intramuscular injection of obestatin significantly enhanced muscle regeneration by simulating satellite stem cell expansion as well as myofiber hypertrophy through a kinase hierarchy. Added to the myogenic action, the obestatin administration resulted in an increased expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) and the consequent microvascularization, with no effect on collagen deposition in skeletal muscle. Furthermore, the potential inhibition of myostatin during obestatin treatment might contribute to its myogenic action improving muscle growth and regeneration. Overall, our data demonstrate successful improvement of muscle regeneration, indicating obestatin is a potential therapeutic agent for skeletal muscle injury and would benefit other myopathies related to muscle regeneration. PMID:25762009

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Skeletal Muscle as a Peripheral Modifier of Behavior

    ERIC Educational Resources Information Center

    Jenkins, Robert R.

    1978-01-01

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

  15. 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...

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

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  17. The impact of vitamin D on skeletal muscle function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Vitamin D and its role in skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. Molecular responses to moderate endurance exercise in skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 +/- 1 yr, body mass 80 +/- 2 kg, and VO(2peak) 45 +/- 1 ml x kg'¹ x min'¹) immediately (0 hr) and...

  20. Obesity, insulin resistance, and skeletal muscle nitric oxide synthase

    PubMed Central

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

    2012-01-01

    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

  1. Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease.

    PubMed

    Argilés, Josep M; Campos, Nefertiti; Lopez-Pedrosa, José M; Rueda, Ricardo; Rodriguez-Mañas, Leocadio

    2016-09-01

    Skeletal muscle is recognized as vital to physical movement, posture, and breathing. In a less known but critically important role, muscle influences energy and protein metabolism throughout the body. Muscle is a primary site for glucose uptake and storage, and it is also a reservoir of amino acids stored as protein. Amino acids are released when supplies are needed elsewhere in the body. These conditions occur with acute and chronic diseases, which decrease dietary intake while increasing metabolic needs. Such metabolic shifts lead to the muscle loss associated with sarcopenia and cachexia, resulting in a variety of adverse health and economic consequences. With loss of skeletal muscle, protein and energy availability is lowered throughout the body. Muscle loss is associated with delayed recovery from illness, slowed wound healing, reduced resting metabolic rate, physical disability, poorer quality of life, and higher health care costs. These adverse effects can be combatted with exercise and nutrition. Studies suggest dietary protein and leucine or its metabolite β-hydroxy β-methylbutyrate (HMB) can improve muscle function, in turn improving functional performance. Considerable evidence shows that use of high-protein oral nutritional supplements (ONS) can help maintain and rebuild muscle mass and strength. We review muscle structure, function, and role in energy and protein balance. We discuss how disease- and age-related malnutrition hamper muscle accretion, ultimately causing whole-body deterioration. Finally, we describe how specialized nutrition and exercise can restore muscle mass, strength, and function, and ultimately reverse the negative health and economic outcomes associated with muscle loss. PMID:27324808

  2. Age-related changes in glucose utilization and fatty acid oxidation in a muscle-specific manner during rabbit growth.

    PubMed

    Gondret, Florence; Damon, Marie; Jadhao, Sanjay B; Houdebine, Louis-Marie; Herpin, Patrick; Hocquette, Jean-François

    2004-01-01

    The optimal utilization of energy substrates in muscle fibers is of primary importance for muscle contraction and whole body physiology. This study aimed to investigate the age-related changes in some indicators of glucose catabolism and fatty acid oxidation in muscles of growing rabbits. Longissimus lumborum (fast-twitch, LL) and semimembranosus proprius (slow-twitch, SMP) muscles were collected at 10 or 20 weeks of age ( n=6 per age). Glucose transporter GLUT4 content was investigated by immunoblot assay. Activity levels of five enzymes were measured: lactate dehydrogenase (LDH) and phosphofructokinase (PFK) for glycolysis; citrate synthase (CS), isocitrate dehydrogenase (ICDH) and -3-hydroxyacyl-coenzyme A dehydrogenase (HAD) for oxidation. Mitochondrial and peroxisomal oxidation rates were assessed on fresh homogenates using [1-14C]-oleate as substrate. At both ages, mitochondrial and peroxisomal oxidations rates, as well as activities of oxidative enzymes were higher in SMP than in LL. In both muscles, the apparent rate of fatty acid oxidation by the mitochondria did not differ between the two ages. However, a decrease in the activities of the three oxidative enzymes was observed in LL, whereas activities of CS and HAD and peroxisomal oxidation rate of oleate increased between the two ages in SMP muscle. In both muscles, LDH activity increased between 10 and 20 weeks, without variations in glucose uptake (GLUT4 transporter content) and in the first step of glucose utilization (PFK activity). In conclusion, mitochondrial oxidation rate of fatty acids and activities of selected mitochondrial enzymes were largely unrelated. Moreover, regulation of energy metabolism with advancing age differed between muscle types.

  3. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Age-related changes in consolidation of perceptual and muscle-based learning of motor skills.

    PubMed

    Pace-Schott, Edward F; Spencer, Rebecca M C

    2013-01-01

    Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater following intervals with wake compared to sleep. While the benefit of sleep on motor sequence learning has been shown to decline with age, how sleep contributes to consolidation of goal-based vs. muscle-based learning in older adults (OA) has not been disentangled. We trained young (n = 62) and older (n = 50) adults on a motor sequence learning task and re-tested learning following 12 h intervals containing overnight sleep or daytime wake. To probe consolidation of goal-based learning of the sequence, half of the participants were re-tested in a configuration in which the stimulus sequence was the same but, due to a shift in stimulus-response mapping, the movement response sequence differed. To probe consolidation of muscle-based learning, the remaining participants were tested in a configuration in which the stimulus sequence was novel, but now the sequence of movements used for responding was unchanged. In young adults, there was a significant condition (goal-based vs. muscle-based learning) by interval (sleep vs. wake) interaction, F(1,58) = 6.58, p = 0.013: goal-based learning tended to be greater following sleep compared to wake, t(29) = 1.47, p = 0.072. Conversely, muscle-based learning was greater following wake than sleep, t(29) = 2.11, p = 0.021. Unlike young adults, this interaction was not significant in OA, F(1,46) = 0.04, p = 0.84, nor was there a main effect of interval, F(1,46) = 1.14, p = 0.29. Thus, OA do not preferentially consolidate sequence learning over wake or sleep.

  6. High skeletal muscle adenylate cyclase in malignant hyperthermia.

    PubMed Central

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

    1981-01-01

    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

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

    PubMed Central

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

    2015-01-01

    Engineered skeletal muscle tissues have been proposed as potential solutions for volumetric muscle losses, and biologic scaffolds have been obtained by decellularization of animal skeletal muscles. The aim of the present work was to analyse the characteristics of a biologic scaffold obtained by decellularization of human skeletal muscles (also through comparison with rats and rabbits) and to evaluate its integration capability in a rabbit model with an abdominal wall defect. Rat, rabbit and human muscle samples were alternatively decellularized with two protocols: n.1, involving sodium deoxycholate and DNase I; n.2, trypsin-EDTA and Triton X-NH4OH. Protocol 2 proved more effective, removing all cellular material and maintaining the three-dimensional networks of collagen and elastic fibers. Ultrastructural analyses with transmission and scanning electron microscopy confirmed the preservation of collagen, elastic fibres, glycosaminoglycans and proteoglycans. Implantation of human scaffolds in rabbits gave good results in terms of integration, although recellularization by muscle cells was not completely achieved. In conclusion, human skeletal muscles may be effectively decellularized to obtain scaffolds preserving the architecture of the extracellular matrix and showing mechanical properties suitable for implantation/integration. Further analyses will be necessary to verify the suitability of these scaffolds for in vitro recolonization by autologous cells before in vivo implantation. PMID:26140375

  8. Compensatory Hypertrophy of Skeletal Muscle: Contractile Characteristics

    ERIC Educational Resources Information Center

    Ianuzzo, C. D.; Chen, V.

    1977-01-01

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

  9. Hypodynamic and hypokinetic condition of skeletal muscles

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  10. Age-related muscle activation profiles and joint stiffness regulation in repetitive hopping.

    PubMed

    Hoffrén, Merja; Ishikawa, Masaki; Rantalainen, Timo; Avela, Janne; Komi, Paavo V

    2011-06-01

    It is well documented that increasing effort during exercise is characterized by an increase in electromyographic activity of the relevant muscles. How aging influences this relationship is a matter of great interest. In the present study, nine young and 24 elderly subjects did repetitive hopping with maximal effort as well as with 50%, 65%, 75% and 90% intensities. During hopping joint kinematics were measured together with electromyographic activity (EMG) from the soleus, gastrocnemius medialis, gastrocnemius lateralis and tibialis anterior muscles. The results showed that agonist activation increased in both age groups with increasing intensity. The highest jumping efficiency (EMG ratio of the braking phase to the push off-phase activation) was achieved with moderate hopping intensities (65-75%) in both the young and in the elderly. Age-comparison showed that elderly subjects had high agonist preactivation but thereafter lower activation during the braking phase. Antagonist coactivation was minimal and did not show age- or intensity-specificity. The elderly had more flexed knees at the instant of ground contact. When intensity increased, the elderly also plantarflexed their ankles more before ground contact. Ankle joint stiffness was lower in elderly subjects only in high hopping intensities (90% and Max). These results confirm that age-specific agonist muscle activation profiles exist during hopping even when exercise intensities are matched on the relative scale. The results suggest further that the elderly can adjust their reduced neuromuscular capacity to match the demands set by different exercise intensities.

  11. Redox proteins are constitutively secreted by skeletal muscle.

    PubMed

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

    2014-11-01

    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.

  12. Growth Factors and Tension-Induced Skeletal Muscle Growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1994-01-01

    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

  13. Effects of aging on mitochondrial function in skeletal muscle of American American Quarter Horses.

    PubMed

    Li, Chengcheng; White, Sarah H; Warren, Lori K; Wohlgemuth, Stephanie E

    2016-07-01

    Skeletal muscle function, aerobic capacity, and mitochondrial (Mt) function have been found to decline with age in humans and rodents. However, not much is known about age-related changes in Mt function in equine skeletal muscle. Here, we compared fiber-type composition and Mt function in gluteus medius and triceps brachii muscle between young (age 1.8 ± 0.1 yr, n = 24) and aged (age 17-25 yr, n = 10) American Quarter Horses. The percentage of myosin heavy chain (MHC) IIX was lower in aged compared with young muscles (gluteus, P = 0.092; triceps, P = 0.012), while the percentages of MHC I (gluteus; P < 0.001) and MHC IIA (triceps; P = 0.023) were increased. Mass-specific Mt density, indicated by citrate synthase activity, was unaffected by age in gluteus, but decreased in aged triceps (P = 0.023). Cytochrome-c oxidase (COX) activity per milligram tissue and per Mt unit decreased with age in gluteus (P < 0.001 for both) and triceps (P < 0.001 and P = 0.003, respectively). Activity of 3-hydroxyacyl-CoA dehydrogenase per milligram tissue was unaffected by age, but increased per Mt unit in aged gluteus and triceps (P = 0.023 and P < 0.001, respectively). Mt respiration of permeabilized muscle fibers per milligram tissue was unaffected by age in both muscles. Main effects of age appeared when respiration was normalized to Mt content, with increases in LEAK, oxidative phosphorylation capacity, and electron transport system capacity (P = 0.038, P = 0.045, and P = 0.007, respectively), independent of muscle. In conclusion, equine skeletal muscle aging was accompanied by a shift in fiber-type composition, decrease in Mt density and COX activity, but preserved Mt respiratory function. PMID:27283918

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

    PubMed

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

    2016-03-01

    Exercise training has been recommended as a nonpharmacological strategy for the prevention and attenuation of skeletal muscle atrophy in distinct pathophysiological conditions. Despite the well-established phenotypic alterations, the molecular mechanisms underlying exercise-induced skeletal muscle remodeling are poorly characterized. Proteomics based on mass spectrometry have been successfully applied for the characterization of skeletal muscle proteome, representing a pivotal approach for the wide characterization of the molecular networks that lead to skeletal muscle remodeling. Nevertheless, few studies were performed to characterize the exercise-induced proteome remodeling of skeletal muscle, with only six research papers focused on the cross-talk between exercise and pathophysiological conditions. In order to add new insights on the impact of distinct exercise programs on skeletal muscle proteome, molecular network analysis was performed with bioinformatics tools. This analysis highlighted an exercise-related proteome signature characterized by the up-regulation of the capacity for ATP generation, oxygen delivery, antioxidant capacity and regulation of mitochondrial protein synthesis. Chronic endurance training up-regulates the tricarboxylic acid cycle and oxidative phosphorylation system, whereas the release of calcium ion into cytosol and amino acid metabolism are the biological processes up-regulated by a single bout of exercise. Other issues as exercise intensity, load, mode and regimen as well as muscle type also influence the exercise-induced proteome signature. The comprehensive analysis of the molecular networks modulated by exercise training in health and disease, taking in consideration all these variables, might not only support the therapeutic effect of exercise but also highlight novel targets for the development of enhanced pharmacological strategies. PMID:26632760

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

    PubMed

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

    2016-11-01

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

  16. Age Related Differences in the Surface EMG Signals on Adolescent's Muscle during Contraction

    NASA Astrophysics Data System (ADS)

    Uddin Ahamed, Nizam; Taha, Zahari; Alqahtani, Mahdi; Altwijri, Omar; Rahman, Matiur; Deboucha, Abdelhakim

    2016-02-01

    The aim of this study was to investigate whether there are differences in the amplitude of the EMG signal among five different age groups of adolescent's muscle. Fifteen healthy adolescents participated in this study and they were divided into five age groups (13, 14, 15, 16 and 17 years). Subjects were performed dynamic contraction during lifting a standard weight (3-kg dumbbell) and EMG signals were recorded from their Biceps Brachii (BB) muscle. Two common EMG analysis techniques namely root mean square (RMS) and mean absolute values (MAV) were used to find the differences. The statistical analysis was included: linear regression to examine the relationships between EMG amplitude and age, repeated measures ANOVA to assess differences among the variables, and finally Coefficient of Variation (CoV) for signal steadiness among the groups of subjects during contraction. The result from RMS and MAV analysis shows that the 17-years age groups exhibited higher activity (0.28 and 0.19 mV respectively) compare to other groups (13-Years: 0.26 and 0.17 mV, 14-years: 0.25 and 0.23 mV, 15-Years: 0.23 and 0.16 mV, 16-years: 0.23 and 0.16 mV respectively). Also, this study shows modest correlation between age and signal activities among all age group's muscle. The experiential results can play a pivotal role for developing EMG prosthetic hand controller, neuromuscular system, EMG based rehabilitation aid and movement biomechanics, which may help to separate age groups among the adolescents.

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

    PubMed

    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

    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

  18. Identification of MicroRNAs Linked to Regulators of Muscle Protein Synthesis and Regeneration in Young and Old Skeletal Muscle

    PubMed Central

    Zacharewicz, Evelyn; Della Gatta, Paul; Reynolds, John; Garnham, Andrew; Crowley, Tamsyn; Russell, Aaron P.; Lamon, Séverine

    2014-01-01

    Background Over the course of ageing there is a natural and progressive loss of skeletal muscle mass. The onset and progression of age-related muscle wasting is associated with an attenuated activation of Akt-mTOR signalling and muscle protein synthesis in response to anabolic stimuli such as resistance exercise. MicroRNAs (miRNAs) are novel and important post-transcriptional regulators of numerous cellular processes. The role of miRNAs in the regulation of muscle protein synthesis following resistance exercise is poorly understood. This study investigated the changes in skeletal muscle miRNA expression following an acute bout of resistance exercise in young and old subjects with a focus on the miRNA species predicted to target Akt-mTOR signalling. Results Ten young (24.2±0.9 years) and 10 old (66.6±1.1 years) males completed an acute resistance exercise bout known to maximise muscle protein synthesis, with muscle biopsies collected before and 2 hours after exercise. We screened the expression of 754 miRNAs in the muscle biopsies and found 26 miRNAs to be regulated with age, exercise or a combination of both factors. Nine of these miRNAs are highly predicted to regulate targets within the Akt-mTOR signalling pathway and 5 miRNAs have validated binding sites within the 3′ UTRs of several members of the Akt-mTOR signalling pathway. The miR-99/100 family of miRNAs notably emerged as potentially important regulators of skeletal muscle mass in young and old subjects. Conclusion This study has identified several miRNAs that were regulated with age or with a single bout of resistance exercise. Some of these miRNAs were predicted to influence Akt-mTOR signalling, and therefore potentially skeletal muscle mass. These miRNAs should be considered as candidate targets for in vivo modulation. PMID:25460913

  19. Control levels of acetylcholinesterase expression in the mammalian skeletal muscle.

    PubMed

    Grubic, Z; Zajc-Kreft, K; Brank, M; Mars, T; Komel, R; Miranda, A F

    1999-05-14

    Protein expression can be controled at different levels. Understanding acetylcholinesterase (EC. 3.1.1.7, AChE) expression in the living organisms therefore necessitates: (1) determination and mapping of control levels of AChE metabolism; (2) identification of the regulatory factors acting at these levels; and (3) detailed insight into the mechanisms of action of these factors. Here we summarize the results of our studies on the regulation of AChE expression in the mammalian skeletal muscle. Three experimental models were employed: in vitro innervated human muscle, mechanically denervated adult fast rat muscle, and the glucocorticoid treated fast rat muscle. In situ hybridization of AChE mRNA, combined with AChE histochemistry, revealed that different distribution patterns of AChE, observed during in vitro ontogenesis and synaptogenesis of human skeletal muscle, reflect alterations in the distribution of AChE mRNA (Z. Grubic, R. Komel, W.F. Walker, A.F. Miranda, Myoblast fusion and innervation with rat motor nerve alter the distribution of acetylcholinesterase and its mRNA in human muscle cultures, Neuron 14 (1995) 317-327). To study the mechanisms of AChE mRNA loss in denervated adult rat skeletal muscle, we exposed deproteinated AChE mRNA to various subcellular fractions in vitro. Fractions were isolated from the normal and denervated rat sternomastoideus muscle. We found significantly increased, but non-specific AChE mRNA degradation capacities in the three fractions studied, suggesting that increased susceptibility of muscle mRNA to degradation might be at least partly responsible for the decreased AChE mRNA observed under such conditions (K. Zajc-Kreft, S. Kreft, Z. Grubic, Degradation of AChE mRNA in the normal and denervated rat skeletal muscle, Book of Abstracts, The Sixth International Meeting on Cholinesterases, La Jolla, CA, March 20-24, 1998, p. A3.). In adult fast rat muscle, treated chronically with glucocorticoids, we found the fraction of early

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

    PubMed

    Gupta, Vandana A; Beggs, Alan H

    2014-01-01

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

  1. Soluble miniagrin enhances contractile function of engineered skeletal muscle

    PubMed Central

    Bian, Weining; Bursac, Nenad

    2012-01-01

    Neural agrin plays a pleiotropic role in skeletal muscle innervation and maturation, but its specific effects on the contractile function of aneural engineered muscle remain unknown. In this study, neonatal rat skeletal myoblasts cultured within 3-dimensional engineered muscle tissue constructs were treated with 10 nM soluble recombinant miniagrin and assessed using histological, biochemical, and functional assays. Depending on the treatment duration and onset time relative to the stage of myogenic differentiation, miniagrin was found to induce up to 1.7-fold increase in twitch and tetanus force amplitude. This effect was associated with the 2.3-fold up-regulation of dystrophin gene expression at 6 d after agrin removal and enhanced ACh receptor (AChR) cluster formation, but no change in cell number, expression of muscle myosin, or important aspects of intracellular Ca2+ handling. In muscle constructs with endogenous ACh levels suppressed by the application of α-NETA, miniagrin increased AChR clustering and twitch force amplitude but failed to improve intracellular Ca2+ handling and increase tetanus-to-twitch ratio. Overall, our studies suggest that besides its synaptogenic function that could promote integration of engineered muscle constructs in vivo, neural agrin can directly promote the contractile function of aneural engineered muscle via mechanisms distinct from those involving endogenous ACh.—Bian, W., Bursac, N. Soluble miniagrin enhances contractile function of engineered skeletal muscle. PMID:22075647

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

    PubMed Central

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

    2015-01-01

    Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC) injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively). Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model. PMID:26039243

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2013-12-01

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

  5. Exercise-Induced Skeletal Muscle Damage.

    ERIC Educational Resources Information Center

    Evans, William J.

    1987-01-01

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

  6. Skeletal muscle fatty acid handling in insulin resistant men.

    PubMed

    van Hees, Anneke M J; Jans, Anneke; Hul, Gabby B; Roche, Helen M; Saris, Wim H M; Blaak, Ellen E

    2011-07-01

    Disturbances in skeletal muscle lipid metabolism may precede or contribute to the development of whole body insulin resistance. In this study, we examined fasting and postprandial skeletal muscle fatty acid (FA) handling in insulin resistant (IR) men. Thirty men with the metabolic syndrome (MetS) (National Cholesterol Education Program-Adult Treatment Panel III) were included in this sub-study to the LIPGENE study, and divided in two groups (IR and control) based on the median of insulin sensitivity (S(I) = 2.06 (mU/l(-1))·min(-1)·10(-4)). Fasting and postprandial skeletal muscle FA handling were examined by combining the forearm balance technique with stable isotopes of palmitate. [(2)H(2)]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free FAs (FFAs) in the circulation and [U-(13)C]-palmitate was incorporated in a high-fat mixed meal (2.6 MJ, 61 E% fat) to label chylomicron-TAG. Muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid (PL) content, their fractional synthetic rates (FSRs) and degree of saturation, as well as messenger RNA (mRNA) expression of genes involved in lipid metabolism. In the first 2 h after meal consumption, forearm muscle [(2)H(2)]-labeled TAG extraction was higher in IR vs. control (P = 0.05). Fasting percentage saturation of muscle DAG was higher in IR vs. control (P = 0.016). No differences were observed for intramuscular TAG, DAG, FFA, and PL content, FSR, and muscle mRNA expression. In conclusion, increased muscle (hepatically derived) TAG extraction during postprandial conditions and increased saturation of intramuscular DAG are associated with insulin resistance, suggesting that disturbances in skeletal muscle FA handling could play a role in the development of whole body insulin resistance and type 2 diabetes. PMID:21331063

  7. Bone and Skeletal Muscle: Neighbors With Close Ties

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-12-01

    The present study describes the isolation, cloning and characterization of adipogenic progenitor cells from rat skeletal muscle. Among the obtained 10 clones, the most highly adipogenic progenitor, 2G11 cells, were further characterized. In addition to their adipogenicity, 2G11 cells retain myogenic potential as revealed by formation of multinucleated myotubes when co-cultured with myoblasts. 2G11 cells were resistant to an inhibitory effect of basic fibroblast growth factor on adipogenesis, while adipogenesis of widely used preadipogenic cell line, 3T3-L1 cells, was suppressed almost completely by the same treatment. In vivo transplantation experiments revealed that 2G11 cells are able to possess both adipogenicity and myogenicity in vivo. These results indicate the presence of bipotent progenitor cells in rat skeletal muscle, and suggest that such cells may contribute to ectopic fat formation in skeletal muscle.

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

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1993-01-01

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

  10. Age-related changes in the flight muscle mitochondria from the blowfly Sarcophaga bullata.

    PubMed

    Wohlrab, H

    1976-05-01

    Flight muscle mitochondria have been isolated from female blowflies (Sarcophaga bullata) of different ages, alpha-Glycerophosphate and pyruvate-proline respiration rates increase during development. Only pyruvate-proline respiration declines toward senescence (30%). This decline can be overcome by ATP-NaHCO3. Cytochrome concentrations and hydrogen peroxide generation rates per protein increase during development but remain constant thereafter. Total NAD+ of metabolically completely oxidized mitochondria decreases during development; a small decline occurs between mature and senescent mitochondria. Respiring young mitochondria do not swell in potassium isethionate, very little in potassium chloride, and relatively slowly in potassium acetate. Mature and senescent mitochondria do swell in these three salts but cannot be differentiated from each other on this basis. None of the preparations swells in sodium chloride, sodium- or potassium Mops. While many differences exist between young and mature mitochondria, only the decline in pyruvate-proline respiration distinguishes mature from senescent mitochondria.

