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Nonheme iron in sickle erythrocyte membranes: association with
phospholipids and potential role in lipid peroxidation
SA Kuross and RP Hebbel
Department of Medicine, University of Minnesota Medical School,
Minneapolis.
Previous studies documented the abnormal association of heme and heme
proteins with the sickle RBC membrane. We have now examined RBC ghosts and
inside-out membranes (IOM) for the presence of nonheme iron as detected by
its formation of a colored complex with ferrozine. Sickle ghosts have 33.8
+/- 18.2 nmol nonheme iron/mg membrane protein, and sickle IOM have 4.3 +/-
3.0 nmol/mg. In contrast, normal RBC ghosts and IOM have no detectable
nonheme iron. The combination of heme and nonheme iron in sickle IOM
averages nine times the amount of membrane- associated iron in normal IOM.
Kinetics of the ferrozine reaction show that some of this nonheme iron on
IOM reacts slowly and is probably in the form of ferritin, but most (72%
+/- 18%) reacts rapidly and is in the form of some other biologic chelate.
The latter iron compartment is removed by deferoxamine and by treatment of
IOM with phospholipase D, which suggests that it represents an abnormal
association of iron with polar head groups of aminophospholipids. The
biologic feasibility of such a chelate was demonstrated by using an
admixture of iron with model liposomes. Even in the presence of tenfold
excess adenosine diphosphate, iron partitions readily into
phosphatidylserine liposomes; there is no detectable association with
phosphatidylcholine liposomes. To examine the bioavailability of membrane
iron, we admixed membranes and t-butylhydroperoxide and found that sickle
membranes show a tenfold greater peroxidation response than do normal
membranes. This is not due simply to a deficiency of vitamin E, and this is
profoundly inhibited by deferoxamine. Thus, while thiol oxidation in sickle
membranes previously was shown to correlate with heme iron, the present
data suggest that lipid peroxidation is related to nonheme iron. In control
studies, we did not find this pathologic association of nonferritin,
nonheme iron with IOM prepared from sickle trait, high-reticulocyte,
postsplenectomy, or iron-overloaded individuals. These data provide
additional support for the concept that iron decompartmentalization is a
characteristic of sickle RBCs.
Volume 72,
Issue 4,
pp. 1278-1285,
10/01/1988
Copyright © 1988 by The American Society of Hematology
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