scholarly journals Oxidative red blood cell membrane injury in the pathophysiology of severe mouse beta-thalassemia

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1064-1067 ◽  
Author(s):  
R Advani ◽  
E Rubin ◽  
N Mohandas ◽  
SL Schrier
Keyword(s):  
Transgenic Mice ◽  
Blood Cell ◽  
Transgenic Mouse ◽  
Red Blood Cell ◽  
Mechanical Stability ◽  
Clinical Status ◽  
Beta Thalassemia ◽  
Membrane Injury ◽  
Protein 4.1 ◽  
Alpha Globin

Abstract In severe human beta-thalassemia, the pathophysiology relates to accumulation of excess alpha-globin chains at the membrane. One hypothesis is that membrane-associated alpha-globin by virtue of it's iron or hemichromes produces oxidation of adjacent membrane proteins. The availability of a mouse model of severe beta-thalassemia, as well as a transgenic (thalassemic-sickle) mouse that expresses 12% of human beta s-chain, has allowed us to study the effect of graded accumulation of alpha-chains at the red blood cell (RBC) membrane on the clinical status of the animal and on the material properties of its RBCs. Proteins from control, beta-thalassemic, and transgenic mouse RBC membranes were analyzed for evidence of oxidation, as measured by thiol- disulfide exchange chromatography, which detects intramolecular sulfhydryl oxidation. Ratios of oxidized globin to protein 7 were calculated and increased amounts were seen in thalassemic mice as compared with control mice and transgenic mice. Furthermore, there were increased amounts of thiol-free protein 4.1 in the thalassemic mice, compared with very small amounts in the control mice and intermediate amounts in the transgenic mice. Membrane mechanical stability as assessed by ektacytometry showed that the thalassemic mouse RBCs were markedly unstable. Transgenic mouse RBCs showed intermediate levels of membrane instability compared with the controls. We propose that this oxidized globin, in conjunction with oxidized protein 4.1, accounts (at least in part) for membrane instability. A 12% increase in beta s- globin chain synthesis (by decreasing excess globin available) confers considerable protection against both oxidative damage and the consequent membrane instability.

scholarly journals Oxidative red blood cell membrane injury in the pathophysiology of severe mouse beta-thalassemia

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1064-1067 ◽  
Author(s):  
R Advani ◽  
E Rubin ◽  
N Mohandas ◽  
SL Schrier
Keyword(s):  
Transgenic Mice ◽  
Blood Cell ◽  
Transgenic Mouse ◽  
Red Blood Cell ◽  
Mechanical Stability ◽  
Clinical Status ◽  
Beta Thalassemia ◽  
Membrane Injury ◽  
Protein 4.1 ◽  
Alpha Globin

In severe human beta-thalassemia, the pathophysiology relates to accumulation of excess alpha-globin chains at the membrane. One hypothesis is that membrane-associated alpha-globin by virtue of it's iron or hemichromes produces oxidation of adjacent membrane proteins. The availability of a mouse model of severe beta-thalassemia, as well as a transgenic (thalassemic-sickle) mouse that expresses 12% of human beta s-chain, has allowed us to study the effect of graded accumulation of alpha-chains at the red blood cell (RBC) membrane on the clinical status of the animal and on the material properties of its RBCs. Proteins from control, beta-thalassemic, and transgenic mouse RBC membranes were analyzed for evidence of oxidation, as measured by thiol- disulfide exchange chromatography, which detects intramolecular sulfhydryl oxidation. Ratios of oxidized globin to protein 7 were calculated and increased amounts were seen in thalassemic mice as compared with control mice and transgenic mice. Furthermore, there were increased amounts of thiol-free protein 4.1 in the thalassemic mice, compared with very small amounts in the control mice and intermediate amounts in the transgenic mice. Membrane mechanical stability as assessed by ektacytometry showed that the thalassemic mouse RBCs were markedly unstable. Transgenic mouse RBCs showed intermediate levels of membrane instability compared with the controls. We propose that this oxidized globin, in conjunction with oxidized protein 4.1, accounts (at least in part) for membrane instability. A 12% increase in beta s- globin chain synthesis (by decreasing excess globin available) confers considerable protection against both oxidative damage and the consequent membrane instability.

