Long-term intercalation of residual hemin in erythrocyte membranes distorts the cell.
The effect of long-term incubation of residual globin-free hemin on whole red blood cell and isolated cytoskeletal proteins was studied. Hemin at concentrations found in pathological red cells was inserted to fresh erythrocytes. Increased hemolysis developed in the hemin-containing cells after a few days at 37 degrees C and after about four weeks at 4 degrees C. Since lipid and hemoglobin peroxidation did not depend on the presence of hemin, time-dependent effects on the cytoskeleton proteins were studied. Observations were: (1) spectrin and protein 4.1 exhibited a time-dependent increasing tendency to undergo hemin-induced peroxidative crosslinking. (2) The ability of the serum proteins, albumin and hemopexin, to draw hemin from spectrin, actin and protein 4.1 decreased with time of incubation with hemin. These results were attributed to time-dependent hemin-induced denaturation of the cytoskeletal proteins. Albumin taken as a control for physiological hemin trap was unaffected by hemin. Small amounts of hemo-spectrin (2-5%) were analyzed in circulating normal cells, and this in vivo hemo-spectrin also failed to release hemin. It was concluded that slow accumulation of hemin, a phenomenon increased in pathological cells, is a toxic event causing erythrocyte destruction.
Solar
I
I
Sackler Institute of Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Israel.
Muller-Eberhard
U
U
Shviro
Y
Y
Shaklai
N
N
D003598:Cytoskeletal Proteins / Q000097:blood / Q000302:isolation & purification; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D006418:Heme / Q000378:metabolism / Q000494:pharmacology*; D006461:Hemolysis; D006801:Humans; D007364:Intercalating Agents; D007700:Kinetics; D046911:Macromolecular Substances; D010084:Oxidation-Reduction; D013049:Spectrin / Q000302:isolation & purification / Q000378:metabolism
D003598:Cytoskeletal Proteins; D007364:Intercalating Agents; D046911:Macromolecular Substances; D013049:Spectrin; D006418:Heme