title: Characterization of cadmium uptake in human intestinal crypt cells HIEC in relation to inorganic metal speciation.
abstract: Cadmium (Cd) uptake was studied under inorganic exposure conditions in normal human intestinal crypt cells HIEC. The uptake time course of 0.3 microM 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+/-1.4pmol/mgprotein and 41.4+/-2.0 pmol/mgprotein, 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 CdCln(2-n) species may contribute to Cd accumulation. Specific mechanisms of transport of very high and similar affinity (Km approximately 5 microM) 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.
authors.affiliation: Département des Sciences Biologiques, Centre TOXEN, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Que., Canada H3C 3P8.
authors.forename: Pierre-Michel
authors.initials: PM
authors.lastname: Bergeron
authors.forename: Catherine
authors.initials: C
authors.lastname: Jumarie
mesh_terms: D000465:Algorithms; D018938:Caco-2 Cells; D002104:Cadmium / Q000378:metabolism*; D002106:Cadmium Radioisotopes; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008670:Metals / Q000737:chemistry / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002104:Cadmium; D002106:Cadmium Radioisotopes; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D033862:Iron-Binding Proteins; D008670:Metals; D012313:RNA; D000099236:Solute Carrier Family 11, Member 2