TY - JOUR
T1 - The effect of amino acid deprivation on the transfer of iron through Caco-2 cell monolayers
AU - Roussel, Guenievre
AU - Stevens, Valerie
AU - Cottin, Sarah
AU - McArdle, Harry J.
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.
PY - 2017/3
Y1 - 2017/3
N2 - 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.
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.
KW - amino acid deprivation
KW - nutrient transfer
KW - gut transport
U2 - 10.1016/j.jtemb.2016.12.016
DO - 10.1016/j.jtemb.2016.12.016
M3 - Article
VL - 40
SP - 82
EP - 90
JO - Journal of Trace Elements in Medicine and Biology
JF - Journal of Trace Elements in Medicine and Biology
SN - 0946-672X
ER -