DMT1 gene expression and cadmium absorption in human absorptive enterocytes

Jonas Tallkvist, Christopher Bowlus, Bo Lönnerdal

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Divalent metal transporter 1 (DMT1) is a transmembrane, proton-coupled metal ion transporter that is upregulated in the duodenum of iron-deficient rodents and in hereditary hemochromatosis patients, suggesting that it may constitute a key factor in the uptake of dietary iron. Functional expression studies in Xenopus oocytes have shown that DMT1 not only mediates transport of iron but also other divalent metal ions, including the toxic metal cadmium. In the present study, the correlation between the cadmium absorption process and gene expression of DMT1 was investigated in an experimental model of human absorptive enterocytes. Fully differentiated Caco-2 cells were grown in monolayers and treated with iron supplemented medium or control medium for 1, 3 or 7 days. At each time point, cadmium transport experiments across the Caco-2 cell monolayers were performed and gene expression of DMT1 measured. Iron treatment for 3 and 7 days resulted in a 50% reduction in the cadmium uptake and a 75% reduction in the transport of the metal across the basolateral membrane. No effects were observed at 24 h. Gene expression of DMT1 in the iron-treated Caco-2 cells was reduced by about 50% at 3 and 7 days and thus, correlated well with the uptake of cadmium. In summary, our results indicate that the uptake of cadmium into human absorptive enterocytes may be mediated by DMT1.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalToxicology Letters
Volume122
Issue number2
DOIs
StatePublished - Jun 20 2001

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Enterocytes
Cadmium
Gene expression
Gene Expression
Iron
Caco-2 Cells
Metals
Metal ions
Monolayers
Ions
Dietary Iron
Hemochromatosis
Poisons
Xenopus
Duodenum
Oocytes
solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
Protons
Rodentia
Theoretical Models

Keywords

  • Absorption
  • Caco-2
  • Cadmium
  • DMT1
  • Human
  • Intestine

ASJC Scopus subject areas

  • Toxicology

Cite this

DMT1 gene expression and cadmium absorption in human absorptive enterocytes. / Tallkvist, Jonas; Bowlus, Christopher; Lönnerdal, Bo.

In: Toxicology Letters, Vol. 122, No. 2, 20.06.2001, p. 171-177.

Research output: Contribution to journalArticle

Tallkvist, Jonas ; Bowlus, Christopher ; Lönnerdal, Bo. / DMT1 gene expression and cadmium absorption in human absorptive enterocytes. In: Toxicology Letters. 2001 ; Vol. 122, No. 2. pp. 171-177.
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