The effect of amino acid deprivation on the transfer of iron through Caco-2 cell monolayers

Guenievre Roussel, Valerie Stevens, Sarah Cottin, Harry J. McArdle

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Abstract

Iron (Fe) metabolism is modified by many nutritional factors. Amino acids (AA) play a central role in various biological processes, such as protein synthesis and energy supply. However, the influence of AA status on iron metabolism has not been investigated. Here, we test whether AA alters iron metabolism in an intestinal cell model. Both Fe uptake and transfer across the cell monolayer were significantly increased by non-essential AA deficiency (both p < 0.001) while only Fe transfer was increased by essential AA deficiency (p < 0.0001). Both essential and non-essential AA deficiency decreased DMT1 (±IRE) exon1A mRNA expression (respectively p = 0.0007 and p = 0.006) and increased expression of ferritin heavy chain. DMT1 + IRE (also expressing exon1A or 1B) mRNA levels were decreased by essential AA deficiency (p = 0.012). The mRNA levels of total DMT1 were also decreased by essential, but not nonessential, AA deficiency (p = 0.006). Hepcidin levels were increased significantly by non-essential amino acid deprivation (p = 0.047). Protein levels of ferroportin and/or ferritin heavy chain were not altered by AA deficiency, suggesting that they had no effect on Fe efflux or storage in the cell, though iron content of ferritin could be increased. Our data demonstrate, for the first time, that AA status affects iron transport and the expression of genes related to iron metabolism in Caco-2 cells, although the changes observed are not sufficient to explain the alteration in iron transport. We hypothesise that the effect on Fe transfer is mediated through an increased movement across the cell layer, rather than transfer across the cell membranes.
Original languageEnglish
Pages (from-to)82-90
Number of pages8
JournalJournal of Trace Elements in Medicine and Biology
Volume40
Early online date4 Jan 2017
DOIs
Publication statusPublished - Mar 2017

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Caco-2 Cells
Monolayers
Iron
Amino Acids
Metabolism
Messenger RNA
Apoferritins
Hepcidins
Biological Phenomena
Cell Movement
Proteins
Genes
Cells
Gene Expression

Keywords

  • amino acid deprivation
  • nutrient transfer
  • gut transport

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The effect of amino acid deprivation on the transfer of iron through Caco-2 cell monolayers. / Roussel, Guenievre; Stevens, Valerie; Cottin, Sarah; McArdle, Harry J.

In: Journal of Trace Elements in Medicine and Biology, Vol. 40, 03.2017, p. 82-90.

Research output: Contribution to journalArticle

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N1 - Funding Source Rural and Environmental Scientific and Analytical Services, the Scottish Government Acknowledgments We thank Dr Helen Hayes for her technical support during this project. We also thank Dr Christine Kennedy for her involvement at the beginning of this project. This study was funded by Rural and Environmental Scientific and Advisory Service of Scottish Government.

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AB - Iron (Fe) metabolism is modified by many nutritional factors. Amino acids (AA) play a central role in various biological processes, such as protein synthesis and energy supply. However, the influence of AA status on iron metabolism has not been investigated. Here, we test whether AA alters iron metabolism in an intestinal cell model. Both Fe uptake and transfer across the cell monolayer were significantly increased by non-essential AA deficiency (both p < 0.001) while only Fe transfer was increased by essential AA deficiency (p < 0.0001). Both essential and non-essential AA deficiency decreased DMT1 (±IRE) exon1A mRNA expression (respectively p = 0.0007 and p = 0.006) and increased expression of ferritin heavy chain. DMT1 + IRE (also expressing exon1A or 1B) mRNA levels were decreased by essential AA deficiency (p = 0.012). The mRNA levels of total DMT1 were also decreased by essential, but not nonessential, AA deficiency (p = 0.006). Hepcidin levels were increased significantly by non-essential amino acid deprivation (p = 0.047). Protein levels of ferroportin and/or ferritin heavy chain were not altered by AA deficiency, suggesting that they had no effect on Fe efflux or storage in the cell, though iron content of ferritin could be increased. Our data demonstrate, for the first time, that AA status affects iron transport and the expression of genes related to iron metabolism in Caco-2 cells, although the changes observed are not sufficient to explain the alteration in iron transport. We hypothesise that the effect on Fe transfer is mediated through an increased movement across the cell layer, rather than transfer across the cell membranes.

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