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Intestinal brush‐border Na + /H + exchangers are required for iron homeostasis in the mouse
Author(s) -
Mackenzie Bryan,
Shawki Ali,
Kim Robert,
Anthony Sarah R,
Knight Patrick B,
Bradford Emily M,
Shull Gary E
Publication year - 2011
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.25.1_supplement.238.1
Subject(s) - dmt1 , brush border , chemistry , hepcidin , small intestine , medicine , homeostasis , endocrinology , biochemistry , transporter , biology , inflammation , vesicle , membrane , gene
Divalent metal‐ion transporter‐1 (DMT1) is critical for intestinal iron absorption. DMT1 is energized by the H + electrochemical potential gradient but the provenance of the H + required to drive apical iron uptake is not known. To assess the roles of gastric acid and the brush‐border acidic microclimate in aiding intestinal iron transport, we have examined iron homeostasis and intestinal iron handling in mouse models lacking the α‐subunit of the gastric H + /K + ‐ATPase (gHKA) or the brush‐border Na + /H + exchangers NHE3 and NHE2. We found that liver nonheme iron stores (a preferred indicator of chronic iron status) in gHKA‐null mice were no different from wildtype mice whether fed normal or low‐iron diets. In animals fed 6 weeks on low‐iron diet, liver nonheme iron stores were depleted by 62% ± 3% (SE) in NHE2‐null mice and by 84% ± 2% in NHE3‐null mice compared with wildtype mice. In preliminary experiments in which we fed mice 59 Fe by oral gavage, lower amounts of 59 Fe appeared in blood (30 min – 4 h) and in enterocytes, liver and spleen (harvested at 4 h) of NHE2‐null and NHE3‐null mice compared with their wildtype littermates, suggesting that loss of NHE2 or NHE3 results in defects in apical intestinal iron uptake. Our data indicate that intestinal Na + /H + exchangers NHE2 and NHE3, but not the gastric H + /K + ‐ATPase, are required to maintain normal iron stores in the mouse, and raise the possibility that the acidic microclimate is critical for DMT1‐mediated iron uptake at the intestinal brush border.