oru.sePublications
Change search
Refine search result
1 - 40 of 40
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Bigard, X.
    et al.
    Chaillou, Thomas
    Université Grenoble Alpes, Saint-Martin-d'Heres, France .
    Sanchez, H.
    Malgoyre, A.
    Koulmann, N,
    How to build high oxidative skeletal muscle?: Interaction between energy stress and muscle growth2010Conference paper (Refereed)
  • 2.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Impaired ribosome biogenesis could contribute to anabolic resistance to strength exercise in the elderly2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 5, p. 1447-1448Article, review/survey (Refereed)
  • 3.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Ribosome specialization and its potential role in the control of protein translation and skeletal muscle size2019In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 127, no 2, p. 599-607Article, review/survey (Refereed)
    Abstract [en]

    The ribosome is typically viewed as a supramolecular complex with constitutive and invariant capacity in mediating translation of mRNA into protein. This view has been challenged by recent research revealing that ribosome composition could be heterogeneous, and this heterogeneity leads to functional ribosome specialization. This review presents the idea that ribosome heterogeneity results from changes in its various components, including variations in ribosomal protein (RP) composition, post-translational modifications of RPs, changes in ribosomal-associated proteins, alternative forms of rRNA and post-transcriptional modifications of rRNAs. Ribosome heterogeneity could be orchestrated at several levels and may depend on numerous factors, such as the subcellular location, cell type and tissue specificity, the development state, cell state, ribosome biogenesis, RP turnover, physiological stimuli and circadian rhythm. Ribosome specialization represents a completely new concept for the regulation of gene expression. Specialized ribosomes could modulate several aspects of translational control, such as mRNA translation selectivity, translation initiation, translational fidelity and translation elongation. Recent research indicates that the expression of Rpl3 is markedly increased, while that of Rpl3l is highly reduced during mouse skeletal muscle hypertrophy. Moreover, Rpl3l overexpression impairs the growth and myogenic fusion of myotubes. Although the function of Rpl3 and Rpl3l in the ribosome remains to be clarified, these findings suggest that ribosome specialization may be potentially involved in the control of protein translation and skeletal muscle size. Limited data concerning ribosome specialization are currently available in skeletal muscle. Future investigations have the potential to delineate the function of specialized ribosomes in skeletal muscle.

  • 4.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1450Article, review/survey (Refereed)
    Abstract [en]

    Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to inducemetabolic adaptations and loss ofmass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1 alpha), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

  • 5.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Cheng, Arthur
    Karolinska Institutet, Stockholm, Sweden.
    A dose of 5,000 km.h of severe hypoxia (at > 5,000 m altitude) is probably required to induce skeletal muscle wasting in humans2017In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 122, no 2, p. 410-410Article in journal (Refereed)
  • 6.
    Chaillou, Thomas
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Cheng, Arthur J.
    Karolinska Institutet, Stockholm, Sweden.
    Integrative biology is needed to understand exercise adaptions from the whole body to the cellular level2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 121, no 2, p. 598-599Article in journal (Refereed)
  • 7.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences.
    Cheng, Arthur J.
    Faculty of Health, School of Kinesiology and Health Sciences, York University, Canada.
    Mechanisms of prolonged low-frequency force depression: in-vivo studies get us closer to the truth2019In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 316, no 5, p. R502-R503Article in journal (Refereed)
  • 8.
    Chaillou, Thomas
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Hynynen, H.
    University of Eastern Finland, Joensuu, Finland.
    Ferreira, D.
    Karolinska Institute, Stockholm, Sweden.
    Pironti, G.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, D.C.
    Karolinska Institute, Stockholm, Sweden.
    Ruas, J.
    Karolinska Institute, Stockholm, Sweden.
    Tavi, P.
    University of Eastern Finland, Joensuu, Finland.
    Lanner, J.T.
    Karolinska Institute, Stockholm, Sweden.
    The mitochondrial NDUFA4L2 protein: a novel modulator of skeletal muscle mass and force2016Conference paper (Refereed)
  • 9.
    Chaillou, Thomas
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Hynynen, H
    University of Eastern Finland, Joensuu, Finland.
    Ferreira, D
    Karolinska Institutet, Stockholm, Sweden.
    Pironti, G
    Karolinska Institutet, Stockholm, Sweden.
    Kenne, E
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, D C
    Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Ruas, J L
    Karolinska Institutet, Stockholm, Sweden.
    Tavi, P
    University of Eastern Finland, Joensuu, Finland.
    Lanner, J T
    Karolinska Institutet, Stockholm, Sweden.
    NDUFA4L2: Connecting metabolic signals and mitochondrial function in cardiac and skeletal muscle2016In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 100, no Suppl., p. S186-S186Article in journal (Refereed)
    Abstract [en]

