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Calcium interferes with iron transport in human intestinal cells
Author(s) -
Lonnerdal Bo,
Bryant Annika,
Kelleher Shan L
Publication year - 2006
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.20.4.a130-b
Subject(s) - calcium , chemistry , microbiology and biotechnology , biology , organic chemistry
Calcium (Ca) can inhibit iron (Fe) absorption; however, the mechanisms responsible for this effect are not known. It is assumed that the interaction between Ca and Fe is a luminal event, affecting Fe uptake through DMT1 at the apical membrane. However, it has also been proposed that inhibition of Feabsorption may occur during Fe transfer into circulation, suggesting major roles for the serosal exporters FPN and hephaestin. The objective of this study was to elucidate mechanisms responsible for the interaction between Ca and Fe on Fe absorption in an intestinal cell culture (Caco‐2) model. Caco‐2 cells were cultured in transwells until 14 d post‐confluent then serum‐depleted for 24 h in Minimum Essential Medium containing 0.2% BSA (SFM). Iron transport ( 59 Fe) was assessed after 1.5 and 4 h following replacement of medium in the top chamber with SFM containing 1μM FeSO 4 and 0 or 100 μM CaCl 2 . Effects of Ca on DMT1 expression (apical Fe uptake), FPN expression and localization by antibody capture (serosal Fe efflux) and hephaestin expression and activity (Fe oxidation) were determined. Although Ca did not affect Fe uptake or DMT1 at 1.5 h, FPN abundance at the plasma membrane (PM) but not total FPN level was decreased, resulting in increased cellular Fe retention and decreased Fe efflux. This effect occurred despite increased hephaestin expression and activity. After 4 h, Fe uptake remained unaffected despite increased DMT1 expression and cellular Fe retention. Decreased Fe efflux remained despite increased FPN levels and unaffected abundance at the PM. These results suggest that the inhibitory effect of Ca on Fe absorption results from rapidly decreased serosal efflux as a primary consequence of decreased FPN abundance at the PM.