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Haemochromatosis protein is expressed on the terminal web of enterocytes in proximal small intestine of the rat

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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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Acknowledgements

The authors would like to thank the NH&MRC of Australia for grant#211940, Alan Light for technical assistance, Deborah Trinder for the DMT1 antibody, Andrea Quaroni for the lactase antibody and Ira Mellman for the Lamp1 antibody.

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  1. M311, Physiology, School of biomedical and chemical sciences, The University of Western Australia, 35 Stirling highway, Crawley, WA, 6009, Western Australia

    A. R. West, C. Thomas, J. Sadlier & P. S. Oates

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  1. A. R. West
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Correspondence to P. S. Oates.

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West, A.R., Thomas, C., Sadlier, J. et al. Haemochromatosis protein is expressed on the terminal web of enterocytes in proximal small intestine of the rat. Histochem Cell Biol 125, 283–292 (2006). https://doi.org/10.1007/s00418-005-0060-6

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