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The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes
dc.creator | Livshits, Leonid | |
dc.creator | Peretz, Sari | |
dc.creator | Bogdanova, Anna | |
dc.creator | Zoabi, Hiba | |
dc.creator | Eitam, Harel | |
dc.creator | Barshtein, Gregory | |
dc.creator | Galindo, Cindy | |
dc.creator | Feldman, Yuri | |
dc.creator | Pajić-Lijaković, Ivana | |
dc.creator | Koren, Ariel | |
dc.creator | Gassmann, Max | |
dc.creator | Levin, Carina | |
dc.date.accessioned | 2024-02-08T09:26:45Z | |
dc.date.available | 2024-02-08T09:26:45Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 2073-4409 | |
dc.identifier.uri | http://TechnoRep.tmf.bg.ac.rs/handle/123456789/7180 | |
dc.description.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. | |
dc.publisher | MDPI AG | en |
dc.relation | This project is partially funded by the Fondation Botnar as well as by the Baugarten Stiftung, Susanne & René Braginsky Stiftung, and Ernst Göhner Stiftung. | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | Cells | en |
dc.subject | calcium | |
dc.subject | hemoglobin A2 | |
dc.subject | hemoglobin distribution | |
dc.subject | red blood cells | |
dc.title | The Impact of Ca2+ on Intracellular Distribution of Hemoglobin in Human Erythrocytes | en |
dc.type | article | en |
dc.rights.license | BY | |
dc.citation.issue | 18 | |
dc.citation.rank | M21~ | |
dc.citation.spage | 2280 | |
dc.citation.volume | 12 | |
dc.identifier.doi | 10.3390/cells12182280 | |
dc.identifier.fulltext | http://TechnoRep.tmf.bg.ac.rs/bitstream/id/19828/The_Impact_of_Ca2_pub_2023.pdf | |
dc.identifier.pmid | 37759502 | |
dc.identifier.scopus | 2-s2.0-85172770196 | |
dc.type.version | publishedVersion |