Skip to main content
SpringerLink
Log in

Roles of Metal Transporters in Cellular Cadmium Transport in Mammals

  • Chapter
  • First Online:
Cadmium Toxicity

Abstract

The mechanisms underlying tissue cadmium (Cd) accumulation in mammals have long been investigated with a focus on the roles of metallothionein, a high-affinity Cd-binding protein. However, the precise mechanisms underlying the influx and efflux of Cd at the cell membrane have remained unclear. As Cd is not an essential element, the transport pathways for essential elements are thought to be utilized for Cd transport, especially for entry into cells. Recently, the roles of metal transporters for iron, calcium, zinc, and manganese in cellular Cd transport have begun to be elucidated. The expression and roles of these transporters vary depending on the tissue or cell types and the nutritional statuses of the elements. Consequently, the usage of metal transporters for Cd transport is also altered depending on the tissue and nutritional status of an element. In this chapter, recent advances in understanding the mechanisms underlying cellular Cd transport from the standpoint of the roles of metal transporters are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Elinder CG, Lind B, Kjellström T, Linnman L, Friberg L. Cadmium in kidney cortex, liver, and pancreas from Swedish autopsies. Estimation of biological half time in kidney cortex, considering calorie intake and smoking habits. Arch Environ Health. 1976;31:292–302.

    CAS  PubMed  Google Scholar 

  2. Kjellström T. Exposure and accumulation of cadmium in populations from Japan, the United States, and Sweden. Environ Health Perspect. 1979;28:169–97.

    PubMed  PubMed Central  Google Scholar 

  3. Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR. A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett. 2003;137:65–83.

    CAS  PubMed  Google Scholar 

  4. Hansen JC, Gron P, Jespersen BA, Voigt J, Simonsen J, Dalgaard JB, Hansen E. Cadmium exposure in Denmark. Based on analyses of liver and kidney tissues. Dan Med Bull. 1989;36:499–502.

    CAS  PubMed  Google Scholar 

  5. Johansen P, Mulvad G, Pedersen HS, Hansen JC, Riget F. Accumulation of cadmium in livers and kidneys in Greenlanders. Sci Total Environ. 2006;372:58–63.

    CAS  PubMed  Google Scholar 

  6. Yoshinaga J, Matsuo N, Imai H, Nakazawa M, Suzuki T, Morita M, Akagi H. Interrelationship between the concentrations of some elements in the organs of Japanese with special reference to selenium-heavy metal relationships. Sci Total Environ. 1990;91:127–40.

    CAS  PubMed  Google Scholar 

  7. Noda H, Sugiyama S, Yamaguchi M, Tatsumi S, Sano Y, Konishi S, Furutani A, Yoshimura M. Study on secular changes of cadmium concentration accumulated in main organs of Japanese. Nihon Hoigaku Zasshi. 1993;47:153–9.

    CAS  PubMed  Google Scholar 

  8. Yoshida M, Ohta H, Yamauchi Y, Seki Y, Sagi M, Yamazaki K, Sumi Y. Age-dependent changes in metallothionein levels in liver and kidney of the Japanese. Biol Trace Elem Res. 1998;63:167–75.

    CAS  PubMed  Google Scholar 

  9. Kjellström T, Elinder CG, Friberg L. Conceptual problems in establishing the critical concentration of cadmium in human kidney cortex. Environ Res. 1984;33:284–95.

    PubMed  Google Scholar 

  10. Roels H, Lauwerys R, Dardenne AN. The critical level of cadmium in human renal cortex: a reevaluation. Toxicol Lett. 1983;15:357–60.

    CAS  PubMed  Google Scholar 

  11. Buchet JP, Lauwerys R, Roels H, Bernard A, Bruaux P, Claeys F, Ducoffre G, de Plaen P, Staessen J, Amery A, Lijnen P, Thijs L, Rondia D, Sartor F, Saint Remy A, Nick L. Renal effects of cadmium body burden of the general population. Lancet. 1990;336:699–702.

    CAS  PubMed  Google Scholar 

  12. Hayashi C, Koizumi N, Nishio H, Ikeda M. Cadmium and other metal levels in autopsy samples from a cadmium-polluted area and non-polluted control areas in Japan. Biol Trace Elem Res. 2012;145:10–22.

