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Adaptation of iron requirement to hypoxic conditions at high altitude


Gassmann, Max; Muckenthaler, Martina U (2015). Adaptation of iron requirement to hypoxic conditions at high altitude. Journal of Applied Physiology, 119(12):1432-1440.

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 (i) in the oxygen sensing process and erythropoietin (Epo) synthesis, (ii) in gene expression control mediated by the hypoxia-inducible factor-2 (HIF-2), and (iii) 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.

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 (i) in the oxygen sensing process and erythropoietin (Epo) synthesis, (ii) in gene expression control mediated by the hypoxia-inducible factor-2 (HIF-2), and (iii) 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:16 July 2015
Deposited On:05 Aug 2015 09:32
Last Modified:08 Dec 2017 13:37
Publisher:American Physiological Society
ISSN:0161-7567
Publisher DOI:https://doi.org/10.1152/japplphysiol.00248.2015
Related URLs:http://jap.physiology.org/content/by/year (Publisher)
PubMed ID:26183475

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