scholarly journals The role of membrane skeletal-associated alpha-globin in the pathophysiology of beta-thalassemia

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1333-1336 ◽  
Author(s):  
S Sorensen ◽  
E Rubin ◽  
H Polster ◽  
N Mohandas ◽  
S Schrier
Keyword(s):  
Transgenic Mice ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Cell Deformability ◽  
Red Blood Cell Deformability ◽  
Alpha Globin

The beta-thalassemic mouse provides a useful model for testing hypotheses about the pathophysiology in human beta-thalassemia. The clinical picture of these mice and their red blood cell deformability characteristics are quite similar to those observed in human beta- thalassemia intermedia. The creation of transgenic mice that express human beta-globin (beta s) has provided an opportunity to study the effect of increasing the non-alpha-globin chain production on the thalassemic phenotype. A small increase in beta-globin production produces transgenic mice that are healthier, have almost normal hemoglobin values, and whose red blood cell deformability is increased. We quantified and characterized the membrane skeletal-associated globin in normal, transgenic thal/sickle, and thalassemic mice and showed that only alpha-globin was associated with the membrane skeleton in the pathologic red blood cells, and that the degree of rigidity as measured in the rheoscope correlated directly and closely with the amount of membrane skeletal-associated globin in these abnormal red blood cells.

scholarly journals Characterization and comparison of the red blood cell membrane damage in severe human alpha- and beta-thalassemia

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1058-1063 ◽  
Author(s):  
R Advani ◽  
S Sorenson ◽  
E Shinar ◽  
W Lande ◽  
E Rachmilewitz ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Membrane Damage ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Cell Membrane Damage ◽  
Protein 4.1 ◽  
Globin Chains ◽  
Alpha Thalassemia ◽  
Alpha Globin

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.

scholarly journals Characterization and comparison of the red blood cell membrane damage in severe human alpha- and beta-thalassemia

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1058-1063 ◽  
Author(s):  
R Advani ◽  
S Sorenson ◽  
E Shinar ◽  
W Lande ◽  
E Rachmilewitz ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Membrane Damage ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Cell Membrane Damage ◽  
Protein 4.1 ◽  
Globin Chains ◽  
Alpha Thalassemia ◽  
Alpha Globin

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.

scholarly journals The role of membrane skeletal-associated alpha-globin in the pathophysiology of beta-thalassemia

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1333-1336 ◽  
Author(s):  
S Sorensen ◽  
E Rubin ◽  
H Polster ◽  
N Mohandas ◽  
S Schrier
Keyword(s):  
Transgenic Mice ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Cell Deformability ◽  
Red Blood Cell Deformability ◽  
Alpha Globin

Abstract The beta-thalassemic mouse provides a useful model for testing hypotheses about the pathophysiology in human beta-thalassemia. The clinical picture of these mice and their red blood cell deformability characteristics are quite similar to those observed in human beta- thalassemia intermedia. The creation of transgenic mice that express human beta-globin (beta s) has provided an opportunity to study the effect of increasing the non-alpha-globin chain production on the thalassemic phenotype. A small increase in beta-globin production produces transgenic mice that are healthier, have almost normal hemoglobin values, and whose red blood cell deformability is increased. We quantified and characterized the membrane skeletal-associated globin in normal, transgenic thal/sickle, and thalassemic mice and showed that only alpha-globin was associated with the membrane skeleton in the pathologic red blood cells, and that the degree of rigidity as measured in the rheoscope correlated directly and closely with the amount of membrane skeletal-associated globin in these abnormal red blood cells.

