title: Erythropoietin-regulated oxidative stress negatively affects enucleation during terminal erythropoiesis.
abstract: Differentiating erythroblasts are exposed to an oxidative environment. The dynamics of oxidative status during terminal erythropoiesis and how they affect cell differentiation in response to erythropoietin (Epo) are unclear. Here, we show that Epo induces reactive oxygen species (ROS) production in the early stages of terminal erythropoiesis. The levels of ROS correlate with CD71 surface expression and the uptake of iron and transferrin. ROS decreases in the late stages of terminal erythropoiesis, when the cells are preparing for enucleation. Consistently, treatment of erythroblasts with a low dose (5 mM) of N-acetyl-cysteine (NAC), a ROS scavenger, promotes enucleation. However, a high dose (20 mM) of NAC leads to significant cell death. Our study reveals an important function of Epo in regulating the dynamics of oxidative status and enucleation.
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Baobing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: ji.peng@northwestern.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D004900:Erythroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology*; D005333:Fetus; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D016130:Immunophenotyping; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000166:cytology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016298:Hematopoietic Cell Growth Factors; D006454:Hemoglobins; D017382:Reactive Oxygen Species; D014168:Transferrin; D004921:Erythropoietin; D007501:Iron