Red-cell-membrane polypeptide aggregates in glucose-6-phosphate dehydrogenase mutants with chronic hemolytic disease. A clue to the mechanism of hemolysis.
Red-cell membranes from patients with glucose-6-phosphate dehydrogenase deficiency were studied with polyacrylamide gel electrophoresis and gel filtration chromatography in sodium dodecyl sulfate. Membranes from each of five such patients who also had chronic hemolytic disease contained polypeptide aggregates within two molecular-weight ranges (4.4 X 10(5) and greater than 50 X 10(6) daltons). The 4.4 X 10(5) dalton aggregates were not detectable in red-cell membranes of patients with the enzyme deficiency without chronic hemolysis or in membranes from normal subjects, and the greater than 50 X 10(6) dalton aggregates were not found in appreciable amounts in these cells. The aggregates were dissociated by mercaptoethanol or dithiothreitol -- indicating that they were formed by intermolecular disulfide bonds. The polypeptide aggregates contained spectrin but not globin. Red-cell deformability was decreased in aggregate-containing cells. We postulate that the polypeptide aggregates are indicators of oxidant damage to the red-cell membrane, which results in decreased deformability and chronic hemolysis.
D000293:Adolescent; D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000097:blood* / Q000150:complications; D002850:Chromatography, Gel; D004220:Disulfides / Q000097:blood; D004229:Dithiothreitol / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000032:analysis*; D004912:Erythrocytes / Q000032:analysis* / Q000473:pathology; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000150:complications; D005978:Glutathione / Q000097:blood; D006801:Humans; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D008875:Middle Aged; D008970:Molecular Weight; D009154:Mutation; D010455:Peptides / Q000097:blood*; D013049:Spectrin / Q000032:analysis
D004220:Disulfides; D010455:Peptides; D013049:Spectrin; D008623:Mercaptoethanol; D005978:Glutathione; D004229:Dithiothreitol