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Sample records for alternatus increases skeletal

  1. Insulin Increases Ceramide Synthesis in Skeletal Muscle

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    M. E. Hansen

    2014-01-01

    Full Text Available 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.

  2. Increased skeletal muscle capillarization enhances insulin sensitivity

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    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole-body...... was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The Prazosin treatment did not affect...

  3. Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle

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    Brandt, Nina; O'Neill, Hayley M; Kleinert, Maximilian

    2015-01-01

    INTRODUCTION: Members of the interleukin-6 (IL-6) family, IL-6 and ciliary neurotrophic factor (CNTF) have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well...

  4. The role of hyperplasia on the increase of skeletal muscle

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    Victor Hugo Maciel Meloni

    2005-06-01

    Full Text Available Skeletal muscle hypertrophy is resulted from the individual increase of the fiber cross-sectional area. This adaptative phenomenon is normally observed in the muscle tissue submitted to a regimen of physical exercises, like strength training. The degree of muscular hypertrophy is directly related to the type of exercise and its intensity. Strength training normally produces a hypertrophy of greater magnitude when compared to other types of physical exercise. However, it is possible that there is another adaptive mechanism contributing for increasing skeletal muscle size. This mechanism is called hyperplasia, and can be defined as an increase in the cells, or fibers, number in the muscle. This brief review aims to verify the role of hyperplasia in the increase of skeletal muscle size. RESUMO A hipertrofia do músculo esquelético é resultado do aumento individual da área transversal da fibra. Este fenômeno adaptativo é comumente observado no tecido muscular submetido à um regime de exercícios físicos, como o treinamento de força. O grau de hipertrofia muscular está diretamente relacionado ao tipo de exercício e sua intensidade. O treinamento de força normalmente produz uma hipertrofia de maior magnitude, quando comparada aos outros tipos de exercício físico. Todavia, é provável que haja outro mecanismo adaptativo contribuindo para a hipertrofia do músculo esquelético. Este mecanismo chama-se hiperplasia, e pode ser traduzida por um aumento no número de células, ou fibras musculares em relação ao número original. Este breve resumo tem por objetivo verificar qual é o papel da hiperplasia na hipertrofia do músculo esquelético.

  5. Sodium nitrate ingestion increases skeletal muscle nitrate content in humans.

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    Nyakayiru, Jean; Kouw, Imre W K; Cermak, Naomi M; Senden, Joan M; van Loon, Luc J C; Verdijk, Lex B

    2017-09-01

    Nitrate ([Formula: see text]) ingestion has been shown to have vasoactive and ergogenic effects that have been attributed to increased nitric oxide (NO) production. Recent observations in rodents suggest that skeletal muscle tissue serves as an endogenous [Formula: see text] "reservoir." The present study determined [Formula: see text] contents in human skeletal muscle tissue in a postabsorptive state and following ingestion of a sodium nitrate bolus (NaNO 3 ). Seventeen male, type 2 diabetes patients (age 72 ± 1 yr; body mass index 26.5 ± 0.5 kg/m 2 ; means ± SE) were randomized to ingest a dose of NaNO 3 (NIT; 9.3 mg [Formula: see text]/kg body wt) or placebo (PLA; 8.8 mg NaCl/kg body wt). Blood and muscle biopsy samples were taken before and up to 7 h following [Formula: see text] or placebo ingestion to assess [Formula: see text] [and plasma nitrite ([Formula: see text])] concentrations. Additionally, basal plasma and muscle [Formula: see text] concentrations were assessed in 10 healthy young (CON-Y; age 21 ± 1 yr) and 10 healthy older (CON-O; age 75 ± 1 yr) control subjects. In all groups, baseline [Formula: see text] concentrations were higher in muscle (NIT, 57 ± 7; PLA, 61 ± 7; CON-Y, 80 ± 10; CON-O, 54 ± 6 µmol/l) than in plasma (NIT, 35 ± 3; PLA, 32 ± 3; CON-Y, 38 ± 3; CON-O, 33 ± 3 µmol/l; P ≤ 0.011). Ingestion of NaNO 3 resulted in a sustained increase in plasma [Formula: see text], plasma [Formula: see text], and muscle [Formula: see text] concentrations (up to 185 ± 25 µmol/l) in the NIT group (time effect P nitrate ingestion is usually limited to the changes observed in plasma nitrate and nitrite concentrations. The present investigation assessed the skeletal muscle nitrate content in humans during the postabsorptive state, as well as following dietary nitrate ingestion. We show that basal nitrate content is higher in skeletal muscle tissue than in plasma and that ingestion of a dietary nitrate bolus strongly increases both plasma

  6. Differential immune responses of Monochamus alternatus against symbiotic and entomopathogenic fungi.

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    Zhang, Wei; Meng, Jie; Ning, Jing; Qin, Peijun; Zhou, Jiao; Zou, Zhen; Wang, Yanhong; Jiang, Hong; Ahmad, Faheem; Zhao, Lilin; Sun, Jianghua

    2017-08-01

    Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has established a symbiotic relationship with a native ectotrophic fungal symbiont, Sporothrix sp. 1, in China. The immune response of M. alternatus to S. sp. 1 in the coexistence of beetles and fungi is, however, unknown. Here, we report that immune responses of M. alternatus pupae to infection caused by ectotrophic symbiotic fungus S. sp. 1 and entomopathogenic fungus Beauveria bassiana differ significantly. The S. sp. 1 did not kill the beetles while B. bassiana killed all upon injection. The transcriptome results showed that the numbers of differentially expressed genes in M. alternatus infected with S. sp. 1 were 2-fold less than those infected with B. bassiana at 48 hours post infection. It was noticed that Toll and IMD pathways played a leading role in the beetle's immune system when infected by symbiotic fungus, but upon infection by entomopathogenic fungus, only the Toll pathway gets triggered actively. Furthermore, the beetles could tolerate the infection of symbiotic fungi by retracing their Toll and IMD pathways at 48 h. This study provided a comprehensive sequence resource of M. alternatus transcriptome for further study of the immune interactions between host and associated fungi.

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

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    Eun-Jeong Lee

    Full Text Available 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.

  8. Effect of Bothrops alternatus snake venom on macrophage phagocytosis and superoxide production: participation of protein kinase C

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    SS Setubal

    2011-01-01

    Full Text Available Envenomations caused by different species of Bothrops snakes result in severe local tissue damage, hemorrhage, pain, myonecrosis, and inflammation with a significant leukocyte accumulation at the bite site. However, the activation state of leukocytes is still unclear. According to clinical cases and experimental work, the local effects observed in envenenomation by Bothrops alternatus are mainly the appearance of edema, hemorrhage, and necrosis. In this study we investigated the ability of Bothrops alternatus crude venom to induce macrophage activation. At 6 to 100 ¼g/mL, BaV is not toxic to thioglycollate-elicited macrophages; at 3 and 6 ¼g/mL, it did not interfere in macrophage adhesion or detachment. Moreover, at concentrations of 1.5, 3, and 6 ¼g/mL the venom induced an increase in phagocytosis via complement receptor one hour after incubation. Pharmacological treatment of thioglycollate-elicited macrophages with staurosporine, a protein kinase (PKC inhibitor, abolished phagocytosis, suggesting that PKC may be involved in the increase of serum-opsonized zymosan phagocytosis induced by BaV. Moreover, BaV also induced the production of anion superoxide (O2_ by thioglycollate-elicited macrophages. This BaV stimulated superoxide production was abolished after treating the cells with staurosporine, indicating that PKC is an important signaling pathway for the production of this radical. Based on these results, we suggest that phagocytosis and reactive oxygen species are involved in the pathogenesis of local tissue damage characteristic of Bothrops spp. envenomations.

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

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

  11. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner

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    Kjøbsted, Rasmus; Treebak, Jonas Thue; Fentz, Joachim

    2015-01-01

    Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased ...

  12. Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism.

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    Gidlund, Eva-Karin; von Walden, Ferdinand; Venojärvi, Mika; Risérus, Ulf; Heinonen, Olli J; Norrbom, Jessica; Sundberg, Carl Johan

    2016-12-01

    Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group. The exercise interventions were performed three times per week for 12 weeks with progressively increased intensity during the intervention period. Biopsies from the vastus lateralis muscle and venous blood samples were taken before and after the intervention. Skeletal muscle and serum protein levels of HN were analyzed as well as skeletal muscle gene expression of the mitochondrially encoded gene MT-RNR2, containing the open reading frame for HN To elucidate mitochondrial training adaptation, mtDNA, and nuclear DNA as well as Citrate synthase were measured. Skeletal muscle HN protein levels increased by 35% after 12 weeks of resistance training. No change in humanin protein levels was seen in serum in any of the intervention groups. There was a significant correlation between humanin levels in serum and the improvements in the 2 h glucose loading test in the resistance training group. The increase in HN protein levels in skeletal muscle after regular resistance training in prediabetic males may suggest a role for HN in the regulation of glucose metabolism. Given the preventative effect of exercise on diabetes type 2, the role of HN as a mitochondrially derived peptide and an exercise-responsive mitokine warrants further investigation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Methotrexate increases skeletal muscle GLUT4 expression and improves metabolic control in experimental diabetes

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    Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue conc...

  14. Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae) Larvae

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    Shao, Ensi; Rebeca, Carballar-Lejarazú; Guo, Yajie; Xiong, Yueting; Mou, Yani; Xu, Runxue; Hu, Xia; Liang, Guanghong; Zou, Shuangquan; Guan, Xiong; Zhang, Feiping

    2016-01-01

    Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO) terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs) database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG). In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies. PMID:26815657

  15. Field Evaluation of Commercial Attractants and Trap Placement for Monitoring Pine Sawyer Beetle, Monochamus alternatus (Coleoptera: Cerambycidae) in Guangdong, China.

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    Ma, Tao; Shi, Xianhui; Shen, Jing; Wang, Cai; Zhang, Shengnan; Lu, Xuelei; Sun, Zhaohui; Chen, Xiaoyang; Wang, Changlu; Xie, Weilong; Wen, Xiujun

    2018-02-09

    The pine sawyer beetle, Monochamus alternatus Hope (Coleoptera: Cerambycidae) is a serious insect pest of pine trees by vectoring the pine wood nematode, Bursaphelenchus xylophilus (Steiner and Buhrer) Nickle (Nematoda: Aphelenchoididae). Field studies were carried out during 2013-2015 in Guangdong (China) to evaluate the effectiveness of commercial attractants, effect of trap placement for monitoring M. alternatus, and temporal patterns of trap catch. Four commercial attractants, three trap placements (0, 1.5, and 3 m above ground) and different trapping distances (50, 200, 400, 600, and 900 m) from forest edge were evaluated for monitoring M. alternatus. Traps baited with a mixture of monochamol and plant volatiles captured significantly more beetles than traps baited with monochamol alone or plant volatiles alone. Traps set up at 1.5 m above the ground captured significantly more M. alternatus than those at 0 m and 3 m height. Based on 2,687 beetles trapped from two locations in 2013 and 2014, the female:male ratio was 2.9-4.1:1. The beetles' natural dispersal distance was approximately 100 m based on traps set at different distances from edge of the forest. Continuous monitoring over 38-wk period indicates the peak of adult M. alternatus emergence was between May and June within a year. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

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    Steven D Kunkel

    Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  17. Skeletal dysplasias with increased bone density: evolution of molecular pathogenesis in the last century.

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    Aggarwal, Shagun

    2013-10-01

    Skeletal dysplasias (SKD) with increased bone density form a discrete group of SKDs as per the Nosology and Classification of Genetic Skeletal Disorders, 2010 Revision. This group, with the prototype disorder being osteopetrosis, has evolved over the last century, with new entities being described & their molecular basis being increasingly elucidated. Osteopetrosis, which remained an enigma in the early part of its description, is now known to be genetically heterogenous. Other disorders in this group, which were initially described as variant forms of osteopetrosis, are now recognised to be distinct conditions. However, all these SKDs with increased bone density share their molecular pathogenesis as majority arise due to mutations in the genes governing osteoclast formation and function. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes.

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    Kwak, Hyo-Bum; Thalacker-Mercer, Anna; Anderson, Ethan J; Lin, Chien-Te; Kane, Daniel A; Lee, Nam-Sihk; Cortright, Ronald N; Bamman, Marcas M; Neufer, P Darrell

    2012-01-01

    Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 μM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoylcarnitine+malate (PCM, complex I and II substrates) and glutamate+malate (GM, complex I substrates), was 32-37% lower (Prespiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin-treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (proapoptotic, +53%) and Bcl-2 (antiapoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial-mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Blockade of Metallothioneins 1 and 2 Increases Skeletal Muscle Mass and Strength

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    Summermatter, Serge; Bouzan, Anais; Pierrel, Eliane; Melly, Stefan; Stauffer, Daniela; Gutzwiller, Sabine; Nolin, Erin; Dornelas, Christina; Fryer, Christy; Leighton-Davies, Juliet; Glass, David J.

    2016-01-01

    ABSTRACT Metallothioneins are proteins that are involved in intracellular zinc storage and transport. Their expression levels have been reported to be elevated in several settings of skeletal muscle atrophy. We therefore investigated the effect of metallothionein blockade on skeletal muscle anabolism in vitro and in vivo. We found that concomitant abrogation of metallothioneins 1 and 2 results in activation of the Akt pathway and increases in myotube size, in type IIb fiber hypertrophy, and ultimately in muscle strength. Importantly, the beneficial effects of metallothionein blockade on muscle mass and function was also observed in the setting of glucocorticoid addition, which is a strong atrophy-inducing stimulus. Given the blockade of atrophy and the preservation of strength in atrophy-inducing settings, these results suggest that blockade of metallothioneins 1 and 2 constitutes a promising approach for the treatment of conditions which result in muscle atrophy. PMID:27956698

  20. Hemograma de cães envenenados experimentalmente com Bothrops alternatus após diferentes tratamentos.

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    D. O. Jacome

    2005-03-01

    inoculação do veneno. O hemograma de cães envenenados por Bothrops alternatus e tratados com soro antibotrópico, flunixina meglumina e extrato aquoso de Curcuma longa é caracterizado por anemia e leucocitose por neutrofilia. Palavras-chave: Hemograma, Bothrops, cão SUMMARY: The aim of this study was to evaluate hemograms of dogs experimentally envenomed with Bothrops alternatus following different therapeutic approaches (specific anti-venom serum, flunixin meglumine and aqueous extract of Curcuma longa. Twelve Mongrel adult dogs were IM inoculated with 0.3 mg/Kg of venom and treated two hours after venom inoculation. The dogs were divided into three groups (I, II and III of four animals each. Group I was treated with specific anti-venom serum diluted in 0.9% saline which can neutralize 0.3mg/Kg of venom. Group II received flunixin meglumine (1,1mg/kg, IM once a day for five days. Group III was treated with aqueous extract of Curcuma longa (10% on the skin at the site of venom inoculation, three times a day, for five days. The results showed a significant decrease (p<0,05 in the mean values of erythrocytes, hemoglobin concentration and packed cell volumes in all groups 168 hours after venom inoculation. The leukograms revelead leukocytosis with neutrophilia (p<0,05 24 hours following venom inoculation. The leukograms revelead leukocytosis with neutrophilia (p<0,05 24 hours following venom inoculation. The mean values of band neutrophils were within the normal ranges, but were increased 30 hours after inoculations in group II, and 24-168 hours after inoculation in group III. The leukograms revelead leukocytosis with neutrophilia (p<0,05 24 hours following venom inoculation. The mean values of band neutrophils were within the normal ranges, but were increased 30 hours after inoculations in group II, and 24-168 hours after inoculation in group III. The numbers of eosinophils dropped significantly (p<0,05 in the three groups between six and 168 hours after

  1. Weight gain reveals dramatic increases in skeletal muscle extracellular matrix remodeling.

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    Tam, Charmaine S; Covington, Jeffrey D; Bajpeyi, Sudip; Tchoukalova, Yourka; Burk, David; Johannsen, Darcy L; Zingaretti, Cristina M; Cinti, Saverio; Ravussin, Eric

    2014-05-01

    In animal models of obesity, chronic inflammation and dysregulated extracellular matrix remodeling in adipose tissue leads to insulin resistance. Whether similar pathophysiology occurs in humans is not clear. The aim of this study was to test whether 10% weight gain induced by overfeeding triggers inflammation and extracellular matrix remodeling (gene expression, protein, histology) in skeletal muscle and sc adipose tissue in humans. We also investigated whether such remodeling was associated with an impaired metabolic response (hyperinsulinemic-euglycemic clamp). Twenty-nine free-living males were fed 40% over their baseline energy requirements for 8 weeks. Ten percent body weight gain prompted dramatic up-regulation of a repertoire of extracellular matrix remodeling genes in muscle and to a lesser degree in adipose tissue. The amount of extracellular matrix genes in the muscle were directly associated with the amount of lean tissue deposited during overfeeding. Despite weight gain and impaired insulin sensitivity, there was no change in local adipose tissue or systemic inflammation, but there was a slight increase in skeletal muscle inflammation. We propose that skeletal muscle extracellular matrix remodeling is another feature of the pathogenic milieu associated with energy excess and obesity, which, if disrupted, may contribute to the development of metabolic dysfunction.

  2. Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation

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    Butcher, Joshua T.; Frisbee, Stephanie J.; Olfert, I. Mark; Chantler, Paul D.; Tabone, Lawrence E.; d'Audiffret, Alexandre C.; Shrader, Carl D.; Goodwill, Adam G.; Stapleton, Phoebe A.; Brooks, Steven D.; Brock, Robert W.; Lombard, Julian H.

    2015-01-01

    To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning “healthy” to “high PVD risk” and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk. PMID:26702145

  3. Increased Stiffness in Aged Skeletal Muscle Impairs Muscle Progenitor Cell Proliferative Activity.

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    Grégory Lacraz

    Full Text Available Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs. Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM, which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.We showed that freshly isolated individual myofibers from aged mouse muscles contain fewer MPCs overall than myofibers from adult muscles, with fewer quiescent MPCs and more proliferative and differentiating MPCs. We observed alterations in cultured MPC behavior in aged animals, where the proliferation and differentiation of MPCs were lower and higher, respectively. These alterations were not linked to the intrinsic properties of aged myofibers, as shown by the similar values for the cumulative population-doubling values and fusion indexes. However, atomic force microscopy (AFM indentation experiments revealed a nearly 4-fold increase in the stiffness of the MPC microenvironment. We further showed that the increase in stiffness is associated with alterations to muscle ECM, including the accumulation of collagen, which was correlated with higher hydroxyproline and advanced glycation end-product content. Lastly, we recapitulated the impaired MPC behavior observed in aging using a hydrogel substrate that mimics the stiffness of myofibers.These findings provide novel evidence that the low regenerative potential of aged skeletal muscle is independent of intrinsic MPC properties but is related to the increase in the stiffness of the MPC microenvironment.

  4. Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

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    Nataša Nikolić

    2012-01-01

    Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

  5. Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle

    International Nuclear Information System (INIS)

    Ikeda, Shin-ichi; Kizaki, Takako; Haga, Shukoh; Ohno, Hideki; Takemasa, Tohru

    2008-01-01

    Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1α and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found that the exercise induced a biphasic increase in the expression of respiratory enzymes mRNA. The second phase of the increase was accompanied by an increase in PGC-1α protein, but the other was not. Administration of SB203580 (SB), an inhibitor of p38 MAPK, suppressed the increase in PGC-1α expression and respiratory enzymes mRNA in both phases. These data suggest that p38 MAPK is associated with the exercise-induced expression of PGC-1α and biphasic increase in respiratory enzyme mRNAs in mouse skeletal muscle under physiological conditions

  6. Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running

    Science.gov (United States)

    Fluck, M.; Waxham, M. N.; Hamilton, M. T.; Booth, F. W.

    2000-01-01

    Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca(2+)/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca(2+), we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca(2+)-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca(2+)/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca(2+)-independent and Ca(2+)/CaM-dependent forms of Ca(2+)/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca(2+)-independent form of CaMKII was increased, like the Ca(2+)-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca(2+)-independent SRF kinase was increased, no alteration occurred in Ca(2+)/CaM-dependent SRF kinase activity. Thus any role of Ca(2+)-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.

  7. Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle.

    Science.gov (United States)

    Jeong, Ji-Woong; Shim, Jae-Jung; Choi, Il-Dong; Kim, Sung-Hwan; Ra, Jehyeon; Ku, Hyung Keun; Lee, Dong Eun; Kim, Tae-Youl; Jeung, Woonhee; Lee, Jung-Hee; Lee, Ki Won; Huh, Chul-Sung; Sim, Jae-Hun; Ahn, Young-Tae

    2015-12-01

    Ursolic acid is a lipophilic pentacyclic triterpenoid found in many fruits and herbs and is used in several herbal folk medicines for diabetes. In this study, we evaluated the effects of apple pomace extract (APE; ursolic acid content, 183 mg/g) on skeletal muscle atrophy. To examine APE therapeutic potential in muscle atrophy, we investigated APE effects on the expression of biomarkers associated with muscle atrophy and hypertrophy. We found that APE inhibited atrophy, while inducing hypertrophy in C2C12 myotubes by decreasing the expression of atrophy-related genes and increasing the expression of hypertrophy-associated genes. The in vivo experiments using mice fed a diet with or without APE showed that APE intake increased skeletal muscle mass, as well as grip strength and exercise capacity. In addition, APE significantly improved endurance in the mice, as evidenced by increased exhaustive running time and muscle weight, and reduced the expression of the genes involved in the development of muscle atrophy. APE also decreased the concentration of serum lactate and lactate dehydrogenase, inorganic phosphate, and creatinine, the indicators of accumulated fatigue and exercise-induced stress. These results suggest that APE may be useful as an ergogenic functional food or dietary supplement.

  8. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

    2017-01-01

    and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand....

  9. Exercise Training-Induced Adaptations Associated with Increases in Skeletal Muscle Glycogen Content

    Science.gov (United States)

    Manabe, Yasuko; Gollisch, Katja S.C.; Holton, Laura; Kim, Young–Bum; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.

    2012-01-01

    Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism for increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4, or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. Compared to sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase 3 (GSK3). Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1, GSK3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks and may function as a negative feedback to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase and PP1activity. PMID:23206309

  10. Increased expression of fibroblast growth factors in a rabbit skeletal muscle model of exercise conditioning.

    Science.gov (United States)

    Morrow, N G; Kraus, W E; Moore, J W; Williams, R S; Swain, J L

    1990-06-01

    Increased tonic contractile activity from exercise or electrical stimulation induces a variety of changes in skeletal muscle, including vascular growth, myoblast proliferation, and fast to slow fiber type conversion. Little is known about the cellular control of such changes, but pleiotropic biochemical modulators such as fibroblast growth factors (FGFs) may be involved in this response and thus may be regulated in response to such stimuli. We examined the regulation of FGF expression in an in vivo model of exercise conditioning previously shown to exhibit vascular growth and fast to slow fiber conversion. FGFs were extracted by heparin-affinity chromatography from extensor digitorum longus muscles of adult rabbits subjected to chronic motor nerve stimulation at 10 Hz. Growth factor activity (expressed in growth factor units [GFUs]) of muscle stimulated for 3 and 21 d was assayed by [3H]thymidine incorporation in 3T3 fibroblasts and compared with that present in the contralateral unstimulated muscle. A small increase in heparin-binding mitogenic activity was observed as early as 3 d of stimulation, and by 21 d mitogenic activity increased significantly when normalized to either wet weight (stimulated, 287 +/- 61 GFU/g; unstimulated, 145 +/- 39 GFU/g) or to protein (stimulated, 5.3 +/- 1.1 GFU/mg; unstimulated, 2.2 +/- 0.6 GFU/mg) (+/- SE, P less than 0.05). Western analysis demonstrated increased amounts of peptides with immunological identity to acidic and basic FGFs in stimulated muscle. The increase in FGF content observed in this study is synchronous with neovascularization, myoblast proliferation, and fast to slow fiber type conversion previously shown in this model. These results demonstrate that increased expression of FGFs is associated with motor nerve stimulation and increased tonic contractile activity of skeletal muscle, and suggests that these proteins may play a regulatory role in the cellular changes that occur during exercise conditioning.

  11. Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

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    Nicolas O. Jørgensen

    2018-04-01

    Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

  12. Aspectos clínico-patológicos e laboratoriais do envenenamento experimental por Bothrops alternatus em bovinos Clinic and pathological and laboratory aspects of experimental poisoning by Bothrops alternatus venom in cattle

    Directory of Open Access Journals (Sweden)

    Saulo A. Caldas

    2008-06-01

    , acompanhada de hemorragia, no entorno do local da inoculação nos animais que receberam o veneno por via intramuscular; essa lesão era discreta nos músculos próximos ao local de inoculação subcutânea. Nos bovinos deste estudo, o aumento de volume observado no local de inoculação e adjacências era constituído por sangue e não edema. Não foram observadas mioglobinúria, nem lesões macro ou microscópicas significativas nos rins. Este estudo indica que exemplares de B. alternatus, caso inoculem todo seu veneno, poderiam levar bovinos adultos à morte. Por outro lado, pelo fato de ofídios serem capazes de regular a quantidade de veneno inoculada e, possivelmente, não considerarem bovinos como presa potencial, é provável que o número de acidentes nessa espécie seja pequeno, o que está de acordo com o observado na maioria dos centros diagnóstico anátomo-patológico no país.The aim of this study was to determine the clinical-pathological alterations and laboratory findings in cattle inoculated with Bothrops alternatus venom, with the intention of providing information for the establishment of diagnosis and differential diagnosis procedures, as well as to elucidate some obscurities observed in the pertinent literature. The lyophilized venom was diluted in 1 ml of physiologic solution. It was administered to 5 bovines by the subcutaneous route at doses of 0.0625, 0.125 and 0.25mg/kg body weight, and to 2 bovines by the intramuscular route at doses of 0.25 e 0.45mg/kg. Six bovines died and the only animal that survived, who had subcutaneously received the venom at a dose of 0.0625mg/kg, recovered. The first clinical signs were observed from 25min to 5h30min after the inoculation. The clinical evolution time varied from 7 hours 18 minutes to 92 hours. Regardless of the dose, the clinical picture was characterized by swelling (hemorrhage/hematoma at the site of inoculation, increase in bleeding time and capillary refill time, paleness of mucous membranes and

  13. Increased cellular proliferation in rat skeletal muscle and tendon in response to exercise

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Bayer, Monika L; Mackey, Abigail

    2010-01-01

    -derived standardized uptake values were calculated for Achilles tendons and calf muscles and compared to gene expression and immunohistochemical evaluations of Ki67. RESULTS: Treadmill running induced increased uptake of FLT uptake in calf muscles (30%; p ...-derived results were supported by a correlation in calf muscle to Ki67 (protein and mRNA level), while this coherence was not found in tendon. CONCLUSION: FLT-PET seems to be a promising tool for imaging of exercise-induced cellular proliferation in musculo-tendinous tissue.......PURPOSE: The purpose of this study is to investigate exercise-induced cellular proliferation in rat skeletal muscle/tendon with the use of 3'-[F-18]fluoro-3'deoxythymidine (FLT) and to quantitatively study concomitant changes in the proliferation-associated factor, Ki67. PROCEDURES: Wistar rats (n...

  14. Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Larsen, S; Stride, N; Hey-Mogensen, Martin

    2011-01-01

    AIMS/HYPOTHESIS: Mitochondrial respiration has been linked to insulin resistance. We studied mitochondrial respiratory capacity and substrate sensitivity in patients with type 2 diabetes (patients), and obese and lean control participants. METHODS: Mitochondrial respiration was measured.......4). Substrate sensitivity for octanoyl-carnitine did not differ between groups. CONCLUSIONS/INTERPRETATION: Increased mitochondrial substrate sensitivity is seen in skeletal muscle from type 2 diabetic patients and is confined to non-lipid substrates. Respiratory capacity per mitochondrion is not decreased....... MHC I content was lowest in patients (37 ± 11% [mean ± SE] vs 53 ± 6% and 56 ± 4%) vs obese controls and lean controls, respectively. VO2 was highest in lean controls (40 ± 3 ml min(-1) kg(-1) [mean ± SE]) compared with patients (25 ± 2) and obese controls (27 ± 2). Mitochondrial content (citrate...

  15. T2 relaxation times are increased in Skeletal muscle of DMD but not BMD patients.

    Science.gov (United States)

    Wokke, Beatrijs H; Van Den Bergen, Janneke C; Hooijmans, Melissa T; Verschuuren, Jan J; Niks, Erik H; Kan, Hermien E

    2016-01-01

    Exon-skipping drugs in Duchenne muscular dystrophy (DMD) aim to restore truncated dystrophin expression, which is present in the milder Becker muscular dystrophy (BMD). MRI skeletal muscle T2 relaxation times as a representation of edema/inflammation could be quantitative outcome parameters for such trials. We studied T2 relaxation times, adjusted for muscle fat fraction using Dixon MRI, in lower leg muscles of DMD and BMD patients and healthy controls. T2 relaxation times correlated significantly with fat fractions in patients only (P relaxation times were significantly increased in 6 muscles of DMD patients (P relaxation times were unchanged. T2 relaxation times could be a useful outcome parameter in exon-skipping trials in DMD but are influenced by fat despite fat suppression. This should be accounted for when using quantitative T2 mapping to investigate edema/inflammation. © 2015 Wiley Periodicals, Inc.

  16. Enteral β-hydroxy-β-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs

    Science.gov (United States)

    Kao, Michelle; Columbus, Daniel A.; Suryawan, Agus; Steinhoff-Wagner, Julia; Hernandez-Garcia, Adriana; Nguyen, Hanh V.; Fiorotto, Marta L.

    2016-01-01

    Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were studied immediately (F) or fed one of five diets for 24 h: low-protein (LP), high-protein (HP), or LP diet supplemented with 4 (HMB4), 40 (HMB40), or 80 (HMB80) μmol HMB·kg body wt−1·day−1. Cell replication was assessed from nuclear incorporation of BrdU in the longissimus dorsi (LD) muscle and jejunum crypt cells. Protein synthesis rates in LD, gastrocnemius, rhomboideus, and diaphragm muscles, lung, and brain were greater in HMB80 and HP and in brain were greater in HMB40 compared with LP and F groups. Formation of the eIF4E·eIF4G complex and S6K1 and 4E-BP1 phosphorylation in LD, gastrocnemius, and rhomboideus muscles were greater in HMB80 and HP than in LP and F groups. Phosphorylation of eIF2α and eEF2 and expression of SNAT2, LAT1, MuRF1, atrogin-1, and LC3-II were unchanged. Numbers of BrdU-positive myonuclei in the LD were greater in HMB80 and HP than in the LP and F groups; there were no differences in jejunum. The results suggest that enteral supplementation with HMB increases skeletal muscle protein anabolism in neonates by stimulation of protein synthesis and satellite cell proliferation. PMID:27143558

  17. Leptin increases skeletal muscle lipoprotein lipase and postprandial lipid metabolism in mice.

    Science.gov (United States)

    Donahoo, William T; Stob, Nicole R; Ammon, Stefen; Levin, Nancy; Eckel, Robert H

    2011-03-01

    The ability of leptin to preserve lean tissue during weight loss may be in part due to differences in nutrient partitioning. Because lipoprotein lipase (LPL) plays a key role in partitioning lipid nutrients, this study was conducted to test the hypothesis that leptin would modify the tissue-specific regulation of LPL and result in increased lipid oxidation and decreased storage. The effects of daily intraperitoneal leptin injections (2 mg/kg body weight) over 2 weeks on LPL activity and postprandial lipid metabolism were tested in both wild-type (WT), leptin-deficient ob/ob obese mice and mice pair fed to the leptin-treated mice. On the experimental day, mice were given food by gavage, blood was drawn periodically, and adipose tissue and skeletal muscle were harvested for measurements of LPL activity at 240 minutes. After 2 weeks of leptin administration, skeletal muscle LPL (SMLPL) activity was increased in leptin-treated compared with pair-fed (P = .012) and WT (P = .002) mice. There was no effect of leptin or pair feeding on postprandial adipose tissue LPL activity. In ob/ob mice, leptin treatment normalized the decrease in postprandial free fatty acid concentration (P = .066). Leptin had no effect on either the area under the triglyceride (TG) excursion or the integrated area under the TG excursion in WT mice. In ob/ob mice, however, the TG excursion was lower in the leptin-treated than the pair-fed mice by area under the TG excursion (P = .012) and was lower than in the WT mice by integrated area under the TG excursion (P = .027). As expected, 2 weeks of leptin treatment decreased body weight in both the WT and ob/ob mice (-2.6% and -10.4%, respectively). Leptin treatment increased SMLPL, an effect that may have contributed to the leptin-induced weight loss. The leptin-induced decreased postprandial TG excursion in ob/ob mice suggests that leptin acts to augment clearance of postprandial TG-rich lipoprotein lipid and that this increase may in part be secondary

  18. Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation.

    Science.gov (United States)

    Wallace, Marita A; Della Gatta, Paul A; Ahmad Mir, Bilal; Kowalski, Greg M; Kloehn, Joachim; McConville, Malcom J; Russell, Aaron P; Lamon, Séverine

    2016-01-01

    Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells. We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism. These findings position STARS as an important regulator of skeletal muscle growth and regeneration.

  19. Dispersal of the Japanese pine sawyer, Monochamus alternatus (Coleoptera: Cerambycidae, in mainland China as inferred from molecular data and associations to indices of human activity.

    Directory of Open Access Journals (Sweden)

    Shao-ji Hu

    Full Text Available The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae, is an important forest pest as well as the principal vector of the pinewood nematode (PWN, Bursaphelenchus xylophilus (Steiner et Buhrer, in mainland China. Despite the economic importance of this insect-disease complex, only a few studies are available on the population genetic structure of M. alternatus and the relationship between its historic dispersal pattern and various human activities. The aim of the present study was to further explore aspects of human activity on the population genetic structure of M. alternatus in mainland China. The molecular data based on the combined mitochondrial cox1 and cox2 gene fragments from 140 individuals representing 14 Chinese populations yielded 54 haplotypes. Overall, a historical (natural expansion that originated from China's eastern coast to the western interior was revealed by the haplotype network, as well as several recent, long-distant population exchanges. Correlation analysis suggested that regional economic status and proximity to marine ports significantly influenced the population genetic structure of M. alternatus as indicated by both the ratio of shared haplotypes and the haplotype diversity, however, the PWN distribution in China was significantly correlated with only the ratio of shared haplotypes. Our results suggested that the modern logistical network (i.e., the transportation system in China is a key medium by which humans have brought about population exchange of M. alternatus in mainland China, likely through inadvertent movement of infested wood packaging material associated with trade, and that this genetic exchange was primarily from the economically well-developed east coast of China, westward, to the less-developed interior. In addition, this study demonstrated the existence of non-local M. alternatus in new PWN-infested localities in China, but not all sites with non-local M. alternatus were

  20. Chronic activation of AMP-activated protein kinase increases monocarboxylate transporter 2 and 4 expression in skeletal muscle.

    Science.gov (United States)

    England, E M; Shi, H; Matarneh, S K; Oliver, E M; Helm, E T; Scheffler, T L; Puolanne, E; Gerrard, D E

    2017-08-01

    Acute activation of AMP-activated protein kinase (AMPK) increases monocarboxylate transporter (MCT) expression in skeletal muscle. However, the impact of chronic activation of AMPK on MCT expression in skeletal muscle is unknown. To investigate, MCT1, MCT2, and MCT4 mRNA expression and protein abundance were measured in the longissimus lumborum (glycolytic), masseter (oxidative), and heart from wild-type (control) and AMPK γ3 pigs. The AMPK γ3 gain in function mutation results in AMPK being constitutively active in glycolytic skeletal muscle and increases energy producing pathways. The MCT1 and MCT2 mRNA expression in muscle was lower ( muscle, but MCT2 was greater ( muscles with an oxidative muscle phenotype. Monocarboxylate transporter 2 was also detected in muscle mitochondria and may explain the differences between muscles. The MCT4 mRNA expression was intermediate among all tissues tested and greater ( muscle.

  1. Could mesenchymal stem cell therapy help in the treatment of muscle damage caused by Bothrops alternatus venom?

    Directory of Open Access Journals (Sweden)

    Thalita da Costa Telles

    2018-03-01

    Full Text Available ABSTRACT: The aim of this study was to evaluate the use of mesenchymal stem cells (MSC in the treatment of myonecrosis induced by Bothrops alternatus venom in rats. Seventy-five male adult Wistar rats were divided into three experimental groups. G1 and G2 were injected in the gastrocnemius muscle with 120μg of B. alternatus venom, while G3 received 200μL of PBS only. Three days after the venom injection, 12 rats from G1 were treated with 5.0 x 106 MSC in PBS, whereas G2 and G3 rats received PBS. Every three days, blood and muscle samples of five animals from each group were taken for serum biochemical and pathological analyses. Histological examinations showed more intense muscle lesions following MSC treatment, characterized by disorganization and loss of muscle fibers, with focal necrosis and inflammatory infiltration by mononuclear cells. In conclusion, the use of MSC for the treatment of local damage caused by inoculation of B. alternatus venom impaired muscle regeneration and interfered in the healing process.

  2. Actovegin, a non-prohibited drug increases oxidative capacity in human skeletal muscle

    DEFF Research Database (Denmark)

    Søndergård, Stine D; Dela, Flemming; Helge, Jørn W

    2016-01-01

    Actovegin, a deproteinized haemodialysate of calf blood, is suggested to have ergogenic properties, but this potential effect has never been investigated in human skeletal muscle. To investigate this purported ergogenic effect, we measured the mitochondrial respiratory capacity in permeabilized h...

  3. Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats.

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    Anette I Öberg

    Full Text Available BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin, plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.

  4. Increased serum inflammatory markers in the absence of clinical and skeletal muscle inflammation in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Piehl-Aulin, Karin; Jones, Ian; Lindvall, Björn; Magnuson, Anders; Abdel-Halim, Samy M

    2009-01-01

    Muscle wasting and cachexia are common occurrences in patients with chronic obstructive pulmonary disease (COPD). The current study aimed to investigate markers of inflammation in the circulation and skeletal muscle that might be associated with development of muscle wasting. Three groups of patients with mild, moderate and severe COPD and matched healthy controls were recruited. Serum levels of C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), IL-6, IL-8, TNF-alpha, cortisol, insulin-like growth factor 1 (IGF-1), leptin and ghrelin were analysed. Skeletal muscle inflammation was investigated microscopically using a panel of antibodies and standard staining for inflammatory cell infiltration. All COPD patients were clinically stable, with no sign of inflammation and normal CRP values. Compared to controls, significantly increased hs-CRP levels were observed in all COPD patient groups. Significant rises in IL-6 levels were first observed in moderate COPD, while IL-8 levels were significantly elevated at the late severe stage. Circulating levels of TNF-alpha, cortisol, IGF-1, leptin and ghrelin were similar to control levels. No microscopic signs of skeletal muscle inflammation were observed. Our results identify hs-CRP as an early marker of inflammation that is significantly increased in the circulation even in mild COPD. Serum interleukin levels appear to be increased with disease progress. These changes were manifested in the absence of any clinical signs of disease exacerbation, evidence of skeletal muscle inflammation or hormonal changes.

  5. Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

    KAUST Repository

    Conti, Antonio

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS\\'s pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V.

  6. Intermittent pneumatic compression of legs increases microcirculation in distant skeletal muscle.

    Science.gov (United States)

    Liu, K; Chen, L E; Seaber, A V; Johnson, G W; Urbaniak, J R

    1999-01-01

    Intermittent pneumatic compression has been established as a method of clinically preventing deep vein thrombosis, but the mechanism has not been documented. This study observed the effects of intermittent pneumatic compression of legs on the microcirculation of distant skeletal muscle. The cremaster muscles of 80 male rats were exposed, a specially designed intermittent pneumatic-compression device was applied to both legs for 60 minutes, and the microcirculation of the muscles was assessed by measurement of the vessel diameter in three categories (10-20, 21-40, and 41-70 microm) for 120 minutes. The results showed significant vasodilation in arterial and venous vessels during the application of intermittent pneumatic compression, which disappeared after termination of the compression. The vasodilation reached a maximum 30 minutes after initiation of the compression and could be completely blocked by an inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (10 micromol/min). A 120-minute infusion of NG-monomethyl-L-arginine, beginning coincident with 60 minutes of intermittent pneumatic compression, resulted in a significant decrease in arterial diameter that remained at almost the same level after termination of the compression. The magnitude of the decrease in diameter in the group treated with intermittent pneumatic compression and NG-monomethyl-L-arginine was comparable with that in the group treated with NG-monomethyl-L-arginine alone. The results imply that the production of nitric oxide is involved in the positive influence of intermittent pneumatic compression on circulation. It is postulated that the rapid increase in venous velocity induced by intermittent pneumatic compression produces strong shear stress on the vascular endothelium, which stimulates an increased release of nitric oxide and thereby causes systemic vasodilation.

  7. A transcriptomic analysis of gene expression in the venom gland of the snake Bothrops alternatus (urutu

    Directory of Open Access Journals (Sweden)

    Menossi Marcelo

    2010-10-01

    Full Text Available Abstract Background The genus Bothrops is widespread throughout Central and South America and is the principal cause of snakebite in these regions. Transcriptomic and proteomic studies have examined the venom composition of several species in this genus, but many others remain to be studied. In this work, we used a transcriptomic approach to examine the venom gland genes of Bothrops alternatus, a clinically important species found in southeastern and southern Brazil, Uruguay, northern Argentina and eastern Paraguay. Results A cDNA library of 5,350 expressed sequence tags (ESTs was produced and assembled into 838 contigs and 4512 singletons. BLAST searches of relevant databases showed 30% hits and 70% no-hits, with toxin-related transcripts accounting for 23% and 78% of the total transcripts and hits, respectively. Gene ontology analysis identified non-toxin genes related to general metabolism, transcription and translation, processing and sorting, (polypeptide degradation, structural functions and cell regulation. The major groups of toxin transcripts identified were metalloproteinases (81%, bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%, phospholipases A2 (5.6%, serine proteinases (1.9% and C-type lectins (1.5%. Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. Phospholipases A2 were essentially acidic; no basic PLA2 were detected. Minor toxin transcripts were related to L-amino acid oxidase, cysteine-rich secretory proteins, dipeptidylpeptidase IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and double-specificity phosphatase Dusp6, showed high sequence identity to similar proteins from other snakes. In addition to the above features, single-nucleotide polymorphisms, microsatellites, transposable elements and inverted repeats that could contribute to toxin diversity were observed. Conclusions Bothrops alternatus venom gland

  8. Alpha adrenergic receptor blockade increases capillarisation and fractional O2 extraction and lowers blood flow in contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Mortensen, Stefan Peter; Egginton, Stuart; Madsen, Mads

    2017-01-01

    . CONCLUSIONS: These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarisation resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate......AIM: To investigate the effect of elevated basal shear stress on angiogenesis in humans, and the role of enhanced skeletal muscle capillarisation on blood flow and O2 extraction. METHODS: Limb haemodynamics and O2 extraction was measured at rest and during one-leg knee-extensor exercise (12 and 24W......) in 10 healthy untrained young men before and after 4 weeks treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day(-1) ). Corresponding biopsies were taken from the m. vastus lateralis. RESULTS: Resting leg blood flow was increased by 57% 6 hours following Terazosin treatment (P

  9. Increased Autolysis of μ-Calpain in Skeletal Muscles of Chronic Alcohol-Fed Rats.

    Science.gov (United States)

    Gritsyna, Yulia V; Salmov, Nikolay N; Bobylev, Alexander G; Ulanova, Anna D; Kukushkin, Nikolay I; Podlubnaya, Zoya A; Vikhlyantsev, Ivan M

    2017-10-01

    Proteolysis can proceed via several distinct pathways such as the lysosomal, calcium-dependent, and ubiquitin-proteasome-dependent pathways. Calpains are the main proteases that cleave a large variety of proteins, including the giant sarcomeric proteins, titin and nebulin. Chronic ethanol feeding for 6 weeks did not affect the activities of μ-calpain and m-calpain in the m. gastrocnemius. In our research, changes in μ-calpain activity were studied in the m. gastrocnemius and m. soleus of chronically alcohol-fed rats after 6 months of alcohol intake. SDS-PAGE analysis was applied to detect changes in titin and nebulin contents. Titin phosphorylation analysis was performed using the fluorescent dye Pro-Q Diamond. Western blotting was used to determine μ-calpain autolysis as well as μ-calpain and calpastatin contents. The titin and nebulin mRNA levels were assessed by real-time PCR. The amounts of the autolysed isoform (78 kDa) of full-length μ-calpain (80 kDa) increased in the m. gastrocnemius and m. soleus of alcohol-fed rats. The calpastatin content increased in m. gastrocnemius. Decreased intact titin-1 (T1) and increased T2-proteolytic fragment contents were found in the m. gastrocnemius and m. soleus of the alcohol-fed rats. The nebulin content decreased in the rat gastrocnemius muscle of the alcohol-fed group. The phosphorylation levels of T1 and T2 were increased in the m. gastrocnemius and m. soleus, and decreased titin and nebulin mRNA levels were observed in the m. gastrocnemius. The nebulin mRNA level was increased in the soleus muscle of the alcohol-fed rats. In summary, our data suggest that prolonged chronic alcohol consumption for 6 months resulted in increased autolysis of μ-calpain in rat skeletal muscles. These changes were accompanied by reduced titin and nebulin contents, titin hyperphosphorylation, and development of hindlimb muscle atrophy in the alcohol-fed rats. Copyright © 2017 by the Research Society on Alcoholism.

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

    NARCIS (Netherlands)

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

    2013-01-01

    Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in

  11. Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals

    DEFF Research Database (Denmark)

    van Hall, Gerrit; Steensberg, Adam; Fischer, Christian

    2008-01-01

    CONTEXT: IL-6 is a key modulator of immune function and suggested to be involved in skeletal muscle wasting as seen in sepsis. OBJECTIVE: Our objective was to determine the role of IL-6 in human in vivo systemic and skeletal muscle amino acid metabolism and protein turnover. SUBJECTS AND METHODS...... differences and m. vastus lateralis biopsies after 2-h basal, 3-h infusion, and 3 h after infusion. RESULTS: The IL-6 concentration after 30-min infusion was approximately 4 (saline) and 140 pg/ml (rhIL-6). Three-hour rhIL-6 infusion caused an approximate 50% decrease in muscle protein turnover, albeit...... synthesis was more suppressed than breakdown, causing a small increase in net muscle protein breakdown. Furthermore, rhIL-6 decreased arterial amino acid concentration with 20-40%, despite the increase net release from muscle. CONCLUSIONS: We demonstrated that IL-6 profoundly alters amino acid turnover...

