Abstract
Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-mk/mk mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl2 aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation, while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was clearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in vivo.
| Original language | English |
|---|---|
| Pages (from-to) | 462-467 |
| Number of pages | 6 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 227 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2008 Mar 15 |
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Keywords
- Cadmium uptake
- DMT1
- Intestine
- Iron deficiency
- mk/mk mice
ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo. / Suzuki, Tomohito; Momoi, Kanae; Hosoyamada, Makoto; Kimura, Masaki; Shibasaki, Toshiaki.
In: Toxicology and Applied Pharmacology, Vol. 227, No. 3, 15.03.2008, p. 462-467.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo
AU - Suzuki, Tomohito
AU - Momoi, Kanae
AU - Hosoyamada, Makoto
AU - Kimura, Masaki
AU - Shibasaki, Toshiaki
PY - 2008/3/15
Y1 - 2008/3/15
N2 - Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-mk/mk mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl2 aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation, while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was clearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in vivo.
AB - Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-mk/mk mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl2 aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation, while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was clearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in vivo.
KW - Cadmium uptake
KW - DMT1
KW - Intestine
KW - Iron deficiency
KW - mk/mk mice
UR - http://www.scopus.com/inward/record.url?scp=39849085963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39849085963&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2007.10.026
DO - 10.1016/j.taap.2007.10.026
M3 - Article
C2 - 18076961
AN - SCOPUS:39849085963
VL - 227
SP - 462
EP - 467
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 3
ER -