TY - JOUR

T1 - Hematin- and Hemin-Induced Spherization and Hemolysis of Human Erythrocytes Are Independent of Extracellular Calcium Concentration

AU - Михайлова, Диана Михайловна

AU - Скверчинская, Е.А.

AU - Судницына, Ю.С.

AU - Бутов, Кирилл

AU - Кольцова, Екатерина

AU - Миндукшев, И.В.

AU - Гамбарян, Степан Петрович

PY - 2024/3/21

Y1 - 2024/3/21

N2 - 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 -) and hemin (liganded with Cl -)-are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe 3. 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 2+] i in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca 2+] i. 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.

AB - 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 -) and hemin (liganded with Cl -)-are the oxidized forms of heme with toxic properties due to their hydrophobicity and the presence of redox-active Fe 3. 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 2+] i in RBC; however, spherization and hemolysis occurred in the presence and absence of calcium, indicating that both processes are independent of [Ca 2+] i. 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.

KW - Calcium/metabolism

KW - Erythrocytes/metabolism

KW - Heme/metabolism

KW - Hemin/metabolism

KW - Hemolysis

KW - Humans

KW - hematin

KW - cell spherization

KW - hemolysis

KW - erythrocytes

KW - albumin

KW - laser diffraction

KW - hemin

UR - https://www.mdpi.com/2073-4409/13/6/554

UR - https://www.mendeley.com/catalogue/911e5392-0775-3814-af7f-a35013f43b58/

U2 - 10.3390/cells13060554

DO - 10.3390/cells13060554

M3 - Article

C2 - 38534398

VL - 13

JO - Cells

JF - Cells

SN - 2073-4409

IS - 6

M1 - 554

ER -