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Aberdeen, United Kingdom

Balesaria S.,University College London | Hanif R.,University College London | Salama M.F.,University College London | Salama M.F.,Mansoura University | And 3 more authors.
Haematologica | Year: 2012

Background Iron metabolism during pregnancy maintains fetal iron levels at the expense of the mother. The mechanism behind this regulation is still not clear despite recent advances. Here we examine the role of maternal and fetal Hfe, its downstream signaling molecule, hepcidin and dietary iron in the regulation of placental iron transfer. Design and Methods Hfe wild-type, knockout and heterozygote dams were fed iron deficient (12.5 ppm), adequate (50 ppm) and replete (150 ppm) iron diets and mated with heterozygote males to produce pups of all genotypes. Dams and pups were sacrificed at Day 18 of gestation; serum, placenta, body and liver iron parameters were measured. Protein and mRNA levels of various iron transporter genes were determined in duodenum, liver and placenta by Western blotting and real time PCR. Results Maternal liver iron levels were dependent on both dietary iron intake and Hfe genotype. Increasing iron levels in the maternal diet resulted in increased total iron in the fetus, primarily in the liver. However, fetuses of Hfe-knockout mothers showed further elevation of liver iron levels, concomitant with elevated expression of Tfr1, Dmt1 and Fpn in the placenta. Hfe-knockout fetuses that express low levels of liver hepcidin accumulated more iron in their liver than wild-type fetuses due to increased ferroportin levels in the placenta. Conclusions Maternal and fetal status, as well as dietary iron, is important in regulating iron transfer across placenta. Maternal Hfe regulates iron transfer by altering gene expression in the placenta. Fetal Hfe is important in regulating placental iron transfer by modulating fetal liver hepcidin expression. © 2012 Ferrata Storti Foundation.

Balesaria S.,University College London | Ramesh B.,University College London | McArdle H.,The Rowett Research Institute | Bayele H.K.,University College London | Srai S.K.S.,University College London
FEBS Letters | Year: 2010

Hepcidin is a small acute phase peptide that regulates iron absorption. It is induced by inflammation and infection, but is repressed by anaemia and hypoxia. Here we further reveal that hepcidin transcription also involves interactions between functional metal response elements (MREs) in its promoter, and the MRE-binding transcription factor-1. Analysis of hepcidin mRNA and protein levels in hepatoma cells suggests that its expression may be regulated by divalent metal ions, with zinc inducing maximal effects on hepcidin levels. These data suggest that this peptide may be a pleiotropic sensor of divalent metals, some of which are xenobiotic environmental toxins. © 2009 Federation of European Biochemical Societies.

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