In vitro effects of temperature on red blood cell deformability and membrane stability in human and various vertebrate species

2021 ◽  
pp. 1-10
Author(s):  
Adam Attila Matrai ◽  
Gabor Varga ◽  
Bence Tanczos ◽  
Barbara Barath ◽  
Adam Varga ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Mechanical Stability ◽  
Cell Deformability ◽  
Blood Samples ◽  
Effects Of Temperature ◽  
The Way ◽  
Rbc Deformability

BACKGROUND: The effects of temperature on micro-rheological variables have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of heat treatment in human, rat, dog, and porcine blood samples. METHODS: Red blood cell (RBC) - buffer suspensions were prepared and immersed in a 37, 40, and 43°C heat-controlled water bath for 10 minutes. Deformability, as well as mechanical stability of RBCs were measured in ektacytometer. These tests were also examined in whole blood samples at various temperatures, gradually between 37 and 45°C in the ektacytometer. RESULTS: RBC deformability significantly worsened in the samples treated at 40 and 43°C degrees, more expressed in human, porcine, rat, and in smaller degree in canine samples. The way of heating (incubation vs. ektacytometer temperation) and the composition of the sample (RBC-PBS suspension or whole blood) resulted in the different magnitude of RBC deformability deterioration. Heating affected RBC membrane (mechanical) stability, showing controversial alterations. CONCLUSION: Significant changes occur in RBC deformability by increasing temperature, showing inter-species differences. The magnitude of alterations is depending on the way of heating and the composition of the sample. The results may contribute to better understanding the micro-rheological deterioration in hyperthermia or fever.

Prevalence of Red Blood Cell Alloimmunization Among Beta-Thalassemia and Sickle Cell Anemia Patients: a Study from Saudi Arabia

2021 ◽  
Vol 67 (10/2021) ◽  
Author(s):  
Raed Felimban ◽  
Ahmed Alsharyufi ◽  
Jasem Aljehani ◽  
Ahmed Sahlool ◽  
Hamead Aljabri ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Blood Cell ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Red Blood Cell ◽  
Beta Thalassemia

scholarly journals Red Blood Cell Mechanical Stability

Engineering ◽  
2012 ◽  
Vol 04 (10) ◽  
pp. 8-10 ◽  
Author(s):  
Oguz K. Baskurt
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Mechanical Stability

scholarly journals Contribution of the band 3-ankyrin interaction to erythrocyte membrane mechanical stability

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1581-1586 ◽  
Author(s):  
PS Low ◽  
BM Willardson ◽  
N Mohandas ◽  
M Rossi ◽  
S Shohet
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Mechanical Stability ◽  
Membrane Integrity ◽  
Membrane Skeleton ◽  
Band 3 ◽  
Cell Membrane Integrity ◽  
The Face ◽  
Cell Stability

Abstract In an effort to evaluate the role of the band 3-ankyrin linkage in maintenance of red blood cell membrane integrity, solution conditions were sought that would selectively dissociate the band 3-ankyrin linkage, leaving other membrane skeletal interactions intact. For this purpose erythrocytes were equilibrated overnight in nutrient-containing buffers at a range of elevated pHs and then examined for changes in mechanical stability and membrane skeletal composition. Band 3 was found to be released from interaction with the membrane skeleton over a pH range (8.4 to 9.5) that was observed to dissociate the band 3- ankyrin interaction in vitro. In contrast, all other membrane skeletal associations appeared to remain intact up to pH 9.3, after which they were also seen to dissociate. Whereas hemolysis of mechanically unstressed cells did not begin until approximately pH 9.3, where the membrane skeletons began to disintegrate, enhanced fragmentation of shear stressed membranes was seen to begin near pH 8, where band 3 dissociation was first observed. Furthermore, the shear-induced fragmentation rate was found to reach a maximum at pH 9.4, ie, where band 3 dissociation was essentially complete. Based on these correlations, we hypothesize that the band 3-ankyrin linkage of the membrane skeleton to the lipid bilayer is essential for red blood cell stability in the face of mechanical distortion but not for cellular integrity in the absence of mechanical stress.

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