    The nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) was recently identified. NDUFAe4L2 is shown to be induced by hypoxia via HIF1α and is thought to inhibit production of mitochondrial reactive oxygen species in fibroblasts exposed to hypoxia. Here the aim was to characterize the role of NDUFA4L2 in the mitochondria-rich tissues skeletal and cardiac muscle. We show hypoxia induced NDUFA4L2 expression in isolated muscle fibers and in cardiomyocytes with full activation after ~3-6 h in hypoxia. The half-maximal O2 level for NDUFA4L2 expression (~4.6 % of ambient O2) suggests sensitivity to changes in O2 tension that occur under physiological conditions (e.g. exercise, moderate ischemia). We identified that the NDUFA4L2 gene promoter has binding sites for transcription factors other than HIF-1α; repetitive sites for PPARα,γ and one for Nrf2. NDUFA4L2 overexpression resulted in functional effects on skeletal and cardiac muscle; e.g. it alters cellular Ca2+ signaling and the expression of Ca2+ handling genes. Further, NDUFA4L2 overexpression reduces muscle mass (~20%), leading to a decreased force production in skeletal muscle. The NDUFA4L2-induced loss of muscle mass was associated with increases in mRNA levels of e.g. MurF1, Mul1, caspase-3 and Bax. Additionally, femoral artery ligation (FAL) induced NDUFA4L2 expression, which correlates with the decreased force production eight days post-FAL in skeletal muscle. Moreover, NDUFA4L2 upregulates antioxidant gene expression and silencing NDUFA4L2 makes cardiac cells less tolerant to hypoxia/re-oxygenation. Our results suggest that NDUFA4L2 expression affects vital functions in muscle cells and at least part of this effect is mediated by a link between NDUFA4L2 and nuclear gene expression. Thus, NDUFA4L2 might act as an integrator of the nutritional, environmental and functional status in muscle cells.

  • 10.
    Chaillou, Thomas
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Ivarsson, N
    Mijwel, S
    Cheng, A
    Rundqvist, H
    Lanner, J
    Breast-cancer-induced muscle weakness: benefits of physical exercise to restore muscle function2015Conference paper (Refereed)
  • 11.
    Chaillou, Thomas
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Jackson, J.R.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    England, J.H.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Kirby, T.J.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    Richards-White, J.
    Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    Esser, K.A.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Dupont-Versteegden, E.E.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA.
    McCarthy, J.J.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 118, p. 86-97Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading.

  • 12. Chaillou, Thomas
    et al.
    Koulmann, N.
    Beaudry, M.
    Bigard, X.
    Molecular mechanisms involved in the muscle mass control2011Conference paper (Refereed)
  • 13.
    Chaillou, Thomas
    et al.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Koulmann, N.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France; Ecole du Val-de-Grâce, Paris, France.
    Meunier, A.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Chapot, R.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Serrurier, B.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, EA2363, Sorbonne-Paris-Cité, Université Paris, Bobigny Cedex, France.
    Bigard, X.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche cedex, France.
    Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration2014In: Molecular and Cellular Biochemistry, ISSN 0300-8177, E-ISSN 1573-4919, Vol. 390, no 1-2, p. 31-40Article in journal (Refereed)
    Abstract [en]

    Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.

  • 14.
    Chaillou, Thomas
    et al.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Koulmann, N.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Meunier, A.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Malgoyre, A.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Serrurier, B.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France.
    Beaudry, M.
    Laboratoire Réponses cellulaires et fonctionnelles à l'hypoxie, Université Paris, Sorbonne-Paris-Cité, France.
    Bigard, X.
    Département Environnements opérationnels, Institut de Recherche Biomédicale des Armées Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload2013In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 209, no 4, p. 272-282Article in journal (Refereed)
    Abstract [en]

    Aim: To determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload.

    Methods: Plantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte-enriched calcineurin-integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc-1α, NRF1 and Tfam) and degradation (BNIP-3).

    Results: Hypoxia did not alter the fast-to-slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload-induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP-3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc-1α mRNA and protein contents did not correlate with changes in oxidative capacity.

    Conclusion: Hypoxia is not a critical stimulus to modulate the fast-to-slow MHC transition associated with overload. Thus, the impairment of the fast-to-slow fibre shift often observed during post-natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.

  • 15.
    Chaillou, Thomas
    et al.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France; Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington KY, United States.
    Koulmann, N.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Meunier, A.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France.
    Pugnière, P.
    Pôle Génomique, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    McCarthy, J.J.
    Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington KY, United States.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, Sorbonne-Paris-Cité, Université Paris13, Paris, France.
    Bigard, X.
    Département Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Antenne de la Tronche, La Tronche, France; Ecole du Val-de-Grâce, Paris, France.
    Ambient hypoxia enhances the loss of muscle mass after extensive injury2014In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 466, no 3, p. 587-598Article in journal (Refereed)
    Abstract [en]

    Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.

