China
Africa
Explore chapters and articles related to this topic
Hemolytic Anemia Associated with Red Cell Membrane Defects
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
A multitude of mutations that cause HE have been identified in several different genes that encode proteins of the erythrocyte membrane skeleton (Fig. 1). The most common mutations causing HE are found in genes for α and β spectrin. These mutations, found mostly in blacks, produce spectrin dimers with defective ability to self-associate into tetramers. Deficient or dysfunctional protein 4.1 is produced by another group of HE mutations. Glycophorin C deficiency, the result of several different mutations, can also give rise to HE. SAO is the consequence of a mutation in band 3.
Inherited Disorders of Red Cell Membrane Proteins
Published in Ronald L. Nagel, Genetically Abnormal Red Cells, 2019
There are three major sialoglycoproteins in the red cell, glycophorins A, B, and C. Each of these proteins has its N-terminal, glycosylated domain on the outside of the cell, a hydrophobic transmembrane region, and a hydrophilic cytoplasmic portion. The glycosylated regions bear the blood group antigens and binding sites for a variety of parasites which invade the red cell. These proteins are generally not visible on polyacrylamide gels stained with Coomassie blue, but can be seen if periodic acid-Schiff stain is used. Glycophorin A is the most abundant glycophorin, and the best characterized. This protein probably exists as a dimer in the cell,50 and binds to protein 3.51 The cytoplasmic domain contains a group of negatively charged amino acids which appear to play an important function in binding to negatively charged phospholipids52,53 and protein 4.1.54 However, the structural significance of these interactions is unclear since individuals with the blood types En (a — ), who have no glycophorin A, and those homozygous for Mk, who have neither glycophorin A nor B, have normal red cell morphology and no anemia.55,56 Individuals who lack glycophorin C have the blood group phenotype Gerbich negative (Ge —), and have hereditary ellipto-cytosis as will be described below.90
Rheology of the Hemolytic Anemias
Published in Gordon D. O. Lowe, Clinical Blood Rheology, 2019
There is a complex interrelationship between the main proteins of the membrane (Figure 1). Spectrin has a particularly long and flexible molecule comprising homologous segments of 106 amino acids folded into a triple helical structure.8 It is probably composed of tetramers in its functional form9 and is located immediately beneath the cytoplasmic surface of the lipid bilayer. Thus it is both ideally suited and located to be the major interconnecting protein of the membrane skeleton.9 The tail end of the tetramer interacts with actin in conjunction with protein 4.1 (see Reference 10 for review). Viscosity studies have shown that spectrin-actin gels have thixotropic properties when formed in the presence of protein 4.1;11 thus protein 4.1 strengthens the otherwise weak spectrin-actin interaction and confers resistance to shear stress. Spectrin also has binding sites for ankyrin which, in turn, is attached to protein 3 (Figure 1), an integral protein of the lipid bilayer.12 The protein skeleton is thereby linked to the bilayer core. Stability is further conferred by linkage between glycophorin and protein 4.1.13
Cutaneous-hemolytic loxoscelism following brown recluse spider envenomation: new understandings
Published in Clinical Toxicology, 2020
Justin K. Loden, Donna L. Seger, Henry A. Spiller, Li Wang, Daniel W. Byrne
The second mechanism involves PLD activity on metalloproteinases. The erythrocyte plasma membrane contains heavily glycosylated proteins, the most prevalent being glycophorin-A, which ensure erythrocyte survival by preventing spontaneous complement deposition. Erythrocyte exposure to Loxosceles PLD results in the activation of an unspecified endogenous metalloproteinase that cleaves extracellular portions of glycophorin-A. This enhances C3b deposition to the erythrocyte membrane and initiates the alternative complement pathway resulting in hemolysis [36–38]. Glycophorin-A cleavage and complement-mediated hemolysis activity is transferred from toxin-exposed erythrocytes to toxin-naïve erythrocytes, which explains the extent of hemolysis observed after envenomation [38]. In vitro incubation of L. reclusa venom with erythrocytes revealed statistically significant reduction in glycophorin-A expression and could be used as a biomarker of venom exposure [39].
A novel EPB41 p.Trp704* mutation in a Korean patient with hereditary elliptocytosis: a case report
Published in Hematology, 2020
Soyoung Shin, Kyung-Ah Hwang, Kyuhyun Paik, Joonhong Park
HE occurs in 0.3–0.5 per 1000 newborns, and patients are asymptomatic in about 90% of cases [9]. Approximately 95% of patients with HE have a mutation in genes responsible for α- and β-spectrin expression, i.e. polypeptides which in tetrameric form compose the basis of the cell cytoskeleton [6]. Mutations associated with the protein 4.1 and glycophorin C are rare [6]. Patients with a mutation on only one allele are asymptomatic, while in cases when it is bilateral suffer moderate or more severe hemolytic anemia [6,9]. In addition, the hereditary nature of the disorder is also supported by the absence of elements indicating other conditions that are associated with the presence of elliptocytes, such as deficiencies in iron, folic acid, or vitamin B12 [9].
Targeting Loxosceles spider Sphingomyelinase D with small-molecule inhibitors as a potential therapeutic approach for loxoscelism
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Priscila Hess Lopes, Mário T. Murakami, Fernanda C. V. Portaro, Kerly Fernanda Mesquita Pasqualoto, Carmen van den Berg, Denise V. Tambourgi
SMases D binding to erythrocytes is an important event in the mechanism of haemolysis. Cleavage of the external portions of the glycophorins by autologous cell membrane proteases, activated after SMase D binding, allows complement activation and lysis10. The three selected compounds significantly reduced the binding of the SMases D present in the whole venom to the erythrocytes membrane, the compound 5 being the most efficient inhibitor (Figure 3A). Analysis of the glycophorin C (GPC) expression on the erythrocyte surface showed that compounds 1 and 5 completely prevented the GPC cleavage induced by L. laeta venom (Figure 3B), while compound 6 showed a partial inhibition of GPC cleavage.