Archives of Toxicology

, Volume 81, Issue 5, pp 327–334 | Cite as

Regulation of metal transporters by dietary iron, and the relationship between body iron levels and cadmium uptake

  • Dong-Won Kim
  • Ki-Young Kim
  • Byung-Sun Choi
  • Pilju Youn
  • Doug-Young Ryu
  • Curtis D. Klaassen
  • Jung-Duck Park
Inorganic Compounds
First Online:
Received:
Accepted:

Abstract

Iron (Fe) plays essential roles in biological processes, whereas cadmium (Cd) is a toxic and non-essential metal. Two metal transporters, divalent metal transporter 1 (DMT1) and metal transporter protein 1 (MTP1), are responsible for Fe transport in mammals. Here, we studied the effect of dietary Fe on the expression of these metal transporters in peripheral tissues, and the uptake by these tissues of Cd. Mice were fed an Fe-sufficient (FeS: 120 mg Fe/kg) or Fe-deficient (FeD: 2–6 mg Fe/kg) diet for 4 weeks. The total Fe levels in the body were evaluated by measuring tissue Fe concentrations. Tissue Cd concentrations were determined 24 h after the mice received a single oral dose of Cd. Animals fed a FeD diet showed depletion of body Fe levels and accumulated 2.8-fold higher levels of Cd than the FeS group. Quantitative real time RT-PCR revealed that whereas DMT1 and MTP1 were both ubiquitously expressed in all FeS peripheral tissues studied, DMT1 was highly expressed in brain, kidney, and testis, whereas MTP1 was highly expressed in liver and spleen. Depletion of the body Fe stores dramatically upregulated DMT1 and MTP1 mRNA expression in the duodenum as well as moderately upregulating their expression in several other peripheral tissues. The iron response element positive isoform of DMT1 was the most prominently upregulated isoform in the duodenum. Thus, DMT1 and MTP1 may play an important role in not only maintaining Fe levels but also facilitating the accumulation of Cd in the body of mammals.

Keywords

Iron (Fe) Cadmium (Cd) Divalent metal transporter 1 (DMT1) Metal transporter protein 1 (MTP1) Duodenum 

Abbreviations

Cd

Cadmium

DMT1

Divalent metal transporter 1

Fe

Iron

FeD

Iron deficient

IRE

Iron response element

FeS

Iron sufficient

Pb

Lead

Mn

Manganese

MTP1

Metal transporter protein 1

RT-PCR

Reverse transcription polymerase chain reaction

UTR

Untranslated region

Zn

Zinc

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Notes

Acknowledgment

This work was supported by grant No. R01-2004-000-10584-0 from the Basic Research Program of the Korea Science and Engineering Foundation.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Dong-Won Kim
    • 1
  • Ki-Young Kim
    • 1
  • Byung-Sun Choi
    • 1
  • Pilju Youn
    • 2
  • Doug-Young Ryu
    • 2
  • Curtis D. Klaassen
    • 3
  • Jung-Duck Park
    • 1
  1. 1.Department of Preventive Medicine, College of MedicineChung-Ang UniversitySeoulSouth Korea
  2. 2.College of Veterinary Medicine, BK21 Program for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
  3. 3.University of Kansas Medical CenterKansas CityUSA

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