Regulation of erythropoiesis after normoxic return from chronic sustained and intermittent hypoxia

Journal of Applied Physiology
Jihyun SongJosef T Prchal

Abstract

Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF), which regulate erythropoietin transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species in reticulocytes mediated by downregulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes. Decreased CAT results from hypoxia-induced miR-21 that downregulates CAT. This correlates with a transient acute decrease of HIF-1 at normoxic return that is associated with normalization of red cell mass.

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Citations

May 20, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hua ZhangJames E Faber
Jun 21, 2018·Frontiers in Physiology·Inmaculada DocioAsuncion Rocher
Oct 14, 2017·Journal of Applied Physiology·Robert C RoachPeter H Hackett

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