| Autor: |
Mikhailova DM; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia.; Department of Cytology and Histology, Saint Petersburg State University, 7/9 Universitetskaya Emb., 199034 Saint Petersburg, Russia., Skverchinskaya E; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia., Sudnitsyna J; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia., Butov KR; Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia., Koltsova EM; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997 Moscow, Russia.; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya st., 109029 Moscow, Russia., Mindukshev IV; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia., Gambaryan S; Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia. |
| Abstrakt: |
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. |
