Oxidative interactions between the erythrocyte membrane and phosphatidylcholine vesicles.
Sonicated unilamellar phosphatidylcholine vesicles induce hemoglobin oxidation in erythrocytes and resealed membrane fragments (buds) at pH 5.5. No such oxidation was observed in vesicle-bud mixtures at pH 7.4, in cells or buds suspended in pH 5.5 buffer, or in cells incubated with multilamellar lipid vesicles at pH 5.5. In buds, vesicle-induced hemoglobin oxidation was accompanied by lipid peroxidation and formation of covalent high molecular weight protein aggregates. The causative relationships among the oxidative events were examined using selective antioxidants and membrane fragments in which the cytoplasmic domain of band 3 was cleaved. Protein cross-linking and lipid peroxidation were found to be independent events, but both were found only in concert with heme oxidation. Further, vesicle-induced hemoglobin oxidation was found to be correlated with quasi-stable adsorption of intact vesicles to cells; intercalation of foreign lipid into the cell bilayer was not required. The inability of multilamellar vesicles to induce these low pH oxidative effects suggests a steric limitation on this cell-vesicle association. The results suggest that membrane component reorganization and patching induced by low pH may enhance vesicle adsorption, which in turn initiates oxidative damage.
Yang
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Department of Chemistry, Stanford University, California 94305.
Huestis
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WH
D015060:1,2-Dipalmitoylphosphatidylcholine; D000328:Adult; D002248:Carbon Monoxide / Q000494:pharmacology; D004134:Dimyristoylphosphatidylcholine; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000378:metabolism*; D010713:Phosphatidylcholines
D006454:Hemoglobins; D008081:Liposomes; D010108:Oxyhemoglobins; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; D002248:Carbon Monoxide; D004134:Dimyristoylphosphatidylcholine