Membrane cation and anion transport activities in erythrocytes of hereditary spherocytosis: Effects of different membrane protein defects

Abstract

Hereditary spherocytosis (HS) is due to different membrane protein defects (i.e., deficiency of spectrin and ankyrin, band 3, or band 4.2). In order to gain new insight into the relationships between band 3 function and proteins associated with the cytoskeleton, we studied erythrocyte anion transport activity in HS characterized by different membrane protein defects. Anion transport activity was increased in HS due to partial band 4.2 deficiency or to band 4.2 absence, while in HS associated with deficiency of spectrin + ankyrin or band 3, the anion transport results were normal or decreased, respectively. Moreover, since HS erythrocytes are characterized by an increased Na and a decreased K, we studied the principal membrane cation transport pathways. Activity of the Na/K pump was increased in all HS studied, while no changes in Na/K/2Cl cotransport and Na/Li exchange were evident between control and HS as well as between forms of HS associated with different membrane protein defects. K/Cl cotransport activity was decreased in all HS studied compared to normal red cells. In all HS, passive membrane permeability to Na and K was increased compared to normal erythrocytes. The increased Na and the low K content can be attributed to the abnormal membrane permeability to cations, which is not related to a specific membrane protein defect. Am.

Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency

“…In both mice and humans, defects in spectrin are associated with membrane instability as well as altered cation transporter activities. 1,9,43,44 Either mechanism could potentially alter the MCV. Other mechanisms are also possible, however.…”

Modularity of CHIP/LDB transcription complexes regulates cell differentiation

“…58 Humans with inherited mutations in this gene and mice homozygous for a targeted mutation of the locus exhibit defective erythrocyte ion transport and spherocytic anemia. [59][60][61] the Dna-binding activity of the LDB-Gata complex and resultant P4.2 gene expression increase with erythroid differentiation 44 and are very sensitive to the levels of ssDP2. 45 thus, the balance between the LDB-LHX and the LDB-Gata complexes is important for normal differentiation of erythrocytes, similarly to our observations for the fly macrochaetae.…”

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

“…With this procedure the internal sites for both transport systems were saturated. 10,12,13 The nystatin loading solution contained 70 mmol/L NaCl, 70 mmol/L KCl and 55 mmol/L sucrose. The Na/K pump activity was estimated as the ouabain-sensitive fraction of Na + efflux into a medium containing 130 mmol/L choline chloride and 10 mmol/L KCl.…”

“…20 Since previous reports suggested a possible functional relationship between red cell membrane proteins and cation transport pathways, 13,14,18,19 we evaluated the activity of the main cation transport pathways in normal and diseased red cells. We observed a significant decrease in the activity of the Na-K ATPase pump in II-2 and III-1 compared to the level in I-2 and in control erythrocytes, suggesting a perturbation in Na-K pump ATPase in our anemic subjects; Na-K-2Cl co-transport, K-Cl co-transport and Na-H exchange were significantly increased in II-2 and III-1 compared to in I-2 and in control erythrocytes ( Figure 3C).…”