  12. Increased CaVβ1a Expression with Aging Contributes to Skeletal Muscle Weakness

    Science.gov (United States)

    Taylor, Jackson R.; Zheng, Zhenlin; Wang, Zhong-Min; Payne, Anthony M.; Messi, María L.; Delbono, Osvaldo

    2009-01-01

    Summary Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation-contraction (E-C) coupling. E-C uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. E-C uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel α1s (CaV1.1) and β1a (CaVβ1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaVβ1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaVβ1a expression over the full lifespan of FVB mice. To examine the specific effects of CaVβ1a overexpression, a CaVβ1a -YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaVβ1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaVβ1a -YFP expression in individual fibers, also showed an inverse relationship with charge movement, measured using the whole-cell patch-clamp technique. Specific force was significantly reduced in young CaVβ1a - YFP electroporated muscle fibers compared to sham-electroporated, age-matched controls. siRNA interference of CaVβ1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaVβ1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaVβ1a during old age may play a role in the loss of specific force. PMID:19663902

  13. Increased CaVbeta1A expression with aging contributes to skeletal muscle weakness.

    Science.gov (United States)

    Taylor, Jackson R; Zheng, Zhenlin; Wang, Zhong-Min; Payne, Anthony M; Messi, María L; Delbono, Osvaldo

    2009-09-01

    Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation-contraction (E-C) coupling. Excitation-contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation-contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel alpha1s (CaV1.1) and beta1a (CaVbeta1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaVbeta1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaVbeta1a expression over the full lifespan of Friend Virus B (FVB) mice. To examine the specific effects of CaVbeta1a overexpression, a CaVbeta1a-YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaVbeta1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaVbeta1a-YFP expression in individual fibers, also showed an inverse relationship with charge movement, measured using the whole-cell patch-clamp technique. Specific force was significantly reduced in young CaVbeta1a-YFP electroporated muscle fibers compared with sham-electroporated, age-matched controls. siRNA interference of CaVbeta1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaVbeta1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaVbeta1a during old age may play a role in the loss of specific force.

  14. Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lin, Chian-Shiung; Hsu, Chih-Chieh; Chen, Li-Jen; Cheng, Kai-Chun; Cheng, Juei-Tang

    2009-11-20

    Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

  15. Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus.

    Science.gov (United States)

    Monteiro, Diana Amaral; Selistre-de-Araújo, Heloisa Sobreiro; Tavares, Driele; Fernandes, Marisa Narciso; Kalinin, Ana Lúcia; Rantin, Francisco Tadeu

    2017-09-28

    Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg -1 , via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus , seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms.

  16. Influence of 60Co γ irradiation on fertility of Japanese pine sawyer beetle Monochamus alternatus hope (Coleoptera: Cerambycidae)

    International Nuclear Information System (INIS)

    Ma Peipei; Zhang Yong'an; Wang Yuzhu; Qu Liangjian; Wang Dengyuan; Jiang Ping; Mou Jianjun

    2008-01-01

    The fertility of the Japanese pine sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) irradiated with 60 Co γ-rays was remarkable reduced at the doses of 30Gy, 35Gy and 40Gy, especially at 40Gy. When the non-irradiated females were coupled with the irradiated males first, and then coupled with non-irradiated males, the hatchability and the fertility had little higher but lower than the control. It explained that radiation has certain influence to the female gonad. It also has difference between the hatching rate and the amount of eggs in different match. (authors)

  17. Increased thermoregulation in cold-exposed transgenic mice overexpressing lipoprotein lipase in skeletal muscle: an avian phenotype?

    Science.gov (United States)

    Jensen, Dalan R; Knaub, Leslie A; Konhilas, John P; Leinwand, Leslie A; MacLean, Paul S; Eckel, Robert H

    2008-04-01

    LPL is an enzyme involved in the breakdown and uptake of lipoprotein triglycerides. In the present study, we examined how the transgenic (Tg) overexpression of human LPL in mouse skeletal muscle affected tolerance to cold temperatures, cold-induced thermogenesis, and fuel utilization during this response. Tg mice and their nontransgenic controls were placed in an environmental chamber and housed in metabolic chambers that monitored oxygen consumption and carbon dioxide production with calorimetry. When exposed to 4 degrees C, an attenuation in the decline in body temperature in Tg mice was accompanied by an increased metabolic rate (15%; P cold tolerance and thermogenesis in Tg mice. The more oxidative type IIa fibers were favored over the more glycolytic type IIb fibers (P cold tolerance by enhancing the capacity for fat oxidation, producing an avian-like phenotype in which skeletal muscle contributes significantly to the thermogenic response to cold temperatures.

  18. Pine wilt disease in Yunnan, China: Evidence of non-local pine sawyer Monochamus alternatus (Coloptera: Cerambycidae) populations revealed by mitochondrial DNA

    Science.gov (United States)

    Da-Ying Fu; Shao-Ji Hu; Hui Ye; Robert A. Haack; Ping-Yang. Zhou

    2010-01-01

    Monochamus alternatus (Hope) specimens were collected from nine geographical populations in China,where the pinewood nematode Bursaphelenchus xylophilus (Steiner et Buhrer) was present. There were seven populations in southwestern China in Yunnan Province (Ruili,Wanding, Lianghe, Pu'er, Huaning, Stone Forest and Yongsheng),...

  19. Fasting Increases Human Skeletal Muscle Net Phenylalanine Release and This Is Associated with Decreased mTOR Signaling

    Science.gov (United States)

    Vendelbo, Mikkel Holm; Møller, Andreas Buch; Christensen, Britt; Nellemann, Birgitte; Clasen, Berthil Frederik Forrest; Nair, K. Sreekumaran; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

    2014-01-01

    Aim Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR), a key regulator of cell growth. Methods Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days. Results Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation. Conclusions Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth. PMID:25020061

  20. Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling.

    Directory of Open Access Journals (Sweden)

    Mikkel Holm Vendelbo

    Full Text Available Fasting is characterised by profound changes in energy metabolism including progressive loss of body proteins. The underlying mechanisms are however unknown and we therefore determined the effects of a 72-hour-fast on human skeletal muscle protein metabolism and activation of mammalian target of rapamycin (mTOR, a key regulator of cell growth.Eight healthy male volunteers were studied twice: in the postabsorptive state and following 72 hours of fasting. Regional muscle amino acid kinetics was measured in the forearm using amino acid tracers. Signaling to protein synthesis and breakdown were assessed in skeletal muscle biopsies obtained during non-insulin and insulin stimulated conditions on both examination days.Fasting significantly increased forearm net phenylalanine release and tended to decrease phenylalanine rate of disappearance. mTOR phosphorylation was decreased by ∼50% following fasting, together with reduced downstream phosphorylation of 4EBP1, ULK1 and rpS6. In addition, the insulin stimulated increase in mTOR and rpS6 phosphorylation was significantly reduced after fasting indicating insulin resistance in this part of the signaling pathway. Autophagy initiation is in part regulated by mTOR through ULK1 and fasting increased expression of the autophagic marker LC3B-II by ∼30%. p62 is degraded during autophagy but was increased by ∼10% during fasting making interpretation of autophagic flux problematic. MAFbx and MURF1 ubiquitin ligases remained unaltered after fasting indicating no change in protesomal protein degradation.Our results show that during fasting increased net phenylalanine release in skeletal muscle is associated to reduced mTOR activation and concomitant decreased downstream signaling to cell growth.

  1. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

    Science.gov (United States)

    Hatazawa, Yukino; Ono, Yusuke; Hirose, Yuma; Kanai, Sayaka; Fujii, Nobuharu L; Machida, Shuichi; Nishino, Ichizo; Shimizu, Takahiko; Okano, Masaki; Kamei, Yasutomi; Ogawa, Yoshihiro

    2018-03-01

    DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5) mRNA was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5) mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.-Hatazawa, Y., Ono, Y., Hirose, Y., Kanai, S., Fujii, N. L., Machida, S., Nishino, I., Shimizu, T., Okano, M., Kamei, Y., Ogawa, Y. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

  2. Pro-inflammatory macrophages increase in skeletal muscle of high fat-fed mice and correlate with metabolic risk markers in humans

    DEFF Research Database (Denmark)

    Fink, Lisbeth N; Costford, Sheila R; Lee, Yun S

    2014-01-01

    In obesity, immune cells infiltrate adipose tissue. Skeletal muscle is the major tissue of insulin-dependent glucose disposal, and indices of muscle inflammation arise during obesity, but whether and which immune cells increase in muscle remain unclear....

  3. Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart.

    Science.gov (United States)

    Monteiro, D A; Kalinin, A L; Selistre-de-Araujo, H S; Vasconcelos, E S; Rantin, F T

    2016-02-01

    Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traíra, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) exchanger); 4) abolishment of the typical negative force-frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca(2+) handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

    Science.gov (United States)

    Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

    2016-12-01

    Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca 2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca 2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca 2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  5. Insulin treatment reverses the increase in atrogin-1 expression in atrophied skeletal muscles of diabetic rats with acute joint inflammation

    Directory of Open Access Journals (Sweden)

    Pinheiro-Dardis CM

    2018-02-01

    Full Text Available Clara Maria Pinheiro-Dardis,1 Vânia Ortega Gutierres,1 Renata Pires Assis,1 Sabrina Messa Peviani,2 Gabriel Borges Delfino,2 João Luiz Quagliotti Durigan,3 Tania de Fátima Salvini,2 Amanda Martins Baviera,1 Iguatemy Lourenço Brunetti1 1São Paulo State University (UNESP, School of Pharmaceutical Sciences, Department of Clinical Analysis, Araraquara, São Paulo, Brazil; 2Federal University of São Carlos (UFSCar, Department of Physical Therapy, São Carlos, São Paulo, Brazil; 3Physical Therapy Division, University of Brasilia, Brasilia, Federal District, Brazil Background: The aim of this study was to evaluate the changes in biomarkers of skeletal muscle proteolysis (atrogin-1, muscle RING finger-1 protein [MuRF-1] and inflammation (nuclear factor kappa-B in skeletal muscles of rats under two catabolic conditions, diabetes mellitus (DM and acute joint inflammation, and the effects of insulin therapy. Materials and methods: Male Wistar rats were divided into groups without diabetes – normal (N, saline (NS, or Ɩ-carrageenan (NCa injection into the tibiotarsal joint – and groups with diabetes – diabetes (D, plus insulin (DI, saline (DS, or Ɩ-carrageenan (DCa injection into the tibiotarsal joint, or Ɩ-carrageenan injection and treatment with insulin (DCaI. Three days after Ɩ-carrageenan injection (17 days after diabetes induction, tibialis anterior (TA and soleus (SO skeletal muscles were used for analysis. Results: DM alone caused a significant decrease in the mass of TA and SO muscles, even with low levels of atrogenes (atrogin-1, MuRF-1, which could be interpreted as an adaptive mechanism to spare muscle proteins under this catabolic condition. The loss of muscle mass was exacerbated when Ɩ-carrageenan was administered in the joints of diabetic rats, in association with increased expression of atrogin-1, MuRF-1, and nuclear factor kappa-B. Treatment with insulin prevented the increase in atrogin-1 (TA, SO and the loss of muscle

  6. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

    DEFF Research Database (Denmark)

    Klefter, O.; Feldt-Rasmussen, U.

    2009-01-01

    OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...

  7. Increase in relative skeletal muscle mass over time and its inverse association with metabolic syndrome development: a 7-year retrospective cohort study.

    Science.gov (United States)

    Kim, Gyuri; Lee, Seung-Eun; Jun, Ji Eun; Lee, You-Bin; Ahn, Jiyeon; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Jee, Jae Hwan; Lee, Moon-Kyu; Kim, Jae Hyeon

    2018-02-05

    Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54-0.68). Furthermore, compared with SMI changes  1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.

  8. S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy.

    Science.gov (United States)

    Marabita, Manuela; Baraldo, Martina; Solagna, Francesca; Ceelen, Judith Johanna Maria; Sartori, Roberta; Nolte, Hendrik; Nemazanyy, Ivan; Pyronnet, Stéphane; Kruger, Marcus; Pende, Mario; Blaauw, Bert

    2016-10-04

    Loss of skeletal muscle mass and force aggravates age-related sarcopenia and numerous pathologies, such as cancer and diabetes. The AKT-mTORC1 pathway plays a major role in stimulating adult muscle growth; however, the functional role of its downstream mediators in vivo is unknown. Here, we show that simultaneous inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT-induced muscle growth and render it insensitive to the mTORC1-inhibitor rapamycin. Surprisingly, lack of mTOR signaling to 4E-BP1 only, or deletion of S6K1 alone, is not sufficient to reduce muscle hypertrophy or alter its sensitivity to rapamycin. However, we report that, while not required for muscle growth, S6K1 is essential for maintaining muscle structure and force production. Hypertrophy in the absence of S6K1 is characterized by compromised ribosome biogenesis and the formation of p62-positive protein aggregates. These findings identify S6K1 as a crucial player for maintaining muscle function during hypertrophy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle

    DEFF Research Database (Denmark)

    Yegutkin, G.G.; Gonzalez-Alonso, J.; Rosenmeier, Jaya Birgitte

    2008-01-01

    Sympathetic vasoconstriction is blunted in the vascular beds of contracting skeletal muscle in humans, presumably due to the action of vasoactive metabolites (functional sympatholysis). Recently, we demonstrated that infusion of ATP into the arterial circulation of the resting human leg increases....../UTP-selective receptors. To this aim, we first measured leg blood flow (LBF), mean arterial pressure (MAP), cardiac output , leg arterial-venous (a-v) O(2) difference, plasma ATP and soluble nucleotidase activities during intrafemoral artery infusion of adenosine, AMP, ADP, ATP or UTP in nine healthy males. Comparison...... of the doses of nucleotides and adenosine required for a similar increase in LBF from approximately 0.5 l min(-1) at baseline to approximately 3.5 l min(-1) (without altering MAP but increasing Q significantly) revealed the following rank order of vasoactive potency: ATP (100) = UTP (100) >> adenosine (5...

  10. Treatment of Bothrops alternatus envenomation by Curcuma longa and Calendula officinalis extracts and ar-turmerone Tratamento local do envenenamento por Bothrops alternatus com extrato de Curcuma longa e Calendula officinalis e ar-turmerone

    Directory of Open Access Journals (Sweden)

    M.M. Melo

    2005-02-01

    Full Text Available It was investigated the efficiency of two extracts of plants and one fraction of their properties against the local effects of bothropic envenomation. Bothrops alternatus venom (1.25µg diluted in 100µl of sterile saline solution was inoculated (intradermally into the shaved dorsal back skin of 30 New Zealand rabbits. The animals were divided in six groups receiving the following treatments: group I: subcutaneous application of Curcuma longa extract (1.0ml; group II: topic treatment of Curcuma longa hydroalcoholic extract (1.0ml; group III: topic application of ar-turmerone in vaseline (1.0g; group IV: topic application of Curcuma longa methanolic extract (1.0ml; group V: topic application of Calendula officinalis ointment (1.0g; group VI: topic application of saline (1.0ml. These treatments were done at 30 minutes, and at 2, 4, 24 and 72 hours after venom inoculation. Intensity of local edema, hemorrhagic halo and necrosis were evaluated until 168h after that. Additionally, seven days after the Bothrops venom inoculation, blood was collected from heart with and without EDTA (10% for hemogram and biochemical parameters (total protein, blood urea nitrogen, creatinine, and fibrinogen and all the animals were anesthetized, sacrificed by ether inhalation and submitted to necropsy. Fragments of tissues were taken for histopathological evaluation. The most efficient treatment for inhibition of edema, necrosis and local hemorrhage after Bothrops alternatus venom was the topic application of ar-turmerone.Investigou-se a eficácia do extrato de plantas no tratamento local do envenenamento botrópico. Veneno de serpentes Bothrops alternatus (1,25µg diluído em 100µl de solução salina estéril foi inoculado (via intradérmica entre as escápulas de 30 coelhos. Os animais foram divididos em seis grupos (tratamentos: grupo I: tratamento subcutâneo com extrato de Curcuma longa; grupo II: tratamento tópico com extrato hidroalcoólico de Curcuma longa

  11. Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

    2015-01-01

    Aging is associated with progressive loss of cardiovascular and skeletal muscle function. The impairment in physical capacity with advancing age could be related to an insufficient peripheral O2 delivery to the exercising muscles. Furthermore, the mechanisms underlying an impaired blood flow...... to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal...... in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age....

  12. Transition from physical activity to inactivity increases skeletal muscle miR-148b content and triggers insulin resistance.

    Science.gov (United States)

    Gastebois, Caroline; Chanon, Stéphanie; Rome, Sophie; Durand, Christine; Pelascini, Elise; Jalabert, Audrey; Euthine, Vanessa; Pialoux, Vincent; Blanc, Stéphane; Simon, Chantal; Lefai, Etienne

    2016-09-01

    This study investigated miR-148b as a potential physiological actor of physical inactivity-induced effects in skeletal muscle. By using animal and human protocols, we demonstrated that the early phase of transition toward inactivity was associated with an increase in muscle miR-148b content, which triggered the downregulation of NRAS and ROCK1 target genes. Using human myotubes, we demonstrated that overexpression of miR-148b decreased NRAS and ROCK1 protein levels, and PKB phosphorylation and glucose uptake in response to insulin. Increase in muscle miR-148b content might thus participate in the decrease in insulin sensitivity at the whole body level during the transition toward physical inactivity. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  13. Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    W. Y. Liu

    2013-01-01

    Full Text Available This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2 and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON, the trained control group (TC, and the exhaustive trained group (ET. Malondialdehyde (MDA, superoxide dismutase (SOD, xanthine oxidase (XOD, ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio. An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

  14. Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle

    DEFF Research Database (Denmark)

    Yegutkin, G.G.; Gonzalez-Alonso, J.; Rosenmeier, Jaya Birgitte

    2008-01-01

    /UTP-selective receptors. To this aim, we first measured leg blood flow (LBF), mean arterial pressure (MAP), cardiac output , leg arterial-venous (a-v) O(2) difference, plasma ATP and soluble nucleotidase activities during intrafemoral artery infusion of adenosine, AMP, ADP, ATP or UTP in nine healthy males. Comparison.......8) > ADP (2.7) > AMP (1.7). The infusions did not cause any shifts in plasma ATP level or soluble serum nucleotidase activities. Combined infusion of the vasodilatory compounds and the sympathetic vasoconstrictor drug tyramine increased plasma noradrenaline in all hyperaemic conditions, but only caused leg......Sympathetic vasoconstriction is blunted in the vascular beds of contracting skeletal muscle in humans, presumably due to the action of vasoactive metabolites (functional sympatholysis). Recently, we demonstrated that infusion of ATP into the arterial circulation of the resting human leg increases...

  15. Hemograma de cães envenenados experimentalmente com Bothrops alternatus após diferentes tratamentos.

    OpenAIRE

    D. O. Jacome; M. M. Melo; M. M. B. Santos; K. M. Ferreira; R. M. Sabaini

    2005-01-01

    RESUMO: O objetivo deste trabalho foi verificar a influência de diferentes tratamentos (soro antibotrópico, flunixina meglumina e extrato aquoso de C. longa) sobre o hemograma de cães envenenados experimentalmente com Bothrops alternatus. Foram utilizados 12 cães adultos, sem raça definida, inoculados com 0,3mg/kg do veneno via IM, tratados duas horas após o envenenamento, divididos em três grupos de 4 animais: Grupo I- soro antibotrópico diluído em solução fisiológica 0,9%, dose ...

  16. BaltDC: purification, characterization and infrared spectroscopy of an antiplatelet DC protein isolated from Bothrops alternatus snake venom.

    Science.gov (United States)

    Matias, Mariana Santos; de Sousa, Bruna Barbosa; da Cunha Pereira, Déborah Fernanda; Dias, Edigar Henrique Vaz; Mamede, Carla Cristine Neves; de Queiroz, Mayara Ribeiro; Silva, Anielle Christine Almeida; Dantas, Noelio Oliveira; Soares, Andreimar Martins; de Oliveira Costa, Júnia; de Oliveira, Fábio

    2017-01-01

    Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO 3 2- groups, present in BaltDC, form hydrogen bonds with the PO 2 - groups present in the non-lipid portion of the membrane platelets. BaltDC may be of medical interest since it was able to inhibit platelet aggregation.

  17. Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Naoki Horii

    Full Text Available Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA, a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats. Male 20-week-old type 2 diabetic rats (OLETF were randomly divided into 3 groups: sedentary control, resistance training (3 times a week on alternate days for 8 weeks, or resistance training with continuous infusion of a 5α-reductase inhibitor (n = 8 each group. Age-matched, healthy nondiabetic Long-Evans Tokushima Otsuka (LETO rats (n = 8 were used as controls. The results indicated that OLETF rats showed significant decrease in muscular DHEA, free testosterone, DHT levels, and protein expression of steroidogenic enzymes, with loss of skeletal muscle mass and hyperglycemia, compared to that of LETO rats. However, 8-week resistance training in OLETF rats significantly increased the levels of muscle sex steroid hormones and protein expression of steroidogenic enzymes with a concomitant increase in skeletal muscle mass, improved fasting glucose level, and insulin sensitivity index. Moreover, resistance training accelerated glucose transporter-4 (GLUT-4 translocation and protein kinase B and C-ζ/λ phosphorylation. Administering the 5α-reductase inhibitor in resistance-trained OLETF rats resulted in suppression of the exercise-induced effects on skeletal muscle mass, fasting glucose level, insulin sensitivity index, and GLUT-4 signaling, with a decline in muscular DHT levels. These findings suggest that resistance training

  18. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

    DEFF Research Database (Denmark)

    Klefter, Oliver; Feldt-Rasmussen, Ulla

    2009-01-01

    OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due...... to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... studied both muscle and bone variables concomitantly. No trials studied the relationship between the changes in muscle and bone measurements. CONCLUSION: Although in vitro studies have shown that GH has a direct effect on bone remodeling, present physiological concepts and the results of clinical trials...

  19. Nitric oxide increases cyclic GMP levels, AMP-activated protein kinase (AMPK)alpha1-specific activity and glucose transport in human skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A S; Long, Y C; de Castro Barbosa, T

    2010-01-01

    an insulin-independent signalling mechanism. Consistent with this, spermine NONOate increased AMP-activated protein kinase (AMPK)-alpha1-associated activity (1.7-fold, p .... CONCLUSIONS/INTERPRETATION: Pharmacological treatment of skeletal muscle with spermine NONOate increases glucose transport via insulin-independent signalling pathways involving increased intracellular cGMP levels and AMPK-alpha1-associated activity....

  20. Ursolic acid increases energy expenditure through enhancing free fatty acid uptake and β-oxidation via an UCP3/AMPK-dependent pathway in skeletal muscle.

    Science.gov (United States)

    Chu, Xia; He, Xuan; Shi, Zhiping; Li, Chunjuan; Guo, Fuchuan; Li, Songtao; Li, Ying; Na, Lixin; Sun, Changhao

    2015-08-01

    Ursolic acid (UA) is a triterpenoid compound with multifold biological functions. Our previous studies have reported that UA protects against high-fat diet-induced obesity and improves insulin resistance (IR). However, the potential mechanisms are still undefined. Free fatty acid (FFA) metabolism in skeletal muscle plays a central role in obesity and IR. Therefore, in this study, we investigated the effect and the potential mechanisms of UA on skeletal muscle FFA metabolism. In diet-induced obese rats, 0.5% UA supplementation for 6 weeks markedly reduced body weight, increased energy expenditure, decreased FFA level in serum and skeletal muscle and triglyceride content in skeletal muscle. In vitro, the data provided directly evidence that UA significantly increased fluorescently labeled FFA uptake and (3) H-labeled palmitic acid β-oxidation. UA-activated AMP-activated protein kinase (AMPK) and downstream targets were involved in the increase of FFA catabolism. Moreover, upregulated uncoupling protein 3 (UCP3) by UA contributed to AMPK activation via elevating adenosine monophosphate/adenosine triphosphate ratio. UA increases FFA burning through enhancing skeletal muscle FFA uptake and β-oxidation via an UCP3/AMPK-dependent pathway, which provides a novel perspective on the biological function of UA against obesity and IR. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Improved fatigue resistance in Gsα-deficient and aging mouse skeletal muscles due to adaptive increases in slow fibers

    Science.gov (United States)

    Feng, Han-Zhong; Chen, Min; Weinstein, Lee S.

    2011-01-01

    Genetically modified mice with deficiency of the G protein α-subunit (Gsα) in skeletal muscle showed metabolic abnormality with reduced glucose tolerance, low muscle mass, and low contractile force, along with a fast-to-slow-fiber-type switch (Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS. Am J Physiol Cell Physiol 296: C930–C940, 2009). Here we investigated a hypothesis that the switching to more slow fibers is an adaptive response with specific benefit. The results showed that, corresponding to the switch of myosin isoforms, the thin-filament regulatory proteins troponin T and troponin I both switched to their slow isoforms in the atrophic soleus muscle of 3-mo-old Gsα-deficient mice. This fiber-type switch involving coordinated changes of both thick- and thin-myofilament proteins progressed in the Gsα-deficient soleus muscles of 18- to 24-mo-old mice, as reflected by the expression of solely slow isoforms of myosin and troponin. Compared with age-matched controls, Gsα-deficient soleus muscles with higher proportion of slow fibers exhibited slower contractile and relaxation kinetics and lower developed force, but significantly increased resistance to fatigue, followed by a better recovery. Gsα-deficient soleus muscles of neonatal and 3-wk-old mice did not show the increase in slow fibers. Therefore, the fast-to-slow-fiber-type switch in Gsα deficiency at older ages was likely an adaptive response. The benefit of higher fatigue resistance in adaption to metabolic deficiency and aging provides a mechanism to sustain skeletal muscle function in diabetic patients and elderly individuals. PMID:21680879

  2. Activation of the dopamine 1 and dopamine 5 receptors increase skeletal muscle mass and force production under non-atrophying and atrophying conditions

    Directory of Open Access Journals (Sweden)

    Dietrich Jeffrey A

    2011-01-01

    Full Text Available Abstract Background Control of skeletal muscle mass and force production is a complex physiological process involving numerous regulatory systems. Agents that increase skeletal muscle cAMP levels have been shown to modulate skeletal muscle mass and force production. The dopamine 1 receptor and its closely related homolog, the dopamine 5 receptor, are G-protein coupled receptors that are expressed in skeletal muscle and increase cAMP levels when activated. Thus we hypothesize that activation of the dopamine 1 and/or 5 receptor will increase skeletal muscle cAMP levels thereby modulating skeletal muscle mass and force production. Methods We treated isolated mouse tibialis anterior (TA and medial gastrocnemius (MG muscles in tissue bath with the selective dopamine 1 receptor and dopamine 5 receptor agonist SKF 81297 to determine if activation of skeletal muscle dopamine 1 and dopamine 5 receptors will increase cAMP. We dosed wild-type mice, dopamine 1 receptor knockout mice and dopamine 5 receptor knockout mice undergoing casting-induced disuse atrophy with SKF 81297 to determine if activation of the dopamine 1 and dopamine 5 receptors results in hypertrophy of non-atrophying skeletal muscle and preservation of atrophying skeletal muscle mass and force production. Results In tissue bath, isolated mouse TA and MG muscles responded to SKF 81297 treatment with increased cAMP levels. Treating wild-type mice with SKF 81297 reduced casting-induced TA and MG muscle mass loss in addition to increasing the mass of non-atrophying TA and MG muscles. In dopamine 1 receptor knockout mice, extensor digitorum longus (EDL and soleus muscle mass and force was not preserved during casting with SKF 81297 treatment, in contrast to significant preservation of casted wild-type mouse EDL and soleus mass and EDL force with SKF 81297 treatment. Dosing dopamine 5 receptor knockout mice with SKF 81297 did not significantly preserve EDL and soleus muscle mass and force

  3. Evaluation of Different Applications of Ethanedinitrile (C2N2) in Various Fumigation Chambers for Control of Monochamus alternatus (Coleoptera: Cerambycidae) in Naturally Infested Logs.

    Science.gov (United States)

    Lee, Byung-Ho; Park, Chung-Gyoo; Ren, Yonglin

    2017-04-01

    Monochamus alternatus Hopeis is an important vector of nematode pests of timber in Korea, particularly Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle. Previously, we reported that ethanedinitrile (C2N2) has the potential to replace methyl bromide and metam sodium to control M. alternatus larvae and B. xylophilus under low-temperature (construction or an ISO shipping container, interior size: 5.90 m length by 2.35 m width by 2.40 m height), log water content (24.1-43.5%), filling ratios (5, 20, and 40%), and temperatures (10.5-17.3 °C). Highest concentration × time (Ct) product values were obtained with the ISO shipping container followed (in order of decreasing Ct values) by a 0.1-mm-thick, low-density polyethylene tarpaulin enclosure, a 0.1-mm-thick polyvinyl chloride (PVC) tarpaulin enclosure, and a 0.05-mm-thick PVC tarpaulin enclosure. The correlation between Ct product value and mortality of M. alternatus larvae was calculated with all treatment combinations. From this, the L(Ct)50 and L(Ct)99 values for C2N2 were determined to be 73.19 and 194.90 g h m-3, respectively. Ethanedinitrile showed promise as a practical alternative fumigant for use on fresh pine logs infested by M. alternatus larvae. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Local applications of myostatin-siRNA with atelocollagen increase skeletal muscle mass and recovery of muscle function.

    Directory of Open Access Journals (Sweden)

    Emi Kawakami

    Full Text Available BACKGROUND: Growing evidence suggests that small-interfering RNA (siRNA can promote gene silencing in mammalian cells without induction of interferon synthesis or nonspecific gene suppression. Recently, a number of highly specific siRNAs targeted against disease-causing or disease-promoting genes have been developed. In this study, we evaluate the effectiveness of atelocollagen (ATCOL-mediated application of siRNA targeting myostatin (Mst, a negative regulator of skeletal muscle growth, into skeletal muscles of muscular dystrophy model mice. METHODS AND FINDINGS: We injected a nanoparticle complex containing myostatin-siRNA and ATCOL (Mst-siRNA/ATCOL into the masseter muscles of mutant caveolin-3 transgenic (mCAV-3Tg mice, an animal model for muscular dystrophy. Scrambled (scr -siRNA/ATCOL complex was injected into the contralateral muscles as a control. Two weeks after injection, the masseter muscles were dissected for histometric analyses. To investigate changes in masseter muscle activity by local administration of Mst-siRNA/ATCOL complex, mouse masseter electromyography (EMG was measured throughout the experimental period via telemetry. After local application of the Mst-siRNA/ATCOL complex, masseter muscles were enlarged, while no significant change was observed on the contralateral side. Histological analysis showed that myofibrils of masseter muscles treated with the Mst-siRNA/ATCOL complex were significantly larger than those of the control side. Real-time PCR analysis revealed a significant downregulation of Mst expression in the treated masseters of mCAV-3Tg mice. In addition, expression of myogenic transcription factors was upregulated in the Mst-siRNA-treated masseter muscle, while expression of adipogenic transcription factors was significantly downregulated. EMG results indicate that masseter muscle activity in mCAV-3Tg mice was increased by local administration of the Mst-siRNA/ATCOL complex. CONCLUSION: These data suggest local

  5. Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, Anneke; Konings, Ellen; Goossens, Gijs H.; Bouwman, Freek G.; Moors, Chantalle C.; Boekschoten, Mark; Afman, Lydia; Muller, Michael; Mariman, Edwin C.; Blaak, Ellen E.

    2012-01-01

    Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin

  6. The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

    DEFF Research Database (Denmark)

    Giebelstein, J; Poschmann, G; Højlund, K

    2012-01-01

    The molecular mechanisms underlying insulin resistance in skeletal muscle are incompletely understood. Here, we aimed to obtain a global picture of changes in protein abundance in skeletal muscle in obesity and type 2 diabetes, and those associated with whole-body measures of insulin action....

  7. Effects of epinephrine and lactate on the increase in oxygen consumption of non-exercising skeletal muscle after aerobic exercise

    Science.gov (United States)

    Murakami, Motohide; Katsumura, Toshihito; Hamaoka, Takatumi; Osada, Takuya; Sako, Takayuki; Higuchi, Hiroyuki; Esaki, Kazuki; Kime, Ryotaro; Shimomitsu, Teruichi

    2000-10-01

    The purpose of this study was to measure O2 consumption of nonexercising skeletal muscles (VO2nonex) at rest and after aerobic exercise and to investigate the stimulant factors of O2 consumption. In experiment 1, we measured the resting metabolic rate of the finger flexor muscles in seven healthy males by 31P-magnetic resonance spectroscopy during a 15 min arterial occlusion. In experiment 2, the VO2nonex of the finger flexor muscles was measured using near infrared continuous wave spectroscopy at rest, immediate postexercise, and 3, 5, 10, 15, and 20 min following a cycling exercise at a workload corresponding to 50% of peak pulmonary O2 uptake for 20 min. We also monitored deep tissue temperature in the VO2nonex measurement area and determined catecholamines and lactate concentrations in the blood at rest and immediate postexercise. VO2nonex at rest was 1.1 +/- 0.1 (mu) M O2/s (mean +/- standard error) and VO2nonex after exercise increased 59.6 +/- 7.2% (p < 0.001) from the resting values. There were significant correlations between the increase in VO2nonex and the increase in epinephrine concentration (p < 0.01), and between the increase in VO2nonex and the increase in lactate concentration (p < 0.05). These results suggest that epinephrine and lactate concentrations are important VO2nonex stimulant factors.

  8. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes...... were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had...

  9. The Root Extract of Pueraria lobata and Its Main Compound, Puerarin, Prevent Obesity by Increasing the Energy Metabolism in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Hyo Won Jung

    2017-01-01

    Full Text Available Radix Pueraria lobata (RP has been reported to prevent obesity and improve glucose metabolism; however, the mechanism responsible for these effects has not been elucidated. The mechanism underlying anti-obesity effect of RP was investigated in high-fat diet (HFD induced obese mice and skeletal muscle cells (C2C12. Five-week-old C5BL/6 mice were fed a HFD containing or not containing RP (100 or 300 mg/kg or metformin (250 mg/kg for 16 weeks. RP reduced body weight gain, lipid accumulation in liver, and adipocyte and blood lipid levels. In addition, RP dose-dependently improved hyperglycemia, insulinemia, and glucose tolerance, and prevented the skeletal muscle atrophy induced by HFD. Furthermore, RP increased the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α expression and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK in skeletal muscle tissues. RP and its main component, puerarin, increased mitochondrial biogenesis and myotube hypertrophy in C2C12 cells. The present study demonstrates that RP can prevent diet-induced obesity, glucose tolerance, and skeletal muscle atrophy in mouse models of obesity. The mechanism responsible for the effect of RP appears to be related to the upregulation of energy metabolism in skeletal muscle, which at the molecular level may be associated with PGC-1α and AMPK activation.

  10. Three minutes of all-out intermittent exercise per week increases skeletal muscle oxidative capacity and improves cardiometabolic health.

    Directory of Open Access Journals (Sweden)

    Jenna B Gillen

    Full Text Available We investigated whether a training protocol that involved 3 min of intense intermittent exercise per week--within a total training time commitment of 30 min including warm up and cool down--could increase skeletal muscle oxidative capacity and markers of health status. Overweight/obese but otherwise healthy men and women (n = 7 each; age = 29±9 y; BMI = 29.8±2.7 kg/m2 performed 18 training sessions over 6 wk on a cycle ergometer. Each session began with a 2 min warm-up at 50 W, followed by 3×20 s "all-out" sprints against 5.0% body mass (mean power output: ∼450-500 W interspersed with 2 min of recovery at 50 W, followed by a 3 min cool-down at 50 W. Peak oxygen uptake increased by 12% after training (32.6±4.5 vs. 29.1±4.2 ml/kg/min and resting mean arterial pressure decreased by 7% (78±10 vs. 83±10 mmHg, with no difference between groups (both p<0.01, main effects for time. Skeletal muscle biopsy samples obtained before and 72 h after training revealed increased maximal activity of citrate synthase and protein content of cytochrome oxidase 4 (p<0.01, main effect, while the maximal activity of β-hydroxy acyl CoA dehydrogenase increased in men only (p<0.05. Continuous glucose monitoring measured under standard dietary conditions before and 48-72 h following training revealed lower 24 h average blood glucose concentration in men following training (5.4±0.6 vs. 5.9±0.5 mmol/L, p<0.05, but not women (5.5±0.4 vs. 5.5±0.6 mmol/L. This was associated with a greater increase in GLUT4 protein content in men compared to women (138% vs. 23%, p<0.05. Short-term interval training using a 10 min protocol that involved only 1 min of hard exercise, 3x/wk, stimulated physiological changes linked to improved health in overweight adults. Despite the small sample size, potential sex-specific adaptations were apparent that warrant further investigation.

  11. Skeletal muscle-specific expression of PGC-1α-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake.

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    Miki Tadaishi

    Full Text Available Maximal oxygen uptake (VO(2max predicts mortality and is associated with endurance performance. Trained subjects have a high VO(2max due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO(2max. There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO(2max and exercise capacity.Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice.Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise

  12. Intense resistance exercise induces early and transient increases in ryanodine receptor 1 phosphorylation in human skeletal muscle.

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    Sebastian Gehlert

    Full Text Available BACKGROUND: While ryanodine receptor 1 (RyR1 critically contributes to skeletal muscle contraction abilities by mediating Ca²⁺ion oscillation between sarcoplasmatic and myofibrillar compartments, AMP-activated protein kinase (AMPK senses contraction-induced energetic stress by phosphorylation at Thr¹⁷². Phosphorylation of RyR1 at serine²⁸⁴³ (pRyR1Ser²⁸⁴³ results in leaky RyR1 channels and impaired Ca²⁺homeostasis. Because acute resistance exercise exerts decreased contraction performance in skeletal muscle, preceded by high rates of Ca²⁺-oscillation and energetic stress, intense myofiber contractions may induce increased RyR1 and AMPK phosphorylation. However, no data are available regarding the time-course and magnitude of early RyR1 and AMPK phosphorylation in human myofibers in response to acute resistance exercise. PURPOSE: Determine the effects and early time-course of resistance exercise on pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² in type I and II myofibers. METHODS: 7 male subjects (age 23±2 years, height: 185±7 cm, weight: 82±5 kg performed 3 sets of 8 repetitions of maximum eccentric knee extensions. Muscle biopsies were taken at rest, 15, 30 and 60 min post exercise. pRyR1Ser²⁸⁴³ and pAMPKThr¹⁷² levels were determined by western blot and semi-quantitative immunohistochemistry techniques. RESULTS: While total RyR1 and total AMPK levels remained unchanged, RyR1 was significantly more abundant in type II than type I myofibers. pRyR1Ser²⁸⁴³ increased 15 min and peaked 30 min (p<0.01 post exercise in both myofiber types. Type I fibers showed relatively higher increases in pRyR1Ser²⁸⁴³ levels than type II myofibers and remained elevated up to 60 min post resistance exercise (p<0.05. pAMPKThr¹⁷² also increased 15 to 30 min post exercise (p<0.01 in type I and II myofibers and in whole skeletal muscle. CONCLUSION: Resistance exercise induces acutely increased pRyR1Ser²⁸⁴³ and

  13. Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle.

    Science.gov (United States)

    Shearer, Jane; Wilson, Rhonda J; Battram, Danielle S; Richter, Erik A; Robinson, Deborah L; Bakovic, Marica; Graham, Terry E

    2005-09-01

    Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% Vo2 max followed by five 30-s sprints at maximal capacity to further deplete glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote rapid glycogen repletion, and muscle biopsies were obtained from the vastus lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free (deglycosylated) glycogenin was detected in muscle, indicating that all glycogenin was complexed to carbohydrate. Glycogenin activity, a measure of the glycosylating ability of the protein, increased at 30 min and remained elevated for the remainder of the study. Quantitative RT-PCR showed elevated glycogenin mRNA at 120 min followed by increases in protein levels at 300 min. Glycogenin specific activity (glycogenin activity/relative protein content) was also elevated at 120 min. Proglycogen increased at all time points, with the highest rate of resynthesis occurring between 0 and 30 min. In comparison, macroglycogen levels did not significantly increase until 300 min postexercise. Together, these results show that, during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle. This may facilitate rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen, the major component of glycogen synthesized in early recovery.

  14. Training increases the concentration of [3H]ouabain-binding sites in rat skeletal muscle

    DEFF Research Database (Denmark)

    Kjeldsen, K; Richter, Erik; Galbo, H

    1986-01-01

    ]ouabain-binding-site concentration in the diaphragm, but in the heart ventricles, the K+-dependent 3-O-methylfluorescein phosphatase activity increased by 20% (P less than 0.001). Muscle inactivity induced by denervation, plaster immobilisation or tenotomy reduced the [3H]ouabain-binding-site concentration by 20-30% (P less than 0...

  15. High-fat feeding inhibits exercise-induced increase in mitochondrial respiratory flux in skeletal muscle

    DEFF Research Database (Denmark)

    Skovbro, Mette; Boushel, Robert Christopher; Hansen, Christina Neigaard

    2011-01-01

    -62%) were seen in HFD and ND, but only in HFD was an elevated (P respiratory rate seen at recovery. With HFD complex I and IV protein expression decreased (P system protein content......) and intramyocellular triacylglycerol content did not change with the intervention in either group. Indexes of mitochondrial density were similar across the groups and intervention. Mitochondrial respiratory rates, measured in permeabilized muscle fibers, showed a 31 ± 11 and 26 ± 9% exercise-induced increase (P

  16. Increasing exercise intensity reduces heterogeneity of glucose uptake in human skeletal muscles.

    Directory of Open Access Journals (Sweden)

    Ilkka Heinonen

    Full Text Available Proper muscle activation is a key feature of survival in different tasks in daily life as well as sports performance, but can be impaired in elderly and in diseases. Therefore it is also clinically important to better understand the phenomenon that can be elucidated in humans non-invasively by positron emission tomography (PET with measurements of spatial heterogeneity of glucose uptake within and among muscles during exercise. We studied six healthy young men during 35 minutes of cycling at relative intensities of 30% (low, 55% (moderate, and 75% (high of maximal oxygen consumption on three separate days. Glucose uptake in the quadriceps femoris muscle group (QF, the main force producing muscle group in recreational cycling, and its four individual muscles, was directly measured using PET and 18F-fluoro-deoxy-glucose. Within-muscle heterogeneity was determined by calculating the coefficient of variance (CV of glucose uptake in PET image voxels within the muscle of interest, and among-muscles heterogeneity of glucose uptake in QF was expressed as CV of the mean glucose uptake values of its separate muscles. With increasing intensity, within-muscle heterogeneity decreased in the entire QF as well as within its all four individual parts. Among-muscles glucose uptake heterogeneity also decreased with increasing intensity. However, mean glucose uptake was consistently lower and heterogeneity higher in rectus femoris muscle that is known to consist of the highest percentage of fast twitch type II fibers, compared to the other three QF muscles. In conclusion, these results show that in addition to increased contribution of distinct muscle parts, with increases in exercise intensity there is also an enhanced recruitment of muscle fibers within all of the four heads of QF, despite established differences in muscle-part specific fiber type distributions. Glucose uptake heterogeneity may serve as a useful non-invasive tool to elucidate muscle activation

  17. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

    2014-01-01

    The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

  18. Assessing the Utility of Soil DNA Extraction Kits for Increasing DNA Yields and Eliminating PCR Inhibitors from Buried Skeletal Remains.

    Science.gov (United States)

    Hebda, Lisa M; Foran, David R

    2015-09-01

    DNA identification of human remains is often necessary when decedents are skeletonized; however, poor DNA recovery and polymerase chain reaction (PCR) inhibition are frequently encountered, a situation exacerbated by burial. In this research, the utility of integrating soil DNA isolation kits into buried skeletal DNA analysis was evaluated and compared to a standard human DNA extraction kit and organic extraction. The soil kits successfully extracted skeletal DNA at quantities similar to standard methods, although the two kits tested, which differ mechanistically, were not equivalent. Further, the PCR inhibitors calcium and humic acid were effectively removed using the soil kits, whereas collagen was less so. Finally, concordant control region sequences were obtained from human skeletal remains using all four methods. Based on these comparisons, soil DNA isolation kits, which quickened the extraction process, proved to be a viable extraction technique for skeletal remains that resulted in positive identification of a decedent. © 2015 American Academy of Forensic Sciences.

  19. Exercise-induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans

    DEFF Research Database (Denmark)

    Langberg, H; Bjørn, C; Boushel, Robert Christopher

    2002-01-01

    Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon-related connective tissue has not yet......-50 %. The interstitial concentration of bradykinin rose in response to exercise both in skeletal muscle (from 23.1 +/- 4.9 nmol l(-1) to 110.5 +/- 37.9 nmol l(-1); P ... of bradykinin and adenosine in both skeletal muscle and the connective tissue around its adjacent tendon. These findings support a role for bradykinin and adenosine in exercise-induced hyperaemia in skeletal muscle and suggest that bradykinin and adenosine are potential regulators of blood flow in peritendinous...

  20. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression.

    Science.gov (United States)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla; Pedersen, Bente Klarlund; Green, Charlotte Jane

    2013-01-01

    Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes derived from human skeletal muscle satellite cells. Satellite cells were obtained from young (22 yrs) normally active or middle-aged (56.6 yrs) individuals who were either lifelong sedentary or lifelong active. Both middle-aged sedentary and middle-aged active myotubes had increased p21 and myosin heavy chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact on the metabolism of human myotubes during aging and may contribute to aging-associated insulin resistance through impaired GLUT4 localization.

  1. Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle

    DEFF Research Database (Denmark)

    Shearer, Jane; Wilson, Rhonda J.; Battram, Danielle S.

    2005-01-01

    Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% VO2 max followed by five 30-s sprints at maximal capacity...... to further deplete glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote rapid glycogen repletion, and muscle biopsies were obtained from the vastus lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free (deglycosylated) glycogenin was detected in muscle, indicating...... min postexercise. Together, these results show that, during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle. This may facilitate rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen, the major component...

  2. Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise

    DEFF Research Database (Denmark)

    Rosendal, Lars; Søgaard, Karen; Kjaer, Michael

    2005-01-01

    Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters...... in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male...... subjects, and the catheters were perfused with Ringer-acetate at 5 microl/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml after 65 and 110 min, respectively (P...

  3. Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle

    DEFF Research Database (Denmark)

    Sahlin, Kent; Nielsen, Jens Steen; Mogensen, Martin

    2006-01-01

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca(2......+) kinetics in human muscle. Ten male subjects performed five bouts of static knee extension with 10-min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque) was maintained to fatigue. Muscle biopsies were taken preexercise and 0.3 and 24 h postexercise from vastus...... lateralis. Mitochondria were isolated and respiratory function measured after incubation with H(2)O(2) (HPX) or control medium (Con). Mitochondrial function was not affected by RSC during Con. However, RSC exacerbated mitochondrial dysfunction during HPX, resulting in decreased respiratory control index...

  4. Exercise increases sphingoid base-1-phosphate levels in human blood and skeletal muscle in a time- and intensity-dependent manner

    DEFF Research Database (Denmark)

    Baranowski, Marcin; Błachnio-Zabielska, Agnieszka U; Charmas, Małgorzata

    2015-01-01

    PURPOSE: Sphingosine-1-phosphate (S1P) regulates cardiovascular function and plays an important role in muscle biology. We have previously reported that cycling exercise increased plasma S1P. Here, we investigated the effect of exercise duration and intensity on plasma and skeletal muscle S1P lev...

