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


METHODS
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 approximately 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.
Tallkvist
J
J
Departments of Nutrition and Internal Medicine, University of California, Davis 95616-8669, USA.
Bowlus
C L
CL
Lönnerdal
B
B
D000042:Absorption; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics; D027682:Cation Transport Proteins; D020895:Enterocytes / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D033862:Iron-Binding Proteins; D008345:Manganese / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes; D015032:Zinc / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D007501:Iron; D033862:Iron-Binding Proteins; D008345:Manganese; D008565:Membrane Proteins; D044763:Ubiquitin-Conjugating Enzymes; D015032:Zinc; D000099236:Solute Carrier Family 11, Member 2; C103673:HFE protein, human; C097308:UBE2D1 protein, human