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Red blood cells of sickle cell disease patients exhibit abnormally high abundance of N ‐methyl D‐aspartate receptors mediating excessive calcium uptake
Author(s) -
Hänggi Pascal,
Makhro Asya,
Gassmann Max,
Schmugge Markus,
Goede Jeroen S.,
Speer Oliver,
Bogdanova Anna
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13028
Subject(s) - memantine , nmda receptor , receptor , calcium , glutamate receptor , oxidative stress , calcium in biology , chemistry , red blood cell , medicine , endocrinology , pharmacology
Summary Recently we showed that N‐methyl D‐aspartate receptors ( NMDAR s) are expressed in erythroid precursors ( EPC s) and present in the circulating red blood cells ( RBC s) of healthy humans, regulating intracellular Ca 2+ in these cells. This study focuses on investigating the possible role of NMDAR s in abnormally high Ca 2+ permeability in the RBC s of patients with sickle cell disease ( SCD ). Protein levels of the NMDAR subunits in the EPC s of SCD patients did not differ from those in EPC s of healthy humans. However, the number and activity of the NMDAR s in circulating SCD ‐ RBC s was substantially up‐regulated, being particularly high during haemolytic crises. The number of active NMDAR s correlated negatively with haematocrit and haemoglobin levels in the blood of SCD patients. Calcium uptake via these non‐selective cation channels was induced by RBC treatment with glycine, glutamate and homocysteine and was facilitated by de‐oxygenation of SCD ‐ RBC s. Oxidative stress and RBC dehydration followed receptor stimulation and Ca 2+ uptake. Inhibition of the NMDAR s with an antagonist memantine caused re‐hydration and largely prevented hypoxia‐induced sickling. The EPC s of SCD patients showed higher tolerance to memantine than those of healthy subjects. Consequently, NMDAR s in the RBC s of SCD patients appear to be an attractive target for pharmacological intervention.