Regulation of metal transporters by dietary iron, and the relationship between body iron levels and cadmium uptake.
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.
Kim
Dong-Won
DW
Department of Preventive Medicine, College of Medicine, Chung-Ang University, 221 Huksukdong, Dongjakgu, Seoul, South Korea.
Kim
Ki-Young
KY
Choi
Byung-Sun
BS
Youn
Pilju
P
Ryu
Doug-Young
DY
Klaassen
Curtis D
CD
Park
Jung-Duck
JD
D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019256:Cadmium Chloride / Q000493:pharmacokinetics* / Q000633:toxicity; D027682:Cation Transport Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D019266:Iron, Dietary / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D035925:Iron-Regulatory Proteins / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D015430:Weight Gain / Q000187:drug effects; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D019256:Cadmium Chloride; D027682:Cation Transport Proteins; D007501:Iron; D019266:Iron, Dietary; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2