Toxicological Sciences 68, 288-294 (2002)
Copyright © 2002 by the Society of Toxicology
BIOTRANSFORMATION AND TOXICOKINETICS |
Intestinal Absorption of Cadmium Is Associated with Divalent Metal Transporter 1 in Rats
Center for Environmental and Occupational Health, Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 2018 Breidenthal Building, 3901 Rainbow Boulevard, Kansas City, Kansas 66160-7417
The intestinal absorption of cadmium (Cd) increases when the body iron (Fe) stores are depleted. The depletion of Fe upregulates the expression of divalent metal transporter 1 (DMT1), which is located at the apical membrane of enterocytes lining the small intestine. DMT1 has been shown to transport Fe and other divalent metal ions in vitro. However, it is not known whether DMT1 mediates the intestinal absorption of Cd. To investigate DMT1 involvement in Cd absorption, rats were fed a diet for 4 weeks either deficient in Fe (FeD diet, 2–6 mg Fe/kg) or supplemented with Fe (FeS diet, 120 mg Fe/kg), followed by a single oral administration of 109 CdCl2. Body Fe status, hemoglobin, and tissue Cd concentration were determined at 48 h after Cd administration. Also, DMT1 mRNA levels were quantified in duodenum, kidney, and liver by the branched DNA signal amplification method. Animals fed the FeD diet exhibited a reduced body weight gain, depletion of body Fe, and Fe deficiency anemia. Tissue Cd concentration was significantly higher in FeD than in FeS diet-fed rats, especially in the duodenum. The amount of Cd retained in the body was 10-fold higher in rats fed the FeD diet than in those fed the FeS diet. DMT1 mRNA was highly expressed in duodenum and was 15-fold higher in the FeD diet group. The levels of DMT1 mRNA were significantly lower in kidney and liver than in duodenum, but were 30 and 40% higher, respectively, in rats fed the FeD diet than in rats fed the FeS diet. These findings suggest that functional DMT1 protein is likely upregulated in the small intestine at the mRNA level by body iron depletion and increases Cd uptake from the gastrointestinal tract with subsequent transfer of Cd to the circulation and body tissues. Furthermore, the data from this study may indicate that DMT1 is a nonspecific metal transporter, which can transport not only Fe, but probably the toxic metal as well.
Key Words: absorption; cadmium; iron; divalent metal transporter 1 (DMT1); duodenum; tissue Cd concentration; total body Cd burden.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Aiba, A. Hossain, and M. T. Kuo Elevated GSH Level Increases Cadmium Resistance through Down-Regulation of Sp1-Dependent Expression of the Cadmium Transporter ZIP8 Mol. Pharmacol., September 1, 2008; 74(3): 823 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Girijashanker, L. He, M. Soleimani, J. M. Reed, H. Li, Z. Liu, B. Wang, T. P. Dalton, and D. W. Nebert Slc39a14 Gene Encodes ZIP14, A Metal/Bicarbonate Symporter: Similarities to the ZIP8 Transporter Mol. Pharmacol., May 1, 2008; 73(5): 1413 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Klaassen and H. Lu Xenobiotic Transporters: Ascribing Function from Gene Knockout and Mutation Studies Toxicol. Sci., February 1, 2008; 101(2): 186 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P Bressler, L. Olivi, J. H. Cheong, Y. Kim, A. Maerten, and D. Bannon Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities Human and Experimental Toxicology, March 1, 2007; 26(3): 221 - 229. [Abstract] [PDF]
|
|
|
|
 |
|
 W.S. Chong, P.C. Kwan, L.Y. Chan, P.Y. Chiu, T.K. Cheung, and T.K. Lau Expression of divalent metal transporter 1 (DMT1) isoforms in first trimester human placenta and embryonic tissues Hum. Reprod., December 1, 2005; 20(12): 3532 - 3538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-M. Yang, S.-J. Chiu, and L.-Y. Lin Differential Effects of Salen and Manganese-Salen Complex (EUK-8) on the Regulation of Cellular Cadmium Uptake and Toxicity Toxicol. Sci., May 1, 2005; 85(1): 551 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Augustine, R. J. Markelewicz Jr., K. Boekelheide, and N. J. Cherrington XENOBIOTIC AND ENDOBIOTIC TRANSPORTER MRNA EXPRESSION IN THE BLOOD-TESTIS BARRIER Drug Metab. Dispos., January 1, 2005; 33(1): 182 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Reeves, R. L. Chaney, R. W. Simmons, and M. G. Cherian Metallothionein Induction Is Not Involved in Cadmium Accumulation in the Duodenum of Mice and Rats Fed Diets Containing High-Cadmium Rice or Sunflower Kernels and a Marginal Supply of Zinc, Iron, and Calcium J. Nutr., January 1, 2005; 135(1): 99 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. BRESSLER, L. OLIVI, J. H. CHEONG, Y. KIM, and D. BANNONA Divalent Metal Transporter 1 in Lead and Cadmium Transport Ann. N.Y. Acad. Sci., March 1, 2004; 1012(1): 142 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Cheong, D. Bannon, L. Olivi, Y. Kim, and J. Bressler Different Mechanisms Mediate Uptake of Lead in a Rat Astroglial Cell Line Toxicol. Sci., February 1, 2004; 77(2): 334 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Choudhuri, N. J. Cherrington, N. Li, and C. D. Klaassen CONSTITUTIVE EXPRESSION OF VARIOUS XENOBIOTIC AND ENDOBIOTIC TRANSPORTER mRNAs IN THE CHOROID PLEXUS OF RATS Drug Metab. Dispos., November 1, 2003; 31(11): 1337 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Leazer and C. D. Klaassen The Presence of Xenobiotic Transporters in Rat Placenta Drug Metab. Dispos., February 1, 2003; 31(2): 153 - 167. [Abstract] [Full Text] [PDF]
|
|