Phosphoinositide metabolism in hereditary ovalocytic red blood cell membranes

Article (PDF Available)inBiochimica et Biophysica Acta 1326(2):342-8 · July 1997with21 Reads
DOI: 10.1016/S0005-2736(97)00037-0 · Source: PubMed
Metabolic depletion of hereditary ovalocytes leads, similar to normal red cells, to decreased intracellular concentrations of ATP and GSH as well as degradation of the phosphoinositides to phosphatidylinositol and diacylglycerol. In contrast to normal red cells, however, loss of ATP does not induce any gross shape transformations; even after extensive depletion the ovalocytes retain their initial elongated stomatocytic character. The mechanical properties of hereditary ovalocytes are associated with a deletion of nine amino acid residues in band 3. Since the deletion appears to increase the stiffness of a normally flexible region of band 3, connecting the N-terminal cytoplasmic domain with the membrane spanning domain, our results indicate that shape changes require a flexible attachment of the cytoskeleton to the membrane-spanning band 3. The results also imply that metabolism of phosphoinositide cannot be the only determinant of cell shape, as suggested by the bilayer-couple hypothesis, but also other factors are involved in metabolically induced shape transformations.
    • "The mechanism would explain the absence of glass effect in this phenotype since the flexibility between the two Band 3 domains and anion transport activity are required for deformations and shape alterations of the erythrocyte. This feature of the mechanism would also explain that the erythrocytes in Southeast Asian ovalocytosis have an increased rigidity, an absence of a significant echinocytosis after metabolic depletion, a reduction of endocytosis by stomatocytogenic amphiphilic compounds and a greater thermal stability (Kidson et al., 1981; Saul et al., 1984; Mohandas et al., 1992; Schofield et al., 1992; Bjork et al., 1997). "
    [Show abstract] [Hide abstract] ABSTRACT: Erythrocytes suspended at a low hematocrit in a non-buffered isotonic saline change from biconcave discs to spheres between glass surfaces of a slide and of a coverslip with the echinocyte as an intermediate. A pH increase is a major factor responsible for this disc-sphere transformation or glass effect. It is also observed between surfaces made of various polymers and of mica provided that the distance between them is controlled (0.1 mm). The glass effect is antagonized by serum, plasma, serum albumin, ammonium salts and CO2. It is not observed above a 1-2% hematocrit, but is enhanced by gamma-globulins. The sites of reappearance of the spicules are the same and the order of their disappearance is the inverse of the order of their reappearance during the repetitive cycle of the disc-sphere transformation and reversal when a small glass rod is alternatively approached near a site on the erythrocyte surface and withdrawn. A mechanism of erythrocyte shape control has been previously hypothesized in which Band 3 (AE1), the anion exchange protein, plays a central role. Specifically, decrease and increase of the ratio of its outward-facing conformation (Band 3o) and inward-facing conformation (Band 3i) contract and relax the membrane skeleton, promoting the echinocytosis and stomatocytosis, respectively. The Band 3o/Band 3i equilibrium ratio is determined by the Donnan equilibrium ratio of Cl-, HCO3- and H+ (r=Cl(i)-/Cl(o)-=HCO3i-/HCO3o-=Ho+/Hi+), increasing with it. The mechanism could explain by a change of the Donnan ratio the above observations with the assumptions that polymers are permeable to CO2 and that an unstirred layer slows the propagation of the change occurring at the site of approach of the glass rod to peripheral sites. The presence of HCO3- in serum or plasma may be the basis for the absence of the glass effect in these fluids.
    Full-text · Article · Apr 2005
  • [Show abstract] [Hide abstract] ABSTRACT: Aged HS erythrocytes with a defined primary defect in band 3 protein or ankyrin were incubated with amphiphiles (detergents) at sublytic concentrations (37 C, 60 min) or glucose-starved (37 C, 24 h). In line with previous studies, the release of AChE (exovesicles) from HS erythrocytes during glucose-starvation was significantly higher (11%) compared to that from control erythrocytes (1%). Control and HS cells responded, however, similarly to amphiphile-treatment (non-starving conditions). Amphiphiles induced similar types of shape alterations and a similar amount of AChE release (14-15%). Furthermore, the size and shape of amphiphile-induced exo- and endovesicles released from control and HS erythrocytes were similar. The results suggest that the stability properties of the membrane are not seriously disturbed in aged HS erythrocytes under non-starving conditions.
    Full-text · Article · Jul 2001
  • [Show abstract] [Hide abstract] ABSTRACT: The AE1/SLC4A1/EPB3 gene is the founding member of the SLC4 bicarbonate transporter superfamily. The SLC4 gene family includes nine known mammalian genes, each of which encodes multiple transcripts encoding variant polypeptides. The SLC4A1 gene is one of three of these genes (SLC4A1-3) which have been shown to encode Na+-independent, electroneutral Cl−/HCO 3− exchanger polypeptides. (Although less thoroughly investigated, SLC4A9 in at least some species has also been reported to express this activity.) The SLC4A1 gene is unique among the human SLC4 Na+-independent Cl−/HCO3− exchanger genes in its association with inherited human disease. The SLC4A l/AE1 polypeptide has recently been reviewed (Alper 2002; Knauf and Pal 2003), as has its roles in human disease (Shayakul and Alper 2000; Alper 2002; Kaset 2002; Sterning and Casey 2002; Tannel 2002; Wrong et al. 2002; Jarolim 2003).
    Chapter · Jan 2003 · Molecular Membrane Biology

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