Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.

Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transpo...

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Autores principales: Supathra Phoaubon, Kornkamon Lertsuwan, Jarinthorn Teerapornpuntakit, Narattaphol Charoenphandhu
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:5db057ce39574f8b8565c58027ac69482021-12-02T20:19:16ZHepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.1932-620310.1371/journal.pone.0258433https://doaj.org/article/5db057ce39574f8b8565c58027ac69482021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258433https://doaj.org/toc/1932-6203Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.Supathra PhoaubonKornkamon LertsuwanJarinthorn TeerapornpuntakitNarattaphol CharoenphandhuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258433 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Supathra Phoaubon
Kornkamon Lertsuwan
Jarinthorn Teerapornpuntakit
Narattaphol Charoenphandhu
Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
description Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.
format article
author Supathra Phoaubon
Kornkamon Lertsuwan
Jarinthorn Teerapornpuntakit
Narattaphol Charoenphandhu
author_facet Supathra Phoaubon
Kornkamon Lertsuwan
Jarinthorn Teerapornpuntakit
Narattaphol Charoenphandhu
author_sort Supathra Phoaubon
title Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_short Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_full Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_fullStr Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_full_unstemmed Hepcidin induces intestinal calcium uptake while suppressing iron uptake in Caco-2 cells.
title_sort hepcidin induces intestinal calcium uptake while suppressing iron uptake in caco-2 cells.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/5db057ce39574f8b8565c58027ac6948
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AT jarinthornteerapornpuntakit hepcidininducesintestinalcalciumuptakewhilesuppressingironuptakeincaco2cells
AT narattapholcharoenphandhu hepcidininducesintestinalcalciumuptakewhilesuppressingironuptakeincaco2cells
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