    CAS  PubMed  Google Scholar 

  13. Baba H, Tsuneyama K, Kumada T, Aoshima K, Imura J. Histopathological analysis for osteomalacia and tubulopathy in itai-itai disease. J Toxicol Sci. 2014;39:91–6.

    PubMed  Google Scholar 

  14. Yasuda M, Miwa A, Kitagawa M. Morphometric studies of renal lesions in Itai-itai disease: chronic cadmium nephropathy. Nephron. 1995;69:14–9.

    CAS  PubMed  Google Scholar 

  15. Klaassen CD, Liu J, Diwan BA. Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol. 2009;238:215–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Ragan HA. Effects of iron deficiency on the absorption and distribution of lead and cadmium in rats. J Lab Clin Med. 1977;90:700–6.

    CAS  PubMed  Google Scholar 

  17. Flanagan PR, McLellan JS, Haist J, Cherian G, Chamberlain MJ, Valberg LS. Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology. 1978;74:841–6.

    CAS  PubMed  Google Scholar 

  18. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997;388:482–8.

    CAS  PubMed  Google Scholar 

  19. Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption. Blood Cells Mol Dis. 2002;29:384–99.

    CAS  PubMed  Google Scholar 

  20. Theil EC. Iron homeostasis and nutritional iron deficiency. J Nutr. 2011;141:724S–8S.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Park JD, Cherrington NJ, Klaassen CD. Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats. Toxicol Sci. 2002;68:288–94.

    CAS  PubMed  Google Scholar 

  22. Min KS, Iwata N, Tetsutikawahara N, Onosaka S, Tanaka K. Effect of hemolytic and iron-deficiency anemia on intestinal absorption and tissue accumulation of cadmium. Toxicol Lett. 2008;179:48–52.

    CAS  PubMed  Google Scholar 

  23. Min KS, Ueda H, Kihara T, Tanaka K. Increased hepatic accumulation of ingested Cd is associated with upregulation of several intestinal transporters in mice fed diets deficient in essential metals. Toxicol Sci. 2008;106:284–9.

    CAS  PubMed  Google Scholar 

  24. Leazer TM, Liu Y, Klaassen CD. Cadmium absorption and its relationship to divalent metal transporter-1 in the pregnant rat. Toxicol Appl Pharmacol. 2002;185:18–24.

    CAS  PubMed  Google Scholar 

  25. Dautry-Varsat A. Receptor-mediated endocytosis: the intracellular journey of transferrin and its receptor. Biochimie. 1986;68:375–81.

    CAS  PubMed  Google Scholar 

  26. Abouhamed M, Gburek J, Liu W, Torchalski B, Wilhelm A, Wolff NA, Christensen EI, Thévenod F, Smith CP. Divalent metal transporter 1 in the kidney proximal tubule is expressed in late endosomes/lysosomal membranes: implications for renal handling of protein-metal complexes. Am J Physiol Renal Physiol. 2006;290:F1525–33.

    CAS  PubMed  Google Scholar 

  27. Abouhamed M, Wolff NA, Lee WK, Smith CP, Thévenod F. Knockdown of endosomal/lysosomal divalent metal transporter 1 by RNA interference prevents cadmium-metallothionein-1 cytotoxicity in renal proximal tubule cells. Am J Physiol Renal Physiol. 2007;293:F705–12.

    CAS  PubMed  Google Scholar 

  28. Washko PW, Cousins RJ. Metabolism of 109Cd in rats fed normal and low-calcium diets. J Toxicol Environ Health. 1976;1:1055–66.

    CAS  PubMed  Google Scholar 

  29. Min KS, Ueda H, Tanaka K. Involvement of intestinal calcium transporter 1 and metallothionein in cadmium accumulation in the liver and kidney of mice fed a low-calcium diet. Toxicol Lett. 2008;176:85–92.

    CAS  PubMed  Google Scholar 

  30. Min KS, Sano E, Ueda H, Sakazaki F, Yamada K, Takano M, Tanaka K. Dietary deficiency of calcium and/or iron, an age-related risk factor for renal accumulation of cadmium in mice. Biol Pharm Bull. 2015;38:1557–63.