  5. Contributions of ADP and ATP to the increase in skeletal muscle blood flow after manual acupuncture stimulation in rats.

    Science.gov (United States)

    Nagaoka, S; Shinbara, H; Okubo, M; Kawakita, T; Hino, K; Sumiya, E

    2016-06-01

    To investigate the contributions of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to the increase in skeletal muscle blood flow (MBF) observed following manual acupuncture (MA) stimulation in rats. Male Sprague-Dawley rats were used as experimental animals (300-370 g, n=40). MA was applied to the right tibialis anterior muscle (TA) for 1 min using a stainless steel acupuncture needle. In eight rats, high-performance liquid chromatography with the microdialysis technique was used to measure local extracellular concentrations of ATP, ADP, adenosine monophosphate (AMP), and adenosine in the TA. In the remaining 32 rats, fluorescent microspheres (15 µm in diameter) were used to measure MBF in the TA following pre-treatment with either the P2 receptor antagonist suramin (100 mg/kg intra-arterially) or saline (control) (n=16 each). Rats receiving MA (Suramin+MA and Saline+MA groups, n=8 each) were compared with untreated rats (Suramin and Saline groups, n=8). MA significantly increased the local extracellular concentration of ATP, ADP, and adenosine (pvs 30 min after MA). In addition, MA significantly increased MBF in rats pre-treated with saline or suramin (pvs Saline+MA; pvs Suramin+MA, respectively). However, suramin significantly suppressed this MA-induced increase in MBF (pvs Suramin+MA). These results suggest that both ATP and ADP partially contribute to the MA-induced increase in MBF via P2 receptors. However, further studies are needed to clarify the contributions of other vasodilators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes

    DEFF Research Database (Denmark)

    Højlund, Kurt; Staehr, Peter; Hansen, Bo Falck

    2003-01-01

    In type 2 diabetes, insulin activation of muscle glycogen synthase (GS) is impaired. This defect plays a major role for the development of insulin resistance and hyperglycemia. In animal muscle, insulin activates GS by reducing phosphorylation at both NH(2)- and COOH-terminal sites, but the mecha...... in the phosphorylation of sites 2 + 2a. This phosphorylation abnormality likely caused the impaired GS activation and glucose storage, thereby contributing to skeletal muscle insulin resistance, and may therefore play a pathophysiological role in type 2 diabetes.......In type 2 diabetes, insulin activation of muscle glycogen synthase (GS) is impaired. This defect plays a major role for the development of insulin resistance and hyperglycemia. In animal muscle, insulin activates GS by reducing phosphorylation at both NH(2)- and COOH-terminal sites....... Despite that, insulin-mediated glucose disposal and storage were reduced and activation of GS was virtually absent in type 2 diabetic subjects. Insulin did not decrease phosphorylation of sites 2 + 2a in healthy human muscle, whereas in diabetic muscle insulin infusion in fact caused a marked increase...

  7. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    Directory of Open Access Journals (Sweden)

    Hirotaka Yamamoto

    2016-01-01

    Full Text Available Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

  8. Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function.

    Science.gov (United States)

    Jacobs, Robert Acton; Flück, Daniela; Bonne, Thomas Christian; Bürgi, Simon; Christensen, Peter Møller; Toigo, Marco; Lundby, Carsten

    2013-09-01

    Six sessions of high-intensity interval training (HIT) are sufficient to improve exercise capacity. The mechanisms explaining such improvements are unclear. Accordingly, the aim of this study was to perform a comprehensive evaluation of physiologically relevant adaptations occurring after six sessions of HIT to determine the mechanisms explaining improvements in exercise performance. Sixteen untrained (43 ± 6 ml·kg(-1)·min(-1)) subjects completed six sessions of repeated (8-12) 60 s intervals of high-intensity cycling (100% peak power output elicited during incremental maximal exercise test) intermixed with 75 s of recovery cycling at a low intensity (30 W) over a 2-wk period. Potential training-induced alterations in skeletal muscle respiratory capacity, mitochondrial content, skeletal muscle oxygenation, cardiac capacity, blood volumes, and peripheral fatigue resistance were all assessed prior to and again following training. Maximal measures of oxygen uptake (Vo2peak; ∼8%; P = 0.026) and cycling time to complete a set amount of work (∼5%; P = 0.008) improved. Skeletal muscle respiratory capacities increased, most likely as a result of an expansion of skeletal muscle mitochondria (∼20%, P = 0.026), as assessed by cytochrome c oxidase activity. Skeletal muscle deoxygenation also increased while maximal cardiac output, total hemoglobin, plasma volume, total blood volume, and relative measures of peripheral fatigue resistance were all unaltered with training. These results suggest that increases in mitochondrial content following six HIT sessions may facilitate improvements in respiratory capacity and oxygen extraction, and ultimately are responsible for the improvements in maximal whole body exercise capacity and endurance performance in previously untrained individuals.

  9. Connective tissue cells expressing fibro/adipogenic progenitor markers increase under chronic damage: relevance in fibroblast-myofibroblast differentiation and skeletal muscle fibrosis.

    Science.gov (United States)

    Contreras, Osvaldo; Rebolledo, Daniela L; Oyarzún, Juan Esteban; Olguín, Hugo C; Brandan, Enrique

    2016-06-01

    Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition.

  10. Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Essman, Stephanie C. [Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States)], E-mail: essmans@missouri.edu; Lewis, Michael R. [Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri-Columbia, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Fox, Derek B. [Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211 (United States)

    2008-02-15

    Introduction: Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate ({sup 153}Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic {sup 153}Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of {sup 153}Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of {sup 153}Sm-EDTMP on growth of long bones. Methods: Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of {sup 153}Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P<.05. Results: Significant differences in lengths of multiple bones were detected between the high-dose group and other treatment groups and controls at each time interval. A significant difference in lengths of the tibias was also noted in the medium-treatment group, compared to controls. Mean reduction of bone length was first detected at 4 months and did not increase significantly over time. Conclusions: These data suggest that clinically significant bone shortening may occur as a result of high-dosage administration of {sup 153}Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted.

  11. Contribution of adenosine to the increase in skeletal muscle blood flow caused by manual acupuncture in rats.

    Science.gov (United States)

    Shinbara, Hisashi; Nagaoka, Satomi; Izutani, Yasuyuki; Okubo, Masamichi; Kimura, Keisaku; Mizunuma, Kunio; Sumiya, Eiji

    2017-08-01

    Adenosine is believed to play an important role in local acupuncture analgesia. The aim of this study was to investigate the contribution of adenosine to the increase in skeletal muscle blood flow (MBF) caused by manual acupuncture (MA). Thirty-two male Sprague-Dawley rats (310-360 g) were anaesthetised and divided into four equal groups (n=8 each): Saline, Saline+MA, Theophylline, and Theophylline+MA. In the two MA groups, the sparrow-pecking MA technique was applied at 30 repetitions per min for 1 min to a depth of 15-18 mm using a stainless steel acupuncture needle (0.20×40 mm). The stimulus point was located on the right tibialis anterior (TA) muscle 7-8 mm below the knee. Animals in the two theophylline groups were intra-arterially injected with 8-(p-sulphophenyl) theophylline, a non-selective adenosine receptor antagonist, at a dose of 30 mg/kg before MA. Animals in the two saline groups received control saline. Fluorescent microspheres (15 µm in diameter, yellow-green fluorescent) were used for MBF measurement in all four groups. MA of the TA muscle significantly increased MBF (Saline+MA vs Saline: p=0.001; Saline+MA vs Theophylline: p=0.008). Pre-treatment with theophylline appeared to inhibit this increase (Theophylline vs Theophylline+MA; p=1.000). MBF in the Theophylline+MA group was 43% lower than in the Saline+MA group, although this was not significantly different (p=0.104). The results suggest that adenosine leads to an increase in MBF caused by MA. Adenosine may play a role in acupuncture analgesia by washing out algesic substances. Further studies are needed in order to elucidate the precise mechanism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Predictors Associated with Increase in Skeletal Muscle Mass after Sustained Virological Response in Chronic Hepatitis C Treated with Direct Acting Antivirals

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    Kazunori Yoh

    2017-10-01

    Full Text Available Aims: We aimed to examine changes in skeletal muscle mass in chronic hepatitis C (CHC patients undergoing interferon (IFN-free direct acting antivirals (DAAs therapy who achieved sustained virological response (SVR. Patients and methods: A total of 69 CHC patients treated with DAAs were analyzed. We compared the changes in skeletal muscle index (SMI using bio-impedance analysis at baseline and SMI at SVR. SMI was calculated as the sum of skeletal muscle mass in upper and lower extremities divided by height squared (cm2/m2. Further, we identified pretreatment parameters contributing to the increased SMI at SVR. Results: SMI in males at baseline ranged from 6.73 to 9.08 cm2/m2 (median, 7.65 cm2/m2, while that in females ranged from 4.45 to 7.27 cm2/m2 (median, 5.81 cm2/m2. At SVR, 36 patients (52.2% had increased SMI as compared with baseline. In the univariate analysis, age (p = 0.0392, hyaluronic acid (p = 0.0143, and branched-chain amino acid to tyrosine ratio (BTR (p = 0.0024 were significant pretreatment factors linked to increased SMI at SVR. In the multivariate analysis, only BTR was an independent predictor linked to the increased SMI at SVR (p = 0.0488. Conclusion: Pretreatment BTR level can be helpful for predicting increased SMI after SVR in CHC patients undergoing IFN-free DAAs therapy.

  13. GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response.

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    Martha Lappas

    Full Text Available Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3 plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM. Thus, the aims of this study were (i to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.

  14. Contribution on the causes of increased degrees of density in the cervical vertebrae during routine skeletal scintiscanning

    International Nuclear Information System (INIS)

    Winkler, U.

    1987-01-01

    On the basis of the findings revealed by this study the scintigraphic image and site of degenerative changes in the in region of the cervical vertebrae (routine examinations in a total of 61 patients) were rated as typical enough to permit benign skeletal diseases to be diagnosed and identified in the majority of cases, the additional use of X-ray procedures thus being rendered superfluous. (TRV) [de

  15. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

    DEFF Research Database (Denmark)

    Steensberg, A; Van Hall, Gerrit; Osada, T

    2000-01-01

    1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL...... followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1...... of IL-6 during muscular exercise. We suggest that IL-6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise....

  16. Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model.

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    Darren T Hwee

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a motor neuron disease characterized by progressive motor neuron loss resulting in muscle atrophy, declining muscle function, and eventual paralysis. Patients typically die from respiratory failure 3 to 5 years from the onset of symptoms. Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to calcium; this mechanism of action amplifies the response of muscle to neuromuscular input producing greater force when nerve input is reduced. Here, we demonstrate that a single dose of tirasemtiv significantly increases submaximal isometric force, forelimb grip strength, grid hang time, and rotarod performance in a female transgenic mouse model (B6SJL-SOD1 G93A of ALS with functional deficits. Additionally, diaphragm force and tidal volume are significantly higher in tirasemtiv-treated female B6SJL-SOD1 G93A mice. These results support the potential of fast skeletal troponin activators to improve muscle function in neuromuscular diseases.

  17. Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle.

    Science.gov (United States)

    Gouspillou, Gilles; Scheede-Bergdahl, Celena; Spendiff, Sally; Vuda, Madhusudanarao; Meehan, Brian; Mlynarski, Heather; Archer-Lahlou, Elodie; Sgarioto, Nicolas; Purves-Smith, Fennigje M; Konokhova, Yana; Rak, Janusz; Chevalier, Stéphanie; Taivassalo, Tanja; Hepple, Russell T; Jagoe, R Thomas

    2015-03-03

    Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivors of childhood ALL and may also be relevant to long-term survivors of other cancers treated with similar regimes.

  18. Mass spectrometry-based proteomic analysis of middle-aged vs. aged vastus lateralis reveals increased levels of carbonic anhydrase isoform 3 in senescent human skeletal muscle.

    Science.gov (United States)

    Staunton, Lisa; Zweyer, Margit; Swandulla, Dieter; Ohlendieck, Kay

    2012-10-01

    The age-related loss of skeletal muscle mass and associated progressive decline in contractile strength is a serious pathophysiological issue in the elderly. In order to investigate global changes in the skeletal muscle proteome after the fifth decade of life, this study analysed total extracts from human vastus lateralis muscle by fluorescence difference in-gel electrophoresis. Tissue specimens were derived from middle-aged (47-62 years) vs. aged (76-82 years) individuals and potential changes in the protein expression profiles were compared between these two age groups by a comprehensive gel electrophoresis-based survey. Age-dependent alterations in the concentration of 19 protein spots were revealed and mass spectrometry identified these components as being involved in the excitation-contraction-relaxation cycle, muscle metabolism, ion handling and the cellular stress response. This indicates a generally perturbed protein expression pattern in senescent human muscle. Increased levels of mitochondrial enzymes and isoform switching of the key contractile protein, actin, support the idea of glycolytic-to-oxidative and fast-to-slow transition processes during muscle aging. Importantly, the carbonic anhydrase (CA)3 isoform displayed an increased abundance during muscle aging, which was independently verified by immunoblotting of differently aged human skeletal muscle samples. Since the CA3 isoform is relatively muscle-specific and exhibits a fibre type-specific expression pattern, this enzyme may represent an interesting new biomarker of sarcopenia. Increased levels of CA are indicative of an increased demand of CO₂-removal in senescent muscle, and also suggest age-related fibre type shifting to slower-contracting muscles during human aging.

  19. Gain-of-function R225W mutation in human AMPKgamma(3 causing increased glycogen and decreased triglyceride in skeletal muscle.

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    Sheila R Costford

    Full Text Available BACKGROUND: AMP-activated protein kinase (AMPK is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory gamma(3 subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations. Here we report the first gain-of-function mutation in the muscle-specific regulatory gamma(3 subunit in humans. METHODS AND FINDINGS: We sequenced the exons and splice junctions of the AMPK gamma(3 gene (PRKAG3 in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The gamma(3 R225W mutation is homologous in location to the gamma(2R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the gamma(3R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN- pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a approximately 90% increase of skeletal muscle glycogen content and a approximately 30% decrease in intramuscular triglyceride (IMTG. CONCLUSIONS: We have identified for the first time a mutation in the skeletal muscle-specific regulatory gamma(3 subunit of AMPK in humans. The gamma(3R225W mutation has significant functional effects as demonstrated by increases in basal and AMP

  20. Chronic hypoxia increases arterial blood pressure and reduces adenosine and ATP induced vasodilatation in skeletal muscle in healthy humans

    DEFF Research Database (Denmark)

    Calbet, J A L; Boushel, Robert Christopher; Robach, P

    2014-01-01

    into the femoral artery at sea level and then after 8-12 days of residence at 4559 m above sea level. At sea level, the infusions were carried out while the subjects breathed room air, acute hypoxia (FI O2 = 0.11) and hyperoxia (FI O2 = 1); and at altitude (FI O2 = 0.21 and 1). Skeletal muscle P2Y2 receptor...... protein expression was determined in muscle biopsies after 4 weeks at 3454 m by Western blot. RESULTS: At altitude, mean arterial blood pressure was 13% higher (91 ± 2 vs. 102 ± 3 mmHg, P sea level and was unaltered by hyperoxic breathing. Baseline leg vascular conductance was 25% lower...... at altitude than at sea level (P sea level by 24 and 38%, during the low and high ATP doses...

  1. Skeletal imaging composition

    International Nuclear Information System (INIS)

    Vanduzee, B.F.; Degenhardt, C.R.

    1983-01-01

    This invention is based on the discovery that the adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate-containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This increased performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent. The process for producing a dry-powder imaging kit comprises the steps of: preparing a solution of a diphosphonate carrier, stannous reductant, and a stabilizer in water; adjusting the pH to between 5.5 and 6.5; and lyophilizing the solution

  2. Caracterização individual do veneno de Bothrops alternatus Duméril, Bibron & Duméril em função da distribuição geográfica no Brasil (Serpentes,Viperidae Individual characterization of Bothrops alternatus Duméril, Bibron & Duméril venoms, according to their geographic distribution in Brazil (Serpentes, Viperidae

    Directory of Open Access Journals (Sweden)

    Marisa M. T. da Rocha

    2005-06-01

    Full Text Available Bothrops alternatus Duméril, Bibron & Duméril, 1854 é uma serpente de importância em saúde pública, com ampla distribuição geográfica, desde o Mato Grosso do Sul até o sudeste do Brasil, chegando até a Argentina e Uruguai, ocupando vários domínios morfoclimáticos. Neste trabalho investigou-se a variação do veneno de adultos de Bothrops alternatus, em função de sua distribuição geográfica no Brasil, comparativamente ao veneno elaborado sob a forma de "pool" desta espécie (veneno referência, que inclui serpentes, em sua maioria, da região do estado de São Paulo. Foram analisadas as atividades letal, coagulante sobre o plasma, proteolítica sobre a caseína e miotóxica, bem como os padrões eletroforéticos de 61 amostras individuais de veneno contrapostas ao "pool". Os resultados mostraram que o veneno de B. alternatus é pouco ativo, comparativamente ao de outros Bothrops Wagler, 1824. A variação individual prevaleceu, não apresentando correlação com as áreas de distribuição geográfica e domínios morfoclimáticos, porém a atividade coagulante das amostras de veneno provenientes do nordeste da distribuição geográfica apresentaram-se menos ativas comparativamente às da porção central da distribuição. Os venenos provenientes das bordas da distribuição apresentaram ações proteolíticas e miotóxicas mais intensas, que estatisticamente não foram significativamente diferentes. As variações individuais prevaleceram.Bothrops alternatus Duméril, Bibron & Duméril, 1854 snakebites are an important public health problem in Brazil. Such snakes are found from Mato Grosso do Sul (central Brazil to southeastern Brazil, reaching even Argentina and Uruguay and thereby occupying different morphoclimatic domains. This work investigated venom variation occurring in adult specimens of B. alternatus specimens, according to their geographic distribution in Brazil. The standard venom pool (reference venom produced by

  3. Effect of Increased Cyclic AMP Concentration on Muscle Protein Synthesis and Beta-Adrenergic Receptor Expression in Chicken Skeletal Muscle Cells in Culture

    Science.gov (United States)

    Young, R. B.; Vaughn, J. R.; Bridge, K. Y.; Smith, C. K.

    1998-01-01

    Analogies of epinephrine are known to cause hypertrophy of skeletal muscle when fed to animals. These compounds presumably exert their physiological action through interaction with the P-adrenergic receptor. Since the intracellular signal generated by the Beta-adrenergic receptor is cyclic AMP (cAMP), experiments were initiated in cell culture to determine if artificial elevation of cAMP by treatment with forskolin would alter muscle protein metabolism and P-adrenergic receptor expression. Chicken skeletal muscle cells after 7 days in culture were treated with 0.2-30 micrometers forskolin for a total of three days. At the end of the treatment period, both the concentration of cAMP and the quantity of myosin heavy chain (MHC) were measured. Concentration of cAMP in forskolin-treated cells increased up to 10-fold in a dose dependent manner. In contrast, the quantity of MHC was increased approximately 50% above control cells at 0.2 micrometers forskolin, but exhibited a gradual decline at higher levels of forskolin so that the quantity of MHC in cells treated with 30 micrometers forskolin was not significantly different from controls. Curiously, the intracellular concentration of cAMP which elicited the maximum increase in the quantity of MHC was only 40% higher than cAMP concentration in control cells.

  4. Passive Repetitive Stretching for a Short Duration within a Week Increases Myogenic Regulatory Factors and Myosin Heavy Chain mRNA in Rats' Skeletal Muscles

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    Yurie Kamikawa

    2013-01-01

    Full Text Available Stretching is a stimulation of muscle growth. Stretching for hours or days has an effect on muscle hypertrophy. However, differences of continuous stretching and repetitive stretching to affect muscle growth are not well known. To clarify the difference of continuous and repetitive stretching within a short duration, we investigated the gene expression of muscle-related genes on stretched skeletal muscles. We used 8-week-old male Wistar rats ( for this study. Animals medial gastrocnemius muscle was stretched continuously or repetitively for 15 min daily and 4 times/week under anesthesia. After stretching, muscles were removed and total RNA was extracted. Then, reverse transcriptional quantitative real-time PCR was done to evaluate the mRNA expression of MyoD, myogenin, and embryonic myosin heavy chain (MyHC. Muscles, either stretched continuously or repetitively, increased mRNA expression of MyoD, myogenin, and embryonic MyHC more than unstretched muscles. Notably, repetitive stretching resulted in more substantial effects on embryonic MyHC gene expression than continuous stretching. In conclusion, passive stretching for a short duration within a week is effective in increasing myogenic factor expression, and repetitive stretching had more effects than continuous stretching for skeletal muscle on muscle growth. These findings are applicable in clinical muscle-strengthening therapy.

  5. Passive repetitive stretching for a short duration within a week increases myogenic regulatory factors and myosin heavy chain mRNA in rats' skeletal muscles.

    Science.gov (United States)

    Kamikawa, Yurie; Ikeda, Satoshi; Harada, Katsuhiro; Ohwatashi, Akihiko; Yoshida, Akira

    2013-01-01

    Stretching is a stimulation of muscle growth. Stretching for hours or days has an effect on muscle hypertrophy. However, differences of continuous stretching and repetitive stretching to affect muscle growth are not well known. To clarify the difference of continuous and repetitive stretching within a short duration, we investigated the gene expression of muscle-related genes on stretched skeletal muscles. We used 8-week-old male Wistar rats (N = 28) for this study. Animals medial gastrocnemius muscle was stretched continuously or repetitively for 15 min daily and 4 times/week under anesthesia. After stretching, muscles were removed and total RNA was extracted. Then, reverse transcriptional quantitative real-time PCR was done to evaluate the mRNA expression of MyoD, myogenin, and embryonic myosin heavy chain (MyHC). Muscles, either stretched continuously or repetitively, increased mRNA expression of MyoD, myogenin, and embryonic MyHC more than unstretched muscles. Notably, repetitive stretching resulted in more substantial effects on embryonic MyHC gene expression than continuous stretching. In conclusion, passive stretching for a short duration within a week is effective in increasing myogenic factor expression, and repetitive stretching had more effects than continuous stretching for skeletal muscle on muscle growth. These findings are applicable in clinical muscle-strengthening therapy.

  6. [Molecular evaluation on the efficacy of sustainable control of Monochamus alternatus by non-woven fabric fungal bands impregnated with Beauveria bassiana].

    Science.gov (United States)

    Ding, De-Gui; Fan, Mei-Zhen; Meng, Yan-Qiong; Li, Zeng-Zhi; Xia, Cheng-Run

    2007-03-01

    By using molecular marker of group I intron, a field evaluation was made on the efficacy of sustainable control of Monochamus alternatus by non-woven fabric bands impregnated with Beauveria bassiana. The results showed that the control efficacy in two treated plots was 19.5% and 10.8%, and 14.2% and 11% when evaluated with conventional and molecular evaluation methods, respectively, suggesting that the conventional method which evaluated the control efficacy in terms of microbes mortality or infection rate couldn't distinguish the efficacies caused by released biocontrol agents and indigenous pathogens, while molecular method could avoid the interference of indigenous pathogens and give an objective and reasonable evaluation on the efficacy of microbial control.

  7. Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

    International Nuclear Information System (INIS)

    Essman, Stephanie C.; Lewis, Michael R.; Fox, Derek B.

    2008-01-01

    Introduction: Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate ( 153 Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic 153 Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of 153 Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of 153 Sm-EDTMP on growth of long bones. Methods: Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of 153 Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P 153 Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted

  8. Beta-Adrenergic Receptor Population is Up-Regulated by Increased Cyclic Amp Concentration in Chicken Skeletal Muscle Cells in Culture

    Science.gov (United States)

    Young, Ronald B.; Bridge, Kristin Y.; Vaughn, Jeffrey R.

    1999-01-01

    Skeletal muscle hypertrophy is promoted in vivo by administration of beta-drenergic receptor (bAR) agonists. Chicken skeletal muscle cells were treated with 1 (mu)M isoproterenol, a strong bAR agonist, between days 7 and 10 in culture. bAR population increased by approximately 40% during this treatment; however, the ability of the cells to synthesize cyclic AMP (cAMP) was diminished by two-fold. The quantity of myosin heavy chain (MHC) was not affected. To understand further the relationship between intracellular cAMP levels, bAR population, and muscle protein accumulation, intracellular cAMP levels were artificially elevated by treatment with 0-10 uM forskolin for up to three days. The basal concentration of CAMP in forskolin-treated cells increased up to 7-fold in a dose dependent manner. Increasing concentrations of forskolin also led to an increase in bAR population, with a maximum increase of approximately 40-60% at 10 uM forskolin. A maximum increase of 40-50% in the quantity of MHC was observed at 0.2 uM forskolin, but higher concentrations of forskolin reduced the quantity of MHC back to control levels. At 0.2 uM forskolin, intracellular levels of cAMP were higher by approximately 35%, and the (beta)AR population was higher by approximately 30%. Neither the number of muscle nuclei fused into myotubes nor the percentage of nuclei in myotubes were affected by forskolin at any of the concentrations studied.

  9. L-arginine supplementation attenuates capillary regression without increasing integrated succinate dehydrogenase activity and VEGF expression in skeletal muscle during hindlimb unloading.

    Science.gov (United States)

    Uchida, Kensaku; Tanaka, Minoru; Kondo, Hiroyo; Ishihara, Akihiko; Fujino, Hidemi

    2016-10-01

    Decreased capillary number is observed in atrophied muscle. The change in capillary number is regulated by angiogenic factors. L-arginine enhances expression of endothelial nitric oxide synthase (eNOS), angiogenic factor, in skeletal muscle. Therefore, the aim of this study was to evaluate the effects of L-arginine supplementation on capillary regression during hindlimb unloading. Twenty-four male Wistar rats were divided into four treatment groups: (1) control, (2) L-arginine supplementation, (3) hindlimb unloading, and (4) hindlimb unloading with L-arginine supplementation. Hindlimb unloading resulted in a decrease of capillary-to-muscle fibre (C/F) ratio, eNOS expression, and integrated succinate dehydrogenase (SDH) activity. L-arginine supplementation attenuated the decrease in both eNOS expression and C/F ratio, although it did not increase integrated SDH activity in skeletal muscle. These results indicate that L-arginine supplementation is effective for maintaining capillary number in atrophied muscle, and that elevation of eNOS expression may be one mechanism associated with these responses.

  10. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth

    Science.gov (United States)

    Brown, D. M.; Williams, H.; Ryan, K. J. P.; Wilson, T. L.; Daniel, Z. C. T. R.; Mareko, M. H. D.; Emes, R. D.; Harris, D. W.; Jones, S.; Wattis, J. A. D.; Dryden, I. L.; Hodgman, T. C.; Brameld, J. M.; Parr, T.

    2016-01-01

    We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth. PMID:27350173

  11. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth.

    Science.gov (United States)

    Brown, D M; Williams, H; Ryan, K J P; Wilson, T L; Daniel, Z C T R; Mareko, M H D; Emes, R D; Harris, D W; Jones, S; Wattis, J A D; Dryden, I L; Hodgman, T C; Brameld, J M; Parr, T

    2016-06-28

    We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth.

  12. PPARα Protein Expression Was Increased by Four Weeks of Intermittent Hypoxic Training via AMPKα2-Dependent Manner in Mouse Skeletal Muscle.

    Directory of Open Access Journals (Sweden)

    Ge Li

    Full Text Available Peroxisome proliferator-activated receptor α (PPARα is critical for muscle endurance due to its role in the regulation of fatty acid oxidation. The 5'-AMP-activated protein kinase (AMPK is an energy sensor in cells, but its role in PPARα regulation in vivo remains unknown. In this study, we examined PPARα expression in the skeletal muscle of AMPKα2 overexpression (OE, knockout (KO and wild-type (WT mice after four weeks of exercise under intermittent hypoxia. WT, OE and KO mice were used at 40 mice/strain and randomly subdivided into four subgroups: control (C, running (R, hypoxia (H, and running plus hypoxia (R+H at 10 mice/group. The treadmill running was performed at the speed of 12 m/min, 60 min/day with a slope of 0 degree for four weeks. The hypoxia treatment was performed in daytime with normobaric hypoxia (11.20% oxygen, 8 hours/day. In the R+H group, the treadmill running was conducted in the hypoxic condition. AMPKα2, phosphor-AMPKα (p-AMPKα (Thr172, nuclear PPARα proteins were measured by Western blot and the medium chain acyl coenzyme A dehydrogenase (MCAD mRNA, the key enzyme for fatty acid oxidation and one of the PPARα target genes, was also measured in skeletal muscles after the interventions. The results showed that nuclear PPARα protein was significantly increased by R+H in WT muscles, the increase was enhanced by 41% (p<0.01 in OE mice, but was reduced by 33% (p<0.01 in KO mice. The MCAD mRNA expression was increased after four weeks of R+H intervention. The change in MCAD mRNA followed a similar trend as that of PPARα protein in OE and KO mice. Our data suggest that the increase in nuclear PPARα protein by four-week exercise training under the intermittent hypoxia was dependent on AMPK activation.

  13. PPARα Protein Expression Was Increased by Four Weeks of Intermittent Hypoxic Training via AMPKα2-Dependent Manner in Mouse Skeletal Muscle.

    Science.gov (United States)

    Li, Ge; Wang, Jianxiong; Ye, Jianping; Zhang, Yimin; Zhang, Ying

    2015-01-01

    Peroxisome proliferator-activated receptor α (PPARα) is critical for muscle endurance due to its role in the regulation of fatty acid oxidation. The 5'-AMP-activated protein kinase (AMPK) is an energy sensor in cells, but its role in PPARα regulation in vivo remains unknown. In this study, we examined PPARα expression in the skeletal muscle of AMPKα2 overexpression (OE), knockout (KO) and wild-type (WT) mice after four weeks of exercise under intermittent hypoxia. WT, OE and KO mice were used at 40 mice/strain and randomly subdivided into four subgroups: control (C), running (R), hypoxia (H), and running plus hypoxia (R+H) at 10 mice/group. The treadmill running was performed at the speed of 12 m/min, 60 min/day with a slope of 0 degree for four weeks. The hypoxia treatment was performed in daytime with normobaric hypoxia (11.20% oxygen, 8 hours/day). In the R+H group, the treadmill running was conducted in the hypoxic condition. AMPKα2, phosphor-AMPKα (p-AMPKα) (Thr172), nuclear PPARα proteins were measured by Western blot and the medium chain acyl coenzyme A dehydrogenase (MCAD) mRNA, the key enzyme for fatty acid oxidation and one of the PPARα target genes, was also measured in skeletal muscles after the interventions. The results showed that nuclear PPARα protein was significantly increased by R+H in WT muscles, the increase was enhanced by 41% (p<0.01) in OE mice, but was reduced by 33% (p<0.01) in KO mice. The MCAD mRNA expression was increased after four weeks of R+H intervention. The change in MCAD mRNA followed a similar trend as that of PPARα protein in OE and KO mice. Our data suggest that the increase in nuclear PPARα protein by four-week exercise training under the intermittent hypoxia was dependent on AMPK activation.

  14. Development of endothermy and concomitant increases in cardiac and skeletal muscle mitochondrial respiration in the precocial Pekin duck (Anas platyrhynchos domestica).

    Science.gov (United States)

    Sirsat, Sarah K G; Sirsat, Tushar S; Faber, Alan; Duquaine, Allison; Winnick, Sarah; Sotherland, Paul R; Dzialowski, Edward M

    2016-04-15

    Attaining endothermic homeothermy occurs at different times post-hatching in birds and is associated with maturation of metabolic and aerobic capacity. Simultaneous measurements at the organism, organ and cellular levels during the transition to endothermy reveal means by which this change in phenotype occurs. We examined development of endothermy in precocial Pekin ducks ( ITALIC! Anas platyrhynchos domestica) by measuring whole-animal O2consumption ( ITALIC! V̇O2 ) as animals cooled from 35 to 15°C. We measured heart ventricle mass, an indicator of O2delivery capacity, and mitochondrial respiration in permeabilized skeletal and cardiac muscle to elucidate associated changes in mitochondrial capacities at the cellular level. We examined animals on day 24 of incubation through 7 days post-hatching. ITALIC! V̇O2  of embryos decreased when cooling from 35 to 15°C; ITALIC! V̇O2  of hatchlings, beginning on day 0 post-hatching, increased during cooling with a lower critical temperature of 32°C. Yolk-free body mass did not change between internal pipping and hatching, but the heart and thigh skeletal muscle grew at faster rates than the rest of the body as the animals transitioned from an externally pipped paranate to a hatchling. Large changes in oxidative phosphorylation capacity occurred during ontogeny in both thigh muscles, the primary site of shivering, and cardiac ventricles. Thus, increased metabolic capacity necessary to attain endothermy was associated with augmented metabolic capacity of the tissue and augmented increasing O2delivery capacity, both of which were attained rapidly at hatching. © 2016. Published by The Company of Biologists Ltd.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. A mechanism accounting for independence on starting length of tension increase in ramp stretches of active skeletal muscle at short half-sarcomere lengths.

    Science.gov (United States)

    Till, Olaf; Siebert, Tobias; Blickhan, Reinhard

    2010-09-07

    Based on previous experimental results of independence on starting length of the tension gradient in constant-velocity stretches of active skeletal muscle at muscle lengths including the ascending limb and the plateau of the tension-length relation, a possible physiological mechanism determining the tension increase in lengthening active muscle is discussed. Considering the sliding filament theory, it is suggested that the tension-length relation of a half-sarcomere in lengthening contractions is different from that in isometric contractions. The assumed mechanism predicts, among others, that the thick filament retains its shortened length in lengthening contractions starting from a half-sarcomere length where this filament is compressed. An example model is implemented and checked with simulations. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Coordinated increase in skeletal muscle fiber area and expression of IGF-I with resistance exercise in elderly post-operative patients

    DEFF Research Database (Denmark)

    Suetta, Charlotte; Clemmensen, Christoffer; Andersen, Jesper L

    2010-01-01

    Hypertrophy of developing skeletal muscle involves stimulation by insulin-like growth factor-I (IGF-I), however, the role of IGF-I in adult muscle is less clarified. In the present study, the mRNA splice variants of IGF-I (IGF-IEa and MGF) and the changes in muscle fiber cross sectional area after...... and in addition induces marked increases in the expression of IGF-I splice variants, supporting the idea that IGF-I is involved in regulating muscle hypertrophy.......-operated-side served as a within subject control. Muscle biopsies were obtained from the vastus lateralis of both limbs at +2d post-operative (baseline), at 5weeks and 12weeks post-surgery to analyze for changes in type 1 and type 2 muscle fiber area. Changes in expression levels of IGF-I mRNA isoforms were determined...

  18. Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1, and enhances skeletal muscle force in aging sedentary mice.

    Science.gov (United States)

    Zhang, Tan; Pereyra, Andrea S; Wang, Zhong-Min; Birbrair, Alexander; Reisz, Julie A; Files, Daniel Clark; Purcell, Lina; Feng, Xin; Messi, Maria L; Feng, Hanzhong; Chalovich, Joseph; Jin, Jian-Ping; Furdui, Cristina; Delbono, Osvaldo

    2016-06-01

    Loss of strength in human and animal models of aging can be partially attributed to a well-recognized decrease in muscle mass; however, starting at middle-age, the normalized force (force/muscle cross-sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca(2+) channel α1 subunit (Cav1.1) with aging leads to excitation-contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function. We recently reported that in addition to its classical cytoplasmic location, fast skeletal muscle troponin T3 (TnT3) is fragmented in aging mice, and both full-length TnT3 (FL-TnT3) and its carboxyl-terminal (CT-TnT3) fragment shuttle to the nucleus. Here, we demonstrate that it regulates transcription of Cacna1s, the gene encoding Cav1.1. Knocking down TnT3 in vivo downregulated Cav1.1. TnT3 downregulation or overexpression decreased or increased, respectively, Cacna1s promoter activity, and the effect was ablated by truncating the TnT3 nuclear localization sequence. Further, we mapped the Cacna1s promoter region and established the consensus sequence for TnT3 binding to Cacna1s promoter. Systemic administration of BDA-410, a specific calpain inhibitor, prevented TnT3 fragmentation, and Cacna1s and Cav1.1 downregulation and improved muscle force generation in sedentary old mice. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy

    Science.gov (United States)

    Pinniger, Gavin J.; Graves, Jamie A.; Grounds, Miranda D.; Arthur, Peter G.

    2016-01-01

    Key points Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis.Cysteine precursor antioxidants such as N‐acetyl cysteine (NAC) and l‐2‐oxothiazolidine‐4‐carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine.We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress.Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug.These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Abstract Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l‐2‐oxothiazolidine‐4‐carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx

  20. Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Terrill, Jessica R; Pinniger, Gavin J; Graves, Jamie A; Grounds, Miranda D; Arthur, Peter G

    2016-06-01

    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease associated with increased inflammation, oxidative stress and myofibre necrosis. Cysteine precursor antioxidants such as N-acetyl cysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) reduce dystropathology in the mdx mouse model for DMD, and we propose this is via increased synthesis of the amino acid taurine. We compared the capacity of OTC and taurine treatment to increase taurine content of mdx muscle, as well as effects on in vivo and ex vivo muscle function, inflammation and oxidative stress. Both treatments increased taurine in muscles, and improved many aspects of muscle function and reduced inflammation. Taurine treatment also reduced protein thiol oxidation and was overall more effective, as OTC treatment reduced body and muscle weight, suggesting some adverse effects of this drug. These data suggest that increasing dietary taurine is a better candidate for a therapeutic intervention for DMD. Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease for which there is no widely available cure. Whilst the mechanism of loss of muscle function in DMD and the mdx mouse model are not fully understood, disruptions in intracellular calcium homeostasis, inflammation and oxidative stress are implicated. We have shown that protein thiol oxidation is increased in mdx muscle, and that the indirect thiol antioxidant l-2-oxothiazolidine-4-carboxylate (OTC), which increases cysteine availability, decreases pathology and increases in vivo strength. We propose that the protective effects of OTC are a consequence of conversion of cysteine to taurine, which has itself been shown to be beneficial to mdx pathology. This study compares the efficacy of taurine with OTC in decreasing dystropathology in mdx mice by measuring in vivo and ex vivo contractile function and measurements of inflammation and protein thiol oxidation. Increasing the taurine content of mdx muscle improved both in vivo and ex

  1. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes......, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...... chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma...

  2. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training

    DEFF Research Database (Denmark)

    Olsen, Steen Schytte

    2006-01-01

    to strength training (STR) while receiving a timed intake of creatine (STR-CRE) (n= 9), protein (STR-PRO) (n= 8) or placebo (STR-CON) (n= 8), or serving as a non-training control group (CON) (n= 7). Supplementation was given daily (STR-CRE: 6–24 g creatine monohydrate, STR-PRO: 20 g protein, STR-CON: placebo...... number was no longer elevated in STR-CRE, while it remained elevated in STR-PRO and STR-CON. Furthermore, creatine supplementation resulted in an increased number of myonuclei per fibre and increases of 14–17% in MFA at week 4, 8 and 16 (P ... in the later (16 week, +8%) and STR-CON only in the early (week 4, +14%) phases of training, respectively (P CRE a positive relationship was found between the percentage increases in MFA and myonuclei from baseline to week 16, respectively (r= 0.67, P

  3. Performance of repetitive tasks induces decreased grip strength and increased fibrogenic proteins in skeletal muscle: role of force and inflammation.

    Directory of Open Access Journals (Sweden)

    Samir M Abdelmagid

    Full Text Available This study elucidates exposure-response relationships between performance of repetitive tasks, grip strength declines, and fibrogenic-related protein changes in muscles, and their link to inflammation. Specifically, we examined forearm flexor digitorum muscles for changes in connective tissue growth factor (CTGF; a matrix protein associated with fibrosis, collagen type I (Col1; a matrix component, and transforming growth factor beta 1 (TGFB1; an upstream modulator of CTGF and collagen, in rats performing one of two repetitive tasks, with or without anti-inflammatory drugs.To examine the roles of force versus repetition, rats performed either a high repetition negligible force food retrieval task (HRNF, or a high repetition high force handle-pulling task (HRHF, for up to 9 weeks, with results compared to trained only (TR-NF or TR-HF and normal control rats. Grip strength declined with both tasks, with the greatest declines in 9-week HRHF rats. Quantitative PCR (qPCR analyses of HRNF muscles showed increased expression of Col1 in weeks 3-9, and CTGF in weeks 6 and 9. Immunohistochemistry confirmed PCR results, and also showed greater increases of CTGF and collagen matrix in 9-week HRHF rats than 9-week HRNF rats. ELISA, and immunohistochemistry revealed greater increases of TGFB1 in TR-HF and 6-week HRHF, compared to 6-week HRNF rats. To examine the role of inflammation, results from 6-week HRHF rats were compared to rats receiving ibuprofen or anti-TNF-α treatment in HRHF weeks 4-6. Both treatments attenuated HRHF-induced increases in CTGF and fibrosis by 6 weeks of task performance. Ibuprofen attenuated TGFB1 increases and grip strength declines, matching our prior results with anti-TNFα.Performance of highly repetitive tasks was associated with force-dependent declines in grip strength and increased fibrogenic-related proteins in flexor digitorum muscles. These changes were attenuated, at least short-term, by anti-inflammatory treatments.

  4. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Cação-Benedini, L.O.; Ribeiro, P.G. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Prado, C.M.; Chesca, D.L. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattiello-Sverzut, A.C. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  5. Increased skeletal muscle 11βHSD1 mRNA is associated with lower muscle strength in ageing.

    Directory of Open Access Journals (Sweden)

    Alixe H M Kilgour

    Full Text Available Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR signaling by increased expression of either GR or the GC-amplifying enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1 in muscle.There were 82 participants; group 1 comprised 33 older men (mean age 70.2 years, SD 4.4 and 19 younger men (22.2 years, 1.7 and group 2 comprised 16 older men (79.1 years, 3.4 and 14 older women (80.1 years, 3.7. We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size.Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity. Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04, but GR mRNA levels were not significantly associated with muscle strength or size.Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia.

  6. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    Directory of Open Access Journals (Sweden)

    L.O. Cação-Benedini

    2014-06-01

    Full Text Available Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68 and Western blot analysis (dystrophin/laminin. Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days, an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  7. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle.

    Science.gov (United States)

    Cação-Benedini, L O; Ribeiro, P G; Prado, C M; Chesca, D L; Mattiello-Sverzut, A C

    2014-06-01

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  8. Activation of Wnt/beta-catenin signaling increases insulin sensitivity through a reciprocal regulation of Wnt10b and SREBP-1c in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Mounira Abiola

    2009-12-01

    Full Text Available Intramyocellular lipid accumulation is strongly related to insulin resistance in humans, and we have shown that high glucose concentration induced de novo lipogenesis and insulin resistance in murin muscle cells. Alterations in Wnt signaling impact the balance between myogenic and adipogenic programs in myoblasts, partly due to the decrease of Wnt10b protein. As recent studies point towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, we hypothesized that activation of Wnt signaling could play a crucial role in muscle insulin sensitivity.Here we demonstrate that SREBP-1c and Wnt10b display inverse expression patterns during muscle ontogenesis and regeneration, as well as during satellite cells differentiation. The Wnt/beta-catenin pathway was reactivated in contracting myotubes using siRNA mediated SREBP-1 knockdown, Wnt10b over-expression or inhibition of GSK-3beta, whereas Wnt signaling was inhibited in myoblasts through silencing of Wnt10b. SREBP-1 knockdown was sufficient to induce Wnt10b protein expression in contracting myotubes and to activate the Wnt/beta-catenin pathway. Conversely, silencing Wnt10b in myoblasts induced SREBP-1c protein expression, suggesting a reciprocal regulation. Stimulation of the Wnt/beta-catenin pathway i drastically decreased SREBP-1c protein and intramyocellular lipid deposition in myotubes; ii increased basal glucose transport in both insulin-sensitive and insulin-resistant myotubes through a differential activation of Akt and AMPK pathways; iii restored insulin sensitivity in insulin-resistant myotubes.We conclude that activation of Wnt/beta-catenin signaling in skeletal muscle cells improved insulin sensitivity by i decreasing intramyocellular lipid deposition through downregulation of SREBP-1c; ii increasing insulin effects through a differential activation of the Akt/PKB and AMPK pathways; iii inhibiting the MAPK pathway. A crosstalk between these pathways and Wnt/beta-catenin signaling

  9. Ames dwarf (Prop1(df)/Prop1(df)) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle.

    Science.gov (United States)

    Miquet, Johanna G; Muñoz, Marina C; Giani, Jorge F; González, Lorena; Dominici, Fernando P; Bartke, Andrzej; Turyn, Daniel; Sotelo, Ana I

    2010-04-01

    Growth hormone (GH) is an anabolic hormone that regulates growth and metabolism. Ames dwarf mice are natural mutants for Prop1, with impaired development of anterior pituitary and undetectable levels of circulating GH, prolactin and TSH. They constitute an endocrine model of life-long GH-deficiency. The main signaling cascades activated by GH binding to its receptor are the JAK2/STATs, PI-3K/Akt and the MAPK Erk1/2 pathways. We have previously reported that GH-induced STAT5 activation was higher in Ames dwarf mice liver compared to non-dwarf controls. The aim of this study was to evaluate the principal components of the main GH-signaling pathways under GH-deficiency in liver and skeletal muscle, another GH-target tissue. Ames dwarf mice and their non-dwarf siblings were assessed. Animals were injected i.p. with GH or saline 15min before tissue removal. Protein content and phosphorylation of signaling mediators were determined by immunoblotting of tissue solubilizates. GH was able to induce STAT5 and STAT3 tyrosine phosphorylation in both liver and muscle, but the response was higher for Ames dwarf mice than for non-dwarf controls. When Erk1/2 activation was assessed in liver, only dwarf mice showed GH-induced phosphorylation, while in muscle no response to the hormone was found in either genotype. GH-induced Akt phosphorylation at Ser473 in liver was only detected in dwarf mice. In skeletal muscle, both normal and dwarf mice responded to a GH stimulus, although dwarf mice presented higher GH activation levels. The phosphorylation of GSK-3, a substrate of Akt, increased upon hormone stimulation only in dwarf mice in both tissues. In contrast, no differences in the phosphorylation of mTOR, another substrate of Akt, were observed after GH stimulus, either in normal or dwarf mice in liver, while we were unable to determine mTOR in muscle. Protein content of GH-receptor and of the signaling mediators studied did not vary between normal and dwarf animals in the assessed

  10. Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to those caused by palmitate treatment.

