Effect of hepcidin on intestinal iron absorption in mice.
The effect of the putative iron regulatory peptide hepcidin on iron absorption was investigated in mice. Hepcidin peptide was synthesized and injected into mice for up to 3 days, and in vivo iron absorption was measured with tied-off segments of duodenum. Liver hepcidin expression was measured by reverse transcriptase-polymerase chain reaction. Hepcidin significantly reduced mucosal iron uptake and transfer to the carcass at doses of at least 10 microg/mouse per day, the reduction in transfer to the carcass being proportional to the reduction in iron uptake. Synthetic hepcidin injections down-regulated endogenous liver hepcidin expression excluding the possibility that synthetic hepcidin was functioning by a secondary induction of endogenous hepcidin. The effect of hepcidin was significant at least 24 hours after injection of hepcidin. Liver iron stores and hemoglobin levels were unaffected by hepcidin injection. Similar effects of hepcidin on iron absorption were seen in iron-deficient and Hfe knockout mice. Hepcidin inhibited the uptake step of duodenal iron absorption but did not affect the proportion of iron transferred to the circulation. The effect was independent of iron status of mice and did not require Hfe gene product. The data support a key role for hepcidin in the regulation of intestinal iron uptake.
Laftah
Abas H
AH
Department of Life Sciences, King's College London, United Kingdom.
Ramesh
Bala
B
Simpson
Robert J
RJ
Solanky
Nita
N
Bahram
Seiamak
S
Schümann
Klaus
K
Debnam
Edward S
ES
Srai
Surjit K S
SK
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000096:biosynthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D010455:Peptides; D007501:Iron