  • 16.
    Chaillou, Thomas
    et al.
    University of Grenoble, Grenoble, France.
    Koulmann, N.
    Simler, N.
    Meunier, A.
    Grégoire, C.
    Chapot, R.
    Serrurier, B.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia enhances the muscle-mass loss after extensive injury2011Conference paper (Refereed)
  • 17.
    Chaillou, Thomas
    et al.
    Université Grenoble Alpes, Grenoble, France .
    Koulmann, N.
    Simler, N.
    Meunier, A.
    Grégoire, C.
    Serrurier, B.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia enhances the muscle-mass loss after extensive injury2011In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 25, no 1 Suppl.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine the effect of ambient hypoxia on the main intracellular pathways involved in muscle regeneration. Left soleus muscles of female rats were degenerated by notexin injection before exposure to either normoxia (N) or ambient hypoxia (H) (10% O2) during 3, 7, 14 and 28 days (d). The expected muscle-mass loss of injured muscles was higher in H than in N rats at d3 and d7, whereas the recovery of muscle mass was similar in H and N rats at d28. The mammalian target of rapamycin (mTOR) activity, assessed from both eIF-4E binding protein (4E-BP1) and P70S6K phosphorylation, was markedly increased during the early period of regeneration, but remained two-fold lower in H than in N groups at d3. The hypoxia-induced alteration of mTOR activity, independently of Akt, was associated with an activation of AMP-activated kinase (AMPK) at d3. In contrast, REDD1, another negative regulator of mTOR, was markedly activated by H at d14 and d28 in intact muscles, but was blunted during the first days of regeneration (d3–7), independently of H. Taken together, we show for the first time, that hypoxia enhances the muscle-mass loss after extensive injury. This could be due to a specific impairment of mTOR activation during muscle regeneration, independently of Akt, at least partly related to AMPK activation, without detectable effect of REDD1.

  • 18.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences. Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Koulmann, N.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Simler, N.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Meunier, A.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Serrurier, B.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Chapot, R.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Peinnequin, A.
    Genomic Core Facility, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Beaudry, M.
    Laboratoire “Réponses cellulaires et fonctionnelles a` l’hypoxie”, Université Paris, Bobigny, France.
    Bigard, X.
    Operational environments, Institut de Recherche Biomédicale des Armées, La Tronche, France.
    Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model2012In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 302, p. R643-R654Article in journal (Refereed)
    Abstract [en]

    Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

  • 19. Chaillou, Thomas
    et al.
    Koulmann, N.
    Simler, N.
    Serrurier, B.
    Meunier, A.
    Chapot, R.
    Peinnequin, A.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia transiently affects muscle growth in a functional overload model in rats2010Conference paper (Refereed)
  • 20. Chaillou, Thomas
    et al.
    Koulmann, N.
    Simler, N.
    Serrurier, B.
    Meunier, A.
    Chapot, R.
    Peinnequin, A.
    Beaudry, M.
    Bigard, X.
    Ambient hypoxia transiently affects muscle growth in a functional overload model in rats2011Conference paper (Refereed)
  • 21.
    Chaillou, Thomas
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity2016In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 12, p. 3929-3941Article, review/survey (Refereed)
    Abstract [en]

    Reduced oxygen (O2) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O2 level could affect their activity during muscle regeneration. In this review, we present the idea that O2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O2 levels to promote muscle regeneration. Severe hypoxia (≤1% O2) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

  • 22.
    Chaillou, Thomas
    et al.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Malgoyre, A.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Banzet, S.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Chapot, R.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Koulmann, N.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Pugnière, P.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Beaudry, M.
    Laboratoire Réponses Cellulaires et Fonctionnelles À l'Hypoxie, Université Paris, Bobigny, France.
    Bigard, X.
    Operational environments, IRBA La Tronche, La Tronche, France.
    Peinnequin, A.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Pitfalls in target mRNA quantification for real-time quantitative RT-PCR in overload-induced skeletal muscle hypertrophy2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 4, p. 228-235Article in journal (Refereed)
    Abstract [en]

    Quantifying target mRNA using real-time quantitative reverse transcription-polymerase chain reaction requires an accurate normalization method. Determination of normalization factors (NFs) based on validated reference genes according to their relative stability is currently the best standard method in most usual situations. This method controls for technical errors, but its physiological relevance requires constant NF values for a fixed weight of tissue. In the functional overload model, the increase in the total RNA concentration must be considered in determining the NF values. Here, we pointed out a limitation of the classical geNorm-derived normalization. geNorm software selected reference genes despite that the NF values extensively varied under experiment. Only the NF values calculated from four intentionally selected genes were constant between groups. However, a normalization based on these genes is questionable. Indeed, three out of four genes belong to the same functional class (negative regulator of muscle mass), and their use is physiological nonsense in a hypertrophic model. Thus, we proposed guidelines for optimizing target mRNA normalization and quantification, useful in models of muscle mass modulation. In our study, the normalization method by multiple reference genes was not appropriate to compare target mRNA levels between overloaded and control muscles. A solution should be to use an absolute quantification of target mRNAs per unit weight of tissue, without any internal normalization. Even if the technical variations will stay present as a part of the intergroup variations, leading to less statistical power, we consider this method acceptable because it will not generate misleading results.

