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A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block
D M Frazer1, S J Wilkins, E M Becker
1Joint Clinical Sciences Program, the Queensland Institute of Medical Research and the University of Queensland, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.
Background:
A large oral dose of iron will reduce the absorption of a subsequent smaller dose of iron in a phenomenon known as mucosal block. Molecular analysis of this process may provide insights into the regulation of intestinal iron absorption.
Aims:
To determine the effect of an oral bolus of iron on duodenal expression of molecules associated with intestinal iron transport in rats and to relate this to changes in iron absorption.
Methods:
Rats were given an oral dose of iron and duodenal expression of divalent metal transporter 1 (DMT1), Dcytb, Ireg1, and hephaestin (Hp) was determined using the ribonuclease protection assay, western blotting, and immunofluorescence. Iron absorption was measured using radioactive (59)Fe.
Results:
A decrease in intestinal iron absorption occurred following an oral dose of iron and this was associated with increased enterocyte iron levels, as assessed by iron regulatory protein activity and immunoblotting for ferritin. Reduced absorption was also accompanied by a rapid decrease in expression of the mRNAs encoding the brush border iron transport molecules Dcytb and the iron responsive element (IRE) containing the splice variant of DMT1. No such change was seen in expression of the non-IRE splice variant of DMT1 or the basolateral iron transport molecules Ireg1 and Hp. Similar changes were observed at the protein level.
Conclusions:
These data indicate that brush border, but not basolateral, iron transport components are regulated locally by enterocyte iron levels and support the hypothesis that systemic stimuli exert their primary effect on basolateral transport molecules.
Insights
A large oral iron dose reduces subsequent iron absorption by decreasing brush border transporter expression, indicating local regulation of intestinal iron uptake.
Area of Science:
- Gastroenterology
- Molecular Biology
- Nutritional Science
Background:
- Oral iron administration can inhibit absorption of subsequent doses, a phenomenon termed mucosal block.
- Understanding the molecular mechanisms of mucosal block is key to regulating intestinal iron absorption.
Purpose of the Study:
- To investigate the impact of an oral iron bolus on duodenal iron transport gene expression in rats.
- To correlate these molecular changes with alterations in iron absorption.
Main Methods:
- Rats received an oral iron dose, followed by analysis of duodenal expression of DMT1, Dcytb, Ireg1, and hephaestin via molecular assays.
- Iron absorption was quantified using radioactive 59Fe tracer.
Main Results:
- Oral iron led to decreased intestinal iron absorption, linked to elevated enterocyte iron levels (ferritin, IRP activity).
- Brush border transporters Dcytb and IRE-containing DMT1 mRNA and protein levels significantly decreased.
- Basolateral transporters Ireg1 and hephaestin showed no significant changes in expression.
Conclusions:
- Enterocyte iron levels locally regulate brush border iron transport components.
- Systemic iron stimuli primarily impact basolateral iron transport molecules, supporting the mucosal block hypothesis.
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