Membrane polypeptide aggregates in glucose 6-phosphate dehydrogenase-deficient and in vitro aged red blood cells

RBC membrane polypeptide aggregates have been quantitated by PAGE SDS and by gel filtration. Aggregates were absent in fresh RBC's from normal controls, but aggregates with MW 4.4 x 10⁵ and greater than 50 x 10⁶ increased progressively as GSH levels fell in RBC's incubated in PBS without added glucose or calcium. Aggregates of both MW ranges were also present in fresh RBC's from a patient with compensated congenital nonspherocytic hemolysis associated with a mutant RBC G-6-PD, Long Prairie. Since the aggregates were dissociable by treatment with mercaptoethanol or dithiothreitol, they are probably cross-linked by intermolecular disulfide bonds. Membranes containing these aggregates may represent an early and sensitive indicator of oxidative damage to red cells.