Globin-chain specificity of oxidation-induced changes in red blood cell membrane properties

Abstract

We have previously shown that excess unpaired α- and β-globin chains in severe α- and β-thalassemia interacting with the membrane skeleton induce different changes in membrane properties of red blood cells (RBCs) in these two phenotypes. We suggest that these differences in membrane material behavior may reflect the specificity of the membrane damage induced by α- and β-globin chains. To further explore this hypothesis, we sought in vitro models that induce similar membrane alterations in normal RBCs. We found that treatment of normal RBCs with phenylhydrazine produced rigid and mechanically unstable membranes in conjunction with selective association of oxidized α-globin chains with the membrane skeleton, features characteristic of RBCs in severe β-thalassemia. Methylhydrazine, in contrast, induced selective association of oxidized β-globin chains with the membrane skeleton and produced rigid but hyperstable membranes, features that mimicked those of RBCs in severe α-thalassemia. These findings suggest that consequences of oxidation induced by globin chains are quite specific in that those agents that cause α-globin chain accumulation at the membrane produce rigid but mechanically unstable membranes, whereas membrane accumulation of β-globin chains results in rigid but mechanically stable membranes. These in vitro experiments lend further support to the hypothesis that membrane-associated α- and β-chains induce oxidative damage to highly specific different skeletal components and that the specificity of this skeletal damage accounts for the differences in material membrane properties of these oxidatively attacked RBCs and perhaps of α- and β-thalassemic RBCs as well. © 1992 by The American Society of Hematology.