Soluble erythropoietin receptor is present in the mouse brain and is required for the ventilatory acclimatization to hypoxia
- 7 August 2007
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 583 (1) , 329-336
- https://doi.org/10.1113/jphysiol.2007.133454
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.Keywords
This publication has 36 references indexed in Scilit:
- HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSIONClinical and Experimental Pharmacology and Physiology, 2006
- Regulation of erythropoietin productionEuropean Journal of Clinical Investigation, 2005
- Effects of short‐term hypoxia on neuroglobin levels and localization in mouse brain tissuesNeuropathology and Applied Neurobiology, 2005
- Impaired ventilatory acclimatization to hypoxia in mice lacking the immediate early gene fos BRespiratory Physiology & Neurobiology, 2005
- Erythropoietin protects from axotomy‐induced degeneration of retinal ganglion cells by activating ERK‐1/‐2The FASEB Journal, 2004
- Pleiotropic Functions of Erythropoietin.Internal Medicine, 2003
- HIF‐1 is expressed in normoxic tissue and displays an organ‐specific regulation under systemic hypoxiaThe FASEB Journal, 2001
- Altered respiratory responses to hypoxia in mutant mice deficient in neuronal nitric oxide synthaseThe Journal of Physiology, 1998
- Production and ligand-binding characteristics of the soluble form of murine erythropoietin receptorBiochemical and Biophysical Research Communications, 1992
- Characterization of murine erythropoietin receptor genesJournal of Molecular Biology, 1990