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Hepcidin‐regulated and hepcidin–independent iron release pathways in hepatocytes and macrophages
Author(s) -
Valore Erika V,
Ganz Tomas
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1191.6
Subject(s) - hepatocyte , hepcidin , chemistry , internalization , cell culture , ferroportin , transferrin , efflux , cell , macrophage , intracellular , microbiology and biotechnology , biochemistry , in vitro , biology , metabolism , immunology , inflammation , genetics , iron homeostasis
Ferroportin (Fpn), a multi‐transmembrane protein, is the only known cellular exporter of Fe. In Fpn‐transfected cells or in macrophages, the iron‐regulatory hormone hepcidin (Hepc) binds to Fpn, induces its internalization and degradation, and thereby inhibits the release of Fe from cells. It is not clear whether the same mechanisms also regulate Fe efflux from hepatocytes. We examined Fe release from primary hepatocytes, hepatocyte cell lines (HepG2 and Hep3B), and macrophage cell lines (J774 and RAW264) with or without 7.5 μg/ml Hepc. After loading with 55 Fe‐nitriloacetic acid, radioactive Fe release was monitored over 72h. In primary hepatocytes, Hep3B cells and macrophage cell lines, Hepc inhibited the total Fe release by up to 50% compared to control. The media were analyzed by gel‐filtration. For all cell types, 55 Fe eluted in two fractions. The major fraction, ≈70 kD, eluted with transferrin, and its 55 Fe content was decreased by Hepc‐treating the cells. A second fraction was > 220 kD and its 55 Fe content was unaffected by Hepc‐treating the cells. On SDS‐PAGE, the 55 Fe‐containing >220 kD fraction was unaffected by reducing conditions but was degraded by boiling. In summary, hepatocytes and hepatocyte‐derived cell lines exhibit Hepc‐regulated and presumably Fpn‐mediated Fe efflux. One or more alternative pathways for Fe export, not regulated by Hepc, also exist in hepatocytes and macrophage cell lines. Support provided by the Will Rogers Fund and NIH RO1 DK 065029