  11. Age-related site-specific muscle loss in the thigh and zigzag walking performance in older men and women.

    PubMed

    Abe, Takashi; Loenneke, J P; Thiebaud, R S; Ogawa, M; Mitsukawa, N

    2014-12-01

    To investigate the relationships between site-specific muscle loss in the thigh, muscle quality and zigzag walking performance, 40 men and 41 women aged 65-79 years had muscle thickness (MTH) measured by ultrasound at nine sites on the anterior and posterior aspects of the body. Skeletal muscle mass (SM) was estimated from an ultrasound-derived prediction equation. Site-specific thigh sarcopenia was calculated using ultrasound-measured MTH at the anterior/posterior aspects of the thigh (AP-MTH ratio). Zigzag walking time (ZWT) and maximum isometric knee extension (KE) and flexion (KF) torques were measured. Muscle quality (torque/thigh SM) and knee joint strength index (torque/body mass) were calculated. There were no significant correlations between SM index and ZWT. However, AP-MTH ratio was inversely correlated (P < 0.05) to ZWT in men (r = -0.335) and women (r = -0.309). ZWT was also inversely correlated (P < 0.05) to KE-strength index in both sexes (men, r = -0.328; women, r = -0.372). Similarly, ZWT was correlated to KF-strength index (r = -0.497) and muscle quality (r = -0.322) in women, but not in men. After adjusting for age, height and body mass, AP-MTH ratio was inversely correlated to ZWT in men (r = -0.325) and tended to be correlated to ZWT in women (r = -0.263). Zigzag walking performance may be associated with site-specific thigh sarcopenia in older men and women.

  12. Subproteomic analysis of basic proteins in aged skeletal muscle following offgel pre-fractionation.

    PubMed

    Gannon, Joan; Ohlendieck, Kay

    2012-04-01

    The progressive loss of skeletal muscle mass is a serious pathophysiological problem in the elderly, which warrants detailed biochemical studies into the underlying mechanism of age-related fiber degeneration. Over the last few years, mass spectrometry (MS)-based proteomics has identified a considerable number of new biomarkers of muscle aging in humans and animal models of sarcopenia. However, interpretation of the proteomic findings is often complicated by technical and biological limitations. Although gel electrophoresis-based approaches represent a highly sensitive analytical way for the large-scale and high-throughput survey of global changes in skeletal muscle proteins during aging, often the presence of components with an isoelectric point in the basic range is underestimated. We, therefore, carried out a comparative subproteomic study of young versus aged rat muscle focusing on potential changes in muscle proteins with an alkaline isoelectric point, using a combination of offgel electrophoresis and two-dimensional (2D) slab gel electrophoresis. Offgel electrophoresis was successfully applied as a prefractionation step to enrich basic protein species from crude tissue extracts representing young adult versus senescent muscle specimens. Proteomics has demonstrated alterations in a small cohort of basic proteins during muscle aging. The mass spectrometric identification of altered proteins and immunoblotting revealed a decrease in the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a concomitant increase in mitochondrial creatine kinase (CK) and ubiquinol cytochrome‑c reductase. This agrees with the idea of a glycolytic-to-oxidative shift during muscle aging, which is indicative of an overall fast-to-slow transition process in senescent rat muscle. Thus, alterations in the abundance of metabolic enzymes appear to play a central role in the molecular pathogenesis of age‑dependent muscle wasting. PMID:22267262

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

    PubMed

    Ørngreen, Mette Cathrine

    2016-07-01

    The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before

  14. Pericapillary basement membrane thickening in human skeletal muscles.

    PubMed

    Baum, Oliver; Bigler, Marius

    2016-09-01

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

  15. Strenuous exercise induces mitochondrial damage in skeletal muscle of old mice

    SciTech Connect

    Lee, Sangho; Kim, Minjung; Lim, Wonchung; Kim, Taeyoung; Kang, Chounghun

    2015-05-29

    Strenuous exercise is known to cause excessive ROS generation and inflammation. However, the mechanisms responsible for the regulation of mitochondrial integrity in the senescent muscle during high-intensity exercise (HE) are not well studied. Here, we show that HE suppresses up-regulation of mitochondrial function despite increase in mitochondrial copy number, following excessive ROS production, proinflammatory cytokines and NFκB activation. Moreover, HE in the old group resulted in the decreasing of both fusion (Mfn2) and fission (Drp1) proteins that may contribute to alteration of mitochondrial morphology. This study suggests that strenuous exercise does not reverse age-related mitochondrial damage and dysfunction by the increased ROS and inflammation. - Highlights: • Effect of exercise on mitochondrial function of aged skeletal muscles was studied. • Strenuous exercise triggered excessive ROS production and inflammatory cytokines. • Strenuous exercise suppressed mitochondrial function in senescent muscle.

  16. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

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

  17. Functional heterogeneity of side population cells in skeletal muscle

    SciTech Connect

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

    2006-03-17

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

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

    PubMed Central

    Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

    2016-01-01

    LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases. PMID:27529282

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

    PubMed

    Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

    2016-01-01

    LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases. PMID:27529282

  20. Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers.

    PubMed

    Claflin, Dennis R; Roche, Stuart M; Gumucio, Jonathan P; Mendias, Christopher L; Brooks, Susan V

    2016-01-01

    Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate contractile behavior in a system that is greatly simplified, yet physiologically relevant. Here we describe the steps required to prepare, permeabilize and preserve small samples of skeletal muscle. We then detail the procedures used to isolate individual fiber segments and attach them to an experimental apparatus for the purpose of controlling activation and measuring force generation. We also describe our technique for estimating the cross-sectional area of fiber segments. The area measurement is necessary for normalizing the absolute force to obtain specific force, a measure of the intrinsic force-generating capability of the contractile system. PMID:27492182

  1. Therapeutic Approaches to Skeletal Muscle Repair and Healing

    PubMed Central

    Danna, Natalie R.; Beutel, Bryan G.; Campbell, Kirk A.; Bosco, Joseph A.

    2014-01-01

    Context: Skeletal muscle is comprised of a highly organized network of cells, neurovascular structures, and connective tissue. Muscle injury is typically followed by a well-orchestrated healing response that consists of the following phases: inflammation, regeneration, and fibrosis. This review presents the mechanisms of action and evidence supporting the effectiveness of various traditional and novel therapies at each phase of the skeletal muscle healing process. Evidence Acquisition: Relevant published articles were identified using MEDLINE (1978-2013). Study Design: Clinical review. Level of Evidence: Level 3. Results: To facilitate muscle healing, surgical techniques involving direct suture repair, as well as the implantation of innovative biologic scaffolds, have been developed. Nonsteroidal anti-inflammatory drugs may be potentially supplanted by nitric oxide and curcumin in modulating the inflammatory pathway. Studies in muscle regeneration have identified stem cells, myogenic factors, and β-agonists capable of enhancing the regenerative capabilities of injured tissue. Furthermore, transforming growth factor-β1 (TGF-β1) and, more recently, myostatin and the rennin-angiotensin system have been implicated in fibrous tissue formation; several antifibrotic agents have demonstrated the ability to disrupt these systems. Conclusion: Effective repair of skeletal muscle after severe injury is unlikely to be achieved with a single intervention. For full functional recovery of muscle there is a need to control inflammation, stimulate regeneration, and limit fibrosis. Strength-of-Recommendation Taxonomy (SORT): B PMID:24982709

  2. Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.

    PubMed

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

    2012-02-01

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

  3. Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation*

    PubMed Central

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

    2010-01-01

    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

  4. Maternal nutrient restriction affects properties of skeletal muscle in offspring

    PubMed Central

    Zhu, Mei J; Ford, Stephen P; Means, Warrie J; Hess, Bret W; Nathanielsz, Peter W; Du, Min

    2006-01-01

    Maternal nutrient restriction (NR) affects fetal development with long-term consequences on postnatal health of offspring, including predisposition to obesity and diabetes. Most studies have been conducted in fetuses in late gestation, and little information is available on the persistent impact of NR from early to mid-gestation on properties of offspring skeletal muscle, which was the aim of this study. Pregnant ewes were subjected to 50% NR from day 28–78 of gestation and allowed to deliver. The longissimus dorsi muscle was sampled from 8-month-old offspring. Maternal NR during early to mid-gestation decreased the number of myofibres in the offspring and increased the ratio of myosin IIb to other isoforms by 17.6 ± 4.9% (P < 0.05) compared with offspring of ad libitum fed ewes. Activity of carnitine palmitoyltransferase-1, a key enzyme controlling fatty acid oxidation, was reduced by 24.7 ± 4.5% (P < 0.05) in skeletal muscle of offspring of NR ewes and would contribute to increased fat accumulation observed in offspring of NR ewes. Intramuscular triglyceride content (IMTG) was increased in skeletal muscle of NR lambs, a finding which may be linked to predisposition to diabetes in offspring of NR mothers, since enhanced IMTG predisposes to insulin resistance in skeletal muscle. Proteomic analysis by two-dimensional gel electrophoresis demonstrated downregulation of several catabolic enzymes in 8-month-old offspring of NR ewes. These data demonstrate that the early to mid-gestation period is important for skeletal muscle development. Impaired muscle development during this stage of gestation affects the number and composition of fibres in offspring which may lead to long-term physiological consequences, including predisposition to obesity and diabetes. PMID:16763001

  5. Age and Diet Affect Gene Expression Profile in Canine Skeletal Muscle

    PubMed Central

    Middelbos, Ingmar S.; Vester, Brittany M.; Karr-Lilienthal, Lisa K.; Schook, Lawrence B.; Swanson, Kelly S.

    2009-01-01

    We evaluated gene transcription in canine skeletal muscle (biceps femoris) using microarray analysis to identify effects of age and diet on gene expression. Twelve female beagles were used (six 1-year olds and six 12-year olds) and they were fed one of two experimental diets for 12 months. One diet contained primarily plant-based protein sources (PPB), whereas the second diet contained primarily animal-based protein sources (APB). Affymetrix GeneChip Canine Genome Arrays were used to hybridize extracted RNA. Age had the greatest effect on gene transcription (262 differentially expressed genes), whereas the effect of diet was relatively small (22 differentially expressed genes). Effects of age (regardless of diet) were most notable on genes related to metabolism, cell cycle and cell development, and transcription function. All these genes were predominantly down-regulated in geriatric dogs. Age-affected genes that were differentially expressed on only one of two diets were primarily noted in the PPB diet group (144/165 genes). Again, genes related to cell cycle (22/35) and metabolism (15/19) had predominantly decreased transcription in geriatric dogs, but 6/8 genes related to muscle development had increased expression. Effects of diet on muscle gene expression were mostly noted in geriatric dogs, but no consistent patterns in transcription were observed. The insight these data provide into gene expression profiles of canine skeletal muscle as affected by age, could serve as a foundation for future research pertaining to age-related muscle diseases. PMID:19221602

  6. Target-derived trophic effect on skeletal muscle innervation in senescent mice.

    PubMed

    Messi, Maria Laura; Delbono, Osvaldo

    2003-02-15

    In the present work, we tested the hypothesis that target-derived insulin-like growth factor-1 (IGF-1) prevents alterations in neuromuscular innervation in aging mammals. To explore this hypothesis, we studied senescent wild-type mice as a model of deficient IGF-1 secretion and signaling and S1S2 transgenic mice as a tool to investigate the role of sustained overexpression of IGF-1 in striated muscle in neuromuscular innervation. The analysis of the nerve terminal in extensor digitorum longus muscles from senescent mice showed that the decrease in the percentage of cholinesterase-stained zones (CSZ) exhibiting nerve terminal branching, number of nerve branches at the CSZ, and nerve branch points was partially or completely reversed by sustained overexpression of IGF-1 in skeletal muscle. Target-derived IGF-1 also prevented age-related decreases in the postterminal alpha-bungarotoxin immunostained area, as well as the reduction in the number and length of postsynaptic folds, and area and density of postsynaptic folds studied with electron microscopy. Overexpression of IGF-1 in skeletal muscle may account for the lack of age-dependent switch in muscle fiber type composition recorded in senescent mice. In summary, the use of the S1S2 IGF-1 transgenic mouse model allowed us to provide morphological evidence for the role of target-derived IGF-1 in spinal cord motor neurons in senescent mice.

  7. Altered cross-bridge properties in skeletal muscle dystrophies

    PubMed Central

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

    2014-01-01

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

  8. Proteomic analysis of bovine skeletal muscle hypertrophy.

    PubMed

    Bouley, Julien; Meunier, Bruno; Chambon, Christophe; De Smet, Stefaan; Hocquette, Jean François; Picard, Brigitte

    2005-02-01

    Myostatin plays a major role in muscle growth and development and animals with disruption of this gene display marked increases in muscle mass. Little is known about muscle physiological adaptations in relation to this muscle hypertrophy. To provide a more comprehensive view, we analyzed bovine muscles from control, heterozygote and homozygote young Belgian blue bulls for myostatin deletion, which results in a normal level of inactive myostatin. Heterozygote and homozygote animals were characterized by a higher proportion of fast-twitch glycolytic fibers in Semitendinosus muscle. Differential proteomic analysis of this muscle was performed using two-dimensional gel electrophoresis followed by mass spectrometry. Thirteen proteins, corresponding to 28 protein spots, were significantly altered in response to the myostatin deletion. The observed changes in protein expression are consistent with an increased fast muscle phenotype, suggesting that myostatin negatively controls mainly fast-twitch glycolytic fiber number. Finally, we demonstrated that differential mRNA splicing of fast troponin T is altered by the loss of myostatin function. The structure of mutually exclusive exon 16 appears predominantly expressed in muscles from heterozygote and homozygote animals. This suggests a role for exon 16 of fast troponin T in the physiological adaptation of the fast muscle phenotype.

  9. Glucocorticoid-induced skeletal muscle atrophy.

    PubMed

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

    2013-10-01

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

  10. Diffusion-Tensor MRI Based Skeletal Muscle Fiber Tracking

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-23

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

  12. AMP decreases the efficiency of skeletal-muscle mitochondria.

    PubMed

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

    2000-10-15

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

  13. AMP decreases the efficiency of skeletal-muscle mitochondria.

    PubMed Central

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

    2000-01-01

    Mitochondrial proton leak in rat muscle is responsible for approx. 15% of the standard metabolic rate, so its modulation could be important in regulating metabolic efficiency. We report in the present paper that physiological concentrations of AMP (K(0.5)=80 microM) increase the resting respiration rate and double the proton conductance of rat skeletal-muscle mitochondria. This effect is specific for AMP. AMP also doubles proton conductance in skeletal-muscle mitochondria from an ectotherm (the frog Rana temporaria), suggesting that AMP activation is not primarily for thermogenesis. AMP activation in rat muscle mitochondria is unchanged when uncoupling protein-3 is doubled by starvation, indicating that this protein is not involved in the AMP effect. AMP activation is, however, abolished by inhibitors and substrates of the adenine nucleotide translocase (ANT), suggesting that this carrier (possibly the ANT1 isoform) mediates AMP activation. AMP activation of ANT could be important for physiological regulation of metabolic rate. PMID:11023814

  14. Insights into skeletal muscle development and applications in regenerative medicine.

    PubMed

    Tran, T; Andersen, R; Sherman, S P; Pyle, A D

    2013-01-01

    Embryonic and postnatal development of skeletal muscle entails highly regulated processes whose complexity continues to be deconstructed. One key stage of development is the satellite cell, whose niche is composed of multiple cell types that eventually contribute to terminally differentiated myotubes. Understanding these developmental processes will ultimately facilitate treatments of myopathies such as Duchenne muscular dystrophy (DMD), a disease characterized by compromised cell membrane structure, resulting in severe muscle wasting. One theoretical approach is to use pluripotent stem cells in a therapeutic setting to help replace degenerated muscle tissue. This chapter discusses key myogenic developmental stages and their regulatory pathways; artificial myogenic induction in pluripotent stem cells; advantages and disadvantages of DMD animal models; and therapeutic approaches targeting DMD. Furthermore, skeletal muscle serves as an excellent paradigm for understanding general cell fate decisions throughout development.

  15. Biomaterial-based delivery for skeletal muscle repair

    PubMed Central

    Cezar, Christine A.; Mooney, David J.

    2015-01-01

    Skeletal muscle possesses a remarkable capacity for regeneration in response to minor damage, but severe injury resulting in a volumetric muscle loss can lead to extensive and irreversible fibrosis, scarring, and loss of muscle function. In early clinical trials, the intramuscular injection of cultured myoblasts was proven to be a safe but ineffective cell therapy, likely due to rapid death, poor migration, and immune rejection of the injected cells. In recent years, appropriate therapeutic cell types and culturing techniques have improved progenitor cell engraftment upon transplantation. Importantly, the identification of several key biophysical and biochemical cues that synergistically regulate satellite cell fate has paved the way for the development of cell-instructive biomaterials that serve as delivery vehicles for cells to promote in vivo regeneration. Material carriers designed to spatially and temporally mimic the satellite cell niche may be of particular importance for the complete regeneration of severely damaged skeletal muscle. PMID:25271446

  16. Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  17. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  18. Leucine supplementation improves regeneration of skeletal muscles from old rats.

    PubMed

    Pereira, Marcelo G; Silva, Meiricris T; da Cunha, Fernanda M; Moriscot, Anselmo S; Aoki, Marcelo S; Miyabara, Elen H

    2015-12-01

    The decreased regenerative capacity of old skeletal muscles involves disrupted turnover of proteins. This study investigated whether leucine supplementation in old rats could improve muscle regenerative capacity. Young and old male Wistar rats were supplemented with leucine; then, the muscles were cryolesioned and examined after 3 and 10 days. Leucine supplementation attenuated the decrease in the expression of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4E (eIF4E) in young and old muscles on day 3 post-injury and promoted an increase in the cross-sectional area of regenerating myofibers from both young and old soleus muscles on day 10 post-injury. This supplementation decreased the levels of ubiquitinated proteins and increased the proteasome activity in young regenerating muscles, but the opposite effect was observed in old regenerating muscles. Moreover, leucine decreased the inflammation area and induced an increase in the number of proliferating satellite cells in both young and old muscles. Our results suggest that leucine supplementation improves the regeneration of skeletal muscles from old rats, through the preservation of certain biological responses upon leucine supplementation. Such responses comprise the decrease in the inflammation area, increase in the number of proliferating satellite cells and size of regenerating myofibers, combined with the modulation of components of the phosphoinositide 3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and ubiquitin-proteasome system.

  19. Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle.

    PubMed

    Rebalka, Irena A; Raleigh, Matthew J; Snook, Laelie A; Rebalka, Alexandra N; MacPherson, Rebecca E K; Wright, David C; Schertzer, Jonathan D; Hawke, Thomas J

    2016-01-01

    While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health) is ill defined. Here, we investigate the effects of fluvastatin treatment on muscle health in wild type (WT) and streptozotocin (STZ)-induced diabetic mice. WT and STZ-diabetic mice received diet enriched with 600 mg/kg fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content were investigated. Our findings indicate that short-term fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes. PMID:27486434

  20. Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle

    PubMed Central

    Rebalka, Irena A.; Raleigh, Matthew J.; Snook, Laelie A.; Rebalka, Alexandra N.; MacPherson, Rebecca E. K.; Wright, David C.; Schertzer, Jonathan D.; Hawke, Thomas J.

    2016-01-01

    While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health) is ill defined. Here, we investigate the effects of fluvastatin treatment on muscle health in wild type (WT) and streptozotocin (STZ)-induced diabetic mice. WT and STZ-diabetic mice received diet enriched with 600 mg/kg fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content were investigated. Our findings indicate that short-term fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes. PMID:27486434

  1. Ultrastructural alterations in skeletal muscle fibers of rats after exercise

    NASA Technical Reports Server (NTRS)

    Akuzawa, M.; Hataya, M.

    1982-01-01

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

  2. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration.

    PubMed

    Choi, Ji Suk; Yoon, Hwa In; Lee, Kyoung Soo; Choi, Young Chan; Yang, Seong Hyun; Kim, In-San; Cho, Yong Woo

    2016-01-28

    Exosomes released from skeletal muscle cells play important roles in myogenesis and muscle development via the transfer of specific signal molecules. In this study, we investigated whether exosomes secreted during myotube differentiation from human skeletal myoblasts (HSkM) could induce a cellular response from human adipose-derived stem cells (HASCs) and enhance muscle regeneration in a muscle laceration mouse model. The exosomes contained various signal molecules including myogenic growth factors related to muscle development, such as insulin-like growth factors (IGFs), hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF2), and platelet-derived growth factor-AA (PDGF-AA). Interestingly, exosome-treated HASCs fused with neighboring cells at early time points and exhibited a myotube-like phenotype with increased expression of myogenic proteins (myosin heavy chain and desmin). On day 21, mRNAs of terminal myogenic genes were also up-regulated in exosome-treated HASCs. Moreover, in vivo studies demonstrated that exosomes from differentiating HSkM reduced the fibrotic area and increased the number of regenerated myofibers in the injury site, resulting in significant improvement of skeletal muscle regeneration. Our findings suggest that exosomes act as a biochemical cue directing stem cell differentiation and provide a cell-free therapeutic approach for muscle regeneration.

  3. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    PubMed

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located. PMID:26585961

  4. Combination of small RNAs for skeletal muscle regeneration.

    PubMed

    Kim, NaJung; Yoo, James J; Atala, Anthony; Lee, Sang Jin

    2016-03-01

    Selectively controlling the expression of the target genes through RNA interference (RNAi) has significant therapeutic potential for injuries or diseases of tissues. We used this strategy to accelerate and enhance skeletal muscle regeneration for the treatment of muscular atrophy. In this study, we used myostatin small interfering (si)RNA (siGDF-8), a major inhibitory factor in the development and postnatal regeneration of skeletal muscle and muscle-specific microRNAs (miR-1 and -206) to further accelerate muscle regeneration. This combination of 3 small RNAs significantly improved the gene expression of myogenic regulatory factors in vitro, suggesting myogenic activation. Moreover, cell proliferation and myotube formation improved without compromising each other, which indicates the myogenic potential of this combination of small RNAs. The recovery of chemically injured tibialis anterior muscles in rats was significantly accelerated, both functionally and structurally. This novel combination of siRNA and miRNAs has promising therapeutic potential to improve in situ skeletal muscle regeneration.

  5. Skeletal muscle disorders associated with selenium deficiency in humans.

    PubMed

    Chariot, Patrick; Bignani, Olivier

    2003-06-01

    Skeletal muscle disorders manifested by muscle pain, fatigue, proximal weakness, and serum creatine kinase (CK) elevation have been reported in patients with selenium deficiency. The object of this report was to review the conditions in which selenium deficiency is associated with human skeletal muscle disorders and to evaluate the importance of mitochondrial alterations in these disorders. A systematic literature review using the Medline database and Cochrane Library provided 38 relevant articles. The main conditions associated with selenium deficiency fell into three categories: (1) insufficient selenium intake in low soil-selenium areas; (2) parenteral or enteral nutrition, or malabsorption; and (3) chronic conditions associated with oxidative stress, such as chronic alcohol abuse and human immunodeficiency virus (HIV) infection. In low soil-selenium areas, reversibility of muscle symptoms was similar after selenium supplementation and placebo administration, suggesting a role for other factors in the development of disease. In parenteral or enteral nutrition, or malabsorption, muscle symptoms improved after selenium supplementation in 18 of 19 patients (median delay: 4 weeks). The reason that only a minority of selenium-deficient patients present with skeletal muscle disorders is unclear and is possibly related to cofactors, such as viral infections and drugs. Prospective studies of selenium-deficient myopathies would be useful in critically ill patients, alcohol abusers, and HIV-infected patients. PMID:12766976

  6. Regulation of skeletal muscle capillary growth in exercise and disease.

    PubMed

    Haas, Tara L; Nwadozi, Emmanuel

    2015-12-01

    Capillaries, which are the smallest and most abundant type of blood vessel, form the primary site of gas, nutrient, and waste transfer between the vascular and tissue compartments. Skeletal muscle exhibits the capacity to generate new capillaries (angiogenesis) as an adaptation to exercise training, thus ensuring that the heightened metabolic demand of the active muscle is matched by an improved capacity for distribution of gases, nutrients, and waste products. This review summarizes the current understanding of the regulation of skeletal muscle capillary growth. The multi-step process of angiogenesis is coordinated through the integration of a diverse array of signals associated with hypoxic, metabolic, hemodynamic, and mechanical stresses within the active muscle. The contributions of metabolic and mechanical factors to the modulation of key pro- and anti-angiogenic molecules are discussed within the context of responses to a single aerobic exercise bout and short-term and long-term training. Finally, the paradoxical lack of angiogenesis in peripheral artery disease and diabetes and the implications for disease progression and muscle health are discussed. Future studies that emphasize an integrated analysis of the mechanisms that control skeletal muscle capillary growth will enable development of targeted exercise programs that effectively promote angiogenesis in healthy individuals and in patient populations. PMID:26554747

  7. Myopathic changes in murine skeletal muscle lacking synemin

    PubMed Central

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

    2015-01-01

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

  8. Regulation of skeletal muscle capillary growth in exercise and disease.

    PubMed

    Haas, Tara L; Nwadozi, Emmanuel

    2015-12-01

    Capillaries, which are the smallest and most abundant type of blood vessel, form the primary site of gas, nutrient, and waste transfer between the vascular and tissue compartments. Skeletal muscle exhibits the capacity to generate new capillaries (angiogenesis) as an adaptation to exercise training, thus ensuring that the heightened metabolic demand of the active muscle is matched by an improved capacity for distribution of gases, nutrients, and waste products. This review summarizes the current understanding of the regulation of skeletal muscle capillary growth. The multi-step process of angiogenesis is coordinated through the integration of a diverse array of signals associated with hypoxic, metabolic, hemodynamic, and mechanical stresses within the active muscle. The contributions of metabolic and mechanical factors to the modulation of key pro- and anti-angiogenic molecules are discussed within the context of responses to a single aerobic exercise bout and short-term and long-term training. Finally, the paradoxical lack of angiogenesis in peripheral artery disease and diabetes and the implications for disease progression and muscle health are discussed. Future studies that emphasize an integrated analysis of the mechanisms that control skeletal muscle capillary growth will enable development of targeted exercise programs that effectively promote angiogenesis in healthy individuals and in patient populations.