  • 23.
    Chaillou, Thomas
    et al.
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    McPeek, Ashley
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy2017In: Physiological Reports, E-ISSN 2051-817X, Vol. 5, no 11, article id e13261Article in journal (Refereed)
    Abstract [en]

    Chemotherapy drugs such as docetaxel are commonly used to treat cancer. Cancer patients treated with chemotherapy experience decreased physical fitness, muscle weakness and fatigue. To date, it is unclear whether these symptoms result only from cancer-derived factors or from the combination of cancer disease and cancer treatments, such as chemotherapy. In this study, we aimed at determining the impact of chemotherapy per se on force production of hind limb muscles from healthy mice treated with docetaxel. We hypothesized that docetaxel will decrease maximal force, exacerbate the force decline during repeated contractions and impair recovery after fatiguing stimulations. We examined the function of soleus and extensor digitorum longus (EDL) muscles 24h and 72h after a single injection of docetaxel (acute treatment), and 7days after the third weekly injection of docetaxel (repeated treatment). Docetaxel was administrated by intravenous injection (20mg/kg) in female FVB/NRj mice and control mice were injected with saline solution. Our results show that neither acute nor repeated docetaxel treatment significantly alters force production during maximal contractions, repeated contractions or recovery. Only a tendency to decreased peak specific force was observed in soleus muscles 24h after a single injection of docetaxel (-17%, P=0.13). In conclusion, docetaxel administered intravenously does not impair force production in hind limb muscles from healthy mice. It remains to be clarified whether docetaxel, or other chemotherapy drugs, affect muscle function in subjects with cancer and whether the side effects associated with chemotherapy (neurotoxicity, central fatigue, decreased physical activity, etc.) are responsible for the experienced muscle weakness and fatigue.

  • 24. Chaillou, Thomas
    et al.
    Zhang, X.
    McCarthy, J.
    Muscle-specific Ribosomal Protein L3-like Inhibits Myotube Growth2014Conference paper (Refereed)
  • 25.
    Chaillou, Thomas
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    Zhang, Xiping
    Center for Muscle Biology, University of Kentucky, Lexington KY,USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    McCarthy, John J
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth2016In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 231, no 9, p. 1894-1902Article in journal (Refereed)
    Abstract [en]

    The ribosome has historically been considered to have no cell-specific function but rather serve in a "housekeeping" capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like (Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ∼fivefold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (-23%) and protein content (-14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (-17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth.

  • 26.
    Cheng, A
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Allodi, I
    Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Karolinska Institutet, Stockholm, Sweden.
    Thams, S
    Karolinska Institutet, Stockholm, Sweden.
    Ivarsson, N
    Karolinska Institutet, Stockholm, Sweden.
    Schlittler, M
    Karolinska Institutet, Stockholm, Sweden.
    Lanner, J
    Karolinska Institutet, Stockholm, Sweden.
    Hedlund, E
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, D
    Karolinska Institutet, Stockholm, Sweden.
    Increased fatigue resistance and preserved specific force in intact single muscle fibres from the SOD1G93A mouse model of ALS2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, no S710, p. 17-17, article id P-28Article in journal (Refereed)
    Abstract [en]

    Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neurone disease characterized by degeneration and loss of motor neurones, leading to severe muscle weakness and paralysis. Although motor neurone degeneration is already a well-characterized symptom that contributes to muscle weakness in the SOD1G93A mouse model of ALS, the purpose of the current study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles of SOD1G93A mice.

    Methods: Experiments were performed on whole muscles and mechanically dissected intact single fibres from the flexor digitorum brevis (FDB) muscle of SOD1G93A mice at three age groups of 50, 125 and 150 days of age (P50, P125 and P150). Myoplasmic free [Ca2+] ([Ca2+]i) was measured using the fluorescent indicator, indo-1.

    Results: Motor neurone loss and decreased force were evident in whole FDB muscles of P125–150 mice. In the intact single muscle fibres however, specific force, tetanic [Ca2+]iand resting [Ca2+]i were similar in single FDB fibres from symptomatic P125–150 SOD1G93A and age-matched wild-type littermates. The most intriguing finding was a markedly greater fatigue resistance in single fibres from P125–150 SOD1G93A vs. wild-type mice, which was not present in asymptomatic young P50 SOD1G93A mice. No shift in fibre-type distribution was observed in whole FDB muscles to explain the increased fatigue resistance of single fibres from P125–150 SOD1G93A mice.

    Conclusion: These results support the hypothesis that muscle weakness in ALS is not attributed to intrinsicdefects in skeletal muscle fibre force generation.

