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Changes of the mRNA Expression Pattern of Zn Transporters: a Probable Mechanism for Cadmium Retention and Zinc Redistribution in the Suckling Rat Tissues

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Abstract

The present study was conducted to provide potential mechanism that may be responsible for Cd retention and Cd-induced Zn redistribution in tissues of suckling rat. For this purpose, suckling rats from mother receiving either tap water, Cd, or Cd + Zn during lactation period were sacrificed on postnatal day (PND) 14 and PND 21 for performing chemical and molecular analysis. Our results show that Cd exposure, although it does not affect the milk consumption, it clearly alters the lactational transfer, absorption, and distribution of Zn in the suckling rat organism. At the molecular level, Cd caused upregulation of ZIP 3, ZIP 4, and ZIP 8 gene expressions in the mammary gland of mothers rats and in the intestine of their pups but decreased the expression of ZnT 2 and ZnT 4 only in the mammary tissue at PND 14 and PND 21. Zn supply reversed the Cd-induced decrease in the neonatal Zn apparent absorption and restores the gastrointestinal, brain, and plasma levels of this essential element in the suckling rat organism at PND 14 and PND 21. Also, with this treatment, the gene expressions of ZnT 1 in the mammary gland and ZnT 4 in the neonatal intestine were found to be upregulated at PND 21. Furthermore, our results show that Cd or Cd + Zn treatment increase the neonatal hepatic MTs accumulation at PND 14 only. These results imply that the downregulation of ZnT as well as the overexpression of ZIP transporters, in responses to the Zn depletion induced by Cd in the tissues of lactating rat and their offspring, play a major role in Cd accumulation and Zn redistribution in tissues of suckling rat.

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References

  1. Whelton BD, Toomey JM, Bhattacharyya MH (1993) Cadmium- 109 metabolism in mice. IV. Diet versus maternal stores as a source of cadmium transfer to mouse fetuses and pups during gestation and lactation. J Toxicol Environ Health 40:531–546

    Article  CAS  PubMed  Google Scholar 

  2. Petersson Grawé K, Oskarsson A (2000) Cadmium in milk and mammary gland in rats and mice. Arch Toxicol 73:519–527

    Article  PubMed  Google Scholar 

  3. Dési I, Nagymajtényi L, Schulz H (1998) Behavioural and neurotoxicological changes caused by cadmium treatment of rats during development. J Appl Toxicol 18:63–70

    Article  PubMed  Google Scholar 

  4. Petersson Grawé K, Pickova J, Dutta PC, Oskarsson A (2004) Fatty acid alterations in liver and milk of cadmium exposed rats and in brain of their suckling offspring. Toxicol Lett 148:73–82

    Article  Google Scholar 

  5. Rigon AP, Cordova FM, Oliveira CS, Posser T, Costa AP, Silva IG, Santos DA, Rossi FM, Rocha JB, Leal RB (2008) Neurotoxicity of cadmium on immature hippocampus and a neuroprotective role for p38 MAPK. Neurotoxicol 29:727–734

    Article  CAS  Google Scholar 

  6. Waalkes MP (1986) Effect of dietary zinc deficiency on the accumulation of cadmium and metallothionein in selected tissues of the rat. J Toxicol Environ Health 18:301–313

    Article  CAS  PubMed  Google Scholar 

  7. Brzóska MM, Rogalska J, Galazyn-Sidorczuk M, Jurczuk M, Roszczenko A, Kulikowska-Karpińska E, Moniuszko-Jakoniuk J (2007) Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium. Toxicology 237:89–103

    Article  PubMed  Google Scholar 

  8. Brzoska MM, Moniuszko-Jakoniuk J (2001) Interactions between cadmium and zinc in the organism. Food Chem Toxicol 39:967–980

