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Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle

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D'Hulst, Gommaar [KU Leuven] Jamart, Cécile [UCL] Van Thienen, Ruud [KU Leuven] Hespel, Peter [KU Leuven] Francaux, Marc [UCL] Deldicque, Louise [KU Leuven]

Hypoxia-induced muscle wasting has been observed in several environmental and pathological conditions. However, the molecular mechanisms behind this loss of muscle mass are far from being completely elucidated, certainly in vivo. When studying the regulation of muscle mass by environmental hypoxia, many confounding factors have to be taken into account, such as decreased protein ingestion, sleep deprivation or reduced physical activity, which make difficult to know whether hypoxia per se causes a reduction in muscle mass. Aim: We hypothesized that acute exposure to normobaric hypoxia (11% O2) would repress the activation of the mTOR pathway usually observed after a meal and would activate the proteolytic pathways in skeletal muscle. Methods: Fifteen subjects were exposed passively for 4h to normoxic and hypoxic conditions in a random order after consumption of a light breakfast. A muscle biopsy and a blood sample were taken before, after 1h and 4h of exposure. Results: After 4h, plasma insulin concentration and the phosphorylation state of PKB and S6K1 in skeletal muscle were higher in hypoxia than in normoxia (p<0.05). At the same time Redd1 mRNA level was upregulated (p<0.05) whilst MAFbx mRNA decreased (p<0.05) in hypoxia compared to normoxia. Proteasome, cathepsin L and calpain activities were not altered by environmental hypoxia. Conclusion: Contrary to our hypothesis, and despite an increase in the mRNA level of Redd1, an inhibitor of the mTORC1 pathway, short term acute environmental hypoxia induced a higher response of PKB and S6K1 to a meal, which may be due to increased plasma insulin concentration.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2013
Language Anglais
Journal information "Acta Physiologica" - Vol. 208, no. 3, p. 251–264
Peer reviewed yes
Publisher Wiley-Blackwell Publishing Ltd.
issn 1748-1708
e-issn 1748-1716
Publication status Publié
Affiliation UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Links
  1. Ameln, FASEB J, 19, 1009 (2005)
  2. Arsham Andrew M., Howell Jessica J., Simon M. Celeste, A Novel Hypoxia-inducible Factor-independent Hypoxic Response Regulating Mammalian Target of Rapamycin and Its Targets, 10.1074/jbc.m212770200
  3. Atherton P. J., Smith K., Muscle protein synthesis in response to nutrition and exercise : Muscle protein synthesis in response to nutrition and exercise, 10.1113/jphysiol.2011.225003
  4. Baldi Simonetta, Fat-free mass change after nutritional rehabilitation in weight losing COPD: role of insulin, C-reactive protein and tissue hypoxia, 10.2147/copd.s7739
  5. Bodine S. C., Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy, 10.1126/science.1065874
  6. Cam Hakan, Easton John B., High Anthony, Houghton Peter J., mTORC1 Signaling under Hypoxic Conditions Is Controlled by ATM-Dependent Phosphorylation of HIF-1α, 10.1016/j.molcel.2010.10.030
  7. Chaudhary Pooja, Suryakumar Geetha, Prasad Rajendra, Singh Som Nath, Ali Shakir, Ilavazhagan Govindsamy, Chronic hypobaric hypoxia mediated skeletal muscle atrophy: role of ubiquitin–proteasome pathway and calpains, 10.1007/s11010-011-1210-x
  8. Deldicque L., Cani P. D., Philp A., Raymackers J.-M., Meakin P. J., Ashford M. L. J., Delzenne N. M., Francaux M., Baar K., The unfolded protein response is activated in skeletal muscle by high-fat feeding: potential role in the downregulation of protein synthesis, 10.1152/ajpendo.00038.2010
  9. Deldicque Louise, De Bock Katrien, Maris Michael, Ramaekers Monique, Nielens Henri, Francaux Marc, Hespel Peter, Increased p70s6k phosphorylation during intake of a protein–carbohydrate drink following resistance exercise in the fasted state, 10.1007/s00421-009-1289-x
  10. DeYoung M. P., Horak P., Sofer A., Sgroi D., Ellisen L. W., Hypoxia regulates TSC1/2 mTOR signaling and tumor suppression through REDD1-mediated 14 3 3 shuttling, 10.1101/gad.1617608
