DMT1, a physiologically relevant apical Cu1+ transporter of intestinal cells.
Arredondo, Miguel, Patricia Muñoz, Casilda V. Mura, and Marco T. Núñez.
1Departamento de Biología, Facultad de Ciencias, 2Millennium Institute for
Advanced Studies in Cell Biology and Biotechnology, and 3Instituto de Nutrición y
Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile
APStracts 10:0070C, 2003.
Despite important advances in the understanding of copper secretion and excretion, the
molecular components of intestinal copper absorption remain a mystery. DMT1, also
known as Nramp2 and DCT1, is the transporter responsible for intestinal iron uptake.
Electrophysiological evidence suggests that DMT1 can also be a copper transporter. Thus
we examined the potential role of DMT1 as a copper transporter in intestinal Caco-2
cells. Treatment of cells with a DMT1 antisense oligonucleotide resulted in 80 and 48%
inhibition of iron and copper uptake, respectively. Cells incorporated considerable
amounts of copper as Cu1+, whereas Cu2+ transport was about 10-fold lower. Cu1+
inhibited apical Fe2+ transport. Fe2+, but not Fe3+, effectively inhibited Cu1+ uptake.
The iron content of the cells influenced both copper and iron uptake. Cells with low iron
content transported fourfold more iron and threefold more copper than cells with high
iron content. These results demonstrate that DMT1 is a physiologically relevant Cu1+
transporter in intestinal cells, indicating that intestinal absorption of copper and iron are
intertwined.
Received 16 October 2002; accepted in final form 3 January 2003
APS Manuscript Number C480-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003