LAUSR

BACKGROUND Previous studies have demonstrated that in contrast to the properties of food-derived copper, water-derived copper exerts neurotoxic effects and exhibits different speciation during digestion. The cellular uptake efficiencies of different speciation of copper are distinct. However, it is unclear if these different speciation share the same transport pathway in intestinal epithelial cells. In this study, the intracellular accumulation of copper derived from copper ion and copper complex solutions was investigated in Caco-2 cells. RESULTS The cellular accumulation of copper derived from copper ions was higher than that of copper derived from the copper complex. Treatment with carboplatin and Ag+ , which are copper transporter receptor 1 (Ctr1, LC31A1) inhibitors, did not inhibit copper accumulation in Caco-2 cells but inhibited copper accumulation in HepG2 cells. Zinc ion significantly decreased the intracellular copper content from 114 ± 7 μg/g protein to 88 ± 4 μg/g protein in the copper ion-treated Caco-2 cells but not in the copper complex-treated Caco-2 cells (84.6 ±14 μg/g protein vs. 87.7±20 μg/g protein, P > 0.05). Additionally, copper accumulation in Caco-2 and HepG2 cells significantly differed depending on different solvents (Hanks' balanced salt solution and NaNO3 , P < 0.05). CONCLUSION These results indicate that the intracellular accumulation of copper derived from copper ion and copper complex is mediated by distinct copper transport pathways. Copper speciation may be an important factor that affects copper absorption and toxicity. This article is protected by copyright. All rights reserved.