  9. Impact of placental insufficiency on fetal skeletal muscle growth.

    PubMed

    Brown, Laura D; Hay, William W

    2016-11-01

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal "catch-up" growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population.

  10. Skeletal muscle ATP kinetics are impaired in frail mice.

    PubMed

    Akki, Ashwin; Yang, Huanle; Gupta, Ashish; Chacko, Vadappuram P; Yano, Toshiyuki; Leppo, Michelle K; Steenbergen, Charles; Walston, Jeremy; Weiss, Robert G

    2014-02-01

    The interleukin-10 knockout mouse (IL10(tm/tm)) has been proposed as a model for human frailty, a geriatric syndrome characterized by skeletal muscle (SM) weakness, because it develops an age-related decline in SM strength compared to control (C57BL/6J) mice. Compromised energy metabolism and energy deprivation appear to play a central role in muscle weakness in metabolic myopathies and muscular dystrophies. Nonetheless, it is not known whether SM energy metabolism is altered in frailty. A combination of in vivo (31)P nuclear magnetic resonance experiments and biochemical assays was used to measure high-energy phosphate concentrations, the rate of ATP synthesis via creatine kinase (CK), the primary energy reserve reaction in SM, as well as the unidirectional rates of ATP synthesis from inorganic phosphate (Pi) in hind limb SM of 92-week-old control (n = 7) and IL10(tm/tm) (n = 6) mice. SM Phosphocreatine (20.2 ± 2.3 vs. 16.8 ± 2.3 μmol/g, control vs. IL10(tm/tm), p < 0.05), ATP flux via CK (5.0 ± 0.9 vs. 3.1 ± 1.1 μmol/g/s, p < 0.01), ATP synthesis from inorganic phosphate (Pi → ATP) (0.58 ± 0.3 vs. 0.26 ± 0.2 μmol/g/s, p < 0.05) and the free energy released from ATP hydrolysis (∆G ∼ATP) were significantly lower and [Pi] (2.8 ± 1.0 vs. 5.3 ± 2.0 μmol/g, control vs. IL10(tm/tm), p < 0.05) markedly higher in IL10(tm/tm) than in control mice. These observations demonstrate that, despite normal in vitro metabolic enzyme activities, in vivo SM ATP kinetics, high-energy phosphate levels and energy release from ATP hydrolysis are reduced and inorganic phosphate is elevated in a murine model of frailty. These observations do not prove, but are consistent with the premise, that energetic abnormalities may contribute metabolically to SM weakness in this geriatric syndrome.

  11. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle.

    PubMed

    Fujimaki, Shin; Machida, Masanao; Wakabayashi, Tamami; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

    2016-01-01

    Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  12. 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...

  13. 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,...

  14. Redox Signaling in Skeletal Muscle: Role of Aging and Exercise

    ERIC Educational Resources Information Center

    Ji, Li Li

    2015-01-01

    Skeletal muscle contraction is associated with the production of ROS due to altered O[subscript 2] distribution and flux in the cell. Despite a highly efficient antioxidant defense, a small surplus of ROS, such as hydrogen peroxide and nitric oxide, may serve as signaling molecules to stimulate cellular adaptation to reach new homeostasis largely…

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

    SciTech Connect

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

    1989-01-01

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

  16. In utero Undernutrition Programs Skeletal and Cardiac Muscle Metabolism

    PubMed Central

    Beauchamp, Brittany; Harper, Mary-Ellen

    2016-01-01

    In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease. PMID:26779032

  17. Differential global gene expression in red and white skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  18. Advancements in stem cells treatment of skeletal muscle wasting

    PubMed Central

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

    2014-01-01

    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

  19. Androgens Regulate Gene Expression in Avian Skeletal Muscles

    PubMed Central

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

    2012-01-01

    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

  20. Androgens regulate gene expression in avian skeletal muscles.

    PubMed

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

    2012-01-01

    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 Ca(2+) 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

  1. Effect of old age on human skeletal muscle force-velocity and fatigue properties

    PubMed Central

    Callahan, Damien M.

    2011-01-01

    It is generally accepted that the muscles of aged individuals contract with less force, have slower relaxation rates, and demonstrate a downward shift in their force-velocity relationship. The factors mediating age-related differences in skeletal muscle fatigue are less clear. The present study was designed to test the hypothesis that age-related shifts in the force-velocity relationship impact the fatigue response in a velocity-dependent manner. Three fatigue protocols, consisting of intermittent, maximum voluntary knee extension contractions performed for 4 min, were performed by 11 young (23.5 ± 0.9 yr, mean ± SE) and 10 older (68.9 ± 4.3) women. The older group fatigued less during isometric contractions than the young group (to 71.1 ± 3.7% initial torque and 59.8 ± 2.5%, respectively; P = 0.02), while the opposite was true during contractions performed at a relatively high angular velocity of 270°·s−1 (old: 28.0 ± 3.9% initial power, young: 52.1 ± 6.9%; P < 0.01). Fatigue was not different (P = 0.74) between groups during contractions at an intermediate velocity, which was selected for each participant based on their force-velocity relationship. There was a significant association between force-velocity properties and fatigue induced by the intermediate-velocity fatigue protocol in the older (r = 0.72; P = 0.02) and young (r = 0.63; P = 0.04) groups. These results indicate that contractile velocity has a profound impact on age-related skeletal muscle fatigue resistance and suggest that changes in the force-velocity relationship partially mediate this effect. PMID:21868683

  2. Proteomic identification of age-dependent protein nitration in rat skeletal muscle.

    PubMed

    Kanski, Jaroslaw; Alterman, Michail A; Schöneich, Christian

    2003-11-15

    Age-related protein nitration was studied in skeletal muscle of Fisher 344 and Fisher 344/Brown Norway (BN) F1 rats by a proteomic approach. Proteins from young (4 months) and old (24 months) Fisher 344 rats and young (6 months) and old (34 months) Fisher 344/BN F1 animals were separated by 2-D gel electrophoresis. Western blot showed an age-related increase in the nitration of a few specific proteins, which were identified by MALDI-TOF MS and ESI-MS/MS. We identified age-dependent apparent nitration of beta-enolase, alpha-fructose aldolase, and creatine kinase, which perform important functions in muscle energy metabolism, suggesting that the nitration of such key proteins can be, in part, responsible for the decline of muscle motor function of the muscle. Furthermore, we have identified the apparent nitration of succinate dehydrogenase, rab GDP dissociation inhibitor beta (GdI-2), triosephosphate isomerase, troponin I, alpha-crystallin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

  3. Exercise-induced histone modifications in human skeletal muscle

    PubMed Central

    McGee, Sean L; Fairlie, Erin; Garnham, Andrew P; Hargreaves, Mark

    2009-01-01

    Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP-activated protein kinase (AMPK) and the calcium–calmodulin-dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation-dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise. PMID:19884317

  4. Influence of spaceflight on rat skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

    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.

  5. Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

    PubMed

    Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

    2016-08-01

    This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline. PMID:27108136

  6. The compliance of contracting skeletal muscle

    PubMed Central

    Bressler, B. H.; Clinch, N. F.

    1974-01-01

    1. The method of controlled releases was used to obtain tension—extension curves in toad (Bufo bufo) sartorii under a variety of conditions at 0° C. 2. The curves obtained were approximately linear over a considerable range of force (0·4P0 to P0) if the releases were given from the plateau of tetanic tension. The slope of this linear region was little affected by changes of release velocity in the range 10-120 mm/sec. 3. Such changes as did occur with alterations in release velocity could be quantitatively accounted for in terms of the internal shortening predicted by A. V. Hill's two-component model. 4. As the muscles were stretched above l0, we found that the maximum stiffness of the tetanized muscles fell in much the same way as the maximum developed force, P0. 5. In another series of experiments we found a rapid change in the overall shape of the tension—extension curve during the early phase of force development in an isometric tetanus. The stiffness of the muscle increased with increasing developed force during this period. 6. The force—velocity curve in these muscles was measured by two methods, both giving a similar result. Surprisingly, toad muscle appears to have about the same intrinsic speed as frog muscle at 0° C. The a.b product from our experiments is considerably greater than the reported values for the maintenance heat rate at 0° C in these muscles. 7. The probable site of the variable compliance in active muscle is discussed. It seems most likely that this is within the A-band, perhaps in the cross-bridges themselves. ImagesFig. 2Fig. 3 PMID:4207658

  7. Preservative solution for skeletal muscle biopsy samples

    PubMed Central

    Kurt, Yasemin Gulcan; Kurt, Bulent; Ozcan, Omer; Topal, Turgut; Kilic, Abdullah; Muftuoglu, Tuba; Acikel, Cengizhan; Sener, Kenan; Sahiner, Fatih; Yigit, Nuri; Aydin, Ibrahim; Alay, Semih; Ekinci, Safak

    2015-01-01

    Context: Muscle biopsy samples must be frozen with liquid nitrogen immediately after excision and maintained at -80°C until analysis. Because of this requirement for tissue processing, patients with neuromuscular diseases often have to travel to centers with on-site muscle pathology laboratories for muscle biopsy sample excision to ensure that samples are properly preserved. Aim: Here, we developed a preservative solution and examined its protectiveness on striated muscle tissues for a minimum of the length of time that would be required to reach a specific muscle pathology laboratory. Materials and Methods: A preservative solution called Kurt-Ozcan (KO) solution was prepared. Eight healthy Sprague-Dawley rats were sacrificed; striated muscle tissue samples were collected and divided into six different groups. Muscle tissue samples were separated into groups for morphological, enzyme histochemical, molecular, and biochemical analysis. Statistical method used: Chi-square and Kruskal Wallis tests. Results: Samples kept in the KO and University of Wisconsin (UW) solutions exhibited very good morphological scores at 3, 6, and 18 hours, but artificial changes were observed at 24 hours. Similar findings were observed for the evaluated enzyme activities. There were no differences between the control group and the samples kept in the KO or UW solution at 3, 6, and 18 hours for morphological, enzyme histochemical, and biochemical features. The messenger ribonucleic acid (mRNA) of β-actin gene was protected up to 6 hours in the KO and UW solutions. Conclusion: The KO solution protects the morphological, enzyme histochemical, and biochemical features of striated muscle tissue of healthy rats for 18 hours and preserves the mRNA for 6 hours. PMID:26019417

  8. Passive in vivo elastography from skeletal muscle noise

    SciTech Connect

    Sabra, Karim G.; Conti, Stephane; Roux, Philippe; Kuperman, W. A.

    2007-05-07

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

  9. Tomographic elastography of contracting skeletal muscles from their natural vibrations

    NASA Astrophysics Data System (ADS)

    Sabra, Karim G.; Archer, Akibi

    2009-11-01

    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.

  10. Noncoding RNAs, Emerging Regulators of Skeletal Muscle Development and Diseases

    PubMed Central

    Nie, Mao; Deng, Zhong-Liang; Liu, Jianming; Wang, Da-Zhi

    2015-01-01

    A healthy and independent life requires skeletal muscles to maintain optimal function throughout the lifespan, which is in turn dependent on efficient activation of processes that regulate muscle development, homeostasis, and metabolism. Thus, identifying mechanisms that modulate these processes is of crucial priority. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have emerged as a class of previously unrecognized transcripts whose importance in a wide range of biological processes and human disease is only starting to be appreciated. In this review, we summarize the roles of recently identified miRNAs and lncRNAs during skeletal muscle development and pathophysiology. We also discuss several molecular mechanisms of these noncoding RNAs. Undoubtedly, further systematic understanding of these noncoding RNAs' functions and mechanisms will not only greatly expand our knowledge of basic skeletal muscle biology, but also significantly facilitate the development of therapies for various muscle diseases, such as muscular dystrophies, cachexia, and sarcopenia. PMID:26258142

  11. Skeletal muscle responses to lower limb suspension in humans

    NASA Technical Reports Server (NTRS)

    Hather, Bruce M.; Adams, Gregory R.; Tesch, Per A.; Dudley, Gary A.

    1992-01-01

    The morphological responses of human skeletal muscle to unweighting were assessed by analyzing multiple transaxial magnetic resonance (MR) images of both lower limbs and skeletal muscle biopsies of the unweighted lower limb before and after six weeks of unilaterial (left) lower limb suspension (ULLS). Results indicated that, as a results of 6 weeks of unweighting (by the subjects walking on crutches using only one limb), the cross sectional area (CSA) of the thigh muscle of the unweighted left limb decreased 12 percent, while the CSA of the right thigh muscle did not change. The decrease was due to a twofold greater response of the knee extensors than the knee flexors. The pre- and post-ULLS biopsies of the left vastus lateralis showed a 14 percent decrease in average fiber CSA due to unweighting. The number of capillaries surrounding the different fiber types was unchanged after ULLS. Results showed that the adaptive responses of human skeletal muscle to unweighting are qualitatively, but not quantitatively, similar to those of lower mammals and not necessarily dependent on the fiber-type composition.

  12. Immunomodulatory effects of massage on nonperturbed skeletal muscle in rats

    PubMed Central

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

    2013-01-01

    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

  13. Compartmentalization of NO signaling cascade in skeletal muscles

    SciTech Connect

    Buchwalow, Igor B. . E-mail: buchwalo@uni-muenster.de; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim

    2005-05-06

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

  14. Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

    NASA Technical Reports Server (NTRS)

    Marquette, Michele L.; Sognier, Marguerite A.

    2013-01-01

    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.

  15. Molecular studies of exercise, skeletal muscle, and ageing

    PubMed Central

    Timmons, James A.; Gallagher, Iain J.

    2016-01-01

    The purpose of an F1000 review is to reflect on the bigger picture, exploring controversies and new concepts as well as providing opinion as to what is limiting progress in a particular field. We reviewed about 200 titles published in 2015 that included reference to ‘skeletal muscle, exercise, and ageing’ with the aim of identifying key articles that help progress our understanding or research capacity while identifying methodological issues which represent, in our opinion, major barriers to progress. Loss of neuromuscular function with chronological age impacts on both health and quality of life. We prioritised articles that studied human skeletal muscle within the context of age or exercise and identified new molecular observations that may explain how muscle responds to exercise or age. An important aspect of this short review is perspective: providing a view on the likely ‘size effect’ of a potential mechanism on physiological capacity or ageing. PMID:27303646

  16. Molecular studies of exercise, skeletal muscle, and ageing.

    PubMed

    Timmons, James A; Gallagher, Iain J

    2016-01-01

    The purpose of an F1000 review is to reflect on the bigger picture, exploring controversies and new concepts as well as providing opinion as to what is limiting progress in a particular field. We reviewed about 200 titles published in 2015 that included reference to 'skeletal muscle, exercise, and ageing' with the aim of identifying key articles that help progress our understanding or research capacity while identifying methodological issues which represent, in our opinion, major barriers to progress. Loss of neuromuscular function with chronological age impacts on both health and quality of life. We prioritised articles that studied human skeletal muscle within the context of age or exercise and identified new molecular observations that may explain how muscle responds to exercise or age. An important aspect of this short review is perspective: providing a view on the likely 'size effect' of a potential mechanism on physiological capacity or ageing. PMID:27303646

  17. Age-Related Changes in Dynamic Postural Control and Attentional Demands are Minimally Affected by Local Muscle Fatigue

    PubMed Central

    Remaud, Anthony; Thuong-Cong, Cécile; Bilodeau, Martin

    2016-01-01

    Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Participants (young adults: n = 15; healthy seniors: n = 13) performed a dynamic postural task along the antero-posterior (AP) and the medio-lateral (ML) axes, with and without the addition of a simple reaction time (RT) task. The dynamic postural task consisted in following a moving circle on a computer screen with the representation of the center of pressure (COP). This protocol was repeated before and after a fatigue task where ankle plantar flexor muscles were targeted. The mean COP-target distance and the mean COP velocity were calculated for each trial. Cross-correlation analyses between the COP and target displacements were also performed. RTs were recorded during dual-task trials. Results showed that while young adults adopted an anticipatory control mode to move their COP as close as possible to the target center, seniors adopted a reactive control mode, lagging behind the target center. This resulted in longer COP-target distance and higher COP velocity in the latter group. Concurrently, RT increased more in seniors when switching from static stance to dynamic postural conditions, suggesting potential alterations in the central nervous system (CNS) functions. Finally, plantar flexor muscle fatigue and dual-tasking had only minor effects on dynamic postural control of both young adults and seniors. Future studies should investigate why the fatigue-induced changes in quiet standing postural control do not seem to transfer to dynamic balance tasks. PMID:26834626

  18. Exercise conditioning in old mice improves skeletal muscle regeneration.

    PubMed

    Joanisse, Sophie; Nederveen, Joshua P; Baker, Jeff M; Snijders, Tim; Iacono, Carlo; Parise, Gianni

    2016-09-01

    Skeletal muscle possesses the ability to regenerate after injury, but this ability is impaired or delayed with aging. Regardless of age, muscle retains the ability to positively respond to stimuli, such as exercise. We examined whether exercise is able to improve regenerative response in skeletal muscle of aged mice. Twenty-two-month-old male C57Bl/6J mice (n = 20) underwent an 8-wk progressive exercise training protocol [old exercised (O-Ex) group]. An old sedentary (O-Sed) and a sedentary young control (Y-Ctl) group were included. Animals were subjected to injections of cardiotoxin into the tibialis anterior muscle. The tibialis anterior were harvested before [O-Ex/O-Sed/Y-Ctl control (CTL); n = 6], 10 d (O-Ex/O-Sed/Y-Ctl d 10; n = 8), and 28 d (O-Ex/O-Sed/Y-Ctl d 28; n = 6) postinjection. Average fiber cross-sectional area was reduced in all groups at d 10 (CTL: O-Ex: 2499 ± 140; O-Sed: 2320 ± 165; Y-Ctl: 2474 ± 269; d 10: O-Ex: 1191 ± 100; O-Sed: 1125 ± 99; Y-Ctl: 1481 ± 167 µm(2); P < 0.05), but was restored to control values in O-Ex and Y-Ctl groups at d 28 (O-Ex: 2257 ± 181; Y-Ctl: 2398 ± 171 µm(2); P > 0.05). Satellite cell content was greater at CTL in O-Ex (2.6 ± 0.4 satellite cells/100 fibers) compared with O-Sed (1.0 ± 0.1% satellite cells/100 fibers; P < 0.05). Exercise conditioning appears to improve ability of skeletal muscle to regenerate after injury in aged mice.-Joanisse, S., Nederveen, J. P., Baker, J. M., Snijders, T., Iacono, C., Parise, G. Exercise conditioning in old mice improves skeletal muscle regeneration. PMID:27306336

  19. Dysregulation of skeletal muscle protein metabolism by alcohol

    PubMed Central

    Steiner, Jennifer L.

    2015-01-01

    Alcohol abuse, either by acute intoxication or prolonged excessive consumption, leads to pathological changes in many organs and tissues including skeletal muscle. As muscle protein serves not only a contractile function but also as a metabolic reserve for amino acids, which are used to support the energy needs of other tissues, its content is tightly regulated and dynamic. This review focuses on the etiology by which alcohol perturbs skeletal muscle protein balance and thereby over time produces muscle wasting and weakness. The preponderance of data suggest that alcohol primarily impairs global protein synthesis, under basal conditions as well as in response to several anabolic stimuli including growth factors, nutrients, and muscle contraction. This inhibitory effect of alcohol is mediated, at least in part, by a reduction in mTOR kinase activity via a mechanism that remains poorly defined but likely involves altered protein-protein interactions within mTOR complex 1. Furthermore, alcohol can exacerbate the decrement in mTOR and/or muscle protein synthesis present in other catabolic states. In contrast, alcohol-induced changes in muscle protein degradation, either global or via specific modulation of the ubiquitin-proteasome or autophagy pathways, are relatively inconsistent and may be model dependent. Herein, changes produced by acute intoxication versus chronic ingestion are contrasted in relation to skeletal muscle metabolism, and limitations as well as opportunities for future research are discussed. As the proportion of more economically developed countries ages and chronic illness becomes more prevalent, a better understanding of the etiology of biomedical consequences of alcohol use disorders is warranted. PMID:25759394

  20. C57BL/6 life span study: age-related declines in muscle power production and contractile velocity.

    PubMed

    Graber, Ted G; Kim, Jong-Hee; Grange, Robert W; McLoon, Linda K; Thompson, LaDora V

    2015-06-01

    Quantification of key outcome measures in animal models of aging is an important step preceding intervention testing. One such measurement, skeletal muscle power generation (force * velocity), is critical for dynamic movement. Prior research focused on maximum power (P max), which occurs around 30-40 % of maximum load. However, movement occurs over the entire load range. Thus, the primary purpose of this study was to determine the effect of age on power generation during concentric contractions in the extensor digitorum longus (EDL) and soleus muscles over the load range from 10 to 90 % of peak isometric tetanic force (P 0). Adult, old, and elderly male C57BL/6 mice were examined for contractile function (6-7 months old, 100 % survival; ~24 months, 75 %; and ~28 months, <50 %, respectively). Mice at other ages (5-32 months) were also tested for regression modeling. We hypothesized and found that power decreased with age not only at P max but also over the load range. Importantly, we found greater age-associated deficits in both power and velocity when the muscles were contracting concentrically against heavy loads (>50 % P 0). The shape of the force-velocity curve also changed with age (a/P 0 increased). In addition, there were prolonged contraction times to maximum force and shifts in the distribution of the myosin light and heavy chain isoforms in the EDL. The results demonstrate that age-associated difficulty in movement during challenging tasks is likely due, in addition to overall reduced force output, to an accelerated deterioration of power production and contractile velocity under heavily loaded conditions.

  1. Mechanical characterization of skeletal muscle myofibrils.

    PubMed Central

    Friedman, A L; Goldman, Y E

    1996-01-01

    A new instrument, based on a technique described previously, is presented for studying mechanics of micron-scale preparations of two to three myofibrils or single myofibrils from muscle. Forces in the nanonewton to micronewton range are measurable with 0.5-ms time resolution. Programmed quick (200-microseconds) steps or ramp length changes are applied to contracting myofibrils to test their mechanical properties. Individual striations can be monitored during force production and shortening. The active isometric force, force-velocity relationship, and force transients after rapid length steps were obtained from bundles of two to three myofibrils from rabbit psoas muscle. Contrary to some earlier reports on myofibrillar mechanics, these properties are generally similar to expectations from studies on intact and skinned muscle fibers. Our experiments provide strong evidence that the mechanical properties of a fiber result from a simple summation of the myofibrillar force and shortening of independently contracting sarcomeres. Images FIGURE 1 FIGURE 2 PMID:8913614

  2. Neuromuscular Electrical Stimulation for Skeletal Muscle Function

    PubMed Central

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

    2012-01-01

    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

  3. Skeletal muscle responses to unweighting in humans

    NASA Technical Reports Server (NTRS)

    Dudley, Gary A.

    1991-01-01

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

  4. Vitamin D and Its Role in Skeletal Muscle

    PubMed Central

    Ceglia, Lisa

    2010-01-01

    Purpose of review Vitamin D is best known for its role in regulating calcium homeostasis and in strengthening bone. However, it has become increasingly clear that it also has important beneficial effects beyond the skeleton, including muscle. This review summarizes current knowledge about the role of vitamin D in skeletal muscle tissue and physical performance. Recent findings Molecular mechanisms of vitamin D action in muscle tissue include genomic and non-genomic effects via a receptor present in muscle cells. Knockout mouse models of the vitamin D receptor provide insight into understanding the direct effects of vitamin D on muscle tissue. Vitamin D status is positively associated with physical performance and inversely associated with risk of falling. Vitamin D supplementation has been shown to improve tests of muscle performance, reduce falls, and possibly impact on muscle fiber composition and morphology in vitamin D deficient older adults. Summary Further studies are needed to fully characterize the underlying mechanisms of vitamin D action in human muscle tissue, to understand how these actions translate into changes in muscle cell morphology and improvements in physical performance, and to define the 25-hydroxyvitamin D level at which to achieve these beneficial effects in muscle. PMID:19770647

  5. Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure.

