Functional plasticity of the N-methyl-d-aspartate receptor in differentiating human erythroid precursor cells.
Bottom Line: Kinetics of this switch in NMDAR properties and abundance varied markedly from donor to donor.Despite this variability, NMDARs were essential for survival of EPCs in any subject tested.Our findings indicate that NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca(2+) homeostasis from the orthochromatic erythroblast stage to circulating red blood cells.
Affiliation: Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Division of Hematology University Hospital Zurich, Zurich, Switzerland; University Children's Hospital, Zurich, Switzerland;Show MeSH
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Mentions: Earlier on, we have shown that high doses of memantine or MK-801 (above 100 or 50 μM, respectively) resulted in cell death, which was particularly pronounced for the early differentiation stages (18, 35). Herein we have extended this observation by analyzing the mechanism of cell death induced by high doses of pore-targeting NMDAR blockers. Incubation of basophilic erythroblasts with 500 μM MK-801 or memantine (the dose toxic for both blockers) for 12 h in the SFEM culture medium induced activation of caspase 3, caspase 8, and caspase 9 in the majority of cells (Fig. 8 and Table 4). Phosphatidylserine exposure was enhanced in EPCs exposed to both NMDAR antagonists (Fig. 8 and Table 5). Hyperactivation of the receptors by additional supplementation of NMDA (500 μM) and glycine (100 μM) to the culture medium caused only modest adverse effects (Table 5).
Affiliation: Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Division of Hematology University Hospital Zurich, Zurich, Switzerland; University Children's Hospital, Zurich, Switzerland;