Plasma Membrane Transporters for Lead and Cadmium

  • Bressler, Joseph P. (Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Kennedy-Krieger Institute) ;
  • Olivi, Luisa (Kennedy-Krieger Institute) ;
  • Kim, Yong-Bae (Department of Preventive Medicine, Soonchunhyang University) ;
  • Bannon, Desmond (US Army, Aberdeen Proving Ground) ;
  • Ko, Hong-Sook (Department of Pharmacy, Sahmyook University) ;
  • Cheong, Jae-Hoon (Department of Pharmacy, Sahmyook University)
  • Published : 2005.03.01

Abstract

Lead and cadmium are potent environmental toxicants that affect populations living in Europe. Americas, and Asia. Identifying transporters for lead and cadmium could potentially 1 help us better understand possible risk factors. The iron transporter, divalent metal transporter 1 (DMT1), mediates intestinal transport of cadmium, and lead in yeast and fobroblasts overexpressing DMT1. In human intestinal cells knocking down expression of DMT1 attenuated uptake of cadmium and iron but not lead. A possible explanation is the expression of a second transporter for lead in intestine. In astrocytes, however, DMT1 appears to transport lead in an extracellular buffer at pH value. At neutral pH, transport was not mediated by DMT1 but rather by a transporter that is stimulated by bicarbonate and inhibited by 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid. The identity of this lead transporter will beverified by future study.

