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Hepcidin inhibits apical iron uptake in intestinal cells.
Am J Physiol Gastrointest Liver Physiol. 2008 Jan; 294(1):G192-8.AJ

Abstract

Hepcidin (Hepc) is considered a key mediator in iron trafficking. Although the mechanism of Hepc action in macrophages is fairly well established, much less is known about its action in intestinal cells, one of the main targets of Hepc. The current study investigated the effects of physiologically generated Hepc on iron transport in Caco-2 cell monolayers and rat duodenal segments compared with the effects on the J774 macrophage cell line. Addition of Hepc to Caco-2 cells or rat duodenal segments strongly inhibited apical (55)Fe uptake without apparent effects on the transfer of (55)Fe from the cells to the basolateral medium. Concurrently, the levels of divalent metal transporter 1 (DMT1) mRNA and protein in Caco-2 cells decreased while the mRNA and protein levels of the iron export transporter ferroportin did not change. Plasma membrane localization of ferroportin was studied by selective biotinylation of apical and basolateral membrane domains; Hepc induced rapid internalization of ferroportin in J774 cells but not in Caco-2 cells These results indicate that the effect of Hepc is cell dependent: in macrophages it inhibits iron export by inducing ferroportin degradation, whereas in enterocytes it inhibits apical iron uptake by inhibiting DMT1 transcription. Our results highlight the crucial role of Hepc in the control of intestinal iron absorption.

Authors+Show Affiliations

Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Santiago, Chile.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17962361

Citation

Mena, Natalia P., et al. "Hepcidin Inhibits Apical Iron Uptake in Intestinal Cells." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 294, no. 1, 2008, pp. G192-8.
Mena NP, Esparza A, Tapia V, et al. Hepcidin inhibits apical iron uptake in intestinal cells. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G192-8.
Mena, N. P., Esparza, A., Tapia, V., Valdés, P., & Núñez, M. T. (2008). Hepcidin inhibits apical iron uptake in intestinal cells. American Journal of Physiology. Gastrointestinal and Liver Physiology, 294(1), G192-8.
Mena NP, et al. Hepcidin Inhibits Apical Iron Uptake in Intestinal Cells. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G192-8. PubMed PMID: 17962361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepcidin inhibits apical iron uptake in intestinal cells. AU - Mena,Natalia P, AU - Esparza,Andrés, AU - Tapia,Victoria, AU - Valdés,Pamela, AU - Núñez,Marco T, Y1 - 2007/10/25/ PY - 2007/10/27/pubmed PY - 2008/2/22/medline PY - 2007/10/27/entrez SP - G192 EP - 8 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 294 IS - 1 N2 - Hepcidin (Hepc) is considered a key mediator in iron trafficking. Although the mechanism of Hepc action in macrophages is fairly well established, much less is known about its action in intestinal cells, one of the main targets of Hepc. The current study investigated the effects of physiologically generated Hepc on iron transport in Caco-2 cell monolayers and rat duodenal segments compared with the effects on the J774 macrophage cell line. Addition of Hepc to Caco-2 cells or rat duodenal segments strongly inhibited apical (55)Fe uptake without apparent effects on the transfer of (55)Fe from the cells to the basolateral medium. Concurrently, the levels of divalent metal transporter 1 (DMT1) mRNA and protein in Caco-2 cells decreased while the mRNA and protein levels of the iron export transporter ferroportin did not change. Plasma membrane localization of ferroportin was studied by selective biotinylation of apical and basolateral membrane domains; Hepc induced rapid internalization of ferroportin in J774 cells but not in Caco-2 cells These results indicate that the effect of Hepc is cell dependent: in macrophages it inhibits iron export by inducing ferroportin degradation, whereas in enterocytes it inhibits apical iron uptake by inhibiting DMT1 transcription. Our results highlight the crucial role of Hepc in the control of intestinal iron absorption. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/17962361/Hepcidin_inhibits_apical_iron_uptake_in_intestinal_cells_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00122.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -