ATP produced by anaerobic glycolysis is essential for enucleation of human erythroblasts

Experimental Hematology
Tatsufumi GotoWataru Nunomura

Abstract

More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O2). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. We examined whether different O2 environments (hypoxic [5% O2] and normoxic [21% O2] conditions) affected human CD34+ cell erythroblast differentiation. We also investigated the regulatory mechanisms underlying energy production in erythroblasts during terminal differentiation under 5% or 21% O2 conditions. The results obtained revealed that the enucleation ratio and intracellular levels of adenosine triphosphate (ATP), lactate dehydrogenase (LDH) M3H, and hypoxia-inducible factor 1α in erythroblasts during terminal differentiation were higher under the 5% O2 condition than under the 21% O2 condition. We also found that the enzymatic inhibition of glyceraldehyde 3-phosphate dehydrogenase and LDH, key enzymes in anaerobic glycolysis, blocked the proliferation of colony-forming units-erythroid and enucleation of erythroblasts, and also reduced ATP levels in erythroblasts under both hypoxic and normoxic conditions. Under ...Continue Reading

Citations

Jul 25, 2020·Haematologica·Paola Bianchi, Elisa Fermo
Jan 14, 2021·Experimental Hematology·Vijay Menon, Saghi Ghaffari
Feb 26, 2021·Scientific Reports·Anastasia RyzhkovaNariman Battulin
Oct 16, 2020·Haematologica·Paola Bianchi, Elisa Fermo

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