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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4724-4731. Prepublished online as a Blood First Edition Paper on February 20, 2007; DOI 10.1182/blood-2006-08-040006. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-040006v1 109/11/4724    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robach, P. Articles by Lundby, C. Search for Related Content PubMed PubMed Citation Articles by Robach, P. Articles by Lundby, C. Related Collections Hematopoiesis and Stem Cells Red Cells Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle Paul Robach1,9, Gaetano Cairo2, Cecilia Gelfi3, Francesca Bernuzzi2, Henriette Pilegaard4, Agnese Viganò3, Paolo Santambrogio5, Paolo Cerretelli3, José A. L. Calbet6, Stéphane Moutereau7, and Carsten Lundby4,8 1 Département médical, Ecole Nationale de Ski et d'Alpinisme, Chamonix, France; 2 Institute of General Pathology, University of Milano, Italy; 3 Department of Sciences and Biomedical Technologies, University of Milano, Segrate, Italy; 4 The Copenhagen Muscle Research Centre and Centre of Inflammation and Metabolism, Institute of Molecular Biology and Physiology, University of Copenhagen, Denmark; 5 Protein Engineering Unit, Dibit, Instituto di Ricerca e Cura a Carattere Scientifico (IRCCS) H.S. Raffaele, Milano, Italy; 6 Department of Physical Education, University of Las Palmas de Gran Canaria, Spain; 7 Laboratoire de Biochimie, Hôpital Henri-Mondor, Créteil, France; 8 Department of Sport Science, University of Århus, Denmark; 9 Laboratoire "Réponses Cellulaires et Fonctionnelles à l'Hypoxie," Association pour la Recherche en Physiologie de l'Environment (ARPE), Université Paris 13, Bobigny, France Iron is essential for oxygen transport because it is incorporated in the heme of the oxygen-binding proteins hemoglobin and myoglobin. An interaction between iron homeostasis and oxygen regulation is further suggested during hypoxia, in which hemoglobin and myoglobin syntheses have been reported to increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells, mobilizes body iron, and increases hemoglobin concentration. However, contrary to our hypothesis that muscle iron proteins and myoglobin would also be up-regulated during HA, this study shows that HA lowers myoglobin expression by 35% and down-regulates iron-related proteins in skeletal muscle, as evidenced by decreases in L-ferritin (43%), transferrin receptor (TfR; 50%), and total iron content (37%). This parallel decrease in L-ferritin and TfR in HA occurs independently of increased hypoxia-inducible factor 1 (HIF-1) mRNA levels and unchanged binding activity of iron regulatory proteins, but concurrently with increased ferroportin mRNA levels, suggesting enhanced iron export. Thus, in HA, the elevated iron requirement associated with enhanced erythropoiesis presumably elicits iron mobilization and myoglobin down-modulation, suggesting an altered muscle oxygen homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Trading muscle iron for erythropoiesis at high altitude Chaim Hershko Blood 2007 109: 4597. [Full Text] [PDF] This article has been cited by other articles: M. A. Bekedam, B. J. van Beek-Harmsen, W. van Mechelen, A. Boonstra, and W. J. van der Laarse Myoglobin concentration in skeletal muscle fibers of chronic heart failure patients J Appl Physiol, October 1, 2009; 107(4): 1138 - 1143. [Abstract] [Full Text] [PDF] R. C. I. Wust, R. T. Jaspers, A. F. van Heijst, M. T. E. Hopman, L. J. C. Hoofd, W. J. van der Laarse, and H. Degens Region-specific adaptations in determinants of rat skeletal muscle oxygenation to chronic hypoxia Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H364 - H374. [Abstract] [Full Text] [PDF] M. Kerenyi and E. W. Mullner Muscle iron in stress erythropoiesis? Blood, June 25, 2009; 113(26): 6507 - 6508. [Full Text] [PDF] P. Robach, S. Recalcati, D. Girelli, C. Gelfi, N. J. Aachmann-Andersen, J. J. Thomsen, A. M. Norgaard, A. Alberghini, N. Campostrini, A. Castagna, et al. Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin Blood, June 25, 2009; 113(26): 6707 - 6715. [Abstract] [Full Text] [PDF] C. Lundby, Y. Hellsten, M. B. F. Jensen, A. S. Munch, and H. Pilegaard Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle J Appl Physiol, April 1, 2008; 104(4): 1154 - 1160. [Abstract] [Full Text] [PDF]

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