Functional and molecular responses of human intestinal Caco-2 cells to iron treatment

J. Tallkvist, Christopher Bowlus, B. Lonnerdal

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Background: Divalent metal transporter 1 (DMT1), HFE, and stimulator of iron transport (SFT) are transmembrane proteins that have been implicated in the regulation of iron homeostasis. Objective: The objective of this study was to investigate whether absorption and transepithelial movement of iron correlated with gene expression of DMT1, HFE, and SFT in an experimental model of human absorptive enterocytes. Design: Caco-2 cells were exposed to iron-supplemented media in either the presence or the absence of serum for 24, 72, and 168 h. At each time point, the uptake and transepithelial movement of iron were examined and gene expression of DMT1, HFE, and SFT was measured. Manganese and zinc absorption was also examined at 168 h. Results: Iron treatment in the presence or absence of serum reduced the uptake and transepithelial movement of iron by ≃50% after 72 and 168 h. No effect was observed at 24 h. The uptake and transepithelial movement of manganese were similar to those of iron at 168 h, whereas the effects on zinc were less pronounced. In the absence of serum, iron treatment was associated with a reduction of DMT1 expression by 50% at 72 and 168 h. HFE expression was dependent on serum, but iron treatment did not alter HFE expression. SFT expression was not affected by iron. Conclusions: Iron treatment decreased cellular uptake of iron, manganese, and zinc, suggesting that these metals may utilize the same apical transporter. The transepithelial movement of iron and manganese, but not of zinc, was reduced across iron-treated Caco 2 cells, suggesting that iron and manganese are regulated by the same mechanism at the basolateral membrane. The gene expression of DMT1, HFE, and SFT did not fully correlate with the functional responses of Caco-2 cells. This may have been a result of posttranscriptional regulation of these genes or regulation of other genes involved in the uptake and transepithelial movement of iron in Caco-2 cells.

Original languageEnglish (US)
Pages (from-to)770-775
Number of pages6
JournalAmerican Journal of Clinical Nutrition
Volume72
Issue number3
StatePublished - 2000

Keywords

  • Caco-2 cells
  • Divalent metal transporter 1
  • DMT-1
  • HFE
  • Intestinal absorption
  • Iron
  • Manganese
  • SFT
  • Stimulator of iron transport
  • Zinc

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

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