    Article  CAS  PubMed  Google Scholar 

  9. Coleman JE (1992) Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins. Annu Rev Biochem 61:897–946

    Article  CAS  PubMed  Google Scholar 

  10. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73:79–118

    CAS  PubMed  Google Scholar 

  11. Davies NT, Williams B (1977) Zinc balance during pregnancy and lactation. Am J Clin Nutr 30:300–302

    CAS  PubMed  Google Scholar 

  12. Fosmire GJ, Greeley S, Sandstead HH (1977) Maternal and fetal response to various suboptimal levels of zinc intake during gestation in the rat. J Nutr 107:1543–1550

    CAS  PubMed  Google Scholar 

  13. Hurley LS, Shrader RE (1975) Abnormal development of preimplantation rat eggs after three days of maternal dietary zinc deficiency. Nature 254:427–490

    Article  CAS  PubMed  Google Scholar 

  14. Sandstead HH, Gillespie DD, Brady RN (1972) Zinc deficiency: effect on brain of the suckling rat. Pediatr Res 6:119–125

    Article  CAS  PubMed  Google Scholar 

  15. Kambe T, Yamaguchi-Iwai Y, Sasaki R, Nagao M (2004) Overview of mammalian zinc transporters. Cell Mol Life Sci 61:49–68

    Article  CAS  PubMed  Google Scholar 

  16. Dalton TP, Fu K, Palmiter RD, Andrews GK (1996) Transgenic mice that over-express metallothionein-I resist dietary zinc deficiency. J Nutr 126:825–833

    CAS  PubMed  Google Scholar 

  17. Brzoska MM, Moniuszko-Jakoniuk J, Jurczuk M, Gaazyn-Sidorczuk M (2002) Cadmium turnover and changes of zinc and copper body status of rats continuously exposed to cadmium and ethanol. Alcohol Alcohol 37:213–221

    Article  CAS  PubMed  Google Scholar 

  18. Messaoudi I, Banni M, Saïd L, Saïd K, Kerkeni A (2010) Evaluation of involvement of testicular metallothionein gene expression in the protective effect of zinc against cadmium-induced testicular pathophysiology in rat. Reprod Toxicol 29:339–345

    Article  CAS  PubMed  Google Scholar 

  19. Viarengo A, Ponzano E, Dondero F, Fabbari R (1997) Simple method for metallothionein evaluation in tissues of marine invertebrates such as Mediterranean and Antarctic mollusk. Mar Environ Res 44:69–84

    Article  CAS  Google Scholar 

  20. Bradford MM (1976) A rapid and sensitive method for the quantification of microgram of protein utilizing the principal of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  21. Ponz F, Ilundain A, Lluch M (1979) Method for successive absorptions with intestinal perfusion in vivo. Rev Esp Fisiol 35:97–104

    CAS  PubMed  Google Scholar 

  22. Morag M (1970) Estimation of milk yield in the rat. Lab Anim 4:259–272

    Article  CAS  PubMed  Google Scholar 

  23. Banni M, Negri A, Mignone F, Boussetta H, Viarengo A, Dondero F (2011) Gene expression rhythms in the mussel Mytilus galloprovincialis (Lam.) across an annual cycle. PLoS ONE 6(5):e18904

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36

    Article  PubMed Central  PubMed  Google Scholar 

  25. Lucis OJ, Lucis R, Shaikh ZA (1972) Cadmium and zinc in pregnancy and lactation. Arch Environ Health 25:14–22

    Article  CAS  PubMed  Google Scholar 

  26. Haouem S, Sakly R (2005) Lactational transfer of cadmium from Meriones shawi shawi mothers to their pups and its effects on calcium homeostasis and bone calcium in pups. Ann Nutr Metab 49:296–299

    Article  CAS  PubMed  Google Scholar 

  27. Barański B (1986) Effect of maternal cadmium exposure on postnatal development and tissue cadmium, copper and zinc concentrations in rats. Arch Toxicol 58:255–260

