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

Academic Article

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.
  • Digital Object Identifier (doi)

    Author List

  • Song J; Sundar K; Gangaraju R; Prchal JT
  • Start Page

  • 1671
  • End Page

  • 1675
  • Volume

  • 123
  • Issue

  • 6