    Science.gov (United States)

    Frangioudakis, Georgia; Diakanastasis, Barbara; Liao, Bing-Qing M; Saville, Jennifer T; Hoffman, Nolan J; Mitchell, Todd W; Schmitz-Peiffer, Carsten

    2013-12-01

    An accumulation of ceramides has been implicated in the generation of insulin resistance in skeletal muscle upon an oversupply of fatty acid. Different ceramide species are generated through the actions of ceramide synthases (CerSs), which incorporate specific acyl side chains. We tested whether particular CerS isoforms promoted insulin resistance through the generation of more inhibitory ceramide species, thus representing potential targets for intervention. CerS isoforms CerS1, CerS2, CerS4, CerS5 and CerS6 were overexpressed in L6 myotubes using adenovirus, and cells were treated with palmitate and stimulated with insulin. Alternatively, CerS isoforms were knocked down using siRNAs. Sphingolipids were examined by mass spectrometry and tracer incorporation. Phosphorylation of IRS1 and Akt was measured by immunoblotting, while glucose disposal was assessed by measuring GLUT4 translocation and the incorporation of [(14)C]glucose into glycogen. Palmitate treatment increased the levels of several ceramides but reduced the levels of sphingomyelins, while insulin had no effect. The fatty acid also inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis. Overexpression of CerS isoforms increased specific ceramides. Unexpectedly, the overexpression of CerS1 and CerS6 promoted insulin action, while no isoform had inhibitory effects. CerS6 knockdown had effects reciprocal to those of CerS6 overexpression. Palmitate may increase intracellular ceramide levels through sphingomyelin hydrolysis as well as de novo synthesis, but no particular species were implicated in the generation of insulin resistance. The modulation of ceramides through an alteration of CerS expression does not affect the action of insulin in the same way as ceramide generation by palmitate treatment. Conversely, certain isoforms promote insulin action, indicating the importance of ceramides in cell function.

  11. 3-O-Acyl-epicatechins Increase Glucose Uptake Activity and GLUT4 Translocation through Activation of PI3K Signaling in Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Manabu Ueda-Wakagi

    2015-07-01

    Full Text Available Tea catechins promote glucose uptake in skeletal muscle cells. In this study, we investigated whether the addition of an acyl group to the C-3 position of catechins to generate 3-O-acyl-catechins promoted glucose uptake in L6 myotubes. 3-O-Myristoyl-(−-epicatechin (EC-C14 and 3-O-palmitoyl-(−-epicatechin (EC-C16 promoted glucose uptake and translocation of glucose transporter (GLUT 4 in the cells. The effect of 3-O-acyl-(−-epicatechins was stronger than that of (−-epicatechin (EC, whereas neither 3-O-myristoyl-(+-catechin (C-C14 nor 3-O-palmitoyl-(+catechin (C-C16 promoted glucose uptake or GLUT4 translocation as well as (+-catechin (C. We further investigated an affinity of catechins and 3-O-acyl-catechins to the lipid bilayer membrane by using surface plasma resonance analysis. Maximum binding amounts of EC-C16 and C-C16 to the lipid bilayer clearly increased compared with that of (−-EC and (+-C, respectively. We also examined the mechanism of GLUT4 translocation and found EC-C14 and EC-C16 induced the phosphorylation of PI3K, but did not affect phosphorylation of Akt or IR. In conclusion, the addition of an acyl group to the C-3 position of (−-EC increases its affinity for the lipid bilayer membrane and promotes GLUT4 translocation through PI3K-dependent pathways in L6 myotubes.

  12. Absence of insulin signalling in skeletal muscle is associated with reduced muscle mass and function: evidence for decreased protein synthesis and not increased degradation.

    Science.gov (United States)

    O'Neill, Elaine D; Wilding, John P H; Kahn, C Ronald; Van Remmen, Holly; McArdle, Anne; Jackson, Malcolm J; Close, Graeme L

    2010-06-01

    Loss of skeletal muscle mass and function is observed in many insulin-resistant disease states such as diabetes, cancer cachexia, renal failure and ageing although the mechanisms for this remain unclear. We hypothesised that impaired insulin signalling results in reduced muscle mass and function and that this decrease in muscle mass and function is due to both increased production of atrogenes and aberrant reactive oxygen species (ROS) generation. Maximum tetanic force of the extensor digitorum longus of muscle insulin receptor knockout (MIRKO) and lox/lox control mice was measured in situ. Muscles were removed for the measurement of mass, histological examination and ROS production. Activation of insulin signalling pathways, markers of muscle atrophy and indices of protein synthesis were determined in a separate group of MIRKO and lox/lox mice 15 min following treatment with insulin. Muscles from MIRKO mice had 36% lower maximum tetanic force generation compared with muscles of lox/lox mice. Muscle fibres of MIRKO mice were significantly smaller than those of lox/lox mice with no apparent structural abnormalities. Muscles from MIRKO mice demonstrated absent phosphorylation of AKT in response to exogenous insulin along with a failure to phosphorylate ribosomal S6 compared with lox/lox mice. Atrogin-1 and MuRF1 relative mRNA expression in muscles from MIRKO mice were decreased compared with muscles from lox/lox mice following insulin treatment. There were no differences in markers of reactive oxygen species damage between muscles from MIRKO mice and lox/lox mice. These data support the hypothesis that the absence of insulin signalling contributes to reduced muscle mass and function though decreased protein synthesis rather than proteasomal atrophic pathways.

  13. Sodium bicarbonate ingestion augments the increase in PGC-1α mRNA expression during recovery from intense interval exercise in human skeletal muscle.

    Science.gov (United States)

    Percival, Michael E; Martin, Brian J; Gillen, Jenna B; Skelly, Lauren E; MacInnis, Martin J; Green, Alex E; Tarnopolsky, Mark A; Gibala, Martin J

    2015-12-01

    We tested the hypothesis that ingestion of sodium bicarbonate (NaHCO3) prior to an acute session of high-intensity interval training (HIIT) would augment signaling cascades and gene expression linked to mitochondrial biogenesis in human skeletal muscle. On two occasions separated by ∼1 wk, nine men (mean ± SD: age 22 ± 2 yr, weight 78 ± 13 kg, V̇O(2 peak) 48 ± 8 ml·kg(-1)·min(-1)) performed 10 × 60-s cycling efforts at an intensity eliciting ∼90% of maximal heart rate (263 ± 40 W), interspersed with 60 s of recovery. In a double-blind, crossover manner, subjects ingested a total of 0.4 g/kg body weight NaHCO3 before exercise (BICARB) or an equimolar amount of a placebo, sodium chloride (PLAC). Venous blood bicarbonate and pH were elevated at all time points after ingestion (P 0.05). However, the increase in PGC-1α mRNA expression after 3 h of recovery was higher in BICARB vs. PLAC (approximately sevenfold vs. fivefold compared with rest, P < 0.05). We conclude that NaHCO3 before HIIT alters the mRNA expression of this key regulatory protein associated with mitochondrial biogenesis. The elevated PGC-1α mRNA response provides a putative mechanism to explain the enhanced mitochondrial adaptation observed after chronic HIIT supplemented with NaHCO3 in rats. Copyright © 2015 the American Physiological Society.

  14. Food restriction increase the expression of mTORC1 complex genes in the skeletal muscle of juvenile pacu (Piaractus mesopotamicus)

    Science.gov (United States)

    de Paula, Tassiana Gutierrez; Zanella, Bruna Tereza Thomazini; Fantinatti, Bruno Evaristo de Almeida; de Moraes, Leonardo Nazário; Duran, Bruno Oliveira da Silva; de Oliveira, Caroline Bredariol; Salomão, Rondinelle Artur Simões; da Silva, Rafaela Nunes; Padovani, Carlos Roberto; dos Santos, Vander Bruno; Mareco, Edson Assunção; Carvalho, Robson Francisco; Dal-Pai-Silva, Maeli

    2017-01-01

    Skeletal muscle is capable of phenotypic adaptation to environmental factors, such as nutrient availability, by altering the balance between muscle catabolism and anabolism that in turn coordinates muscle growth. Small noncoding RNAs, known as microRNAs (miRNAs), repress the expression of target mRNAs, and many studies have demonstrated that miRNAs regulate the mRNAs of catabolic and anabolic genes. We evaluated muscle morphology, gene expression of components involved in catabolism, anabolism and energetic metabolism and miRNAs expression in both the fast and slow muscle of juvenile pacu (Piaractus mesopotamicus) during food restriction and refeeding. Our analysis revealed that short periods of food restriction followed by refeeding predominantly affected fast muscle, with changes in muscle fiber diameter and miRNAs expression. There was an increase in the mRNA levels of catabolic pathways components (FBXO25, ATG12, BCL2) and energetic metabolism-related genes (PGC1α and SDHA), together with a decrease in PPARβ/δ mRNA levels. Interestingly, an increase in mRNA levels of anabolic genes (PI3K and mTORC1 complex: mTOR, mLST8 and RAPTOR) was also observed during food restriction. After refeeding, muscle morphology showed similar patterns of the control group; the majority of genes were slightly up- or down-regulated in fast and slow muscle, respectively; the levels of all miRNAs increased in fast muscle and some of them decreased in slow muscle. Our findings demonstrated that a short period of food restriction in juvenile pacu had a considerable impact on fast muscle, increasing the expression of anabolic (PI3K and mTORC1 complex: mTOR, mLST8 and RAPTOR) and energetic metabolism genes. The miRNAs (miR-1, miR-206, miR-199 and miR-23a) were more expressed during refeeding and while their target genes (IGF-1, mTOR, PGC1α and MAFbx), presented a decreased expression. The alterations in mTORC1 complex observed during fasting may have influenced the rates of protein

  15. Food restriction increase the expression of mTORC1 complex genes in the skeletal muscle of juvenile pacu (Piaractus mesopotamicus.

    Directory of Open Access Journals (Sweden)

    Tassiana Gutierrez de Paula

    Full Text Available Skeletal muscle is capable of phenotypic adaptation to environmental factors, such as nutrient availability, by altering the balance between muscle catabolism and anabolism that in turn coordinates muscle growth. Small noncoding RNAs, known as microRNAs (miRNAs, repress the expression of target mRNAs, and many studies have demonstrated that miRNAs regulate the mRNAs of catabolic and anabolic genes. We evaluated muscle morphology, gene expression of components involved in catabolism, anabolism and energetic metabolism and miRNAs expression in both the fast and slow muscle of juvenile pacu (Piaractus mesopotamicus during food restriction and refeeding. Our analysis revealed that short periods of food restriction followed by refeeding predominantly affected fast muscle, with changes in muscle fiber diameter and miRNAs expression. There was an increase in the mRNA levels of catabolic pathways components (FBXO25, ATG12, BCL2 and energetic metabolism-related genes (PGC1α and SDHA, together with a decrease in PPARβ/δ mRNA levels. Interestingly, an increase in mRNA levels of anabolic genes (PI3K and mTORC1 complex: mTOR, mLST8 and RAPTOR was also observed during food restriction. After refeeding, muscle morphology showed similar patterns of the control group; the majority of genes were slightly up- or down-regulated in fast and slow muscle, respectively; the levels of all miRNAs increased in fast muscle and some of them decreased in slow muscle. Our findings demonstrated that a short period of food restriction in juvenile pacu had a considerable impact on fast muscle, increasing the expression of anabolic (PI3K and mTORC1 complex: mTOR, mLST8 and RAPTOR and energetic metabolism genes. The miRNAs (miR-1, miR-206, miR-199 and miR-23a were more expressed during refeeding and while their target genes (IGF-1, mTOR, PGC1α and MAFbx, presented a decreased expression. The alterations in mTORC1 complex observed during fasting may have influenced the rates of

  16. Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates a2ß1 integrin-mediated cell adhesion, migration and proliferation

    Directory of Open Access Journals (Sweden)

    Selistre-de-Araujo H.S.

    2005-01-01

    Full Text Available The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C, a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of ~10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.

  17. Skeletal muscle performance and ageing.

    Science.gov (United States)

    Tieland, Michael; Trouwborst, Inez; Clark, Brian C

    2018-02-01

    The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co-morbidity, and premature death. An important cause of physical limitations is the age-related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation-contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  18. Improvements in exercise performance with high-intensity interval training coincide with an increase in skeletal muscle mitochondrial content and function

    DEFF Research Database (Denmark)

    Jacobs, Robert Acton; Flueck, Daniela; Bonne, Thomas Christian

    2013-01-01

    Six sessions of high-intensity interval training (HIT) are sufficient to improve exercise capacity. The mechanisms explaining such improvements are unclear. Accordingly, the aim of this study was to perform a comprehensive evaluation of physiologically relevant adaptations occurring after six...... sessions of HIT to determine the mechanisms explaining improvements in exercise performance. Sixteen untrained (43 +/- 6 ml.kg(-1).min(-1)) subjects completed six sessions of repeated (8-12) 60 s intervals of high-intensity cycling (100% peak power output elicited during incremental maximal exercise test......) intermixed with 75 s of recovery cycling at a low intensity (30 W) over a 2-wk period. Potential training-induced alterations in skeletal muscle respiratory capacity, mitochondrial content, skeletal muscle oxygenation, cardiac capacity, blood volumes, and peripheral fatigue resistance were all assessed prior...

  19. Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats.

    Science.gov (United States)

    Sharma, Naveen; Arias, Edward B; Bhat, Abhijit D; Sequea, Donel A; Ho, Steve; Croff, Kelsey K; Sajan, Mini P; Farese, Robert V; Cartee, Gregory D

    2011-06-01

    Calorie restriction [CR; ~65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-mo-old male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[(3)H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr(308) and Ser(473)) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle- and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser(588) and Thr(642)) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows: 1) elevated Akt phosphorylation is fundamental, regardless of muscle or insulin dose; 2) altered Akt binding to regulatory proteins (HSP90 and unidentified Akt partners) is involved in the effects of CR on Akt phosphorylation; 3) Akt effects on GU depend on muscle- and insulin dose-specific elevation in phosphorylation of Akt substrates, including, but not limited to, AS160; and 4) greater IR phosphorylation and aPKC activity may contribute at higher insulin doses.

  20. Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats

    Science.gov (United States)

    Sharma, Naveen; Arias, Edward B.; Bhat, Abhijit D.; Sequea, Donel A.; Ho, Steve; Croff, Kelsey K.; Sajan, Mini P.; Farese, Robert V.

    2011-01-01

    Calorie restriction [CR; ∼65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-mo-old male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[3H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr308 and Ser473) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle- and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser588 and Thr642) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows: 1) elevated Akt phosphorylation is fundamental, regardless of muscle or insulin dose; 2) altered Akt binding to regulatory proteins (HSP90 and unidentified Akt partners) is involved in the effects of CR on Akt phosphorylation; 3) Akt effects on GU depend on muscle- and insulin dose-specific elevation in phosphorylation of Akt substrates, including, but not limited to, AS160; and 4) greater IR phosphorylation and aPKC activity may contribute at higher insulin doses. PMID:21386065

  1. Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

    Science.gov (United States)

    Gras, F; Brunmair, B; Quarré, L; Szöcs, Z; Waldhäusl, W; Fürnsinn, C

    2007-12-01

    The aim of the study was to gain better insight into the mechanisms responsible for impaired glucose metabolism during late pregnancy. We explored the direct effects of progesterone on glucose metabolism of skeletal muscle. Specimens of skeletal muscle from untreated rats were incubated with progesterone and rates of substrate fluxes through the various pathways of glucose metabolism were analysed. Progesterone dose-dependently reduced the rates of glucose and pyruvate oxidation (insulin-stimulated rates after 5 h of exposure to 1 and 10 mumol/l progesterone: glucose oxidation, -6 +/- 4%, NS, and -39 +/- 4%, p respiration, e.g. by the specific inhibitor rotenone, is known to trigger a compensatory increase in glucose transport, but this response was blunted in the case of progesterone (change of glucose transport in response to 10 mumol/l progesterone vs 60 nmol/l rotenone, both causing a reduction in glucose oxidation by -39%: progesterone, +14 +/- 8% vs rotenone, +84 +/- 23%, p respiration and at the same time suppresses a compensatory increase in glucose transport, causing cellular carbohydrate deficiency in isolated rat skeletal muscle. This effect is mediated by a direct, rapid and non-genomic mechanism and could contribute to pregnancy-associated changes in glucose homeostasis.

  2. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  3. Role of microRNAs in skeletal muscle hypertrophy

    OpenAIRE

    Hitachi, Keisuke; Tsuchida, Kunihiro

    2014-01-01

    Skeletal muscle comprises approximately 40% of body weight, and is important for locomotion, as well as for metabolic homeostasis. Adult skeletal muscle mass is maintained by a fine balance between muscle protein synthesis and degradation. In response to cytokines, nutrients, and mechanical stimuli, skeletal muscle mass is increased (hypertrophy), whereas skeletal muscle mass is decreased (atrophy) in a variety of conditions, including cancer cachexia, starvation, immobilization, aging, and n...

  4. Skeletal muscle sodium channelopathies.

    Science.gov (United States)

    Nicole, Sophie; Fontaine, Bertrand

    2015-10-01

    This is an update on skeletal muscle sodium channelopathies since knowledge in the field have dramatically increased in the past years. The relationship between two phenotypes and SCN4A has been confirmed with additional cases that remain extremely rare: severe neonatal episodic laryngospasm mimicking encephalopathy, which should be actively searched for since patients respond well to sodium channel blockers; congenital myasthenic syndromes, which have the particularity to be the first recessive Nav1.4 channelopathy. Deep DNA sequencing suggests the contribution of other ion channels in the clinical expressivity of sodium channelopathies, which may be one of the factors modulating the latter. The increased knowledge of channel molecular structure, the quantity of sodium channel blockers, and the availability of preclinical models would permit a most personalized choice of medication for patients suffering from these debilitating neuromuscular diseases. Advances in the understanding of the molecular structure of voltage-gated sodium channels, as well as availability of preclinical models, would lead to improved medical care of patients suffering from skeletal muscle, as well as other sodium channelopathies.

  5. Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase.

    Science.gov (United States)

    Bakke, Siril S; Moro, Cedric; Nikolić, Nataša; Hessvik, Nina P; Badin, Pierre-Marie; Lauvhaug, Line; Fredriksson, Katarina; Hesselink, Matthijs K C; Boekschoten, Mark V; Kersten, Sander; Gaster, Michael; Thoresen, G Hege; Rustan, Arild C

    2012-10-01

    Development of insulin resistance is positively associated with dietary saturated fatty acids and negatively associated with monounsaturated fatty acids. To clarify aspects of this difference we have compared the metabolism of oleic (OA, monounsaturated) and palmitic acids (PA, saturated) in human myotubes. Human myotubes were treated with 100μM OA or PA and the metabolism of [(14)C]-labeled fatty acid was studied. We observed that PA had a lower lipolysis rate than OA, despite a more than two-fold higher protein level of adipose triglyceride lipase after 24h incubation with PA. PA was less incorporated into triacylglycerol and more incorporated into phospholipids after 24h. Supporting this, incubation with compounds modifying lipolysis and reesterification pathways suggested a less influenced PA than OA metabolism. In addition, PA showed a lower accumulation than OA, though PA was oxidized to a relatively higher extent than OA. Gene set enrichment analysis revealed that 24h of PA treatment upregulated lipogenesis and fatty acid β-oxidation and downregulated oxidative phosphorylation compared to OA. The differences in lipid accumulation and lipolysis between OA and PA were eliminated in combination with eicosapentaenoic acid (polyunsaturated fatty acid). In conclusion, this study reveals that the two most abundant fatty acids in our diet are partitioned toward different metabolic pathways in muscle cells, and this may be relevant to understand the link between dietary fat and skeletal muscle insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Signaling pathways controlling skeletal muscle mass

    Science.gov (United States)

    Egerman, Marc A.

    2014-01-01

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

  7. Lyophilized skeletal imaging composition

    International Nuclear Information System (INIS)

    Vanduzee, B.F.

    1983-01-01

    This invention encompasses a process for producing a dry-powder skeletal imaging kit. An aqueous solution of a diphosphonate, a stannous reductant, and, optionally, a stabilizer is prepared. The solution is adjusted to a pH within the range 4.2 to 4.8 and the pH-adjusted solution is then lyophilized. The adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This improved performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent

  8. Small teleost fish provide new insights into human skeletal diseases.

    Science.gov (United States)

    Witten, P E; Harris, M P; Huysseune, A; Winkler, C

    2017-01-01

    Small teleost fish such as zebrafish and medaka are increasingly studied as models for human skeletal diseases. Efficient new genome editing tools combined with advances in the analysis of skeletal phenotypes provide new insights into fundamental processes of skeletal development. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. Several unique features of the skeleton relate to the extremely small size of early fish embryos and the small size of adult fish used as models. A detailed analysis of the plethora of interesting skeletal phenotypes in zebrafish and medaka pushes available skeletal imaging techniques to their respective limits and promotes the development of new imaging techniques. Impressive numbers of zebrafish and medaka mutants with interesting skeletal phenotypes have been characterized, complemented by transgenic zebrafish and medaka lines. The advent of efficient genome editing tools, such as TALEN and CRISPR/Cas9, allows to introduce targeted deficiencies in genes of model teleosts to generate skeletal phenotypes that resemble human skeletal diseases. This review will also discuss other attractive aspects of the teleost skeleton. This includes the capacity for lifelong tooth replacement and for the regeneration of dermal skeletal elements, such as scales and fin rays, which further increases the value of zebrafish and medaka models for skeletal research. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle.

    Science.gov (United States)

    Shang, Fei-Fei; Xia, Qing-Jie; Liu, Wei; Xia, Lei; Qian, Bao-Jiang; You, Ling; He, Mu; Yang, Jin-Liang; Wang, Ting-Hua

    2016-03-11

    Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.

  10. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of m...

  11. Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications.

    Science.gov (United States)

    Burks, Scott R; Ziadloo, Ali; Kim, Saejeong J; Nguyen, Ben A; Frank, Joseph A

    2013-11-01

    Stem cells are promising therapeutics for cardiovascular diseases, and i.v. injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemoattractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (pFUS), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemoattractant expression in pFUS-treated tissue prior to cell infusions. We demonstrate that pFUS is nondestructive to murine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate that local upregulation of chemoattractants in pFUS-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when pFUS treatments and cell infusions were repeated daily. This study demonstrates that pFUS defines transient "molecular zip codes" of elevated chemoattractants in targeted muscle tissue, which effectively provides spatiotemporal control and tunability of the homing process for multiple stem cell types. pFUS is a clinically translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. © AlphaMed Press.

  12. Skeletal muscle mitochondrial H2O2 emission increases with immobilization and decreases after aerobic training in young and older men

    DEFF Research Database (Denmark)

    Gram, Martin; Vigelsø, Andreas; Yokota, Takashi

    2015-01-01

    ZnSOD), catalase and gluthathione peroxidase 1 (GPX1) were measured by Western Blotting. Immobilization decreased ATP generating respiration using PM and increased H2O2 emission using both PM and SR similarly in young and older men. Both were restored to baseline after the training period. Furthermore, Mn......SOD and catalase content increased with endurance training. The young men had a higher leak respiration at inclusion using PM and a higher membrane potential in state 3 using both substrate combinations. Collectively, this study supports the notion that increased mitochondrial ROS mediates the detrimental effects...

  13. [Molecular mechanisms of skeletal muscle hypertrophy].

    Science.gov (United States)

    Astratenkova, I V; Rogozkin, V A

    2014-06-01

    Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

  14. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, S.B.; Madsbad, S.; Høy, Carl-Erik

    2006-01-01

    . Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Results The mean weight loss was 5.1 kg (range -15.3 to +1.3 kg). BMI decreased from 36.5 to 34.9 kg/m(2) (P = 0.003). Saturated FA (SFA) decreased 11% (P = 0.0001). Polyunsaturated FA (PUFA)n-6 increased 4% (P = 0.003). Long......-chain PUFAn-3 increased 51% (P = 0.0001), mainly due to a 75% increase (P SFA (R = 0.58, P ... analysis that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R-2 = 0.33, P

  15. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, S.B.; Madsbad, S.; Høy, Carl-Erik

    2006-01-01

    . Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Results The mean weight loss was 5.1 kg (range -15.3 to +1.3 kg). BMI decreased from 36.5 to 34.9 kg/m(2) (P = 0.003). Saturated FA (SFA) decreased 11% (P = 0.0001). Polyunsaturated FA (PUFA)n-6 increased 4% (P = 0.003). Long......-chain PUFAn-3 increased 51% (P = 0.0001), mainly due to a 75% increase (P HOMA-IR correlated significantly with changes in long-chain PUFAn-3 (R = -0.57, P ... analysis that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R-2 = 0.33, P

  16. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: a randomized study using FDG PET imaging

    DEFF Research Database (Denmark)

    Reichkendler, M. H.; Auerbach, P.; Rosenkilde, M.

    2013-01-01

    Physical exercise increases peripheral insulin sensitivity, but regional differences are poorly elucidated in humans. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions, us...

  17. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    Science.gov (United States)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal muscle weakness can increase the duration of hospitalization, result in exercise limitation, and contribute to a poor quality of life. Importantly, skeletal muscle atrophy is also associated with increased morbidity and mortality of patients. Therefore, improving our understanding of the mechanism(s) responsible for skeletal muscle weakness and fatigue in patients is a required first step to develop clinical protocols to prevent these skeletal muscle problems. This review will highlight the consequences and potential mechanisms responsible for skeletal muscle atrophy and fatigue in patients suffering from acute critical illness, cancer, chronic inflammatory diseases, and neurological disorders. PMID:27128663

  18. Suppression of mTOR Signaling Pathways in Skeletal Muscle of Finishing Pigs by Increasing the Ratios of Ether Extract and Neutral Detergent Fiber at the Expense of Starch in Iso-energetic Diets.

    Science.gov (United States)

    Yu, Changning; Li, Yanjiao; Zhang, Bolin; Lin, Meng; Li, Jiaolong; Zhang, Lin; Wang, Tianjiao; Gao, Feng; Zhou, Guanghong

    2016-02-24

    Three iso-energetic and iso-nitrogenous diets were fed to finishing pigs for 28 days to investigate the mammalian target of rapamycin (mTOR) and ubiquitin-proteasome signaling pathways of skeletal muscle by altering compositions of dietary energy sources. Diet A, diet B, and diet C contained 44.1%, 37.6%, and 30.9% starch; 5.9%, 9.5%, and 14.3% ether extract (EE); and 12.6%, 15.4%, and 17.8% neutral detergent fiber (NDF), respectively. An increase of mRNA expression of MuRF1 (1.09 ± 0.10 vs 1.00 ± 0.08) and MAFbx (1.10 ± 0.06 vs 1.00 ± 0.11) and a decrease of concentrations of plasma insulin (8.2 ± 0.8 vs 10.8 ± 1.2) and glucose (5.76 ± 0.12 vs 6.43 ± 0.33) together with mRNA expression of IRS (0.78 ± 0.19 vs 1.01 ± 0.05) and Akt (0.92 ± 0.01 vs 1.00 ± 0.05) were observed in pigs fed diet C compared with diet A. Protein levels of total and phosphorylated mTOR (0.31 ± 0.04 vs 0.48 ± 0.03 and 0.39 ± 0.01 vs 0.56 ± 0.02), 4EBP1 (0.66 ± 0.06 vs 0.90 ± 0.09 and 0.60 ± 0.12 vs 0.84 ± 0.09), and S6K1 (0.66 ± 0.01 vs 0.89 ± 0.01 and 0.48 ± 0.03 vs 0.79 ± 0.02) were decreased; however, total and phosphorylated AMPK (0.96 ± 0.06 vs 0.64 ± 0.04 and 0.97 ± 0.09 vs 0.61 ± 0.09) were increased in pigs fed diet C compared with diet A. In conclusion, diet C suppressed the mTOR pathway and accelerated the ubiquitin-proteasome pathway in skeletal muscle of finishing pigs.

  19. Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event

    DEFF Research Database (Denmark)

    Laye, Matthew J; Solomon, Thomas; Karstoft, Kristian

    2012-01-01

    Located at the end of chromosomes, telomeres are progressively shortened with each replication of DNA during aging. Integral to the regulation of telomere length is a group of proteins making up the shelterin complex, whose tissue-specific function during physiological stress is not well understood....... In this study, we examine the mRNA and protein levels of proteins within and associated with the shelterin complex in subjects (n = 8, mean age = 44 yr) who completed a physiological stress of seven marathons in 7 days. Twenty-two to 24 h after the last marathon, subjects had increased mRNA levels of DNA repair...... enzymes Ku70 and Ku80 (P muscle and peripheral blood mononuclear cells (PBMCs). Additionally, the PBMCs displayed an increment in three shelterin protein mRNA levels (TRF1, TRF2, and Pot-1, P

  20. Measurement of skeletal muscle collagen breakdown by microdialysis

    DEFF Research Database (Denmark)

    Miller, B F; Ellis, D; Robinson, M M

    2011-01-01

    Exercise increases the synthesis of collagen in the extracellular matrix of skeletal muscle. Breakdown of skeletal muscle collagen has not yet been determined because of technical limitations. The purpose of the present study was to use local sampling to determine skeletal muscle collagen breakdown...... collagen breakdown 17–21 h post-exercise, and our measurement of OHP using GC–MS was in agreement with traditional assays....

  1. The skeletal muscle circadian clock: current insights

    Directory of Open Access Journals (Sweden)

    Nakao R

    2017-11-01

    Full Text Available Reiko Nakao,1 Takeshi Nikawa,2 Katsutaka Oishi1,3,4 1Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST, Tsukuba, 2Department of Nutritional Physiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 3Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, 4Department of Computational and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Japan Abstract: Skeletal muscle functions in locomotion, postural support, and energy metabolism. The loss of skeletal muscle mass and function leads to diseases such as sarcopenia and metabolic disorders. Inactivity (lack of exercise and an imbalanced diet (increased fat or decreased protein intake are thought to be involved in the prevalence of such pathologies. On the other hand, recent epidemiological studies of humans have suggested that circadian disruption caused by shift work, jet lag, and sleep disorders is associated with obesity and metabolic syndrome. Experimental studies of mice deficient in clock genes have also identified skeletal muscle defects, suggesting a molecular link between circadian clock machinery and skeletal muscle physiology. Furthermore, accumulating evidence about chronotherapy, including chronopharmacology, chrononutrition, and chronoexercise, has indicated that timing is important to optimize medical intervention for various diseases. The present review addresses current understanding of the functional roles of the molecular clock with respect to skeletal muscle and the potential of chronotherapy for diseases associated with skeletal muscle. Keywords: biological rhythm, metabolic syndrome, physical activity, neural signal, chronotherapy

  2. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    Science.gov (United States)

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  3. Increase in skeletal muscle protein content by the ß-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet

    Directory of Open Access Journals (Sweden)

    A.L. Sawaya

    1998-06-01

    Full Text Available This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the ß-2 selective agonist clenbuterol (CL. Males (4 weeks old from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group. CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A, were further reduced in CL rats (A = 25.05 ± 0.31 vs CL = 23.64 ± 0.30 g/l, P<0.05. Total liver protein decreased below the level seen in either pair-fed animals (group P or animals with free access to the low-protein diet (A = 736.56 ± 26 vs CL = 535.41 ± 54 mg, P<0.05, whereas gastrocnemius muscle protein was higher than the values normally described for control (C animals (C = 210.88 ± 3.2 vs CL = 227.14 ± 1.7 mg/g, P<0.05. Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 ± 1.1 vs CL = -10.2 ± 1.9 g, P<0.05. This was associated with a marked decrease in fat stores (P = 5.35 ± 0.81 vs CL = 2.02 ± 0.16 g, P<0.05. Brown adipose tissue (BAT cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 ± 16.20 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05, was still much higher than in control rats (C = 159.55 ± 11.54 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05. The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

  4. Contraction-induced increases in Na+-K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Thomassen, Martin; Lundby, Carsten

    2005-01-01

    4, ß1, ß2, and ß3 mRNA in human skeletal muscle was investigated. On two occasions, eight subjects performed one-legged knee extension exercise (L) or combined one-legged knee extension and bilateral arm cranking (AL) for 5.00, 4.25, 3.50, 2.75, and 2.00 min separated by 3 min of rest. Leg exercise...... power output was the same in AL and L, but heart rate at the end of each exercise interval was higher in AL compared with L. One minute after exercise, arm venous blood lactate was higher in AL than in L. A higher level of blood epinephrine and norepinephrine was evident 3 min after exercise in AL...... compared with L. Nevertheless, none of the exercise-induced increases in a1, a2, ß1, and ß3 mRNA expression levels were higher in AL compared with L. The most abundant Na+-K+-ATPase subunit at the mRNA level was ß1, which was expressed 3.4 times than a2. Expression of a1, ß2, and ß3 was less than 5...

  5. Regulation of PDH, GS and insulin signalling in skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    of inflammation on resting and exercise-induced PDH regulation in human skeletal muscle and 4) The effect of IL-6 on PDH regulation in mouse skeletal muscle. Study I demonstrated that bed rest–induced insulin resistance was associated with reduced insulinstimulated GS activity and Akt signaling as well......The aims of the present thesis were to investigate 1) The impact of physical inactivity on insulinstimulated Akt, TBC1D4 and GS regulation in human skeletal muscle, 2) The impact of exercise training on glucose-mediated regulation of PDH and GS in skeletal muscle in elderly men, 3) The impact...... as decreased protein level of HKII and GLUT4 in skeletal muscle. Iαn addition, the ability of acute exercise to increase insulin-stimulated glucose extraction was maintained after 7 days of bed rest. However, acute exercise after bed rest did not fully normalize the ability of skeletal muscle to extract...

  6. Role of Cranial Base Morphology in Determining Skeletal Anteroposterior Relationship of the Jaws

    Directory of Open Access Journals (Sweden)

    Meghna Vandekar

    2013-01-01

    Conclusion : Decreased basicranial angulation associated with increase in mandibular length was clearly confirmed for skeletal Class III patients. The correlation between cranial base morphology and Class II skeletal base remains unclear.

  7. Role of microRNAs in skeletal muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Keisuke eHitachi

    2014-01-01

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

  8. Unorthodox angiogenesis in skeletal muscle.

    Science.gov (United States)

    Egginton, S; Zhou, A L; Brown, M D; Hudlická, O

    2001-02-16

    The morphological pattern of angiogenesis occurring in mature, differentiated skeletal muscle in response to chronically increased muscle blood flow, muscle stretch or repetitious muscle contractions was examined to determine (a) whether capillary neoformation follows the generally accepted temporal paradigm, and (b) how the growth pattern is influenced by mechanical stimuli. Adult rats were treated for a maximum of 14 days either with the vasodilator prazosin, to elevate skeletal muscle blood flow, or underwent surgical removal of one ankle flexor, to induce compensatory overload in the remaining muscles, or had muscles chronically stimulated by implanted electrodes. Extensor digitorum longus and/or extensor hallucis proprius muscles were removed at intervals and processed for electron microscopy. A systematic examination of capillaries and their ultrastructure characterised the sequence of morphological changes indicative of angiogenesis, i.e., basement membrane disruption, endothelial cell (EC) sprouting and proliferation [immunogold labelling after bromodeoxyuridine (BrdU) incorporation]. Capillary growth in response to increased blood flow occurred by luminal division without sprouting or basement membrane (BM) breakage. In stretched muscles, EC proliferation and abluminal sprouting gave rise to new capillaries, with BM loss only at sprout tips. These distinct mechanisms appear to be additive as in chronically stimulated muscles (increased blood flow with repetitive stretch and shortening during muscle contractions) both forms of capillary growth occurred. Endothelial cell numbers per capillary profile, mitotic EC nuclei, and BrdU labelling confirmed cell proliferation prior to overt angiogenesis. Physiological angiogenesis within adult skeletal muscle progresses by mechanisms that do not readily conform to the consensus view of capillary growth, derived mainly from observations made during development, pathological vessel growth, or from in vitro systems. The

  9. Maxillofacial skeletal injuries following boat accidents in a Coastal ...

    African Journals Online (AJOL)

    Objectives: The purpose of this article is to highlight the increasing occurrence of maxillofacial skeletal injuries from boat accidents in our environment and also to present our management modalities as experienced in our center. Materials and Methods: The case notes of the 6 maxillofacial skeletal injuries from boat ...

  10. Skeletal scintigraphy following incidental trauma

    International Nuclear Information System (INIS)

    Kim, H.R.; Thrall, J.H.; Keyes, J.W. Jr.

    1979-01-01

    The significance of antecedent trauma in skeletal scintigraphy was assessed in 503 patients, of whom 241 (46%) had prior fracture or tooth extraction. In patients with sufficiently accurate histories for site-by-site analysis, 33 of 131 fracture sites and 16 of 83 dental-procedure sites were positive scintigraphically. In general, the frequency of scan positivity diminished as the interval between trauma and scanning increased, but a significant number of patients showed prolonged uptake at fracture sites. Several patterns of uptake suggested trauma rather than metastatic disease. Knowledge of a history of trauma is often critical in bone scan interpretation

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

    Science.gov (United States)

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

    2014-01-01

    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. Mail-Based Intervention for Sarcopenia Prevention Increased Anabolic Hormone and Skeletal Muscle Mass in Community-Dwelling Japanese Older Adults: The INE (Intervention by Nutrition and Exercise) Study.

    Science.gov (United States)

    Yamada, Minoru; Nishiguchi, Shu; Fukutani, Naoto; Aoyama, Tomoki; Arai, Hidenori

    2015-08-01

    The aim of the Intervention by Nutrition and Exercise (INE) study was to investigate the effects of a mail-based intervention for sarcopenia prevention on muscle mass and anabolic hormones in community-dwelling older adults. A cluster-randomized controlled trial. This trial recruited community-dwelling adults aged 65 years and older in Japan. The 227 participants were cluster randomized into a walking and nutrition (W/N) group (n = 79), a walking (W) group (n = 71), and a control (C) group (n = 77). We analyzed the physical and biochemical measurements in this substudy. Six months of mail-based intervention (a pedometer-based walking program and nutritional supplementation). The skeletal muscle mass index (SMI) using the bioelectrical impedance data acquisition system, biochemical measurements, such as those of insulinlike growth factor (IGF-1), dehydroepiandrosterone sulfate (DHEA-S), and 25-hydroxy vitamin D (25[OH]D), as well as frailty, were assessed by the Cardiovascular Health Study criteria. Participants in the W/N and W groups had significantly greater improvements in SMI, IGF-1, and 25(OH)D (P < .05) than those in the C group. Participants in the W/N group had significantly greater improvements in DHEA-S (P < .05) than in the other groups. These effects were more pronounced in frail, older adults. These results suggest that the mail-based walking intervention of the remote monitoring type for sarcopenia prevention can increase anabolic hormone levels and SMI in community-dwelling older adults, particularly in those who are frail. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  13. The contraction induced increase in gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1alpha (PGC-1alpha), mitochondrial uncoupling protein 3 (UCP3) and hexokinase II (HKII) in primary rat skeletal muscle cells is dependent on reactive oxygen species

    DEFF Research Database (Denmark)

    Silveira, Leonardo R.; Pilegaard, Henriette; Kusuhara, Keiko

    2006-01-01

    to an increased H2O2 formation, as measured by oxidation of H2HFF. Acute contraction of the muscle cells lead to a transient increase in PGC-1alpha and UCP3 mRNA by 172 and 65%, respectively (pcontraction sessions induced......We evaluated the role of reactive oxygen species (ROS) for the contraction induced increase in expression of PGC-1alpha, HKII and UCP3 mRNA. Rat skeletal muscle cells were subjected to acute or repeated electrostimulation in the presence and absence of antioxidants. Contraction of muscle cells lead......alpha, HKII and UCP3 mRNA by 175, 58 and 115%, respectively (p0.05). The present data demonstrate that contraction of skeletal muscle cells leads to an enhanced formation of ROS...

  14. The skeletal system

    NARCIS (Netherlands)

    Nikkels, PGJ

    2015-01-01

    Skeletal dysplasias are a group of disorders with a disturbance in development and/or growth of cartilage and/or bone. Epiphysis, metaphysis, and diaphysis of long bones are affected in a generalized manner with or without involvement of membranous bone of the skull. A dysostosis affects one or some

  15. Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro

    Directory of Open Access Journals (Sweden)

    Noemí de Luna

    2015-05-01

    Full Text Available McArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM. It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL and brain (GP-BB isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA, a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease.

  16. Skeletal muscle as an immunogenic organ

    DEFF Research Database (Denmark)

    Nielsen, Søren; Pedersen, Bente Klarlund

    2008-01-01

    During the past few years, a possible link between skeletal muscle contractile activity and immune changes has been established. This concept is based on the finding that exercise provokes an increase in a number of cytokines. We have suggested that cytokines and other peptides that are produced...

  17. PDH regulation in skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian

    is determined by the overall content / activity of the regulatory proteins PDH kinase (PDK), of which there are 4 isoforms, and PDH phosphatase (PDP), of which there are 2 isoforms. The overall aim of the PhD project was to elucidate 4 issues. 1: Role of muscle type in resting and exercise-induced PDH...... in arm than leg muscles during exercise in humans may be the result of lower PDH-E1? content and not a muscle type dependent difference in PDH regulation. Both low muscle glycogen and increased plasma FFA are associated with upregulation of PDK4 protein and less exercise-induced increase in PDHa activity...... in human skeletal muscle. It may be noted that the increased PDK4 protein associated with elevated plasma FFA occurs already 2 hours after different dietary intake. A week of physical inactivity (bed rest), leading to whole body glucose intolerance, does not affect muscle PDH-E1? content, or the exercise...

  18. Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation

    DEFF Research Database (Denmark)

    Henningsen, Jeanette; Rigbolt, Kristoffer T G; Blagoev, Blagoy

    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 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...

  19. Lipolysis in Skeletal Muscle

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck

    of AMPK in regulation of lipid handling and lipolysis in the basal non-contracting state and during muscle contractions in skeletal muscle. To evaluate the role of AMPK, we measured protein expression and phosphorylation as well as gene expression of proteins important for regulation of lipid handling...... and lipolysis in skeletal muscle from wildtype mice and mice overexpressing a kinase dead AMPKα2 construct (AMPKα2 KD) in the basal non-contracting state and during in situ stimulated muscle contractions. We found, that IMTG levels were ~50% lower in AMPKα2 KD in the basal resting state, explained by a lower....... IMTG was in wildtype mice reduced with ~50% after muscle contractions with no effect of contractions in AMPKα2 KD mice. Concomitantly, ATGL was phosphorylated at ser406 and HSL on ser565 with muscle contractions in an AMPK dependent manner, suggesting that these sites actives lipolysis during muscle...

  20. Engineering Skeletal Muscle Repair

    OpenAIRE

    Juhas, Mark; Bursac, Nenad

    2013-01-01

    Healthy skeletal muscle has a remarkable capacity for regeneration. Even at a mature age, muscle tissue can undergo a robust rebuilding process that involves the formation of new muscle cells and extracellular matrix and the re-establishment of vascular and neural networks. Understanding and reverse-engineering components of this process is essential for our ability to restore loss of muscle mass and function in cases where the natural ability of muscle for self-repair is exhausted or impaire...

  1. Essentials of skeletal radiology

    Energy Technology Data Exchange (ETDEWEB)

    Yochum, T.R.; Rowe, L.J.

    1987-01-01

    This book discusses the following topics of skeletal radiology: Positioning of patients for diagnostic radiology and normal anatomy; congenital malformations of skeleton; measurements in radiology; spondylolisthesis; metabolic and endocrine diseases of bone and their diagnostic aspects; image processing of vertebrae, skeleton, bone fractures evaluations and epidemiological and social aspects of some bone diseases. Various modalities as CT scanning, NMR imaging, ultrasonography and biomedical radiography are briefly discussed in relation to bone pathology.

  2. Skeletal (stromal) stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Kermani, Abbas Jafari; Zaher, Walid

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy....../preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone....

  3. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  4. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  5. Skeletal sarcoidosis; Skelettsarkoidose

    Energy Technology Data Exchange (ETDEWEB)

    Freyschmidt, J. [Klinikum Bremen-Mitte, Beratungsstelle und Referenzzentrum fuer Osteoradiologie, Bremen (Germany); Freyschmidt, P. [Dermatologische Gemeinschaftspraxis, Schwalmstadt (Germany)

    2016-10-15

    Presentation of the etiology, pathology, clinical course, radiology and differential diagnostics of skeletal sarcoidosis. Noncaseating epithelioid cell granulomas can trigger solitary, multiple or disseminated osteolysis, reactive osteosclerosis and/or granulomatous synovitis. The incidence of sarcoidosis is 10-12 per 100,000 inhabitants per year. Skeletal involvement is approximately 14 %. Skeletal involvement occurs almost exclusively in the stage of lymph node and pulmonary manifestation. Most cases of skeletal involvement are clinically asymptomatic. In the case of synovial involvement, unspecific joint complaints (arthralgia) or less commonly arthritis can occur. Typical skin alterations can be diagnostically significant. Punch out lesions osteolysis, coarse destruction and osteosclerosis can occur, which are best visualized with projection radiography and/or computed tomography. Pure bone marrow foci without interaction with the bone can only be detected with magnetic resonance imaging (MRI) and more recently with positron emission tomography (PET), mostly as incidental findings. There is a predeliction for the hand and trunk skeleton. Skeletal tuberculosis, metastases, multiple myeloma, Langerhans cell histiocytosis and sarcoid-like reactions in solid tumors must be differentiated. The key factors for correct diagnosis are thorax radiography, thorax CT and dermatological manifestations. (orig.) [German] Darstellung von Aetiologie, Pathologie, Klinik, Radiologie und Differenzialdiagnose der Skelettsarkoidose. Nichtverkaesende Epitheloidzellgranulome koennen solitaere, multiple oder disseminierte Osteolysen, reaktive Osteosklerosen und/oder eine granulomatoese Synovialitis ausloesen. Inzidenz der Sarkoidose: 10-12/100.000 Einwohner/Jahr. Skelettbeteiligung ca. 14 %. Skelettbeteiligungen kommen fast ausschliesslich im Stadium einer Lymphknoten- und pulmonalen Manifestation vor. Die meisten Skelettbeteiligungen verlaufen klinisch stumm. Bei synovialer

  6. Skeletal imaging of child abuse (non-accidental injury)

    NARCIS (Netherlands)

    Offiah, Amaka; van Rijn, Rick R.; Perez-Rossello, Jeanette Mercedes; Kleinman, Paul K.

    2009-01-01

    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse

  7. Childhood obesity and skeletal-dental maturity.

    Science.gov (United States)

    Costacurta, M; Sicuro, L; Di Renzo, L; Condò, R; De Lorenzo, A; Docimo, R

    2012-06-01

    significant. The correlation between dental and skeletal age is almost the highest (Pearson correlation coefficient=0.994) and statistically significant (p=0.01). According to FM% McCarthy classification, it is observed that with an increase in the FM% , that is passing from normal weight to obese children, the skeletal-dental age always increases with respect to the chronological age. The difference between chronological and skeletal-dental age is statistically significant for pre-obese (p=0.01) and obese (p<0.001) children, while it is not significant for underweight (p=0.46) and normal weight (p=0.33) children. According to the BMI classification, from the Anova analysis no statistically significant differences were observed among the groups as for chronological, dental and skeletal age. Applying the same inferential analyses and taking into account the BMI classification, in the obese subjects were observed not statistically significant differences as for chronological and skeletal-dental age (p=0.09). The results highlighted a relation between skeletal-dental age acceleration and body fat percentage measured by DXA.