  • 27.
    Cheng, Arthur
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Gineste, Charlotte
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schlittler, Maja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Intracellular Ca(2+) handling and myofibrillar Ca(2+) sensitivity are defective in single muscle fibres of aged humans2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 593, no 15, p. 3237-3238Article in journal (Refereed)
  • 28.
    Cheng, Arthur J.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; School of Kinesiology and Health Sciences, York University, Toronto, Canada.
    Allodi, Ilary
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schlittler, Maja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas, Lithuania.
    Ivarsson, Niklas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Thams, Sebastian
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hedlund, Eva
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Daniel C.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme; Section for Heart Failure, Arrhythmia and GUCH; Karolinska University Hospital, Stockholm, Sweden.
    Intact single muscle fibres from SOD1(G93A) amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations2019In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 597, no 12, p. 3133-3146Article in journal (Refereed)
    Abstract [en]

    Key points:

    • How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated.
    • Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force.
    • On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance.
    • These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype.

    Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.

  • 29.
    Cheng, Arthur J.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Willis, Sarah J.
    Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Zinner, Christoph
    Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences. Karolinska Institutet, Stockholm, Sweden.
    Ivarsson, Niklas
    Karolinska Institutet, Stockholm, Sweden.
    Ørtenblad, Niels
    University of Southern Denmark, Odense, Denmark.
    Lanner, Johanna T.
    Karolinska Institutet, Stockholm, Sweden.
    Holmberg, Hans-Christer
    Karolinska Institutet, Stockholm, Sweden; Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden.
    Westerblad, Håkan
    Karolinska Institutet, Stockholm, Sweden.
    Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle2017In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 595, no 24, p. 7413-7426Article in journal (Refereed)
    Abstract [en]

    Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by two hours recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca(2+) ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole FDB muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.

  • 30.
    Ferreira, DMS
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Cheng, AJ
    Karolinska Institutet, Stockholm, Sweden.
    Edsgärd, D
    Royal Institute of Technology (KTH), Stockholm, Sweden.
    Chaillou, Thomas
    Karolinska Institutet, Stockholm, Sweden.
    Porsmyr-Palmertz, M
    Karolinska Institutet, Stockholm, Sweden.
    da Silva, P
    Karolinska Institutet, Stockholm, Sweden.
    Izadi, M
    Karolinska Institutet, Stockholm, Sweden.
    Agudelo, L
    Karolinska Institutet, Stockholm, Sweden.
    Martínez-Redondo, V
    Karolinska Institutet, Stockholm, Sweden.
    Petersson-Klein, A
    Ruas, J
    LMCD1B: A novel regulator of skeletal muscle metabolism2017Conference paper (Refereed)
  • 31.
    Kirby, T.J.
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington KY, USA.
    Chaillou, Thomas
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington KY, USA.
    McCarthy, J.J.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington KY, USA.
    The role of microRNAs in skeletal muscle health and disease2015In: Frontiers in Bioscience, ISSN 1093-9946, E-ISSN 1093-4715, Vol. 20, p. 37-77Article in journal (Refereed)
    Abstract [en]

    Over the last decade non-coding RNAs have emerged as importance regulators of gene expression. In particular, microRNAs are a class of small RNAs of ∼ 22 nucleotides that repress gene expression through a post-transcriptional mechanism. MicroRNAs have been shown to be involved in a broader range of biological processes, both physiological and pathological, including myogenesis, adaptation to exercise and various myopathies. The purpose of this review is to provide a comprehensive summary of what is currently known about the role of microRNAs in skeletal muscle health and disease.

  • 32.
    Kirby, T.J.
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Lee, J.D.
    Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, Kentucky, USA; Department of Molecular and Integrative Physiology, Medical School, University of Michigan, Ann Arbor, Michigan, USA.
    England, J.H.
    Department of Physiology, College of Medicine University of Kentucky, Lexington, Kentucky, USA.
    Chaillou, Thomas
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Esser, K.A.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    McCarthy, J.J.
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
    Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis2015In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 4, p. 321-327Article in journal (Refereed)
    Abstract [en]

    The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.

