TY  - JOUR
AU  - Livshits, Leonid
AU  - Peretz, Sari
AU  - Bogdanova, Anna
AU  - Zoabi, Hiba
AU  - Eitam, Harel
AU  - Barshtein, Gregory
AU  - Galindo, Cindy
AU  - Feldman, Yuri
AU  - Pajić-Lijaković, Ivana
AU  - Koren, Ariel
AU  - Gassmann, Max
AU  - Levin, Carina
PY  - 2023
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/7180
AB  - 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 O2 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 Ca2+ by chelators, or its omission from the extracellular medium, leads to membrane-bound Hb release into the cytosol. The removal of extracellular Ca2+ 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 Ca2+ into the extracellular medium. Fluctuations of cytosolic Ca2+ 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 Ca2+ regulation of the intracellular Hb distribution.
PB  - MDPI AG
T2  - Cells
T1  - The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes
IS  - 18
SP  - 2280
VL  - 12
DO  - 10.3390/cells12182280
ER  - 

@article{
author = "Livshits, Leonid and Peretz, Sari and Bogdanova, Anna and Zoabi, Hiba and Eitam, Harel and Barshtein, Gregory and Galindo, Cindy and Feldman, Yuri and Pajić-Lijaković, Ivana and Koren, Ariel and Gassmann, Max and Levin, Carina",
year = "2023",
abstract = "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 O2 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 Ca2+ by chelators, or its omission from the extracellular medium, leads to membrane-bound Hb release into the cytosol. The removal of extracellular Ca2+ 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 Ca2+ into the extracellular medium. Fluctuations of cytosolic Ca2+ 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 Ca2+ regulation of the intracellular Hb distribution.",
publisher = "MDPI AG",
journal = "Cells",
title = "The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes",
number = "18",
pages = "2280",
volume = "12",
doi = "10.3390/cells12182280"
}

Livshits, L., Peretz, S., Bogdanova, A., Zoabi, H., Eitam, H., Barshtein, G., Galindo, C., Feldman, Y., Pajić-Lijaković, I., Koren, A., Gassmann, M.,& Levin, C.. (2023). The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes. in Cells
MDPI AG., 12(18), 2280.
https://doi.org/10.3390/cells12182280

Livshits L, Peretz S, Bogdanova A, Zoabi H, Eitam H, Barshtein G, Galindo C, Feldman Y, Pajić-Lijaković I, Koren A, Gassmann M, Levin C. The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes. in Cells. 2023;12(18):2280.
doi:10.3390/cells12182280 .

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, "The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes" in Cells, 12, no. 18 (2023):2280,
https://doi.org/10.3390/cells12182280 . .