    CAS  PubMed  Google Scholar 

  31. Leslie EM, Liu J, Klaassen CD, Waalkes MP. Acquired cadmium resistance in metallothionein-I/II(−/−) knockout cells: role of the T-type calcium channel Cacnα1G in cadmium uptake. Mol Pharmacol. 2006;69:629–39.

    CAS  PubMed  Google Scholar 

  32. Fujishiro H, Okugaki S, Nagao S, Satoh M, Himeno S. Characterization of gene expression profiles of metallothionein null cadmium-resistant cells. J Health Sci. 2006;52:292–9.

    CAS  Google Scholar 

  33. Fujishiro H, Okugaki S, Kubota K, Fujiyama T, Miyataka H, Himeno S. The role of ZIP8 down-regulation in cadmium-resistant metallothionein-null cells. J Appl Toxicol. 2009;29:367–73.

    CAS  PubMed  Google Scholar 

  34. Fujishiro H, Kubota K, Inoue D, Inoue A, Yanagiya T, Enomoto S, Himeno S. Cross-resistance of cadmium-resistant cells to manganese is associated with reduced accumulation of both cadmium and manganese. Toxicology. 2011;280:118–25.

    CAS  PubMed  Google Scholar 

  35. Waalkes MP, Perantoni A. In vitro assessment of target cell specificity in cadmium carcinogenesis: interactions of cadmium and zinc with isolated interstitial cells of the rat testes. In Vitro Cell Dev Biol. 1988;24:558–65.

    CAS  PubMed  Google Scholar 

  36. Barbier O, Dauby A, Jacquillet G, Tauc M, Poujeol P, Cougnon M. Zinc and cadmium interactions in a renal cell line derived from rabbit proximal tubule. Nephron Physiol. 2005;99:p74–84.

    CAS  PubMed  Google Scholar 

  37. Dalton TP, He L, Wang B, Miller ML, Jin L, Stringer KF, Chang X, Baxter CS, Nebert DW. Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis. Proc Natl Acad Sci U S A. 2005;102:3401–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Girijashanker K, He L, Soleimani M, Reed JM, Li H, Liu Z, Wang B, Dalton TP, Nebert DW. Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter. Mol Pharmacol. 2008;73:1413–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Grady DL, Moyzis RK, Hildebrand CE. Molecular and cellular mechanisms of cadmium resistance in cultured cells. Experientia Suppl. 1987;52:447–56.

    CAS  PubMed  Google Scholar 

  40. Li W, Kagan HM, Chou IN. Alterations in cytoskeletal organization and homeostasis of cellular thiols in cadmium-resistant cells. Toxicol Appl Pharmacol. 1994;126:114–23.

    CAS  PubMed  Google Scholar 

  41. Crawford BD, Enger MD, Griffith BB, Griffith JK, Hanners JL, Longmire JL, Munk AC, Stallings RL, Tesmer JG, Walters RA, et al. Coordinate amplification of metallothionein I and II genes in cadmium-resistant Chinese hamster cells: implications for mechanisms regulating metallothionein gene expression. Mol Cell Biol. 1985;5:320–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Yanagiya T, Imura N, Kondo Y, Himeno S. Reduced uptake and enhanced release of cadmium in cadmium-resistant metallothionein null fibroblasts. Life Sci. 1999;65:PL177–82.

    CAS  PubMed  Google Scholar 

  43. Yanagiya T, Imura N, Enomoto S, Kondo Y, Himeno S. Suppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells. J Pharmacol Exp Ther. 2000;292:1080–6.

    CAS  PubMed  Google Scholar 

  44. He L, Girijashanker K, Dalton TP, Reed J, Li H, Soleimani M, Nebert DW. ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family: characterization of transporter properties. Mol Pharmacol. 2006;70:171–80.

    CAS  PubMed  Google Scholar 

  45. Kambe T, Tsuji T, Hashimoto A, Itsumura N. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol Rev. 2015;95:749–84.

