Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2598240 | Toxicology | 2006 | 11 Pages |
Cadmium (Cd) uptake was studied under inorganic exposure conditions in normal human intestinal crypt cells HIEC. The uptake time course of 0.3 μM Cd in a serum-free chloride medium was analyzed according to a first order equation with rapid initial (U0) and maximal (Umax) accumulation values of 14.1 ± 1.4 pmol/mg protein and 41.4 ± 2.0 pmol/mg protein, respectively. The presence of a 300-fold excess of unlabeled Cd dramatically decreased tracer uptake, showing the involvement of specific mechanism(s) of transport. Our speciation studies revealed the preferential uptake of the free ion Cd2+, but also suggested that CdCln2−n species may contribute to Cd accumulation. Specific mechanisms of transport of very high and similar affinity (Km ∼ 5 μM) have been characterized under both chloride and nitrate exposure conditions, but a two-fold higher capacity (Vmax) was estimated in the nitrate medium used to increase [Cd2+] over chlorocomplex formation. A clear inhibition of 109Cd uptake was observed at external acidic pH under both exposure media. An La-inhibitible 46% increase in 109Cd uptake was obtained in nominally Ca-free nitrate medium, whereas Zn provided additional inhibition. These results show different kinetic parameters for Cd uptake as a function of inorganic metal speciation. Cd2+ uptake would not involve the H+-coupled symport NRAMP2 but would be related instead to the Ca and/or Zn pathways. Because proliferative crypt cells play a critical role in the renewal process of the entire intestinal epithelium, studies on the impact of Cd on HIEC cell functions clearly deserve further investigation.