DMT1 gene expression and cadmium absorption in human absorptive enterocytes.
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.
Tallkvist
J
J
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Uppsala Biomedical Center, Swedish University of Agricultural Sciences, Box 573, SE-751 23, Uppsala, Sweden. jonas.tallkvist@farmtox.slu.se
Bowlus
C L
CL
Lönnerdal
B
B
D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D002104:Cadmium / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D020895:Enterocytes / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000494:pharmacology; D033862:Iron-Binding Proteins; D051379:Mice; D000099236:Solute Carrier Family 11, Member 2
D002104:Cadmium; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D000099236:Solute Carrier Family 11, Member 2