Regulatory effects of gallium on transferrin-independent iron uptake by human leukemic HL60 cells. Blood 1992 Jul 15;80(2):505-11
Date
07/15/1992Pubmed ID
1627803Scopus ID
2-s2.0-0026632436 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
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.
Author List
Chitambar CR, Sax DMESH terms used to index this publication - Major topics in bold
Antibodies, MonoclonalAntineoplastic Agents
Biological Transport
Cell Division
Cell Line
Chlorides
Ferric Compounds
Gallium
Humans
Iron
Kinetics
Leukemia, Promyelocytic, Acute
Receptors, Transferrin
Transferrin
