Pre-treatment of Caco-2 cells with zinc during the differentiation phase alters the kinetics of zinc uptake and transport

The Caco-2 cell model was used to study the efficiency of absorption and en dogenous excretion of zinc (Zn) regulated by dietary Zn concentration. Cell s were seeded onto high pore-density membranes and maintained in medium sup plemented with 10% FBS. After confluence. cells were treated with 5 or 25 m u mol Zn/L for 7 d, and Zn uptake and transport were measured in both apica l (AP) and basolateral (BL) directions by using Zn-65. Similar cells were l abeled with Zn-65 and the release of Zn to the AP and BL sides was measured . The AP uptake of Zn in cells exposed to 25 mu mol Zn/L was slower (p < 0. 05) than that in cells exposed to 5 mu mol Zn/L. The AP to BL transport rat e in the 25 mu mol Zn/L group was only 40% (p < 0.05) of that in the 5 muM group. In contrast, the rate of BL Zn uptake was 4-fold higher in cells tre ated with 25 mu mol Zn/L than in those treated with 5 mu mol Zn/L (p < 0.05 ). The BL to AP transport rate was 2-fold higher in cells treated with 25 m u mol Zn/L than in those treated with 5 mu mol Zn/L (p < 0.05). Basolateral uptake was 6 to 25 times greater (p < 0.05) than AP uptake for cells treat ed with 5 and 25 mu mol Zn/L, respectively. The rate of Zn release was enha nced about 4-fold (p < 0.05) by 25 mu mol Zn/L treatment. Release to the BL side was 10 times greater than to the AP side. Zn-induced metallothionein (MT), thought to down-regulate AP to BL Zn transport, was 4-fold higher (p < 0.001) in the 25 mu mol Zn/L group than in the 5 muM group, but the rate of BL Zn release was higher in cells treated with 25 mu mol Zn/L than in th ose treated with 5 mu mol Zn/L (p < 0.05). Induced changes in transport rat es by media Zn concentrations could involve the up- and/or down-regulation of Zn influx and efflux proteins such as the ZIP and ZnT families of Zn tra nsporters. (C) 2001 Elsevier Science Inc. All rights reserved.