Globin-chain specificity of oxidation-induced changes in red blood cell membrane properties

Schrier, SL; Mohandas, Narla

doi:10.1182/blood.v79.6.1586.1586

Cited by 53 publications

(28 citation statements)

References 18 publications

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“…Relative to the functionality of band 3, the data presented here show a decreased rate constant of sulfate uptake in thalassaemic cells compared with control ones (Figure 1; Table 1). Furthermore, some studies have shown that thalassaemic cells can be reproduced by exposure of normal RBCs to the oxidant PHZ (Schrier and Mohandas, 1992;Olivieri et al, 1994). Our findings show that the impaired ability of band 3 to regulate anion transport observed in thalassaemia was also confirmed in thalassaemic-like cells (Figure 2).…”

Section: Discussionsupporting

confidence: 76%

“…Furthermore, previous studies have shown that the membrane protein abnormalities observed in severe b-thalassaemia can be reproduced in normal RBCs by exposure to the oxidant PHZ (phenylhydrazine) (Schrier and Mohandas, 1992;Olivieri et al, 1994). So, to investigate the influence of oxidative stress on band 3 efficiency, some experiments were performed by thalassaemic cells and by b-thalassaemia-like cells and tested for sulfate uptake.…”

Section: Introductionmentioning

confidence: 99%

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Erythrocytes anion transport and oxidative change in β‐thalassaemias

Maria

Romano²,

Romano

et al. 2010

Cell Biology International

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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.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Erythrocytes anion transport and oxidative change in β‐thalassaemias

Maria

Romano²,

Romano

et al. 2010

Cell Biology International

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“…A preponderance of recent evidence indicates that the enhanced destruction of thalassemic red cells in vivo is largely attributed to increased oxidative stress to these cells (54)(55)(56)(57)(58). Furthermore, recent studies have pointed out that the enhanced oxidative damage to the cell membrane is largely due to the increased binding of globin chains to the membrane (54)(55)(56)(57)(58). Such increased binding of the globin chain to the membrane could lead to the release of heme moiety from the globin chain to the membrane followed by deleterious oxidative reactions initiated by the heme moiety.…”

Section: Enhanced Oxidative Stress In Sca Thalassemia and G6pd-deficmentioning

confidence: 99%

Interaction of Antioxidants and Their Implication in Genetic Anemia

Chan

Chow

Chiu

1999

Proc Soc Exp Biol Med

133

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The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.

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“…They found increased membrane rigidity in both thalassaemias; however, the beta-thalassaemic membranes differed from the alphas in that they were also unstable and fragile. These physical properties can be replicated by treatment of normal red cells either by phenylhydrazine or methylhydrazine, which selectively deposit oxidized alpha or beta globin chains, respectively, on the membrane (Schrier & Mohandas, 1992).…”

Section: Discussionmentioning

confidence: 97%

Isolated beta‐globin chains reproduce, in normal red cell membranes, the defective binding of spectrin to alpha‐thalassaemic membranes

1996

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Alpha-thalassaemic erythrocytes develop a specific membrane skeletal defect that is manifest as a loss of normal spectrin-binding sites on the inner surface of the thalassaemic membranes. To test whether this lesion could be caused by the excess free beta-globin chains that accumulate in alpha-thalassaemic red cells, we incubated normal red cell membranes with native, haem-containing alpha or beta globin chains or with haemoglobin A. Spectrin-depleted inside-out membrane vesicles (IOVs) derived from membranes incubated with beta-globin chains bound only 9 +/- 3% as much spectrin as IOVs from control membranes incubated with bovine serum albumin. In contrast. IOVs from membranes incubated with alpha-globin chains or haemoglobin A were nearly normal (79 +/- 3% and 86 +/- 5% of controls, respectively). This differential effect of globin chains was not seen when membranes were first transformed into spectrin-depleted IOVs and then incubated with the isolated globin chains. Under these conditions, both alpha and beta globin chains reduced the spectrin-binding capacity of the IOVs by approximately 45% (alpha 46 +/- 7%, beta 43 +/- 6%) whereas haemoglobin A had no effect. Unlike IOVs, spectrin isolated from membranes exposed to alpha or beta globin chains bound normally to IOVs and to actin (in the presence of protein 4.1). These studies show that isolated beta-globin chains (but not alpha-globin chains) can produce a spectrin-binding defect in normal red cell membranes similar to that seen in alpha thalassaemia. The existence of similar defects in the membrane skeletons of red cells from other diseases with unstable beta globins suggests a common pathophysiology for the premature destruction of these cells.

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Globin-chain specificity of oxidation-induced changes in red blood cell membrane properties

Cited by 53 publications

References 18 publications

Erythrocytes anion transport and oxidative change in β‐thalassaemias

Erythrocytes anion transport and oxidative change in β‐thalassaemias

Interaction of Antioxidants and Their Implication in Genetic Anemia

Isolated beta‐globin chains reproduce, in normal red cell membranes, the defective binding of spectrin to alpha‐thalassaemic membranes

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