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The soluble form of HFE protein regulates hephaestin mRNA expression in the duodenum through an endocytosis-dependent mechanism

2014-07-27Journal article Restricted access
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dc.contributor.authorSilva, Bruno
dc.contributor.authorFerreira, Joana
dc.contributor.authorSantos, Vera
dc.contributor.authorBaldaia, Cilénia
dc.contributor.authorSerejo, Fátima
dc.contributor.authorFaustino, Paula
dc.date.accessioned2014-09-24T14:14:22Z
dc.date.available2015-08-01T00:30:06Z
dc.date.issued2014-07-27
dc.description.abstractDietary iron absorption regulation is one of the key steps for the maintenance of the body iron homeostasis. HFE gene expression undergoes a complex post-transcriptional alternative splicing mechanism through which two alternative transcripts are originated and translated to a soluble HFE protein isoform (sHFE). The first purpose of this study was to determine if sHFE transcript levels respond to different iron conditions in duodenal and macrophage cell models. In addition, we aimed to determine the functional effect of the sHFE protein on the expression of iron metabolism-related genes in a duodenal cell model as well as, in vivo, in duodenumbiopsy samples. Levels of sHFE transcripts were measured in HuTu-80, Caco-2, HT-29 and activated THP1 cells, after holo-Tf stimulus, and in total RNA from duodenum biopsies of functional dyspepsia patients. Also, the expression of several iron metabolism-related genes was determined after endogenous and exogenous overexpression of sHFE protein in a duodenal cell model. sHFE endocytosis mechanism was studied using endocytosis inhibitors. Our results showed that sHFE transcript expression was up-regulated after holo-Tf stimuli. Hephaestin and duodenal cytochrome b expressions were down-regulated by both endogenous HFE and sHFE proteins in a duodenal cell model. Exogenous sHFE was able to down-regulate hephaestin mRNA levels by a clathrin-independent, dynamin-mediated, and RhoA-regulated endocytosis mechanism. Moreover, HEPH levels negatively correlated with sHFE levels in the duodenum of functional dyspepsia patients. Thus, sHFE seems to be an important iron metabolism regulator playing a role in the control of dietary iron absorption in the duodenum.por
dc.description.sponsorshipThis study was partially supported by Fundação para a Ciência e a Tecnologia (FCT) — grants PTDC/SAU-GMG/64494/2006 and PTDC/ SAU-GMG/103307/2008, CIGMH and Pest-OE/SAU/UI00009/2011. BS was supported by a FCT fellowship — SFRH/BD/60718/2009.por
dc.identifier.citationBiochim Biophys Acta. 2014 Jul 27;1842(11):2298-2305. doi: 10.1016/j.bbadis.2014.07.017.por
dc.identifier.doi10.1016/j.bbadis.2014.07.017
dc.identifier.issn0006-3002
dc.identifier.urihttp://hdl.handle.net/10400.18/2365
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0925443914002294
dc.subjectHFEpor
dc.subjectMetabolismo do Ferropor
dc.subjectEndocitosepor
dc.subjectDuodenopor
dc.subjectDoenças Genéticaspor
dc.subjectAlternative Splicingpor
dc.subjectIron Metabolismpor
dc.subjectEnterocytepor
dc.subjectIron Absorptionpor
dc.subjectMacrophagepor
dc.subjectEndocytosispor
dc.titleThe soluble form of HFE protein regulates hephaestin mRNA expression in the duodenum through an endocytosis-dependent mechanismpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2305por
oaire.citation.startPage2298por
oaire.citation.titleBiochimica et Biophysica Acta - Molecular Basis of Diseasepor
oaire.citation.volume1842(11)por
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor

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