    PubMed

    Coggan, Andrew R; Peterson, Linda R

    2016-08-01

    Heart failure (HF) patients suffer from exercise intolerance that diminishes their ability to perform normal activities of daily living and hence compromises their quality of life. This is due largely to detrimental changes in skeletal muscle mass, structure, metabolism, and function. This includes an impairment of muscle contractile performance, i.e., a decline in the maximal force, speed, and power of muscle shortening. Although numerous mechanisms underlie this reduction in contractility, one contributing factor may be a decrease in nitric oxide (NO) bioavailability. Consistent with this, recent data demonstrate that acute ingestion of NO3 (-)-rich beetroot juice, a source of NO via the NO synthase-independent enterosalivary pathway, markedly increases maximal muscle speed and power in HF patients. This review discusses the role of muscle contractile dysfunction in the exercise intolerance characteristic of HF, and the evidence that dietary NO3 (-) supplementation may represent a novel and simple therapy for this currently underappreciated problem. PMID:27271563

  6. Activity Dependent Signal Transduction in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Hamilton, Susan L.

    1999-01-01

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

  7. Mechanical signal transduction in skeletal muscle growth and adaptation.

    PubMed

    Tidball, James G

    2005-05-01

    The adaptability of skeletal muscle to changes in the mechanical environment has been well characterized at the tissue and system levels, but the mechanisms through which mechanical signals are transduced to chemical signals that influence muscle growth and metabolism remain largely unidentified. However, several findings have suggested that mechanical signal transduction in muscle may occur through signaling pathways that are shared with insulin-like growth factor (IGF)-I. The involvement of IGF-I-mediated signaling for mechanical signal transduction in muscle was originally suggested by the observations that muscle releases IGF-I on mechanical stimulation, that IGF-I is a potent agent for promoting muscle growth and affecting phenotype, and that IGF-I can function as an autocrine hormone in muscle. Accumulating evidence shows that at least two signaling pathways downstream of IGF-I binding can influence muscle growth and adaptation. Signaling via the calcineurin/nuclear factor of activated T-cell pathway has been shown to have a powerful influence on promoting the slow/type I phenotype in muscle but can also increase muscle mass. Neural stimulation of muscle can activate this pathway, although whether neural activation of the pathway can occur independent of mechanical activation or independent of IGF-I-mediated signaling remains to be explored. Signaling via the Akt/mammalian target of rapamycin pathway can also increase muscle growth, and recent findings show that activation of this pathway can occur as a response to mechanical stimulation applied directly to muscle cells, independent of signals derived from other cells. In addition, mechanical activation of mammalian target of rapamycin, Akt, and other downstream signals is apparently independent of autocrine factors, which suggests that activation of the mechanical pathway occurs independent of muscle-mediated IGF-I release.

  8. The creation of a measurable contusion injury in skeletal muscle.

    PubMed

    Deane, Margaret N; Gregory, Michael; Mars, Maurice

    2014-08-26

    The effect that compressed air massage (CAM) has on skeletal muscle has been ascertained by the morphological and morphometric evaluation of healthy vervet monkey and rabbit skeletal muscle. How CAM may influence the process of healing following a contusion injury is not known. To determine how CAM or other physiotherapeutic modalities may influence healing, it is necessary to create a minor injury that is both reproducible and quantifiable at the termination of a pre-determined healing period. An earlier study described changes in the morphology of skeletal muscle following a reproducible contusion injury. This study extended that work in that it attempted to quantify the 'severity' of such an injury. A 201 g, elongated oval-shaped weight was dropped seven times through a 1 m tube onto the left vastus lateralis muscle of four New Zealand white rabbits. Biopsies were obtained 6 days after injury from the left healing juxta-bone and sub-dermal muscle and uninjured (control) right vastus lateralis of each animal. The tissue was fixed in formal saline, embedded in wax, cut and stained with haematoxylin and phosphotungstic haematoxylin. The muscle was examined by light microscopy and quantification of the severity of injury made using a modified, 'in-house' morphological index and by the comparative morphometric measurement of the cross-sectioned epimysium and myofibres in injured and control muscle. The results showed that a single contusion causes multiple, quantifiable degrees of injury from skin to bone - observations of particular importance to others wishing to investigate contusion injury in human or animal models.

  9. Cardiovascular regulation by skeletal muscle reflexes in health and disease

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2013-01-01

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

  11. Sarcocystis fayeri in skeletal muscle of horses with neuromuscular disease.

    PubMed

    Aleman, Monica; Shapiro, Karen; Sisó, Silvia; Williams, Diane C; Rejmanek, Daniel; Aguilar, Beatriz; Conrad, Patricia A

    2016-01-01

    Recent reports of Sarcocystis fayeri-induced toxicity in people consuming horse meat warrant investigation on the prevalence and molecular characterization of Sarcocystis spp. infection in horses. Sarcocysts in skeletal muscle of horses have been commonly regarded as an incidental finding. In this study, we investigated the prevalence of sarcocysts in skeletal muscle of horses with neuromuscular disease. Our findings indicated that S. fayeri infection was common in young mature horses with neuromuscular disease and could be associated with myopathic and neurogenic processes. The number of infected muscles and number of sarcocysts per muscle were significantly higher in diseased than in control horses. S. fayeri was predominantly found in low oxidative highly glycolytic myofibers. This pathogen had a high glycolytic metabolism. Common clinical signs of disease included muscle atrophy, weakness with or without apparent muscle pain, gait deficits, and dysphagia in horses with involvement of the tongue and esophagus. Horses with myositis were lethargic, apparently painful, stiff, and reluctant to move. Similar to humans, sarcocystosis and cardiomyopathy can occur in horses. This study did not establish causality but supported a possible association (8.9% of cases) with disease. The assumption of Sarcocysts spp. being an incidental finding in every case might be inaccurate.

  12. Aging and regenerative capacity of skeletal muscle in rats.

    PubMed

    Kaasik, Priit; Aru, Maire; Alev, Karin; Seene, Teet

    2012-07-01

    The objective of the study was to examine skeletal muscle regeneration capacity of young and very old rats during autotransplantation. In 3.5 and 30 month-old Wistar rats, gastrocnemius muscle was removed and grafted back to its original bed. Incorporation of 3H leucine into myofibrillar and sarcoplasmic protein fractions, their relative contents in autografts and synthesis rate of MyHC and actin were recorded. The relative muscle mass of old rats was about 67% of that of young rats; the absolute mass of autografted muscle was 61% intact in the young rat group and 51% in the old rat group. Content of myofibrillar protein in the autografts of young rats was 46% of the intact muscle content, and 39% in the old rat group. In conclusion, the difference in skeletal muscle regeneration capacity of young and very old rats is about ten percent. In the autografts of both young and old rats, the regeneration of the contractile apparatus is less effective in comparison with the sarcoplasmic compartment.

  13. Imaging two-dimensional mechanical waves of skeletal muscle contraction.

    PubMed

    Grönlund, Christer; Claesson, Kenji; Holtermann, Andreas

    2013-02-01

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

  14. Mitochondrial respiratory chain function in skeletal muscle of ALS patients.

    PubMed

    Echaniz-Laguna, Andoni; Zoll, Joffrey; Ribera, Florence; Tranchant, Christine; Warter, Jean-Marie; Lonsdorfer, Jean; Lampert, Eliane

    2002-11-01

    Evidence implicating mitochondrial dysfunction in the central nervous system of patients with sporadic amyotrophic lateral sclerosis (SALS) has recently been accumulating. In contrast, data on mitochondrial function in skeletal muscle in SALS are scarce and controversial. We investigated the in situ properties of muscle mitochondria in patients with early-stage SALS and sedentary (SED) controls using the skinned fiber technique to determine whether respiration of muscle tissue is altered in early-stage SALS in comparison with SED. Musculus vastus lateralis biopsies were obtained from 7 SED group members and 14 patients with early-stage SALS (mean disease duration, 9 months). Muscle fibers were permeabilized with saponine and then skinned and placed in an oxygraphic chamber to measure basal (V(0)) and maximal (V(max)) adenosine diphosphate-stimulated respiration rates and to assess mitochondrial regulation by adenosine diphosphate. Muscle oxidative capacity, evaluated with V(max), was identical in patients in the SALS and SED groups (V(0): SALS, 1.1 +/- 0.1; SED, 0.8 +/- 0.1, micromol 0(2). min(-1). gm(-1)dw and V(max): SALS, 3.1 +/- 0.3; SED, 2.5 +/- 0.3, micromol 0(2). min(-1). gm(-1)dw). This study shows an absence of large mitochondrial damage in skeletal muscle of patients with early-stage SALS, suggesting that mitochondrial dysfunction in the earlier stages of SALS is almost certainly not systemic. PMID:12402260

  15. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration

    PubMed Central

    Calve, Sarah; Simon, Hans-Georg

    2012-01-01

    During forelimb regeneration in the newt Notophthalmus viridescens, the dynamic expression of a transitional matrix rich in hyaluronic acid, tenascin-C, and fibronectin controls muscle cell behavior in vivo and in vitro. However, the influence of extracellular matrix (ECM) remodeling on tissue stiffness and the cellular response to mechanical variations during regeneration was unknown. By measuring the transverse stiffness of tissues in situ, we found undifferentiated regenerative blastemas were less stiff than differentiated stump muscle (13.3±1.6 vs. 16.6±1.2 kPa). To directly determine how ECM and stiffness combine to affect skeletal muscle fragmentation, migration, and fusion, we coated silicone-based substrates ranging from 2 to 100 kPa with matrices representative of transitional (tenascin-C and fibronectin) and differentiated environments (laminin and Matrigel). Using live-cell imaging, we found softer tenascin-C-coated substrates significantly enhanced migration and fragmentation of primary newt muscle cells. In contrast, stiffer substrates coated with laminin, Matrigel, or fibronectin increased differentiation while suppressing migration and fragmentation. These data support our in vivo observations that a transitional matrix of reduced stiffness regulates muscle plasticity and progenitor cell recruitment into the regenerative blastema. These new findings will enable the determination of how biochemical and mechanical cues from the ECM control genetic pathways that drive regeneration.—Calve, S., Simon, H.-G. Biochemical and mechanical environment cooperatively regulate skeletal muscle regeneration. PMID:22415307

  16. Skeletal muscle mitochondrial uncoupling in a murine cancer cachexia model.

    PubMed

    Tzika, A Aria; Fontes-Oliveira, Cibely Cristine; Shestov, Alexander A; Constantinou, Caterina; Psychogios, Nikolaos; Righi, Valeria; Mintzopoulos, Dionyssios; Busquets, Silvia; Lopez-Soriano, Francisco J; Milot, Sylvain; Lepine, Francois; Mindrinos, Michael N; Rahme, Laurence G; Argiles, Josep M

    2013-09-01

    Approximately half of all cancer patients present with cachexia, a condition in which disease-associated metabolic changes lead to a severe loss of skeletal muscle mass. Working toward an integrated and mechanistic view of cancer cachexia, we investigated the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We subjected mice to in vivo phosphorous-31 nuclear magnetic resonance (31P NMR) spectroscopy and subjected murine skeletal muscle samples to gas chromatography/mass spectrometry (GC/MS). The mice used in both experiments were Lewis lung carcinoma models of cancer cachexia. A novel 'fragmented mass isotopomer' approach was used in our dynamic analysis of 13C mass isotopomer data. Our 31P NMR and GC/MS results indicated that the adenosine triphosphate (ATP) synthesis rate and tricarboxylic acid (TCA) cycle flux were reduced by 49% and 22%, respectively, in the cancer-bearing mice (p<0.008; t-test vs. controls). The ratio of ATP synthesis rate to the TCA cycle flux (an index of mitochondrial coupling) was reduced by 32% in the cancer-bearing mice (p=0.036; t-test vs. controls). Genomic analysis revealed aberrant expression levels for key regulatory genes and transmission electron microscopy (TEM) revealed ultrastructural abnormalities in the muscle fiber, consistent with the presence of abnormal, giant mitochondria. Taken together, these data suggest that mitochondrial uncoupling occurs in cancer cachexia and thus point to the mitochondria as a potential pharmaceutical target for the treatment of cachexia. These findings may prove relevant to elucidating the mechanisms underlying skeletal muscle wasting observed in other chronic diseases, as well as in aging.

  17. Skeletal muscle microvascular function in girls with Turner syndrome

    PubMed Central

    West, Sarah L.; O'Gorman, Clodagh S.; Elzibak, Alyaa H.; Caterini, Jessica; Noseworthy, Michael D.; Rayner, Tammy; Hamilton, Jill; Wells, Greg D.

    2014-01-01

    Background Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal responses during recovery from exercise compared to HC. Methods Thirteen TS participants and 8 HC completed testing. BOLD MRI was used to measure skeletal muscle microvascular response during 60 second recovery, following 60 s of exercise at 65% of maximal workload. Exercise and recovery were repeated four times, and the BOLD signal time course was fit to a four-parameter sigmoid function. Results Participants were 13.7 ± 3.1 years old and weighed 47.9 ± 14.6 kg. The mean change in BOLD signal intensity following exercise at the end of recovery, the mean response time of the function/the washout of deoxyhemoglobin, and the mean half-time of recovery were similar between the TS and HC groups. Conclusions Our results demonstrate that compared to HC, peripheral skeletal muscle microvascular function following exercise in girls with TS is not impaired. General significance This study supports the idea that the aerobic energy pathway is not impaired in children with TS in response to submaximal exercise. Other mechanisms are likely responsible for exercise intolerance in TS; this needs to be further investigated. PMID:26676172

  18. Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  19. Leucine supplementation improves skeletal muscle regeneration after cryolesion in rats.

    PubMed

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

    2014-01-01

    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.

  20. Insulin action in denervated skeletal muscle

    SciTech Connect

    Smith, R.L.

    1987-01-01

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

  1. Effects of Nonsteroidal Anti-Inflammatory Drugs on Amyloid-βPathology in Mouse Skeletal Muscle

    PubMed Central

    Beckett, Tina L.; Niedowicz, Dana M.; Studzinski, Christa M.; Weidner, Adam M.; Webb, Robin L.; Holler, Christopher J.; Ahmed, Rachel R.; LeVine, Harry; Murphy, M. Paul

    2010-01-01

    Sporadic inclusion body myositis (sIBM) is a common age-related inflammatory myopathy characterized by the presence of intracellular inclusions that contain the amyloid-β (Aβ) peptide, a derivative of the amyloid precursor protein (APP). Aβ is believed to cause Alzheimer's disease (AD), suggesting that a link may exist between the two diseases. If AD and sIBM are linked, then treatments that lower Aβ in brain may prove useful for sIBM. To test this hypothesis, transgenic mice that over express APP in skeletal muscle were treated for 6 months with a variety of nonsteroidal anti-inflammatory drugs (NSAIDs; naproxen, ibuprofen, carprofen or R-flurbiprofen), a subset of which reduce Aβ in brain and cultured cells. Only ibuprofen lowered Aβ in muscle, and this was not accompanied by corresponding improvements in phenotype. These results indicate that the effects of NSAIDs in the brain may be different from other tissues, and that Aβ alone cannot account for skeletal muscle dysfunction in these mice. PMID:20493261

  2. Effects of aging and exercise training on skeletal muscle blood flow and resistance artery morphology

    PubMed Central

    Ramsey, Michael W.; Stabley, John N.; Dominguez, James M.; Davis, Robert T.; McCullough, Danielle J.; Muller-Delp, Judy M.; Delp, Michael D.

    2012-01-01

    With old age, blood flow to the high-oxidative red skeletal muscle is reduced and blood flow to the low-oxidative white muscle is elevated during exercise. Changes in the number of feed arteries perforating the muscle are thought to contribute to this altered hyperemic response during exercise. We tested the hypothesis that exercise training would ameliorate age-related differences in blood flow during exercise and feed artery structure in skeletal muscle. Young (6–7 mo old, n = 36) and old (24 mo old, n = 25) male Fischer 344 rats were divided into young sedentary (Sed), old Sed, young exercise-trained (ET), and old ET groups, where training consisted of 10–12 wk of treadmill exercise. In Sed and ET rats, blood flow to the red and white portions of the gastrocnemius muscle (GastRed and GastWhite) and the number and luminal cross-sectional area (CSA) of all feed arteries perforating the muscle were measured at rest and during exercise. In the old ET group, blood flow was greater to GastRed (264 ± 13 and 195 ± 9 ml·min−1·100 g−1 in old ET and old Sed, respectively) and lower to GastWhite (78 ± 5 and 120 ± 6 ml·min−1·100 g−1 in old ET and old Sed, respectively) than in the old Sed group. There was no difference in the number of feed arteries between the old ET and old Sed group, although the CSA of feed arteries from old ET rats was larger. In young ET rats, there was an increase in the number of feed arteries perforating the muscle. Exercise training mitigated old age-associated differences in blood flow during exercise within gastrocnemius muscle. However, training-induced adaptations in resistance artery morphology differed between young (increase in feed artery number) and old (increase in artery CSA) animals. The altered blood flow pattern induced by exercise training with old age would improve the local matching of O2 delivery to consumption within the skeletal muscle. PMID:23042906

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

    PubMed

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

    2013-01-01

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

  4. Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease.

    PubMed

    Talbot, Jared; Maves, Lisa

    2016-07-01

    Skeletal muscle fibers are classified into fiber types, in particular, slow twitch versus fast twitch. Muscle fiber types are generally defined by the particular myosin heavy chain isoforms that they express, but many other components contribute to a fiber's physiological characteristics. Skeletal muscle fiber type can have a profound impact on muscle diseases, including certain muscular dystrophies and sarcopenia, the aging-induced loss of muscle mass and strength. These findings suggest that some muscle diseases may be treated by shifting fiber type characteristics either from slow to fast, or fast to slow phenotypes, depending on the disease. Recent studies have begun to address which components of muscle fiber types mediate their susceptibility or resistance to muscle disease. However, for many diseases it remains largely unclear why certain fiber types are affected. A substantial body of work has revealed molecular pathways that regulate muscle fiber type plasticity and early developmental muscle fiber identity. For instance, recent studies have revealed many factors that regulate muscle fiber type through modulating the activity of the muscle regulatory transcription factor MYOD1. Future studies of muscle fiber type development in animal models will continue to enhance our understanding of factors and pathways that may provide therapeutic targets to treat muscle diseases. WIREs Dev Biol 2016, 5:518-534. doi: 10.1002/wdev.230 For further resources related to this article, please visit the WIREs website. PMID:27199166

  5. Mitochondrial function in skeletal muscle in type 2 diabetes.

    PubMed

    Rabøl, Rasmus

    2011-04-01

    Reduced skeletal muscle mitochondrial function has been proposed to lead to insulin resistance and type 2 diabetes. It has been known for several years that oxidative capacity of skeletal muscle is reduced in patients with type 2 diabetes compared to weight matched controls. The reduction in oxidative capacity supposedly leads to the accumulation of intramyocellular lipid which inhibits insulin signalling and causes insulin resistance. It is not known whether this reduction in mitochondrial capacity is the cause or the effect of type 2 diabetes. This PhD-thesis describes the effect of different pharmacological interventions on mitochondrial function in type 2 diabetes and describe whether mitochondrial function is uniformly distributed to both upper and lower extremities. Furthermore, a hypothesis on the molecular mechanism for weight gain observed with anthyperglycaemic treatment will be presented.

  6. Innervation and neuromuscular control in ageing skeletal muscle.

    PubMed

    Hepple, Russell T; Rice, Charles L

    2016-04-15

    Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation-reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age-related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan. PMID:26437581

  7. Turning terminally differentiated skeletal muscle cells into regenerative progenitors.

    PubMed

    Wang, Heng; Lööf, Sara; Borg, Paula; Nader, Gustavo A; Blau, Helen M; Simon, András

    2015-01-01

    The ability to repeatedly regenerate limbs during the entire lifespan of an animal is restricted to certain salamander species among vertebrates. This ability involves dedifferentiation of post-mitotic cells into progenitors that in turn form new structures. A long-term enigma has been how injury leads to dedifferentiation. Here we show that skeletal muscle dedifferentiation during newt limb regeneration depends on a programmed cell death response by myofibres. We find that programmed cell death-induced muscle fragmentation produces a population of 'undead' intermediate cells, which have the capacity to resume proliferation and contribute to muscle regeneration. We demonstrate the derivation of proliferating progeny from differentiated, multinucleated muscle cells by first inducing and subsequently intercepting a programmed cell death response. We conclude that cell survival may be manifested by the production of a dedifferentiated cell with broader potential and that the diversion of a programmed cell death response is an instrument to achieve dedifferentiation. PMID:26243583

  8. Developmental Programming of Fetal Skeletal Muscle and Adipose Tissue Development

    PubMed Central

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

    2013-01-01

    All important developmental milestones are accomplished during the fetal stage, and nutrient fluctuation during this stage produces lasting effects on offspring health, so called fetal programming or developmental programming. The fetal stage is critical for skeletal muscle development, as well as adipose and connective tissue development. Maternal under-nutrition at this stage affects the proliferation of myogenic precursor cells and reduces the number of muscle fibers formed. Maternal over-nutrition results in impaired myogenesis and elevated adipogenesis. Because myocytes, adipocytes and fibrocytes are all derived from mesenchymal stem cells, molecular events which regulate the commitment of stem cells to different lineages directly impact fetal muscle and adipose tissue development. Recent studies indicate that microRNA is intensively involved in myogenic and adipogenic differentiation from mesenchymal stem cells, and epigenetic changes such as DNA methylation are expected to alter cell lineage commitment during fetal muscle and adipose tissue development. PMID:25031653

  9. Turning terminally differentiated skeletal muscle cells into regenerative progenitors.

    PubMed

    Wang, Heng; Lööf, Sara; Borg, Paula; Nader, Gustavo A; Blau, Helen M; Simon, András

    2015-01-01

    The ability to repeatedly regenerate limbs during the entire lifespan of an animal is restricted to certain salamander species among vertebrates. This ability involves dedifferentiation of post-mitotic cells into progenitors that in turn form new structures. A long-term enigma has been how injury leads to dedifferentiation. Here we show that skeletal muscle dedifferentiation during newt limb regeneration depends on a programmed cell death response by myofibres. We find that programmed cell death-induced muscle fragmentation produces a population of 'undead' intermediate cells, which have the capacity to resume proliferation and contribute to muscle regeneration. We demonstrate the derivation of proliferating progeny from differentiated, multinucleated muscle cells by first inducing and subsequently intercepting a programmed cell death response. We conclude that cell survival may be manifested by the production of a dedifferentiated cell with broader potential and that the diversion of a programmed cell death response is an instrument to achieve dedifferentiation.

  10. Atrophy of rat skeletal muscles in simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Feller, D. D.; Ginoza, H. S.; Morey, E. R.

    1982-01-01

    A hypokinetic rat model was used for elucidation of the mechanism of skeletal muscle wasting which occurs in weightlessness. Rats were suspended from a back-harness with the head tilted downward and the hind limbs totally unloaded. A progressive decrease in the size of the soleus muscle from suspended rats was observed as a function of time. The rate of protein degradation of the homogenates from the soleus muscles of suspended and control animals was not significantly different. The rate of cell-free protein synthesis was severely repressed in the atrophied muscle. An initial rise in the levels of plasma glucose and corticosterone was observed on the second day of suspension, but they subsequently returned to normal values.

  11. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

    PubMed

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F

    2015-10-13

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  12. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy

    PubMed Central

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F.

    2015-01-01

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies. PMID:26460719

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

    SciTech Connect

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

    1983-11-01

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

  14. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.

    1993-01-01

    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.

  15. Methods for the Organogenesis of Skeletal Muscle in Tissue Culture

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

    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.

  16. Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration.

    PubMed

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

    2003-01-01

    Currently, there is no known medical treatment that hastens the repair of damaged nerve and muscle. Using IGF-1 transgenic mice that specifically express human recombinant IGF-1 in skeletal muscle, we test the hypotheses that targeted gene expression of IGF-1 in skeletal muscle enhances motor nerve regeneration after a nerve crush injury. The IGF-1 transgene affects the initiation of the muscle repair process after nerve injury as shown by increased activation of SCA-1positive myogenic stem cells. Increased satellite cell differentiation and proliferation are observed in IGF-1 transgenic mice, shown by increased expression of Cyclin D1, MyoD, and myogenin. Expression of myogenin and nicotinic acetylcholine receptor subunits, initially increased in both wild-type and IGF-1 transgenic mice, are restored to normal levels at a faster rate in IGF-1 transgenic mice, which indicates a rescue of nerve-evoked muscle activity. Expression of the IGF-1 transgene in skeletal muscle results in accelerated recovery of saltatory nerve conduction, increased innervation as detected by neurofilament expression, and faster recovery of muscle mass. These studies demonstrate that local expression of IGF-1 augments the repair of injured nerve and muscle.

  17. An In Vitro Model of Skeletal Muscle Volume Regulation

    PubMed Central

    Wibberley, Anna; Staunton, Caroline A.; Feetham, Claire H.; Vereninov, Alexey A.; Barrett-Jolley, Richard

    2015-01-01

    Introduction Hypertonic media causes cells to shrink due to water loss through aquaporin channels. After acute shrinkage, cells either regulate their volume or, alternatively, undergo a number of metabolic changes which ultimately lead to cell death. In many cell types, hypertonic shrinkage is followed by apoptosis. Due to the complex 3D morphology of skeletal muscle and the difficulty in obtaining isolated human tissue, we have begun skeletal muscle volume regulation studies using the human skeletal muscle cell line TE671RD. In this study we investigated whether hypertonic challenge of the human skeletal muscle cell line TE671RD triggered cell death or evoked a cell volume recovery response. Methods The cellular volume of TE671RD cells was calculated from the 2D surface area. Cell death was assessed by both the trypan blue live/dead assay and the TUNEL assay. Results Medium osmolality was increased by addition of up to 200mM sucrose. Addition of 200mM sucrose resulted in mean cell shrinkage of 44±1% after 30mins. At later time points (2 and 4 hrs) two separate cell subpopulations with differing mean cell volume became apparent. The first subpopulation (15±2% of the total cell number) continued to shrink whereas the second subpopulation had an increased cell volume. Cell death was observed in a small proportion of cells (approximately 6-8%). Conclusion We have established that a substantial proportion of TE671RD cells respond to hypertonic challenge with RVI, but that these cells are resistant to hypertonicity triggered cell death. PMID:26029913

  18. Dysferlin overexpression in skeletal muscle produces a progressive myopathy

    PubMed Central

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

    2013-01-01

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

  19. Mechanical stimulation improves tissue-engineered human skeletal muscle

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

    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.

