Soluble erythropoietin receptor is present in the mouse brain and is required for the ventilatory acclimatization to hypoxia |
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| Authors: | Jorge Soliz Max Gassmann Vincent Joseph |
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| Institution: | Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland;Department of Pediatrics, Laval University, Center de Recherché(DO-711), Hôpital St-Francois d'Assise, 10 rue de l'Espinay, Quebec (QC), G1L 3L5, Canada |
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| Abstract: | While erythropoietin (Epo) and its receptor (EpoR) have been widely investigated in brain, the expression and function of the soluble Epo receptor (sEpoR) remain unknown. Here we demonstrate that sEpoR, a negative regulator of Epo's binding to the EpoR, is present in the mouse brain and is down-regulated by 62% after exposure to normobaric chronic hypoxia (10% O2 for 3 days). Furthermore, while normoxic minute ventilation increased by 58% in control mice following hypoxic acclimatization, sEpoR infusion in brain during the hypoxic challenge efficiently reduced brain Epo concentration and abolished the ventilatory acclimatization to hypoxia (VAH). These observations imply that hypoxic downregulation of sEpoR is required for adequate ventilatory acclimatization to hypoxia, thereby underlying the function of Epo as a key factor regulating oxygen delivery not only by its classical activity on red blood cell production, but also by regulating ventilation. |
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