B. Corsi et al., Overexpression of the hereditary hemochromatosis protein, HFE, in HeLa cells induces an iron-deficient phenotype, FEBS LETTER, 460(1), 1999, pp. 149-152
A transfectant HeLa cell clone expressing HFE under the control of a tetrac
ycline-repressible promoter was generated. HFE expression was fully repress
ed by the presence of doxycycline, while it was strongly induced by growth
in the absence of doxycycline, HFE accumulation was accompanied by a large
(similar to 10-fold) decrease in H- and L-ferritin levels, by a similar to
3-4-fold increase in transferrin receptor, and a similar to 2-fold increase
in iron regulatory protein activity. These indices of cellular iron defici
ency were reversed by iron supplementation complexes, The overexpressed HFE
immunoprecipitated together with transferrin receptor, indicating a physic
al association which is the likely cause for the observed similar to 30% de
crease in Fe-55-transferrin incorporation after 18 h incubation. In the HFE
-expressing cells the reduction in transferrin-mediated iron incorporation
was partially compensated by a similar to 30% increase in non-transferrin i
ron incorporation from Fe-55-NTA, evident after prolonged, 18 h, incubation
s. The findings indicate that HFE binding to transferrin receptor reduces c
ellular iron availability and regulates the balance between transferrin-med
iated and non-transferrin-mediated cellular iron incorporation, (C) 1999 Fe
deration of European Biochemical Societies.