  20. Receptor Expression in Rat Skeletal Muscle Cell Cultures

    NASA Technical Reports Server (NTRS)

    Young, Ronald B.

    1996-01-01

    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.

  1. Vasodilator interactions in skeletal muscle blood flow regulation

    PubMed Central

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

    2012-01-01

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

  2. In vivo myosin step-size from zebrafish skeletal muscle

    PubMed Central

    Ajtai, Katalin; Sun, Xiaojing; Takubo, Naoko; Wang, Yihua

    2016-01-01

    Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the ‘bottom-up’ myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive ‘top-down’ phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP-depleted (rigor) muscle. PMID:27249818

  3. In vivo myosin step-size from zebrafish skeletal muscle.

    PubMed

    Burghardt, Thomas P; Ajtai, Katalin; Sun, Xiaojing; Takubo, Naoko; Wang, Yihua

    2016-05-01

    Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the 'bottom-up' myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive 'top-down' phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP-depleted (rigor) muscle. PMID:27249818

  4. Beta2-integrins contribute to skeletal muscle hypertrophy in mice.

    PubMed

    Marino, Joseph S; Tausch, Brian J; Dearth, Christopher L; Manacci, Marc V; McLoughlin, Thomas J; Rakyta, Samuel J; Linsenmayer, Matthew P; Pizza, Francis X

    2008-10-01

    We tested the contribution of beta(2)-integrins, which are important for normal function of neutrophils and macrophages, to skeletal muscle hypertrophy after mechanical loading. Using the synergist ablation model of hypertrophy and mice deficient in the common beta-subunit of beta(2)-integrins (CD18(-/-)), we found that overloaded muscles of wild-type mice had greater myofiber size, dry muscle mass, and total protein content compared with CD18(-/-) mice. The hypertrophy in wild-type mice was preceded by elevations in neutrophils, macrophages, satellite cell/myoblast proliferation (5'-bromo-2'-deoxyuridine- and desmin-positive cells), markers of muscle differentiation (MyoD1 and myogenin gene expression and formation and size of regenerating myofibers), signaling for protein synthesis [phosphorylation of Akt and 70-kDa ribosomal protein S6 kinase (p70S6k)], and reduced signaling for protein degradation (decreased gene expression of muscle atrophy F box/atrogin-1). The deficiency in beta(2)-integrins, however, altered the accumulation profile of neutrophils and macrophages, disrupted the temporal profile of satellite cell/myoblast proliferation, reduced the markers of muscle differentiation, and impaired the p70S6k signaling, all of which could serve as mechanisms for the impaired hypertrophy in overloaded CD18(-/-) mice. In conclusion, our findings indicate that beta(2)-integrins contribute to the hypertrophic response to muscle overload by temporally regulating satellite cells/myoblast proliferation and by enhancing muscle differentiation and p70S6k signaling.

  5. Prioritization of skeletal muscle growth for emergence from hibernation.

    PubMed

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

    2015-01-15

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

  6. Prioritization of skeletal muscle growth for emergence from hibernation

    PubMed Central

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

    2015-01-01

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

  7. Magnetic resonance imaging of skeletal muscle disease.

    PubMed

    Damon, Bruce M; Li, Ke; Bryant, Nathan D

    2016-01-01

    Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multifaceted pathology. The goals of this chapter are to describe and evaluate the use of quantitative magnetic resonance imaging (MRI) methods to characterize muscle pathology. The following criteria are used for this evaluation: objective measurement of continuously distributed variables; clear and well-understood relationship to the pathology of interest; sensitivity to improvement or worsening of clinical status; and the measurement properties of accuracy and precision. Two major classes of MRI methods meet all of these criteria: (1) MRI methods for measuring muscle contractile volume or cross-sectional area by combining structural MRI and quantitative fat-water MRI; and (2) an MRI method for characterizing the edema caused by inflammation, the measurement of the transverse relaxation time constant (T2). These methods are evaluated with respect to the four criteria listed above and examples from neuromuscular disorders are provided. Finally, these methods are summarized and synthesized and recommendations for additional quantitative MRI developments are made. PMID:27430444

  8. Effect of trifluoperazine on skeletal muscle mitochondrial respiration.

    PubMed

    Cheah, K S; Waring, J C

    1983-04-22

    The effect of trifluoperazine on the respiration of porcine liver and skeletal muscle mitochondria was investigated by polarographic and spectroscopic techniques. Low concentrations of trifluoperazine (88 nmol/mg protein) inhibited both the ADP- and Ca2+-stimulated oxidation of succinate, and reduced the values of the respiratory control index and the ADP/O and Ca2+/O ratio. High concentrations inhibited both succinate and ascorbate plus tetramethyl-p-phenylenediame (TMPD) oxidations, and uncoupler (carbonyl cyanide p-trifluromethoxyphenylhydrazone) and Ca2+-stimulated respiration. Porcine liver mitochondria were more sensitive to trifluoperazine than skeletal muscle mitochondria. Trifluoperazine inhibited the electron transport of succinate oxidation of skeletal muscle mitochondria within the cytochrome b-c1 and cytochrome c1-aa3 segments of the respiratory chain system. 233 nmol trifluoperazine/mg protein inhibited the aerobic steady-state reduction of cytochrome c1 by 92% with succinate as substrate, and of cytochrome c and cytochrome aa3 by 50-60% with ascorbate plus TMPD as electron donors. Trifluoperazine can thus inhibit calmodulin-independent reactions particularly when used at high concentrations.

  9. Signalling and the control of skeletal muscle size

    SciTech Connect

    Otto, Anthony; Patel, Ketan

    2010-11-01

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

  10. Proteasomes are tightly associated to myofibrils in mature skeletal muscle.

    PubMed

    Bassaglia, Yann; Cebrian, José; Covan, Silvia; Garcia, Monica; Foucrier, Jean

    2005-01-15

    Proteasomes are the major actors of nonlysosomal cytoplasmic protein degradation. In particular, these large protein complexes (about 2500 kDa) are considered to be responsible for muscular degradation during skeletal muscle atrophy. Despite their unusual and important size, they are widely described as soluble and mobile in the cytoplasm. In mature skeletal muscle, we have previously observed a sarcomeric distribution of proteasomes, as revealed by the distribution of alpha1/p27K, a subunit of the 20S core-particle (prosome) of proteasome. Here, we extend these observations at the electron microscopic level in vivo. We also show that this sarcomeric pattern is dependent of the extension of the sarcomere. Using isolated myofibrils, we demonstrate that proteasomes are still attached to the myofibrils after the isolation procedure, and reproduce the observations made in vivo. In addition, the extraction of actin by gelsolin largely removes proteasomes from isolated myofibrils, but some of them are held in place after this extraction, showing a sarcomeric disposition in the absence of any detectable actin, and suggesting the existence of another molecular partner for these interactions. From these results, we conclude that most of detectable 20S proteasomes in skeletal muscle cells is tightly attached to the myofibrils. PMID:15561103

  11. Low Intensity Exercise Training Improves Skeletal Muscle Regeneration Potential

    PubMed Central

    Pietrangelo, Tiziana; Di Filippo, Ester S.; Mancinelli, Rosa; Doria, Christian; Rotini, Alessio; Fanò-Illic, Giorgio; Fulle, Stefania

    2015-01-01

    Purpose: The aim of this study was to determine whether 12 days of low-to-moderate exercise training at low altitude (598 m a.s.l.) improves skeletal muscle regeneration in sedentary adult women. Methods: Satellite cells were obtained from the vastus lateralis skeletal muscle of seven women before and after this exercise training at low altitude. They were investigated for differentiation aspects, superoxide anion production, antioxidant enzymes, mitochondrial potential variation after a depolarizing insult, intracellular Ca2+ concentrations, and micro (mi)RNA expression (miR-1, miR-133, miR-206). Results: In these myogenic populations of adult stem cells, those obtained after exercise training, showed increased Fusion Index and intracellular Ca2+ concentrations. This exercise training also generally reduced superoxide anion production in cells (by 12–67%), although not in two women, where there was an increase of ~15% along with a reduced superoxide dismutase activity. miRNA expression showed an exercise-induced epigenetic transcription profile that was specific according to the reduced or increased superoxide anion production of the cells. Conclusions: The present study shows that low-to-moderate exercise training at low altitude improves the regenerative capacity of skeletal muscle in adult women. The differentiation of cells was favored by increased intracellular calcium concentration and increased the fusion index. This low-to-moderate training at low altitude also depicted the epigenetic signature of cells. PMID:26733888

  12. A novel potassium channel in skeletal muscle mitochondria.

    PubMed

    Skalska, Jolanta; Piwońska, Marta; Wyroba, Elzbieta; Surmacz, Liliana; Wieczorek, Rafal; Koszela-Piotrowska, Izabela; Zielińska, Joanna; Bednarczyk, Piotr; Dołowy, Krzysztof; Wilczynski, Grzegorz M; Szewczyk, Adam; Kunz, Wolfram S

    2008-01-01

    In this work we provide evidence for the potential presence of a potassium channel in skeletal muscle mitochondria. In isolated rat skeletal muscle mitochondria, Ca(2+) was able to depolarize the mitochondrial inner membrane and stimulate respiration in a strictly potassium-dependent manner. These potassium-specific effects of Ca(2+) were completely abolished by 200 nM charybdotoxin or 50 nM iberiotoxin, which are well-known inhibitors of large conductance, calcium-activated potassium channels (BK(Ca) channel). Furthermore, NS1619, a BK(Ca)-channel opener, mimicked the potassium-specific effects of calcium on respiration and mitochondrial membrane potential. In agreement with these functional data, light and electron microscopy, planar lipid bilayer reconstruction and immunological studies identified the BK(Ca) channel to be preferentially located in the inner mitochondrial membrane of rat skeletal muscle fibers. We propose that activation of mitochondrial K(+) transport by opening of the BK(Ca) channel may be important for myoprotection since the channel opener NS1619 protected the myoblast cell line C2C12 against oxidative injury.

  13. Regrowth after skeletal muscle atrophy is impaired in aged rats, despite similar responses in signaling pathways

    PubMed Central

    White, Jena R.; Confides, Amy L.; Moore-Reed, Stephanie; Hoch, Johanna M.; Dupont-Versteegden, Esther E.

    2015-01-01

    Skeletal muscle regrowth after atrophy is impaired in the aged and in this study we hypothesized that this can be explained by a blunted response of signaling pathways and cellular processes during reloading after hind limb suspension in muscles from old rats. Male Brown Norway Fisher 344 rats at 6 (young) and 32 (old) months of age were subjected to normal ambulatory conditions (amb), hind limb suspension for 14 days (HS), and HS followed by reloading through normal ambulation for 14 days (RE); soleus muscles were used for analysis of intracellular signaling pathways and cellular processes. Soleus muscle regrowth was blunted in old compared to young rats which coincided with a recovery of serum IGF-1 and IGFBP-3 levels in young but not old. However, the response to reloading for p-Akt, p-p70s6k and p-GSK3β protein abundance was similar between muscles from young and old rats, even though main effects for age indicate an increase in activation of this protein synthesis pathway in the aged. Similarly, MAFbx mRNA levels in soleus muscle from old rats recovered to the same extent as in the young, while Murf-1 was unchanged. mRNA abundance of autophagy markers Atg5 and Atg7 showed an identical response in muscle from old compared to young rats, but beclin did not. Autophagic flux was not changed at either age at the measured time point. Apoptosis was elevated in soleus muscle from old rats particularly with HS, but recovered in HSRE and these changes were not associated with differences in caspase-3, -8 or-9 activity in any group. Protein abundance of apoptosis repressor with caspase-recruitment domain (ARC), cytosolic EndoG, as well as cytosolic and nuclear apoptosis inducing factor (AIF) were lower in muscle from old rats, and there was no age-related difference in the response to atrophy or regrowth. Soleus muscles from old rats had a higher number of ED2 positive macrophages in all groups and these decreased with HS, but recovered in HSRE in the old, while no

  14. Optical reflectance in fibrous tissues and skeletal muscles

    NASA Astrophysics Data System (ADS)

    Ranasinghesagara, Janaka C.

    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

  15. Comprehensive analysis of tropomyosin isoforms in skeletal muscles by top-down proteomics.

    PubMed

    Jin, Yutong; Peng, Ying; Lin, Ziqing; Chen, Yi-Chen; Wei, Liming; Hacker, Timothy A; Larsson, Lars; Ge, Ying

    2016-04-01

    Mammalian skeletal muscles are heterogeneous in nature and are capable of performing various functions. Tropomyosin (Tpm) is a major component of the thin filament in skeletal muscles and plays an important role in controlling muscle contraction and relaxation. Tpm is known to consist of multiple isoforms resulting from different encoding genes and alternative splicing, along with post-translational modifications. However, a systematic characterization of Tpm isoforms in skeletal muscles is still lacking. Therefore, we employed top-down mass spectrometry (MS) to identify and characterize Tpm isoforms present in different skeletal muscles from multiple species, including swine, rat, and human. Our study revealed that Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. Tandem MS was utilized to identify the sequences of the major Tpm isoforms. Furthermore, quantitative analysis revealed muscle-type specific differences in the abundance of un-modified and modified Tpm isoforms in rat and human skeletal muscles. This study represents the first systematic investigation of Tpm isoforms in skeletal muscles, which not only demonstrates the capabilities of top-down MS for the comprehensive characterization of skeletal myofilament proteins but also provides the basis for further studies on these Tpm isoforms in muscle-related diseases. PMID:27090236

  16. Comprehensive analysis of tropomyosin isoforms in skeletal muscles by top-down proteomics.

    PubMed

    Jin, Yutong; Peng, Ying; Lin, Ziqing; Chen, Yi-Chen; Wei, Liming; Hacker, Timothy A; Larsson, Lars; Ge, Ying

    2016-04-01

    Mammalian skeletal muscles are heterogeneous in nature and are capable of performing various functions. Tropomyosin (Tpm) is a major component of the thin filament in skeletal muscles and plays an important role in controlling muscle contraction and relaxation. Tpm is known to consist of multiple isoforms resulting from different encoding genes and alternative splicing, along with post-translational modifications. However, a systematic characterization of Tpm isoforms in skeletal muscles is still lacking. Therefore, we employed top-down mass spectrometry (MS) to identify and characterize Tpm isoforms present in different skeletal muscles from multiple species, including swine, rat, and human. Our study revealed that Tpm1.1 and Tpm2.2 are the two major Tpm isoforms in swine and rat skeletal muscles, whereas Tpm1.1, Tpm2.2, and Tpm3.12 are present in human skeletal muscles. Tandem MS was utilized to identify the sequences of the major Tpm isoforms. Furthermore, quantitative analysis revealed muscle-type specific differences in the abundance of un-modified and modified Tpm isoforms in rat and human skeletal muscles. This study represents the first systematic investigation of Tpm isoforms in skeletal muscles, which not only demonstrates the capabilities of top-down MS for the comprehensive characterization of skeletal myofilament proteins but also provides the basis for further studies on these Tpm isoforms in muscle-related diseases.

  17. Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression

    PubMed Central

    Yabumoto, Chizuru; Akazawa, Hiroshi; Yamamoto, Rie; Yano, Masamichi; Kudo-Sakamoto, Yoko; Sumida, Tomokazu; Kamo, Takehiro; Yagi, Hiroki; Shimizu, Yu; Saga-Kamo, Akiko; Naito, Atsuhiko T.; Oka, Toru; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Uejima, Etsuko; Komuro, Issei

    2015-01-01

    Disruption of angiotensin II type 1 (AT1) receptor prolonged life span in mice. Since aging-related decline in skeletal muscle function was retarded in Atgr1a−/− mice, we examined the role of AT1 receptor in muscle regeneration after injury. Administration of AT1 receptor blocker irbesartan increased the size of regenerating myofibers, decreased fibrosis, and enhanced functional muscle recovery after cryoinjury. We recently reported that complement C1q, secreted by macrophages, activated Wnt/β-catenin signaling and promoted aging-related decline in regenerative capacity of skeletal muscle. Notably, irbesartan induced M2 polarization of macrophages, but reduced C1q expression in cryoinjured muscles and in cultured macrophage cells. Irbesartan inhibited up-regulation of Axin2, a downstream gene of Wnt/β-catenin pathway, in cryoinjured muscles. In addition, topical administration of C1q reversed beneficial effects of irbesartan on skeletal muscle regeneration after injury. These results suggest that AT1 receptor blockade improves muscle repair and regeneration through down-regulation of the aging-promoting C1q-Wnt/β-catenin signaling pathway. PMID:26571361

  18. Impact of oxidative stress on exercising skeletal muscle.

    PubMed

    Steinbacher, Peter; Eckl, Peter

    2015-04-10

    It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

  19. Customized Platelet-Rich Plasma for Skeletal Muscle Injuries

    PubMed Central

    Hicks, Justin James; Li, Hongshuai; Philippon, Marc J.; Hurwitz, Shepard R.; Huard, Johnny; Hogan, MaCalus Vinson

    2016-01-01

    Objectives: Skeletal muscle injuries are among the most common sports-related trauma. Current treatment strategies result in formation of fibrous tissue that hinders the healing process before complete recovery. Incomplete recovery impairs muscle function and predisposes to re-injury. Platelet-Rich-Plasma (PRP) contains a multitude of growth factors and is an autologous source of growth factors for various tissue repairs. It is well established that PRP contains beneficial growth factors for muscle repair; however, it also contains high concentrations of deleterious growth factors for optimal muscle healing, such as transforming growth factor-beta 1 (TGF-β1). TGF-β1 leads to increased fibrosis impeding muscle healing. We therefore hypothesized that neutralization of TGF-β1’s action within PRP could improve PRP’s beneficial effect on skeletal muscle repair. Methods: Sixteen week old in-bred Fisher rats were used. Three rats were used for PRP isolation. 10 ml of blood were extracted from abdominal aorta and mixed with citrate phosphate dextrose solution. PRP were isolated by twice centrifugation. 24 rats were randomly assigned to four groups. A small incision was made along the tibialis anterior (TA) muscle; 50 µl cardiotoxin (CTX) (0.15ug/ul) was injected intramuscularly to the TA. One day after CTX injection, the animals were treated with PBS (control), plain PRP (PRP group), customized PRP+Ab-1x, and PRP+Ab-5x. Animals were sacrificed, and TA muscles were dissected on week 1 and 2 for assessment of muscle regeneration, fibrosis, macrophage infiltration, and satellite cell activation. Results: We observed significantly more regenerative myofibers in the PRP and customized PRP groups compared to control (Fig 1A-C). Collagen deposition (fibrosis) was detected in all groups at week 1 and week 2 after injury; while customized PRP group showed significantly decreased collagen deposition at week 1 and week 2 when compare to control and PRP groups (Fig. 1D-F). PRP

  20. Skeletal muscle mass and composition during mammalian hibernation.

    PubMed

    Cotton, Clark J

    2016-01-01

    Hibernation is characterized by prolonged periods of inactivity with concomitantly low nutrient intake, conditions that would typically result in muscle atrophy combined with a loss of oxidative fibers. Yet, hibernators consistently emerge from winter with very little atrophy, frequently accompanied by a slight shift in fiber ratios to more oxidative fiber types. Preservation of muscle morphology is combined with down-regulation of glycolytic pathways and increased reliance on lipid metabolism instead. Furthermore, while rates of protein synthesis are reduced during hibernation, balance is maintained by correspondingly low rates of protein degradation. Proposed mechanisms include a number of signaling pathways and transcription factors that lead to increased oxidative fiber expression, enhanced protein synthesis and reduced protein degradation, ultimately resulting in minimal loss of skeletal muscle protein and oxidative capacity. The functional significance of these outcomes is maintenance of skeletal muscle strength and fatigue resistance, which enables hibernating animals to resume active behaviors such as predator avoidance, foraging and mating immediately following terminal arousal in the spring.

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

    PubMed

    Calbet, Jose A L; Lundby, Carsten

    2012-12-15

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

  2. Endurance training increases the efficiency of rat skeletal muscle mitochondria.

    PubMed

    Zoladz, Jerzy A; Koziel, Agnieszka; Woyda-Ploszczyca, Andrzej; Celichowski, Jan; Jarmuszkiewicz, Wieslawa

    2016-10-01

    Endurance training enhances mitochondrial oxidative capacity, but its effect on mitochondria functioning is poorly understood. In the present study, the influence of an 8-week endurance training on the bioenergetic functioning of rat skeletal muscle mitochondria under different assay temperatures (25, 35, and 42 °C) was investigated. The study was performed on 24 adult 4-month-old male Wistar rats, which were randomly assigned to either a treadmill training group (n = 12) or a sedentary control group (n = 12). In skeletal muscles, endurance training stimulated mitochondrial biogenesis and oxidative capacity. In isolated mitochondria, endurance training increased the phosphorylation rate and elevated levels of coenzyme Q. Moreover, a decrease in mitochondrial uncoupling, including uncoupling protein-mediated proton leak, was observed after training, which could explain the increased reactive oxygen species production (in nonphosphorylating mitochondria) and enhanced oxidative phosphorylation efficiency. At all studied temperatures, endurance training significantly augmented H2O2 production (and coenzyme Q reduction level) in nonphosphorylating mitochondria and decreased H2O2 production (and coenzyme Q reduction level) in phosphorylating mitochondria. Endurance training magnified the hyperthermia-induced increase in oxidative capacity and attenuated the hyperthermia-induced decline in oxidative phosphorylation efficiency and reactive oxygen species formation of nonphosphorylating mitochondria via proton leak enhancement. Thus, endurance training induces both quantitative and qualitative changes in muscle mitochondria that are important for cell signaling as well as for maintaining muscle energy homeostasis, especially at high temperatures. PMID:27568192

  3. Glucagon-like peptide-1 binding to rat skeletal muscle.

    PubMed

    Delgado, E; Luque, M A; Alcántara, A; Trapote, M A; Clemente, F; Galera, C; Valverde, I; Villanueva-Peñacarrillo, M L

    1995-01-01

    We have found [125I]glucagon-like peptide-1(7-36)-amide-specific binding activity in rat skeletal muscle plasma membranes, with an estimated M(r) of 63,000 by cross-linking and SDS-PAGE. The specific binding was time and membrane protein concentration dependent, and displaceable by unlabeled GLP-1(7-36)-amide with an ID50 of 3 x 10(-9) M of the peptide; GLP-1(1-36)-amide also competed, whereas glucagon and insulin did not. GLP-1(7-36)-amide did not modify the basal adenylate cyclase activity in skeletal muscle plasma membranes. These data, together with our previous finding of a potent glycogenic effect of GLP-1(7-36)-amide in rat soleus muscle, and also in isolated hepatocytes, which was not accompanied by a rise in the cell cyclic AMP content, lead use to believe that the insulin-like effects of this peptide on glucose metabolism in the muscle could be mediated by a type of receptor somehow different to that described for GLP-1 in pancreatic B cells, where GLP-1 action is mediated by the cyclic AMP-adenylate cyclase system.

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

    PubMed Central

    Calbet, Jose A L; Lundby, Carsten

    2012-01-01

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

  5. Modest hyperglycemia prevents interstitial dispersion of insulin in skeletal muscle

    PubMed Central

    Kolka, Cathryn M.; Castro, Ana Valeria B.; Kirkman, Erlinda L.; Bergman, Richard N.