Keywords

References

  1. Alper, S.L. (1998) The band 3-related AE anion exchange gene family. Cell Physiol. Biochem. 4, 265-281 https://doi.org/10.1159/000154730
  2. Alper, S.L., et al. (2002) The AE gene family of Cl/HCO3-exchangers. J. Nephrol. 15 Suppl 5, S41-53
  3. Bannon, D.I., Abounader, R., Lees, P.S.J. and Bressler, J.P. (2003b) Effect of DMTl Knockdown on iron, cadmium and lead uptake in Caco-2 cells. Am. J. Psysiol. 28, C44-50
  4. Bannon, D.I., et al. (2002) Uptake of lead and iron by divalent metal transporter 1 in yeast and mammalian cells. Biochem. Biophys. Res. Commun. 295(4), 978-984 https://doi.org/10.1016/S0006-291X(02)00756-8
  5. Bannon, D.I., et al. (2003a) Effect of DMTl knockdown on iron, cadmium, and lead uptake in Caco-2 cells. Am. J. Physiol. Cell. Physiol. 284(1), C44-50 https://doi.org/10.1152/ajpcell.00184.2002
  6. Bebe, F.N. and Panemangalore, M. (1996) Modulation of tissue trace metal concentrations in weanling rats fed different levels of zinc and exposed to oral lead and cadmium. Nutrition Res. 16(8), 1369-1380 https://doi.org/10.1016/0271-5317(96)00144-3
  7. Bellinger, D. (1994) Low-level lead exposure and childrens cognitive function in the preschool years. Peds. 93(2), A28
  8. Berglund, M., et al. (1994) Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ. Health Perspect. 102(12), 1058-1066 https://doi.org/10.2307/3431993
  9. Bevensee, M.O., Apkon, M. and Boron, W.F. (1997a) Intracellular pH regulation in cultured astrocytes from rat hippocampus. II. Electrogenic Na/HCO3 cotransport. J. Gen. Physiol. 110(4), 467-483 https://doi.org/10.1085/jgp.110.4.467
  10. Bevensee, M.O., Weed, R.A. and Boron, W.F. (1997b) Intracellular pH regulation in cultured astrocytes from rat hippocampus. I. Role Of HCO3. J. Gen. Physiol. 110(4), 453-465 https://doi.org/10.1085/jgp.110.4.453
  11. Calabrese, E.J., et al. (1997) Soil ingestion: a concern for acute toxicity in children. Environ Health Perspect, 1997. 105(12), 1354-1358 https://doi.org/10.2307/3433755
  12. Canfield, R.L., et al. (2003) Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N. Engl. J. Med. 348(16), 1517-1526 https://doi.org/10.1056/NEJMoa022848
  13. Cerklewski, F.L. and Forbes, R.M. (1976) Influence of dietary zinc on lead toxicity in the rat. J. Nutr. 106(5), 689-696 https://doi.org/10.1093/jn/106.5.689
  14. Cheng, Y, et al. (2001) Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the Normative Aging Study. Am. J. Epidemiol. 153(2), 164-171 https://doi.org/10.1093/aje/153.2.164
  15. Cheong, J.H., Bannon D.I., Olivi L., Kim, Y.B. and Bressler, J.P. (2004) Different Mechanisms Mediate Uptake of Lead in a Rat Astroglial Cell Line. Toxicol. Sci. 77, 334-340 https://doi.org/10.1093/toxsci/kfh024
  16. Cobbett, C.S. (2000) Phytochelatins and their roles in heavy metal detoxification. Plant Physiol. 123(3), 825-832 https://doi.org/10.1104/pp.123.3.825
  17. Crowe, A. and Morgan E.H. (1996) Interactions between tissue uptake of lead and iron in normal and iron-deficient rats during development. Biol. Trace Elem. Res. 52(3), 249-261 https://doi.org/10.1007/BF02789166
  18. de Kloet, E.R. and M.S. Oitzl (2003) Who cares for a stressed brain? The mother, the kid or both? Neurobiol. Aging 24 Suppl 1, S61-65; discussion S67-68
  19. Donovan, A., et al. (2000) Positional cloning of zebrafish ferroportinl identifies a conserved vertebrate iron exporter [see comments]. Nature 403(6771), 776-781 https://doi.org/10.1038/35001596
  20. Drasch, G.A., et al. (1983) An increase of cadmium body burden for this century--an investigation on human tissues. Sci. Total Environ. 26(2), 111-119 https://doi.org/10.1016/0048-9697(83)90105-5
  21. Dufner-Beattie, J., et al. (2003) The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice. J. Biol. Chem. 278(35), 33474-33481 https://doi.org/10.1074/jbc.M305000200
  22. Eide, D.J. (2004) The SLC39 family of metal ion transporters. Pflugers Arch. 447(5), 796-800 https://doi.org/10.1007/s00424-003-1074-3
  23. el-Waseef, A. and Hashim, M.M. (1985) Zinc lead-interaction in the rabbit. Acta. Med. Hung. 42(3-4), 199-207
  24. Flanagan, P.R., et al. (1978) Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology. 74(5 Pt 1), 841-846
  25. Fleming, M.D., et al. (1998) Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc. Natl. Acad. Sci. 95(3), 1148-1153
  26. Gaither, L.A. and Eide, D.J. (2000) Functional expression of the human hZIP2 zinc transporter. J. Biol. Chem. 275(8), 5560-5564 https://doi.org/10.1074/jbc.275.8.5560
  27. Groten, J.P., Luten, J.B. and van Bladeren, P.J. (1992) Dietary iron lowers the intestinal uptake of cadmium-metallothionein in rats. Eur. J.Pharmacol. 228(1), 23-28
  28. Guerinot, M.L. (2000) The ZIP family of metal transporters. Biochim. Biophys. Acta. 1465(1-2), 190-198 https://doi.org/10.1016/S0005-2736(00)00138-3
  29. Gunshin, H., et al. (1997) Cloning and characterization of a mam-malian proton-coupled metal-ion transporter. Nature 388(6641), 482-488 https://doi.org/10.1038/41343
  30. Hediger, M.A., et al. (2004) The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflugers Arch. 447(5), 465-468 https://doi.org/10.1007/s00424-003-1192-y
  31. Hertz-Picciotto, I. and Croft, J. (1993) Review of the relation between blood lead and blood pressure. Epidemiol. Rev. 15(2), 352-373 https://doi.org/10.1093/oxfordjournals.epirev.a036125
  32. Holtzman, D., et al.(1984) Maturation of resistance to lead encephalopathy: Cellular and subcellular mechanisms. Neurotoxicology 5(3), 97-124
  33. Jarup, L., et al. (2000) Low level exposure to cadmium and early kidney damage: The OSCAR study. Occup. Environ. Med. 57 (10), 668-672 https://doi.org/10.1136/oem.57.10.668
  34. Klein, D., Greim, H. and Summer K.H. (1986) Stability of metallothionein in gastric juice. Toxicology 41(2), 121-129 https://doi.org/10.1016/0300-483X(86)90193-9
  35. Lal, B., Goldstein, G.W. and Bressler, J.P. (1996) Role of anion exchange and thiol groups in the regulation of potassium efflux by lead in human erythrocytes. J. Cell. Phys. 167, 222-228 https://doi.org/10.1002/(SICI)1097-4652(199605)167:2<222::AID-JCP5>3.0.CO;2-R
  36. Lou, M., Garay, R. and Aida, J.O. (1991) Cadmium uptake through the anion exchanger in human red blood cells. J. Physiology 443, 123-136 https://doi.org/10.1113/jphysiol.1991.sp018826
  37. Lupien, S.J., et al. (2000) Child's stress hormone levels correlate with mother's socioeconomic status and depressive state. Biol. Psychiatry 48(10), 976-980 https://doi.org/10.1016/S0006-3223(00)00965-3
  38. Markovich, D. and Murer, H. (2004) The SLC13 gene family of sodium sulphate/carboxylate cotransporters. Pflugers Arch. 447(5), 594-602 https://doi.org/10.1007/s00424-003-1128-6
  39. Mount, D.B. and Romero M.F. (2004) The SLC26 gene family of multifunctional anion exchangers. Pflugers Arch. 447(5), 710-721 https://doi.org/10.1007/s00424-003-1090-3
  40. Ohta, H. and Cherian, M.G. (1991) Gastrointestinal absorption of cadmium and metallothionein. Toxicol. Appl.Pharmacol. 107(1), 63-72 https://doi.org/10.1016/0041-008X(91)90331-8
  41. Olson, C.M. (1999) Nutrition and health outcomes associated with food insecurity and hunger. J. Nutr. 129(2S Suppl), 521S-524S https://doi.org/10.1093/jn/129.2.521S
  42. Oomen, A.G., et al. (2003) In vitro intestinal lead uptake and transport in relation to speciation. Arch. Environ. Contam. Toxicol. 44(1), 116-124 https://doi.org/10.1007/s00244-002-1226-z
  43. Paschal, D.C., et al. (2003) Exposure of the U.S. population aged 6 years and older to cadmium: 1988- 1994. Arch. Environ. Contam. Toxicol. 38(3), 377-383
  44. Ragan, H.A. (1977) Effects of iron deficiency on the absorption and distribution of lead and cadmium in rats. J. Lab. Clin. Med. 90(4), 700-706
  45. Romero, M.F., Fulton, C.M. and Boron, W.F. (2004) The SLC4 family of HCO3 - transporters. Pflugers Arch. 447(5), 495-509 https://doi.org/10.1007/s00424-003-1180-2
  46. Satarug, S., Haswell-Elkins, M.R. and Moore, M.R. (2000) Safe levels of cadmium intake to prevent renal toxicity in human subjects. Br. J. Nutr. 84(6), 791-802
  47. Schopfer, L.M. and Salhany, J.M. (1995) Characterization of the stilbenedisulfonate binding site on band 3. Biochemistry 34(26), 8320-8329 https://doi.org/10.1021/bi00026a013
  48. Selevan, S.G., et. al. (2003) Blood lead concentration and delayed puberty in girls. N. Engl. J. Med. 348(16), 1527-1536 https://doi.org/10.1056/NEJMoa020880
  49. Simons, T.J.B. (1986) The role of anion transport in the passive movement of lead across the human red cell membrane. J. Physiol. (Land) 378, 287-312 https://doi.org/10.1113/jphysiol.1986.sp016220
  50. Simpson, R.J. and Peters, T.J. (1986) Mouse intestinal Fe3+ uptake kinetics in vivo. The significance of brush-border membrane vesicle transport in the mechanism of mucosal Fe3+ uptake. Biochim. Biophys. Acta., 856(1), 115-122 https://doi.org/10.1016/0005-2736(86)90017-9
  51. Stanek, E.J., 3rd and Calabrese, E.J. (2000) Daily soil ingestion estimates for children at a Superfund site. Risk Anal. 20(5), 627-635 https://doi.org/10.1111/0272-4332.205057
  52. Stewart, W.F., et al. (1999) Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers. Neurology 52(8), 1610-1617 https://doi.org/10.1212/WNL.52.8.1610
  53. Sugawara, N. and Sugawara, C. (1991) Gastrointestinal absorption of Cd-metallothionein and cadmium chloride in mice. Arch. Toxicol. 65(8), 689-692 https://doi.org/10.1007/BF02098039
  54. Trinder, D., et al. (2000) Localization of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload [see comments]. Gut 46(2), 270-276 https://doi.org/10.1136/gut.46.2.270
  55. Vahter, M., et al. (1996) Bioavailability of cadmium from shellfish and mixed diet in women. Toxicol. Appl. Pharmacol. 136(2), 332-341 https://doi.org/10.1006/taap.1996.0040
  56. Valberg, L.S., Sorbie, J. and Hamilton, D.L. (1976) Gastrointestinal metabolism of cadmium in experimental iron deficiency. Am. J. Physiol. 231(2), 462-467
  57. Vulpe, C.D., et al. (1999) Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat. Genet. 21(2), 195-199 https://doi.org/10.1038/5979