The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes
Аутори
Livshits, LeonidPeretz, Sari
Bogdanova, Anna
Zoabi, Hiba
Eitam, Harel
Barshtein, Gregory
Galindo, Cindy
Feldman, Yuri
Pajić-Lijaković, Ivana
Koren, Ariel
Gassmann, Max
Levin, Carina
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
calcium / hemoglobin A2 / hemoglobin distribution / red blood cellsИзвор:
Cells, 2023, 12, 18, 2280-Издавач:
- MDPI AG
Финансирање / пројекти:
- This project is partially funded by the Fondation Botnar as well as by the Baugarten Stiftung, Susanne & René Braginsky Stiftung, and Ernst Göhner Stiftung.
DOI: 10.3390/cells12182280
ISSN: 2073-4409
PubMed: 37759502
Scopus: 2-s2.0-85172770196
Институција/група
Tehnološko-metalurški fakultetTY - 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 . .