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Regulatory effects of gallium on transferrin-independent iron uptake by
human leukemic HL60 cells
CR Chitambar and D Sax
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Gallium, a pharmacologically important metal, resembles iron with respect
to transferrin (Tf) binding and Tf receptor-mediated cellular uptake. In
the present study, we examined the effect of gallium on Tf- independent
iron uptake by HL60 cells. In contrast to the inhibitory effect of
Tf-gallium on Tf-iron uptake, gallium nitrate, in a time-, temperature-,
and concentration-dependent manner, stimulated Tf- independent uptake of
iron-nitrilotriacetic acid (Fe-NTA). Preexposure of cells to gallium
followed by removal of gallium also resulted in sustained stimulation of
iron uptake. The anti-Tf receptor monoclonal antibody 42/6 blocked Tf-iron
uptake, but had no effect on gallium- induced stimulation of Tf-independent
iron uptake. Gallium increased the number of cell membrane iron-binding
sites, without a change in their affinity for iron. Ferric chloride
stimulated Tf-independent gallium uptake. Although gallium nitrate
inhibited cell growth in Tf- free medium, cellular proliferation was
restored by Fe-NTA. Gallium and iron appear to share the same
Tf-independent cellular uptake system in HL60 cells. Exposure of cells to
gallium results in the activation of cell membrane non-Tf iron carriers
that may play a role in overcoming the Tf-independent growth-inhibitory
effects of gallium.
Volume 80,
Issue 2,
pp. 505-511,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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