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Hemolytic Anemia Associated with Red Cell Membrane Defects
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
HS is produced by mutations in the genes encoding several different component proteins of the membrane skeleton (Fig. 1). The most frequent mutations that give rise to HS affect the genes for ankyrin and band 3 (anion channel). Mutations also occur in α spectrin, β spectrin, and protein 4.2 (pallidin). The final common pathophysiologic pathway produced by most HS mutations is spectrin deficiency. Spectrin deficiency leads to membrane loss and spherocytosis. It is a consistent characteristic of HS that most hemolysis occurs selectively in the spleen.
Anion Exchanger in Hypertension
Published in Antonio Coca, Ricardo P. Garay, Ionic Transport in Hypertension: New Perspectives, 2019
Band 3 is a transmembrane protein with a molecular weight of approximately 95 kDa.16 This protein consists of two structurally distinct domains. Exposure of the cytoplasmic side of the red cell membranes to proteolytic enzymes under very mild conditions causes the cleavage of band 3 at a site that is located about 43 kDa from the N terminus.18 The resultant N-terminal fragment represents a water-soluble cytoplasmic domain. The remainder of the protein, the membrane domain, has a molecular weight of 52 kDa and is hydrophobically associated with the lipid bi-layer.18,19
The computational mechanical simulation of healthy and pathological red blood cells with meshless methods
Published in J. Belinha, R.M. Natal Jorge, J.C. Reis Campos, Mário A.P. Vaz, João Manuel, R.S. Tavares, Biodental Engineering V, 2019
S.D. Ferreira, J. Belinha, R.M. Natal Jorge
Another pathology that changes the shape and biomechanical properties of RBCs is ovalocytosis. This pathology occurs due to a mutation in the band 3 protein. As a consequence of this mutation, the RBCs increase their stiffness and become more oval. Some evidence seem to show that the carriers of this pathology are more resistant to several parasites that cause malaria (Paquette et al., 2015; Wong, 2004).
Emerging drug targets for sickle cell disease: shedding light on new knowledge and advances at the molecular level
Published in Expert Opinion on Therapeutic Targets, 2023
Tyrosine kinase inhibitors, for example imatinib, to reduce band 3 phosphorylation and stabilize the cytoskeleton are also currently under clinical trials. Interestingly, however, this site also binds WNK1, a kinase inhibitor of KCl cotransport, and increased phosphorylation to displace the enzyme may therefore co-incidentally alter cotransporter activity. In addition, tyrosine kinase inhibition, in the opposite way to serine-threonine kinase inhibition, can itself lower transport activity. The exact pathways involved, their interactions, and the degree to which their modulation may be beneficial or not requires further elucidation. The many roles of band 3 in red cell physiology and pathology remain incompletely understood and represent a rich ground for future work, as evidenced by recent advances in clinical trials for malaria and SCD using tyrosine kinase inhibitors.
Screening tools for hereditary hemolytic anemia: new concepts and strategies
Published in Expert Review of Hematology, 2021
Elisa Fermo, Cristina Vercellati, Paola Bianchi
RBC membrane defects are characterized by qualitative or quantitative abnormalities of the erythrocyte cytoskeletal proteins, which constitute a complex structure that determines the erythrocyte shape and deformability, and regulates the hydration state and cell volume. These alterations result in typical abnormalities in RBC morphology that can be observed at peripheral blood smear examination. The most common defects involve alterations in the membrane structural organization; in hereditary spherocytosis (HS), defects of ankyrin, spectrin, protein band 3, and band 4.2 impair the vertical linkage between the cytoskeleton and the membrane lipidic bilayer, leading to the release of microvesicles and loss of surface; conversely, impairment of the horizontal associations of the RBC cytoskeleton due to alterations in spectrin dimers or spectrin-actin-protein 4.1 complexes, results in hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP). Given the constitutional expression and the double function (structural and membrane channel) of band 3, abnormalities in this protein may be associated to the severe form of distal renal tubular acidosis (dRTA), with or without HS [1,2].
Efficacy of cytochemical tests in gene analysis of hereditary spherocytosis: a case study of six patients with different disease subtypes
Published in Hematology, 2021
Atsushi Shibuya, Hiroaki Kawashima, Masato Tanaka
Finally, the patient with a mutation in SLC4A1 (which encodes band 3) was clinically diagnosed as non-anaemic, and biochemical analysis revealed no or very little low-molecular-weight band 3 remaining, with a slightly reduced amount of spectrin peptide detected by mass spectrometry only in the band 3 region. The erythrocytes were microspherocytic, and EMA staining was reduced; anaemia was not observed, and intracellular band 3 staining showed a thin ring-like pattern similar to in the controls. This was likely because the free band 3 dimer had not bound to spectrin and ankyrin. Alternatively, band 3 itself may have undergone a conformational change to become extracellular band 3 with a lysine residue buried in the membrane or was fragile with weak fixation ability to the membrane, thereby escaping from the erythrocyte membrane during circulation in the spleen. The absence of anaemia with moderate haemolysis (hyperbilirubinemia) in this case may have occurred because only a small part of extracellular band 3 was phagocytosed by splenic macrophages and was corrected by the production of red blood cells in the bone marrow. In this patient and in HS4, based on SPTB mutation analysis, hyperbilirubinemia was predicted to be due to moderate anaemia in the presence of the UGT1A1 (Gilbert’s) mutation, which is associated with congenital indirect hyperbilirubinemia and sometimes coexists with HS [13].