Inhibition of iron transport across human intestinal epithelial cells by hepcidin.
We investigated the effects of the iron regulatory peptide hepcidin on iron transport by the human intestinal epithelial Caco-2 cell line. Caco-2 cells were exposed to hepcidin for 24 hours prior to the measurement of both iron transport and transporter protein and mRNA expression. Incubation with hepcidin significantly decreased apical iron uptake by Caco-2 cells. This was accompanied by a decrease in both the protein and the mRNA expression of the iron-response element containing variant of the divalent metal transporter (DMT1[+IRE]). In contrast, iron efflux and iron-regulated gene1 (IREG1) expression were unaffected by hepcidin. Hepcidin interacts directly with a model intestinal epithelium. The primary effect of this regulatory peptide is to modulate the apical membrane uptake machinery, thereby controlling the amount of iron absorbed from the diet.
Yamaji
Sachie
S
Department of Biochemistry and Molecular Biology, Royal Free and University College London Medical School, London, United Kingdom.
Sharp
Paul
P
Ramesh
Bala
B
Srai
Surjit Kaila
SK
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D018938:Caco-2 Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism*; D064451:Hepcidins; D006801:Humans; D007422:Intestines / Q000166:cytology*; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; C578702:HAMP protein, human; D064451:Hepcidins; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D007501:Iron