Regulation of copper absorption by copper availability in the Caco-2 cell intestinal model.
Regulation of copper absorption by copper availability in the Caco-2 cell intestinal model.
复制标题
Caco-2 细胞肠道模型中铜的可用性对铜吸收的调节。
DOI：
10.1152/ajpgi.00415.2002
复制
发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Linder,MariaC
中科院分区：
文献类型：
--
作者：
Zerounian,NoraR;Redekosky,Carmen;Malpe,Rashmi;Linder,MariaC
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 of64Cu(II) to the brush border. In the range of 0.2–2 μM, uptake was dose dependent and was ∼20% of dose/90 min. Overall transport of64Cu across the basolateral surface was ∼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 of64Cu 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 with64Cu and by atomic absorption. As previously reported, preexposure of the cells to excess copper (10 μM, 18 h) also enhanced copper uptake (∼3-fold). In contrast, ascorbate (10–1,000 μM) failed to significantly alter uptake and transport of 1 μM64Cu. 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.