  8. Mesenchymal cells for skeletal tissue engineering.

    Science.gov (United States)

    Panetta, N J; Gupta, D M; Quarto, N; Longaker, M T

    2009-03-01

    Today, surgical intervention remains the mainstay of treatment to intervene upon a multitude of skeletal deficits and defects attributable to congenital malformations, oncologic resection, pathologic degenerative bone destruction, and post-traumatic loss. Despite this significant demand, the tools with which surgeons remain equipped are plagued with a surfeit of inadequacies, often resulting in less than ideal patient outcomes. The failings of current techniques largely arise secondary to their inability to produce a regenerate which closely resembles lost tissue. As such, focus has shifted to the potential of mesenchymal stem cell (MSC)-based skeletal tissue engineering. The successful development of such techniques would represent a paradigm shift from current approaches, carrying with it the potential to regenerate tissues which mimic the form and function of endogenous bone. Lessons learned from investigations probing the endogenous regenerative capacity of skeletal tissues have provided direction to early studies investigating the osteogenic potential of MSC. Additionally, increasing attention is being turned to the role of targeted molecular manipulations in augmenting MSC osteogenesis, as well as the development of an ideal scaffold ''vehicle'' with which to deliver progenitor cells. The following discussion presents the authors' current working knowledge regarding these critical aspects of MSC application in cell-based skeletal tissue engineering strategies, as well as provides insight towards what future steps must be taken to make their clinical translation a reality.

  9. Tissue engineering skeletal muscle for orthopaedic applications

    Science.gov (United States)

    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.

  10. Skeletal adaptations to bipedalism

    Directory of Open Access Journals (Sweden)

    Vasiljević Perica

    2014-01-01

    Full Text Available Bipedalism is the main characteristic of humans. During evolutin bipedalism emerged probably as an adaptation to a changing environment. Major changes in skeletal system included femur, pelvis, skull and spine. The significance of bipedal locomotion: Bipedalism freed the forelimbs for carrying objects, creation and usage of tools. In the upright position animals have a broader view of the environment and the early detection of predators is crucial for survival. Bipedal locomotion makes larger distances easier to pass, which is very important in the migration of hominids.

  11. Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

    2011-01-01

    The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

  12. A metabolic link to skeletal muscle wasting and regeneration

    Directory of Open Access Journals (Sweden)

    René eKoopman

    2014-02-01

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

  13. Magnetic resonance imaging of the skeletal musculature

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Marc-Andre (ed.) [Univ. Hospital Heidelberg (Germany). Diagnostic and Intverventional Radiology

    2014-07-01

    Comprehensive overview of the value of cutting-edge MRI for the assessment of normal and diseased skeletal muscle. Presents research findings in respect of the role of modern morphological and functional MRI techniques. Provides examples of the added value provided by these techniques when evaluating muscular diseases. Although muscular diseases are a huge and heterogeneous group, in most cases of progressive disease the result is focal or general muscular weakness that presents as an unspecific symptom. Imaging techniques that offer differential diagnostic clues are therefore urgently needed. Despite this, MRI has to date often been assigned a subsidiary role in the diagnostic work-up of these diseases owing to the frequent inability of routine MRI protocols to detect pathognomonic findings. This situation is changing with the advent of modern MRI techniques that offer deeper insights into surrogate pathophysiologic parameters, such as muscular microcirculation, sodium homeostasis, energy and lipid metabolism, and muscle fiber architecture. Much higher levels of acceptance and demand by clinicians can be anticipated for these new techniques in the near future, and radiologists will have to face up to the increasing value of MRI of the skeletal musculature. In this book, recognized experts from around the world provide a comprehensive overview of the value of cutting-edge MRI for the assessment of normal and diseased skeletal muscle. A range of aspects are covered, from the general role of MRI in imaging the skeletal musculature, including in comparison with ultrasonography, through to the current value of MRI in the diagnostic work-up of different diseases. In addition, several chapters present research findings in respect of modern morphological and functional MRI techniques for assessment of the skeletal musculature and provide examples of the added value provided by these techniques when evaluating muscular diseases.

  14. Extrarenal potassium adaptation: role of skeletal muscle

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 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 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

  15. Low Po2 conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers

    OpenAIRE

    Zuo, Li; Shiah, Amy; Roberts, William J.; Chien, Michael T.; Wagner, Peter D.; Hogan, Michael C.

    2013-01-01

    Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po2 conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po2 compared wi...

  16. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

      The connective tissue content of skeletal muscle is believed to be the major factor responsible for defining the eating quality of different meat cuts, although attempts to correlate quantifications based on traditional histological methods have not as yet been able to prove this relation...... that collagen plays a significant role in determining the tenderness of meat. What are we missing? Therefore, fundamental aspects of connective tissue research have been the centre of attention throughout this thesis. A holistic view has been applied, glancing at this complex tissue which has many facets...... in this thesis that alpha-ketoglutarate, a tricarboxylic acid cycle metabolite, has the potential to control the metabolism of this particular tissue. Finally, a new microscopic method is introduced which allows the study of thermal denaturation of fibrillar collagen and myofibers in real time without any label...

  17. Axial skeletal CT densitometry

    International Nuclear Information System (INIS)

    Lampmann, L.E.H.

    1982-01-01

    Since the discovery of the Roentgen ray a precise and accurate assessment of bone mineral content has been a challenge to many investigators. A number of methods have been developed but no one satisfied. Considering its technical possibilities computed tomography is very promising in determination of bone mineral content (BMC). The new modality enables BMC estimations in the axial skeletal trabecular bone. CT densitometry can be performed on a normal commercially available third generation whole body CT scanner. No dedicated device in a special clinical set-up is necessary. In this study 106 patients, most of them clinically suspected of osteoporosis, were examined. The new method CT densitometry has been evaluated. The results have been correlated to alternative BMC determination methods. (Auth.)

  18. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

    that collagen plays a significant role in determining the tenderness of meat. What are we missing? Therefore, fundamental aspects of connective tissue research have been the centre of attention throughout this thesis. A holistic view has been applied, glancing at this complex tissue which has many facets......  The connective tissue content of skeletal muscle is believed to be the major factor responsible for defining the eating quality of different meat cuts, although attempts to correlate quantifications based on traditional histological methods have not as yet been able to prove this relation....... Collagen, being the major protein in connective tissue, has been extensively investigated with regard to its relation to meat tenderness, but the results have been rather conflicting. Meat from older animals is tougher than that from younger animals, and changes in the properties of the collagen due...

  19. , 1584), increase in lean body mass (ID 1579, 1582, 1583), increase in muscle strength (ID 1578, 1583, 1587), increase in endurance performance (ID 1580, 1581), skeletal muscle tissue repair (ID 1586) and faster recovery from muscle fatigue after exercise (ID 1576, 1585) pursuant to Article 13, EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to β-hydroxy β-methylbutyrate monohydrate (HMB) alone or in combination with α-ketoisocaproic acid (KIC) and reduction of muscle tissue damage during exercise (ID 1577

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to β-hydroxy β-methylbutyrate monohydrate (HMB) alone or in combination with α-ketoisocaproic acid (KIC) and reduction of muscle tissue damage during exercise, increase in lean body mass, increase in muscle strength, increase in endurance performance, skeletal muscle tissue repair...... and faster recovery from muscle fatigue after exercise. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders. The food constituent...

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

    Science.gov (United States)

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

    2014-04-01

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

  1. DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH

    Science.gov (United States)

    Liu, Zhongbo; Kennedy, Oran D.; Cardoso, Luis; Basta-Pljakic, Jelena; Partridge, Nicola C.; Schaffler, Mitchell B.; Rosen, Clifford J.; Yakar, Shoshana

    2016-01-01

    Bone minerals are acquired during growth and are key determinants of adult skeletal health. During puberty, the serum levels of growth hormone (GH) and its downstream effector IGF-1 increase and play critical roles in bone acquisition. The goal of the current study was to determine how bone cells integrate signals from the GH/IGF-1 to enhance skeletal mineralization and strength during pubertal growth. Osteocytes, the most abundant bone cells, were shown to orchestrate bone modeling during growth. We used dentin matrix protein (Dmp)-1-mediated Ghr knockout (DMP-GHRKO) mice to address the role of the GH/IGF axis in osteocytes. We found that DMP-GHRKO did not affect linear growth but compromised overall bone accrual. DMP-GHRKO mice exhibited reduced serum inorganic phosphate and parathyroid hormone (PTH) levels and decreased bone formation indices and were associated with an impaired response to intermittent PTH treatment. Using an osteocyte-like cell line along with in vivo studies, we found that PTH sensitized the response of bone to GH by increasing Janus kinase-2 and IGF-1R protein levels. We concluded that endogenously secreted PTH and GHR signaling in bone are necessary to establish radial bone growth and optimize mineral acquisition during growth.—Liu, Z., Kennedy, O. D., Cardoso, L., Basta-Pljakic, J., Partridge, N. C., Schaffler, M. B., Rosen, C. J., Yakar, S. DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH. PMID:26481310

  2. Lactate oxidation in human skeletal muscle mitochondria

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Meinild, Anne-Kristine; Nordsborg, Nikolai B

    2013-01-01

    Lactate is an important intermediate metabolite in human bioenergetics and is oxidized in many different tissues including the heart, brain, kidney, adipose tissue, liver, and skeletal muscle. The mechanism(s) explaining the metabolism of lactate in these tissues, however, remains unclear. Here, we...... of four separate and specific substrate titration protocols, the respirometric analysis revealed that mitochondria were capable of oxidizing lactate in the absence of exogenous LDH. The titration of lactate and NAD(+) into the respiration medium stimulated respiration (P = 0.003). The addition...... of exogenous LDH failed to increase lactate-stimulated respiration (P = 1.0). The results further demonstrate that human skeletal muscle mitochondria cannot directly oxidize lactate within the mitochondrial matrix. Alternately, these data support previous claims that lactate is converted to pyruvate within...

  3. Oxidative proteome alterations during skeletal muscle ageing

    Directory of Open Access Journals (Sweden)

    Sofia Lourenço dos Santos

    2015-08-01

    Full Text Available Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

  4. Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function.

    Directory of Open Access Journals (Sweden)

    Brian Lin

    Full Text Available 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.

  5. Purinergic effects on Na,K-ATPase activity differ in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten; Nordsborg, Nikolai Baastrup; Bangsbo, Jens

    2014-01-01

    P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle.......P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle....

  6. Simvastatin effects on skeletal muscle

    DEFF Research Database (Denmark)

    Larsen, Steen; Stride, Nis; Hey-Mogensen, Martin

    2013-01-01

    Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9)....

  7. Skeletal anatomy of the hand.

    Science.gov (United States)

    Panchal-Kildare, Surbhi; Malone, Kevin

    2013-11-01

    The skeletal anatomy of the hand is composed of phalanges, metacarpal bones, and carpal bones. Its function is a product of the complex interactions between the power provided by the intrinsic and extrinsic musculature, the stability provided by the ligaments, and the structure provided by the bones, which serve as insertion and attachment sites for the muscles and ligaments. This article provides a detailed description of the skeletal anatomy of the human hand. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Retrospective review to determine the utility of follow-up skeletal surveys in child abuse evaluations when the initial skeletal survey is normal

    Directory of Open Access Journals (Sweden)

    Kachelmeyer Andrea

    2011-09-01

    Full Text Available Abstract Objective The AAP recommends that a follow-up skeletal survey be obtained for all children Methods A retrospective review of radiology records from September 1, 1998 - January 31, 2007 was conducted. Suspected victims of child abuse who were Results Forty-seven children had a negative initial skeletal survey and were included for analysis. The mean age was 6.9 months (SD 5.7; the mean number of days between skeletal surveys was 18.7 (SD 10.1 Four children (8.5% had signs of healing bone trauma on a follow-up skeletal survey. Three of these children (75% had healing rib fractures and one child had a healing proximal humerus fracture. The findings on the follow-up skeletal survey yielded forensically important information in all 4 cases and strengthened the diagnosis of non-accidental trauma. Conclusion 8.5 percent of children with negative initial skeletal surveys had forensically important findings on follow-up skeletal survey that increased the certainty of the diagnosis of non-accidental trauma. A follow-up skeletal survey can be useful even when the initial skeletal survey is negative.

  9. The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-09-01

    Conclusions: Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity.

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

    OpenAIRE

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

    2012-01-01

    Sustained periods of negative energy balance decrease body mass due to losses of both fat and skeletal muscle mass. Decreases in skeletal muscle mass are associated with a myriad of negative consequences, including suppressed basal metabolic rate, decreased protein turnover, decreased physical performance, and increased risk of injury. Decreases in skeletal muscle mass in response to negative energy balance are due to imbalanced rates of muscle protein synthesis and degradation. However, the ...

  11. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

    LENUS (Irish Health Repository)

    Morgan, Stuart A

    2009-11-01

    Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

  12. Molecular Signals and Skeletal Muscle Adaptation to Exercise

    Directory of Open Access Journals (Sweden)

    Mark Wilson

    2013-08-01

    Full Text Available The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing. However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely

  13. FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

    Directory of Open Access Journals (Sweden)

    Gerrard Dave

    2007-04-01

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

  14. Peripheral endocannabinoids regulate skeletal muscle development and maintenance

    Directory of Open Access Journals (Sweden)

    Dongjiao Zhao

    2010-12-01

    Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

  15. Exercise and obesity-induced insulin resistance in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Hyo-Bum Kwak

    2013-12-01

    Full Text Available The skeletal muscle in our body is a major site for bioenergetics and metabolism during exercise. Carbohydrates and fats are the primary nutrients that provide the necessary energy required to maintain cellular activities during exercise. The metabolic responses to exercise in glucose and lipid regulation depend on the intensity and duration of exercise. Because of the increasing prevalence of obesity, recent studies have focused on the cellular and molecular mechanisms of obesity-induced insulin resistance in skeletal muscle. Accumulation of intramyocellular lipid may lead to insulin resistance in skeletal muscle. In addition, lipid intermediates (e.g., fatty acyl-coenzyme A, diacylglycerol, and ceramide impair insulin signaling in skeletal muscle. Recently, emerging evidence linking obesity-induced insulin resistance to excessive lipid oxidation, mitochondrial overload, and mitochondrial oxidative stress have been provided with mitochondrial function. This review will provide a brief comprehensive summary on exercise and skeletal muscle metabolism, and discuss the potential mechanisms of obesity-induced insulin resistance in skeletal muscle.

  16. Skeletal dysplasias: 38 prenatal cases.

    Science.gov (United States)

    Witters, I; Moerman, Ph; Fryns, J P

    2008-01-01

    To assess the prenatal diagnosis of skeletal dysplasias in a single center over a ten-years period. All antenatal detected skeletal dysplasias during the period January 1st 1996 until December 31 2005 (10 years) were retrieved from the genetic database. This database includes all skeletal dysplasias where invasive prenatal diagnosis (chorionic villus sampling/amniocentesis) was performed. The final diagnosis was sought on the basis of fetopathological examination, radiographic studies and if possible molecular testing. A total of 46 antenatal skeletal dysplasias were diagnosed during this period. Follow-up was only available in 38 cases. The other 8 cases involved prenatally presumed lethal skeletal dysplasias that were interrupted in the referral hospital with no further information sent to us. The mean gestational age at diagnosis was 23 weeks (range 12-33 weeks). A diagnosis 30 weeks (29%) and these included all achondroplasias (n = 6), hypophosphatasia (n = 1), Jeune syndrome (n = 1), osteogenesis imperfecta type II (n = l), type I (n = 1) and type III (n = 1). In 27 cases a lethal skeletal dysplasia was present (71%) and these were all correctly predicted. Of the lethal skeletal dysplasias 5 cases were diagnosed only after 24 weeks of pregnancy (19%) and 3 were only referred after 30 weeks (11.5%). A final diagnosis was obtained in 36 cases by fetopathological examination and radiographic studies and molecular testing as deemed necessary. Specific diagnoses included: achondroplasia (n = 6), achondrogenesis (n = 2), osteogenesis imperfecta type II (n = 9), osteogenesis imperfecta type I (n = 1), osteogenesis imperfecta type III (n = 1), thanatophoric dysplasia (n = 7), hypophosphatasia (n = 1), Majewski syndrome (n = 11), Mohr-Majewski syndrome (n = 11), Jeune syndrome (n = 2), Ellis-van Creveld syndrome (n = 2), Roberts syndrome (n = 1), campomelic dysplasia (n = 2). In two cases postnatal investigation revealed no certain diagnosis and these included one

  17. Glucocorticoids and inhibition of bone formation induced by skeletal unloading

    Energy Technology Data Exchange (ETDEWEB)

    Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E. (Univ. of California, San Francisco (USA) Veterans Administration Medical Center, San Francisco, CA (USA) NASA-Ames Research Center, Moffett Field, CA (USA))

    1988-12-01

    Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of {sup 45}Ca and ({sup 3}H)proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly.

  18. Aging of Skeletal Muscle Fibers

    Science.gov (United States)

    Miljkovic, Natasa; Lim, Jae-Young; Miljkovic, Iva

    2015-01-01

    Aging has become an important topic for scientific research because life expectancy and the number of men and women in older age groups have increased dramatically in the last century. This is true in most countries of the world including the Republic of Korea and the United States. From a rehabilitation perspective, the most important associated issue is a progressive decline in functional capacity and independence. Sarcopenia is partly responsible for this decline. Many changes underlying the loss of muscle mass and force-generating capacity of skeletal muscle can be understood at the cellular and molecular levels. Muscle size and architecture are both altered with advanced adult age. Further, changes in myofibers include impairments in several physiological domains including muscle fiber activation, excitation-contraction coupling, actin-myosin cross-bridge interaction, energy production, and repair and regeneration. A thorough understanding of these alterations can lead to the design of improved preventative and rehabilitative interventions, such as personalized exercise training programs. PMID:25932410

  19. Skeletal muscle ischemia and reperfusion in rats increase lipid peroxidation in rats Isquemia e reperfusão do músculo esquelético aumenta a peroxidação lipídica em ratos

    Directory of Open Access Journals (Sweden)

    Carlos Eli Piccinato

    2004-10-01

    Full Text Available PURPOSE: To determine the effects of 30 minutes of ischemia followed by 30 minutes of reperfusion in skeletal muscle of rats receiving three different diets (supplemented, normal and vitamin E deficient on lipoperoxidation (LP. METHODS: LP measured by TBARS levels, and plasma and hepatic concentrations of vitamin E measured by HPLC. RESULTS: The deficient group presented higher lipoperoxidation levels in muscle compared to the control and supplemented groups. CONCLUSION: Supplementation with vitamin E decrease the free radicals production in ischemia/reperfusion in skeletal muscle of rats.OBJETIVO: Existem evidências que nos processos de isquemia e reperfusão do músculo esquelético pode ocorrer uma maior formação de radicais livres e que os efeitos deletérios destes radicais podem ser inibidos pela presença de substâncias antioxidantes, como a vitamina E. MÉTODOS: O presente trabalho demonstra os efeitos de 30 minutos de isquemia seguido de 30 minutos de reperfusão em músculo esquelético de ratos Wistar recebendo 3 diferentes dietas: suplementada 20 vezes (GS, controle (GC e deficiente em vitamina E por 30 dias (GD, sobre a taxa de peroxidação lipídica e níveis plasmáticos e musculares de vitamina E. RESULTADOS: As médias de pesos e de ingestão dietética dos grupos experimentais a cada semana mostrou que não houve diferença estatística significativa entre os 3 grupos que receberam dietas com teores diferentes de vitamina E. Quanto aos valores de vitamina E existiu diferença entre os 3 grupos no músculo, sendo respectivamente o deficiente menor que o controle e menor que o suplementado (GD 2.15 ± 0.44, GC 6.37 ± 1.66 e GS 18.43 ± 1.80, p < 0,05. Os valores musculares das peroxidação lipídica foram altamente influenciados pela dieta, tendo um aumento significativo no grupo deficiente em vitamina E. Estes resultados fortalecem a hipótese de que a isquemia e reperfusão são processos geradores de radicais livres e

  20. Significance of insulin for glucose metabolism in skeletal muscle during contractions

    DEFF Research Database (Denmark)

    Hespel, P; Vergauwen, Lieven; Vandenberghe, K

    1996-01-01

    Glucose uptake rate in active skeletal muscles is markedly increased during exercise. This increase reflects a multifactorial process involving both local and systemic mechanisms that cooperate to stimulate glucose extraction and glucose delivery to the muscle cells. Increased glucose extraction ...

  1. FDG-PET/CT in Skeletal Muscle: Pitfalls and Pathologies.

    Science.gov (United States)

    Parida, Girish Kumar; Roy, Shambo Guha; Kumar, Rakesh

    2017-07-01

    FDG-PET/CT is an integral part of modern-day practice of medicine. By detecting increased cellular metabolism, FDG-PET/CT can help us detect infection, inflammatory disorders, or tumors, and also help us in prognostication of patients. However, one of the most important challenges is to correctly differentiate the abnormal uptake that is potentially pathologic from the physiological uptake. So while interpreting a PET/CT, one must be aware of normal biodistribution and different physiological variants of FDG uptake. Skeletal muscles constitute a large part of our body mass and one of the major users of glucose. Naturally, they are often the site of increased FDG uptake in a PET study. We as a nuclear medicine physician must be aware of all the pitfalls of increased skeletal muscle uptake to differentiate between physiological and pathologic causes. In this review, we have discussed the different causes and patterns of physiological FDG uptake in skeletal muscles. This knowledge of normal physiological variants of FDG uptake in the skeletal muscles is essential for differentiating pathologic uptake from the physiological ones. Also, we reviewed the role of FDG-PET/CT in various benign and malignant diseases involving skeletal muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Deep bite malocclusion: exploration of the skeletal and dental factors

    International Nuclear Information System (INIS)

    Bhateja, N.K.; Fida, M.; Shaikh, A.

    2016-01-01

    Correction of deep bite is crucial for maintenance of dental hard and soft tissue structures and for prevention of temporomandibular joint disorders. Exploration of underlying skeletal and dental factors is essential for efficient and individualized treatment planning. To date etiological factors of dental and skeletal deep bite have not been explored in Pakistani orthodontic patients. The objectives of this study were to explore frequencies of dental and skeletal etiological factors in deep bite patients and to determine correlations amongst dental and skeletal etiological factors of deep bite. Methods: The study included a total of 113 subjects (males=35; females=78) with no craniofacial syndromes or prior orthodontic treatment. Pre-treatment orthodontic records were used to evaluate various dental and skeletal parameters. Descriptive statistics of each parameter were calculated. The various study parameters were correlated using Pearson's Correlation. Results: Deep curve of Spee was most frequently seen factor of dental deep bite (72.6%), followed by increased coronal length of upper incisors (28.3%), retroclined upper incisors (17.7%), retroclined lower incisors (8%) and increased coronal length of lower incisors (5.3%). Decreased gonial angle was most commonly found factor of skeletal deep bite (43.4%), followed by decreased mandibular plane angle (27.4%) and maxillary plane's clockwise rotation (26.5%). Frankfort mandibular plane angle and gonial angle showed a strong positive correlation (r=0.66, p=0.000). Conclusions: Reduced gonial angle is most frequently seen skeletal factor, signifying the importance of angulation and growth of ramus in development of deep bite. Deep curve of Spee is most frequently seen dental etiological component in deep bite subjects, hence signifying the importance of intruding the lower anterior teeth. (author)

  3. Skeletal complications of eating disorders.

    Science.gov (United States)

    Donaldson, Abigail A; Gordon, Catherine M

    2015-09-01

    Anorexia nervosa (AN) is a psychiatric illness with profound medical consequences. Among the many adverse physical sequelae of AN, bone health is impacted by starvation and can be permanently impaired over the course of the illness. In this review of skeletal complications associated with eating disorders, we discuss the epidemiology, neuroendocrine changes, adolescent vs. adult skeletal considerations, orthopedic concerns, assessment of bone health, and treatment options for individuals with AN. The focus of the review is the skeletal sequelae associated with anorexia nervosa, but we also briefly consider other eating disorders that may afflict adolescents and young adults. The review presents updates to the field of bone health in AN, and also suggests knowledge gaps and areas for future investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Techniques and applications of skeletal muscle diffusion tensor imaging: A review

    NARCIS (Netherlands)

    Oudeman, Jos; Nederveen, Aart J.; Strijkers, Gustav J.; Maas, Mario; Luijten, Peter R.; Froeling, Martijn

    2016-01-01

    Diffusion tensor imaging (DTI) is increasingly applied to study skeletal muscle physiology, anatomy, and pathology. The reason for this growing interest is that DTI offers unique, noninvasive, and potentially diagnostically relevant imaging readouts of skeletal muscle structure that are difficult or

  5. Techniques and applications of skeletal muscle diffusion tensor imaging : A review

    NARCIS (Netherlands)

    Oudeman, Jos; Nederveen, Aart J; Strijkers, Gustav J; Maas, Mario; Luijten, Peter R|info:eu-repo/dai/nl/304821098; Froeling, Martijn|info:eu-repo/dai/nl/413648354

    Diffusion tensor imaging (DTI) is increasingly applied to study skeletal muscle physiology, anatomy, and pathology. The reason for this growing interest is that DTI offers unique, noninvasive, and potentially diagnostically relevant imaging readouts of skeletal muscle structure that are difficult or

  6. Responses of mouse skeletal muscle to endurance exercise. Functional, metabolic, and genomic adaptations

    NARCIS (Netherlands)

    de Snoo, M.W.

    2009-01-01

    Endurance exercise is commonly known to improve skeletal muscle performance with respect to fatigue resistance. The exact mechanisms, however, as to how skeletal muscle adapts to increased physical demand are still largely unknown, despite extensive research. These processes were originally studied

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

    Science.gov (United States)

    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…

  8. PGC-1α-mediated adaptations in skeletal muscle

    DEFF Research Database (Denmark)

    Olesen, Jesper; Kiilerich, Kristian; Pilegaard, Henriette

    2010-01-01

    multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle......Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each...... involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested...

  9. Does Skeletal Muscle Mass Influence Breast Cancer? Evaluating Mammary Tumorigenesis and Progression in Genetically Hyper-Muscular Mice

    National Research Council Canada - National Science Library

    Zimmers, Teresa

    2007-01-01

    .... To determine the role of increased skeletal muscle mass on breast cancer, the authors sought to measure rates of chemically induced mammary tumorigenesis and progression in genetically hypermuscular...

  10. Extraction of DNA from Skeletal Remains.

    Science.gov (United States)

    Edson, Suni M; McMahon, Timothy P

    2016-01-01

    Acquisition of DNA from skeletal remains can be a delicate process. With the advent of improved extraction buffers that provide complete demineralization of the osseous materials, extraction of total genomic DNA from nearly any skeletal element is possible. This chapter describes both traditional organic and more newly developed inorganic extraction methods for fresh and dried skeletal remains.

  11. Mechanisms regulating skeletal muscle growth and atrophy.

    Science.gov (United States)

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

    2013-09-01

    Skeletal muscle mass increases during postnatal development through a process of hypertrophy, i.e. enlargement of individual muscle fibers, and a similar process may be induced in adult skeletal muscle in response to contractile activity, such as strength exercise, and specific hormones, such as androgens and β-adrenergic agonists. Muscle hypertrophy occurs when the overall rates of protein synthesis exceed the rates of protein degradation. Two major signaling pathways control protein synthesis, the IGF1-Akt-mTOR pathway, acting as a positive regulator, and the myostatin-Smad2/3 pathway, acting as a negative regulator, and additional pathways have recently been identified. Proliferation and fusion of satellite cells, leading to an increase in the number of myonuclei, may also contribute to muscle growth during early but not late stages of postnatal development and in some forms of muscle hypertrophy in the adult. Muscle atrophy occurs when protein degradation rates exceed protein synthesis, and may be induced in adult skeletal muscle in a variety of conditions, including starvation, denervation, cancer cachexia, heart failure and aging. Two major protein degradation pathways, the proteasomal and the autophagic-lysosomal pathways, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These pathways involve a variety of atrophy-related genes or atrogenes, which are controlled by specific transcription factors, such as FoxO3, which is negatively regulated by Akt, and NF-κB, which is activated by inflammatory cytokines. © 2013 The Authors Journal compilation © 2013 FEBS.

  12. Correlating skeletal and dental developmental stages using radiographic parameters.

    Science.gov (United States)

    Cericato, Graziela Oro; Franco, Ademir; Bittencourt, Marcos Alan Vieira; Nunes, Marco Antonio Prado; Paranhos, Luiz Renato

    2016-08-01

    The demand for age estimation of living and deceased children considerably increased in the last years. It was mainly justified by the growing globalization trend and the enlarged amount of violent crimes involving young victims. The present research aims to correlate skeletal and dental developmental stages using radiographic parameters. Lateral cephalometric (n = 576) and panoramic (n = 576) radiographs taken in the same moment were used to asses skeletal and dental development according to the methods of Hassel and Farman (1995) and Bacetti et al. (2002), and Demirjian et al. (1973), respectively. Likelihood-ratio test was used to verify the positive prediction in correlations between developmental stages. Spearman's correlation coefficient was calculated between skeletal and dental developmental stages, as well between estimated and chronological ages. Higher prediction in correlation for the skeletal starting stage (stage 1) with stage E in mandibular canines, and with stage D in mandibular premolars and second molars was detected. Higher staging correlations were observed considering the mandibular left second premolar (0.652, p stages, the results must be carefully interpreted once it reached moderate values (<0.652). Further researches must test different classifications of skeletal and dental development, in order to verify the possibility of replacing one technique for another with stronger correlation. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  13. Story of skeletally substituted benzenes

    Indian Academy of Sciences (India)

    Unknown

    corresponds to the out-of-plane distortion of the hydrogen atom connected to the heteroatoms, which is then ..... etc. exhibits significant localization.24 The skeletally substituted benzenes considered in the study with a wide ... involving cationic and anionic systems are expected to show considerable localization. In. Table 3.

  14. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

    2012-01-01

    Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

  15. AMPK in skeletal muscle function and metabolism

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Hingst, Janne Rasmuss; Fentz, Joachim

    2018-01-01

    highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation......, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives...

  16. Obestatin controls skeletal muscle fiber-type determination.

    Science.gov (United States)

    Santos-Zas, Icía; Cid-Díaz, Tania; González-Sánchez, Jessica; Gurriarán-Rodriguez, Uxía; Seoane-Mosteiro, Carlos; Porteiro, Begoña; Nogueiras, Rubén; Casabiell, Xesús; Luis Relova, José; Gallego, Rosalía; Mouly, Vincent; Pazos, Yolanda; Camiña, Jesus P

    2017-05-18

    Obestatin/GPR39 signaling stimulates skeletal muscle growth and repair by inducing both G-protein-dependent and -independent mechanisms linking the activated GPR39 receptor with distinct sets of accessory and effector proteins. In this work, we describe a new level of activity where obestatin signaling plays a role in the formation, contractile properties and metabolic profile of skeletal muscle through determination of oxidative fiber type. Our data indicate that obestatin regulates Mef2 activity and PGC-1α expression. Both mechanisms result in a shift in muscle metabolism and function. The increase in Mef2 and PGC-1α signaling activates oxidative capacity, whereas Akt/mTOR signaling positively regulates myofiber growth. Taken together, these data indicate that the obestatin signaling acts on muscle fiber-type program in skeletal muscle.

  17. Regulation of the skeletal muscle blood flow in humans

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Saltin, Bengt

    2014-01-01

    hyperaemia whereas the role of ATP remains uncertain due to lack of specific purinergic receptor blockers for human use. The purpose of this review is to address the interaction between vasodilator systems and to discuss the multiple proposed roles of ATP in human skeletal muscle blood flow regulation......In humans, skeletal muscle blood flow is regulated by an interaction between several locally formed vasodilators including nitric oxide (NO) and prostaglandins. In plasma, ATP is a potent vasodilator that stimulates the formation of NO and prostaglandins and very importantly can offset local...... sympathetic vasoconstriction. ATP is released into plasma from erythrocytes and endothelial cells and the plasma concentration increases in both the feeding artery and the vein draining the contracting skeletal muscle. Adenosine also stimulates the formation of NO and prostaglandins, but the plasma adenosine...

  18. Treatment of Anterior Cruciate Ligament Injury in Skeletally Immature Patients

    Directory of Open Access Journals (Sweden)

    Joshua L. Hudgens

    2012-01-01

    Full Text Available The incidence of ACL tears is rising in the pediatric and adolescent populations as these individuals succumb to traumatic and nontraumatic athletic injuries. Management of this condition in the skeletally immature patient poses a challenge and is controversial. Operative reconstruction carries the concern for damage to the physis with resultant limb length inequality and angular joint deformity but provides stability to the knee and allows return of function in most patients. On the other hand, nonoperative treatment has been shown to carry an increased risk of meniscal and articular cartilage damage and is difficult from a compliance standpoint in this demographic. For the majority of skeletally immature patients, operative treatment is recommended as it has shown good clinical and functional results with minimal risk of growth disturbance. This paper aims to address the natural course of ACL injuries in the skeletally immature patient, treatment options with associated complications, and current preventative strategies.

  19. Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers

    Directory of Open Access Journals (Sweden)

    Styliana Philippou

    2018-03-01

    Full Text Available Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show loss of therapeutic molecules to non-target tissues leading to lower target efficacy. Therefore, strategies that increase uptake efficiency would be particularly compelling. To address this need, we applied a cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment approach and identified a skeletal muscle-specific RNA aptamer. A01B RNA aptamer preferentially internalizes in skeletal muscle cells and exhibits decreased affinity for off-target cells. Moreover, this in vitro selected aptamer retained its functionality in vivo, suggesting a potential new approach for targeting skeletal muscles. Ultimately, this will aid in the development of targeted oligonucleotide therapies against muscular dystrophies.

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

    Science.gov (United States)

    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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Wave biomechanics of the skeletal muscle

    Science.gov (United States)

    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.

  2. Skeletal Muscle Mitochondria and Aging: A Review

    Directory of Open Access Journals (Sweden)

    Courtney M. Peterson

    2012-01-01

    Full Text Available Aging is characterized by a progressive loss of muscle mass and muscle strength. Declines in skeletal muscle mitochondria are thought to play a primary role in this process. Mitochondria are the major producers of reactive oxygen species, which damage DNA, proteins, and lipids if not rapidly quenched. Animal and human studies typically show that skeletal muscle mitochondria are altered with aging, including increased mutations in mitochondrial DNA, decreased activity of some mitochondrial enzymes, altered respiration with reduced maximal capacity at least in sedentary individuals, and reduced total mitochondrial content with increased morphological changes. However, there has been much controversy over measurements of mitochondrial energy production, which may largely be explained by differences in approach and by whether physical activity is controlled for. These changes may in turn alter mitochondrial dynamics, such as fusion and fission rates, and mitochondrially induced apoptosis, which may also lead to net muscle fiber loss and age-related sarcopenia. Fortunately, strategies such as exercise and caloric restriction that reduce oxidative damage also improve mitochondrial function. While these strategies may not completely prevent the primary effects of aging, they may help to attenuate the rate of decline.

  3. Skeletal anchorage for intrusion of bimaxillary molars in a patient with skeletal open bite and temporomandibular disorders.

    Science.gov (United States)

    Iwasa, Akihiko; Horiuchi, Shinya; Kinouchi, Nao; Izawa, Takashi; Hiasa, Masahiro; Kawai, Nobuhiko; Yasue, Akihiro; Hassan, Ali H; Tanaka, Eiji

    2017-01-01

    The treatment of severe skeletal anterior open bite is extremely difficult in adults, and orthognathic surgery is generally selected for its treatment. We report the case of an 18-year-old adult patient with skeletal anterior open bite and temporomandibular disorders who was successfully treated using temporary anchorage devices. She had an open bite of -2.0 mm and an increased facial height. Miniplates were implanted in both the maxilla and mandible, and molar intrusion resulted in counterclockwise rotation of the mandible over a period of 12 months. After active treatment, her upper and lower first molars were intruded by approximately 2 mm and her overbite became +2.5 mm. Her retrognathic profile improved with counterclockwise rotation of the mandible. Orthodontic treatment aided with skeletal anchorage is beneficial for intrusion of bimaxillary molars in patients with anterior open bite.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Skeletal imaging of child abuse (non-accidental injury)

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, Amaka [Great Ormond Street Hospital, Radiology Department, London (United Kingdom); Rijn, Rick R. van [Academic Medical Centre Amsterdam, Department of Radiology, Amsterdam Zuid-Oost (Netherlands); Perez-Rossello, Jeanette Mercedes; Kleinman, Paul K. [Children' s Hospital Boston, Radiology Department, Boston, MA (United States)

    2009-05-15

    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse. (orig.)

  6. Skeletal imaging of child abuse (non-accidental injury)

    International Nuclear Information System (INIS)

    Offiah, Amaka; Rijn, Rick R. van; Perez-Rossello, Jeanette Mercedes; Kleinman, Paul K.

    2009-01-01

    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse. (orig.)

  7. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man

    DEFF Research Database (Denmark)

    Astrup, A; Bülow, J; Madsen, J

    1985-01-01

    was estimated by measurements of leg blood flow and arteriovenous oxygen difference. The perirenal adipose tissue blood flow increased approximately twofold, whereas the local temperature increased approximately 0.1 degrees C on an average. Assuming that man possesses 700 g of BAT with a similar thermogenic...... skeletal muscle, approximately 50% of the increase in oxygen consumption induced by ephedrine may take place in skeletal muscle. It is concluded that skeletal muscle is a tissue of importance with respect to the thermogenic effect of sympathomimetics in man, whereas the results do not support a major role...

  8. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Birk, Jesper Bratz

    2015-01-01

    The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα md.......01), indicating a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPKα mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 (cluster of differentiation 36...... to sarcolemma, respectively. AMPKα is thus required for normal FA metabolism during exercise and muscle contraction.-Fentz, J., Kjøbsted, R., Birk, J. B., Jordy, A. B., Jeppesen, J., Thorsen, K., Schjerling, P., Kiens, B., Jessen, N., Viollet, B., Wojtaszewski, J. F. P. AMPKα is critical for enhancing skeletal...

  9. Coffee consumption promotes skeletal muscle hypertrophy and myoblast differentiation.

    Science.gov (United States)

    Jang, Young Jin; Son, Hyo Jeong; Kim, Ji-Sun; Jung, Chang Hwa; Ahn, Jiyun; Hur, Jinyoung; Ha, Tae Youl

    2018-02-21

    Coffee is a widely consumed beverage worldwide and is believed to help prevent the occurrence of various chronic diseases. However, the effect of coffee on skeletal muscle hypertrophy, differentiation and the mechanisms of action responsible have remained unclear. To investigate the effect of coffee on skeletal muscle hypertrophy, mice were fed a normal diet or a normal diet supplemented with 0.3% coffee or 1% coffee. Coffee supplementation was observed to increase skeletal muscle hypertrophy, while simultaneously upregulating protein expression of total MHC, MHC2A, and MHC2B in quadricep muscle. Myostatin expression was also attenuated, and IGF1 was upregulated with subsequent phosphorylation of Akt and mTOR, while AMPK phosphorylation was attenuated. Coffee also increased the grip strength and PGC-1α protein expression, and decreased the expressions of TGF-β and myostatin in tricep muscle. Coffee activated the MKK3/6-p38 pathway and upregulated PGC-1α, which may play a role in promoting myogenic differentiation and myogenin expression in C2C12 cells. These results suggest that coffee increases skeletal muscle function and hypertrophy by regulating the TGF-β/myostatin - Akt - mTORC1.

  10. Skeletal and dentoalveolar features in patients with deep overbite malocclusion.

    Science.gov (United States)

    Fattahi, Hamidreza; Pakshir, Hamidreza; Afzali Baghdadabadi, Neda; Shahian Jahromi, Shervin

    2014-11-01

    An increased overbite may be due to a skeletal or dental etiology that may influence treatment. The purpose of this study was to evaluate the skeletal and dentoalveolar features in patients with deep bite malocclusion in an Iranian population and to determine the most and least effective and contributory variables causing deep bite. Lateral cephalograms and study casts of normal (n=85) and deep bite (n=85) subjects were used to evaluate skeletal and dentoalveolar variables. Data were analyzed statistically by independent t-test. The percentages of each variable within normal limits, less and more than one standard deviation were calculated for deep bite subjects. The most significant skeletal contributing factors were gonial and basal angles, as well as the posterior facial height, ramus length, lower anterior facial height and upper anterior facial height. An increased curve of spee and decreased mandibular first molar height were predominant dental variables in the deep bite group. The variables with the greatest variances from the normal limit were the ratio of the lower anterior facial height to the total anterior facial height, the lower anterior facial height to the upper anterior facial height and the ramus length. The counterclockwise rotation of the mandible and the increased curve of spee were the dominant feature of deep bite malocclusion.

  11. Skeletal muscle abnormalities in pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Ana Paula Breda

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

  12. MR appearance of skeletal neoplasms following cryotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, M.L. [Dept. of Radiology SB-05, Washington Univ., Seattle, WA (United States); Lough, L.R. [Pitts Radiological Associates, Columbia, SC (United States); Shuman, W.P. [Dept. of Radiology, Medical Center Hospital of Vermont, Burlington, VT (United States); Lazerte, G.D. [Dept. of Pathology RC-72, Washington Univ., Medical Center Hospital of Vermont, Burlington, VT (United States); Conrad, E.U. [Dept. of Orthopedic Surgery RK-10, Washington Univ., Medical Center of Vermont, Burlington, VT (United States)

    1994-02-01

    Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

  13. MR appearance of skeletal neoplasms following cryotherapy

    International Nuclear Information System (INIS)

    Richardson, M.L.; Lough, L.R.; Shuman, W.P.; Lazerte, G.D.; Conrad, E.U.

    1994-01-01

    Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

  14. Immunology Guides Skeletal Muscle Regeneration

    OpenAIRE

    F. Andrea Sass; Michael Fuchs; Matthias Pumberger; Sven Geissler; Georg N. Duda; Carsten Perka; Katharina Schmidt-Bleek

    2018-01-01

    Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is d...

  15. Bioactive Androgens and Glucuronidated Androgen Metabolites are Associated with Subcutaneous and Ectopic Skeletal Muscle Adiposity among Older Black Men

    OpenAIRE

    Miljkovic, Iva; Cauley, Jane A; Dressen, Amy S; Gordon, Christopher L; Goodpaster, Bret H; Kuller, Lewis H; Bunker, Clareann H; Patrick, Alan L; Wheeler, Victor W; Orwoll, Eric S; Zmuda, Joseph M

    2011-01-01

    Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T...

  16. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Al-Khazraji, Baraa K; Mortensen, Stefan P

    2013-01-01

    During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However...... studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1-10 µM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition...... in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation....

  17. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans

    DEFF Research Database (Denmark)

    Karamouzis, M; Langberg, Henning; Skovgaard, D

    2001-01-01

    Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis...... amounts of prostaglandins and thromboxanes in the interstitial space of skeletal muscle. Furthermore, the concentration of prostaglandin E2 is unchanged during static calf exercise and increased markedly with dynamic thigh muscle exercise, which together with an exercise induced increase in muscle blood...... flow indicate, that prostaglandin E2 is released from skeletal muscle during exercise in humans....

  18. Space medicine considerations: Skeletal and calcium homeostasis

    Science.gov (United States)

    Schneider, Victor B.

    1989-01-01

    Based on the information obtained from space missions, particularly Skylab and the longer Salyut missions, it is clear that bone and mineral metabolism is substantially altered during space flight. Calcium balance becomes increasingly more negative throughout the flight, and the bone mineral content of the os calcis declines. The major health hazards associated with skeletal changes include the signs and symptoms of hypercalcemia with rapid bone turnover, the risk of kidney stones because of hypercalciuria, the lengthy recovery of lost bone mass after flight, the possibility of irreversible bone loss (particularly the trabecular bone), the possible effects of metastated calcification in the soft tissues, and the possible increase in fracture potential. For these reasons, major efforts need to be directed toward elucidating the fundamental mechanisms by which bone is lost in space and developing more effective countermeasures to prevent both short-term and long-term complications.

  19. Changes in skeletal muscle gene expression following clenbuterol administration

    Directory of Open Access Journals (Sweden)

    McIntyre Lauren M

    2006-12-01

    Full Text Available Abstract Background Beta-adrenergic receptor agonists (BA induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P P Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle.

  20. In utero undernutrition programs skeletal and cardiac muscle metabolism

    Directory of Open Access Journals (Sweden)

    Brittany eBeauchamp

    2016-01-01

    Full Text Available 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.

  1. Upwelling, species, and depth effects on coral skeletal cadmium-to-calcium ratios (Cd/Ca)

    Science.gov (United States)

    Matthews, Kathryn A.; Grottoli, Andréa G.; McDonough, William F.; Palardy, James E.

    2008-09-01

    Skeletal cadmium-to-calcium (Cd/Ca) ratios in hermatypic stony corals have been used to reconstruct changes in upwelling over time, yet there has not been a systematic evaluation of this tracer's natural variability within and among coral species, between depths and across environmental conditions. Here, coral skeletal Cd/Ca ratios were measured in multiple colonies of Pavona clavus, Pavona gigantea and Porites lobata reared at two depths (1 and 7 m) during both upwelling and nonupwelling intervals in the Gulf of Panama (Pacific). Overall, skeletal Cd/Ca ratios were significantly higher during upwelling than during nonupwelling, in shallow than in deep corals, and in both species of Pavona than in P. lobata. P. lobata skeletal Cd/Ca ratios were uniformly low compared to those in the other species, with no significant differences between upwelling and nonupwelling values. Among colonies of the same species, skeletal Cd/Ca ratios were always higher in all shallow P. gigantea colonies during upwelling compared to nonupwelling, though the magnitude of the increase varied among colonies. For P. lobata, P. clavus and deep P. gigantea, changes in skeletal Cd/Ca ratios were not consistent among all colonies, with some colonies having lower ratios during upwelling than during nonupwelling. No statistically significant relationships were found between skeletal Cd/Ca ratios and maximum linear skeletal extension, δ 13C or δ 18O, suggesting that at seasonal resolution the Cd/Ca signal was decoupled from growth rate, coral metabolism, and ocean temperature and salinity, respectively. These results led to the following conclusions, (1) coral skeletal Cd/Ca ratios are independent of skeletal extension, coral metabolism and ambient temperature/salinity, (2) shallow P. gigantea is the most reliable species for paleoupwelling reconstruction and (3) the average Cd/Ca record of several colonies, rather than of a single coral, is needed to reliably reconstruct paleoupwelling events.

  2. Skeletal stem cells and their contribution to skeletal fragility

    DEFF Research Database (Denmark)

    Aldahmash, A.

    2016-01-01

    Age-related osteoporotic fractures are major health care problem worldwide and are the result of impaired bone formation, decreased bone mass and bone fragility. Bone formation is accomplished by skeletal stem cells (SSC) that are recruited to bone surfaces from bone marrow microenvironment....... This review discusses targeting SSC to enhance bone formation and to abolish age-related bone fragility in the context of using stem cells for treatment of age-related disorders. Recent studies are presented that have demonstrated that SSC exhibit impaired functions during aging due to intrinsic senescence...