  • 33.
    Mader, Theresa
    et al.
    Karolinska Institutet, Solna, Sweden.
    Kenne, Ellinor
    Karolinska Institutet, Solna, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Petkovic, Monika
    Karolinska Institutet, Solna, Sweden.
    Steinz, Maarten
    Karolinska Institutet, Solna, Sweden.
    Liu, Zhengye
    Karolinska Institutet, Solna, Sweden.
    Kalakoutis, Michaeljohn
    Karolinska Institutet, Solna, Sweden.
    Lanner, Johanna
    Karolinska Institutet, Solna, Sweden.
    Metabolic alteration and muscle dysfunction in mice with breast cancer2018Conference paper (Refereed)
    Abstract [en]

    Breast cancer accounts for ~25% of diagnosed cancer types in woman [1]. Decreased physical fitness and muscle weakness are common complications in patients with breast cancer. In cancer, muscle weakness has traditionally been linked to muscle wasting and significant weight loss (cachexia) [2]. However, muscle weakness is present in non-cachectic, weight-stable patients with breast cancer [3]. In fact, cancer-induced muscle dysfunction is a broad clinical challenge that is not restricted to palliative or advanced stage patients, but also observed in newly diagnosed patients with low tumor burden [4]. Further, with the breast cancer treatment improving, it is important to take a look on the patients quality of life [5]. However, little is known about the features underlying breast cancer-induced muscle impairments and no drug preventing cancer-induced muscle weakness is clinically proven. Here we aim at characterizing the metabolic status and the muscle function in mice with breast cancer.

    The breast cancer mouse-model MMTV-PyMT (PyMT) used here, is characterized by an early onset of mammary cancer (from 5 weeks of age) and follows a similar progression pattern as the one observed in human patients [6]. Soleus muscle from PyMT mice exhibited ~30% lower specific force (kN/m2) than soleus muscle from wildtype (WT) mice (n=28-29, p ≤ 0.05, mice were 12 week old at sacrifice). There were no significant differences in muscle mass, fiber size or fiber type distribution between PyMT and WT muscle. Furthermore, there were no differences in glycogen content (μg/g muscle) in soleus muscle from PyMT and WT mice. Simultaneous measurement of numerous parameters (e.g. oxygen consumption (VO2), carbon dioxide production (VCO2), and food and water intake) was carried out using comprehensive lab animal monitoring system (CLAMS) to gain insight into the metabolic status of the mice. The mice were monitored over a week and the average respiratory exchange ratio (RER = CO2production: O2 uptake) were significantly differed between PyMT and WT mice, with mean PyMT RER of 0.95±0.01 and WT RER of 1.0±0.01 (mean data +/-SEM, n=8, p<0.001). Thus, indicative that PyMT have an altered metabolism towards fatty acid utilization.

    In summary, soleus muscles are weaker and the whole-body metabolism appears altered in mice with breast cancer as compared with healthy control mice. Gene and molecular analysis are currently being performed to further assess mitochondrial and glucose metabolism. Nevertheless, further studies are needed to gain insight into cancer-derived factors that contributes to skeletal muscle dysfunction and altered metabolism.

    1. Jemal, A., et al., Cancer statistics, 2008. CA Cancer J Clin, 2008. 58(2): p. 71-96.

    2. Johns, N., N.A. Stephens, and K.C. Fearon, Muscle wasting in cancer. Int J Biochem Cell Biol, 2013. 45(10): p. 2215-29.

    3. Klassen, O., et al., Muscle strength in breast cancer patients receiving different treatment regimes. Journal of Cachexia, Sarcopenia and Muscle, 2017. 8(2): p. 305-316.

    4. Villasenor, A., et al., Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study. J Cancer Surviv, 2012. 6(4): p. 398-406.

    5. Perry, S., T.L. Kowalski, and C.H. Chang, Quality of life assessment in women with breast cancer: benefits, acceptability and utilization. Health Qual Life Outcomes, 2007. 5: p. 24.

    6. Fantozzi, A. and G. Christofori, Mouse models of breast cancer metastasis. Breast Cancer Res, 2006. 8(4): p. 212.

  • 34.
    Malgoyre, A
    et al.
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Sanchez, H
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Tonini, J
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Serrurier, B
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Prola, A
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Chaillou, Thomas
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Simler, N
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Bigard, X
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Aerobic performance improvment and mitochondrial adaptations after endurance training in hypoxia2011In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, no Suppl. 685Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to examine the effects of hypoxic endurance training on both aerobic performance and mitochondrial changes within plantaris muscle, independently of hematopoietic modifications.

    Methods: Four groups of female rats were constituted either sedentary (S) or trained (T), in either hypoxia (H) or normoxia (N). H conditions corresponded to 14% O2 and the training program to 5 running sessions/week for 5 weeks. Duration and intensity reached progressively 75Õ up to 80% of individual maximal aerobic running velocity (MAV) in either H or N. Performances of each rat were analysed through MAV values and time to exhaustion at 65% MAV (T65). Mitochondrial oxidative capacities (Vmax) for pyruvate (pyr), palmitoyl-carnitine (PC) and palmitoyl-CoA (PCoA) were measured in plantaris skinned fibers. Citrate synthase (CS) and HAD activities were also measured.