    2014-01-01

    Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake, but this is blocked in insulin resistance. As glucotoxicity is associated with endothelial dysfunction, the observed hyperglycemia in diet-induced obese dogs may inhibit insulin access to muscle cells, and exacerbate insulin resistance. Here we asked whether interstitial insulin diffusion is reduced in modest hyperglycemia, similar to that induced by a high fat diet. METHODS During normoglycemic (100mg/dl) and moderately hyperglycemic (120mg/dl) clamps in anesthetized canines, sequential doses of insulin were injected into the vastus medialis of one hindlimb; the contra-lateral limb served as a control. Plasma samples were collected and analyzed for insulin content. Lymph vessels of the hind leg were also catheterized, and lymph samples were analyzed as an indicator of interstitial insulin concentration. RESULTS Insulin injection increased lymph insulin in normoglycemic animals, but not in hyperglycemic animals. Muscle glucose uptake was elevated in response to hyperglycemia, however the insulin-mediated glucose uptake in normoglycemic controls was not observed in hyperglycemia. Modest hyperglycemia prevented intra-muscularly injected insulin from diffusing through the interstitial space reduced insulin-mediated glucose uptake. CONCLUSION Hyperglycemia prevents the appearance of injected insulin in the interstitial space, thus reducing insulin action on skeletal muscle cells. PMID:25468139

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

    PubMed Central

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

    2012-01-01

    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

  7. Age- and stroke-related skeletal muscle changes: a review for the geriatric clinician.

    PubMed

    Sions, Jaclyn Megan; Tyrell, Christine M; Knarr, Brian A; Jancosko, Angela; Binder-Macleod, Stuart A

    2012-01-01

    Independently, aging and stroke each have a significant negative impact on skeletal muscle, but the potential cumulative effects of aging and stroke have not been explored. Optimal interventions for individuals post stroke may include those that specifically target skeletal muscle. Addressing changes in muscles may minimize activity limitations and enhance participation post stroke. This article reviews the impact of aging and stroke on muscle morphology and composition, including fiber atrophy, reductions in muscle cross-sectional area, changes in muscle fiber distributions, and increases in intramuscular fat. Relationships between changes in muscle structure, muscle function, and physical mobility are reviewed. Clinical recommendations that preserve and enhance skeletal muscle in the aging adult and individuals post stroke are discussed. Future research directions that include systematic comparison of the differences in skeletal muscle between younger and older adults who have sustained a stroke are suggested.

  8. Muscle size explains low passive skeletal muscle force in heart failure patients

    PubMed Central

    Maiorana, Andrew J.; Naylor, Louise H.; Dembo, Lawrence G.; Lloyd, David G.; Green, Daniel J.; Rubenson, Jonas

    2016-01-01

    Background Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. Methods Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. Results We found reduced passive SOL forces (∼30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. Discussion These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening. PMID:27672504

  9. Muscle size explains low passive skeletal muscle force in heart failure patients

    PubMed Central

    Maiorana, Andrew J.; Naylor, Louise H.; Dembo, Lawrence G.; Lloyd, David G.; Green, Daniel J.; Rubenson, Jonas

    2016-01-01

    Background Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. Methods Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. Results We found reduced passive SOL forces (∼30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. Discussion These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening.

  10. The impact of obesity on skeletal muscle architecture in untrained young vs. old women.

    PubMed

    Tomlinson, D J; Erskine, R M; Winwood, K; Morse, C I; Onambélé, G L

    2014-12-01

    It is unknown whether loading of the lower limbs through additional storage of fat mass as evident in obesity would promote muscular adaptations similar to those seen with resistance exercise. It is also unclear whether ageing modulates any such adjustments. This study aimed to examine the relationships between adiposity, ageing and skeletal muscle size and architecture. A total of 100 untrained healthy women were categorised by age into young (Y) (mean ± SD: 26.7 ± 9.4 years) vs. old (O) (65.1 ± 7.2 years) and body mass index (BMI) classification (underweight, normal weight, overweight and obese). Participants were assessed for body fat using dual energy x-ray absorptiometry, and for gastrocnemius medialis (GM) muscle architecture (skeletal muscle fascicle pennation angle and length) and size [GM muscle volume and physiological cross-sectional area (PCSA)] using B-mode ultrasonography. GM fascicle pennation angle (FPA) in the obese Y females was 25% greater than underweight (P = 0.001) and 25% greater than normal weight (P = 0.001) individuals, while O females had 32 and 22% greater FPA than their underweight (P = 0.008) and normal weight (P = 0.003) counterparts. Furthermore, FPA correlated with body mass in both Y and O females (Y r = 0.303; P < 0.001; O r = 0.223; P = 0.001), yet no age-related differences in the slope or r-values were observed (P > 0.05). Both GM muscle volume (P = 0.003) and PCSA (P = 0.004) exhibited significant age × BMI interactions. In addition, muscle volume and PCSA correlated with BMI, body mass and fat mass. Interestingly, ageing reduced both the degree of association in these correlations (P < 0.05) and the slope of the regressions (P < 0.05). Our findings partly support our hypotheses in that obesity-associated changes in GM PCSA and volume differed between the young and old. The younger GM muscle adapted to the loading induced by high levels of body mass, adiposity and BMI by increasing its volume and increasing its pennation

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

    PubMed

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

    2015-02-01

    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.

  12. Dietary Magnesium Is Positively Associated With Skeletal Muscle Power and Indices of Muscle Mass and May Attenuate the Association Between Circulating C-Reactive Protein and Muscle Mass in Women.

    PubMed

    Welch, Ailsa A; Kelaiditi, Eirini; Jennings, Amy; Steves, Claire J; Spector, Tim D; MacGregor, Alexander

    2016-02-01

    Age-related loss of skeletal muscle mass and strength are risk factors for sarcopenia, osteoporosis, falls, fractures, frailty, and mortality. Dietary magnesium (Mg) could play a role in prevention of age-related loss of skeletal muscle mass, power, and strength directly through physiological mechanisms or indirectly through an impact on chronic low-grade inflammation, itself a risk factor for loss of skeletal muscle mass and strength. In a cross-sectional study of 2570 women aged 18 to 79 years, we examined associations between intakes of Mg, estimated using a food-frequency questionnaire (FFQ), dual-energy X-ray absorptiometry (DXA)-derived measures of muscle mass (fat-free mass as a percentage of body weight [FFM%], fat-free mass index [FFMI, kg/m(2)]), leg explosive power (LEP), and grip strength (n = 949 only). We also examined associations between circulating hs-CRP (C-reactive protein) and muscle mass and LEP, and explored the potential attenuation of these relationships by Mg. We compared our findings with those of age and protein intake. Endpoints were calculated by quintile of Mg and adjusted for relevant confounders. Significant positive associations were found between a higher Mg and indices of skeletal muscle mass and LEP, and also with hs-CRP, after adjustment for covariates. Contrasting extreme quintiles of Mg intake showed differences of 2.6% for FFM% (p trend < 0.001), 0.4 kg/m(2) for FFMI (p trend = 0.005), and 19.6 watts/kg for LEP (p trend < 0.001). Compared with protein, these positive associations were 7 times greater for FFM% and 2.5 times greater for LEP. We also found that higher hs-CRP was negatively associated with skeletal muscle mass and, in statistical modeling, that a higher dietary Mg attenuated this negative relationship by 6.5%, with greater attenuation in women older than 50 years. No association was found between Mg and grip strength. Our results suggest that dietary magnesium may aid conservation of age-related loss of skeletal

  13. Citrulline malate supplementation increases muscle efficiency in rat skeletal muscle.

    PubMed

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

    2011-09-30

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

  14. Human skeletal muscle protein breakdown during spaceflight

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

    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.

  15. The peculiar apoptotic behavior of skeletal muscle cells.

    PubMed

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

    2013-08-01

    Apoptosis plays an active role in maintaining skeletal muscle homeostasis. Its deregulation is involved in several skeletal muscle disorders such as dystrophies, myopathies, disuse and sarcopenia. The aim of this work was to study in vitro the apoptotic behavior induced by etoposide, staurosporine and hydrogen peroxide in the C2C12 skeletal muscle cell line, comparing myoblast vs myotube sensitivity, investigated by means of morphological and cytofluorimetric analyses. Myotubes appeared more resistant than myoblasts to apoptotic induction. In myoblasts treated with etoposide, nuclei with chromatin condensation were observed, in the presence of a diffuse DNA fragmentation, as shown by confocal microscopy. The latter also appeared in myotubes, where apoptotic and normal nuclei coexisted inside the same syncytium. After staurosporine treatment, myobalsts evidenced late apoptotic features and a high number of TUNEL-positive nuclei. Secondary necrosis appeared in myotubes, where myonuclei with cleaved DNA again coexisted with normal myonuclei. After H₂O₂ exposure, myotubes, differently from myoblasts, showed a poor sensitivity to cell death. Intriguingly, autophagic granules appeared abundantly in myotubes after each treatment. In myotubes, mitochondria were better preserved than in myoblasts since those which were damaged were probably degraded through autophagic processes. These findings demonstrate a scarce sensitivity of myotubes to apoptotic stimuli due to acquisition of an apoptosis-resistant phenotype during differentiation. The presence of nuclear-dependent "territorial" death domains in the syncytium could explain a slower death of myotubes compared to mononucleated cells. In addition, autophagy could preserve and protect muscle cell integrity against chemical stimuli, making C2C12 cells, in particular myotubes, more resistant to apoptosis induction. PMID:23400589

  16. Role of hydrogen sulfide in skeletal muscle biology and metabolism

    PubMed Central

    Veeranki, Sudhakar; Tyagi, Suresh C.

    2014-01-01

    Hydrogen sulfide (H2S) is a novel endogenous gaseous signal transducer (gasotransmittor). 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

  17. Three-dimensionally printed biological machines powered by skeletal muscle

    PubMed Central

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

    2014-01-01

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

  18. Differential gene expression in skeletal muscle cells after membrane depolarization.

    PubMed

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

    2007-03-01

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

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

    PubMed Central

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

    2013-01-01

    Myosin binding protein-C (MyBP-C) exists in three major isoforms: slow skeletal, fast skeletal, and cardiac. While cardiac MyBP-C (cMyBP-C) expression is restricted to the heart in the adult, it is transiently expressed in neonatal stages of some skeletal muscles. However, it is unclear whether this expression is necessary for the proper development and function of skeletal muscle. Our aim was to determine whether the absence of cMyBP-C alters the structure, function, or MyBP-C isoform expression in adult skeletal muscle using a cMyBP-C null mouse model (cMyBP-C(t/t)). Slow MyBP-C was expressed in both slow and fast skeletal muscles, whereas fast MyBP-C was mostly restricted to fast skeletal muscles. Expression of these isoforms was unaffected in skeletal muscle from cMyBP-C(t/t) mice. Slow and fast skeletal muscles in cMyBP-C(t/t) mice showed no histological or ultrastructural changes in comparison to the wild-type control. In addition, slow muscle twitch, tetanus tension, and susceptibility to injury were all similar to the wild-type controls. Interestingly, fMyBP-C expression was significantly increased in the cMyBP-C(t/t) hearts undergoing severe dilated cardiomyopathy, though this does not seem to prevent dysfunction. Additionally, expression of both slow and fast isoforms was increased in myopathic skeletal muscles. Our data demonstrate that i) MyBP-C isoforms are differentially regulated in both cardiac and skeletal muscles, ii) cMyBP-C is dispensable for the development of skeletal muscle with no functional or structural consequences in the adult myocyte, and iii) skeletal isoforms can transcomplement in the heart in the absence of cMyBP-C. PMID:23936073

  20. Impact of age on the vasodilatory function of human skeletal muscle feed arteries.

    PubMed

    Park, Song-Young; Ives, Stephen J; Gifford, Jayson R; Andtbacka, Robert H I; Hyngstrom, John R; Reese, Van; Layec, Gwenael; Bharath, Leena P; Symons, John D; Richardson, Russell S

    2016-01-15

    Although advancing age is often associated with attenuated skeletal muscle blood flow and skeletal muscle feed arteries (SMFAs) have been recognized to play a regulatory role in the vasculature, little is known about the impact of age on the vasodilatory capacity of human SMFAs. Therefore, endothelium-dependent and -independent vasodilation were assessed in SMFAs (diameter: 544 ± 63 μm) obtained from 24 (equally represented) young (33 ± 2 yr) and old (71 ± 2 yr) subjects in response to three stimuli: 1) flow-induced shear stress, 2) ACh, and 3) sodium nitropusside (SNP). Both assessments of endothelium-dependent vasodilation, flow (young subjects: 68 ± 1% and old subjects: 32 ± 7%) and ACh (young subjects: 92 ± 3% and old subjects: 73 ± 4%), were significantly blunted (P < 0.05) in SMFAs of old compared with young subjects, with no such age-related differences in endothelium-independent vasodilation (SNP). In response to an increase in flow-induced shear stress, vasodilation kinetics (time constant to reach 63% of the amplitude of the response: 55 ± 1 s in young subjects and 92 ± 7 s in old subjects) and endothelial nitric oxide synthase (eNOS) activation (phospho-eNOS(s1177)/total eNOS: 1.0 ± 0.1 in young subjects and 0.2 ± 0.1 in old subjects) were also significantly attenuated in old compared with young subjects (P < 0.05). Furthermore, the vessel superoxide concentration was greater in old subjects (old subjects: 3.9 ± 1.0 area under curve/mg and young subjects: 1.7 ± 0.1 area under the curve/mg, P < 0.05). These findings reveal that the endothelium-dependent vasodilatory capacity, including vasodilation kinetics but not smooth muscle function, of human SMFAs is blunted with age and may be due to free radicals. Given the potential regulatory role of SMFAs in skeletal muscle blood flow, these findings may explain, at least in part, the often observed attenuated perfusion of skeletal muscle with advancing age that may contribute to exercise

  1. Muscle contractile activity regulates Sirt3 protein expression in rat skeletal muscles.

    PubMed

    Hokari, Fumi; Kawasaki, Emi; Sakai, Atsushi; Koshinaka, Keiichi; Sakuma, Kunihiro; Kawanaka, Kentaro

    2010-08-01

    Sirt3, a member of the sirtuin family, is known to control cellular mitochondrial function. Furthermore, because sirtuins require NAD for their deacetylase activity, nicotinamide phosphoribosyltransferase (Nampt), which is a rate-limiting enzyme in the intracellular NAD biosynthetic pathway, influences their activity. We examined the effects of exercise training and normal postural contractile activity on Sirt3 and Nampt protein expression in rat skeletal muscles. Male rats were trained by treadmill running at 20 m/min, 60 min/day, 7 days/wk for 4 wk. This treadmill training program increased the Sirt3 protein expression in the soleus and plantaris muscles by 49% and 41%, respectively (P < 0.05). Moreover, a 4-wk voluntary wheel-running program also induced 66% and 95% increases in Sirt3 protein in the plantaris and triceps muscles of rats, respectively (P < 0.05). Treadmill-running and voluntary running training induced no significant changes in Nampt protein expression in skeletal muscles. In resting rats, the soleus muscle, which is recruited during normal postural activity, possessed the greatest expression levels of the Sirt3 and Nampt proteins, followed by the plantaris and triceps muscles. Furthermore, the Sirt3, but not Nampt, protein level was reduced in the soleus muscles from immobilized hindlimbs compared with that shown in the contralateral control muscle. These results demonstrated that 1) Sirt3 protein expression is upregulated by exercise training in skeletal muscles and 2) local postural contractile activity plays an important role in maintaining a high level of Sirt3 protein expression in postural muscle.

  2. Hyperinsulinemia and skeletal muscle fatty acid trafficking.

    PubMed

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

    2013-08-15

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

  3. The skeletal muscle vascular supply closely correlates with the muscle fiber surface area in the rat.

    PubMed

    Ichinose, Emiko; Kurose, Tomoyuki; Daitoku, Daisuke; Kawamata, Seiichi

    2008-05-01

    The skeletal muscle capillary supply (capillarity) dynamically changes in response to muscle conditions such as growth, atrophy, and hypertrophy. The capillary number-to-fiber ratio is reported to correlate closely with the muscle fiber cross sectional area. However, little information is available regarding the capillarity of neonatal and very young skeletal muscles. In this study, the vascular endothelium was reliably stained with an anti-PECAM-1 antibody, and relationships between the capillarity and muscle fiber parameters were analyzed. For assessment of the capillarity, we used the capillary length-to-fiber ratio, due to the presence of transversely running vessels. In young and adult rats, the capillary length-to-fiber ratio was proportional to both the muscle fiber cross sectional area and muscle fiber radius. However, when these data were analyzed together with data from neonatal and very young rats, the capillary length-to-fiber ratio correlated more closely with the muscle fiber radius than the muscle fiber cross sectional area in the tibialis anterior muscle. The capillary number-to-fiber ratio demonstrated results very similar to the capillary length-to-fiber ratio. During muscle atrophy after denervation, the number of capillaries was decreased in a non-apoptotic manner as revealed by electron microscopy, maintaining the close relationship between the parameters described above. In conclusion, capillarity was closely correlated with the muscle fiber radius (which represents the perimeter) during growth and atrophy. This indicates that the capillarity is linked to the muscle fiber surface area (which is determined by perimeter and section thickness), in agreement with the essential role of the cell membrane in the transport of materials by simple diffusion or active transport.

  4. Viscoelasticity-based MR elastography of skeletal muscle

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

  5. Hyaluronidase increases electrogene transfer efficiency in skeletal muscle.

    PubMed

    Mennuni, Carmela; Calvaruso, Francesco; Zampaglione, Immacolata; Rizzuto, Gabriella; Rinaudo, Daniela; Dammassa, Ernesta; Ciliberto, Gennaro; Fattori, Elena; La Monica, Nicola

    2002-02-10

    Electrogene transfer (EGT) of plasmid DNA into skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. We report here that preinjecting hyaluronidase (HYAse) significantly increases the gene transfer efficiency of muscle EGT. Three constructs encoding mouse erythropoietin (pCMV/mEPO), secreted alkaline phosphatase (pCMV/SeAP), and luciferase (pGGluc) were electroinjected intramuscularly in BALB/c mice and rabbits with and without HYAse pretreatment. Preinjection 1 or 4 hr before EGT increased EPO gene expression by about 5-fold in mice and maintained higher gene expression than plasmid EGT alone. A similar increment in gene expression was observed on pretreatment with HYAse and electroinjection of pCMV/mEPO into rabbit tibialis muscle. The increment of gene expression in rabbits reached 17-fold on injection of plasmid pCMV/SeAP and 24-fold with plasmid pGGluc. Injection of a plasmid encoding beta-galactosidase (pCMV/beta gal/NLS) and subsequent staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside indicated that HYAse increased the tissue area involved in gene expression. No irreversible tissue damage was observed on histological analysis of treated muscles. HYAse is used in a variety of clinical applications, and thus the combination of HYAse pretreatment and muscle EGT may constitute an efficient gene transfer method to achieve therapeutic levels of gene expression.

  6. Leucine incorporation into mixed skeletal muscle protein in humans

    SciTech Connect

    Nair, K.S.; Halliday, D.; Griggs, R.C. Clinical Research Centre, Harrow )

    1988-02-01

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

  7. Mitochondrial Ca(2+) uptake in skeletal muscle health and disease.

    PubMed

    Zhou, Jingsong; Dhakal, Kamal; Yi, Jianxun

    2016-08-01

    Muscle uses Ca(2+) as a messenger to control contraction and relies on ATP to maintain the intracellular Ca(2+) homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca(2+) from their surroundings, a process called mitochondrial Ca(2+) uptake. Under physiological conditions, Ca(2+) uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca(2+) overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca(2+) uptake could shape spatio-temporal patterns of intracellular Ca(2+) signaling. Malfunction of mitochondrial Ca(2+) uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca(2+) levels. Besides the sudden elevation of Ca(2+) level induced by action potentials, Ca(2+) transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca(2+) uptake is fast and big enough to shape intracellular Ca(2+) signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca(2+) inside mitochondria. This review focuses on characterization of mitochondrial Ca(2+) uptake in skeletal muscle and its role in muscle physiology and diseases. PMID:27430885

  8. Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

    NASA Technical Reports Server (NTRS)

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

    1986-01-01

    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.

  9. Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition

    PubMed Central

    Haizlip, K. M.; Harrison, B. C.

    2015-01-01

    Previous studies have identified over 3,000 genes that are differentially expressed in male and female skeletal muscle. Here, we review the sex-based differences in skeletal muscle fiber composition, myosin heavy chain expression, contractile function, and the regulation of these physiological differences by thyroid hormone, estrogen, and testosterone. The findings presented lay the basis for the continued work needed to fully understand the skeletal muscle differences between males and females. PMID:25559153

  10. Lower skeletal muscle capillarization in hypertensive elderly men.

    PubMed

    Gueugneau, Marine; Coudy-Gandilhon, Cécile; Meunier, Bruno; Combaret, Lydie; Taillandier, Daniel; Polge, Cécile; Attaix, Didier; Roche, Frédéric; Féasson, Léonard; Barthélémy, Jean-Claude; Béchet, Daniel

    2016-04-01

    Aging strongly affects the skeletal muscle and is associated with microvascular dysfunctions. Age is also a primary risk factor for the metabolic syndrome, which is a cluster of metabolic and cardiovascular symptoms. Among the metabolic syndrome components, hypertension is the most prevalent in elderly subjects and has a central role in vascular alterations. Despite critical clinical outcomes, the effects of hypertension and metabolic syndrome on skeletal muscle capillarization have poorly been investigated during aging. In the present study, muscle biopsies from normotensive young (YO) and elderly (ELc) men, and elderly men with hypertension (EL-HT) or metabolic syndrome (EL-MS) were assessed for the number of capillaries around a fiber (CAF), capillary-to-fiber perimeter exchange (CFPE), length of contact to perimeter of fiber ratio (LC/PF), capillary tortuosity, and for extracellular matrix (ECM) embedding capillaries. As capillarization and muscle mitochondrial oxidative capacity may be associated, we also investigated cytochrome c oxidase (COX) content. Our findings indicate that capillarization and COX did not change between normotensive adult and old individuals. They further reveal that hypertension in elderly men is associated with reduced CAF (ELc: 5.2 ± 0.4, EL-HT: 4.1 ± 0.2, P<0.02 for type I fibers; ELc: 4.1 ± 0.2, EL-HT: 3.1 ± 0.3, P<0.03 for type IIA fibers), CFPE (ELc: 7.9 ± 0.7, EL-HT: 6.4 ± 0.4 capillaries/1000 μm, P<0.03 for type I fibers; ELc: 6.5 ± 0.4, EL-HT: 5.2 ± 0.4 capillaries/1000 μm, P<0.03 for type IIA fibers), LC/PF (ELc: 23.3 ± 1.2, EL-HT: 17.8 ± 0.6%, P<0.01 for type I fibers; ELc: 19.8 ± 1.1, EL-HT: 15.6 ± 0.8%, P<0.01 for type IIA fibers) and capillary tortuosity, and with ECM endomysium fibrosis. Capillary rarefaction also correlated with lower COX content in the old hypertensive muscle. No further modification occurred with metabolic syndrome in elderly men. Collectively, our results suggest that hypertension plays

  11. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4*♦

    PubMed Central

    Bullard, Steven A.; Seo, Seongjin; Schilling, Birgit; Dyle, Michael C.; Dierdorff, Jason M.; Ebert, Scott M.; DeLau, Austin D.; Gibson, Bradford W.; Adams, Christopher M.

    2016-01-01

    Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. PMID:27358404

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

    PubMed Central

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

    2015-01-01

    Mitochondrial fission and fusion are essential processes in the maintenance of the skeletal muscle function. The contribution of these processes to muscle development has not been properly investigated in vivo because of the early lethality of the models generated so far. To define the role of mitochondrial fission in muscle development and repair, we have generated a transgenic mouse line that overexpresses the fission-inducing protein Drp1 specifically in skeletal muscle. These mice displayed a drastic impairment in postnatal muscle growth, with reorganisation of the mitochondrial network and reduction of mtDNA quantity, without the deficiency of mitochondrial bioenergetics. Importantly we found that Drp1 overexpression activates the stress-induced PKR/eIF2α/Fgf21 pathway thus leading to an attenuated protein synthesis and downregulation of the growth hormone pathway. These results reveal for the first time how mitochondrial network dynamics influence muscle growth and shed light on aspects of muscle physiology relevant in human muscle pathologies. PMID:25719247

  13. Pro-Insulin-Like Growth Factor-II Ameliorates Age-Related Inefficient Regenerative Response by Orchestrating Self-Reinforcement Mechanism of Muscle Regeneration.

    PubMed

    Ikemoto-Uezumi, Madoka; Uezumi, Akiyoshi; Tsuchida, Kunihiro; Fukada, So-ichiro; Yamamoto, Hiroshi; Yamamoto, Naoki; Shiomi, Kosuke; Hashimoto, Naohiro

    2015-08-01

    Sarcopenia, age-related muscle weakness, increases the frequency of falls and fractures in elderly people, which can trigger severe muscle injury. Rapid and successful recovery from muscle injury is essential not to cause further frailty and loss of independence. In fact, we showed insufficient muscle regeneration in aged mice. Although the number of satellite cells, muscle stem cells, decreases with age, the remaining satellite cells maintain the myogenic capacity equivalent to young mice. Transplantation of young green fluorescent protein (GFP)-Tg mice-derived satellite cells into young and aged mice revealed that age-related deterioration of the muscle environment contributes to the decline in regenerative capacity of satellite cells. Thus, extrinsic changes rather than intrinsic changes in satellite cells appear to be a major determinant of inefficient muscle regeneration with age. Comprehensive protein expression analysis identified a decrease in insulin-like growth factor-II (IGF-II) level in regenerating muscle of aged mice. We found that pro- and big-IGF-II but not mature IGF-II specifically express during muscle regeneration and the expressions are not only delayed but also decreased in absolute quantity with age. Supplementation of pro-IGF-II in aged mice ameliorated the inefficient regenerative response by promoting proliferation of satellite cells, angiogenesis, and suppressing adipogenic differentiation of platelet derived growth factor receptor (PDGFR)α(+) mesenchymal progenitors. We further revealed that pro-IGF-II but not mature IGF-II specifically inhibits the pathological adipogenesis of PDGFRα(+) cells. Together, these results uncovered a distinctive pro-IGF-II-mediated self-reinforcement mechanism of muscle regeneration and suggest that supplementation of pro-IGF-II could be one of the most effective therapeutic approaches for muscle injury in elderly people.

