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Adaptation of iron requirement to hypoxic conditions at high altitude

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dc.contributor.author Gassmann, Max
dc.contributor.author Muckenthaler, Martina U.
dc.date.accessioned 2019-02-06T14:59:06Z
dc.date.available 2019-02-06T14:59:06Z
dc.date.issued 2015
dc.identifier.uri https://hdl.handle.net/20.500.12866/5529
dc.description.abstract Adequate acclimatization time to enable adjustment to hypoxic conditions is one of the most important aspects for mountaineers ascending to high altitude. Accordingly, most reviews emphasize mechanisms that cope with reduced oxygen supply. However, during sojourns to high altitude adjustment to elevated iron demand is equally critical. Thus in this review we focus on the interaction between oxygen and iron homeostasis. We review the role of iron 1) in the oxygen sensing process and erythropoietin (Epo) synthesis, 2) in gene expression control mediated by the hypoxia-inducible factor-2 (HIF-2), and 3) as an oxygen carrier in hemoglobin, myoglobin, and cytochromes. The blood hormone Epo that is abundantly expressed by the kidney under hypoxic conditions stimulates erythropoiesis in the bone marrow, a process requiring high iron levels. To ensure that sufficient iron is provided, Epo-controlled erythroferrone that is expressed in erythroid precursor cells acts in the liver to reduce expression of the iron hormone hepcidin. Consequently, suppression of hepcidin allows for elevated iron release from storage organs and enhanced absorption of dietary iron by enterocytes. As recently observed in sojourners at high altitude, however, iron uptake may be hampered by reduced appetite and gastrointestinal bleeding. Reduced iron availability, as observed in a hypoxic mountaineer, enhances hypoxia-induced pulmonary hypertension and may contribute to other hypoxia-related diseases. Overall, adequate systemic iron availability is an important prerequisite to adjust to high-altitude hypoxia and may have additional implications for disease-related hypoxic conditions. en_US
dc.language.iso eng
dc.publisher American Physiological Society
dc.relation.ispartofseries Journal of Applied Physiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject Animals en_US
dc.subject Altitude en_US
dc.subject erythropoietin en_US
dc.subject pulmonary hypertension en_US
dc.subject Iron/metabolism en_US
dc.subject Acclimatization en_US
dc.subject erythroferron en_US
dc.subject ferroportin en_US
dc.subject HAPE en_US
dc.subject hepcidin en_US
dc.subject hypoxia-inducible factor en_US
dc.subject Hypoxia/metabolism/physiopathology en_US
dc.subject iron homeostasis en_US
dc.subject iron sensor en_US
dc.subject low oxygen en_US
dc.subject mountaineer en_US
dc.subject oxygen sensor en_US
dc.subject PHD2 en_US
dc.subject prolyl hydroxylase en_US
dc.subject transferrin en_US
dc.title Adaptation of iron requirement to hypoxic conditions at high altitude en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1152/japplphysiol.00248.2015
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.08
dc.relation.issn 1522-1601


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