Effect of hemoglobin oxidation products on the stability of red cell
membrane skeletons and the associations of skeletal proteins: correlation
with a release of hemin
P Jarolim, M Lahav, SC Liu and J Palek
Department of Biomedical Research, St. Elizabeth's Hospital, Boston, MA
02135.
Oxidative injury to hemoglobin (Hb) leads to formation of methemoglobin
(MetHb), reversible hemichromes (rHCRs), and irreversible hemichromes
(iHCRs). iHCRs precipitate and form Heinz bodies that attach to the red
cell membrane causing injury that leads to hemolysis. The molecular
mechanisms of this membrane damage have not been fully elucidated. We have
studied the effect of Hb oxidation products on the mechanical stability of
red cell membrane skeletons and the associations of membrane skeletal
proteins. Hb and MetHb stabilized the isolated membrane skeletons, whereas
further oxidation to rHCRs abolished this stabilizing effect. Crude iHCRs
prepared by phenylhydrazine oxidation of Hb destabilized membrane skeletons
by decreasing formation of the spectrin-protein 4.1-actin complex, the
effect similar to that of pure hemin. Whereas virtually no hemin was
released from Hb and MetHb, high concentrations of hemin were released from
crude iHCR preparations. After removal of this hemin fraction by Dowex
resin, the iHCRs lost their destabilizing effect. We conclude that as the
oxidation of Hb proceeds, the stabilizing effect of Hb on the membrane
skeleton is gradually lost and the deleterious effect increases. The
destabilization of the red cell membrane skeleton in the presence of crude
iHCR is caused by release of hemin, which lowers the stability of membrane
skeleton by weakening the spectrin-protein 4.1-actin interaction.
Volume 76,
Issue 10,
pp. 2125-2131,
11/15/1990
Copyright © 1990 by The American Society of Hematology