    Article  PubMed  Google Scholar 

  28. Chouchene L, Banni M, Kerkeni A, Saïd K, Messaoudi I (2011) Cadmium-induced ovarian pathophysiology is mediated by change in gene expression pattern of zinc transporters in zebrafish (Danio rerio). Chem Biol Interact 193:172–179

    Article  CAS  PubMed  Google Scholar 

  29. Nakazato K, Nagamine T, Suzuki K, Kusakabe T, Moon HD, Oikawa M, Sakai K, Arakawa T (2008) Subcellular changes of essential metal shown by in-air micro-PIXE in oral cadmium-exposed mice. BioMetals 21:83–91

    Article  CAS  PubMed  Google Scholar 

  30. Banni M, Messaoudi I, Said L, El Heni J, Kerkeni A, Said K (2010) Metallothionein gene expression in liver of rats exposed to cadmium and supplemented with zinc and selenium. Arch Environ Contam Toxicol 59:513–519

    Article  CAS  PubMed  Google Scholar 

  31. Kelly EJ, Quaife CJ, Froelick G, Palmiter RD (1996) Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice. J Nutr 126:1782–1790

    CAS  PubMed  Google Scholar 

  32. Goering PL, Klaassen CD (1984) Resistance to cadmium-induced hepatotoxicity in immature rats. Toxicol Appl Pharmacol 74:321–329

    Article  CAS  PubMed  Google Scholar 

  33. Panemangalore M, Cherian MG (1983) Metabolism of parenterally administered zinc and cadmium in liver of newborn rats. Chem Biol Interact 45:327–339

    Article  CAS  PubMed  Google Scholar 

  34. Ueda F, Seki H, Fujiward H, Ebara K, Minomiya S, Shimaki Y (1987) Interacting effects of Zinc and cadmium on the cadmium distribution in the mouse. Vet Hum Toxicol 29:367–372

    CAS  PubMed  Google Scholar 

  35. Hammouda F, Messaoudi I, El Hani J, Baati T, Saïd K, Kerkeni A (2008) Reversal of cadmium-induced thyroid dysfunction by selenium, zinc, or their combination in rat. Biol Trace Elem Res 126:194–203

    Article  CAS  PubMed  Google Scholar 

  36. Messaoudi I, El Heni J, Hammouda F, Saïd K, Kerkeni A (2009) Protective effects of selenium, zinc, or their combination on cadmium-induced oxidative stress in rat kidney. Biol Trace Elem Res 130:152–161

    Article  CAS  PubMed  Google Scholar 

  37. El Heni J, Messaoudi I, Hammouda F, Kerkeni A (2009) Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver of the rat: effects on the oxidative stress. Ecotoxicol Environ Saf 72:1559–1564

    Article  Google Scholar 

  38. Girotti AW, Thomas JP, Jordan JE (1985) Inhibitory effect of zinc (II) on free radical lipid peroxidation in erythrocyte membranes. Free Radic Biol Med 1:395–401

    Article  CAS  Google Scholar 

  39. Bridges CC, Zalups RK (2005) Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol 204:274–308

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Martinez-Finley EJ, Chakraborty S, Fretham SJ, Aschner M (2012) Cellular transport and homeostasis of essential and nonessential metals. Metallomics 4:593–605

    Article  CAS  PubMed  Google Scholar 

  41. Bhattacharyya MH, Whelton BD, Peterson DE (1982) Gastrointestinal absorption of cadmium in mice during gestation and lactation. II. Continuous exposure studies. Toxicol Appl Pharmacol 66:368–375

    Article  CAS  PubMed  Google Scholar 

  42. Ohrvik H, Yoshioka M, Oskarsson A, Tallkvist J (2006) Cadmium-induced disturbances in lactating mammary glands of mice. Toxicol Lett 164:207–213

    Article  PubMed  Google Scholar 

  43. Kippler M, Lönnerdal B, Goessler W, Ekström EC, Arifeen SE, Vahter M (2009) Cadmium interacts with the transport of essential micronutrients in the mammary gland - a study in rural Bangladeshi women. Toxicology 257:64–69