    CAS  PubMed  Google Scholar 

  46. Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A. 2005;102:6843–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Fujishiro H, Doi M, Enomoto S, Himeno S. High sensitivity of RBL-2H3 cells to cadmium and manganese: an implication of the role of ZIP8. Metallomics. 2011;3:710–8.

    CAS  PubMed  Google Scholar 

  48. Fujishiro H, Ohashi T, Takuma M, Himeno S. Suppression of ZIP8 expression is a common feature of cadmium-resistant and manganese-resistant RBL-2H3 cells. Metallomics. 2013;5:437–44.

    CAS  PubMed  Google Scholar 

  49. Drakesmith H, Nemeth E, Ganz T. Ironing out Ferroportin. Cell Metab. 2015;22:777–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Choi KC, Jeung EB. Molecular mechanism of regulation of the calcium-binding protein calbindin-D9k, and its physiological role(s) in mammals: a review of current research. J Cell Mol Med. 2008;12:409–20.

    CAS  PubMed  Google Scholar 

  51. Min KS, Fujita Y, Onosaka S, Tanaka K. Role of intestinal metallothionein in absorption and distribution of orally administered cadmium. Toxicol Appl Pharmacol. 1991;109:7–16.

    CAS  PubMed  Google Scholar 

  52. Min KS, Nakatsubo T, Kawamura S, Fujita Y, Onosaka S, Tanaka K. Effects of mucosal metallothionein in small intestine on tissue distribution of cadmium after oral administration of cadmium compounds. Toxicol Appl Pharmacol. 1992;113:306–10.

    CAS  PubMed  Google Scholar 

  53. Sabolic I, Breljak D, Skarica M, Herak-Kramberger CM. Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals. 2010;23:897–926.

    CAS  PubMed  Google Scholar 

  54. Waalkes MP. Effect of dietary zinc deficiency on the accumulation of cadmium and metallothionein in selected tissues of the rat. J Toxicol Environ Health. 1986;18:301–13.

    CAS  PubMed  Google Scholar 

  55. Reeves PG, Chaney RL. Marginal nutritional status of zinc, iron, and calcium increases cadmium retention in the duodenum and other organs of rats fed rice-based diets. Environ Res. 2004;96:311–22.

    CAS  PubMed  Google Scholar 

  56. Guthrie GJ, Aydemir TB, Troche C, Martin AB, Chang SM, Cousins RJ. Influence of ZIP14 (slc39A14) on intestinal zinc processing and barrier function. Am J Physiol Gastrointest Liver Physiol. 2015;308:G171–8.

    CAS  PubMed  Google Scholar 

  57. Fujishiro H, Hamao S, Tanaka R, Kambe T, Himeno S. Concentration-dependent roles of DMT1 and ZIP14 in cadmium absorption in Caco-2 cells. J Toxicol Sci. 2017;42:559–67.

    CAS  PubMed  Google Scholar 

  58. Souza V, Bucio L, Gutierrez-Ruiz MC. Cadmium uptake by a human hepatic cell line (WRL-68 cells). Toxicology. 1997;120:215–20.

    CAS  PubMed  Google Scholar 

  59. Souza V, Bucio L, Jay D, Chavez E, Gutierrez-Ruiz MC. Effect of cadmium on calcium transport in a human fetal hepatic cell line (WRL-68 cells). Toxicology. 1996;112:97–104.

    CAS  PubMed  Google Scholar 

  60. Jorge-Nebert LF, Galvez-Peralta M, Landero Figueroa J, Somarathna M, Hojyo S, Fukada T, Nebert DW. Comparing gene expression during cadmium uptake and distribution: untreated versus oral Cd-treated wild-type and ZIP14 knockout mice. Toxicol Sci. 2015;143:26–35.

    CAS  PubMed  Google Scholar 

  61. Min KS, Takano M, Amako K, Ueda H, Tanaka K. Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation. Toxicol Lett. 2013;218:91–6.

    CAS  PubMed  Google Scholar 

  62. Shaikh ZA, Blazka ME, Endo T. Metal transport in cells: cadmium uptake by rat hepatocytes and renal cortical epithelial cells. Environ Health Perspect. 1995;103(Suppl 1):73–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Shimada H, Yasutake A, Hirashima T, Takamure Y, Kitano T, Waalkes MP, Imamura Y. Strain difference of cadmium accumulation by liver slices of inbred Wistar-Imamichi and Fischer 344 rats. Toxicol In Vitro. 2008;22:338–43.

