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Calcium and zinc decrease intracellular iron by decreasing transport during iron repletion in an in vitro model

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Abstract

Purpose

Iron is an essential micronutrient that participates in a number of vital reactions and its absorption may be altered by various nutritional factors such as other micronutrients. Our hypothesis is that iron absorption is decreased because of the interactions with zinc and calcium. We evaluated the interaction between calcium and zinc on iron uptake and transport, intracellular Fe and Zn levels and mRNA expression of DMT1, ferroportin, Zip4 and ZnT1 in an in vitro model.

Methods

Caco-2 cells were cultivated with 1 mM Ca; 10 or 30 µM Zn and/or 10, 20 or 30 µM Fe for 24 h.

Results

Intracellular Fe decreased in cells incubated with 30 µM Zn or with the mix Ca/10 µM Zn/Fe. Zn mostly increased under Ca, Zn and Fe treatment. DMT1 mRNA expression decreased when intracellular Fe increased. Ferroportin expression displayed no change in cells cultured with different Fe concentrations. The mix of Ca, Zn and Fe increased DMT1 and ferroportin expression mainly under high Zn concentration. Zip4 expression was mostly augmented by Ca and Fe; however, ZnT1 showed no change in all conditions studied. Fe uptake was higher in all the conditions studied compared to control cells; however, Fe transport increased only in cells incubated with Fe alone. In all the other conditions, Fe transport was lower than that in control cells.

Conclusions

The present findings suggest that Ca and Zn interfere with iron metabolism. This interference is through an increase in ferroportin activity, which results in a diminished net iron absorption.

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Abbreviations

DMT1:

Divalent metal transporter 1

ZnT:

Zinc transporter

IRP/IRE:

Iron-regulatory protein/iron-responsive elements

FBS:

Fetal bovine serum

NTA:

Nitrile acetate

qRT-PCR:

Quantitative reverse transcription-polymerase chain reaction

B2M:

Beta-2 microglobulin

TEER:

Transepithelial electrical resistance

PBS:

Phosphate-buffered saline

AAS:

Atomic absorption spectrometer

ANOVA:

Analysis of variance

SEM:

Standard error of the mean

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Acknowledgements

This study was supported by grant FONDECYT No. 1130090. We thank Sotiris Chaniotakis for editing this manuscript.

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Authors and Affiliations

  1. Micronutrient Laboratory, Institute of Nutrition and Food Technology (INTA), University of Chile, El Líbano 5524, Macul, Santiago, Chile

    Andrews Mónica, Briones Lautaro, Pizarro Fernando & Arredondo Miguel

Authors
  1. Andrews Mónica
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  2. Briones Lautaro
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  3. Pizarro Fernando
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  4. Arredondo Miguel
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Contributions

AM, BL and PF designed the research; AM and BL conducted the research; AM analyzed data; and AM wrote the paper and had primary responsibility for the final content. All authors read and approved the final manuscript.

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Correspondence to Arredondo Miguel.

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All authors have no financial disclosures and no conflict of interest.

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Mónica, A., Lautaro, B., Fernando, P. et al. Calcium and zinc decrease intracellular iron by decreasing transport during iron repletion in an in vitro model. Eur J Nutr 57, 2693–2700 (2018). https://doi.org/10.1007/s00394-017-1535-7

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  • DOI: https://doi.org/10.1007/s00394-017-1535-7

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