    Article  CAS  PubMed  Google Scholar 

  44. Kelleher SL, Seo YA, Lopez V (2009) Mammary gland zinc metabolism: regulation and dysregulation. Gene Nutr 4:83–94

    Article  CAS  Google Scholar 

  45. Kelleher SL, Lönnerdal B (2003) Zn transporter levels and localization change throughout lactation in rat mammary gland and are regulated by Zn in mammary cells. J Nutr 133:3378–3385

    CAS  PubMed  Google Scholar 

  46. Kelleher SL, Velasquez V, Croxford TP, McCormick NH, Lopez V, MacDavid J (2012) Mapping the zinc-transporting system in mammary cells: molecular analysis reveals a phenotype-dependent zinc-transporting network during lactation. J Cell Physiol 227:1761–1770

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Le Huërou-Luron I, Blat S, Boudry G (2010) Breast- v. formula-feeding: impacts on the digestive tract and immediate and long-term health effects. Nutr Res Rev 23:23–36

    Article  PubMed  Google Scholar 

  48. Huang ZL, Dufner-Beattie J, Andrews GK (2006) Expression and regulation of SLC39A family zinc transporters in the developing mouse intestine. Dev Biol 295:571–579

    Article  CAS  PubMed  Google Scholar 

  49. Dufner-Beattie J, Langmade SJ, Wang F, Eide D, Andrews GK (2003) Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J Biol Chem 278(50):50142–50150

    Article  CAS  PubMed  Google Scholar 

  50. Liuzzi JP, Bobo JA, Lichten LA, Samuelson DA, Cousins RJ (2004) Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis. Proc Natl Acad Sci U S A 101(40):14355–14360

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Liu Z, Li H, Soleimani M, Girijashanker K, Reed JM, He L (2008) Cd2+ versus Zn2+ uptake by the ZIP8 HCO3− dependent symporter: kinetics, electrogenicity and trafficking. Biochem Biophys Res Commun 365:814–820

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Kelleher SL, Lonnerdal B (2003) Zn transporter levels and localization change throughout lactation in rat mammary gland and are regulated by Zn in mammary cells. J Nutr 133:3378–3385

    CAS  PubMed  Google Scholar 

  53. Min KS, Takano M, Amako K, Ueda H, Tanaka K (2013) Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation. Toxicol Lett 27:91–96

    Article  Google Scholar 

  54. Napolitano JR, Liu MJ, Bao S, Crawford M, Nana-Sinkam P, Cormet-Boyaka E, Knoell DL (2012) Cadmium-mediated toxicity of lung epithelia is enhanced through NF-κB-mediated transcriptional activation of the human zinc transporter ZIP8. Am J Physiol Lung Cell Mol Physiol 302:909–918

    Article  Google Scholar 

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Authors and Affiliations

  1. LR11ES41: Génétique, Biodiversité et Valorisation des Bioressources, Institut de Biotechnologie, 5000, Monastir, Tunisia

    Marouane Chemek, Sana Boughammoura, Safa Ben Mimouna, Lina Chouchene & Imed Messaoudi

  2. Laboratoire de Biochimie et Toxicologie Environnementale, ISA, Chott-Mariem, 4042, Sousse, Tunisia

    Mohamed Banni

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  1. Marouane Chemek
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  2. Sana Boughammoura
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  4. Lina Chouchene
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  5. Mohamed Banni
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  6. Imed Messaoudi
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Correspondence to Imed Messaoudi.

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Chemek, M., Boughammoura, S., Mimouna, S.B. et al. Changes of the mRNA Expression Pattern of Zn Transporters: a Probable Mechanism for Cadmium Retention and Zinc Redistribution in the Suckling Rat Tissues. Biol Trace Elem Res 165, 173–182 (2015). https://doi.org/10.1007/s12011-015-0255-1

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  • DOI: https://doi.org/10.1007/s12011-015-0255-1

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