title: Erythrocytes anion transport and oxidative change in beta-thalassaemias.
abstract: beta-Thalassaemia is characterized by a decrease in globin beta-chain synthesis and an excess in free alpha-globin chains. This induces alterations in membrane lipids and proteins resulting from a reduction in spectrin/band 3 ratio, partial oxidation of band 4.1 and clustering of band 3. The membrane injury provokes hyperhaemolysis and bone marrow hyperplasia. The pathophysiology of thalassaemia is associated with iron overload that generates oxygen free radicals and oxidative tissue injury with ocular vessel alterations. The aim of this research is to investigate the influence of oxidative stress on band 3 efficiency, which is an integral membrane protein of RBCs (red blood cells). Band 3 protein, of which there are more than 1 million copies per cell, is the most abundant membrane protein in human RBCs. It mediates the anion exchange and acid-base equilibrium through the RBC membrane. Some experiments were performed on thalassaemic cells and beta-thalassaemia-like cells and tested for sulfate uptake. To test the antioxidant effect of Mg(2+), other experiments were performed using normal and pathological cells in the presence of Mg(2+). The oxidant status in thalassaemic cells was verified by increased K(+) efflux, by lower GSH levels and by increased G6PDH (glucose-6-phosphate dehydrogenase) activity. The rate constant of SO(4)(2-) uptake decreases in thalassaemic cells as well as in beta-thalassaemia-like cells when compared with normal cells. It increases when both cells are incubated with Mg(2+). Our data show that oxidative stress plays a relevant role in band 3 function of thalassaemic cells and that antioxidant treatment with Mg(2+) could reduce oxidative damage to the RBC membrane and improve the anion transport efficiency regulated by band 3 protein.
authors.affiliation: Department of Experimental Pathology and Microbiology, Section of Experimental Pathology, Faculty of Medicine and Surgery, Torre Biologica IV Piano, Policlinico G. Martino, 98125 Messina, Italy. crupi.maria@gmail.com
authors.forename: Crupi
authors.initials: C
authors.lastname: Maria
authors.forename: Romano
authors.initials: R
authors.lastname: Leonardo
authors.forename: Romano
authors.initials: R
authors.lastname: Pietro
authors.forename: Venza
authors.initials: V
authors.lastname: Mario
authors.forename: Venza
authors.initials: V
authors.lastname: Isabella
authors.forename: Teti
authors.initials: T
authors.lastname: Diana
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007501:Iron / Q000032:analysis / Q000097:blood; D008274:Magnesium / Q000494:pharmacology; D018384:Oxidative Stress; D011188:Potassium / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D017086:beta-Thalassemia / Q000378:metabolism* / Q000473:pathology
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000975:Antioxidants; D013431:Sulfates; D007501:Iron; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; D008274:Magnesium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium