title: Regulation of copper absorption by copper availability in the Caco-2 cell intestinal model.
abstract: Relatively little is known about the individual steps in intestinal copper absorption and whether or how they may be regulated. Polarized Caco-2 cell monolayers with tight junctions offer an already tested model in which to study intestinal metal transport. This model was used to examine potential effects of cellular copper availability on copper absorption. Uptake and transport were determined on application of (64)Cu(II) to the brush border. In the range of 0.2-2 micro M, uptake was dose dependent and was approximately 20% of dose/90 min. Overall transport of (64)Cu across the basolateral surface was approximately 0.3%. When cellular copper levels were depleted 40% by 18-h pretreatment with the specific copper chelator triethylenetetraamine, uptake and overall transport were markedly increased, going to 80 and 65% of dose, respectively. Cellular retention of (64)Cu fell fourfold, from 6 to 1.5%. Depletion of copper with the chelator was rapid and preceded initial changes in uptake and overall transport by 4 h. A lesser depletion of cellular copper (13%) failed to enhance copper uptake but doubled the rate of overall transport, as measured with (64)Cu and by atomic absorption. As previously reported, preexposure of the cells to excess copper (10 micro M, 18 h) also enhanced copper uptake ( approximately 3-fold). In contrast, ascorbate (10-1,000 micro M) failed to significantly alter uptake and transport of 1 micro M (64)Cu. Our findings are consistent with the concepts that, in the low physiological range, copper availability alters the absorption capacity of the intestine to support whole body homeostasis and that basolateral transport is more sensitively regulated than uptake.
authors.affiliation: Department of Chemistry and Biochemistry and Institute for Molecular Biology and Nutrition, California State University, Fullerton, California 92834-6866, USA.
authors.forename: Nora R
authors.initials: NR
authors.lastname: Zerounian
authors.forename: Carmen
authors.initials: C
authors.lastname: Redekosky
authors.forename: Rashmi
authors.initials: R
authors.lastname: Malpe
authors.forename: Maria C
authors.initials: MC
authors.lastname: Linder
mesh_terms: D000042:Absorption / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D003300:Copper / Q000172:deficiency / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D014266:Trientine / Q000494:pharmacology
chemical_list: D003300:Copper; D001205:Ascorbic Acid; D014266:Trientine