  11. Drogat B., Auguste P., Nguyen D. T., Bouchecareilh M., Pineau R., Nalbantoglu J., Kaufman R. J., Chevet E., Bikfalvi A., Moenner M., IRE1 Signaling Is Essential for Ischemia-Induced Vascular Endothelial Growth Factor-A Expression and Contributes to Angiogenesis and Tumor Growth In vivo, 10.1158/0008-5472.can-06-3235
  12. Etheridge T., Atherton P. J., Wilkinson D., Selby A., Rankin D., Webborn N., Smith K., Watt P. W., Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise, 10.1152/ajpendo.00276.2011
  13. Favier F. B., Costes F., Defour A., Bonnefoy R., Lefai E., Bauge S., Peinnequin A., Benoit H., Freyssenet D., Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia, 10.1152/ajpregu.00550.2009
  14. Ferrari Marco, Mottola Leonardo, Quaresima Valentina, Principles, Techniques, and Limitations of Near Infrared Spectroscopy, 10.1139/h04-031
  15. Frost Robert A., Huber Danuta, Pruznak Anne, Lang Charles H., Regulation of REDD1 by insulin-like growth factor-I in skeletal muscle and myotubes, 10.1002/jcb.22349
  16. Garvey J. F., Taylor C. T., McNicholas W. T., Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation, 10.1183/09031936.00111208
  17. Gingras A.-C., Gygi S. P., Raught B., Polakiewicz R. D., Abraham R. T., Hoekstra M. F., Aebersold R., Sonenberg N., Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism, 10.1101/gad.13.11.1422
  18. Gingras, Genes Dev, 15, 2852 (2001)
  19. Greenhaff P. L., Karagounis L. G., Peirce N., Simpson E. J., Hazell M., Layfield R., Wackerhage H., Smith K., Atherton P., Selby A., Rennie M. J., Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle, 10.1152/ajpendo.90411.2008
  20. Greer Samantha N, Metcalf Julie L, Wang Yi, Ohh Michael, The updated biology of hypoxia-inducible factor : The updated biology of HIF, 10.1038/emboj.2012.125
  21. Grocott Michael, Montgomery Hugh, Vercueil Andre, 10.1186/cc5142
  22. Hoppeler H., Kleinert E., Schlegel C., Claassen H., Howald H., Kayar S., Cerretelli P., II. Morphological Adaptations of Human Skeletal Muscle to Chronic Hypoxia*, 10.1055/s-2007-1024846
  23. Jackman R. W., The molecular basis of skeletal muscle atrophy, 10.1152/ajpcell.00579.2003
  24. Jamart Cécile, Francaux Marc, Millet Guillaume Y., Deldicque Louise, Frère Delphine, Féasson Léonard, Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running, 10.1152/japplphysiol.00952.2011
  25. Jamart Cecile, Raymackers Jean-Marc, Li An Gang, Deldicque Louise, Francaux Marc, Prevention of muscle disuse atrophy by MG132 proteasome inhibitor, 10.1002/mus.21949
  26. Koritzinsky Marianne, Magagnin Michaël G, van den Beucken Twan, Seigneuric Renaud, Savelkouls Kim, Dostie Josée, Pyronnet Stéphane, Kaufman Randal J, Weppler Sherry A, Voncken Jan Willem, Lambin Philippe, Koumenis Constantinos, Sonenberg Nahum, Wouters Bradly G, Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control, 10.1038/sj.emboj.7600998
  27. Koumenis C., Naczki C., Koritzinsky M., Rastani S., Diehl A., Sonenberg N., Koromilas A., Wouters B. G., Regulation of Protein Synthesis by Hypoxia via Activation of the Endoplasmic Reticulum Kinase PERK and Phosphorylation of the Translation Initiation Factor eIF2 , 10.1128/mcb.22.21.7405-7416.2002
  28. Koumenis C., "Translating" Tumor Hypoxia: Unfolded Protein Response (UPR)-Dependent and UPR-Independent Pathways, 10.1158/1541-7786.mcr-06-0150
  29. Lacey R. J., Cable H. C., James R. F. L., London N. J. M., Scarpello J. H. B., Morgan N. G., Concentration-dependent effects of adrenaline on the profile of insulin secretion from isolated human islets of Langerhans, 10.1677/joe.0.1380555
  30. Laplante Mathieu, Sabatini David M., mTOR Signaling in Growth Control and Disease, 10.1016/j.cell.2012.03.017
  31. Larsen Jens Jørn, Hansen Jesper Melchior, Olsen Niels Vidiendal, Galbo Henrik, Dela Flemming, The effect of altitude hypoxia on glucose homeostasis in men, 10.1111/j.1469-7793.1997.241bf.x
  32. Lee W. H., Kim Y. W., Choi J. H., Brooks S. C., Lee M.-O., Kim S. G., Oltipraz and dithiolethione congeners inhibit hypoxia-inducible factor-1  activity through p70 ribosomal S6 kinase-1 inhibition and H2O2-scavenging effect, 10.1158/1535-7163.mct-09-0420
  33. Liu Liping, Cash Timothy P., Jones Russell G., Keith Brian, Thompson Craig B., Simon M. Celeste, Hypoxia-Induced Energy Stress Regulates mRNA Translation and Cell Growth, 10.1016/j.molcel.2006.01.010
