Interaction of sickle cell hemoglobin with erythrocyte membranes.

Shaklai, Nurith; Sharma, Vandna; Ranney, Helen M.

doi:10.1073/pnas.78.1.65

Cited by 72 publications

(48 citation statements)

References 18 publications

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“…Increasing the amount of HbF decreases the amount of degradation product present, which may be due either to reduction of polymer formation by γ, or to stabilization of β S in the heterotetramer (α H 2 β S γ). Both HbS [24] and HbC [25] have an excess positive charge relative to HbA and have been shown to preferentially bind to Band 3. The presence of γ or α mouse in heterotetramers may reduce the amount of membrane-associated, unstable β-chains.…”

Section: Discussion Fluorescence In Pathological Rbcmentioning

confidence: 99%

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Heme degradation and oxidative stress in murine models for hemoglobinopathies: Thalassemia, sickle cell disease and hemoglobin C disease

Nagababu

Fabry

Nagel

et al. 2008

Blood Cells, Molecules, and Diseases

102

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Red blood cells with abnormal hemoglobins (Hb) are frequently associated with increased hemoglobin autoxidation, accumulation of iron in membranes, increased membrane damage and a shorter red cell life span. The mechanisms for many of these changes have not been elucidated. We have shown in our previous studies that hydrogen peroxide formed in association with hemoglobin autoxidation reacts with hemoglobin and initiates a cascade of reactions that results in heme degradation with the formation of two fluorescent emission bands and the release of iron. Heme degradation was assessed by measuring the fluorescent band at ex 321 nm. A 5.6 fold increase in fluorescence was found in red cells from sickle transgenic mice that expressed exclusively human globins when compared to red cells from control mice. When sickle transgenic mice co-express the γM transgene, that expresses HbF and inhibits polymerization, heme degradation is decreased. Mice expressing exclusively hemoglobin C had a 6.9 fold increase in fluorescence compared to control. Heme degradation was also increased 3.5 fold in β-thalassemic mice generated by deletion of murine β major . Membrane bound IgG and red cell metHb were highly correlated with the intensity of the fluorescent heme degradation band. These results suggest that degradation of the heme moiety in intact hemoglobin and/or degradation of free heme by peroxides are higher in pathological RBCs. Concomitant release of iron appears to be responsible for the membrane damage that leads to IgG binding and the removal of red cells from circulation.

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Section: Discussion Fluorescence In Pathological Rbcmentioning

confidence: 99%

“…HbS and HbC have a higher affinity for band 3 than HbA [24,25]. Hydrogen peroxide generated by autoxidation of membrane associated Hb may be relatively inaccessible to catalase and generate more heme degradation products [29].…”

Section: Membrane Damage Associated With In Vivo Heme Degradationmentioning

confidence: 99%

Heme degradation and oxidative stress in murine models for hemoglobinopathies: Thalassemia, sickle cell disease and hemoglobin C disease

Nagababu

Fabry

Nagel

et al. 2008

Blood Cells, Molecules, and Diseases

102

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“…Negative charges at the surface of sickle RBCs, presumably carried by glycophorins, may be abnormally clustered (27,28), although this finding is controversial (29). Elevated levels of hemoglobin are found at the inner surface of sickle RBC membranes, presumably bound to band 3 (30). Sickle RBC membranes have increased lipid peroxidation (31 ) and intraprotein disulfide bonds ( 1 ) as manifestations of oxidant damage induced by increased levels of activated oxygen products (32; for review see reference 33).…”

Section: Introductionmentioning

confidence: 99%

Band 3 and glycophorin are progressively aggregated in density-fractionated sickle and normal red blood cells. Evidence from rotational and lateral mobility studies.

Corbett¹,

Golan²

1993

J. Clin. Invest.

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Band 3 aggregation in the plane of the red blood cell (RBC) membrane is postulated to be important in the pathophysiology of hemolysis of dense sickle and normal RBCs. We used the fluorescence photobleaching recovery and polarized fluorescence depletion techniques to measure the lateral and rotational mobility of band 3, glycophorins, and phospholipid analogues in membranes of density-separated intact RBCs from seven patients with sickle cell disease and eight normal controls. The fractions of laterally mobile band 3 and glycophorin decreased progressively as sickle RBC density increased. Normal RBCs also showed a progressive decrease in band 3 fractional mobility with increasing buoyant density. Rapidly rotating, slowly rotating, and rotationally immobile forms of band 3 were observed in both sickle and normal RBC membranes. The fraction of rapidly rotating band 3 progressively decreased and the fraction of rotationally immobile band 3 progressively increased with increasing sickle RBC density. Changes in the fraction of rotationally immobile band 3 were not reversible upon hypotonic swelling of dense sickle RBCs, and normal RBCs osmotically shrunken in sucrose buffers failed to manifest band 3 immobilization at median cell hemoglobin concentration values characteristic of dense sickle RBCs. We conclude that dense sickle and normal RBCs acquire irreversible membrane abnormalities that cause transmembrane protein immobilization and band 3 aggregation. Band 3 aggregates could serve as cell surface sites of autologous antibody binding and thereby lead to removal of dense sickle and normal (senescent)

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“…In the case of sickle cells, hypotheses relating the molecular defect in the hemoglobin to the altered properties of the membrane e.g., flexibility, Ca2+ permeability, lipid asymmetry, cytoskeletal structure, surface charge distribution, autologous antibody affinity, etc. (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), have generally attributed the membrane lesions either to the tendency of sickle hemoglobin (HbS)' to polymerize and distort the cell, or to its predisposition to denature and catalyze the production of oxidizing agents. In the latter hypothesis, the oxidizing agents are believed to react with membrane proteins and/or lipids in causing the defective membrane behavior (15).…”

Section: Introductionmentioning

confidence: 99%

Heinz bodies induce clustering of band 3, glycophorin, and ankyrin in sickle cell erythrocytes.

Waugh¹,

Willardson²,

Kannan³

et al. 1986

J. Clin. Invest.

104

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In earlier model studies we demonstrated that artificially denatured hemoglobin binds to and clusters the protein, band 3, in the plane of the erythrocyte membrane. To determine whether denatured hemoglobin also clusters band 3 in vivo, we have compared the locations of denatured hemoglobin aggregates (Heinz bodies) with band 3 in sickle cells using phase contrast and immunofluorescence microscopy. We report that where Heinz bodies are found associated with the cytoplasmic surface of the membrane, clusters of band 3 are usually colocalized within the membrane. In contrast, normal erythrocyte membranes and regions of sickle cell membranes devoid of Heinz bodies display an uninterrupted staining of band 3. Similarly, ankyrin and glycophorin are periodically seen to aggregate at Heinz body sites, but the degree of colocalization is lower than for band 3. These data demonstrate that the binding of denatured hemoglobin to the membrane forces a redistribution of several major membrane components.

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Interaction of sickle cell hemoglobin with erythrocyte membranes.

Cited by 72 publications

References 18 publications

Heme degradation and oxidative stress in murine models for hemoglobinopathies: Thalassemia, sickle cell disease and hemoglobin C disease

Heme degradation and oxidative stress in murine models for hemoglobinopathies: Thalassemia, sickle cell disease and hemoglobin C disease

Band 3 and glycophorin are progressively aggregated in density-fractionated sickle and normal red blood cells. Evidence from rotational and lateral mobility studies.

Heinz bodies induce clustering of band 3, glycophorin, and ankyrin in sickle cell erythrocytes.

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