Arredondo M, Cambiazo V, Tapia L, González-Agüero M, Núñez M T, Uauy R, González M
Microminerals Laboratory, Institute of Nutrition and Food Technology, University of Chile, Casillo 138-11, Santiago, Chile.
Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G27-32. doi: 10.1152/ajpgi.00297.2003. Epub 2004 Feb 26.
Divalent metal transporter #1 (DMT1) is responsible for intestinal nonheme Fe apical uptake. However, DMT1 appears to have an additional function in Cu transport in intestinal cells. Because the liver has an essential role in body Cu homeostasis, we examined the potential involvement of Cu in the regulation of DMT1 expression and activity in Hep-G2 cells. Cells exposed to 10 microM Cu exhibited a 22-fold increase in Cu content and a twofold decrease in Fe content compared with cells maintained in 0.4 microM Cu. (64)Cu uptake in Cu-deficient Hep-G2 cells showed a twofold decrease in K(m) compared with cells grown in 10 microM Cu. The decreased K(m) may represent an adaptive response to Cu deficiency. Cells treated with >50 microM Cu, showed an eightfold increase in cytosolic metallothionein. DMT1 protein decreased (35%), suggesting that intracellular Cu caused a reduction of DMT1 protein levels. Our data indicate that, as a result of Cu overload, Hep-G2 cells reduced their Fe content and their DMT1 protein levels. These findings strongly suggest a relationship between Cu and Fe homeostasis in Hep-G2 cells in which Cu accumulation downregulates DMT1 activity.
二价金属转运蛋白1（DMT1）负责肠道非血红素铁的顶端摄取。然而，DMT1似乎在肠道细胞的铜转运中具有额外功能。由于肝脏在机体铜稳态中起着至关重要的作用，我们研究了铜在调节Hep-G2细胞中DMT1表达和活性方面的潜在作用。与维持在0.4 microM铜环境中的细胞相比，暴露于10 microM铜的细胞铜含量增加了22倍，铁含量降低了两倍。与在10 microM铜环境中生长的细胞相比，铜缺乏的Hep-G2细胞对（64）铜的摄取显示其米氏常数（K(m)）降低了两倍。K(m)的降低可能代表对铜缺乏的一种适应性反应。用>50 microM铜处理的细胞，其胞质金属硫蛋白增加了八倍。DMT1蛋白减少了（35%），这表明细胞内铜导致DMT1蛋白水平降低。我们的数据表明，由于铜过载，Hep-G2细胞降低了其铁含量和DMT1蛋白水平。这些发现强烈表明Hep-G2细胞中铜与铁稳态之间存在一种关系，其中铜积累会下调DMT1活性。
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