  34. Lundby C., Acclimatization to 4100 m does not change capillary density or mRNA expression of potential angiogenesis regulatory factors in human skeletal muscle, 10.1242/jeb.01225
  35. MacDOUGALL J. D., GREEN H. J., SUTTON J. R., COATES G., CYMERMAN A., YOUNG P., HOUSTON C. S., Operation Everest II: structural adaptations in skeletal muscle in response to extreme simulated altitude, 10.1111/j.1748-1716.1991.tb09176.x
  36. Martin Daniel S, Levett Denny ZH, Mythen Michael, Grocott Mike PW, , Changes in skeletal muscle oxygenation during exercise measured by near-infrared spectroscopy on ascent to altitude, 10.1186/cc8005
  37. Masschelein E., Van Thienen R., Wang X., Van Schepdael A., Thomis M., Hespel P., Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia, 10.1152/japplphysiol.01253.2011
  38. Mazzeo Robert S., Wolfel Eugene E., Butterfield Gail E., Reeves John T., Sympathetic response during 21 days at high altitude (4,300 m) as determined by urinary and arterial catecholamines, 10.1016/0026-0495(94)90215-1
  39. McGee Sean L., Hargreaves Mark, AMPK-mediated regulation of transcription in skeletal muscle, 10.1042/cs20090533
  40. Mizuno Masao, Savard Gabrielle K, Areskog Nils-Holger, Lundby Carsten, Saltin Bengt, Skeletal Muscle Adaptations to Prolonged Exposure to Extreme Altitude: A Role of Physical Activity?, 10.1089/ham.2008.1009
  41. Navegantes L. C. C., Effect of sympathetic denervation on the rate of protein synthesis in rat skeletal muscle, 10.1152/ajpendo.00371.2003
  42. Navegantes, Am J Physiol Endocrinol Metab, 279, E663 (2000)
  43. Ordway G. A., Myoglobin: an essential hemoprotein in striated muscle, 10.1242/jeb.01172
  44. Oyadomari S, Mori M, Roles of CHOP/GADD153 in endoplasmic reticulum stress, 10.1038/sj.cdd.4401373
  45. Ron David, Walter Peter, Signal integration in the endoplasmic reticulum unfolded protein response, 10.1038/nrm2199
  46. Schols, Am J Clin Nutr, 82, 53 (2005)
  47. Schwarzer Rolf, Tondera Daniel, Arnold Wolfgang, Giese Klaus, Klippel Anke, Kaufmann Jörg, REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase, 10.1038/sj.onc.1208236
  48. Shoshani T., Faerman A., Mett I., Zelin E., Tenne T., Gorodin S., Moshel Y., Elbaz S., Budanov A., Chajut A., Kalinski H., Kamer I., Rozen A., Mor O., Keshet E., Leshkowitz D., Einat P., Skaliter R., Feinstein E., Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis, 10.1128/mcb.22.7.2283-2293.2002
  49. Stitt Trevor N., Drujan Doreen, Clarke Brian A., Panaro Frank, Timofeyva Yekatarina, Kline William O., Gonzalez Michael, Yancopoulos George D., Glass David J., The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors, 10.1016/s1097-2765(04)00211-4
  50. Tagliavacca Luigina, Caretti Anna, Bianciardi Paola, Samaja Michele, In vivo up-regulation of the unfolded protein response after hypoxia, 10.1016/j.bbagen.2012.02.016
  51. Tracy K., Dibling B. C., Spike B. T., Knabb J. R., Schumacker P., Macleod K. F., BNIP3 Is an RB/E2F Target Gene Required for Hypoxia-Induced Autophagy, 10.1128/mcb.02246-06
  52. Vandesompele Jo, De Preter Katleen, Pattyn Filip, Poppe Bruce, Van Roy Nadine, De Paepe Anne, Speleman Frank, 10.1186/gb-2002-3-7-research0034
  53. Viganò Agnese, Ripamonti Marilena, De Palma Sara, Capitanio Daniele, Vasso Michele, Wait Robin, Lundby Carsten, Cerretelli Paolo, Gelfi Cecilia, Proteins modulation in human skeletal muscle in the early phase of adaptation to hypobaric hypoxia, 10.1002/pmic.200800232
  54. Vincent B., Windelinckx A., Nielens H., Ramaekers M., Van Leemputte M., Hespel P., Thomis M. A., Protective role of  -actinin-3 in the response to an acute eccentric exercise bout, 10.1152/japplphysiol.01007.2009
  55. Whitney Michael L., Jefferson Leonard S., Kimball Scot R., ATF4 is necessary and sufficient for ER stress-induced upregulation of REDD1 expression, 10.1016/j.bbrc.2008.12.079
  56. Wouters Bradly G., Koritzinsky Marianne, Hypoxia signalling through mTOR and the unfolded protein response in cancer, 10.1038/nrc2501
  57. Wust, Int J Chron Obstruct Pulmon Dis, 2, 289 (2007)
Bibliographic reference D'Hulst, Gommaar ; Jamart, Cécile ; Van Thienen, Ruud ; Hespel, Peter ; Francaux, Marc ; et. al. Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle. In: Acta Physiologica, Vol. 208, no. 3, p. 251–264
Permanent URL http://hdl.handle.net/2078/124233