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

• Published in: Journal of applied physiology (1985) Vol. 123; no. 6; pp. 1671 - 1675
• Main Authors: Song, Jihyun, Sundar, Krishna, Gangaraju, Radhika, Prchal, Josef T
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.12.2017
• Series: Hypoxia 2017
• Subjects: Animals; Catalase - metabolism; Disease Models, Animal; Erythrocytes - enzymology; Erythropoiesis; Erythropoietin - metabolism; Humans; Hypoxia - physiopathology; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Membrane Proteins - metabolism; Mice; Mitochondrial Degradation; Proto-Oncogene Proteins - metabolism; Reactive Oxygen Species - metabolism; Review; Tumor Suppressor Proteins - metabolism; hypoxia; sustained and intermittent hypoxia; neocytolysis; erythropoiesis; normoxic return from hypoxia
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00119.2017

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.