Evidence for cadmium uptake through Nramp2: metal speciation studies with Caco-2 cells.
The specific uptake of 0.3 microM (109)Cd by the TC7 clone of the human enterocytic-like Caco-2 cells increased 4-fold as the pH(out) was lowered from 7.5 to 5.5; the stimulatory effect of acidic media being more pronounced when the level of the free ion (109)Cd(2+), relative to total (109)Cd, was increased. The initial uptake rate was 12-fold higher under conditions, optimizing (109)Cd(2+) accumulation over that of (109)CdCl(2-n)(n) (NO(-)(3)/pH(out) 5.5); a saturable system of transport has been characterized (K(m) = 1.1 +/- 0.1 microM, V(max) = 87 +/- 3 pmol/3 min/mg protein). An excess of Fe(2+) failed to affect (109)Cd uptake when the pH(out) was 7.4, whereas a strong inhibition was observed under NO(-)(3)/pH(out) 5.5 conditions. In contrast, the maximal inhibitory effect of Zn(2+) was observed under Cl(-)/pH(out) 7.4 conditions. This results strongly suggest that Fe(2+) may compete with Cd(2+) for Nramp2, whereas Zn and CdCl(2-n)(n) compete for another system of transport that has yet to be identified.
Elisma
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F
Département des Sciences Biologiques, Université du Québec à Montréal, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8.
Jumarie
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C
D000143:Acids / Q000378:metabolism / Q000494:pharmacology; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism*; D002104:Cadmium / Q000493:pharmacokinetics*; D002106:Cadmium Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D033862:Iron-Binding Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D013379:Substrate Specificity; D015032:Zinc / Q000494:pharmacology; D000099236:Solute Carrier Family 11, Member 2
D000143:Acids; D002104:Cadmium; D002106:Cadmium Radioisotopes; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002712:Chlorides; D005296:Ferrous Compounds; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D009566:Nitrates; D015032:Zinc; D000099236:Solute Carrier Family 11, Member 2