Increased Erythrocyte Cation Permeability in Thalassemia and Conditions of Marrow Stress

Wiley, James S.

doi:10.1172/jci110140

Cited by 32 publications

(13 citation statements)

References 29 publications

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“…Increased cation leak in the oocyte might alternatively or additionally reflect endoplasmic reticulum stress specific to overexpression of AE1 E758K, as reported for oocyte overexpression of pathogenic mutants of the voltage-gated Ca 2ϩ channel Ca V 2.2 associated with episodic ataxia-2 (39), and elicited even by physiological Ca V 2.2 inhibition by either of the two auxiliary channel subunits ␥ 2 or ␥ 3 (42). Either interpretation is compatible with elevated cation permeability of human erythrocytes subjected to stress conditions such as thalassemia and dyserythropoietic anemia (53) or of normal red blood cells exposed to oxidizing agents or to replacement of extracellular Cl Ϫ or Na ϩ by impermeant ions (13,16).…”

Section: Discussionmentioning

confidence: 94%

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes

Stewart

Vandorpe

Heneghan

et al. 2010

American Journal of Physiology-Cell Physiology

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The previously undescribed heterozygous missense mutation E758K was discovered in the human AE1/SLC4A1/band 3 gene in two unrelated patients with well-compensated hereditary spherostomatocytic anemia (HSt). Oocyte surface expression of AE1 E758K, in contrast to that of wild-type AE1, required coexpressed glycophorin A (GPA). The mutant polypeptide exhibited, in parallel, strong GPA dependence of DIDS-sensitive (36)Cl(-) influx, trans-anion-dependent (36)Cl(-) efflux, and Cl(-)/HCO(3)(-) exchange activities at near wild-type levels. AE1 E758K expression was also associated with GPA-dependent increases of DIDS-sensitive pH-independent SO(4)(2-) uptake and oxalate uptake with altered pH dependence. In marked contrast, the bumetanide- and ouabain-insensitive (86)Rb(+) influx associated with AE1 E758K expression was largely GPA-independent in Xenopus oocytes and completely GPA-independent in Ambystoma oocytes. AE1 E758K-associated currents in Xenopus oocytes also exhibited little or no GPA dependence. (86)Rb(+) influx was higher but inward cation current was lower in oocytes expressing AE1 E758K than previously reported in oocytes expressing the AE1 HSt mutants S731P and H734R. The pharmacological inhibition profile of AE1 E758K-associated (36)Cl(-) influx differed from that of AE1 E758K-associated (86)Rb(+) influx, as well as from that of wild-type AE1-mediated Cl(-) transport. Thus AE1 E758K-expressing oocytes displayed GPA-dependent surface polypeptide expression and anion transport, accompanied by substantially GPA-independent, pharmacologically distinct Rb(+) flux and by small, GPA-independent currents. The data strongly suggest that most of the increased cation transport associated with the novel HSt mutant AE1 E758K reflects activation of endogenous oocyte cation permeability pathways, rather than cation translocation through the mutant polypeptide.

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Section: Discussionmentioning

confidence: 94%

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes

Stewart

Vandorpe

Heneghan

et al. 2010

American Journal of Physiology-Cell Physiology

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“…More affected by the oxidant stress is the mem brane which presents a lot of functional and structu ral abnormalities: cation passive permeability is strongly increased and the membrane proteins elec trophoretic pattern is altered [22], Also, membrane lipids are affected by activated oxygen: unsaturated fatty acids undergo peroxidation with a concomitant production of a number of mono-and bifunctional aldehydes [9]; the amount of unsaturated fatty acids (mainly arachidonic acid) in thalassemic red blood cell membrane is drastically reduced; vitamin E, whose protective role against peroxidation is well known, has a very low concentration too [8].…”

Section: Discussionmentioning

confidence: 99%

Pyrimidine 5′-Nucleotidase Acquired Deficiency in β-Thalassemia: Involvement of Enzyme-SH Groups in the Inactivation Process

David¹,

Vota²,

Piga³

et al. 1989

Acta Haematol

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Pyrimidine 5′-nucleotidase (P5′N) partial deficiency has been described in several hematological disorders and also in the β-thalassemic trait. To check if the P5’N deficiency in thalassemia was acquired we used thalassemic red cells (from either homo- or heterozygous subjects), whose P5′N activity was lower than in control cells. After separation on a density gradient, activity in lighter cells was similar to controls and less than 50% in denser cells. The most probable mechanism for this faster inactivation involves enzyme -SH groups modification by oxidation and reaction with monofunctional aldehydes produced by membrane lipid peroxidation. In vitro challenge of thiol enzymes as pyruvate kinase (PK), adenylate kinase (AK) and P5′N with increasing concentrations of GSSG, hexanal (HEX) and 4-hydroxynonenal (HNE), showed that HNE is the most powerful among the enzyme inhibitors tested and that P5′N activity is a more sensitive index of -SH groups damage, when compared to PK and AK.

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“…“Leakiness” of RBC plasma membrane for Ca 2+ that could not be compensated for by the activation of PMCA was reported for patients with SCD [157–159], beta-thalassemia (although most of the Ca 2+ seem to be sequestered in vesicles or bound to cytosolic proteins) [160–162], phosphofructokinase deficiency [163]. Most of the information on Ca 2+ transport in diseased RBCs was so far obtained for SCD patients.…”

Section: Ca2+ Dysbalance and Haemolytic Anaemiamentioning

confidence: 99%

Calcium in Red Blood Cells—A Perilous Balance

Bogdanova

Makhro

Wang

et al. 2013

IJMS

206

190

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Ca2+ is a universal signalling molecule involved in regulating cell cycle and fate, metabolism and structural integrity, motility and volume. Like other cells, red blood cells (RBCs) rely on Ca2+ dependent signalling during differentiation from precursor cells. Intracellular Ca2+ levels in the circulating human RBCs take part not only in controlling biophysical properties such as membrane composition, volume and rheological properties, but also physiological parameters such as metabolic activity, redox state and cell clearance. Extremely low basal permeability of the human RBC membrane to Ca2+ and a powerful Ca2+ pump maintains intracellular free Ca2+ levels between 30 and 60 nM, whereas blood plasma Ca2+ is approximately 1.8 mM. Thus, activation of Ca2+ uptake has an impressive impact on multiple processes in the cells rendering Ca2+ a master regulator in RBCs. Malfunction of Ca2+ transporters in human RBCs leads to excessive accumulation of Ca2+ within the cells. This is associated with a number of pathological states including sickle cell disease, thalassemia, phosphofructokinase deficiency and other forms of hereditary anaemia. Continuous progress in unravelling the molecular nature of Ca2+ transport pathways allows harnessing Ca2+ uptake, avoiding premature RBC clearance and thrombotic complications. This review summarizes our current knowledge of Ca2+ signalling in RBCs emphasizing the importance of this inorganic cation in RBC function and survival.

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Increased Erythrocyte Cation Permeability in Thalassemia and Conditions of Marrow Stress

Cited by 32 publications

References 29 publications

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes

The GPA-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes

Pyrimidine 5′-Nucleotidase Acquired Deficiency in β-Thalassemia: Involvement of Enzyme-SH Groups in the Inactivation Process

Calcium in Red Blood Cells—A Perilous Balance

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