Impaired erythrocyte methemoglobin reduction in sickle cell disease:
dependence of methemoglobin reduction on reduced nicotinamide adenine
dinucleotide content
CR Zerez, NA Lachant and KR Tanaka
Department of Medicine, Harbor-UCLA Medical Center, Torrance 90502.
We have examined aspects of methemoglobin (metHb) reduction in sickle and
in thalassemic red blood cells (RBCs). NADH metHb reductase activity in
sickle and thalassemic RBCs was significantly increased compared with
normal RBCs. Because in vitro enzyme activity does not necessarily
represent in vivo activity, we measured the rate of metHb reduction in
intact RBCs. Intact thalassemic RBCs demonstrated a significantly increased
rate of metHb reduction compared with normal RBCs. In contrast, intact
sickle RBCs had a rate of metHb reduction that was similar to normal RBCs
and significantly decreased relative to high reticulocyte RBCs of
equivalent cell age. To determine the mechanism for the relative impairment
of metHb reduction in sickle RBCs, we measured intraerythrocytic NADH, a
cofactor in the metHb reduction reaction. Thalassemic RBCs had a
significantly increased NADH content relative to normal RBCs. In contrast,
sickle RBCs did not have an increase in NADH content. Furthermore,
incubating normal RBCs under conditions that increase the NADH content
resulted in an increased rate of metHb reduction. In contrast, conditions
that decrease the NADH content in normal RBC resulted in a decreased rate
of metHb reduction. These data and other results suggest that metHb
reduction in intact RBCs is dependent on NADH content, and that the
impaired metHb reduction rate in sickle RBCs may be a result of a lack of
increase in NADH content. The dependence of metHb reduction on RBC NADH
content and the ability to manipulate NADH content in vitro suggest a new
strategy for decreasing oxidant damage to sickle RBCs in vivo.
Volume 76,
Issue 5,
pp. 1008-1014,
09/01/1990
Copyright © 1990 by The American Society of Hematology
