Differentiation of erythroblast requires the dimeric form of acetylcholinesterase: Interference with erythropoietin receptor

Abstract

Acetylcholinesterase (AChE) hydrolyzes acetylcholine at cholinergic synapses, and which has various isoforms of AChE, i.e. AChE_R, AChE_H and AChE_T, deriving from single gene. AChE_H exists as a glycophosphatidylinositol (GPI)-linked dimer (G2), presents mainly in plasma membrane of mammalian erythrocyte. Transgenic mice with ACHE gene depletion were employed here to investigate the possible role of AChE in blood cell formation. ACHE knock-out mice were found to suffer normocytic anemia. In erythrocyte of ACHE-/- mice, the amount of hemoglobin, especially α-globin, was found to be markedly reduced. In addition, the number of erythrocyte and hematocrit of ACHE-/- mice were significantly lowered. To probe the role of AChE isoforms in erythroid differentiation, erythroblast-like cells (TF-1) over-expressed with different AChE isoforms were induced to differentiate by erythropoietin (EPO): this differentiation induced the expression of each AChE isoform. Only in the TF-1 cells over-expressed with AChE_H, the EPO-induced transcriptions and protein expressions of α- and β-globins could be significantly enhanced, which therefore suggested that AChE_H might regulate the responsiveness of TF-1 cells to EPO. The alternation of EPO-induced downstream signaling might be accounted by association of AChE with EPO receptor in cell surface. The findings indicated the significance of AChE in erythroblast maturation, which provided an insight in elucidating possible mechanisms in regulating erythropoiesis.

Keywords: Acetylcholinesterase; Differentiation; Erythrocyte; Erythropoietin; Hemoglobin.