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Red blood cells of sickle cell disease patients exhibit abnormally high abundance of <scp>N</scp> ‐methyl D‐aspartate receptors mediating excessive calcium uptake
- Source :
- British Journal of Haematology. 167:252-264
- Publication Year :
- 2014
- Publisher :
- Wiley, 2014.
-
Abstract
- Summary Recently we showed that N-methyl D-aspartate receptors (NMDARs) are expressed in erythroid precursors (EPCs) and present in the circulating red blood cells (RBCs) of healthy humans, regulating intracellular Ca2+ in these cells. This study focuses on investigating the possible role of NMDARs in abnormally high Ca2+ permeability in the RBCs of patients with sickle cell disease (SCD). Protein levels of the NMDAR subunits in the EPCs of SCD patients did not differ from those in EPCs of healthy humans. However, the number and activity of the NMDARs in circulating SCD-RBCs was substantially up-regulated, being particularly high during haemolytic crises. The number of active NMDARs 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-RBCs. Oxidative stress and RBC dehydration followed receptor stimulation and Ca2+ uptake. Inhibition of the NMDARs with an antagonist memantine caused re-hydration and largely prevented hypoxia-induced sickling. The EPCs of SCD patients showed higher tolerance to memantine than those of healthy subjects. Consequently, NMDARs in the RBCs of SCD patients appear to be an attractive target for pharmacological intervention.
- Subjects :
- Adult
medicine.medical_specialty
Erythrocytes
Homocysteine
chemistry.chemical_element
Anemia, Sickle Cell
Calcium
Biology
medicine.disease_cause
Receptors, N-Methyl-D-Aspartate
Young Adult
chemistry.chemical_compound
hemic and lymphatic diseases
Internal medicine
medicine
Humans
Erythropoiesis
Receptor
Cells, Cultured
Erythrocyte Volume
Erythroid Precursor Cells
Memantine
Glutamate receptor
Hematology
Glutathione
Cell Hypoxia
Endocrinology
nervous system
chemistry
Case-Control Studies
Immunology
NMDA receptor
Oxidation-Reduction
Intracellular
Oxidative stress
circulatory and respiratory physiology
medicine.drug
Subjects
Details
- ISSN :
- 13652141 and 00071048
- Volume :
- 167
- Database :
- OpenAIRE
- Journal :
- British Journal of Haematology
- Accession number :
- edsair.doi.dedup.....f1e664e1c31cf65220ca842bc2bde81e