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Involvement of polyamines in iron(III) transport in human intestinal Caco-2 cell lines

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Abstract

Natural polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm), which are present in the human diet in large amounts, associated with their active transporter, are assumed to play a role in non-heme iron uptake and iron bioavailability from nutrients. Enterocytes and hepatocytes play pivotal roles in the regulation of body iron homeostasis. In this study, we report the effects of natural polyamines on iron transport in the Caco-2 cell line. In enterocyte-like Caco-2 cells, polyamines did not significantly modulate the transepithelial iron flux across the cell monolayer cultured on permeable membranes. In contrast, Spd, Spm, and to a lesser extent, Put were shown to activate Caco-2 cell iron uptake and to induce an increase in the ferritin level. This iron co-transport in enterocytes, which involved an interaction between iron and polyamine then cell uptake of the polyamine–iron complexes by the polyamine transport system, was more pronounced in proliferating than in differentiated Caco-2 cells. Moreover, it was observed at physiological concentrations of both polyamines and iron. It could thus play a role in the rapid renewal of enterocytes. These data suggest the involvement of polyamines as components of the pool of transferrin-independent iron-chelating vectors. Further investigations are needed to demonstrate their biological relevance in physiological situations.

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Abbreviations

DMEM:

Dulbecco’s modified eagle medium

DMSO:

Dimethyl sulfoxide

PBS:

Phosphate-buffered saline

Tf:

Transferrin

Put:

Putrescine

Spd:

Spermidine

Spm:

Spermine

TEF:

Transepithelial flux

AB:

From apical to basolateral side

BA:

From basolateral to apical side

TEER:

Transepithelial electrical resistance

NTBI:

Non-transferrin-bound iron

LPI:

Labile plasma iron

LC/MSMS:

Tandem mass spectrometry coupled to liquid chromatography

ODC:

Ornithine decarboxylase

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Acknowledgments

This study was supported by Région Bretagne (PRIR 211-B1-8, Polabfer) and the French National Ligue Contre le Cancer (35 and 44 committees).

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Correspondence to François Gaboriau.

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Lescoat, G., Gouffier, L., Cannie, I. et al. Involvement of polyamines in iron(III) transport in human intestinal Caco-2 cell lines. Mol Cell Biochem 378, 205–215 (2013). https://doi.org/10.1007/s11010-013-1611-0

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