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

  • Inorganic Compounds
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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.

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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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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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Authors and Affiliations

  1. Department of Preventive Medicine, College of Medicine, Chung-Ang University, 221 Huksukdong, Dongjakgu, Seoul, 156-756, South Korea

    Dong-Won Kim, Ki-Young Kim, Byung-Sun Choi & Jung-Duck Park

  2. College of Veterinary Medicine, BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Pilju Youn & Doug-Young Ryu

  3. University of Kansas Medical Center, Kansas City, KS, 66160-7417, USA

    Curtis D. Klaassen

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  1. Dong-Won Kim
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  2. Ki-Young Kim
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  3. Byung-Sun Choi
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  4. Pilju Youn
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  6. Curtis D. Klaassen
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  7. Jung-Duck Park
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Correspondence to Jung-Duck Park.

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Kim, DW., Kim, KY., Choi, BS. et al. Regulation of metal transporters by dietary iron, and the relationship between body iron levels and cadmium uptake. Arch Toxicol 81, 327–334 (2007). https://doi.org/10.1007/s00204-006-0160-7

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  • DOI: https://doi.org/10.1007/s00204-006-0160-7

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