title: Characterization and comparison of the red blood cell membrane damage in severe human alpha- and beta-thalassemia.
abstract: 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.
authors.affiliation: Department of Hematology, Stanford University School of Medicine, CA.
authors.forename: R
authors.initials: R
authors.lastname: Advani
authors.forename: S
authors.initials: S
authors.lastname: Sorenson
authors.forename: E
authors.initials: E
authors.lastname: Shinar
authors.forename: W
authors.initials: W
authors.lastname: Lande
authors.forename: E
authors.initials: E
authors.lastname: Rachmilewitz
authors.forename: S L
authors.initials: SL
authors.lastname: Schrier
mesh_terms: D015153:Blotting, Western; D002845:Chromatography; D003598:Cytoskeletal Proteins; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000473:pathology*; D005914:Globins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009479:Neuropeptides; D010084:Oxidation-Reduction; D013049:Spectrin / Q000378:metabolism; D013156:Splenectomy; D013438:Sulfhydryl Compounds / Q000097:blood; D013789:Thalassemia / Q000097:blood*
chemical_list: D003598:Cytoskeletal Proteins; D004220:Disulfides; D008565:Membrane Proteins; D009479:Neuropeptides; D013438:Sulfhydryl Compounds; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D013049:Spectrin; D005914:Globins