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United States Department of Agriculture

Agricultural Research Service

Title: Physiologic Concentrations of Zinc Affect the Kinetics of Copper Uptake Andtransport in the Human Intestinal Cell Model, Caco-2

Authors
item Reeves, Phillip
item Briske Anderson, Mary
item Johnson, Luann - UNIV OF NORTH DAKOTA

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 12, 1998
Publication Date: N/A

Interpretive Summary: It is important to know how one nutrient in the diet affects the absorption and utilization of another. For example, diets containing zinc at amounts equal to that found in an over-the-counter mineral supplement, will reduce the absorption of copper into the body. It has been discovered by others that specific transporter proteins in the membrane of cells aid in the transport (absorption) of copper. We postulated that zinc might be inhibiting the function of these proteins. In the whole animal there are too many factors to control at one time; therefore, in the present study we used a single cell type that acts like the intestinal cell and grew it in culture dishes with a normal and a high amount of zinc. We then watched to see if the zinc content in the fluid bathing the cells reduced the amount of copper taken up by the cell or the amount transported across to the other side. We found that copper uptake into cells was increased and copper transport out of the cells was reduced when zinc concentration was increased in the culture medium. These studies strongly suggest that high zinc is enhancing the copper transporter that puts copper into the cell and is inhibiting the copper transporter that takes copper out of the cells. This might explain how high dietary zinc reduces copper absorption and thus copper status in humans.

Technical Abstract: Previously we showed that copper uptake was enhanced and copper transport was reduced in Caco-2 cells cultured in media containing high concentrations of zinc. Cells were seeded onto Falcon membranes with high pore density and maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum, nonessential amino acids, glucose, and glutamine. This medium normally contained 0.5 umol copper and 5 umol zinc/L. In one experiment the cells were exposed from d 15 to 21, to the control medium (5 umol zinc/L) and to one containing 25 umol zinc/L. Then, copper uptake and transport, in both apical and basolateral directions, were measured by using 64**Cu. In another experiment, zinc-exposed cells were labeled with 64**Cu and the release of the label to the apical and basolateral sides was measured over time. Cells exposed to 25 umol zinc/L had a 30% higher uptake of 64**Cu from the apical side than those exposed to 5 umol zinc/L. There was no effect of zinc on 64**Cu uptake from the basolateral side, even though the amount of label taken up was 3-fold higher than from the apical rate. Transport of 64**Cu across the cell layer was 50% less after 160 min in those cells exposed to 25 umol zinc/L whether measured from the apical or the basolateral side. Transport rates in both directions were similar. The rate of release of 64**Cu from the cell to the apical side was not affected by media zinc concentration; however, release to the basolateral side was reduced by 35% by the higher zinc concentration. Cellular zinc concentrations were proportional to the zinc concentrations in the media. Although the data suggest that high media zinc inhibited the copper efflux transporter and an enhanced the influx transporter, copper did not accumulate in the cell.

Last Modified: 10/21/2014
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