Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle

Blood - Tập 109 Số 11 - Trang 4724-4731 - 2007
Paul Robach1,2, Gaetano Cairo3, Cecilia Gelfi4, Francesca Bernuzzi3, Henriette Pilegaard5, Agnese Viganò4, Paolo Santambrogio6, P. Cerretelli4, J. A. L. Calbet7, Stéphane Moutereau8, Carsten Lundby9,5
1Département Médical, Ecole Nationale de Ski et d’Alpinisme, Chamonix, France
2Laboratoire “Réponses Cellulaires et Fonctionnelles à l'Hypoxie,” Association pour la Recherche en Physiologie de l'Environment (ARPE), Université Paris 13, Bobigny, France
3Institute of General Pathology, University of Milano, Italy;
4Department of Sciences and Biomedical Technologies, University of Milano, Segrate, Italy;
5The Copenhagen Muscle Research Centre and Centre of Inflammation and Metabolism, Institute of Molecular Biology and Physiology, University of Copenhagen, Denmark;
6Protein Engineering Unit, Dibit, Instituto di Ricerca e Cura a Carattere Scientifico (IRCCS) H.S. Raffaele, Milano, Italy;
7Department of Physical Education, University of Las Palmas de Gran Canaria, Spain;
8Laboratoire de Biochimie, Hôpital Henri-Mondor, Créteil, France;
9Department of Sport Science, University of Århus, Denmark;

Tóm tắt

AbstractIron 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.

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Blood

Tập 109 Số 11

4724-4731

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