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PMID:12734107

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Citation

Arredondo, M, Muñoz, P, Mura, CV and Nùñez, MT (2003) DMT1, a physiologically relevant apical Cu1+ transporter of intestinal cells. Am. J. Physiol., Cell Physiol. 284:C1525-30

Abstract

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 Cu(1+), whereas Cu(2+) transport was about 10-fold lower. Cu(1+) inhibited apical Fe(2+) transport. Fe(2+), but not Fe(3+), effectively inhibited Cu(1+) 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 Cu(1+) transporter in intestinal cells, indicating that intestinal absorption of copper and iron are intertwined.

Links

PubMed Online version:10.1152/ajpcell.00480.2002

Keywords

Animals; Antioxidants/metabolism; Ascorbic Acid/metabolism; Caco-2 Cells; Cation Transport Proteins/antagonists & inhibitors; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Copper/metabolism; Humans; Intestinal Absorption/physiology; Intestinal Mucosa/cytology; Intestinal Mucosa/metabolism; Iron/metabolism; Iron-Binding Proteins/antagonists & inhibitors; Iron-Binding Proteins/genetics; Iron-Binding Proteins/metabolism; Oligonucleotides, Antisense/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NRAM2

GO:0005375: copper ion transmembrane transporter activity

ECO:0000314:

F

complete

HUMAN:NRAM2

GO:0006825: copper ion transport

ECO:0000314:

P

complete

HUMAN:NRAM2

involved_in

GO:0010039: response to iron ion

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NRAM2

enables

GO:0005375: copper ion transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NRAM2

involved_in

GO:0006825: copper ion transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NRAM2

enables

GO:0015093: ferrous iron transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NRAM2

involved_in

GO:0006826: iron ion transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q8IUD7

involved_in

GO:0006826: iron ion transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q8IUD7

enables

GO:0015093: ferrous iron transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:Q8IUD7

involved_in

GO:0006825: copper ion transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:Q8IUD7

enables

GO:0005375: copper ion transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:Q8IUD7

involved_in

GO:0010039: response to iron ion

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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