부산대학교 도서관

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 [micro]M Cu exhibited a 22-fold increase in Cu content and a twofold decrease in Fe content compared with cells maintained in 0.4 [micro]M Cu. [sup.64]Cu uptake in Cu-deficient Hep-G2 cells showed a twofold decrease in [K.sub.m] compared with cells grown in 10 [micro]M Cu. The decreased [K.sub.m] may represent an adaptive response to Cu deficiency. Cells treated with >50 [micro]M Cu, showed an eightfold increase in cytosolic metallothionein. DMT1 protein decreased (35%), suggesting that intracellular Cu caused a reduction of DMTI 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. uptake; iron; copper; divalent metal transporter #1; metallothionein