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The Impact of Ca(2+) on Intracellular Distribution of Hemoglobin in Human Erythrocytes

The membrane-bound hemoglobin (Hb) fraction impacts red blood cell (RBC) rheology and metabolism. Therefore, Hb–RBC membrane interactions are precisely controlled. For instance, the signaling function of membrane-bound deoxy-Hb and the structure of the docking sites in the cytosolic domain of the an...

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Detalles Bibliográficos
Autores principales: Livshits, Leonid, Peretz, Sari, Bogdanova, Anna, Zoabi, Hiba, Eitam, Harel, Barshtein, Gregory, Galindo, Cindy, Feldman, Yuri, Pajić-Lijaković, Ivana, Koren, Ariel, Gassmann, Max, Levin, Carina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10526966/
https://www.ncbi.nlm.nih.gov/pubmed/37759502
http://dx.doi.org/10.3390/cells12182280
Descripción
Sumario:The membrane-bound hemoglobin (Hb) fraction impacts red blood cell (RBC) rheology and metabolism. Therefore, Hb–RBC membrane interactions are precisely controlled. For instance, the signaling function of membrane-bound deoxy-Hb and the structure of the docking sites in the cytosolic domain of the anion exchanger 1 (AE-1) protein are well documented; however, much less is known about the interaction of Hb variants with the erythrocyte’s membrane. Here, we identified factors other than O(2) availability that control Hb abundance in the membrane-bound fraction and the possible variant-specific binding selectivity of Hb to the membrane. We show that depletion of extracellular Ca(2+) by chelators, or its omission from the extracellular medium, leads to membrane-bound Hb release into the cytosol. The removal of extracellular Ca(2+) further triggers the redistribution of HbA0 and HbA2 variants between the membrane and the cytosol in favor of membrane-bound HbA2. Both effects are reversible and are no longer observed upon reintroduction of Ca(2+) into the extracellular medium. Fluctuations of cytosolic Ca(2+) also impact the pre-membrane Hb pool, resulting in the massive transfer of Hb to the cellular cytosol. We hypothesize that AE-1 is the specific membrane target and discuss the physiological outcomes and possible clinical implications of the Ca(2+) regulation of the intracellular Hb distribution.