  3. Pelvic radiograph in skeletal dysplasias: An approach

    Directory of Open Access Journals (Sweden)

    Manisha Jana

    2017-01-01

    Full Text Available The bony pelvis is constituted by the ilium, ischium, pubis, and sacrum. The pelvic radiograph is an important component of the skeletal survey performed in suspected skeletal dysplasia. Most of the common skeletal dysplasias have either minor or major radiological abnormalities; hence, knowledge of the normal radiological appearance of bony pelvis is vital for recognizing the early signs of various skeletal dysplasias. This article discusses many common and some uncommon radiological findings on pelvic radiographs along with the specific dysplasia in which they are seen; common differential diagnostic considerations are also discussed.

  4. Sex hormones and skeletal muscle weakness

    DEFF Research Database (Denmark)

    Sipilä, Sarianna; Narici, Marco; Kjaer, Michael

    2013-01-01

    in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical...... properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal...

  5. Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

    Science.gov (United States)

    Globus, Ruth K.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Terada, Masahiro; Alwood, Joshua; Halloran, Bernard; Tahimic, Candice

    2016-01-01

    Future long-duration space exploration beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure causes progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility.

  6. Skeletal muscle pathology in Huntington’s Disease.

    Directory of Open Access Journals (Sweden)

    Daniel eZielonka

    2014-10-01

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

  7. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways.

    Science.gov (United States)

    Rodriguez, J; Vernus, B; Chelh, I; Cassar-Malek, I; Gabillard, J C; Hadj Sassi, A; Seiliez, I; Picard, B; Bonnieu, A

    2014-11-01

    Myostatin, a member of the transforming growth factor-β superfamily, is a potent negative regulator of skeletal muscle growth and is conserved in many species, from rodents to humans. Myostatin inactivation can induce skeletal muscle hypertrophy, while its overexpression or systemic administration causes muscle atrophy. As it represents a potential target for stimulating muscle growth and/or preventing muscle wasting, myostatin regulation and functions in the control of muscle mass have been extensively studied. A wealth of data strongly suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression. Moreover, myostatin plays a central role in integrating/mediating anabolic and catabolic responses. Myostatin negatively regulates the activity of the Akt pathway, which promotes protein synthesis, and increases the activity of the ubiquitin-proteasome system to induce atrophy. Several new studies have brought new information on how myostatin may affect both ribosomal biogenesis and translation efficiency of specific mRNA subclasses. In addition, although myostatin has been identified as a modulator of the major catabolic pathways, including the ubiquitin-proteasome and the autophagy-lysosome systems, the underlying mechanisms are only partially understood. The goal of this review is to highlight outstanding questions about myostatin-mediated regulation of the anabolic and catabolic signaling pathways in skeletal muscle. Particular emphasis has been placed on (1) the cross-regulation between myostatin, the growth-promoting pathways and the proteolytic systems; (2) how myostatin inhibition leads to muscle hypertrophy; and (3) the regulation of translation by myostatin.

  8. Changes in skeletal muscle gene expression following clenbuterol administration

    Science.gov (United States)

    Spurlock, Diane M; McDaneld, Tara G; McIntyre, Lauren M

    2006-01-01

    Background Beta-adrenergic receptor agonists (BA) induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P clenbuterol treatment. A total of 22,605 probesets were evaluated with 52 probesets defined as differentially expressed based on a false discovery rate of 10%. Differential mRNA abundance of four of these genes was validated in an independent experiment by quantitative PCR. Functional characterization of differentially expressed genes revealed several categories that participate in biological processes important to skeletal muscle growth, including regulators of transcription and translation, mediators of cell-signalling pathways, and genes involved in polyamine metabolism. Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally, numerous other genes and physiological pathways were identified that will be important targets for

  9. Radiological diagnosis of skeletal metastases

    International Nuclear Information System (INIS)

    Soederlund, V.

    1996-01-01

    The clinical management of patients with skeletal metastases puts new demands on imaging. The radiological imaging in screening for skeletal metastases entails detection, metastatic site description and radiologically guided biopsy for morphological typing and diagnosis. Regarding sensitivity and the ease in performing surveys of the whole skeleton, radionuclide bone scintigraphy still is the first choice in routine follow-up of asymptomatic patients with metastatic disease of the skeleton. A negative scan has to be re-evaluated with other findings, with emphasis on the possibility of a false-negative result. Screening for metastases in patients with local symptoms or pain is best accomplished by a combination of radiography and MRI. Water-weighted sequences are superior in sensitivity and in detection of metastases. Standard spin-echo sequences on the other hand are superior in metastatic site description and in detection of intraspinal metastases. MRI is helpful in differentiating between malignant disease, infection, benign vertebral collapse, insufficiency fracture after radiation therapy, degenerative vertebral disease and benign skeletal lesions. About 30% of patients with known cancer have benign causes of radiographic abnormalities. Most of these are related to degenerative diseases and are often easily diagnosed. However, due to overlap in MRI characteristics, bone biopsy sometimes is essential for differentiating between malignant and nonmalignant lesions. Performing bone biopsy and aspiration cytology by radiologist and cytologist in co-operation has proven highly accurate in diagnosing bone lesions. The procedure involves low risk to the patient and provides a morphological diagnosis. Once a suspected metastatic lesion is detected, irrespective of modality, the morphological diagnosis determines the appropriate work-up imaging with respect to the therapy alternatives. (orig./VHE)

  10. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    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

  11. Comparative Study of Skeletal Stability between Postoperative Skeletal Intermaxillary Fixation and No Skeletal Fixation after Bilateral Sagittal Split Ramus Osteotomy

    DEFF Research Database (Denmark)

    Hartlev, Jens; Godtfredsen, Erik; Andersen, Niels Trolle

    2014-01-01

    OBJECTIVES: The purpose of the present study was to evaluate skeletal stability after mandibular advancement with bilateral sagittal split osteotomy. MATERIAL AND METHODS: Twenty-six patients underwent single-jaw bilateral sagittal split osteotomy (BSSO) to correct skeletal Class II malocclusion....

  12. Diagnostic imaging of skeletal metastases

    International Nuclear Information System (INIS)

    Scutellari, P. N.; Addonisio, G.; Righi, R.; Giganti, M.

    2000-01-01

    Purpose of this article is to present an algorithm for detection and diagnosis of skeletal metastases, which may be applied differently in symptomatic and asymptomatic cancer patients. February to March 1999 it was randomly selected and retrospectively reviewed the clinical charts of 100 cancer patients (70 women and 30 men; mean age: 63 years, range: 55-87). All the patients had been staged according to TNM criteria and had undergone conventional radiography and bone scan; when findings were equivocal, CT and MRI had been performed too. The primary lesions responsible for bone metastases were sited in the: breast (51 cases), colon (30 cases: 17 men and 13 women), lung (7 cases: 6 men and 1 woman), stomach (4 cases: 2 men and 2 women), skin (4 cases: 3 men and 1 woman), kidney (2 men), pleura (1 woman), and finally liver (1 man). The most frequent radiographic pattern was the lytic type (52%), followed by osteosclerotic, mixed, lytic vs mixed and osteosclerotic vs lytic patterns. The patients were divided into two groups: group A patients were asymptomatic and group B patients had local symptoms and/or pain. Skeletal metastases are the most common malignant bone tumors: the spine and the pelvis are the most frequent sites of metastasis, because of the presence of high amounts of red (hematopoietic active) bone marrow. Pain is the main symptom, even though many bone metastases are asymptomatic. Pathological fractures are the most severe consequences. With the algorithm for detection and diagnosis of skeletal metastases two different diagnostic courses are available for asymptomatic and symptomatic patients. Bone scintigraphy remains the technique of choice in asymptomatic patients in whom skeletal metastases are suspected. However this technique, though very sensitive, is poorly specific, and thus a negative bone scan finding is double-checked with another physical examination: if the findings remain negative, the diagnostic workup is over. On the contrary, in

  13. Ciclazindol and mazindol on glucose uptake into human isolated skeletal muscle: no interaction of mazindol with methysergide.

    Science.gov (United States)

    Kirby, M J; Turner, P

    1977-01-01

    1 Ciclazindol, like mazindol, produced a significant concentration-dependent increase in glucose-uptake into human skeletal muscle in both the presence and absence of insulin. 2 Methysergide, which inhibits the action of fenfluramine on glucose-uptake into skeletal muscle, did not influence the effect of mazindol. PMID:901738

  14. Mechanical modeling of skeletal muscle functioning

    NARCIS (Netherlands)

    van der Linden, B.J.J.J.

    1998-01-01

    For movement of body or body segments is combined effort needed of the central nervous system and the muscular-skeletal system. This thesis deals with the mechanical functioning of skeletal muscle. That muscles come in a large variety of geometries, suggest the existence of a relation between muscle

  15. Skeletal stem cells in space and time

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Bianco, Paolo

    2015-01-01

    The nature, biological characteristics, and contribution to organ physiology of skeletal stem cells are not completely determined. Chan et al. and Worthley et al. demonstrate that a stem cell for skeletal tissues, and a system of more restricted, downstream progenitors, can be identified in mice...

  16. Sympathetic actions on the skeletal muscle.

    Science.gov (United States)

    Roatta, Silvestro; Farina, Dario

    2010-01-01

    The sympathetic nervous system (SNS) modulates several functions in skeletal muscle fibers, including metabolism, ionic transport across the membrane, and contractility. These actions, together with the sympathetic control of other organ systems, support intense motor activity. However, some SNS actions on skeletal muscles may not always be functionally advantageous. Implications for motor control and sport performance are discussed.

  17. Molar height and dentoalveolar compensation in adult subjects with skeletal open bite.

    Science.gov (United States)

    Kucera, Josef; Marek, Ivo; Tycova, Hana; Baccetti, Tiziano

    2011-07-01

    To evaluate the skeletal and dentoalveolar components in adult subjects with skeletal open bite in the presence or absence of dental compensation. The study sample included 69 adult female subjects who belonged to three groups according to skeletal vertical relationships and overbite. A total of 15 variables (5 angular, 10 linear) were evaluated. Values in the dentally compensated open bite group (COBG), the dentally noncompensated open bite group (NCOBG), and the control group with normal vertical skeletal relationships and overbite (CG) were compared by means of parametric statistics. The COBG and the NCOBG showed significantly greater incisor and molar heights in both jaws than the CG. No significant difference in upper or lower molar height was found between COBG and NCOBG. Incisor height was significantly greater in COBG than in NCOBG. Elongation in the incisor region was accompanied by significant narrowing of the lower anterior alveolar process in both skeletal open bite groups. Proclination of the upper incisors was significantly smaller in the COBG than in the other groups. Dentoalveolar components consisting of incisor elongation and inclination play a significant role in compensating for skeletal open bite configuration in adult subjects. Increased molar height is a common finding in adults with skeletal open bite.

  18. The Effect of Skeletal Maturity on Functional Healing of the Anterior Cruciate Ligament

    Science.gov (United States)

    Murray, Martha M.; Magarian, Elise M.; Harrison, Sophia L.; Mastrangelo, Ashley N.; Zurakowski, David; Fleming, Braden C.

    2010-01-01

    Background: The effects of skeletal maturity on functional ligament healing are unknown. Prior studies have suggested that ligament injuries in skeletally mature animals heal with improved mechanical properties. In this study, we hypothesized that skeletally immature animals have improved functional healing compared with skeletally mature animals. Methods: Twenty-one Yucatan minipigs (eight juvenile, eight adolescent, and five adult animals) underwent bilateral anterior cruciate ligament transection. On one side, the ligament injury was left untreated to determine the intrinsic healing response as a function of age. On the contralateral side, an enhanced suture repair incorporating a collagen-platelet composite was performed. Biomechanical properties of the repairs were measured after fifteen weeks of healing, and histologic analysis was performed. Results: Anterior cruciate ligaments from skeletally immature animals had significantly improved structural properties over those of adult animals at three months after transection in both the untreated and repair groups. Use of the enhanced suture technique provided the most improvement in the adolescent group, in which an increase of 85% in maximum load was noted with repair. The repair tissue in the adult tissue had the highest degree of hypercellularity at the fifteen-week time point. Conclusions: Functional ligament healing depends on the level of skeletal maturity of the animal, with immature animals having a more productive healing response than mature animals. Clinical Relevance: As future investigations assess new techniques of ligament healing in animal models, skeletal maturity should be considered in the design and the interpretation of those experiments. PMID:20810854

  19. Low intensity exercise training improves skeletal muscle regeneration potential

    Directory of Open Access Journals (Sweden)

    Tiziana ePietrangelo

    2015-12-01

    Full Text Available 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 (miRNA 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% to 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.

  20. Immunology Guides Skeletal Muscle Regeneration

    Directory of Open Access Journals (Sweden)

    F. Andrea Sass

    2018-03-01

    Full Text Available Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

  1. Immunology Guides Skeletal Muscle Regeneration.

    Science.gov (United States)

    Sass, F Andrea; Fuchs, Michael; Pumberger, Matthias; Geissler, Sven; Duda, Georg N; Perka, Carsten; Schmidt-Bleek, Katharina

    2018-03-13

    Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

  2. The Skeletal Muscle Satellite Cell

    Science.gov (United States)

    2011-01-01

    The skeletal muscle satellite cell was first described and named based on its anatomic location between the myofiber plasma and basement membranes. In 1961, two independent studies by Alexander Mauro and Bernard Katz provided the first electron microscopic descriptions of satellite cells in frog and rat muscles. These cells were soon detected in other vertebrates and acquired candidacy as the source of myogenic cells needed for myofiber growth and repair throughout life. Cultures of isolated myofibers and, subsequently, transplantation of single myofibers demonstrated that satellite cells were myogenic progenitors. More recently, satellite cells were redefined as myogenic stem cells given their ability to self-renew in addition to producing differentiated progeny. Identification of distinctively expressed molecular markers, in particular Pax7, has facilitated detection of satellite cells using light microscopy. Notwithstanding the remarkable progress made since the discovery of satellite cells, researchers have looked for alternative cells with myogenic capacity that can potentially be used for whole body cell-based therapy of skeletal muscle. Yet, new studies show that inducible ablation of satellite cells in adult muscle impairs myofiber regeneration. Thus, on the 50th anniversary since its discovery, the satellite cell’s indispensable role in muscle repair has been reaffirmed. PMID:22147605

  3. PGC-1αand fasting-induced PDH regulation in mouse skeletal muscle.

    Science.gov (United States)

    Gudiksen, Anders; Pilegaard, Henriette

    2017-04-01

    The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α ) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1 α knockout (MKO) mice and floxed littermate controls were fed or fasted for 24 h. Fasting reduced PDHa activity, increased phosphorylation of all four known sites on PDH-E1 α and increased pyruvate dehydrogenase kinase (PDK4) and sirtuin 3 (SIRT3) protein levels, but did not alter total acetylation of PDH-E1 α Lack of muscle PGC-1 α did not affect the switch from glucose to fat oxidation in the transition from the fed to fasted state, but was associated with lower and higher respiratory exchange ratio (RER) in the fed and fasted state, respectively. PGC-1 α MKO mice had lower skeletal muscle PDH-E1 α , PDK1, 2, 4, and pyruvate dehydrogenase phosphatase (PDP1) protein content than controls, but this did not prevent the fasting-induced increase in PDH-E1 α phosphorylation in PGC-1 α MKO mice. However, lack of skeletal muscle PGC-1 α reduced SIRT3 protein content, increased total lysine PDH-E1 α acetylation in the fed state, and prevented a fasting-induced increase in SIRT3 protein. In conclusion, skeletal muscle PGC-1 α is required for fasting-induced upregulation of skeletal muscle SIRT3 and maintaining high fat oxidation in the fasted state, but is dispensable for preserving the capability to switch substrate during the transition from the fed to the fasted state and for fasting-induced PDH regulation in skeletal muscle. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  4. Defective skeletal mineralization in pediatric CKD.

    Science.gov (United States)

    Wesseling-Perry, Katherine

    2015-04-01

    Although traditional diagnosis and treatment of renal osteodystrophy focused on changes in bone turnover, current data demonstrate that abnormalities in skeletal mineralization are also prevalent in pediatric chronic kidney disease (CKD) and likely contribute to skeletal morbidities that continue to plague this population. It is now clear that alterations in osteocyte biology, manifested by changes in osteocytic protein expression, occur in early CKD before abnormalities in traditional measures of mineral metabolism are apparent and may contribute to defective skeletal mineralization. Current treatment paradigms advocate the use of 1,25(OH)2vitamin D for the control of secondary hyperparathyroidism; however, these agents fail to correct defective skeletal mineralization and may exacerbate already altered osteocyte biology. Further studies are critically needed to identify the initial trigger for abnormalities of skeletal mineralization as well as the potential effects that current therapeutic options may have on osteocyte biology and bone mineralization.

  5. Cerebellar medulloblastoma presenting with skeletal metastasis

    Directory of Open Access Journals (Sweden)

    Barai Sukanta

    2004-04-01

    Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

  6. Regulation of angiogenesis in human skeletal muscle with specific focus on pro- angiogenic and angiostatic factors

    DEFF Research Database (Denmark)

    Høier, Birgitte

    It is well established that acute exercise promotes an angiogenic response and that a period of exercise training results in capillary growth. Skeletal muscle angiogenesis is a complex process that requires a coordinated interplay of multiple factors and compounds to ensure proper vascular functi...... and a concurrent increase in the angiostatic factors occur when capillary growth no longer is required. Thus the balance of pro-angiogenic and angiostatic factors is a determining regulator of exercise-induced angiogenesis in human skeletal muscle....

  7. Sarcolipin: a key thermogenic and metabolic regulator in skeletal muscle

    OpenAIRE

    Pant, Meghna; Bal, Naresh. C; Periasamy, Muthu

    2016-01-01

    Skeletal muscle constitutes ∼40 % of body mass and has the capacity to play a major role as thermogenic, metabolic and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis, heat production an...

  8. [Immobilization and skeletal system of the human body].

    Science.gov (United States)

    Kisała, Aleksander; Pluskiewicz, Wojciech

    2015-01-01

    Shaping the process of evolution musculoskeletal and nervous systems in animals has allowed these organisms steady increase mobility and mastery of new environments to life. Movement is the essence of life and health. But health is not a permanent condition. Its absence often results in limited mobility of the body. The aim of this study is to assess the impact of immobilization on the state of the skeletal system and the evaluation of the effectiveness of various measures to reduce this impact.

  9. Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

    OpenAIRE

    Murray, IR; Baily, JE; Chen, WCW; Dar, A; Gonzalez, ZN; Jensen, AR; Petrigliano, FA; Deb, A; Henderson, NC

    2017-01-01

    Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. I...

  10. Magnesium for skeletal muscle cramps.

    Science.gov (United States)

    Garrison, Scott R; Allan, G Michael; Sekhon, Ravneet K; Musini, Vijaya M; Khan, Karim M

    2012-09-12

    Skeletal muscle cramps are common and often presented to physicians in association with pregnancy, advanced age, exercise or disorders of the motor neuron (such as amyotrophic lateral sclerosis). Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this indication has never been evaluated by systematic review. To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps.   We searched the Cochrane Neuromuscular Disease Group Specialized Register (11 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 3), MEDLINE (January 1966 to September 2011), EMBASE (January 1980 to September 2011), LILACS (January 1982 to September 2011), CINAHL Plus (January 1937 to September 2011), AMED (January 1985 to October 2011) and SPORTDiscus (January 1975 to September 2011). Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy. Two authors independently selected trials for inclusion and extracted data. Two authors assessed risk of bias. We attempted to contact all study authors and obtained patient level data for three of the included trials, one of which was unpublished. All data on adverse effects were collected from the included RCTs. We identified seven trials (five parallel, two cross-over) enrolling a total of 406 individuals amongst whom 118 cross-over participants additionally served as their own controls. Three trials enrolled women with pregnancy-associated leg cramps (N = 202) and four trials enrolled idiopathic cramp sufferers (N = 322 including cross-over controls). Magnesium was compared to placebo in six trials and to no treatment in one trial.For idiopathic cramps (largely older

  11. Signalling and the control of skeletal muscle size

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  12. Expression of androgen receptor target genes in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Kesha Rana

    2014-10-01

    Full Text Available We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor (AR-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity (ARΔZF2 versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR∆ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7 , p57 Kip2, Igf2 and calcineurin Aa, was increased in AR∆ZF2 muscle, and the expression of all but p57 Kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.

  13. Redox Control of Skeletal Muscle Regeneration.

    Science.gov (United States)

    Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

    2017-08-10

    Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

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

    Science.gov (United States)

    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

  15. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, T W; Kjaer, M; Mackey, A L

    2011-01-01

    in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some......The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...

  16. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, T W; Kjaer, M; Mackey, A L

    2011-01-01

    The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

  17. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

    2011-01-01

    -links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes......The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

  18. DNA Methylation in Skeletal Muscle Stem Cell Specification, Proliferation, and Differentiation

    Directory of Open Access Journals (Sweden)

    Rhianna C. Laker

    2016-01-01

    Full Text Available An unresolved and critically important question in skeletal muscle biology is how muscle stem cells initiate and regulate the genetic program during muscle development. Epigenetic dynamics are essential for cellular development and organogenesis in early life and it is becoming increasingly clear that epigenetic remodeling may also be responsible for the cellular adaptations that occur in later life. DNA methylation of cytosine bases within CpG dinucleotide pairs is an important epigenetic modification that reduces gene expression when located within a promoter or enhancer region. Recent advances in the field suggest that epigenetic regulation is essential for skeletal muscle stem cell identity and subsequent cell development. This review summarizes what is currently known about how skeletal muscle stem cells regulate the myogenic program through DNA methylation, discusses a novel role for metabolism in this process, and addresses DNA methylation dynamics in adult skeletal muscle in response to physical activity.

  19. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle.

    Science.gov (United States)

    Dagdeviren, Sezin; Jung, Dae Young; Friedline, Randall H; Noh, Hye Lim; Kim, Jong Hun; Patel, Payal R; Tsitsilianos, Nicholas; Inashima, Kunikazu; Tran, Duy A; Hu, Xiaodi; Loubato, Marilia M; Craige, Siobhan M; Kwon, Jung Yeon; Lee, Ki Won; Kim, Jason K

    2017-02-01

    Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging-associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18-mo-old transgenic mice with muscle-specific overexpression of IL-10 (M IL10 ) and in wild-type mice during hyperinsulinemic-euglycemic clamping. Despite similar fat mass and energy balance, M IL10 mice were protected from aging-associated insulin resistance with significant increases in glucose infusion rates, whole-body glucose turnover, and skeletal muscle glucose uptake (∼60%; P Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle. © FASEB.

  20. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Kiens, Bente

    2014-01-01

    It has become increasingly apparent that substrate metabolism is subject to gender-specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have...... a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole-body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual...... higher insulin sensitivity of female skeletal muscle can be related to gender-specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism...

  1.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  2. Deciphering skeletal patterning: clues from the limb.

    Science.gov (United States)

    Mariani, Francesca V; Martin, Gail R

    2003-05-15

    Even young children can distinguish a Tyrannosaurus rex from a Brontosaurus by observing differences in bone size, shape, number and arrangement, that is, skeletal pattern. But despite our extensive knowledge about cartilage and bone formation per se, it is still largely a mystery how skeletal pattern is established. Much of what we do know has been learned from studying limb development in chicken and mouse embryos. Based on the data from such studies, models for how limb skeletal pattern is established have been proposed and continue to be hotly debated.

  3. Exercise Promotes Healthy Aging of Skeletal Muscle

    Science.gov (United States)

    Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

    2016-01-01

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

  4. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

    Science.gov (United States)

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

    2016-10-14

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

    Science.gov (United States)

    Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

    2016-01-01

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

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

    Science.gov (United States)

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

    2014-10-01

    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.

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

    Science.gov (United States)

    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

  8. Unilateral and bilateral dental transpositions in the maxilla-dental and skeletal findings in 63 individuals.

    Science.gov (United States)

    Danielsen, J C; Karimian, K; Ciarlantini, R; Melsen, B; Kjær, I

    2015-12-01

    This was to elucidate dental and skeletal findings in individuals with unilateral and bilateral maxillary dental transpositions. The sample comprised of radiographic materials from 63 individuals with maxillary dental transpositions from the Departments of Odontology at the Universities of Copenhagen and Aarhus and by the Danish municipal orthodontic service. The cases were divided into three groups: unilateral transposition of the canine and first premolar (Type 1U), bilateral transposition of canine and first premolar (Type 1B), and unilateral transposition of canine and lateral incisor (Type 2). The dentitions were analysed regarding agenesis and dental morphological anomalies on panoramic radiographs, and craniofacial aspects were cephalometrically analysed on profile images The results were statistically evaluated. All groups demonstrated increased occurrences of agenesis (Type 1U and Type 1B: 31 agenesis in 15 patients; and Type 2 three agenesis in three patients). Taurodontic root morphology was most dominant in Type 1U. Peg-shaped lateral incisors showed an increased occurrence, though not in Type 1U. Skeletally, Type 1B and Type 1U demonstrated maxillary retrognathia (more pronounced in Type 1B). Type 2 showed a significant posterior inclination of the maxilla. Transpositions of maxillary canines involve dental and skeletal deviations. Dental deviations were predominantly taurodontic root morphology and agenesis. Regarding skeletal deviations, bilateral transpositions of the canines and the first premolars are associated with skeletal changes. Unilateral transpositions are possibly a localised deviation with minor or no skeletal involvements. The results indicate a possible difference in the aetiologies of unilateral and bilateral transpositions.

  9. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice.

    Science.gov (United States)

    Lindegaard, Birgitte; Matthews, Vance B; Brandt, Claus; Hojman, Pernille; Allen, Tamara L; Estevez, Emma; Watt, Matthew J; Bruce, Clinton R; Mortensen, Ole H; Syberg, Susanne; Rudnicka, Caroline; Abildgaard, Julie; Pilegaard, Henriette; Hidalgo, Juan; Ditlevsen, Susanne; Alsted, Thomas J; Madsen, Andreas N; Pedersen, Bente K; Febbraio, Mark A

    2013-09-01

    Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high-fat diet (HFD)-induced insulin resistance by activating AMP-activated protein kinase (AMPK). We studied mice with a global deletion of the α-isoform of the IL-18 receptor (IL-18R(-/-)) fed a standard chow or HFD. We next performed gain-of-function experiments in skeletal muscle, in vitro, ex vivo, and in vivo. We show that IL-18 is implicated in metabolic homeostasis, inflammation, and insulin resistance via mechanisms involving the activation of AMPK in skeletal muscle. IL-18R(-/-) mice display increased weight gain, ectopic lipid deposition, inflammation, and reduced AMPK signaling in skeletal muscle. Treating myotubes or skeletal muscle strips with IL-18 activated AMPK and increased fat oxidation. Moreover, in vivo electroporation of IL-18 into skeletal muscle activated AMPK and concomitantly inhibited HFD-induced weight gain. In summary, IL-18 enhances AMPK signaling and lipid oxidation in skeletal muscle implicating IL-18 in metabolic homeostasis.

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

    Science.gov (United States)

    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

  11. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    Science.gov (United States)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  12. Effect of Lithium on the Mechanism of Glucose Transport in Skeletal Muscles.

    Science.gov (United States)

    Jung, Suryun; Koh, Jinho; Kim, Sanghyun; Kim, Kijin

    2017-01-01

    While lithium is known to stimulate glucose transport into skeletal muscle, the mechanisms of the increased glucose transport by lithium in skeletal muscle are not well defined yet. We excised epitrochlearis muscles from male Wistar rats and measured the transport rates of a glucose analog into lithium-, insulin-, and muscular contraction-stimulated skeletal muscle tissue and we also analyzed the levels of cell surface glucose transport 4 using a photolabeling and multicolor immunofluorescence method. In addition, we generated a cell line that stably expresses myc-tagged GLUT4 to measure the rates of GLUT4 internalization and externalization. Lithium significantly increased 2-DG glucose transport rate in skeletal muscles; however, it was significantly lower than the stimulation induced by the maximum concentration of insulin or tetanic contraction. But co-treatment of lithium with insulin or tetanic contraction increased glucose transport rate by ∼200% more than lithium alone. When skeletal muscle tissues were treated with lithium, insulin, and muscular contraction, the levels of cell surface GLUT4 protein contents were increased similarly by ∼6-fold compared with the basal levels. When insulin or lithium stimuli were maintained, the rate of GLUT4myc internalization was significantly lower, and lithium was found to suppress the internalization of GLUT4myc more strongly. The lithium-induced increase in glucose uptake of skeletal muscles appears to increase in cell surface GLUT4 levels caused by decreased internalization of GLUT4. It is concluded that co-treatment of lithium with insulin and muscular contraction had a synergistic effect on glucose transport rate in skeletal muscle.

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

    OpenAIRE

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

    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 technic...

  14. Skeletal muscle injury and repair in marathon runners after competition.

    Science.gov (United States)

    Warhol, M J; Siegel, A J; Evans, W J; Silverman, L M

    1985-02-01

    Elevated serum creatine kinase MB isoenzyme (CK-MB) activity in marathon runners after competition may arise from injury to skeletal muscle, myocardium, or a combined tissue source. Normal radionuclide myocardial scintigraphy and the selective increase in skeletal muscle CK-MB reported in such runners strongly suggest a peripheral source. To understand this biochemical finding, the authors examined gastrocnemius muscles by electron microscopy from 40 male marathon runners at intervals after competition and from 12 male nonrunners. Muscle from runners showed post-race ultrastructural changes of focal fiber injury and repair: intra- and extracellular edema with endothelial injury; myofibrillar lysis, dilation and disruption of the T-tubule system, and focal mitochondrial degeneration without inflammatory infiltrate (1-3 days). The mitochondrial and myofibrillar damage showed progressive repair by 3-4 weeks. Late biopsies showed central nuclei and satellite cells characteristic of the regenerative response (8-12 weeks). Muscle from veteran runners showed intercellular collagen deposition suggestive of a fibrotic response to repetitive injury. Control tissue from nonrunners showed none of these findings. The sequential morphologic changes in runners suggest that the increase in skeletal muscle CK-MB is a marker of cellular regeneration.

  15. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

    Science.gov (United States)

    McCarthy, John J.; Mula, Jyothi; Miyazaki, Mitsunori; Erfani, Rod; Garrison, Kelcye; Farooqui, Amreen B.; Srikuea, Ratchakrit; Lawson, Benjamin A.; Grimes, Barry; Keller, Charles; Van Zant, Gary; Campbell, Kenneth S.; Esser, Karyn A.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.

    2011-01-01

    An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells. PMID:21828094

  16. An in vitro model of skeletal muscle volume regulation.

    Science.gov (United States)

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

    2015-01-01

    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. 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. Medium osmolality was increased by addition of up to 200 mM sucrose. Addition of 200 mM sucrose resulted in mean cell shrinkage of 44±1% after 30 mins. 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%). 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.

  17. An in vitro model of skeletal muscle volume regulation.

    Directory of Open Access Journals (Sweden)

    Anna Wibberley

    Full Text Available 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.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.Medium osmolality was increased by addition of up to 200 mM sucrose. Addition of 200 mM sucrose resulted in mean cell shrinkage of 44±1% after 30 mins. 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%.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.

  18. Cardiac, Skeletal, and smooth muscle mitochondrial respiration

    DEFF Research Database (Denmark)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I

    2014-01-01

    in cardiac, skeletal, and smooth muscle suggest all mitochondria are created equal, the contrasting RCR and non-phosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation...

  19. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  20. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis.

    Science.gov (United States)

    Kumar, Avinash; Davuluri, Gangarao; Silva, Rafaella Nascimento E; Engelen, Marielle P K J; Ten Have, Gabrie A M; Prayson, Richard; Deutz, Nicolaas E P; Dasarathy, Srinivasan

    2017-06-01

    Sarcopenia or skeletal muscle loss is a frequent, potentially reversible complication in cirrhosis that adversely affects clinical outcomes. Hyperammonemia is a consistent abnormality in cirrhosis that results in impaired skeletal muscle protein synthesis and breakdown (proteostasis). Despite the availability of effective ammonia-lowering therapies, whether lowering ammonia restores proteostasis and increases muscle mass is unknown. Myotube diameter, protein synthesis, and molecular responses in C2C12 murine myotubes to withdrawal of ammonium acetate following 24-hour exposure to 10 mM ammonium acetate were complemented by in vivo studies in the hyperammonemic portacaval anastomosis rat and sham-operated, pair-fed Sprague-Dawley rats treated with ammonia-lowering therapy by l-ornithine l-aspartate and rifaximin orally for 4 weeks. We observed reduced myotube diameter, impaired protein synthesis, and increased autophagy flux in response to hyperammonemia, which were partially reversed following 24-hour and 48-hour withdrawal of ammonium acetate. Consistently, 4 weeks of ammonia-lowering therapy resulted in significant lowering of blood and skeletal muscle ammonia, increase in lean body mass, improved grip strength, higher skeletal muscle mass and diameter, and an increase in type 2 fibers in treated compared to untreated portacaval anastomosis rats. The increased skeletal muscle myostatin expression, reduced mammalian target of rapamycin complex 1 function, and hyperammonemic stress response including autophagy markers normally found in portacaval anastomosis rats were reversed by treatment with ammonia-lowering therapy. Despite significant improvement, molecular and functional readouts were not completely reversed by ammonia-lowering measures. Ammonia-lowering therapy results in improvement in skeletal muscle phenotype and function and molecular perturbations of hyperammonemia; these preclinical studies complement previous studies on ammonia-induced skeletal muscle

  1. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M

    2016-01-01

    caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial...... respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle....

  2. Skeletal Aging and Osteoporosis Biomechanics and Mechanobiology

    CERN Document Server

    2013-01-01

    The focus of this book is on mechanical aspects of skeletal fragility related to aging and osteoporosis. Topics include: Age-related changes in trabecular structure and strength; age-related changes in cortical material properties; age-related changes in whole-bone structure; predicting bone strength and fracture risk using image-based methods and finite element analysis; animal models of osteoporosis and aging; age-related changes in skeletal mechano responsiveness; exercise and physical interventions for osteoporosis.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

    Science.gov (United States)

    Al-Khazraji, Baraa K.; Mortensen, Stefan P.; Jackson, Dwayne N.; Ellis, Christopher G.; Hellsten, Ylva

    2013-01-01

    During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1–10 μM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition of NO and prostanoid formation. Inhibition of these systems abolished the vasodilator effect of ATP. Cell-culture experiments verified ATP-induced formation of NO and prostacyclin in rat skeletal muscle microvascular endothelial cells, and ATP-induced formation of NO in rat skeletal muscle cells. To confirm these findings in humans, ATP was infused into skeletal muscle interstitium of healthy subjects via microdialysis probes and found to increase muscle interstitial concentrations of NO and prostacyclin by ∼60% and ∼40%, respectively. Collectively, these data suggest that a physiologically relevant elevation in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation. PMID:23761642

  5. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to L-carnitine and faster recovery from muscle fatigue after exercise (ID 738, 1492, 1493), skeletal muscle tissue repair (ID 738, 1492, 1493), increase in endurance, capacity (ID 4305, 4684), maintenance of normal blood LDL-cholesterol concentrations (ID 1494, 4684), contribution to normal spermatogenesis (ID 1822), “energy metabolism” (ID 1821), and increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy (ID 1495) pursuant

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to L-carnitine and faster recovery from muscle fatigue after exercise, skeletal muscle tissue repair, increase in endurance capacity, maintenance of normal blood LDL-cholesterol concentrations, contribution to normal spermatogenesis, “energy metabolism”, and increasing L-carnitine....... The food constituent that is the subject of the health claims is carnitine (as L-carnitine). The Panel considers that L-carnitine is sufficiently characterised.......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...

  6. Deletion of Pofut1 in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes in cis and in trans

    Science.gov (United States)

    Zygmunt, Deborah A.; Singhal, Neha; Kim, Mi-Lyang; Cramer, Megan L.; Crowe, Kelly E.; Xu, Rui; Jia, Ying; Adair, Jessica; Martinez-Pena y Valenzuela, Isabel; Akaaboune, Mohammed; White, Peter; Janssen, Paulus M.

    2017-01-01

    ABSTRACT Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the protein O-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction. Changed phenotypes include reduced skeletal muscle size and strength, decreased myofiber size, increased slow fiber (type 1) density, increased muscle degeneration and regeneration in aged muscles, decreased satellite cell self-renewal and regenerative potential, and increased neuromuscular fragmentation and occasional denervation. Pofut1 deletion in skeletal myofibers reduced NotchR signaling in young adult muscles, but this effect was lost with age. Increasing muscle NotchR signaling also reduced muscle size. Gene expression studies point to regulation of cell cycle genes, muscle myosins, NotchR and Wnt pathway genes, and connective tissue growth factor by Pofut1 in skeletal muscle, with additional effects on α dystroglycan glycosylation. PMID:28265002

  7. Skeletal shape correspondence via entropy minimization

    Science.gov (United States)

    Tu, Liyun; Styner, Martin; Vicory, Jared; Paniagua, Beatriz; Prieto, Juan Carlos; Yang, Dan; Pizer, Stephen M.

    2015-03-01

    Purpose: Improving the shape statistics of medical image objects by generating correspondence of interior skeletal points. Data: Synthetic objects and real world lateral ventricles segmented from MR images. Method(s): Each object's interior is modeled by a skeletal representation called the s-rep, which is a quadrilaterally sampled, folded 2-sided skeletal sheet with spoke vectors proceeding from the sheet to the boundary. The skeleton is divided into three parts: up-side, down-side and fold-curve. The spokes on each part are treated separately and, using spoke interpolation, are shifted along their skeletal parts in each training sample so as to tighten the probability distribution on those spokes' geometric properties while sampling the object interior regularly. As with the surface-based correspondence method of Cates et al., entropy is used to measure both the probability distribution tightness and sampling regularity. The spokes' geometric properties are skeletal position, spoke length and spoke direction. The properties used to measure the regularity are the volumetric subregions bounded by the spokes, their quadrilateral sub-area and edge lengths on the skeletal surface and on the boundary. Results: Evaluation on synthetic and real world lateral ventricles demonstrated improvement in the performance of statistics using the resulting probability distributions, as compared to methods based on boundary models. The evaluation measures used were generalization, specificity, and compactness. Conclusions: S-rep models with the proposed improved correspondence provide significantly enhanced statistics as compared to standard boundary models.

  8. Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

    Science.gov (United States)

    McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

    2017-01-01

    More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and

  9. Channelopathies of skeletal muscle excitability.

    Science.gov (United States)

    Cannon, Stephen C

    2015-04-01

    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, and 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. © 2015 American Physiological Society.

  10. Diagnosis of skeletal muscle channelopathies.

    Science.gov (United States)

    Spillane, Jennifer; Fialho, Doreen; Hanna, Michael G

    2013-11-01

    Skeletal muscle channelopathies are rare disorders of muscle membrane excitability. Their episodic nature may result in diagnostic difficulty and delays in diagnosis. Advances in diagnostic clinical electrophysiology combined with DNA-based diagnosis have improved diagnostic accuracy and efficiency. Ascribing pathogenic status to identified genetic variants in muscle channel genes may be complex and functional analysis, including molecular expression, may help with this. Accurate clinical and genetic diagnosis enables genetic counselling, advice regarding prognosis and aids treatment selection. An approach to accurate and efficient diagnosis is outlined. The importance of detailed clinical evaluation including careful history, examination and family history is emphasised. The role of specialised electrodiagnostics combined with DNA testing and molecular expression is considered. New potential biomarkers including muscle MRI using MRC Centre protocols are discussed. A combined diagnostic approach using careful clinical assessment, specialised neurophysiology and DNA testing will now achieve a clear diagnosis in most patients with muscle channelopathies. An accurate diagnosis enables genetic counselling and provides information regarding prognosis and treatment selection. Genetic analysis often identifies new variants of uncertain significance. In this situation, functional expression studies as part of a diagnostic service will enable determination of pathogenic status of novel genetic variants.

  11. Radiological diagnosis of skeletal tuberculosis

    International Nuclear Information System (INIS)

    Numberger, J.

    1982-01-01

    The general X-ray-symptoms follow one another or appear at the same time: Swelling of soft tissues by fungus; toxic perifocal and sometimes parafocal osteoporosis; osteolysis by specific granulation tissues; destruction of adjacent discs and articulation cartilages; formation of sequesters; cold abscess and formation of fistulas because of perforation of the corticalis by liquified tuberculous tissue; bone compression and deformation; amorphous calcifications; perifocal osteosclerosis as a repairing process. The spondylitis tuberculosis is the most frequent form with about 50%; usually narrowing of the discspace is the earliest X-ray-finding. On the second and third place follow the tuberculosis of the hip- and the knee-joint, the rest shows up at other locations of red bone marrow. Very often the perifocal osteoporosis is the earliest X-ray-symptom of joint tuberculosis. All X-ray-findings, even the earliest, in reality are late symptoms, because at that time the disease exists at least some months. Radiologically only the differential diagnosis can be made, final diagnosis is established by histologic examination only. Because the course of untreated skeletal tuberculosis usually is chronic and destructive and, on the other hand early antituberculous chemotherapy as well as surgical treatment show excellent results early radiological suggestion of tuberculosis is of great importance for initiating other diagnostic procedures to establish the diagnosis. (orig./MG) [de

  12. Long-lasting effect of obesity on skeletal muscle transcriptome.

    Science.gov (United States)

    Messaoudi, Ilhem; Handu, Mithila; Rais, Maham; Sureshchandra, Suhas; Park, Byung S; Fei, Suzanne S; Wright, Hollis; White, Ashley E; Jain, Ruhee; Cameron, Judy L; Winters-Stone, Kerri M; Varlamov, Oleg

    2017-05-25

    Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. Six male rhesus macaques of 12-13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitivity, the majority of WSD-induced (n = 457) and WSD-suppressed (n = 47) genes remained significantly dysregulated after caloric restriction (FDR ≤0.05). The Metacore TM pathway analysis reveals that western-style diet induced the sustained activation of the transforming growth factor-β gene network, associated with extracellular matrix remodeling, and the downregulation of genes involved in muscle structure development and nutritional processes. Western-style diet, in the absence of exercise, induced skeletal muscle transcriptional programing, which persisted even after insulin resistance and glucose intolerance were completely reversed with caloric restriction.

  13. Role of pericytes in skeletal muscle regeneration and fat accumulation.

    Science.gov (United States)

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

    2013-08-15

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

  14. Overweight in elderly people induces impaired autophagy in skeletal muscle.

    Science.gov (United States)

    Potes, Yaiza; de Luxán-Delgado, Beatriz; Rodriguez-González, Susana; Guimarães, Marcela Rodrigues Moreira; Solano, Juan J; Fernández-Fernández, María; Bermúdez, Manuel; Boga, Jose A; Vega-Naredo, Ignacio; Coto-Montes, Ana

    2017-09-01

    Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Premature aging in skeletal muscle lacking serum response factor.

    Directory of Open Access Journals (Sweden)

    Charlotte Lahoute

    Full Text Available 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.

  16. Proteomics analysis of the zebrafish skeletal extracellular matrix.

    Directory of Open Access Journals (Sweden)

    Maurijn Y Kessels

    Full Text Available The extracellular matrix of the immature and mature skeleton is key to the development and function of the skeletal system. Notwithstanding its importance, it has been technically challenging to obtain a comprehensive picture of the changes in skeletal composition throughout the development of bone and cartilage. In this study, we analyzed the extracellular protein composition of the zebrafish skeleton using a mass spectrometry-based approach, resulting in the identification of 262 extracellular proteins, including most of the bone and cartilage specific proteins previously reported in mammalian species. By comparing these extracellular proteins at larval, juvenile, and adult developmental stages, 123 proteins were found that differed significantly in abundance during development. Proteins with a reported function in bone formation increased in abundance during zebrafish development, while analysis of the cartilage matrix revealed major compositional changes during development. The protein list includes ligands and inhibitors of various signaling pathways implicated in skeletogenesis such as the Int/Wingless as well as the insulin-like growth factor signaling pathways. This first proteomic analysis of zebrafish skeletal development reveals that the zebrafish skeleton is comparable with the skeleton of other vertebrate species including mammals. In addition, our study reveals 6 novel proteins that have never been related to vertebrate skeletogenesis and shows a surprisingly large number of differences in the cartilage and bone proteome between the head, axis and caudal fin regions. Our study provides the first systematic assessment of bone and cartilage protein composition in an entire vertebrate at different stages of development.

  17. Approach to Investigating Congenital Skeletal Abnormalities in Livestock.

    Science.gov (United States)

    Dittmer, K E; Thompson, K G

    2015-09-01

    Congenital skeletal abnormalities may be genetic, teratogenic, or nutritional in origin; distinguishing among these different causes is essential in the management of the disease but may be challenging. In some cases, teratogenic or nutritional causes of skeletal abnormalities may appear very similar to genetic causes. For example, chondrodysplasia associated with intrauterine zinc or manganese deficiency and mild forms of hereditary chondrodysplasia have very similar clinical features and histologic lesions. Therefore, historical data are essential in any attempt to distinguish genetic and acquired causes of skeletal lesions; as many animals as possible should be examined; and samples should be collected for future analysis, such as genetic testing. Acquired causes of defects often show substantial variation in presentation and may improve with time, while genetic causes frequently have a consistent presentation. If a disease is determined to be of genetic origin, a number of approaches may be used to detect mutations, each with advantages and disadvantages. These approaches include sequencing candidate genes, single-nucleotide polymorphism array with genomewide association studies, and exome or whole genome sequencing. Despite advances in technology and increased cost-effectiveness of these techniques, a good clinical history and description of the pathology and a reliable diagnosis are still key components of any investigation. © The Author(s) 2015.

  18. Protein Availability and Satellite Cell Dynamics in Skeletal Muscle.

    Science.gov (United States)

    Shamim, Baubak; Hawley, John A; Camera, Donny M

    2018-03-20

    Human skeletal muscle satellite cells are activated in response to both resistance and endurance exercise. It was initially proposed that satellite cell proliferation and differentiation were only required to support resistance exercise-induced hypertrophy. However, satellite cells may also play a role in muscle fibre remodelling after endurance-based exercise and extracellular matrix regulation. Given the importance of dietary protein, particularly branched chain amino acids, in supporting myofibrillar and mitochondrial adaptations to both resistance and endurance-based training, a greater understanding of how protein intake impacts satellite cell activity would provide further insight into the mechanisms governing skeletal muscle remodelling with exercise. While many studies have investigated the capacity for protein ingestion to increase post-exercise rates of muscle protein synthesis, few investigations have examined the role for protein ingestion to modulate satellite cell activity. Here we review the molecular mechanisms controlling the activation of satellite cells in response to mechanical stress and protein intake in both in vitro and in vivo models. We provide a mechanistic framework that describes how protein ingestion may enhance satellite activity and promote exercise adaptations in human skeletal muscle.

  19. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  20. Macrophage Plasticity in Skeletal Muscle Repair

    Directory of Open Access Journals (Sweden)

    Elena Rigamonti

    2014-01-01

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

  1. Endurance training enhances skeletal muscle interleukin-15 in human male subjects

    DEFF Research Database (Denmark)

    Rinnov, Anders; Yfanti, Christina; Nielsen, Søren

    2014-01-01

    Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular...... endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer...... weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p...

  2. Human skeletal muscle aging and the oxidative system: cellular events.

    Science.gov (United States)

    Rossi, Paola; Marzani, Barbara; Giardina, Silvana; Negro, Massimo; Marzatico, Fulvio

    2008-12-01

    As we age, the aerobic and functional capacities of our major physiological systems progressively decline. In the case of the neuromuscular system, reductions in strength and mobility cause a deterioration in motor performance and in turn a greater tendency to fall (with increased risk of fractures), impaired mobility, disability and loss of independence in the elderly. Given the increase in our life expectancy and the consequent growth in the elderly population, these conditions will have an increasing impact on modern healthcare systems, and their prevention and attenuation needs to be addressed. Several intervention strategies have been used to improve motor performance among the aging. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS) generated by the addition of a single electron to the oxygen molecule As the level of oxidative stress in skeletal muscle increases with age, the production of some antioxidant enzymes increases adaptively to compensate in part. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fiber composition, muscle type and function).

  3. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Zheng, Timothy S.; Burkly, Linda C. [Department of Immunology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142 (United States); Kumar, Ashok, E-mail: ashok.kumar@louisville.edu [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States)

    2014-04-18

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways.

  4. Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, Ana, E-mail: ana-sierra@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Subbotina, Ekaterina, E-mail: ekaterina-subbotina@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Zhu, Zhiyong, E-mail: zhiyong-zhu@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Gao, Zhan, E-mail: zhan-gao@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Koganti, Siva Rama Krishna, E-mail: sivaramakrishna.koganti@ttuhc.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Coetzee, William A., E-mail: william.coetzee@nyumc.org [Department of Pediatrics, NYU School of Medicine, New York, NY 10016 (United States); Goldhamer, David J., E-mail: david.goldhamer@uconn.edu [Center for Regenerative Biology, Department of Molecular and Cell Biology, Advanced Technology Laboratory, University of Connecticut, 1392 Storrs Road Unit 4243, Storrs, Connecticut 06269 (United States); Hodgson-Zingman, Denice M., E-mail: denice-zingman@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, Iowa City, IA 52242 (United States); Zingman, Leonid V., E-mail: leonid-zingman@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Veterans Affairs, Medical Center, Iowa City, IA 52242 (United States)

    2016-02-26

    Sarcolemmal ATP-sensitive potassium (K{sub ATP}) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle K{sub ATP} channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle K{sub ATP} channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of K{sub ATP} channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) – an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish K{sub ATP} channel-dependent musclin production as a potential mechanistic link coupling “local” skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. - Highlights: • ATP-sensitive K{sup +} channels regulate musclin production by skeletal muscles. • Lipolytic ANP signaling is promoted by augmented skeletal muscle musclin production. • Skeletal muscle musclin transcription is promoted by a CaMKII/HDAC/FOXO1 pathway. • Musclin links adipose mobilization to energy use in K{sub ATP} channel deficient skeletal muscle.

  5. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    International Nuclear Information System (INIS)

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

    2014-01-01

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways

  6. Oxidative stress (glutathionylation and Na,K-ATPase activity in rat skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Carsten Juel

    Full Text Available Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation on the Na,K-ATPase in rat skeletal muscle membranes.Immunoprecipitation with an anti-glutathione antibody and subsequent immunodetection of Na,K-ATPase protein subunits demonstrated 9.0±1.3% and 4.1±1.0% glutathionylation of the α isoforms in oxidative and glycolytic skeletal muscle, respectively. In oxidative muscle, 20.0±6.1% of the β1 units were glutathionylated, whereas 14.8±2.8% of the β2-subunits appear to be glutathionylated in glycolytic muscle. Treatment with the reducing agent dithiothreitol (DTT, 1 mM increased the in vitro maximal Na,K-ATPase activity by 19% (P<0.05 in membranes from glycolytic muscle. Oxidized glutathione (GSSG, 0-10 mM increased the in vitro glutathionylation level detected with antibodies, and decreased the in vitro maximal Na,K-ATPase activity in a dose-dependent manner, and with a larger effect in oxidative compared to glycolytic skeletal muscle.This study demonstrates the existence of basal glutathionylation of both the α and the β units of rat skeletal muscle Na,K-ATPase. In addition, the study suggests a negative correlation between glutathionylation levels and maximal Na,K-ATPase activity.Glutathionylation likely contributes to the complex regulation of Na,K-ATPase function in skeletal muscle. Especially, glutathionylation induced by oxidative stress may have a role in Na,K-ATPase regulation during prolonged muscle activity.

  7. Skeletal Stem Cells: Origins, Functions and Uncertainties.

    Science.gov (United States)

    Mohamed, Fatma F; Franceschi, Renny T

    2017-12-01

    The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

  8. Heparan sulfate in skeletal muscle development

    International Nuclear Information System (INIS)

    Noonan, D.M.

    1985-01-01

    In this study, chick breast skeletal muscle cells developing in vitro from myoblasts to myotubes were found to synthesize heparan sulfate (HS), chrondroitin-6-sulfate, chrondroitin-4-sulfate, dermatan sulfate, unsulfated chrondroitin and hyaluronic acid in both the substratum attached material (SAM) and the cellular fraction. SAM was found to contain predominantly chrondroitin-6-sulfate and relatively little HS whereas the cellular fraction contained relatively higher levels of HS and lower levels of chrondroitin-6-sulfate. Hyaluronic acid was also a major component in both fractions with the other glycosaminoglycan isomers present as minor components. Muscle derived fibroblast cultures had higher levels of dermatan sulfate in the cell layer and higher levels of HS in the SAM fraction than did muscle cultures. The structure of the proteoglycans were partially characterized in 35 SO 4 2- radio-labeled cultures which indicated an apparent increase in the hydrodynamic size of the cell fraction heparan sulfate proteoglycan (HS PG). Myotubes incorporated 35 SO 4 2- into HS PG at a rate 3 times higher than myoblasts. The turnover rate of HS in the cellular fraction was the same for myoblasts and myotubes, with a t/sub 1/2/ of approximately 5 hours. Fibroblasts in culture synthesized the smallest HS PG, and incorporated 35 SO 4 2- into HS PG at a rate lower than that of myotubes. Studies in which fusion was reversibly inhibited with decreased medium [Ca ++ ] closely linked the increased synthesis of cell fraction, but not SAM fraction, HS with myotube formation. However, decreasing medium calcium appeared to cause significant alterations in the metabolism of inorganic sulfate

  9. Genetic engineering for skeletal regenerative medicine.

    Science.gov (United States)

    Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

    2007-01-01

    The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

  10. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

    PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue...... noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro expanded muscle...... with its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...

  11. Skeletal dysplasia: Respiratory management during infancy.

    Science.gov (United States)

    Alapati, Deepthi; Shaffer, Thomas H

    2017-10-01

    Skeletal dysplasia encompasses a variety of developmental disorders of the bone and cartilage that manifest as disproportionate shortening of limbs and trunk in the neonate. Many types of skeletal dysplasia are complicated by respiratory failure at or soon after birth and require intensive care and prolonged hospitalization. Respiratory complications in these infants are complex and are characterized by airway anomalies, restrictive lung disease due to a narrow and abnormally compliant chest wall, pulmonary hypoplasia, and central apnea. Appropriate management of these unique patients requires a clear understanding of the pathophysiology and use of pulmonary function tests for early recognition and management of complications. This review provides an overview of the underlying respiratory pathology and a practical guide to the newborn care provider for the diagnosis and management of respiratory complications in infants with skeletal dysplasia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    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.

  13. In situ microdialysis of intramuscular prostaglandin and thromboxane in contracting skeletal muscle in humans

    DEFF Research Database (Denmark)

    Karamouzis, M; Langberg, Henning; Skovgaard, D

    2001-01-01

    Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis.......97 +/- 0.75 (exercise), P measurable...... amounts of prostaglandins and thromboxanes in the interstitial space of skeletal muscle. Furthermore, the concentration of prostaglandin E2 is unchanged during static calf exercise and increased markedly with dynamic thigh muscle exercise, which together with an exercise induced increase in muscle blood...

  14. Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway.

    Science.gov (United States)

    Markworth, James F; Cameron-Smith, David

    2013-01-01

    Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro. C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF(2α) and PGE(2); however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.

  15. Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model

    Directory of Open Access Journals (Sweden)

    Jenna N. Regan

    2017-12-01

    Full Text Available Muscle weakness and cachexia are significant paraneoplastic syndromes of many advanced cancers. Osteolytic bone metastases are common in advanced breast cancer and are a major contributor to decreased survival, performance, and quality of life for patients. Pathologic fracture caused by osteolytic cancer in bone (OCIB leads to a significant (32% increased risk of death compared to patients without fracture. Since muscle weakness is linked to risk of falls which are a major cause of fracture, we have investigated skeletal muscle response to OCIB. Here, we show that a syngeneic mouse model of OCIB (4T1 mammary tumor cells leads to cachexia and skeletal muscle weakness associated with oxidation of the ryanodine receptor and calcium (Ca2+ release channel (RyR1. Muscle atrophy follows known pathways via both myostatin signaling and expression of muscle-specific ubiquitin ligases, atrogin-1 and MuRF1. We have identified a mechanism for skeletal muscle weakness due to increased oxidative stress on RyR1 via NAPDH oxidases [NADPH oxidase 2 (Nox2 and NADPH oxidase 4 (Nox4]. In addition, SMAD3 phosphorylation is higher in muscle from tumor-bearing mice, a critical step in the intracellular signaling pathway that transmits TGFβ signaling to the nucleus. This is the first time that skeletal muscle weakness has been described in a syngeneic model of OCIB and represents a unique model system in which to study cachexia and changes in skeletal muscle.

  16. Sumoylated α-skeletal muscle actin in the skeletal muscle of adult rats.

    Science.gov (United States)

    Uda, Munehiro; Kawasaki, Hiroaki; Iizumi, Kyoichi; Shigenaga, Ayako; Baba, Takeshi; Naito, Hisashi; Yoshioka, Toshitada; Yamakura, Fumiyuki

    2015-11-01

    Skeletal muscles are composed of two major muscle fiber types: slow-twitch oxidative fibers and fast-twitch glycolytic fibers. The proteins in these muscle fibers are known to differ in their expression, relative abundance, and post-translational modifications. In this study, we report a previously unreported post-translational modification of α-skeletal muscle actin in the skeletal muscles of adult male F344 rats in vivo. Using two-dimensional electrophoresis (2D-PAGE), we first examined the differences in the protein expression profiles between the soleus and plantaris muscles. We found higher intensity protein spots at approximately 60 kDa and pH 9 on 2D-PAGE for the soleus muscle compared with the plantaris muscle. These spots were identified as α-skeletal muscle actin by liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry and western blot analyses. In addition, we found that the 60 kDa α-skeletal muscle actin is modified by small ubiquitin-like modifier (SUMO) 1, using 2D-PAGE and western blot analyses. Furthermore, we found that α-skeletal muscle actin with larger molecular weight was localized in the nuclear and cytosol of the skeletal muscle, but not in the myofibrillar fraction by the combination of subcellular fractionation and western blot analyses. These results suggest that α-skeletal muscle actin is modified by SUMO-1 in the skeletal muscles, localized in nuclear and cytosolic fractions, and the extent of this modification is much higher in the slow muscles than in the fast muscles. This is the first study to show the presence of SUMOylated actin in animal tissues.

  17. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

    Science.gov (United States)

    Ono, Taisuke; Takada, Shingo; Kinugawa, Shintaro; Tsutsui, Hiroyuki

    2015-09-01

    What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative

  18. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    NARCIS (Netherlands)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal

  19. Contraction-induced changes in skeletal muscle Na(+), K(+) pump mRNA expression - importance of exercise intensity and Ca(2+)-mediated signalling

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai Baastrup; Kusuhara, K; Hellsten, Ylva

    2010-01-01

    Abstract Aim: To investigate if exercise intensity and Ca(2+) signalling regulate Na(+), K(+) pump mRNA expression in skeletal muscle. Methods: The importance of exercise intensity was evaluated by having trained and untrained humans perform intense intermittent and prolonged exercise...... skeletal muscles increased (PNa(+), K(+) pump alpha1 and beta1 mRNA expression in trained subjects are more...

  20. Exercise induced capillary growth in human skeletal muscle and the dynamics of VEGF

    DEFF Research Database (Denmark)

    Høier, Birgitte; Hellsten, Ylva

    2014-01-01

    In skeletal muscle, growth of capillaries is an important adaptation to exercise training that secures adequate diffusion capacity for oxygen and nutrients even at high intensity exercise when increases in muscle blood flow are profound. Mechanical forces present during muscle activity......, such as shear stress and passive stretch, lead to cellular signalling, enhanced expression of angiogenic factors and initiation of capillary growth. The most central angiogenic factor in skeletal muscle capillary growth is vascular endothelial growth factor (VEGF). During muscle contraction, VEGF increases...... in the muscle interstitium, acts on VEGF receptors on the capillary endothelium and thereby stimulates angiogenic processes. A primary source of muscle interstitial VEGF during exercise is the skeletal muscle fibers which contain large stores of VEGF within vesicles. We propose that, during muscle activity...

  1. Effect of hindlimb suspension and clenbuterol treatment on polyamine levels in skeletal muscle

    Science.gov (United States)

    Abukhalaf, Imad K.; von Deutsch, Daniel A.; Wineski, Lawrence E.; Silvestrov, Natalia A.; Abera, Saare A.; Sahlu, Sinafikish W.; Potter, David E.; Thierry-Palmer, M. (Principal Investigator)

    2002-01-01

    Polyamines are unbiquitous, naturally occurring small aliphatic, polycationic, endogenous compounds. They are involved in many cellular processes and may serve as secondary or tertiary messengers to hormonal regulation. The relationship of polyamines and skeletal muscle mass of adductor longus, extensor digitorum longus, and gastrocnemius under unloading (hindlimb suspension) conditions was investigated. Unloading significantly affected skeletal muscle polyamine levels in a fiber-type-specific fashion. Under loading conditions, clenbuterol treatment increased all polyamine levels, whereas under unloading conditions, only the spermidine levels were consistently increased. Unloading attenuated the anabolic effects of clenbuterol in predominately slow-twitch muscles (adductor longus), but had little impact on clenbuterol's action as a countermeasure in fast- twitch muscles such as the extensor digitorum longus. Spermidine appeared to be the primary polyamine involved in skeletal muscle atrophy/hypertrophy. Copyright 2002 S. Karger AG, Basel.

  2. Noradrenaline spillover during exercise in active versus resting skeletal muscle in man

    DEFF Research Database (Denmark)

    Savard, G; Strange, S; Kiens, Bente

    1987-01-01

    Increases in plasma noradrenaline (NA) concentration occur during moderate to heavy exercise in man. This study was undertaken to examine the spillover of NA from both resting and contracting skeletal muscle during exercise. Six male subjects performed one-legged knee-extension so that all...... in the exercising leg than in the resting leg both during 50% and 100% leg exercise. These results suggest that contracting skeletal muscle may contribute to a larger extent than resting skeletal muscle to increasing the level of plasma NA during exercise. Contractile activity may influence the NA spillover from...... measurements could be made both in the exercising and in the resting leg. Subjects exercised for 10 min at each of 50% and 100% of the peak performance capacity of the leg. Leg blood flow was measured by thermodilution and blood samples were drawn for the determination of plasma NA and adrenaline, first...

  3. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Anne-Marie eLundsgaard

    2014-11-01

    Full Text Available It has become increasingly apparent that substrate metabolism is subject to gender specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual higher insulin sensitivity of female skeletal muscle can be related to gender specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism in men and women. In particular, the molecular machinery for glucose and fatty acid oxidative and storage capacities in skeletal muscle and its implications for substrate utilization during metabolic situations of daily living are discussed, emphasizing their relevance for substrate choice in the fed and fasted state, and during periods of physical activity and recovery. Together, handling of carbohydrate and lipids and regulation of their utilization in skeletal muscle have implications for whole body glucose homeostasis in men and women. 17-β estradiol is the most important female sex hormone, and the identification of estradiol receptors in skeletal muscle has opened for a role in regulation of substrate metabolism. Also, higher levels of circulating adipokines as adiponectin and leptin in women and their implications for muscle metabolism will be considered.

  4. External skeletal robusticity of children and adolescents - European references from birth to adulthood and international comparisons.

    Science.gov (United States)

    Mumm, Rebekka; Godina, Elena; Koziel, Slawomir; Musalek, Martin; Sedlak, Petr; Wittwer-Backofen, Ursula; Hesse, Volker; Dasgupta, Parasmani; Henneberg, Maciej; Scheffler, Christiane

    2018-02-20

    Background: In our modern world, the way of life in nutritional and activity behaviour has changed. As a consequence, parallel trends of an epidemic of overweight and a decline in external skeletal robusticity are observed in children and adolescents. Aim: We aim to develop reference centiles for external skeletal robusticity of European girls and boys aged 0 to 18 years using the Frame Index as an indicator and identify population specific age-related patterns. Methods: We analysed cross-sectional & longitudinal data on body height and elbow breadth of boys and girls from Europe (0-18 years, n = 41.679), India (7-18 years, n = 3.297) and South Africa (3-18 years, n = 4.346). As an indicator of external skeletal robusticity Frame Index after Frisancho (1990) was used. We developed centiles for boys and girls using the LMS-method and its extension. Results: Boys have greater external skeletal robusticity than girls. Whereas in girls Frame Index decreases continuously during growth, an increase of Frame Index from 12 to 16 years in European boys can be observed. Indian and South African boys are almost similar in Frame Index to European boys. In girls, the pattern is slightly different. Whereas South African girls are similar to European girls, Indian girls show a lesser external skeletal robusticity. Conclusion: Accurate references for external skeletal robusticity are needed to evaluate if skeletal development is adequate per age. They should be used to monitor effects of changes in way of life and physical activity levels in children and adolescents to avoid negative health outcomes like osteoporosis and arthrosis.

  5. Skeletal muscle expression of the adhesion-GPCR CD97: CD97 deletion induces an abnormal structure of the sarcoplasmatic reticulum but does not impair skeletal muscle function.

    Directory of Open Access Journals (Sweden)

    Tatiana Zyryanova

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

  6. Proton microprobe analysis of zinc in skeletal tissues

    International Nuclear Information System (INIS)

    Doty, S.B.; Jones, K.W.; Kraner, H.W.; Shroy, R.E.; Hanson, A.L.

    1981-01-01

    A proton microprobe with windowless exit port has been used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton micorprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Our measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage. (orig.)

  7. Proton microprobe analysis of zinc in skeletal tissues

    International Nuclear Information System (INIS)

    Doty, S.B.; Jones, K.W.; Kraner, H.W.; Shroy, R.E.; Hanson, A.L.

    1980-06-01

    A proton microprobe with windowless exit port was used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determinations in thick samples with good spatial resolution. Measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage

  8. Proton microprobe analysis of zinc in skeletal tissues

    Science.gov (United States)

    Doty, S. B.; Jones, K. W.; Kraner, H. W.; Shroy, R. E.; Hanson, A. L.

    1981-03-01

    A proton microprobe with windowless exit port has been used to study zinc distributions in various types of skeletal tissues. The use of an external beam facilitated positioning of the targets for examination of particular points of interest. The proton microprobe is uniquely suited to this work since it combines high sensitivity for zinc determination in thick samples with good spatial resolution. Our measurements on rat and rabbit Achilles tendon showed a significant increase in zinc concentrations as the beam moved from the unmineralized collagen into the mineralized attachment site. Cartilage gave a similar result, with calcified cartilage having a greater zinc level than the articular surface on unmineralized epiphyseal cartilage.

  9. Acute exercise remodels promoter methylation in human skeletal muscle

    DEFF Research Database (Denmark)

    Barrès, Romain; Yan, Jie; Egan, Brendan

    2012-01-01

    DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene...... methylation of PGC-1a, PDK4, and PPAR-d was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene...

  10. Omega-3 Fatty Acids and Skeletal Muscle Health

    OpenAIRE

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

    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 muscl...

  11. Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects

    DEFF Research Database (Denmark)

    Vestergaard, H; Weinreb, J E; Rosen, A S

    1995-01-01

    A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus, longitu......A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus......-maintaining diet. Gliclazide treatment results in increased serum C-peptide, decreased hemoglobin-A1c, decreased glucose excursion on glucose tolerance test, and 35% increased insulin-stimulated glucose disposal. Gliclazide therapy is not associated with any change in DNA or protein content per g muscle or any...

  12. Passive stiffness of rat skeletal muscle undernourished during fetal development

    Directory of Open Access Journals (Sweden)

    Ana Elisa Toscano

    2010-01-01

    Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

  13. Atomoxetine prevents dexamethasone-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

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

    2014-12-01

    Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator-activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1-Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. U.S. Government work not protected by U

  14. An analysis of human skeletal remains with cerebral palsy: associated skeletal age delay and dental pathologies.

    Science.gov (United States)

    Megyesi, Mary S; Tubbs, Ryan M; Sauer, Norman J

    2009-03-01

    In 2002 the authors were asked to examine the skeletal remains of an individual with a known history of severe cerebral palsy (CP) who was 21-23 years old at death. Skeletal age estimates of 11-15 years and dental age estimates of c. 16 years are younger than the known age of the decedent. Skeletal analysis also identified dental pathologies such as chronic tooth grinding and substantial calculus deposits. Scarce literature exists on forensic human remains cases with CP, and this study contrasts the age discrepancy and other features of this case with typical clinical characteristics of CP. A review of the CP literature suggests that delayed skeletal maturation and dental pathologies such as those observed in this case are indicative of complications related to CP. This article may alert future investigators to some of the osteological signs of CP and the probability that age indicators may be misleading.

  15. Calpain inhibition attenuated morphological and molecular changes in skeletal muscle of experimental allergic encephalomyelitis rats.

    Science.gov (United States)

    Park, Sookyoung; Nozaki, Kenkichi; Guyton, M Kelly; Smith, Joshua A; Ray, Swapan K; Banik, Naren L

    2012-11-01

    Muscle weakness and atrophy are important manifestations of multiple sclerosis (MS). To investigate the pathophysiological mechanisms of skeletal muscle change in MS, we induced experimental autoimmune encephalomyelitis (EAE) in Lewis male rats and examined morphological and molecular changes in skeletal muscle. We also treated EAE rats with calpepetin, a calpain inhibitor, to examine its beneficial effects on skeletal muscle damage. Morphological changes in muscle tissue of EAE rats included smaller and irregularly shaped muscle fibers and fibrosis. Western blot analysis demonstrated increased calpain:calpastatin ratio, inflammation-related transcription factors (nuclear factor-κB:inhibitor of κB α ratio), and proinflammatory enzymes (cyclooxygenase-2). TUNEL-positive myonuclei in skeletal muscle cells of EAE rats indicated cell death. In addition, markers of apoptotic cell death (Bax:Bcl-2 ratio and caspase-12 protein levels) were elevated. Expression of muscle-specific ubiquitin ligases (muscle atrophy F-box and muscle ring finger protein 1), was upregulated in muscle tissue of EAE-vehicle animals. Both prophylactic and therapeutic treatment with calpeptin partially attenuated muscle changes noted in EAE animals. These results indicate that morphological and molecular changes including apoptotic cell death and protein breakdown develop in skeletal muscle of EAE animals and that these changes can be reversed by calpain inhibition. Copyright © 2012 Wiley Periodicals, Inc.

  16. Colostrum supplementation protects against exercise - induced oxidative stress in skeletal muscle in mice

    Directory of Open Access Journals (Sweden)

    Appukutty Mahenderan

    2012-11-01

    Full Text Available Abstract Background This study examined the effects of bovine colostrum on exercise –induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum and each group had three subgroups (day 0, 21 and 42. Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle. Results Exercise—induced a significant oxidative stress in skeletal muscles as evidenced by the elevated lipid hydroperoxides and xanthine oxidase levels. There was a significant decrease in skeletal muscle total antioxidants and superoxide dismutase levels. Daily colostrum supplement significantly reduced the lipid hydroperoxides and xanthine oxidase enzyme level and increased the total antioxidant levels in the leg muscle. Conclusion Thus, the findings of this study showed that daily bovine colostrum supplementation was beneficial to skeletal muscle to reduce the oxidant-induced damage during muscular exercise.

  17. Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3.

    Science.gov (United States)

    Pérez-Schindler, Joaquín; Esparza, Mary C; McKendry, James; Breen, Leigh; Philp, Andrew; Schenk, Simon

    2017-09-01

    Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle. Copyright © 2017 the American Physiological Society.

  18. Radium-223 in treatment of castration-resistant prostate cancer with skeletal metastases

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2017-01-01

    Full Text Available More than 90 % of patients with metastatic castration-resistant prostate cancer (CRPC have radiologically confirmed skeletal metastases. Traditional treatment methods such as administration of painkillers, external beam therapy, bisphosphonates or denosumab, as well as injections of strontium-89 or samarium-153 radionuclides, have only palliative effect and in some cases can postpone development of skeletal complications. Alpha-emitter radium-223 dichloride (Ra-223; alpharadin previously is currently one of the known drugs with proven effectiveness in relation to increasing overall survival of patients with CRPC. Ra-223 was developed specifically for patients with CRPC and symptomatic skeletal metastases. The drug targets the areas of skeletal tissue remodeling. Ra-223 is the therapy of choice in patients with CRPC and skeletal metastases and without confirmed visceral metastases before and after docetaxel chemotherapy. Chemotherapy after treatment with Ra-223 is a possible and satisfactory tolerable treatment option. Combination of Ra-223 with abiraterone, enzalutamide, or denosumab is, apparently, effective and safe, but further studies are necessary.

  19. Uniaxial cyclic strain enhances adipose-derived stem cell fusion with skeletal myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Jens Isak; Juhl, Morten; Nielsen, Thøger; Emmersen, Jeppe; Fink, Trine; Zachar, Vladimir; Pennisi, Cristian Pablo, E-mail: cpennisi@hst.aau.dk

    2014-07-25

    Highlights: • Uniaxial cyclic tensile strain (CTS) applied to ASCs alone or in coculture with myogenic precursors. • CTS promoted the formation of a highly ordered array of parallel ASCs. • Without biochemical supplements, CTS did not support advanced myogenic differentiation of ASCs. • Mechanical stimulation of cocultures boosted fusion of ASCs with skeletal myoblasts. - Abstract: Although adult muscle tissue possesses an exceptional capacity for regeneration, in the case of large defects, the restoration to original state is not possible. A well-known source for the de novo regeneration is the adipose-derived stem cells (ASCs), which can be readily isolated and have been shown to have a broad differentiation and regenerative potential. In this work, we employed uniaxial cyclic tensile strain (CTS), to mechanically stimulate human ASCs to participate in the formation skeletal myotubes in an in vitro model of myogenesis. The application of CTS for 48 h resulted in the formation of a highly ordered array of parallel ASCs, but failed to support skeletal muscle terminal differentiation. When the same stimulation paradigm was applied to cocultures with mouse skeletal muscle myoblasts, the percentage of ASCs contributing to the formation of myotubes significantly exceeded the levels reported in the literature hitherto. In perspective, the mechanical strain may be used to increase the efficiency of incorporation of ASCs in the skeletal muscles, which could be found useful in diverse traumatic or pathologic scenarios.

  20. In vitro effects of Beta-2 agonists on skeletal muscle differentiation, hypertrophy, and atrophy.

    Science.gov (United States)

    Wannenes, Francesca; Magni, Loretta; Bonini, Matteo; Dimauro, Ivan; Caporossi, Daniela; Moretti, Costanzo; Bonini, Sergio

    2012-06-01

    : Beta-2 agonists are widely used in the treatment of asthma and chronic obstructive pulmonary disease for their effect on airway smooth muscle relaxation. They also act on skeletal muscle, although their reported ergogenic effect is controversial. : To evaluate the in vitro effects of short-acting and long-acting beta-2 agonists on adrenergic receptor (ADR) expression, hypertrophy, and atrophy markers, in a skeletal muscle cell line. : The C2C12 cell line was used as a model of skeletal muscle differentiation. ADR messenger RNA expression was evaluated in proliferating myoblasts, committed cells, and differentiated myotubes, in basal conditions and after treatment with 10 M clenbuterol, salbutamol, salmeterol, and formoterol. Effect of beta-2 agonists on gene and protein expression of hypertrophy and atrophy markers was assessed in differentiated myotubes. : Our study shows that beta-2 ADR messenger RNA was expressed and progressively increased during cell differentiation. Beta-2 agonist treatment did not affect its expression. Skeletal muscle hypertrophy markers (fast and slow myosin, myogenin) were not modulated by any of the beta-2 agonists evaluated. However, clenbuterol induced a significant, dose-dependent downregulation of skeletal muscle atrophy genes (atrogin-1, MuRF-1, and cathepsin L). : The reported ergogenic effect of beta-2 agonists, if any, should be considered as drug-specific and not class-specific and that of clenbuterol is mediated by the inhibition of the atrophic pathway.

  1. Mechanisms of Hyperhomocysteinemia Induced Skeletal Muscle Myopathy after Ischemia in the CBS−/+ Mouse Model

    Directory of Open Access Journals (Sweden)

    Sudhakar Veeranki

    2015-01-01

    Full Text Available Although hyperhomocysteinemia (HHcy elicits lower than normal body weights and skeletal muscle weakness, the mechanisms remain unclear. Despite the fact that HHcy-mediated enhancement in ROS and consequent damage to regulators of different cellular processes is relatively well established in other organs, the nature of such events is unknown in skeletal muscles. Previously, we reported that HHcy attenuation of PGC-1α and HIF-1α levels enhanced the likelihood of muscle atrophy and declined function after ischemia. In the current study, we examined muscle levels of homocysteine (Hcy metabolizing enzymes, anti-oxidant capacity and focused on protein modifications that might compromise PGC-1α function during ischemic angiogenesis. Although skeletal muscles express the key enzyme (MTHFR that participates in re-methylation of Hcy into methionine, lack of trans-sulfuration enzymes (CBS and CSE make skeletal muscles more susceptible to the HHcy-induced myopathy. Our study indicates that elevated Hcy levels in the CBS−/+ mouse skeletal muscles caused diminished anti-oxidant capacity and contributed to enhanced total protein as well as PGC-1α specific nitrotyrosylation after ischemia. Furthermore, in the presence of NO donor SNP, either homocysteine (Hcy or its cyclized version, Hcy thiolactone, not only increased PGC-1α specific protein nitrotyrosylation but also reduced its association with PPARγ in C2C12 cells. Altogether these results suggest that HHcy exerts its myopathic effects via reduction of the PGC-1/PPARγ axis after ischemia.

  2. Regulation of the concentration of 3H-ouabain binding sites in mammalian skeletal muscle

    International Nuclear Information System (INIS)

    Kjeldsen, K.

    1986-01-01

    The major purpose of the present study was the identification and quantification of changes in Na,K-pumps in skeletal muscles with age, K-depletion and thyroid status. Furthermore, the putative difference in skeletal muscle Na,K-pump concentration between spontaneously hypertensive rats and normotensive controls was investigated. On the basis of the observation of major changes in 3 H-ouabain binding site concentration in skeletal muscle with age, K-depletion and thyroid status and the large increase in skeletal muscle Na/K-ratio with K-depletion, the consequences of these variations for cell properties, K-homeostasis and digitalis distribution was evaluated. The present investigation was carried out mainly by measurements of Na,K-pump concentrations, Na,K-contents and K-uptake in skeletal muscles. Hitherto, the Na,K-pump concentration in muscle has mainly been quantified by measurements of the Na,K-ATPase activity in purified membrane fractions. The use of such preparations are, however, complicated by a recovery of plasma membranes of often less than 5% of that in intact tissue. Although this low yield may not affect the interpretation of qualitative studies, it represents a potentially large source of error in quantitative determinations of the Na,K-pumps. Thus, in the present study the Na,K-pumps were quantified by measurements of 3 -ouabain binding, as this method allows the determination of the total Na,K-pump concentration after identification and correction for methodological problems. (author)

  3. Quantitative sonoelastography for the in vivo assessment of skeletal muscle viscoelasticity

    International Nuclear Information System (INIS)

    Hoyt, Kenneth; Kneezel, Timothy; Castaneda, Benjamin; Parker, Kevin J

    2008-01-01

    A novel quantitative sonoelastography technique for assessing the viscoelastic properties of skeletal muscle tissue was developed. Slowly propagating shear wave interference patterns (termed crawling waves) were generated using a two-source configuration vibrating normal to the surface. Theoretical models predict crawling wave displacement fields, which were validated through phantom studies. In experiments, a viscoelastic model was fit to dispersive shear wave speed sonoelastographic data using nonlinear least-squares techniques to determine frequency-independent shear modulus and viscosity estimates. Shear modulus estimates derived using the viscoelastic model were in agreement with that obtained by mechanical testing on phantom samples. Preliminary sonoelastographic data acquired in healthy human skeletal muscles confirm that high-quality quantitative elasticity data can be acquired in vivo. Studies on relaxed muscle indicate discernible differences in both shear modulus and viscosity estimates between different skeletal muscle groups. Investigations into the dynamic viscoelastic properties of (healthy) human skeletal muscles revealed that voluntarily contracted muscles exhibit considerable increases in both shear modulus and viscosity estimates as compared to the relaxed state. Overall, preliminary results are encouraging and quantitative sonoelastography may prove clinically feasible for in vivo characterization of the dynamic viscoelastic properties of human skeletal muscle

  4. A skeletal revision of Nepenthes (Nepenthaceae)

    NARCIS (Netherlands)

    Jebb, Matthew; Cheek, Martin

    1997-01-01

    A skeletal world revision of the genus is presented to accompany a family account for Flora Malesiana. 82 species are recognised, of which 74 occur in the Malesiana region. Six species are described as new, one species is raised from infraspecific status, and five species are restored from synonymy.

  5. Vasodilatory mechanisms in contracting skeletal muscle

    DEFF Research Database (Denmark)

    Clifford, Philip S.; Hellsten, Ylva

    2004-01-01

    and stabilizes within 30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise...

  6. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    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.

  7. Converting skeletal structures to quad dominant meshes

    DEFF Research Database (Denmark)

    Bærentzen, Jakob Andreas; Misztal, Marek Krzysztof; Welnicka, Katarzyna

    2012-01-01

    We propose the Skeleton to Quad-dominant polygonal Mesh algorithm (SQM), which converts skeletal structures to meshes composed entirely of polar and annular regions. Both types of regions have a regular structure where all faces are quads except for a single ring of triangles at the center of eac...

  8. Interleukin-6 myokine signaling in skeletal muscle

    DEFF Research Database (Denmark)

    Muñoz-Cánoves, Pura; Scheele, Camilla; Pedersen, Bente K

    2013-01-01

    Interleukin (IL)-6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL-6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL-6 signaling has...

  9. SKELETAL ABNORMAUTIES IN CROHN'S DISEASE* m

    African Journals Online (AJOL)

    Crohn's disease is a chronic disorder which primarily involves the bowel but may be associated with changes in the joints,' eyes' and skin.' The association between. Crohn's disease and skeletal structures other than those of the joints appears to have been less frequently noted. In this article an outline is presented of the ...

  10. Dysphagia due to diffuseidiopathic skeletal hyperostosis (DISH ...

    African Journals Online (AJOL)

    Diffuse idiopathic skeletal hyperostosis (DISH) or Forestier's disease isa form of degenerative arthritiswith unique spinal and extra spinal manifestations. Dysphagia due to DISH is uncommon but when present DISH should be suspected. Surgical decompression can relieve some of the symptoms. We report a case of a 60 ...

  11. Diffuse idiopathic skeletal hyperostosis in ancient clergymen.

    NARCIS (Netherlands)

    Verlaan, J.J.; Oner, F.C.; Maat, G.J.

    2007-01-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a common but often unrecognized systemic disorder observed mainly in the elderly. DISH is diagnosed when the anterior longitudinal ligament of the spine is ossified on at least four contiguous spinal levels or when multiple peripheral enthesopathies

  12. Diffuse idiopathic skeletal hyperostosis in ancient clergymen

    NARCIS (Netherlands)

    Verlaan, J.J.; Oner, F.C.; Maat, G.R.J.

    2007-01-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a common but often unrecognized systemic disorder observed mainly in the elderly. DISH is diagnosed when the anterior longitudinal ligament of the spine is ossified on at least four contiguous spinal levels or when multiple peripheral

  13. Nutrition and skeletal health in blacks

    Science.gov (United States)

    Vitamin D deficiency is much more common among African Americans than other American groups, but there is as yet little compelling evidence that improving vitamin D status in this group will have an important benefit on skeletal health. It is possible that some African Americans have adaptive physio...

  14. Signalling role of skeletal muscle during exercise

    NARCIS (Netherlands)

    Catoire, M.

    2014-01-01

    Abstract Upon  acute exercise skeletal muscle is immediately and heavily recruited, while other organs appear to play only a minor role during exercise. These other organs show significant changes and improvements in function, although they are not directly targeted by

  15. Signalling role of skeletal muscle during exercise

    NARCIS (Netherlands)

    Catoire, M.

    2014-01-01

    Abstract

    Upon acute exercise skeletal muscle is immediately and heavily recruited, while other organs appear to play only a minor role during exercise. These other organs show significant changes and improvements in function, although they are not directly targeted by

  16. Moebius syndrome with macular hyperpigmentation, skeletal ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-11-08

    Nov 8, 2014 ... Moebius syndrome with macular hyperpigmentation, skeletal anomalies, and hypoplasia of pectoralis major muscle in an Egyptian child. Rabah M. Shawky a, ... examination which was not reported previously in Moebius syndrome cases. .... or absence of middle cerebellar peduncles, depression of the.

  17. Calcium model for mammalian skeletal muscle

    NARCIS (Netherlands)

    Wallinga, W.; Boom, H.B.K.; Heijink, R.J.; van der Vliet, G.H.

    1981-01-01

    A model is presented describing quantitatively the events between excitation and force development in skeletal muscle. It consists of a calcium mediated activation model (c.m.a.m.) in series with a force generator model (f.g.m.). The c.m.a.m. was based on intracellular processes such as cisternal

  18. Osteomyelitis in burn patients requiring skeletal fixation

    NARCIS (Netherlands)

    Barret, JP; Desai, MH; Herndon, DN

    Deep and severe burns often present with the exposure of musculoskeletal structures and severe deformities. Skeletal fixation, suspension and/or traction are part of their comprehensive treatment. Several factors put burn patients at risk for osteomyelitis, osteosynthesis material being one of them.

  19. Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

    Directory of Open Access Journals (Sweden)

    JA DeQuach

    2012-06-01

    Full Text Available Peripheral artery disease (PAD currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI, which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold’s degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 µL of skeletal muscle matrix or collagen 1 week post-injury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue-specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.

  20. Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal

    Science.gov (United States)

    Vermillion, Katie L.; Anderson, Kyle J.; Hampton, Marshall

    2015-01-01

    Throughout the hibernation season, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) experiences extreme fluctuations in heart rate, metabolism, oxygen consumption, and body temperature, along with prolonged fasting and immobility. These conditions necessitate different functional requirements for the heart, which maintains contractile function throughout hibernation, and the skeletal muscle, which remains largely inactive. The adaptations used to maintain these contractile organs under such variable conditions serves as a natural model to study a variety of medically relevant conditions including heart failure and disuse atrophy. To better understand how two different muscle tissues maintain function throughout the extreme fluctuations of hibernation we performed Illumina HiSeq 2000 sequencing of cDNAs to compare the transcriptome of heart and skeletal muscle across the circannual cycle. This analysis resulted in the identification of 1,076 and 1,466 differentially expressed genes in heart and skeletal muscle, respectively. In both heart and skeletal muscle we identified a distinct cold-tolerant mechanism utilizing peroxisomal metabolism to make use of elevated levels of unsaturated depot fats. The skeletal muscle transcriptome also shows an early increase in oxidative capacity necessary for the altered fuel utilization and increased oxygen demand of shivering. Expression of the fetal gene expression profile is used to maintain cardiac tissue, either through increasing myocyte size or proliferation of resident cardiomyocytes, while skeletal muscle function and mass are protected through transcriptional regulation of pathways involved in protein turnover. This study provides insight into how two functionally distinct muscles maintain function under the extreme conditions of mammalian hibernation. PMID:25572546

  1. Maxillary protraction using skeletal anchorage and intermaxillary elastics in Skeletal Class III patients

    OpenAIRE

    Esenlik, El?in; A?larc?, Cahide; Albayrak, Gayem Ero?lu; F?nd?k, Yavuz

    2015-01-01

    The aim of this case report is to describe the treatment of a patient with skeletal Class III malocclusion with maxillary retrognathia using skeletal anchorage devices and intermaxillary elastics. Miniplates were inserted between the mandibular lateral incisor and canine teeth on both sides in a male patient aged 14 years 5 months. Self-drilling mini-implants (1.6 mm diameter, 10 mm length) were installed between the maxillary second premolar and molar teeth, and Class III elastics were used ...

  2. Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation

    DEFF Research Database (Denmark)

    Schwartz, Kristoffer; Rodrigo, Maria; Jensen, Thomas

    2016-01-01

    OBJECTIVES: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. MATERIAL AND METHO...

  3. AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

    Directory of Open Access Journals (Sweden)

    Laia Vil

    2016-01-01

    Full Text Available Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1 specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice. AAV1-Sirt1-treated mice showed up-regulated expression of key genes related to β-oxidation together with increased levels of phosphorylated AMP protein kinase. Moreover, SIRT1 overexpression in skeletal muscle also increased basal phosphorylated levels of AKT. However, AAV1-Sirt1 treatment was not enough to prevent high fat diet-induced obesity and insulin resistance. Although Sirt1 gene transfer to skeletal muscle induced changes at the muscular level related with lipid and glucose homeostasis, our data indicate that overexpression of SIRT1 in skeletal muscle is not enough to improve whole-body insulin resistance and that suggests that SIRT1 has to be increased in other metabolic tissues to prevent insulin resistance.

  4. Role of skeletal muscle in lung development.

    Science.gov (United States)

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

    2012-07-01

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

  5. The skeletal endocannabinoid system: clinical and experimental insights.

    Science.gov (United States)

    Raphael, Bitya; Gabet, Yankel

    2016-05-01

    Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

  6. Optimizing hyaluronidase dose and plasmid DNA delivery greatly improves gene electrotransfer efficiency in rat skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Vedel, Kenneth; Needham Andersen, Josefine

    2015-01-01

    Transfection of rat skeletal muscle in vivo is a widely used research model. However, gene electrotransfer protocols have been developed for mice and yield variable results in rats. We investigated whether changes in hyaluronidase pre-treatment and plasmid DNA delivery can improve transfection...... efficiency in rat skeletal muscle. We found that pre-treating the muscle with a hyaluronidase dose suitable for rats (0.56. U/g b.w.) prior to plasmid DNA injection increased transfection efficiency by >200% whereas timing of the pre-treatment did not affect efficiency. Uniformly distributing plasmid DNA...... with a homogenous distribution. We also show that transfection was stable over five weeks of regular exercise or inactivity. Our findings show that species-specific plasmid DNA delivery and hyaluronidase pre-treatment greatly improves transfection efficiency in rat skeletal muscle....

  7. Effects of botulinum toxin type A on healing of injured skeletal muscles

    Directory of Open Access Journals (Sweden)

    Shokravi Ramin

    2007-01-01

    Full Text Available Objectives: (1 Evaluation of microscopic healing of skeletal muscle fibers after injuries, especially the arrangement of new muscle fibers and scar tissue diameter in the injury region. (2 Evaluation of alterations in microscopy of the healing procedure within skeletal muscles after injury following botulinum toxin type A (BTX -A induced muscle immobilization. Materials and Methods: The study was done on 12 white lab rabbits of either sex in a 6-month period. Results: The immobilization of skeletal muscle fibers as a result of the use of BTX-A after injury caused a qualitative increase in fibrous tissue formation in the area of injury, and the BTX-A-induced immobilization for a period of 6 months led to muscle atrophy.

  8. The Recent Understanding of the Neurotrophin's Role in Skeletal Muscle Adaptation

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2011-01-01

    Full Text Available This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression. In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease.

  9. SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation

    DEFF Research Database (Denmark)

    Petersson, Stine Juhl; Jørgensen, Louise Helskov; Andersen, Ditte C

    2013-01-01

    Skeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up......-regulated during skeletal muscle disease, but its function remains elusive. In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6......, Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen...

  10. Factors regulating fat oxidation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiens, Bente; Alsted, Thomas Junker; Jeppesen, Jacob

    2011-01-01

    In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin...... sensitivity. Consequently, enhanced fat oxidation might be beneficial in counteracting lipid accumulation. Exercise is the most effective way to increase fat oxidation, because it increases metabolic rate. Lipid metabolism can also be altered by dietary manipulations. Thus, a fat rich diet leads to increased...... potential for fat oxidation by increasing the content of several of the proteins in the fat oxidative pathway. The regulation of both exercise and diet induced lipid oxidation will be discussed in this review....

  11. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Albers, Peter Hjorth; Rose, Adam John

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FAT/CD36 translocation and fatty acid uptake in skeletal muscle during contractions. In one model, WT and AMPK KD mice were exercised or EDL and SOL muscles were contracted, ex vivo. In separate studies, FAT/CD36...... with increased fatty acid uptake, both in EDL and SOL muscle from WT and AMPK KD mice and in the perfused rat hindlimb. This suggests that AMPK is not essential in regulation of FAT/CD36 translocation and fatty acid uptake in skeletal muscle during contractions. However, AMPK could be important in regulation...

  12. Assessment of satellite cell number and activity status in human skeletal muscle biopsies

    DEFF Research Database (Denmark)

    Mackey, Abigail L; Kjær, Michael; Charifi, Nadia

    2009-01-01

    The primary aim of our study was to validate the assessment of myonuclear and satellite cell number in biopsies from human skeletal muscle. We found that 25 type I and 25 type II fibers are sufficient to estimate the mean number of myonuclei per fiber. In contrast, the assessment of satellite cells...... observed very few (up to 1.3%) active satellite cells in healthy adult skeletal muscle at rest, but they increased significantly (up to 7-fold) following muscle activity. This study provides valuable tools to assess the behavior of satellite cells, both in pathological conditions and in response...

  13. Kinetics of contraction-induced GLUT4 translocation in skeletal muscle fibers from living mice

    DEFF Research Database (Denmark)

    Lauritzen, Hans Peter M. Mortensen; Galbo, Henrik; Toyoda, Taro

    2010-01-01

    Exercise is an important strategy for the treatment of type 2 diabetes. This is due in part to an increase in glucose transport that occurs in the working skeletal muscles. Glucose transport is regulated by GLUT4 translocation in muscle, but the molecular machinery mediating this process is poorly...... understood. The purpose of this study was to 1) use a novel imaging system to elucidate the kinetics of contraction-induced GLUT4 translocation in skeletal muscle and 2) determine the function of AMP-activated protein kinase alpha2 (AMPKalpha2) in this process....

