Characterization and comparison of the red blood cell membrane damage in severe human α- and β-thalassemia

• Published in: Blood Vol. 79; no. 4; pp. 1058 - 1063
• Main Authors: ADVANI, R, SORENSON, S, SHINAR, E, LANDE, W, RACHMILEWITZ, E, SCHRIER, S. L
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.02.1992
• Subjects: Anemias. Hemoglobinopathies; Biological and medical sciences; Blotting, Western; Chromatography; Cytoskeletal Proteins; Diseases of red blood cells; Disulfides; Electrophoresis, Polyacrylamide Gel; Erythrocyte Membrane - metabolism; Erythrocyte Membrane - pathology; Globins - metabolism; Hematologic and hematopoietic diseases; Humans; Medical sciences; Membrane Proteins - metabolism; Neuropeptides; Oxidation-Reduction; Spectrin - metabolism; Splenectomy; Sulfhydryl Compounds - blood; Thalassemia - blood; Human; Hemoglobinopathy; Pathophysiology; β-Thalassemia; α-Thalassemia; Plasma membrane; Red blood cell; Exploration; Hemopathy; Chromatography; Comparative study
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V79.4.1058.1058

The aim of the present work was to understand the pathophysiology of the severe human thalassemias as represented by beta-thalassemia intermedia and hemoglobin (Hb) H (alpha-thalassemia) disease. We have previously shown that the material properties of the red blood cell (RBC) and its membrane differ in severe alpha- and beta-thalassemia, and we now show that this difference is probably caused by accumulation of alpha-globin chains at the cytoskeleton in beta-thalassemia, whereas beta-globin chains are associated with the cytoskeleton in alpha-thalassemia. In both alpha- and beta-thalassemia, some of these globin chains have become oxidized as evidenced by loss of the free thiols. Furthermore, there is similar evidence of oxidation of protein 4.1 in beta-thalassemia, whereas beta-spectrin appears to be subject to oxidation in alpha-thalassemia. These observations support the idea that the association of partly oxidized globin chains with the cytoskeleton results in oxidation of adjacent skeletal proteins. The abnormality of protein 4.1 in beta-thalassemia is consistent with a prior observation, and is also in accord with the known importance of protein 4.1 in maintenance of membrane stability, a property that is abnormal in beta-thalassemic membranes.