  14. Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation.

    PubMed

    Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

    2015-01-05

    Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca(2+) 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, Ca(2+) regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca(2+)-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca(2+) ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca(2+) ions in adult muscle but also highlight recent findings of critical Ca(2+)-dependent mechanisms essential for skeletal muscle-regulation and maintenance.

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

    PubMed Central

    Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

    2015-01-01

    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

  16. Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation.

    PubMed

    Gehlert, Sebastian; Bloch, Wilhelm; Suhr, Frank

    2015-01-01

    Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures the functionality of an organism. In skeletal muscle fibers, Ca(2+) 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, Ca(2+) regulates also intracellular processes, such as myosin-actin cross bridging, protein synthesis, protein degradation and fiber type shifting by the control of Ca(2+)-sensitive proteases and transcription factors, as well as mitochondrial adaptations, plasticity and respiration. These data highlight the overwhelming significance of Ca(2+) ions for the integrity of skeletal muscle tissue. In this review, we address the major functions of Ca(2+) ions in adult muscle but also highlight recent findings of critical Ca(2+)-dependent mechanisms essential for skeletal muscle-regulation and maintenance. PMID:25569087

  17. Time-dependent behavior of passive skeletal muscle

    NASA Astrophysics Data System (ADS)

    Ahamed, T.; Rubin, M. B.; Trimmer, B. A.; Dorfmann, L.

    2016-03-01

    An isotropic three-dimensional nonlinear viscoelastic model is developed to simulate the time-dependent behavior of passive skeletal muscle. The development of the model is stimulated by experimental data that characterize the response during simple uniaxial stress cyclic loading and unloading. Of particular interest is the rate-dependent response, the recovery of muscle properties from the preconditioned to the unconditioned state and stress relaxation at constant stretch during loading and unloading. The model considers the material to be a composite of a nonlinear hyperelastic component in parallel with a nonlinear dissipative component. The strain energy and the corresponding stress measures are separated additively into hyperelastic and dissipative parts. In contrast to standard nonlinear inelastic models, here the dissipative component is modeled using an evolution equation that combines rate-independent and rate-dependent responses smoothly with no finite elastic range. Large deformation evolution equations for the distortional deformations in the elastic and in the dissipative component are presented. A robust, strongly objective numerical integration algorithm is used to model rate-dependent and rate-independent inelastic responses. The constitutive formulation is specialized to simulate the experimental data. The nonlinear viscoelastic model accurately represents the time-dependent passive response of skeletal muscle.

  18. Thyroid hormones regulate skeletal muscle regeneration after acute injury.

    PubMed

    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

    2015-02-01

    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 μg/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.

  19. Optogenetic control of contractile function in skeletal muscle

    PubMed Central

    Bruegmann, Tobias; van Bremen, Tobias; Vogt, Christoph C.; Send, Thorsten; Fleischmann, Bernd K.; Sasse, Philipp

    2015-01-01

    Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis. PMID:26035411

  20. Determination of MiRNA Targets in Skeletal Muscle Cells

    PubMed Central

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

    2014-01-01

    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

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

    SciTech Connect

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

    2015-02-01

    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{sup −/−} 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. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

  2. Site-specific thigh muscle loss as an independent phenomenon for age-related muscle loss in middle-aged and older men and women.

    PubMed

    Abe, Takashi; Patterson, Kaitlyn M; Stover, Caitlin D; Geddam, David A R; Tribby, Aaron C; Lajza, David G; Young, Kaelin C

    2014-06-01

    The purpose of this study was to examine the relationships between dual-energy X-ray absorptiometry (DXA)-determined appendicular lean mass (aLM) and ultrasound-measured thigh muscle thickness (MTH) ratio and between aLM or thigh MTH ratio and zigzag walking performance. Eighty-one middle-aged and older adults (41 men and 40 women) aged 50 to 74 years volunteered for the study. Approximately two thirds of the subjects (34 men and 17 women) carried out regular sports activity (at least >2 times a week) including running and cycling exercise. MTH was measured using B-mode ultrasound at two sites on the anterior (A50) and posterior (P50) aspects of the mid-thigh. A50:P50 MTH ratio was calculated to evaluate site-specific thigh muscle loss. aLM and percent body fat were also determined using a DXA. Men had lower body fat and higher aLM than women. Anterior and posterior thigh MTH as well as A50:P50 MTH ratio was higher in men than in women. Zigzag walking time was faster in men than in women. Anterior and posterior thigh MTH was positively (p < 0.001) correlated to aLM and aLM index in men and women. However, A50:P50 MTH ratio was not significantly correlated with aLM and aLM index in both sexes. There was no significant correlation between aLM index and zigzag walking time in men and women. A50:P50 MTH ratio was inversely (p < 0.05) correlated to zigzag walking time in both men and women. Our results suggest that thigh MTH ratio is independent of age-related muscle mass loss detected by aLM.

  3. Preservation of rat skeletal muscle energy metabolism by illumination.

    PubMed

    Lindgård, Ann; Lundberg, Jonas; Rakotonirainy, Olivier; Elander, Anna; Soussi, Bassam

    2003-04-25

    Skeletal muscle viability is crucially dependent on the tissue levels of its high energy phosphates. In this study we investigated the effect of the preservation medium Perfadex and illumination with Singlet Oxygen Energy (SOE). Singlet oxygen can be produced photochemically by energy transfer from an excited photosensitizer. The energy emitted from singlet oxygen upon relaxation to its triplet state is captured as photons at 634 nm and is here referred to as SOE. Rat hind limb rectus femoris muscles were preserved for five hours at 22 degrees C in Perfadex, saline, SOE illuminated Perfadex or SOE illuminated saline. Extracts of the muscles were analysed by 31P NMR. Data were analysed using two-way analysis of variance and are given as mean values micromol/g dry weight) +/- SEM. The ATP concentration was higher (p = 0.006) in saline groups (4.52) compared with Perfadex groups (2.82). There was no statistically significant difference in PCr between the saline groups (1.25) and Perfadex groups (0.82). However, there were higher (p = 0.003) ATP in the SOE illuminated groups (4.61) compared with the non-illuminated groups (2.73). The PCr was also higher (p < 0.0001) in the SOE illuminated groups (1.89) compared with the non-illuminated groups (0.18). In conclusion, Perfadex in this experimental model was incapable of preserving the high energy phosphates in skeletal muscle during 5 hours of ischemia. Illumination with SOE at 634 nm improved the preservation potential, in terms of a positive effect on the energy status of the muscle cell.

  4. Skeletal muscle signature of a champion sprint runner

    PubMed Central

    Luden, Nicholas; Minchev, Kiril; Raue, Ulrika; Jemiolo, Bozena; Trappe, Todd A.

    2015-01-01

    We had the unique opportunity to study the skeletal muscle characteristics, at the single fiber level, of a world champion sprint runner who is the current indoor world record holder in the 60-m hurdles (7.30 s) and former world record holder in 110-m hurdles (12.91 s). Muscle biopsies were obtained from the vastus lateralis at rest and 4 h after a high-intensity exercise challenge (4 × 7 repetitions of resistance exercise). Single muscle fiber analyses were conducted for fiber type distribution (myosin heavy chain, MHC), fiber size, contractile function (strength, speed, and power) and mRNA expression (before and after the exercise bout). The world-class sprinter's leg muscle had a high abundance (24%) of the pure MHC IIx muscle fibers with a total fast-twitch fiber population of 71%. Power output of the MHC IIx fibers (35.1 ± 1.4 W/l) was 2-fold higher than MHC IIa fibers (17.1 ± 0.5 W/l) and 14-fold greater than MHC I fibers (2.5 ± 0.1 W/l). Additionally, the MHC IIx fibers were highly responsive to intense exercise at the transcriptional level for genes involved with muscle growth and remodeling (Fn14 and myostatin). To our knowledge, the abundance of pure MHC IIx muscle fibers is the highest observed in an elite sprinter. Further, the power output of the MHC IIa and MHC IIx muscle fibers was greater than any human values reported to date. These data provide a myocellular basis for the high level of sprinting success achieved by this individual. PMID:25749440

  5. Postexercise Dietary Protein Strategies to Maximize Skeletal Muscle Repair and Remodeling in Masters Endurance Athletes: A Review.

    PubMed

    Doering, Thomas M; Reaburn, Peter R; Phillips, Stuart M; Jenkins, David G

    2016-04-01

    Participation rates of masters athletes in endurance events such as long-distance triathlon and running continue to increase. Given the physical and metabolic demands of endurance training, recovery practices influence the quality of successive training sessions and, consequently, adaptations to training. Research has suggested that, after muscle-damaging endurance exercise, masters athletes experience slower recovery rates in comparison with younger, similarly trained athletes. Given that these discrepancies in recovery rates are not observed after non-muscle-damaging exercise, it is suggested that masters athletes have impairments of the protein remodeling mechanisms within skeletal muscle. The importance of postexercise protein feeding for endurance athletes is increasingly being acknowledged, and its role in creating a positive net muscle protein balance postexercise is well known. The potential benefits of postexercise protein feeding include elevating muscle protein synthesis and satellite cell activity for muscle repair and remodeling, as well as facilitating muscle glycogen resynthesis. Despite extensive investigation into age-related anabolic resistance in sedentary aging populations, little is known about how anabolic resistance affects postexercise muscle protein synthesis and thus muscle remodeling in aging athletes. Despite evidence suggesting that physical training can attenuate but not eliminate age-related anabolic resistance, masters athletes are currently recommended to consume the same postexercise dietary protein dose (approximately 20 g or 0.25 g/kg/meal) as younger athletes. Given the slower recovery rates of masters athletes after muscle-damaging exercise, which may be due to impaired muscle remodeling mechanisms, masters athletes may benefit from higher doses of postexercise dietary protein, with particular attention directed to the leucine content of the postexercise bolus.

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

    PubMed

    Lienbacher, Karoline; Horn, Anja K E

    2012-12-01

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

  7. Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres

    PubMed Central

    Zanou, Nadège; Mondin, Ludivine; Fuster, Clarisse; Seghers, François; Dufour, Inès; de Clippele, Marie; Schakman, Olivier; Tajeddine, Nicolas; Iwata, Yuko; Wakabayashi, Shigeo; Voets, Thomas; Allard, Bruno; Gailly, Philippe

    2015-01-01

    Abstract Increased plasma osmolarity induces intracellular water depletion and cell shrinkage followed by activation of a regulatory volume increase (RVI). In skeletal muscle, this is accompanied by transverse tubule (TT) dilatation and by a membrane depolarization responsible for a release of Ca2+ from intracellular pools. We observed that both hyperosmotic shock-induced Ca2+ transients and RVI were inhibited by Gd3+, ruthenium red and GsMTx4 toxin, three inhibitors of mechanosensitive ion channels. The response was also completely absent in muscle fibres overexpressing a non-permeant, dominant negative (DN) mutant of the transient receptor potential, V2 isoform (TRPV2) ion channel, suggesting the involvement of TRPV2 or of a TRP isoform susceptible to heterotetramerization with TRPV2. The release of Ca2+ induced by hyperosmotic shock was increased by cannabidiol, an activator of TRPV2, and decreased by tranilast, an inhibitor of TRPV2, suggesting a role for the TRPV2 channel itself. Hyperosmotic shock-induced membrane depolarization was impaired in TRPV2-DN fibres, suggesting that TRPV2 activation triggers the release of Ca2+ from the sarcoplasmic reticulum by depolarizing TTs. RVI requires the sequential activation of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NKCC1, a Na+–K+–Cl− cotransporter, allowing ion entry and driving osmotic water flow. In fibres overexpressing TRPV2-DN as well as in fibres in which Ca2+ transients were abolished by the Ca2+ chelator BAPTA, the level of P-SPAKSer373 in response to hyperosmotic shock was reduced, suggesting a modulation of SPAK phosphorylation by intracellular Ca2+. We conclude that TRPV2 is involved in osmosensation in skeletal muscle fibres, acting in concert with P-SPAK-activated NKCC1. Key points Increased plasma osmolarity induces intracellular water depletion and cell shrinkage (CS) followed by activation of a regulatory volume increase (RVI). In skeletal muscle, the hyperosmotic shock

  8. Effects of calcium phosphate bioceramics on skeletal muscle cells.

    PubMed

    Sun, J S; Tsuang, Y H; Yao, C H; Liu, H C; Lin, F H; Hang, Y S

    1997-02-01

    With advances in ceramics technology, calcium phosphate bioceramics have been applied as bone substitutes. The effects of implants on bony tissue have been investigated. The effects upon adjacent skeletal muscles have not been determined. The focus of this work is to elucidate the biological effects of various calcium phosphate bioceramics on skeletal muscles. Four different kinds of powder of calcium phosphate biomaterials including beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA), beta-dicalcium pyrophosphate (beta-DCP) and sintered beta-dicalcium pyrophosphate (SDCP), were tested by myoblast cell cultures. The results were analyzed by cell count, cell morphology and concentration of transforming growth factor beta 1 (TGF-beta 1) in culture medium. The cell population and TGF-beta 1 concentration of the control sample increased persistently as the time of culture increased. The changes in cell population and TGF-beta 1 concentration in culture medium of the beta-TCP and HA were quite low in the first 3 days of culture, then increased gradually toward the seventh day. The changes in cell population and TGF-beta 1 concentration in culture medium of the silica, beta-DCP, and SDCP were quite similar. They were lower during the first day of culture but increased and reached that of the control medium after 7 days' culture. Most cells on B-TCP and HA diminished in size with radially spread, long pseudopods. We conclude that HA and beta-TCP are thought to have an inhibitory effect on growth of the myoblasts. The HA and beta-TCP may interfere with the repair and regeneration of injured skeletal muscle after orthopedic surgery.

  9. Enzyme activities and adenine nucleotide content in aorta, heart muscle and skeletal muscle from uraemic rats.

    PubMed Central

    Krog, M.; Ejerblad, S.; Agren, A.

    1986-01-01

    A prominent feature of arterial and myocardial lesions in uraemia is necrosis of the smooth muscle cells. In this study the possibility of detecting metabolic disturbances before necroses appear was investigated. The investigation was made on rats with moderate uraemia (mean serum creatinine 165 mumol/l) of 12 weeks duration. Enzyme activities and concentrations of adenine nucleotides were measured in aorta, heart and skeletal muscles. Histological examination disclosed no changes in these organs. Hexokinase, an important glycolytic enzyme, showed decreased activity in the skeletal muscle and aorta, whereas the hexosemonophosphate shunt enzyme glucose-6-phosphate dehydrogenase remained unchanged. The aspartate aminotransferase was increased in the skeletal muscle. Fat metabolism was not disturbed as reflected by unchanged activity of hydroxyacyl-CoA-dehydrogenase. Adenylatekinase which is important for the energy supply showed markedly increased activities in all tissues examined from the uraemic rats. Decreased ATP levels were found in the heart muscle and the aorta of the uraemic animals, whereas the total pool of adenosine phosphates remained unchanged in all tissues. The animal model described offers a useful means of detecting early changes in uraemia and should be useful for studying the effects of different treatments of uraemic complications. PMID:3718844

  10. Fluorescent staining of acetylcholine receptors in vertebrate skeletal muscle

    PubMed Central

    Anderson, M. J.; Cohen, M. W.

    1974-01-01

    1. α-Bungarotoxin was labelled with fluorescent dyes and used as a stain for visualizing the distribution of acetylcholine receptors in vertebrate skeletal muscle fibres. 2. Dye-toxin conjugates had the same pharmacological properties as native toxin, but their potencies were lower. 3. Fluorescent staining was examined in teased muscle fibres. The stain was found to be confined to the neuromuscular junction and associated with the subsynaptic membrane. 4. Staining intensity was reduced by curare and even more so by carbachol, but not by atropine or neostigmine. Pre-treatment of muscles with unlabelled α-bungarotoxin entirely prevented staining. 5. The staining at amphibian neuromuscular junctions was characterized by a pattern of intense transverse bands occurring at intervals of approximately 0·5-1 μm, with fluorescence of lower intensity between them. Fluorescent staining was not detected on adjacent, extrasynaptic, muscle membrane. In side views the staining appeared as a fine line with small protuberances occurring at the same intervals as the intense bands seen face-on. These results indicate that acetylcholine receptors are associated with the entire subsynaptic membrane, including the membrane of the junctional folds and that their density changes abruptly at the border between synaptic and extrasynaptic muscle membrane. ImagesPlate 3Plate 4Plate 1Plate 2 PMID:4133039

  11. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

    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.

  12. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

    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.

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    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.

  14. PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells

    PubMed Central

    Ho, Tsung-Chuan; Chiang, Yi-Pin; Chuang, Chih-Kuang; Chen, Show-Li; Hsieh, Jui-Wen; Lan, Yu-Wen

    2015-01-01

    In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser93-Leu112) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2′-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration. PMID:26040897

  15. The STARS signaling pathway: a key regulator of skeletal muscle function.

    PubMed

    Lamon, Séverine; Wallace, Marita A; Russell, Aaron P

    2014-09-01

    During the last decade, the striated muscle activator of Rho signaling (STARS), a muscle-specific protein, has been proposed to play an increasingly important role in skeletal muscle growth, metabolism, regeneration and stress adaptation. STARS influences actin dynamics and, as a consequence, regulates the myocardin-related transcription factor A/serum response factor (MRTF-A/SRF) transcriptional program, a well-known pathway controlling skeletal muscle development and function. Muscle-specific stress conditions, such as exercise, positively regulates, while disuse and degenerative muscle diseases are associated with a downregulation of STARS and its downstream partners, suggesting a pivotal role for STARS in skeletal muscle health. This review provides a comprehensive overview of the known role and regulation of STARS and the members of its signaling pathway, RhoA, MRTF-A and SRF, in skeletal muscle.

  16. In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use.

    PubMed

    Cho, Su Han; Kim, Jang Hoe; Song, Wook

    2016-03-01

    Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies. PMID:26996420

  17. In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use

    PubMed Central

    Cho, Su Han; Kim, Jang Hoe

    2016-01-01

    Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies. PMID:26996420

  18. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

    PubMed

    Jiang, Shih Sheng; Chen, Chung-Hsing; Tseng, Kuo-Yun; Tsai, Fang-Yu; Wang, Ming Jen; Chang, I-Shou; Lin, Jiunn-Liang; Lin, Shankung

    2011-07-01

    Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

  19. Skeletal muscle satellite cells cultured in simulated microgravity

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

    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

  20. Skeletal muscle water and electrolytes following prolonged dehydrating exercise.

    PubMed

    Mora-Rodríguez, R; Fernández-Elías, V E; Hamouti, N; Ortega, J F

    2015-06-01

    We studied if dehydrating exercise would reduce muscle water (H2Omuscle ) and affect muscle electrolyte concentrations. Vastus lateralis muscle biopsies were collected prior, immediately after, and 1 and 4 h after prolonged dehydrating exercise (150 min at 33 ± 1 °C, 25% ± 2% humidity) on nine endurance-trained cyclists (VO2max  = 54.4 ± 1.05 mL/kg/min). Plasma volume (PV) changes and fluid shifts between compartments (Cl(-) method) were measured. Exercise dehydrated subjects 4.7% ± 0.3% of body mass by losing 2.75 ± 0.15 L of water and reducing PV 18.4% ± 1% below pre-exercise values (P < 0.05). Right after exercise H2Omuscle remained at pre-exercise values (i.e., 398 ± 6 mL/100 g dw muscle(-1)) but declined 13% ± 2% (342 ± 12 mL/100 g dw muscle(-1); P < 0.05) after 1 h of supine rest. At that time, PV recovered toward pre-exercise levels. The Cl(-) method corroborated the shift of fluid between extracellular and intracellular compartments. After 4 h of recovery, PV returned to pre-exercise values; however, H2Omuscle remained reduced at the same level. Muscle Na(+) and K(+) increased (P < 0.05) in response to the H2Omuscle reductions. Our findings suggest that active skeletal muscle does not show a net loss of H2O during prolonged dehydrating exercise. However, during the first hour of recovery H2Omuscle decreases seemly to restore PV and thus cardiovascular stability.

  1. Costameres: repeating structures at the sarcolemma of skeletal muscle.

    PubMed

    Bloch, Robert J; Capetanaki, Yassemi; O'Neill, Andrea; Reed, Patrick; Williams, McRae W; Resneck, Wendy G; Porter, Neil C; Ursitti, Jeanine A

    2002-10-01

    Costameres, structures at the plasma membrane of skeletal muscle, are present in a rectilinear array that parallels the organization of the underlying contractile apparatus. Costameres have three major functions: to keep the plasma membrane, or sarcolemma, aligned and in register with nearby contractile structures; to protect the sarcolemma against contraction-induced damage; and to transmit some of the forces of contraction laterally, to the extracellular matrix. These functions require that costameres link the contractile apparatus through the membrane to the extracellular matrix. Mutations to key components of costameres cause these structures to lose their rectilinear organization and can result in muscle weakness or death. This article summarizes the evidence that costameres are composed of large complexes of integral and peripheral membrane proteins that are linked to the contractile apparatus by intermediate filaments and to the extracellular matrix by laminin. They also present evidence that costameres are altered when key costameric components are missing, as in a murine form of muscular dystrophy.

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

    NASA Technical Reports Server (NTRS)

    Adams, Gregory R.

    2002-01-01

    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.

  3. Extracellular vesicle microRNAs mediate skeletal muscle myogenesis and disease

    PubMed Central

    Wang, Haidong; Wang, Bin

    2016-01-01

    Skeletal muscle function is important for good health and independent living, and has been subject to numerous studies focused on skeletal muscle development, function and metabolism. However, progressive and degenerative changes in skeletal muscle function often occur following physiological and pathological stress, and these lead to the progression of diabetes, obesity, chronic kidney disease, and cardiovascular or respiratory diseases. Identifying the mechanisms that influence the processes regulating skeletal muscle function is a key priority. Recently, studies have demonstrated that microRNAs (miRNAs) play important roles in regulating biological processes. For instance, exosomes are key tools for communication between cells. Therefore, by determining how select miRNAs are transported to target organs and initiate their effects, these results will help explain muscle and organ crosstalk, improve our understanding and application of current therapeutic approaches and lead to the identification of new therapeutic strategies and targets aimed at maintaining and/or improving skeletal muscle health. PMID:27588172

  4. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

    PubMed Central

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal

    2015-01-01

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues. PMID:26304725

  5. APC is required for muscle stem cell proliferation and skeletal muscle tissue repair.

    PubMed

    Parisi, Alice; Lacour, Floriane; Giordani, Lorenzo; Colnot, Sabine; Maire, Pascal; Le Grand, Fabien

    2015-08-31

    The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues. PMID:26304725

  6. Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism.

    PubMed

    Lee, Kevin Y; Singh, Manvendra K; Ussar, Siegfried; Wetzel, Petra; Hirshman, Michael F; Goodyear, Laurie J; Kispert, Andreas; Kahn, C Ronald

    2015-01-01

    Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism. PMID:26299309

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

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  9. Robust internal elastic lamina fenestration in skeletal muscle arteries.

    PubMed

    Kirby, Brett S; Bruhl, Allison; Sullivan, Michelle N; Francis, Michael; Dinenno, Frank A; Earley, Scott

    2013-01-01

    Holes within the internal elastic lamina (IEL) of blood vessels are sites of fenestration allowing for passage of diffusible vasoactive substances and interface of endothelial cell membrane projections with underlying vascular smooth muscle. Endothelial projections are sites of dynamic Ca(2+) events leading to endothelium dependent hyperpolarization (EDH)-mediated relaxations and the activity of these events increase as vessel diameter decreases. We tested the hypothesis that IEL fenestration is greater in distal vs. proximal arteries in skeletal muscle, and is unlike other vascular beds (mesentery). We also determined ion channel protein composition within the endothelium of intramuscular and non-intramuscular skeletal muscle arteries. Popliteal arteries, subsequent gastrocnemius feed arteries, and first and second order intramuscular arterioles from rat hindlimb were isolated, cut longitudinally, fixed, and imaged using confocal microscopy. Quantitative analysis revealed a significantly larger total fenestration area in second and first order arterioles vs. feed and popliteal arteries (58% and 16% vs. 5% and 3%; N = 10 images/artery), due to a noticeably greater average size of holes (9.5 and 3.9 µm(2) vs 1.5 and 1.9 µm(2)). Next, we investigated via immunolabeling procedures whether proteins involved in EDH often embedded in endothelial cell projections were disparate between arterial segments. Specific proteins involved in EDH, such as inositol trisphosphate receptors, small and intermediate conductance Ca(2+)-activated K(+) channels, and the canonical (C) transient receptor potential (TRP) channel TRPC3 were present in both popliteal and first order intramuscular arterioles. However due to larger IEL fenestration in first order arterioles, a larger spanning area of EDH proteins is observed proximal to the smooth muscle cell plasma membrane. These observations highlight the robust area of fenestration within intramuscular arterioles and indicate that the

  10. D-Galactose Induces a Mitochondrial Complex I Deficiency in Mouse Skeletal Muscle: Potential Benefits of Nutrient Combination in Ameliorating Muscle Impairment

    PubMed Central

    Chang, Liao; Liu, Xin; Liu, Jing; Li, Hua; Yang, Yanshen; Liu, Jia; Guo, Zihao; Xiao, Ke; Zhang, Chen; Liu, Jiankang

    2014-01-01

    Abstract Accumulating research has shown that chronic D-galactose (D-gal) exposure induces symptoms similar to natural aging in animals. Therefore, rodents chronically exposed to D-gal are increasingly used as a model for aging and delay-of-aging pharmacological research. Mitochondrial dysfunction is thought to play a vital role in aging and age-related diseases; however, whether mitochondrial dysfunction plays a significant role in mice exposed to D-gal remains unknown. In the present study, we investigated cognitive dysfunction, locomotor activity, and mitochondrial dysfunction involved in D-gal exposure in mice. We found that D-gal exposure (125 mg/kg/day, 8 weeks) resulted in a serious impairment in grip strength in mice, whereas spatial memory and locomotor coordination remained intact. Interestingly, muscular mitochondrial complex I deficiency occurred in the skeletal muscle of mice exposed to D-gal. Mitochondrial ultrastructure abnormality was implicated as a contributing factor in D-gal-induced muscular impairment. Moreover, three combinations (A, B, and C) of nutrients applied in this study effectively reversed D-gal-induced muscular impairment. Nutrient formulas B and C were especially effective in reversing complex I dysfunction in both skeletal muscle and heart muscle. These findings suggest the following: (1) chronic exposure to D-gal first results in specific muscular impairment in mice, rather than causing general, premature aging; (2) poor skeletal muscle strength induced by D-gal might be due to the mitochondrial dysfunction caused by complex I deficiency; and (3) the nutrient complexes applied in the study attenuated the skeletal muscle impairment, most likely by improving mitochondrial function. PMID:24476218

  11. Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

    PubMed

    Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2016-10-01

    Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults. PMID:26447161

  12. Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

    PubMed

    Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2016-10-01

    Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults.

  13. On the mechanism by which dietary nitrate improves human skeletal muscle function

    PubMed Central

    Affourtit, Charles; Bailey, Stephen J.; Jones, Andrew M.; Smallwood, Miranda J.; Winyard, Paul G.

    2015-01-01

    Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favorably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome—both aging-related medical disorders—has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects. PMID:26283970

  14. On the mechanism by which dietary nitrate improves human skeletal muscle function.

    PubMed

    Affourtit, Charles; Bailey, Stephen J; Jones, Andrew M; Smallwood, Miranda J; Winyard, Paul G

    2015-01-01

    Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favorably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome-both aging-related medical disorders-has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects. PMID:26283970

  15. Inefficient functional sympatholysis is an overlooked cause of malperfusion in contracting skeletal muscle

    PubMed Central

    Saltin, Bengt; Mortensen, Stefan P

    2012-01-01

    Contracting skeletal muscle can overcome sympathetic vasoconstrictor activity (functional sympatholysis), which allows for a blood supply that matches the metabolic demand. This ability is thought to be mediated by locally released substances that modulate the effect of noradrenaline (NA) on the α-receptor. Tyramine induces local NA release and can be used in humans to investigate the underlying mechanisms and physiological importance of functional sympatholysis in the muscles of healthy and diseased individuals as well as the impact of the active muscles’ training status. In sedentary elderly men, functional sympatholysis and muscle blood flow are impaired compared to young men, but regular physical activity can prevent these age related impairments. In young subjects, two weeks of leg immobilization causes a reduced ability for functional sympatholysis, whereas the trained leg maintained this function. Patients with essential hypertension have impaired functional sympatholysis in the forearm, and reduced exercise hyperaemia in the leg, but this can be normalized by aerobic exercise training. The effect of physical activity on the local mechanisms that modulate sympathetic vasoconstriction is clear, but it remains uncertain which locally released substance(s) block the effect of NA and how this is accomplished. NO and ATP have been proposed as important inhibitors of NA mediated vasoconstriction and presently an inhibitory effect of ATP on NA signalling via P2 receptors appears most likely. PMID:22988143

  16. Feasibility of using magnetic resonance elastography to study the effect of aging on shear modulus of skeletal muscle.

    PubMed

    Domire, Zachary J; McCullough, Matthew B; Chen, Qingshan; An, Kai-Nan

    2009-02-01

    A common complication associated with aging is the stiffening of skeletal muscles. The purpose of this study was to determine the ability of magnetic resonance elastography (MRE) to study this phenomenon in vivo. Twenty female subjects were included in the study with an age range of 50 to 70 years. Shear modulus was calculated for the tibialis anterior of each subject. There was not a significant relationship between age and shear modulus. However, three subjects had abnormally high values and were among the oldest subjects tested. There was a significant relationship between age and tissue stiffness homogeneity. More research is needed to determine whether the changes seen here are reflective of increased tissue cross-linking or related to reduced muscle quality. However, MRE shows promise as a tool to study aging-related muscle stiffness changes or to evaluate treatments to counteract these changes.

  17. Skeletal muscle insulin resistance is fundamental to the cardiometabolic syndrome.

    PubMed

    Nistala, Ravi; Stump, Craig S

    2006-01-01

    The cardiometabolic syndrome is associated with insulin resistance and a dysregulation of glucose and lipid metabolism that occurs in multiple tissues. Of these, skeletal muscle is the most abundant insulin-sensitive tissue, handling > 40% of the postprandial glucose uptake, while consuming 20% of the body's energy. The inability to efficiently take up and store fuel, and to transition from fat to glucose as the primary source of fuel during times of plenty (increased insulin), has been termed metabolic inflexibility. This resistance to insulin is thought to be a major contributor to the whole-body metabolic dysregulation that leads to increased cardiovascular risk. Recent investigation has identified specific defects in postinsulin receptor signaling in skeletal muscle from resistant humans and animals. Potential mechanisms contributing to this reduced insulin signaling and action include decreases in mitochondrial oxidative capacity, increased intramuscular lipid accumulation, increased reactive oxygen species generation, and up-regulated inflammatory pathways. Future research is focused on understanding these and other potential mechanisms to identify therapeutic targets for reducing cardiometabolic syndrome risk. PMID:17675899

  18. Skeletal muscle grids for assessing current distributions from defibrillation shocks.

    PubMed

    Schmidt, J; Gatlin, B; Eason, J; Koomullil, G; Pilkington, T

    1992-01-01

    This paper utilizes a structured and an unstructured grid representation of a torso with an anisotropic skeletal muscle to assess current distributions from defibrillation shocks. The results show that a finite-element solution on an unstructured grid of 400,000 elements (60,000 nodes) achieves comparable current distributions with a finite-difference solution on a structured grid that uses approximately the same number of nodes. Moreover, a finite-element solution on a 65,000-element (10,500 nodes) unstructured grid yielded fractional percent current results within 5% of the finer grids. The structured and unstructured grid models are used to investigate recent interpretations of experimental data that concluded that more than 80% of the total defibrillation current is shunted by the anisotropic skeletal muscle thoracic cage. It is concluded that these interpretations, which were based on a one-dimensional resistive network representation of the three-dimensional defibrillation situation, overestimate by 25% the current shunted by the anisotropic thoracic cage. PMID:1424684

  19. Effects of ethanol on rat heart and skeletal muscles

    SciTech Connect

    Pagala, M.; Ravindran, K.; Namba, T.; Grob, D. State Univ. of New York, Brooklyn )

    1991-03-11

    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.

  20. Genomic organization of the human skeletal muscle sodium channel gene

    SciTech Connect

    George, A.L. Jr.; Iyer, G.S.; Kleinfield, R.; Kallen, R.G.; Barchi, R.L. )

    1993-03-01

    Voltage-dependent sodium channels are essential for normal membrane excitability and contractility in adult skeletal muscle. The gene encoding the principal sodium channel [alpha]-subunit isoform in human skeletal muscle (SCN4A) has recently been shown to harbor point mutations in certain hereditary forms of periodic paralysis. The authors have carried out an analysis of the detailed structure of this gene including delination of intron-exon boundaries by genomic DNA cloning and sequence analysis. The complete coding region of SCN4A is found in 32.5 kb of genomic DNA and consists of 24 exons (54 to >2.2 kb) and 23 introns (97 bp-4.85 kb). The exon organization of the gene shows no relationship to the predicted functional domains of the channel protein and splice junctions interrupt many of the transmembrane segments. The genomic organization of sodium channels may have been partially conserved during evolution as evidenced by the observation that 10 of the 24 splice junctions in SCN4A are positioned in homologous locations in a putative sodium channel gene in Drosophila (para). The information presented here should be extremely useful both for further identifying sodium channel mutations and for gaining a better understanding of sodium channel evolution. 39 refs., 5 figs., 2 tabs.

  1. Lysophosphatidic acid mediates pleiotropic responses in skeletal muscle cells

    SciTech Connect

    Jean-Baptiste, Gael; Yang Zhao; Khoury, Chamel; Greenwood, Michael T.; E-mail: michael.greenwood@mcgill.ca

    2005-10-07

    Lysophosphatidic acid (LPA) is a potent modulator of growth, cell survival, and apoptosis. Although all four LPA receptors are expressed in skeletal muscle, very little is known regarding the role they play in this tissue. We used RT-PCR to demonstrate that cultured skeletal muscle C2C12 cells endogenously express multiple LPA receptor subtypes. The demonstration that LPA mediates the activation of ERK1/2 MAP kinase and Akt/PKB in C2C12 cells is consistent with the widely observed mitogenic properties of LPA. In spite of these observations, LPA did not induce proliferation in C2C12 cells. Paradoxically, we found that prolonged treatment of C2C12 cells with LPA led to caspase 3 and PARP cleavage as well as the activation of stress-associated MAP kinases JNK and p38. In spite of these typically pro-apoptotic responses, LPA did not induce cell death. Blocking ERK1/2 and Akt/PKB activation with specific pharmacological inhibitors, nevertheless, stimulated LPA-mediated apoptosis. Taken together, these results suggest that both mitogenic and apoptotic responses serve to counterbalance the effects of LPA in cultured C2C12 cells.

  2. Therapeutic strategies for preventing skeletal muscle fibrosis after injury

    PubMed Central

    Garg, Koyal; Corona, Benjamin T.; Walters, Thomas J.

    2015-01-01

    Skeletal muscle repair after injury includes a complex and well-coordinated regenerative response. However, fibrosis often manifests, leading to aberrant regeneration and incomplete functional recovery. Research efforts have focused on the use of anti-fibrotic agents aimed at reducing the fibrotic response and improving functional recovery. While there are a number of mediators involved in the development of post-injury fibrosis, TGF-β1 is the primary pro-fibrogenic growth factor and several agents that inactivate TGF-β1 signaling cascade have emerged as promising anti-fibrotic therapies. A number of these agents are FDA approved for other conditions, clearing the way for rapid translation into clinical treatment. In this article, we provide an overview of muscle's host response to injury with special emphasis on the cellular and non-cellular mediators involved in the development of fibrosis. This article also reviews the findings of several pre-clinical studies that have utilized anti-fibrotic agents to improve muscle healing following most common forms of muscle injuries. Although some studies have shown positive results with anti-fibrotic treatment, others have indicated adverse outcomes. Some concerns and questions regarding the clinical potential of these anti-fibrotic agents have also been presented. PMID:25954202

  3. The calcineurin-NFAT pathway controls activity-dependent circadian gene expression in slow skeletal muscle

    PubMed Central

    Dyar, Kenneth A.; Ciciliot, Stefano; Tagliazucchi, Guidantonio Malagoli; Pallafacchina, Giorgia; Tothova, Jana; Argentini, Carla; Agatea, Lisa; Abraham, Reimar; Ahdesmäki, Miika; Forcato, Mattia; Bicciato, Silvio; Schiaffino, Stefano; Blaauw, Bert

    2015-01-01

    Objective Physical activity and circadian rhythms are well-established determinants of human health and disease, but the relationship between muscle activity and the circadian regulation of muscle genes is a relatively new area of research. It is unknown whether muscle activity and muscle clock rhythms are coupled together, nor whether activity rhythms can drive circadian gene expression in skeletal muscle. Methods We compared the circadian transcriptomes of two mouse hindlimb muscles with vastly different circadian activity patterns, the continuously active slow soleus and the sporadically active fast tibialis anterior, in the presence or absence of a functional skeletal muscle clock (skeletal muscle-specific Bmal1 KO). In addition, we compared the effect of denervation on muscle circadian gene expression. Results We found that different skeletal muscles exhibit major differences in their circadian transcriptomes, yet core clock gene oscillations were essentially identical in fast and slow muscles. Furthermore, denervation caused relatively minor changes in circadian expression of most core clock genes, yet major differences in expression level, phase and amplitude of many muscle circadian genes. Conclusions We report that activity controls the oscillation of around 15% of skeletal muscle circadian genes independently of the core muscle clock, and we have identified the Ca2+-dependent calcineurin-NFAT pathway as an important mediator of activity-dependent circadian gene expression, showing that circadian locomotor activity rhythms drive circadian rhythms of NFAT nuclear translocation and target gene expression. PMID:26629406

  4. Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin content in rat skeletal muscle arterioles.

    PubMed

    Delp, Michael D; Behnke, Bradley J; Spier, Scott A; Wu, Guoyao; Muller-Delp, Judy M

    2008-02-15

    Ageing reduces endothelium-dependent vasodilatation through an endothelial nitric oxide synthase (NOS) signalling pathway. The purpose of this study was to determine whether arginase activity diminishes endothelium-dependent vasodilatation in skeletal muscle arterioles from old rats, and whether NOS substrate (L-arginine) and cofactor (tetrahydrobiopterin; BH(4)) concentrations are reduced. First-order arterioles were isolated from the soleus muscle of young (6 months old) and old (24 months old) male Fischer 344 rats. In vitro changes in luminal diameter in response to stepwise increases in flow were determined in the presence of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME, 10(-5) mol l(-1)), the arginase inhibitor N(omega)-hydroxy-nor-L-arginine (NOHA, 5 x 10(-4) mol l(-1)), exogenous L-arginine (3 x 10(-3) mol l(-1)) or the precursor for BH(4) synthesis sepiapterin (1 micromol l(-1)). Arteriolar L-arginine and BH(4) content were determined via HPLC. Ageing decreased flow-mediated vasodilatation by 52%, and this difference was abolished with NOS inhibition. Neither inhibition of arginase activity nor addition of exogenous L-arginine had any effect on flow-mediated vasodilatation; arteriolar l-arginine content was also not different between age groups. BH(4) content was lower in arterioles from old rats (94 +/- 8 fmol (mg tissue)(-1)) relative to controls (234 +/- 21 fmol (mg tissue)(-1)), and sepiapterin elevated flow-mediated vasodilatation in arterioles from old rats. These results demonstrate that the impairment of endothelium-dependent vasodilatation induced by old age is due to an altered nitric oxide signalling mechanism in skeletal muscle arterioles, but is not the result of increased arginase activity and limited L-arginine substrate. Rather, the age-related deficit in flow-mediated vasodilatation appears to be the result, in part, of limited BH(4) bioavailability.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

    Stanford, Kristin I.; Goodyear, Laurie J.

    2014-01-01

    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…

  7. Long-term skeletal muscle mitochondrial dysfunction is associated with hypermetabolism in severely burned children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The long-term impact of burn trauma on skeletal muscle bioenergetics remains unknown. Here, we determined respiratory capacity and function of skeletal muscle mitochondria in healthy individuals and in burn victims for up to two years post-injury. Biopsies were collected from the m. vastus lateralis...

  8. Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

    PubMed

    Sharples, Adam P; Stewart, Claire E; Seaborne, Robert A

    2016-08-01

    Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging.

  9. Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies.

    PubMed

    Malm, C; Nyberg, P; Engstrom, M; Sjodin, B; Lenkei, R; Ekblom, B; Lundberg, I

    2000-11-15

    1. A role of the immune system in muscular adaptation to physical exercise has been suggested but data from controlled human studies are scarce. The present study investigated immunological events in human blood and skeletal muscle by immunohistochemistry and flow cytometry after eccentric cycling exercise and multiple biopsies. 2. Immunohistochemical detection of neutrophil- (CD11b, CD15), macrophage- (CD163), satellite cell- (CD56) and IL-1beta-specific antigens increased similarly in human skeletal muscle after eccentric cycling exercise together with multiple muscle biopsies, or multiple biopsies only. 3. Changes in immunological variables in blood and muscle were related, and monocytes and natural killer (NK) cells appeared to have governing functions over immunological events in human skeletal muscle. 4. Delayed onset muscle soreness, serum creatine kinase activity and C-reactive protein concentration were not related to leukocyte infiltration in human skeletal muscle. 5. Eccentric cycling and/or muscle biopsies did not result in T cell infiltration in human skeletal muscle. Modes of stress other than eccentric cycling should therefore be evaluated as a myositis model in human. 6. Based on results from the present study, and in the light of previously published data, it appears plausible that muscular adaptation to physical exercise occurs without preceding muscle inflammation. Nevertheless, leukocytes seem important for repair, regeneration and adaptation of human skeletal muscle.

  10. Specificity of a protein phosphatase inhibitor from rabbit skeletal muscle.

    PubMed Central

    Cohen, P; Nimmo, G A; Antoniw, J F

    1977-01-01

    A hear-stable protein, which is a specific inhibitor of protein phosphatase-III, was purified 700-fold from skeletal muscle by a procedure that involved heat-treatment at 95 degrees C, chromatography on DEAE-cellulose and gel filtration on Sephadex G-100. The final step completely resolved the protein phosphatase inhibitor from the protein inhibitor of cyclic AMP-dependent protein kinase. The phosphorylase phosphatase, beta-phosphorylase kinase phosphatase, glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities of protein phosphatase-III [Antoniw, J. F., Nimmo, H. G., Yeaman, S. J. & Cohen, P.(1977) Biochem.J. 162, 423-433] were inhibited in a very similar manner by the protein phosphatase inhibitor and at least 95% inhibition was observed at high concentrations of inhibitor. The two forms of protein phosphatase-III, termed IIIA and IIIB, were equally susceptible to the protein phosphatase inhibitor. The protein phosphatase inhibitor was at least 200 times less effective in inhibiting the activity of protein phosphatase-I and protein phosphatase-II. The high degree of specificity of the inhibitor for protein phosphatase-III was used to show that 90% of the phosphorylase phosphatase and glycogen synthase phosphatase activities measured in muscle extracts are catalysed by protein phosphatase-III. Protein phosphatase-III was tightly associated with the protein-glycogen complex that can be isolated from skeletal muscle, whereas the protein phosphatase inhibitor and protein phosphatase-II were not. The results provide further evidence that the enzyme that catalyses the dephosphorylation of the alpha-subunit of phosphorylase kinase (protein phosphatase-II) and the enzyme that catalyses the dephosphorylation of the beta-subunit of phosphorylase kinase (protein phosphatase-III) are distinct. The results suggest that the protein phosphatase inhibitor may be a useful probe for differentiating different classes of protein phosphatases in mammalian

  11. Frequency analysis of ultrasonic echo intensities of the skeletal muscle in elderly and young individuals

    PubMed Central

    Nishihara, Ken; Kawai, Hisashi; Hayashi, Hiroyuki; Naruse, Hideo; Kimura, Akihiko; Gomi, Toshiaki; Hoshi, Fumihiko

    2014-01-01

    Background The skeletal muscle echo intensity (EI) during ultrasound imaging has been investigated to evaluate the muscle quality. However, EI fluctuates according to the scanning conditions. Methods The motor functions and ultrasound images of 19 elderly (73±3.2 years) and 19 young (22±1.5 years) individuals were investigated and an EI frequency component was assessed for more reliable evaluations. Healthy elderly and young subjects participated in this study. The motor functions were assessed during walking and according to the knee extension muscle strength. The muscle thicknesses of rectus femoris (RF), vastus intermedius (VI), and quadriceps femoris (QF) were investigated. EIs were calculated and the mean frequencies of the regions of interest (MFROIs) for RF and VI were analyzed. Results EIs and MFROIs were greater in elderly subjects than in young subjects (P<0.01 for RF, and P<0.001 for VI, in EIs; and P<0.01 for RF, and P<0.05 for VI, in MFROIs). In young subjects, EI of RF was greater than that of VI; however, there was no difference between the RF and VI MFROIs in both elderly and young subjects. EIs of VI exhibited a significantly negative correlation with the QF thickness in both elderly and young subjects. RF MFROIs negatively correlated with the QF thickness and positively correlated with EI of VI in elderly subjects alone. Conclusion These findings suggest that MFROIs of elderly individuals would have a larger value than those of young individuals; moreover, MFROIs did not fluctuate greatly with the tissue depth and scanning conditions. MFROIs might be thus useful for further investigations of muscle quality and applications for the early prevention of age-related motor functional decline. PMID:25228800

  12. Human skeletal muscle xenograft as a new preclinical model for muscle disorders

    PubMed Central

    Zhang, Yuanfan; King, Oliver D.; Rahimov, Fedik; Jones, Takako I.; Ward, Christopher W.; Kerr, Jaclyn P.; Liu, Naili; Emerson, Charles P.; Kunkel, Louis M.; Partridge, Terence A.; Wagner, Kathryn R.

    2014-01-01

    Development of novel therapeutics requires good animal models of disease. Disorders for which good animal models do not exist have very few drugs in development or clinical trial. Even where there are accepted, albeit imperfect models, the leap from promising preclinical drug results to positive clinical trials commonly fails, including in disorders of skeletal muscle. The main alternative model for early drug development, tissue culture, lacks both the architecture and, usually, the metabolic fidelity of the normal tissue in vivo. Herein, we demonstrate the feasibility and validity of human to mouse xenografts as a preclinical model of myopathy. Human skeletal muscle biopsies transplanted into the anterior tibial compartment of the hindlimbs of NOD-Rag1null IL2rγnull immunodeficient host mice regenerate new vascularized and innervated myofibers from human myogenic precursor cells. The grafts exhibit contractile and calcium release behavior, characteristic of functional muscle tissue. The validity of the human graft as a model of facioscapulohumeral muscular dystrophy is demonstrated in disease biomarker studies, showing that gene expression profiles of xenografts mirror those of the fresh donor biopsies. These findings illustrate the value of a new experimental model of muscle disease, the human muscle xenograft in mice, as a feasible and valid preclinical tool to better investigate the pathogenesis of human genetic myopathies and to more accurately predict their response to novel therapeutics. PMID:24452336

  13. Carbonic anhydrase in the sarcoplasmic reticulum of rabbit skeletal muscle.

    PubMed Central

    Bruns, W; Dermietzel, R; Gros, G

    1986-01-01

    Sarcoplasmic reticulum vesicles and mitochondria were prepared from red and white skeletal muscles of the rabbit. The preparations were characterized in terms of their specific activities of citrate synthase, basal (Mg2+-dependent) and Ca2+-dependent ATPase (the latter two in the presence of NaN3 and ouabain), and their specific carbonic anhydrase activities were determined. Skeletal muscle mitochondria had high specific activities of citrate synthase (700-1200 mu. mg protein-1) and low carbonic anhydrase activities (0.1-0.4 u. ml mg protein-1). The latter are likely to be due to a contamination of the preparations with sarcoplasmic reticulum (s.r.) Preparations of s.r. vesicles showed negligible activities of citrate synthase and the expected differing patterns of basal and Ca2+-dependent ATPase in red and white muscles. Specific carbonic anhydrase activities in s.r. from both muscle types were high (2-4 u. ml mg protein-1). The highest carbonic anhydrase activity, 11 u. ml mg protein-1, was found in s.r. from rabbit m. masseter. The inhibition constant of s.r. carbonic anhydrase towards acetazolamide was 4-6 X 10(-8) M and similar but not identical to that of cytosolic carbonic anhydrase II. It appears possible that the carbonic anhydrase II-like enzyme previously found by us in muscle homogenates (Siffert & Gros, 1982) originates from the s.r. Histochemical studies using the dansylsuphonamide method described previously (Dermietzel, Leibstein, Siffert, Zamboglou & Gros, 1985) showed an intracellular pattern of carbonic anhydrase staining compatible with the presence of the enzyme in s.r.: spots homogeneously distributed across the fibre cross-sections in transversely sectioned fibres and thin, longitudinally oriented, bands in longitudinally sectioned fibres. It is estimated that s.r. carbonic anhydrase accelerates CO2 hydration within the s.r. approximately 1000-fold. Thus, CO2 and HCO3- react fast enough to provide a rapid source and sink for protons leaving