Haemochromatosis protein is expressed on the terminal web of enterocytes in proximal small intestine of the rat |
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Authors: | A R West C Thomas J Sadlier P S Oates |
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Institution: | (1) M311, Physiology, School of biomedical and chemical sciences, The University of Western Australia, 35 Stirling highway, Crawley, WA, 6009, Western Australia |
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Abstract: | The haemochromatosis protein (HFE) is an important regulator of body iron stores. In the liver, HFE is required for appropriate
expression of hepcidin, a humoral mediator of iron absorption. HFE is also present in enterocytes, though its function in
the intestine is unknown; it is not intrinsically required for iron absorption, but can augment iron absorption when over-expressed—independent
of hepcidin regulation by the liver. In this study, an antibody was raised against rat HFE and validated by enzyme-linked
immunosorbent assay, Western blot and quenching of antibody function by the immunising peptide. The sub-cellular location
of HFE in enterocytes of iron-deficient and control rats was determined by double-labelling experiments with markers for the
microvillus membrane, terminal web, early endosomes, lysosomes and the transferrin receptor. Parallel studies were performed
for the primary iron absorption protein, divalent metal transporter 1 (DMT1). HFE co-localised exclusively with the terminal
web of intestinal enterocytes. HFE expression was increased in iron deficiency, consistent with a second regulatory role for
HFE in iron absorption, independent of hepcidin from the liver. DMT1 was localised primarily on the microvillus membrane,
but did partially co-localise with HFE raising the possibility that the two proteins may interact to regulate iron absorption. |
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Keywords: | Haemochromatosis HFE Enterocyte Terminal web Iron absorption |
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