    Results: MAV increased in both TN and TH rats (respectively +52%, +39%, P<0.001) without difference between H and N, whereas hypoxia specifically increased T65 (+ 39%, P<0.05) independently of training effect. The training-induced increase in CS activity (P<0.001) was more marked in TN than in TH group (+39% vs +26%, P<0.001) whereas HAD activity rose similarly in TN and TH (respectively +83%, +64%, P<0.05). Physical training increased Vmaxpyr only in N rats (+30%, P<0.001), while VmaxPCoA decreased in hypoxia (P<0.05) without change in VmaxPC. This suggests that LCFA transport by CPT-1 was limiting in hypoxia. As expected, training improved creatine kinase efficiency in N rats (+80%, P<0.005), but no change was shown in H rats.

    Conclusion: Regarding the modest changes in mitochondrial function, it is likely that other factors contribute to explain the improvement of physical performance after an endurance training in hypoxia.

  • 35.
    Pugnière, P
    et al.
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Banzet, S
    Operational Environments, IRBA La Tronche, La Tronche, France.
    Chaillou, Thomas
    Operational Environments, IRBA La Tronche, La Tronche, France.
    Mouret, C
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Peinnequin, A
    Genomic Core Facility, IRBA La Tronche, La Tronche, France.
    Pitfalls of reverse transcription quantitative polymerase chain reaction standardization: Volume-related inhibitors of reverse transcription2011In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 415, no 2, p. 151-157Article in journal (Refereed)
    Abstract [en]

    A large part of the reliability of reverse transcription quantitative polymerase chain reaction (RT-qPCR) data depends on technical variations. Such variations are mainly attributable to the reverse transcription step. Standardization is a key factor in decreasing the intersample variability. However, an ideal standardization is not always possible, and compromises must be found. Due to technical requirements, the current consensus is that a constant amount of total RNA should be used for the RT step (CA-RT). Because RNA isolation yields are variable, such a practice requires the use of variable volumes of nucleic acid extracts in RT reaction. We demonstrate that some RNA extracts contain both exogenous and endogenous inhibitors. These inhibitors induce a decrease in RT efficiency that significantly impairs the reliability of RT-qPCR data. Conversely, these inhibitors have a slight effect on the qPCR step. To overcome such drawbacks, we proposed to carry out the RT reaction with a constant volume of RNA extract by preserving a constant RNA amount through the supplementation of yeast transfer RNA (CV-RT). We show that CV-RT, compared with the usual CA-RT, allows us to decrease the RT-qPCR variability induced by intersample differences. Such a decrease is a prerequisite for the reliability of messenger RNA quantification.

  • 36. Pugnière, P.
    et al.
    Banzet, S.
    Chaillou, Thomas
    University of Kentucky, Lexington KY, United States .
    Mouret, C
    Peinnequin, A.
    Volume-related inhibitors standardization for reverse transcription quantitative polymerase chain reaction experiments2012Conference paper (Refereed)
    Abstract [en]

    A large part of the reliability of reverse transcription quantitative polymerase chain reaction (RT-qPCR) data depends on technical variations. Such variations are mainly attributable to the reverse transcription step. Standardization is a key factor in decreasing the intersample variability. However, an ideal standardization is not always possible, and compromises must be found. Due to technical requirements, the current consensus is that a constant amount of total RNA should be used for the RT step (CA-RT). Because RNA isolation yields are variable, such a practice requires the use of variable volumes of nucleic acid extracts in RT reaction. We demonstrate that some RNA extracts contain both exogenous and endogenous inhibitors. These inhibitors induce a decreased RT efficiency that significantly impairs the reliability of RT-qPCR data. Conversely, these inhibitors have slight effects on the qPCR step. To overcome such drawbacks, we proposed to carry out the RT reaction with a constant volume of RNA extract by preserving a constant RNA amount through the supplementation of yeast transfer RNA (CV-RT). We show that CV-RT, compared with the usual CA-RT, allows us to decrease the RT-qPCR variability induced by intersample differences. Such a decrease is a prerequisite for the reliability of messenger RNA quantification.

  • 37.
    Rantala, Robert
    et al.
    Department of Health Sciences, Örebro University, Örebro, Sweden.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Mild hypothermia affects the morphology and impairs glutamine-induced anabolic response in human primary myotubes2019In: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 317, no 1, p. C101-C110Article in journal (Refereed)
    Abstract [en]

    The specific impact of reduced temperature on skeletal muscle adaptation has been poorly investigated. Cold water immersion, one situation leading to decreased skeletal muscle temperature, is commonly proposed to reduce the perception of fatigue and muscle soreness after strenuous exercise. In contrast, it may impair long-term benefits of resistance exercise training on muscle strength and hypertrophy. To date, the physiological factors responsible for this blunted muscle adaptation remain unclear. Here, we used a cell culture model of human primary myotubes to specifically investigate the intrinsic behavior of muscle cells during mild hypothermia (MH). Newly formed myotubes were exposed to either 37°C or 32°C to evaluate the effect of MH on myotube size and morphology, protein synthesis and anabolic signaling. We also compared the glutamine (GLUT)-induced hypertrophic response between myotubes incubated at 32°C or 37°C. We showed that 48 h exposure to MH altered the cellular morphology (greater myotube area, shorter myosegments, myotubes with irregular shape), and impaired GLUT-induced myotube hypertrophy. Moreover, MH specifically reduced protein synthesis at 8 h. This result may be explained by an altered regulation of ribosome biogenesis, as evidenced by a lower expression of 45S pre-rRNA and MYC protein, and a lower total RNA concentration. Furthermore, MH blunted GLUT-induced increase in protein synthesis at 8 h, a finding consistent with an impaired activation of the mechanistic target of rapamycin (mTOR) pathway. In conclusion, this study demonstrates that MH impairs the morphology of human myotubes and alters the hypertrophic response to GLUT.