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...

  15. The duration of pubertal growth peak among three skeletal classes

    Directory of Open Access Journals (Sweden)

    Waqar Jeelani

    Full Text Available ABSTRACT Introduction: Pubertal growth peak is closely associated with a rapid increase in mandibular length and offers a wide range of therapeutic modifiability. Objective: The aim of the present study was to determine and compare the mean ages of onset and duration of pubertal growth peak among three skeletal classes. Methods: A retrospective cross-sectional study was conducted using lateral cephalograms of 230 subjects with growth potential (110 males, 120 females. Subjects were categorized into three classes (Class I = 81, Class II = 82, Class III = 67, according to the sagittal relationship established between the maxilla and the mandible. The cervical vertebral maturation stage was recorded by means of Baccetti's method. The mean ages at CS3 and CS4 and the CS3-CS4 age interval were compared between boys and girls and among three skeletal classes. Results: Pubertal growth peak occurred on average four months earlier in girls than boys (p = 0.050. The average duration of pubertal growth peak was 11 months in Class I, seven months in Class II and 17 months in Class III subjects. Interclass differences were highly significant (Cohen's d > 0.08. However, no significant difference was found in the timing of pubertal growth peak onset among three skeletal classes (p = 0.126 in boys, p = 0.262 in girls. Conclusions: Girls enter pubertal growth peak on average four months earlier than boys. Moreover, the duration of pubertal growth peak is on average four months shorter in Class II and six months longer in Class III subjects as compared to Class I subjects.

  16. Mitochondrial Involvement and Impact in Aging Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Russell T. Hepple

    2014-09-01

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

  17. Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement

    Science.gov (United States)

    Rubin, Mishaela R.; Bilezikian, John P.

    2013-01-01

    Objective Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. Subjects and methods Standard histomorphometric and μCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. Results Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. Conclusion Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D. PMID:20485912

  18. Skeletal muscle aging: influence of oxidative stress and physical exercise.

    Science.gov (United States)

    Gomes, Mariana Janini; Martinez, Paula Felippe; Pagan, Luana Urbano; Damatto, Ricardo Luiz; Cezar, Marcelo Diacardia Mariano; Lima, Aline Regina Ruiz; Okoshi, Katashi; Okoshi, Marina Politi

    2017-03-21

    Skeletal muscle abnormalities are responsible for significant disability in the elderly. Sarcopenia is the main alteration occurring during senescence and a key public health issue as it predicts frailty, poor quality of life, and mortality. Several factors such as reduced physical activity, hormonal changes, insulin resistance, genetic susceptibility, appetite loss, and nutritional deficiencies are involved in the physiopathology of muscle changes. Sarcopenia is characterized by structural, biochemical, molecular and functional muscle changes. An imbalance between anabolic and catabolic intracellular signaling pathways and an increase in oxidative stress both play important roles in muscle abnormalities. Currently, despite the discovery of new targets and development of new drugs, nonpharmacological therapies such as physical exercise and nutritional support are considered the basis for prevention and treatment of age-associated muscle abnormalities. There has been an increase in information on signaling pathways beneficially modulated by exercise; nonetheless, studies are needed to establish the best type, intensity, and frequency of exercise to prevent or treat age-induced skeletal muscle alterations.

  19. Skeletal muscle: energy metabolism, fiber types, fatigue and adaptability.

    Science.gov (United States)

    Westerblad, Håkan; Bruton, Joseph D; Katz, Abram

    2010-11-01

    Skeletal muscles cope with a large range of activities, from being able to support the body weight during long periods of upright standing to perform explosive movements in response to an unexpected threat. This requires systems for energy metabolism that can provide energy during long periods of moderately increased energy consumption as well as being able to rapidly increasing the rate of energy production more than 100-fold in response to explosive contractions. In this short review we discuss how muscles can deal with these divergent demands. We first outline the major energy metabolism pathways in skeletal muscle. Next we describe metabolic differences between different muscle fiber types. Contractile performance declines during intense activation, i.e. fatigue develops, and we discuss likely underlying mechanisms. Finally, we discuss the ability of muscle fibers to adapt to altered demands, and mechanisms behind these adaptations. The accumulated experimental evidence forces us to conclude that most aspects of energy metabolism involve multiple and overlapping signaling pathways, which indicates that the control of energy metabolism is too important to depend on one single molecule or mechanism. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    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.

  1. Monitoring of the clinical manifestations of skeletal birth injuries

    Directory of Open Access Journals (Sweden)

    D. V. Chekmareva

    2017-01-01

    Full Text Available One of the most common types of birth injuries is locomotor trauma: cephalohematomas of the parietal and occipital regions, injuries of the clavicles and tubular bones. The main clinical manifestations of birth trauma are subperiosteal hemorrhages, fractures, local swelling, limited movements; common symptoms (a negative response and a baby’s crying, changes in heart rate, cardiac auscultatory pattern, blood pressure, pale skin, etc.. The purpose of this study is to improve the quality of medical care for the newborns, by monitoring the clinical manifestations of birth trauma.Sixty-seven newborn infants with skeletal birth trauma were examined. Significant changes were found in the function of the cardiovascular system (reduced systolic and diastolic blood pressure, increased pulse pressure, tachycardia, more rarely bradycardia, pale skin, and muffled heart sounds; indicators of pain syndrome (moderate and severe pain according to the Neonatal Infant Pain Scale (NIPS in one-third of the patients; electrocardiographic changes (shortening of the QT and RR intervals, extension of the QRS complex, increased systolic index; neurosonographic changes (periventricular edema and hypoxic changes in all newborns with birth trauma.The findings are objective criteria for the severity of neonatal conditions and will assist in optimizing combination therapy for little patients with skeletal birth trauma. 

  2. Cell death induced by gamma irradiation of developing skeletal muscle

    International Nuclear Information System (INIS)

    Olive, M.; Blanco, R.; Rivera, R.; Cinos, C.; Ferrer, I.

    1995-01-01

    Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 μg/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle. (author)

  3. Skeletal muscle mass and composition during mammalian hibernation.

    Science.gov (United States)

    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. © 2016. Published by The Company of Biologists Ltd.

  4. Factors related to skeletal muscle mass in the frail elderly.

    Science.gov (United States)

    Sagawa, Keiichiro; Kikutani, Takeshi; Tamura, Fumiyo; Yoshida, Mitsuyoshi

    2017-01-01

    It is important for the elderly to maintain their skeletal muscle mass, which in turn helps to maintain physical functions. This study aimed to clarify factors related to skeletal muscle mass maintenance. Home-bound elderly (94 men and 216 women), at least 75 years of age, attending a day-care center in Tokyo, were enrolled in this study. Dentists specializing in dysphagia rehabilitation evaluated skeletal muscle mass, occlusal status and swallowing function. Physical function, cognitive function and nutritional status were also evaluated by interviewing caregivers. Correlations of skeletal muscle mass with various factors were determined in each gender group. Multiple regression analysis revealed that skeletal muscle mass was significantly related to nutritional status in both men and women. In men, there was a significant difference in skeletal muscle mass between those with and without occlusion of the natural teeth. Our results suggest that dental treatments and dentures would be useful for maintaining skeletal muscle mass, especially in men.

  5. Characterising skeletal muscle under large strain using eccentric and Fourier Transform-rheology.

    Science.gov (United States)

    Tan, Kristy; Cheng, Shaokoon; Jugé, Lauriane; Bilston, Lynne E

    2015-11-05

    Characterising the passive anisotropic properties of soft tissues has been largely limited to the linear viscoelastic regime and shear loading is rarely done in the large deformation regime, despite the physiological significance of such properties. This paper demonstrates the use of eccentric rheology, which allows the anisotropy of skeletal muscle to be investigated. The large amplitude oscillatory strain properties of skeletal muscle were also investigated using Fourier Transform-rheology. Histology was used to qualitatively assess the microstructure changes induced by large strain. Results showed that skeletal muscle was strongly anisotropic in the linear regime. The storage and loss moduli were found to be significantly different (p<0.05) between the three fibre alignment groups; for the group tested with fibres perpendicular to plane of shear was 12.3±1.3 kPa and 3.0±0.35 kPa, parallel to shear direction was 10.6±1.2 kPa and 2.4±0.23 kPa, and perpendicular to shear direction was 5.5±0.90 kPa and 1.3±0.21 kPa. The appearance and growth of higher order harmonics at large strain was different in the three testing directions indicating that the anisotropy of muscle affects skeletal muscle behaviour in the nonlinear regime. Histological analysis showed an increasing destruction of extracellular matrix and the rearrangement of fibres with increasing strain indicating mechanical damage at strains of larger than 10%. These microstructural changes could contribute to the complex nonlinear behaviour in skeletal muscle. This paper demonstrates a method of characterising the anisotropic properties in skeletal muscle under large strain whilst giving meaningful information on the physical response of tissue at various strains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Relative Skeletal Muscle Mass Is Associated with Development of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Byung Sam Park

    2013-12-01

    Full Text Available BackgroundVisceral adiposity is related to insulin resistance. Skeletal muscle plays a central role in insulin-mediated glucose disposal; however, little is known about the association between muscle mass and metabolic syndrome (MS. This study is to clarify the clinical role of skeletal muscle mass in development of MS.MethodsA total of 1,042 subjects were enrolled. Subjects with prior MS and chronic diseases were excluded. After 24 months, development of MS was assessed using NCEP-ATP III criteria. Skeletal muscle mass (SMM; kg, body fat mass (BFM; kg, and visceral fat area (VFA; cm2 were obtained from bioelectrical analysis. Then, the following values were calculated as follows: percent of SMM (SMM%; %: SMM (kg/weight (kg, skeletal muscle index (SMI; kg/m2: SMM (kg/height (m2, skeletal muscle to body fat ratio (MFR: SMM (kg/BFM (kg, and skeletal muscle to visceral fat ratio (SVR; kg/cm2: SMM (kg/VFA (cm2.ResultsAmong 838 subjects, 88 (10.5% were newly diagnosed with MS. Development of MS increased according to increasing quintiles of BMI, SMM, VFA, and SMI, but was negatively associated with SMM%, MFR, and SVR. VFA was positively associated with high waist circumference (WC, high blood pressure (BP, dysglycemia, and high triglyceride (TG. In contrast, MFR was negatively associated with high WC, high BP, dysglycemia, and high TG. SVR was negatively associated with all components of MS.ConclusionRelative SMM ratio to body composition, rather than absolute mass, may play a critical role in development of MS and could be used as a strong predictor.

  7. Skeletal muscle performance and ageing

    NARCIS (Netherlands)

    Tieland, Michael; Trouwborst, Inez; Clark, Brian C

    The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical

  8. Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man

    DEFF Research Database (Denmark)

    Simonsen, L; Stallknecht, B; Bülow, J

    1993-01-01

    Elevated plasma adrenaline is known to increase whole body energy expenditure. We studied the thermogenic effect and the effects on substrate utilization in man during infusion of adrenaline. Two series were performed: in one series skeletal muscle metabolism was investigated and in another series......% of the whole body adrenaline-induced thermogenesis....

  9. Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics

    NARCIS (Netherlands)

    Chin, Yeen; Sandham, John; de Vries, Jacob; van der Mei, Henderina; Busscher, Hendrik

    Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess

  10. A review of imaging protocols for suspected skeletal dysplasia and a proposal for standardisation

    International Nuclear Information System (INIS)

    Watson, Sarah G.; Calder, Alistair D.; Offiah, Amaka C.; Negus, Samantha

    2015-01-01

    Expert radiology opinions are often requested to aid diagnosis of skeletal dysplasias or dysostoses, but due to variability in the imaging protocols used at different centres the views presented may be considered inadequate or incomplete resulting in diagnostic delays and increased patient and family anxiety. We propose the introduction of a standardised protocol that may be adapted in certain specific situations. (orig.)

  11. A review of imaging protocols for suspected skeletal dysplasia and a proposal for standardisation

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Sarah G. [Royal Surrey County Hospital, Department of Radiology, Surrey (United Kingdom); Calder, Alistair D. [Great Ormond Street Hospital for Children, NHS Foundation Trust, Department of Radiology, London (United Kingdom); Offiah, Amaka C. [Sheffield Children' s NHS Foundation Trust, The University of Sheffield Academic Unit of Child Health, Sheffield (United Kingdom); Negus, Samantha [St George' s Hospital, Department of Radiology, London (United Kingdom)

    2015-11-15

    Expert radiology opinions are often requested to aid diagnosis of skeletal dysplasias or dysostoses, but due to variability in the imaging protocols used at different centres the views presented may be considered inadequate or incomplete resulting in diagnostic delays and increased patient and family anxiety. We propose the introduction of a standardised protocol that may be adapted in certain specific situations. (orig.)

  12. A Skeleton Tells Its Own Story: Forensic Analyses of Skeletal Elements for the Science Classroom Laboratory

    Science.gov (United States)

    Naples, Virginia L.; Breed, David; Miller, Jon S.

    2010-01-01

    The techniques of forensic anthropology and pathology can provide new information to increase student interest in studying the structural details of the human skeleton. We present a simplified methodology for assessing skeletal ethnicity, sex, age, and stature. An inexpensive method has been devised for constructing an osteometric board to allow…

  13. MiR-27b promotes sheep skeletal muscle satellite cell proliferation ...

    Indian Academy of Sciences (India)

    Administrator

    strong negative regulator of muscle formation, so the mutations in MSTN always cause increasing skeletal muscle mass in animal. In sheep, if MSTN gene was knocked out using CRISPR/Cas9 system, they show heavier body weight than wild type counterparts (Crispo et al., 2015). MSTN null mice causes hypertrophy and ...

  14. Role of buccal corridor in smile esthetics and its correlation with underlying skeletal and dental structures

    Directory of Open Access Journals (Sweden)

    Tripti Tikku

    2012-01-01

    Conclusion: As the amount of buccal corridor display was increased, smiling images were scored less attractive by the evaluators. The buccal corridor is not influenced by underlying skeletal hard tissues but have mild to moderate inverse correlation with the intercanine and intermolar width.

  15. Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man

    DEFF Research Database (Denmark)

    Simonsen, L; Stallknecht, B; Bülow, J

    1993-01-01

    Elevated plasma adrenaline is known to increase whole body energy expenditure. We studied the thermogenic effect and the effects on substrate utilization in man during infusion of adrenaline. Two series were performed: in one series skeletal muscle metabolism was investigated and in another series...

  16. Mechanical ventilation induces myokine expression and catabolism in peripheral skeletal muscle in pigs

    Science.gov (United States)

    Endotoxin (LPS)-induced sepsis increases circulating cytokines which have been associated with skeletal muscle catabolism. During critical illness, it has been postulated that muscle wasting associated with mechanical ventilation (MV) occurs due to inactivity. We hypothesize that MV and sepsis promo...

  17. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase...

  18. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

    DEFF Research Database (Denmark)

    Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke

    2013-01-01

    Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin ...

  19. Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle

    DEFF Research Database (Denmark)

    Broholm, Christa; Mortensen, Ole Hartvig; Nielsen, Søren

    2008-01-01

    the exercise trial. Skeletal muscle LIF mRNA increased immediately after the exercise and declined gradually during recovery. However, LIF protein was unchanged at the investigated time points. Moreover, we tested the hypothesis that LIF mRNA and protein expressions are modulated by calcium (Ca(2+)) in primary...

  20. Curcumin attenuates skeletal muscle mitochondrial impairment in COPD rats: PGC-1α/SIRT3 pathway involved.

    Science.gov (United States)

    Zhang, Ming; Tang, Jingjing; Li, Yali; Xie, Yingying; Shan, Hu; Chen, Mingxia; Zhang, Jie; Yang, Xia; Zhang, Qiuhong; Yang, Xudong

    2017-11-01

    Curcumin has been widely used to treat numerous diseases due to its antioxidant property. The aim of the present study is to investigate the effect of curcumin on skeletal muscle mitochondria in chronic obstructive pulmonary disease (COPD) and its underlying mechanism. The rat model of COPD was established by cigarette smoke exposure combined with intratracheal administration of lipopolysaccharide. Airway inflammation and emphysema were notably ameliorated by the treatment with curcumin. Oral administration of curcumin significantly improved muscle fiber atrophy, myofibril disorganization, interstitial fibrosis and mitochondrial structure damage in the skeletal muscle of COPD rats. Mitochondrial enzyme activities of cytochrome c oxidase, succinate dehydrogenase, Na + /K + -ATPase and Ca 2+ -ATPase in skeletal muscle mitochondria from COPD rats were significantly increased after treatment with curcumin. Moreover, curcumin significantly decreased oxidative stress and inflammation by determining the levels of malondialdehyde, manganese superoxide dismutase, glutathione peroxidase, catalase, IL-6 and TNF-α in skeletal muscle of COPD rats. Furthermore, curcumin significantly increased the mRNA and protein expression of PGC-1α and SIRT3 in the skeletal muscle tissues of COPD rats. These results suggested that curcumin can attenuate skeletal muscle mitochondrial impairment in COPD rats possibly by the up-regulation of PGC-1α/SIRT3 signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice.

    Science.gov (United States)

    Yokota, Takashi; Kinugawa, Shintaro; Hirabayashi, Kagami; Matsushima, Shouji; Inoue, Naoki; Ohta, Yukihiro; Hamaguchi, Sanae; Sobirin, Mochamad A; Ono, Taisuke; Suga, Tadashi; Kuroda, Satoshi; Tanaka, Shinya; Terasaki, Fumio; Okita, Koichi; Tsutsui, Hiroyuki

    2009-09-01

    Insulin resistance or diabetes is associated with limited exercise capacity, which can be caused by the abnormal energy metabolism in skeletal muscle. Oxidative stress is involved in mitochondrial dysfunction in diabetes. We hypothesized that increased oxidative stress could cause mitochondrial dysfunction in skeletal muscle and make contribution to exercise intolerance in diabetes. C57/BL6J mice were fed on normal diet or high fat diet (HFD) for 8 wk to induce obesity with insulin resistance and diabetes. Treadmill tests with expired gas analysis were performed to determine the exercise capacity and whole body oxygen uptake (Vo(2)). The work (vertical distance x body weight) to exhaustion was reduced in the HFD mice by 36%, accompanied by a 16% decrease of peak Vo(2). Mitochondrial ADP-stimulated respiration, electron transport chain complex I and III activities, and mitochondrial content in skeletal muscle were decreased in the HFD mice. Furthermore, superoxide production and NAD(P)H oxidase activity in skeletal muscle were significantly increased in the HFD mice. Intriguingly, the treatment of HFD-fed mice with apocynin [10 mmol/l; an inhibitor of NAD(P)H oxidase activation] improved exercise intolerance and mitochondrial dysfunction in skeletal muscle without affecting glucose metabolism itself. The exercise capacity and mitochondrial function in skeletal muscle were impaired in type 2 diabetes, which might be due to enhanced oxidative stress. Therapies designed to regulate oxidative stress and maintain mitochondrial function could be beneficial to improve the exercise capacity in type 2 diabetes.

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Skeletal and dental variables related to the stability of orthognathic surgery in skeletal Class III malocclusion with a surgery-first approach.

    Science.gov (United States)

    Ko, Ellen Wen-Ching; Lin, Shao Cheng; Chen, Yu Ray; Huang, Chiung Shing

    2013-05-01

    The objectives of the study were to identify the parameters related to skeletal stability after orthognathic surgery in skeletal Class III malocclusion using a surgery-first approach and to analyze the factors correlated with surgical relapse. Forty-five consecutive patients were included. Serial cephalometric radiographs were traced and superimposed to investigate surgical stability at the initial examination, 1 week postoperatively, and after orthodontic debonding (12.22 mo after surgery). Patient grouping was based on the amount of horizontal relapse at the innermost point of the contour of the mandible between the incisor tooth and the bony chin, the B point (less stable group, n = 15; highly stable group, n = 18). Parameters, such as presurgical skeletal and dental variables, the amount of surgical setback, and total treatment duration, were compared between groups and analyzed for correlations with surgical stability. The mean setback at the innermost point of the contour of the mandible between the incisor tooth and the bony chin was 11.19 mm, and the mean relapse rate was 12.46%. The amount of surgical setback, overbite (positive values), overjet, depth of the curve of Spee, and lower anterior facial height showed statistically significant differences between groups. The amount of surgical setback, overbite (positive values), overjet, and depth of the curve of Spee showed statistically significant correlations with the amount of relapse. Skeletal relapse of the mandible increased significantly as the overbite increased. The factors for instability in the surgery-first approach include a larger overbite, a deeper curve of Spee, a greater negative overjet, and a greater mandibular setback. The initial overbite may be an indicator to predict possible skeletal relapse of mandibular setback. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Meniscus transplantation in skeletally immature patients.

    Science.gov (United States)

    Kocher, Mininder S; Tepolt, Frances A; Vavken, Patrick

    2016-07-01

    Meniscal pathology in skeletally immature patients includes meniscal tears and discoid lateral meniscus. Total or subtotal meniscectomy may occur in patients with discoid lateral meniscus or severe meniscal tears. Meniscal transplantation may be an option in skeletally immature patients status after total or subtotal meniscectomy with knee symptoms or dysfunction. This study focuses on the surgical technique and short-term outcomes of meniscus transplantation in skeletally immature patients. We reviewed our clinical database for skeletally immature patients who had undergone meniscus transplantation with a minimum of 2 years of follow-up. Patients were contacted, invited for a physical exam, and asked to complete a Pedi-IKDC, Lysholm, and Tegner outcomes questionnaire. The study protocol was approved by the responsible institutional review board. Three patients (two females/one male) were eligible for the study, each of whom responded to our invitation indicating availability for physical exam and questionnaire. Two patients had undergone subtotal discoid meniscus resection, leading to early lateral compartment degeneration. One patient developed advanced degeneration after a delay in treatment for a medial bucket-handle tear associated with anterior cruciate ligament rupture. The mean age of the patients at the time of surgery was 12.6±2.3 years. At a mean follow-up of 31±20 months, the mean Pedi-IKDC score was 68.3±4, the mean Lysholm was 55.7±22.3, and the median Tegner was 7 points. There were no indications of growth deformity during the regular postoperative radiological assessments. One patient required subsequent lysis of adhesions along the lateral mini arthrotomy and mobilization under anesthesia. The other two patients were able to return to sports at the same level as before meniscus transplantation and were able to do so within 9 months postoperatively. Over-resection of discoid menisci as well as untreated meniscus injury, the latter typically in

  5. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  6. Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

    Science.gov (United States)

    Fogelman, Ignac

    Bone scan imaging with the current bone seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, has dramatically improved our ability to evaluate skeletal pathology. In this thesis, chapter 1 presents a review of the history of bone scanning, summarises present concepts as to the mechanism of uptake of bone seeking agents and briefly illustrates the role of bone scanning in clinical practice. In chapter 2 the applications of bone scan imaging and quantitative tracer techniques derived from the bone scan in the detection of metabolic bone disease are discussed. Since skeletal uptake of Tc-99m diphosphonate depends upon skeletal metabolism one might expect that the bone scan would be of considerable value in the assessment of metabolic bone disease. However in these disorders the whole skeleton is often diffusely involved by the metabolic process and simple visual inspection of the scan image may not reveal the uniformly increased uptake of tracer. Certain patterns of bone scan abnormality have, however, been reported in patients with primary hyperparathyroidism and renal osteo-dystrophy; the present studies extend these observations and introduce the concept of "metabolic features" which are often recognisable in conditions with generalised increased bone turnover. As an aid to systematic recognition of these features on a given bone scan image a semi-quantitative scoring system, the metabolic index, was introduced. The metabolic index allowed differentiation between various groups of patients with metabolic disorders and a control population. In addition, in a bone scan study of patients with acromegaly, it was found that the metabolic index correlated well with disease activity as measured by serum growth hormone levels. The metabolic index was, however, found to be a relatively insensitive means of identifying disease in individual patients. Patients with increased bone turnover will have an absolute increase in skeletal uptake of tracer. As a

  7. Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs.

    Science.gov (United States)

    Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kanno, Shota; Kawabe, Yoshinori; Kamihira, Masamichi

    2017-05-01

    Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a l-ascorbic acid derivative, l-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37°C, mouse C2C12 myoblast cells cultured at 39°C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Skeletal muscle-specific ablation of gamma(cyto-actin does not exacerbate the mdx phenotype.

    Directory of Open Access Journals (Sweden)

    Kurt W Prins

    2008-06-01

    Full Text Available We previously documented a ten-fold increase in gamma(cyto-actin expression in dystrophin-deficient skeletal muscle and hypothesized that increased gamma(cyto-actin expression may participate in an adaptive cytoskeletal remodeling response. To explore whether increased gamma(cyto-actin fortifies the cortical cytoskeleton in dystrophic skeletal muscle, we generated double knockout mice lacking both dystrophin and gamma(cyto-actin specifically in skeletal muscle (ms-DKO. Surprisingly, dystrophin-deficient mdx and ms-DKO mice presented with comparable levels of myofiber necrosis, membrane instability, and deficits in muscle function. The lack of an exacerbated phenotype in ms-DKO mice suggests gamma(cyto-actin and dystrophin function in a common pathway. Finally, because both mdx and ms-DKO skeletal muscle showed similar levels of utrophin expression and presented with identical dystrophies, we conclude utrophin can partially compensate for the loss of dystrophin independent of a gamma(cyto-actin-utrophin interaction.

  9. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-07-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature ( P < 0.05). This result indicated that repeated local muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  10. Time-dependent expression and distribution of Egr-1 during skeletal muscle wound healing in rats.

    Science.gov (United States)

    Fan, Yan-Yan; Ye, Guang-Hua; Lin, Ke-Zhi; Yu, Lin-Sheng; Wu, Shu-Zhen; Dong, Miao-Wu; Han, Jun-Ge; Feng, Xiang-Ping; Li, Xing-Biao

    2013-02-01

    Recent studies have shown that early growth response factor-1 (Egr-1) plays an important role in regulation of inflammation and tissue repair, but little is known about its expression after trauma to skeletal muscles. A preliminary study on time-dependent expression and distribution of Egr-1 was performed by immunohistochemistry, immunofluorescence and Western blotting during skeletal muscle wound healing in rats. An animal model of skeletal muscle contusion was established in 45 Sprague-Dawley male rats. Samples were taken at 6 h, 12 h, 1 day, 3 days, 5 days, 7 days, 10 days, 14 days and 21 days post-injury, respectively (5 rats in each posttraumatic interval). 5 rats were employed as control. In the uninjured controls, Egr-1 positive staining was observed in the sarcoplasm and nuclei of normal myofibers. In wounded specimens, a small number of polymorphonuclear cells (PMNs), a number of mononuclear cells (MNCs), fibroblastic cells (FBCs) and regenerated multinucleated myotubes showed positive reaction for Egr-1 in contused zones. By morphometric analysis, an increase in Egr-1 expression was verified at inflammatory phase after contusion, which reached a peak in the regenerated phase overlapping with the fibrotic phase during skeletal muscle wound healing. The expression tendency was further confirmed by Western blotting assay. By immunofluorescent staining for co-localization, the Egr-1-positive MNCs and FBCs in wounds were identified as macrophages and myofibroblasts. The results demonstrate that the expression of Egr-1 is up-regulated and temporally distributed in certain cell types after trauma to skeletal muscles, which may be closely involved in inflammatory response, fibrotic repair and muscle regeneration during skeletal muscle wound healing.

  11. Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

    Science.gov (United States)

    Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I; Trinity, Joel D; Hyngstrom, John R; Garten, Ryan S; Diakos, Nikolaos A; Ives, Stephen J; Dela, Flemming; Larsen, Steen; Drakos, Stavros; Richardson, Russell S

    2014-08-01

    Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s(-1)·mg(-1), P muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g(-1)·min(-1), P respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s(-1)·mg(-1), P muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.

  12. YAP-mediated mechanotransduction in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Martina eFischer

    2016-02-01

    Full Text Available 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 paralogue, 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.

  13. Metformin protects skeletal muscle from cardiotoxin induced degeneration.

    Directory of Open Access Journals (Sweden)

    Francesca Langone

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

  14. Coexistence of potentiation and fatigue in skeletal muscle

    Directory of Open Access Journals (Sweden)

    D.E. Rassier

    2000-05-01

    Full Text Available Twitch potentiation and fatigue in skeletal muscle are two conditions in which force production is affected by the stimulation history. Twitch potentiation is the increase in the twitch active force observed after a tetanic contraction or during and following low-frequency stimulation. There is evidence that the mechanism responsible for potentiation is phosphorylation of the regulatory light chains of myosin, a Ca2+-dependent process. Fatigue is the force decrease observed after a period of repeated muscle stimulation. Fatigue has also been associated with a Ca2+-related mechanism: decreased peak Ca2+ concentration in the myoplasm is observed during fatigue. This decrease is probably due to an inhibition of Ca2+ release from the sarcoplasmic reticulum. Although potentiation and fatigue have opposing effects on force production in skeletal muscle, these two presumed mechanisms can coexist. When peak myoplasmic Ca2+ concentration is depressed, but myosin light chains are relatively phosphorylated, the force response can be attenuated, not different, or enhanced, relative to previous values. In circumstances where there is interaction between potentiation and fatigue, care must be taken in interpreting the contractile responses.

  15. Therapeutic interventions against reperfusion injury in skeletal muscle.

    Science.gov (United States)

    Wang, Wei Z; Baynosa, Richard C; Zamboni, William A

    2011-11-01

    Ischemia/reperfusion (I/R) injury in the skeletal muscle is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive and transplantation surgeries. Although skeletal muscle has a higher tolerance to ischemia than other organs, prolonged ischemia can still result in significant complications, including muscle necrosis and apoptosis. One of the major goals in the treatment of ischemia is early restoration of blood flow (reperfusion) to the area at risk. However, reperfusion has led to a new pathophysiologic condition called "reperfusion injury," a phenomenon which actually provokes a distinct degree of tissue injury. The purpose of this review is to examine the current state of understanding of I/R injury as well as to highlight recent developments on I/R interventions including our own experience in this particular field. We expect, as our acquired experience and the increased knowledge of underlying mechanisms of I/R injury, more effective interventions aimed to reduce I/R injury will be developed to interfere with or modulate this particular pathophysiologic processes. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Fibroblast growth factor (FGF) signaling in development and skeletal diseases.

    Science.gov (United States)

    Teven, Chad M; Farina, Evan M; Rivas, Jane; Reid, Russell R

    2014-12-01

    Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

  17. Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system

    Directory of Open Access Journals (Sweden)

    Manish Gutch

    2013-01-01

    Full Text Available Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

  18. Association between Tooth Agenesis and Skeletal Malocclusions.

    Science.gov (United States)

    Costa, Ana Maria Guerra; Trevizan, Mariana; Matsumoto, Mírian Aiko Nakane; da Silva, Raquel Assed Bezerra; da Silva, Lea Assed Bezerra; Horta, Karla Carpio; Romano, Fabio Lourenço; Nelson-Filho, Paulo; Küchler, Erika Calvano

    2017-01-01

    The aim of this study was to evaluate the association between tooth agenesis and skeletal malocclusions in Brazilian non-syndromic orthodontic patients. Pretreatment orthodontic records of 348 patients of both genders and with various skeletal malocclusions were examined. Tooth agenesis was evaluated in panoramic radiographs. Angular measurements were taken from lateral cephalometric radiographs to classify the patient's malocclusion as skeletal Class I, Class II and Class III. Subjects were divided into 2 groups, "with tooth agenesis" and "without tooth agenesis". Chi-square or Fisher exact test was used to compare categorical data. ANOVA with Tukey's post-test was used for means comparisons. An alpha of 5% was established. From 348 analysed patients, 28 presented tooth agenesis. There was no difference between genders (P = 0.27) nor mean age (P = 0.16). The most prevalent skeletal malocclusion was Class I (63.11%), followed by Class II (25.94%), and Class III (10.95%). The mean of congenitally missing teeth was 1.3 (SD 0.13). Thirteen subjects had premolar agenesis, 13 upper lateral incisor agenesis, 4 lower incisor agenesis and 2 molars agenesis. The group with tooth agenesis presented A point-nasion-B point (ANB) angle smaller (1.66 [SD 2.52]) than the group without tooth agenesis (2.86 [SD 2.49]) (P = 0.01). ANB angle had a negative correlation with the number of congenitally missing teeth (P = 0.039; r = -0.39). Tooth agenesis is associated with a smaller A point-nasion-B point angle and is negatively correlated with the number of congenitally missing teeth.

  19. Silychristin: Skeletal Alterations and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Biedermann, David; Buchta, M.; Holečková, Veronika; Sedlák, David; Valentová, Kateřina; Cvačka, Josef; Bednárová, Lucie; Křenková, Alena; Kuzma, Marek; Škuta, Ctibor; Peikerová, Žaneta; Bartůněk, Petr; Křen, Vladimír

    2016-01-01

    Roč. 79, č. 12 (2016), s. 3086-3092 ISSN 0163-3864 R&D Projects: GA ČR(CZ) GA15-03037S; GA MZd(CZ) NV16-27317A; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk(CZ) LD15081 Institutional support: RVO:61388971 ; RVO:68378050 ; RVO:61388963 Keywords : Silychristin * skeletal alterations * biological activities Subject RIV: CC - Organic Chemistry Impact factor: 3.281, year: 2016

  20. Cellular Players in Skeletal Muscle Regeneration

    OpenAIRE

    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 ther...

  1. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  2. Heat stress inhibits skeletal muscle hypertrophy

    OpenAIRE

    Frier, Bruce C.; Locke, Marius

    2007-01-01

    Heat shock proteins (Hsps) are molecular chaperones that aid in protein synthesis and trafficking and have been shown to protect cells/tissues from various protein damaging stressors. To determine the extent to which a single heat stress and the concurrent accumulation of Hsps influences the early events of skeletal muscle hypertrophy, Sprague-Dawley rats were heat stressed (42°C, 15 minutes) 24 hours prior to overloading 1 plantaris muscle by surgical removal of the gastrocnemius muscle. The...

  3. Satellite cells in human skeletal muscle plasticity

    Directory of Open Access Journals (Sweden)

    Tim eSnijders

    2015-10-01

    Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. 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/remodelling 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/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  4. Redox characterization of functioning skeletal muscle

    Directory of Open Access Journals (Sweden)

    Li eZuo

    2015-11-01

    Full Text Available 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 (DMD. 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.

  5. Mechanisms of internal emitter skeletal toxicity

    International Nuclear Information System (INIS)

    Jee, W.S.S.

    1985-01-01

    The purpose of this program is to determine the mechanisms for the induction of skeletal cancers in dogs and man by α-emitting bone-seeking radionuclides from the nuclear fuel cycle. The role of microdistribution of radium-226 and plutonium-239, bone metabolism, bone cell turnover, and localized bone cell dosimetry in bone can induction will be determined. The osteogenic cell dose will be measured in dogs to develop better quantitative dose response information. Skeletal carcinogenesis models will be developed by correlating the local dosimetry, tumor site and incidence, age-dependent skeletal biology (bone morphometry, bone cell at risk, bone cell turnover, residence time and fate, remodeling rate, growth pattern and rate, hormonal influences, manipulation of bone cell populations of the bone modeling and remodeling systems, etc.). The authors will test the hypothesis that the frequency of osteosarcomas is proportional to the average dose delivered to cells at risk. They will also attempt to explain experimentally found toxicity ratios between volume- and bone surface-seeking radionuclides on the basis of radiation dose ratios

  6. The effect of high-fat--high-fructose diet on skeletal muscle mitochondrial energetics in adult rats.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Coppola, Paola; Mazzoli, Arianna; Cigliano, Luisa; Liverini, Giovanna; Iossa, Susanna

    2015-03-01

    To study the effect of isoenergetic administration to adult rats of high-fat or high-fat--high-fructose diet for 2 weeks on skeletal muscle mitochondrial energetic. Body and skeletal muscle composition, energy balance, plasma lipid profile and glucose tolerance were measured, together with mitochondrial functionality, oxidative stress and antioxidant defense. Rats fed high-fat--high-fructose diet exhibited significantly higher plasma triglycerides and non-esterified fatty acids, together with significantly higher plasma glucose and insulin response to glucose load. Skeletal muscle triglycerides and ceramide were significantly higher in rats fed high-fat--high-fructose diet. Skeletal muscle mitochondrial energetic efficiency and uncoupling protein 3 content were significantly higher, while adenine nucleotide translocase content was significantly lower, in rats fed high-fat or high-fat--high-fructose diet. The results suggest that a high-fat--high-fructose diet even without hyperphagia is able to increase lipid flow to skeletal muscle and mitochondrial energetic efficiency, with two detrimental effects: (a) energy sparing that contributes to the early onset of obesity and (b) reduced oxidation of fatty acids and lipid accumulation in skeletal muscle, which could generate insulin resistance.

  7. Skeletal muscle mitochondrial bioenergetics and morphology in high fat diet induced obesity and insulin resistance: focus on dietary fat source

    Directory of Open Access Journals (Sweden)

    Rosalba ePutti

    2016-01-01

    Full Text Available It has been suggested that skeletal muscle mitochondria play a key role in high fat diet induced insulin resistance. Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle insulin resistance. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to insulin resistance. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of insulin resistance. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift towards mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and insulin resistance development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle insulin resistance and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle insulin resistance, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance.

  8. Astragalus Polysaccharide Suppresses Skeletal Muscle Myostatin Expression in Diabetes: Involvement of ROS-ERK and NF-κB Pathways

    Directory of Open Access Journals (Sweden)

    Min Liu

    2013-01-01

    Full Text Available Objective. The antidiabetes drug astragalus polysaccharide (APS is capable of increasing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth factor myostatin plays an important role in regulating insulin signaling and insulin resistance. We hypothesized that regulation of skeletal muscle myostatin expression may be involved in the improvement of insulin sensitivity by APS. Methods. APS was administered to 13-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the saturated acid palmitate-induced insulin resistance and myostatin expression in C2C12 cells. Results. APS treatment ameliorated hyperglycemia, hyperlipidemia, and insulin resistance and decreased the elevation of myostatin expression and malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired glucose uptake, overproduction of ROS, activation of extracellular regulated protein kinases (ERK, and NF-κB were partially restored by APS treatment. The protective effects of APS were mimicked by ERK and NF-κB inhibitors, respectively. Conclusion. Our study demonstrates elevated myostatin expression in skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed to palmitate. APS is capable of improving insulin sensitivity and decreasing myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-κB pathway.

  9. Deterioration of bone quality in the tibia and fibula in growing mice during skeletal unloading: gender-related differences.

    Science.gov (United States)

    Ko, Chang-Yong; Seo, Dong Hyun; Kim, Han Sung

    2011-11-01

    Skeletal unloading causes bone loss in both men and women; however, only a few studies have been performed on the effects of gender differences on bone quality during skeletal unloading. Moreover, although the fibula also plays an important role in load bearing and ankle stability, the effects of unloading on the fibula have been rarely investigated. The present study aimed to investigate the effects of skeletal unloading on bone quality of the tibia and fibula in growing animals and to determine whether differences existed between genders. Six-week-old female and male mice were randomly allocated into two groups. The right hindlimb of each mouse in the skeletal unloading group was subjected to sciatic neurectomy. After two weeks of skeletal unloading, the structural characteristics of the tibia and fibula in both genders were worsened. In addition, the bone mineralization density distribution (MDD) of the tibia and fibula in both genders were altered. However, the magnitude of deterioration and alteration of the MDD in the bones of females were larger than in those of males. These results demonstrate that skeletal unloading diminishes bone quality in the tibia and fibula, leading to an increase in bone fracture risks, particularly in females.

  10. Extracellular matrix adaptation of tendon and skeletal muscle to exercise

    DEFF Research Database (Denmark)

    Kjaer, Michael; Magnusson, Peter; Krogsgaard, Michael

    2006-01-01

    The extracellular matrix (ECM) of connective tissues enables linking to other tissues, and plays a key role in force transmission and tissue structure maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by physical activity, and both collagen synthesis and metalloprotease......-beta and IL-6 is enhanced following exercise. For tendons, metabolic activity (e.g. detected by positron emission tomography scanning), circulatory responses (e.g. as measured by near-infrared spectroscopy and dye dilution) and collagen turnover are markedly increased after exercise. Tendon blood flow...... is regulated by cyclooxygenase-2 (COX-2)-mediated pathways, and glucose uptake is regulated by specific pathways in tendons that differ from those in skeletal muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as to some degree of net collagen synthesis...

  11. Characterizing the Effects of Chronic 2G Centrifugation on the Rat Skeletal System

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    Johnson, Aimee; Scott, Ryan; Ronca, April E.; Hoban-Higgins, Tana M.; Fuller, Charles A.; Alwood, Joshua S.

    2017-01-01

    During weightlessness, the skeletal system of astronauts is negatively affected by decreased calcium absorption and bone mass loss. Therefore, it is necessary to counteract these changes for long-term skeletal health during space flights. Our long-term plan is to assess artificial gravity (AG) as a possible solution to mitigate these changes. In this study, we aim to determine the skeletal acclimation to chronic centrifugation. We hypothesize that a 2G hypergravity environment causes an anabolic response in growing male rats. Specifically, we predict chronic 2G to increase tissue mineral density, bone volume fraction of the cancellous tissue and to increase overall bone strength. Systemically, we predict that bone formation markers (i.e., osteocalcin) are elevated and resorption markers (i.e., tartrate resistant acid phosphatase) are decreased or unchanged from controls. The experiment has three groups, each with an n8: chronic 2g, cage control (housed on the centrifuge, but not spun), and a vivarium control (normal rat caging). Pre-pubescent, male Long-Evans rats were used to assess our hypothesis. This group was subject to 90 days of 2G via centrifugation performed at the Chronic Acceleration Research Unit (CARU) at University of California Davis. After 90 days, animals were euthanized and tissues collected. Blood was drawn via cardiac puncture and the right leg collected for structural (via microcomputed tomography) and strength quantification. Understanding how counteract these skeletal changes will have major impacts for both the space-faring astronauts and the people living on Earth.

  12. Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction.

    Science.gov (United States)

    Gilliam, Laura A A; Lark, Daniel S; Reese, Lauren R; Torres, Maria J; Ryan, Terence E; Lin, Chien-Te; Cathey, Brook L; Neufer, P Darrell

    2016-08-01

    The loss of strength in combination with constant fatigue is a burden on cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and increases mitochondrial H2O2 We hypothesized that the combined effect of cancer and chemotherapy in an immunocompetent breast cancer mouse model (E0771) would compromise skeletal muscle mitochondrial respiratory function, leading to an increase in H2O2-emitting potential and impaired muscle function. Here, we demonstrate that cancer chemotherapy decreases mitochondrial respiratory capacity supported with complex I (pyruvate/glutamate/malate) and complex II (succinate) substrates. Mitochondrial H2O2-emitting potential was altered in skeletal muscle, and global protein oxidation was elevated with cancer chemotherapy. Muscle contractile function was impaired following exposure to cancer chemotherapy. Genetically engineering the overexpression of catalase in mitochondria of muscle attenuated mitochondrial H2O2 emission and protein oxidation, preserving mitochondrial and whole muscle function despite cancer chemotherapy. These findings suggest mitochondrial oxidants as a mediator of cancer chemotherapy-induced skeletal muscle dysfunction. Copyright © 2016 the American Physiological Society.

  13. Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress.

    Science.gov (United States)

    Davuluri, Gangarao; Allawy, Allawy; Thapaliya, Samjhana; Rennison, Julie H; Singh, Dharmvir; Kumar, Avinash; Sandlers, Yana; Van Wagoner, David R; Flask, Chris A; Hoppel, Charles; Kasumov, Takhar; Dasarathy, Srinivasan

    2016-12-15

    Hyperammonaemia occurs in hepatic, cardiac and pulmonary diseases with increased muscle concentration of ammonia. We found that ammonia results in reduced skeletal muscle mitochondrial respiration, electron transport chain complex I dysfunction, as well as lower NAD + /NADH ratio and ATP content. During hyperammonaemia, leak of electrons from complex III results in oxidative modification of proteins and lipids. Tricarboxylic acid cycle intermediates are decreased during hyperammonaemia, and providing a cell-permeable ester of αKG reversed the lower TCA cycle intermediate concentrations and increased ATP content. Our observations have high clinical relevance given the potential for novel approaches to reverse skeletal muscle ammonia toxicity by targeting the TCA cycle intermediates and mitochondrial ROS. Ammonia is a cytotoxic metabolite that is removed primarily by hepatic ureagenesis in humans. Hyperammonaemia occurs in advanced hepatic, cardiac and pulmonary disease, and in urea cycle enzyme deficiencies. Increased skeletal muscle ammonia uptake and metabolism are the major mechanism of non-hepatic ammonia disposal. Non-hepatic ammonia disposal occurs in the mitochondria via glutamate synthesis from α-ketoglutarate resulting in cataplerosis. We show skeletal muscle mitochondrial dysfunction during hyperammonaemia in a comprehensive array of human, rodent and cellular models. ATP synthesis, oxygen consumption, generation of reactive oxygen species with oxidative stress, and tricarboxylic acid (TCA) cycle intermediates were quantified. ATP content was lower in the skeletal muscle from cirrhotic patients, hyperammonaemic portacaval anastomosis rat, and C2C12 myotubes compared to appropriate controls. Hyperammonaemia in C2C12 myotubes resulted in impaired intact cell respiration, reduced complex I/NADH oxidase activity and electron leak occurring at complex III of the electron transport chain. Consistently, lower NAD + /NADH ratio was observed during

  14. Hyperammonaemia‐induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress

    Science.gov (United States)

    Davuluri, Gangarao; Allawy, Allawy; Thapaliya, Samjhana; Rennison, Julie H.; Singh, Dharmvir; Kumar, Avinash; Sandlers, Yana; Van Wagoner, David R.; Flask, Chris A.; Hoppel, Charles; Kasumov, Takhar

    2016-01-01

    Key points Hyperammonaemia occurs in hepatic, cardiac and pulmonary diseases with increased muscle concentration of ammonia.We found that ammonia results in reduced skeletal muscle mitochondrial respiration, electron transport chain complex I dysfunction, as well as lower NAD+/NADH ratio and ATP content.During hyperammonaemia, leak of electrons from complex III results in oxidative modification of proteins and lipids.Tricarboxylic acid cycle intermediates are decreased during hyperammonaemia, and providing a cell‐permeable ester of αKG reversed the lower TCA cycle intermediate concentrations and increased ATP content.Our observations have high clinical relevance given the potential for novel approaches to reverse skeletal muscle ammonia toxicity by targeting the TCA cycle intermediates and mitochondrial ROS. Abstract Ammonia is a cytotoxic metabolite that is removed primarily by hepatic ureagenesis in humans. Hyperammonaemia occurs in advanced hepatic, cardiac and pulmonary disease, and in urea cycle enzyme deficiencies. Increased skeletal muscle ammonia uptake and metabolism are the major mechanism of non‐hepatic ammonia disposal. Non‐hepatic ammonia disposal occurs in the mitochondria via glutamate synthesis from α‐ketoglutarate resulting in cataplerosis. We show skeletal muscle mitochondrial dysfunction during