    CAS  PubMed  Google Scholar 

  64. Poisson J, Lemoinne S, Boulanger C, Durand F, Moreau R, Valla D, Rautou PE. Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J Hepatol. 2017;66:212–27.

    CAS  PubMed  Google Scholar 

  65. Min KS, Onosaka S, Tanaka K. Renal accumulation of cadmium and nephropathy following long-term administration of cadmium-metallothionein. Toxicol Appl Pharmacol. 1996;141:102–9.

    CAS  PubMed  Google Scholar 

  66. Dorian C, Gattone VH 2nd, Klaassen CD. Discrepancy between the nephrotoxic potencies of cadmium-metallothionein and cadmium chloride and the renal concentration of cadmium in the proximal convoluted tubules. Toxicol Appl Pharmacol. 1995;130:161–8.

    CAS  PubMed  Google Scholar 

  67. Ohta H, Cherian MG. Gastrointestinal absorption of cadmium and metallothionein. Toxicol Appl Pharmacol. 1991;107:63–72.

    CAS  PubMed  Google Scholar 

  68. Dudley RE, Gammal LM, Klaassen CD. Cadmium-induced hepatic and renal injury in chronically exposed rats: likely role of hepatic cadmium-metallothionein in nephrotoxicity. Toxicol Appl Pharmacol. 1985;77:414–26.

    CAS  PubMed  Google Scholar 

  69. Sugawara N, Lai YR, Arizono K, Kitajima T, Inoue H. Lack of biliary excretion of Cd linked to an inherent defect of the canalicular isoform of multidrug resistance protein (cMrp) does not abnormally stimulate accumulation of Cd in the Eisai hyperbilirubinemic (EHB) rat liver. Arch Toxicol. 1997;71:336–9.

    CAS  PubMed  Google Scholar 

  70. Nordberg M, Jin T, Nordberg GF. Cadmium, metallothionein and renal tubular toxicity. IARC Sci Publ. 1992;118:293–7.

    CAS  Google Scholar 

  71. Klassen RB, Crenshaw K, Kozyraki R, Verroust PJ, Tio L, Atrian S, Allen PL, Hammond TG. Megalin mediates renal uptake of heavy metal metallothionein complexes. Am J Physiol Renal Physiol. 2004;287:F393–403.

    CAS  PubMed  Google Scholar 

  72. Wolff NA, Abouhamed M, Verroust PJ, Thévenod F. Megalin-dependent internalization of cadmium-metallothionein and cytotoxicity in cultured renal proximal tubule cells. J Pharmacol Exp Ther. 2006;318:782–91.

    CAS  PubMed  Google Scholar 

  73. Onodera A, Tani M, Michigami T, Yamagata M, Min KS, Tanaka K, Nakanishi T, Kimura T, Itoh N. Role of megalin and the soluble form of its ligand RAP in Cd-metallothionein endocytosis and Cd-metallothionein-induced nephrotoxicity in vivo. Toxicol Lett. 2012;212:91–6.

    CAS  PubMed  Google Scholar 

  74. Thévenod F. Catch me if you can! Novel aspects of cadmium transport in mammalian cells. Biometals. 2010;23:857–75.

    PubMed  Google Scholar 

  75. Fujishiro H, Yano Y, Takada Y, Tanihara M, Himeno S. Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. Metallomics. 2012;4:700–8.

    CAS  PubMed  Google Scholar 

  76. Dorian C, Gattone VH 2nd, Klaasen CD. Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein (CdMT) by the proximal convoluted tubules--A light microscopic autoradiography study with 109CdMT. Toxicol Appl Pharmacol. 1992;114:173–81.