  • 38.
    Rantala, Robert
    et al.
    School of Health Sciences, Örebro University, Örebro, Sweden.
    Kadi, Fawzi
    Örebro University, School of Health Sciences.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Low temperature affects the morphology and impairs glutamine-induced hypertrophic response in human primary myotubes2018Conference paper (Refereed)
    Abstract [en]

    Cold water immersion and other strategies are extensively used by athletes to reduce muscle temperature (TEMP) and are believed to limit muscle soreness and improve recovery after strenuous exercise. However, it remains unclear whether low TEMP affects skeletal muscle hypertrophy and protein synthesis in response to anabolic stimuli. In this study, we used an in vitro model to investigate whether a reduced TEMP (32°C, TEMP in skeletal muscle during cold water immersion vs. 37°C, core TEMP) affects the growth and impairs glutamine (GLUT)-induced hypertrophic response in human myotubes. Myoblasts from human muscle biopsies (n=8) were first differentiated into myotubes during 48h at 37°C. Then, myotubes were treated with GLUT to induce hypertrophy and were incubated at either 37 or 32°C during 1h (T1), 8h (T8) or 48h (T48). Myotube area (a marker of myotube size) was assessed at T48 by using immunocytology. Protein synthesis (puromycin incorporation) and phosphorylation levels of two components of the mechanistic target of rapamycin (mTOR) pathway [P70 S6 kinase (P70S6K) and eukaryotic translation initiation factor 4E (4E-BP1] were assessed at T1 and T8 from western blot analysis. Ribosome biogenesis was evaluated at T8 by determining total RNA concentration, and by assessing the levels of 18S ribosomal RNA (18S rRNA), precursor 45S rRNA (pre-45S rRNA) and MYC mRNA from quantitative polymerase chain reaction. Data were analysed by a two-way ANOVA for repeated measures. A first major observation was that low TEMP induced morphological alterations (short myotube segments and larger myotube area). Importantly, GLUT-induced myotube hypertrophy was only observed at 37°C (+40%, P<0,01 at 37°C; +4%, NS at 32°C). Similarly, GLUT stimulated protein synthesis at T1 (main effect, P<0,01), with a 53% increase at 37°C (P<0,05) and a 23% increase at 32°C (NS). Protein synthesis was reduced at 32°C at T8 (main effect, P<0,01), while GLUT increased protein synthesis at 37°C (+17%, P<0,01) but not at 32°C (-7%, NS). GLUT-induced 4E-BP1 phosphorylation at T1 was found at 37°C (+16%, P<0,01) but not at 32°C (-1%, NS). Moreover, GLUT increased the phosphorylation of P70S6K at T8 by 50% at 37°C (P<0,01) and by 26% at 32°C (P<0,05). Overall, total RNA concentration, levels of MYC mRNA, 18S rRNA and pre-45S rRNA were reduced at 32°C. In conclusion, this study indicates that low TEMP affects myotube morphology. In addition, we demonstrate that low TEMP impairs GLUT-induced myotube hypertrophy and protein synthesis, a result accompanied by a minored activation of the mTOR pathway. The impaired ribosome biogenesis observed at 32°C at T8 may also contribute to the reduced protein synthesis at this time point. These findings suggest that reducing muscle TEMP after resistance exercise may be detrimental for muscle hypertrophy and training adaptations.

     

  • 39. Simler, N.
    et al.
    Meunier, A.
    Chaillou, Thomas
    Université Grenoble Alpes, Grenoble, France .
    Gangloff, K.
    Bigard, X.
    Activating AMPK signalling in hypothalamus supresses hypoxia-induced hypophagia in rats2011Conference paper (Refereed)
  • 40.
    Vechetti, Ivan J
    et al.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA; Department of Morphology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil.
    Wen, Yuan
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Murach, Kevin A.
    Department of Rehabilitation Sciences, College of Health Sciences, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Alimov, Alexander P.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Figueiredo, Vandre C.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Dal-Pai-Silva, Maeli
    Department of Morphology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil.
    McCarthy, John J.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 5483Article in journal (Refereed)
    Abstract [en]

    We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to ~50% of WT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle.

1 - 40 of 40
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf