Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration
Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH<sup>−</sup>) and hemin (liganded with Cl<sup>−</sup>)—are the oxidized forms...
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MDPI AG
2024-03-01
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| author | Diana M. Mikhailova Elisaveta Skverchinskaya Julia Sudnitsyna Kirill R. Butov Ekaterina M. Koltsova Igor V. Mindukshev Stepan Gambaryan |
| author_facet | Diana M. Mikhailova Elisaveta Skverchinskaya Julia Sudnitsyna Kirill R. Butov Ekaterina M. Koltsova Igor V. Mindukshev Stepan Gambaryan |
| author_sort | Diana M. Mikhailova |
| collection | DOAJ |
| description | Pathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH<sup>−</sup>) and hemin (liganded with Cl<sup>−</sup>)—are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe<sup>3</sup>. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation. Hematin and hemin at nanomolar concentrations increased [Ca<sup>2+</sup>]<sub>i</sub> in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca<sup>2+</sup>]<sub>i</sub>. Both compounds triggered acute phosphatidylserine exposure on the membrane surface, reversible after 60 min of incubation. A comparison of hematin and hemin effects on RBCs revealed that hematin is a more reactive toxic metabolite than hemin towards human RBCs. The toxic effects of heme derivatives were reduced and even reversed in the presence of albumin, indicating the presence in RBCs of the own recovery system against the toxic effects of heme derivatives. |
| first_indexed | 2024-04-24T18:26:37Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T18:26:37Z |
| publishDate | 2024-03-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-397e3ab6b2e24735ae240dcd4862f0842024-03-27T13:30:44ZengMDPI AGCells2073-44092024-03-0113655410.3390/cells13060554Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium ConcentrationDiana M. Mikhailova0Elisaveta Skverchinskaya1Julia Sudnitsyna2Kirill R. Butov3Ekaterina M. Koltsova4Igor V. Mindukshev5Stepan Gambaryan6Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, RussiaDepartment of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, 117997 Moscow, RussiaDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, RussiaPathologies such as malaria, hemorrhagic stroke, sickle cell disease, and thalassemia are characterized by the release of hemoglobin degradation products from damaged RBCs. Hematin (liganded with OH<sup>−</sup>) and hemin (liganded with Cl<sup>−</sup>)—are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe<sup>3</sup>. In the present study, using the original LaSca-TM laser particle analyzer, flow cytometry, and confocal microscopy, we showed that both hematin and hemin induce dose-dependent RBC spherization and hemolysis with ghost formation. Hematin and hemin at nanomolar concentrations increased [Ca<sup>2+</sup>]<sub>i</sub> in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca<sup>2+</sup>]<sub>i</sub>. Both compounds triggered acute phosphatidylserine exposure on the membrane surface, reversible after 60 min of incubation. A comparison of hematin and hemin effects on RBCs revealed that hematin is a more reactive toxic metabolite than hemin towards human RBCs. The toxic effects of heme derivatives were reduced and even reversed in the presence of albumin, indicating the presence in RBCs of the own recovery system against the toxic effects of heme derivatives.https://www.mdpi.com/2073-4409/13/6/554erythrocyteshematinhemincell spherizationhemolysisalbumin |
| spellingShingle | Diana M. Mikhailova Elisaveta Skverchinskaya Julia Sudnitsyna Kirill R. Butov Ekaterina M. Koltsova Igor V. Mindukshev Stepan Gambaryan Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration Cells erythrocytes hematin hemin cell spherization hemolysis albumin |
| title | Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration |
| title_full | Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration |
| title_fullStr | Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration |
| title_full_unstemmed | Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration |
| title_short | Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration |
| title_sort | hematin and hemin induced spherization and hemolysis of human erythrocytes are independent of extracellular calcium concentration |
| topic | erythrocytes hematin hemin cell spherization hemolysis albumin |
| url | https://www.mdpi.com/2073-4409/13/6/554 |
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