    CAS  PubMed  Google Scholar 

  77. Park JH, Hogrebe M, Gruneberg M, DuChesne I, von der Heiden AL, Reunert J, Schlingmann KP, Boycott KM, Beaulieu CL, Mhanni AA, Innes AM, Hortnagel K, Biskup S, Gleixner EM, Kurlemann G, Fiedler B, Omran H, Rutsch F, Wada Y, Tsiakas K, Santer R, Nebert DW, Rust S, Marquardt T. SLC39A8 deficiency: a disorder of manganese transport and glycosylation. Am J Hum Genet. 2015;97:894–903.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Boycott KM, Beaulieu CL, Kernohan KD, Gebril OH, Mhanni A, Chudley AE, Redl D, Qin W, Hampson S, Kury S, Tetreault M, Puffenberger EG, Scott JN, Bezieau S, Reis A, Uebe S, Schumacher J, Hegele RA, McLeod DR, Galvez-Peralta M, Majewski J, Ramaekers VT, Nebert DW, Innes AM, Parboosingh JS, Abou Jamra R. Autosomal-recessive intellectual disability with cerebellar atrophy syndrome caused by mutation of the manganese and zinc transporter gene SLC39A8. Am J Hum Genet. 2015;97:886–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Park JH, Hogrebe M, Fobker M, Brackmann R, Fiedler B, Reunert J, Rust S, Tsiakas K, Santer R, Gruneberg M, Marquardt T. SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy. Genet Med. 2018;20:259–68.

    CAS  PubMed  Google Scholar 

  80. Rentschler G, Kippler M, Axmon A, Raqib R, Skerfving S, Vahter M, Broberg K. Cadmium concentrations in human blood and urine are associated with polymorphisms in zinc transporter genes. Metallomics. 2014;6:885–91.

    CAS  PubMed  Google Scholar 

  81. Ng E, Lind PM, Lindgren C, Ingelsson E, Mahajan A, Morris A, Lind L. Genome-wide association study of toxic metals and trace elements reveals novel associations. Hum Mol Genet. 2015;24:4739–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Waterworth DM, Ricketts SL, Song K, Chen L, Zhao JH, Ripatti S, Aulchenko YS, Zhang W, Yuan X, Lim N, Luan J, Ashford S, Wheeler E, Young EH, Hadley D, Thompson JR, Braund PS, Johnson T, Struchalin M, Surakka I, Luben R, Khaw KT, Rodwell SA, Loos RJ, Boekholdt SM, Inouye M, Deloukas P, Elliott P, Schlessinger D, Sanna S, Scuteri A, Jackson A, Mohlke KL, Tuomilehto J, Roberts R, Stewart A, Kesaniemi YA, Mahley RW, Grundy SM, McArdle W, Cardon L, Waeber G, Vollenweider P, Chambers JC, Boehnke M, Abecasis GR, Salomaa V, Jarvelin MR, Ruokonen A, Barroso I, Epstein SE, Hakonarson HH, Rader DJ, Reilly MP, Witteman JC, Hall AS, Samani NJ, Strachan DP, Barter P, van Duijn CM, Kooner JS, Peltonen L, Wareham NJ, McPherson R, Mooser V, Sandhu MS. Genetic variants influencing circulating lipid levels and risk of coronary artery disease. Arterioscler Thromb Vasc Biol. 2010;30:2264–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhang R, Witkowska K, Ng F, Caulfield MJ, Ye S. Lb03.08: Hypertension Related Variant of Solute Carrier Family 39 Member 8 Gene Influences Cadmium Uptake and Cell Toxicity. J Hypertens. 2015;33(Suppl 1):e128.

    Google Scholar 

  84. Costas J. The highly pleiotropic gene SLC39A8 as an opportunity to gain insight into the molecular pathogenesis of schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2018;177:274–83.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan

    Seiichiro Himeno & Hitomi Fujishiro

Authors
  1. Seiichiro Himeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hitomi Fujishiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seiichiro Himeno .

Editor information

Editors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan

    Seiichiro Himeno

  2. Hagino Hospital, Toyama, Japan

    Keiko Aoshima

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Himeno, S., Fujishiro, H. (2019). Roles of Metal Transporters in Cellular Cadmium Transport in Mammals. In: Himeno, S., Aoshima, K. (eds) Cadmium Toxicity. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-13-3630-0_13

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-3630-0_13

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-3629-4

  • Online ISBN: 978-981-13-3630-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation