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BioMed Research International
Volume 2015 (2015), Article ID 949514, 10 pages
http://dx.doi.org/10.1155/2015/949514
Research Article

Impact of Cadmium on Intracellular Zinc Levels in HepG2 Cells: Quantitative Evaluations and Molecular Effects

1Department of Earth and Environmental Sciences, University of Milan Bicocca, Piazza della Scienza 1, 20126 Milan, Italy
2Department of Clinical and Experimental Medicine, University of Insubria, 21100 Varese, Italy
3Molecular Biology and Genomics Unit, Institute for Health and Consumer Protection, DG JRC, European Commission, Via Enrico Fermi 2749, 21027 Ispra, Italy
4Chemical Assessment and Testing Unit (CAT), Institute for Health and Consumer Protection, DG JRC, European Commission, Via Enrico Fermi 2749, 21027 Ispra, Italy

Received 17 December 2014; Accepted 2 March 2015

Academic Editor: Luciana dos Reis Vasques

Copyright © 2015 Chiara Urani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Agency for Toxic Substances and Disease Registry, Toxicological Profile for Cadmium, Centers for Disease Control and Prevention, Atlanta, Ga, USA, 2012, http://www.atsdr.cdc.gov/toxprofiles/tp5.pdf.
  2. IARC, A Review of Human Carcinogens; Part C: Arsenic, Metals, Fibers, and Dusts, IARC, Lyon, France, 2012.
  3. A. Martelli, E. Rousselet, C. Dycke, A. Bouron, and J.-M. Moulis, “Cadmium toxicity in animal cells by interference with essential metals,” Biochimie, vol. 88, no. 11, pp. 1807–1814, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. B. Bocca, A. Pino, A. Alimonti, and G. Forte, “Toxic metals contained in cosmetics: a status report,” Regulatory Toxicology and Pharmacology, vol. 68, no. 3, pp. 447–467, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. F. Thévenod, “Catch me if you can! Novel aspects of cadmium transport in mammalian cells,” BioMetals, vol. 23, no. 5, pp. 857–875, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. K. V. Lopin, F. Thévenod, J. C. Page, and S. W. Jones, “Cd2+ block and permeation of CaV3.1 (α1G) T-type calcium channels: candidate mechanism for Cd2+ influx,” Molecular Pharmacology, vol. 82, no. 6, pp. 1183–1193, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Méplan, K. Mann, and P. Hainaut, “Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells,” The Journal of Biological Chemistry, vol. 274, no. 44, pp. 31663–31670, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. M. A. Namdarghanbari, J. Bertling, S. Krezoski, and D. H. Petering, “Toxic metal proteomics: reaction of the mammalian zinc proteome with Cd2+,” Journal of Inorganic Biochemistry, vol. 136, pp. 115–121, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. P. D. Zalewski, I. J. Forbes, and W. H. Betts, “Correlation of apoptosis with change in intracellular labile Zn(II) using Zinquin [(2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetic acid], a new specific fluorescent probe for Zn(II),” Biochemical Journal, vol. 296, no. 2, pp. 403–408, 1993. View at Google Scholar · View at Scopus
  10. D. Beyersmann and H. Haase, “Functions of zinc in signaling, proliferation and differentiation of mammalian cells,” BioMetals, vol. 14, no. 3-4, pp. 331–341, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Yamasaki, K. Sakata-Sogawa, A. Hasegawa et al., “Zinc is a novel intracellular second messenger,” Journal of Cell Biology, vol. 177, no. 4, pp. 637–645, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. P. F. Dehn, C. M. White, D. E. Conners, G. Shipkey, and T. A. Cumbo, “Characterization of the human hepatocellular carcinoma (HEPG2) cell line as an in vitro model for cadmium toxicity studies,” In Vitro Cellular & Developmental Biology—Animal, vol. 40, no. 5-6, pp. 172–182, 2004. View at Publisher · View at Google Scholar
  13. C. Urani, V. Calini, P. Melchioretto, F. Morazzoni, C. Canevali, and M. Camatini, “Different induction of metallothioneins and Hsp70 and presence of the membrane transporter ZnT-1 in HepG2 cells exposed to copper and zinc,” Toxicology in Vitro, vol. 17, no. 5-6, pp. 553–559, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. C. Urani, P. Melchioretto, C. Canevali, F. Morazzoni, and L. Gribaldo, “Metallothionein and hsp70 expression in HepG2 cells after prolonged cadmium exposure,” Toxicology in Vitro, vol. 21, no. 2, pp. 314–319, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. J. G. Hengstler, S. Hammad, A. Ghallab, R. Reif, and P. Godoy, “In vitro systems for hepatotoxicity testing,” in In Vitro Toxicology Systems, A. Bal-Price and P. Jennings, Eds., chapter 2, pp. 27–44, 2014. View at Google Scholar
  16. C. Urani, P. Melchioretto, C. Canevali, F. Morazzoni, and M. Camatini, “Copper and zinc uptake and hsp70 expression in HepG2 cells,” Toxicology in Vitro, vol. 15, no. 4-5, pp. 497–502, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. C. Urani, P. Melchioretto, C. Canevali, and G. F. Crosta, “Cytotoxicity and induction of protective mechanisms in HepG2 cells exposed to cadmium,” Toxicology in Vitro, vol. 19, no. 7, pp. 887–892, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. L. Tang, R. Qiu, Y. Tang, and S. Wang, “Cadmium–zinc exchange and their binary relationship in the structure of Zn-related proteins: a mini review,” Metallomics, vol. 6, no. 8, p. 1313, 2014. View at Publisher · View at Google Scholar
  19. C. Urani, P. Melchioretto, M. Fabbri, G. Bowe, E. Maserati, and L. Gribaldo, “Cadmium Impairs p53 Activity in HepG2 Cells,” ISRN Toxicology, vol. 2014, Article ID 976428, 9 pages, 2014. View at Publisher · View at Google Scholar
  20. N. H. Kim, H. S. Kim, X.-Y. Li et al., “A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition,” Journal of Cell Biology, vol. 195, no. 3, pp. 417–433, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Sarwar Nasir, C. J. Fahrni, D. A. Suhy, K. J. Kolodsick, C. P. Singer, and T. V. O'Halloran, “The chemical cell biology of zinc: structure and intracellular fluorescence of a zinc-quinolinesulfonamide complex,” Journal of Biological Inorganic Chemistry, vol. 4, no. 6, pp. 775–783, 1999. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Coyle, P. D. Zaleewski, J. C. Philcox et al., “Measurement of zinc in hepatocytes by using a fluorescent probe, zinquin: relationship to metallothioneins and intracellular zinc,” Biochemical Journal, vol. 303, no. 3, pp. 781–786, 1994. View at Google Scholar · View at Scopus
  23. M. Fabbri, C. Urani, M. G. Sacco, C. Procaccianti, and L. Gribaldo, “Whole genome analysis and microRNAs regulation in HepG2 cells exposed to cadmium,” ALTEX, vol. 29, no. 2, pp. 173–182, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. G. K. Smyth, “Linear models and empirical Bayes methods for assessing differential expression in microarray experiments,” Statistical Applications in Genetics and Molecular Biology, vol. 3, no. 1, article 3, 25 pages, 2004. View at Publisher · View at Google Scholar · View at MathSciNet
  25. M. Kanehisa, S. Goto, M. Furumichi, M. Tanabe, and M. Hirakawa, “KEGG for representation and analysis of molecular networks involving diseases and drugs,” Nucleic Acids Research, vol. 38, no. 1, pp. D355–D360, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. A. I. Saeed, V. Sharov, J. White et al., “TM4: a free, open-source system for microarray data management and analysis,” BioTechniques, vol. 34, no. 2, pp. 374–378, 2003. View at Google Scholar · View at Scopus
  27. A. Krężel and W. Maret, “Zinc-buffering capacity of a eukaryotic cell at physiological pZn,” Journal of Biological Inorganic Chemistry, vol. 11, no. 8, pp. 1049–1062, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. C. E. Outten and T. V. O'Halloran, “Femtomolar sensitivity of metalloregulatory proteins controlling zinc homeostasis,” Science, vol. 292, no. 5526, pp. 2488–2492, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. J. L. Vinkenborg, T. J. Nicolson, E. A. Bellomo, M. S. Koay, G. A. Rutter, and M. Merkx, “Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis,” Nature Methods, vol. 6, no. 10, pp. 737–740, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. D. J. Eide, “Zinc transporters and the cellular trafficking of zinc,” Biochimica et Biophysica Acta, vol. 1763, no. 7, pp. 711–722, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. A. B. Nowakowski and D. H. Petering, “Reactions of the fluorescent sensor, zinquin, with the zinc-proteome: adduct formation and ligand substitution,” Inorganic Chemistry, vol. 50, no. 20, pp. 10124–10133, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. J. A. L. Figueroa, K. S. Vignesh, G. S. Deepe Jr., and J. Caruso, “Selectivity and specificity of small molecule fluorescent dyes/probes used for the detection of Zn2+ and Ca2+ in cells,” Metallomics, vol. 6, no. 2, pp. 301–315, 2014. View at Publisher · View at Google Scholar · View at Scopus
  33. G. Malgieri, M. Palmieri, S. Esposito et al., “Zinc to cadmium replacement in the prokaryotic zinc-finger domain,” Metallomics, vol. 6, no. 1, pp. 96–104, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. M. A. Nieto, “The Snail superfamily of zinc-finger transcription factors,” Nature Reviews Molecular Cell Biology, vol. 3, pp. 155–166, 2002. View at Publisher · View at Google Scholar
  35. C. Hogstrand, P. Kille, M. L. Ackland, S. Hiscox, and K. M. Taylor, “A mechanism for epithelial-mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3),” Biochemical Journal, vol. 455, no. 2, pp. 229–237, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. L. Trusolino, A. Bertotti, and P. M. Comoglio, “MET signalling: principles and functions in development, organ regeneration and cancer,” Nature Reviews Molecular Cell Biology, vol. 11, no. 12, pp. 834–848, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Massagué, “TGFβ in cancer,” Cell, vol. 134, no. 2, pp. 215–230, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Sadok and C. J. Marshall, “Rho GTPases—masters of cell migration,” Small GTPases, vol. 5, no. 4, Article ID e29710, pp. 1–7, 2014. View at Publisher · View at Google Scholar
  39. J. Zheng, X.-X. Zhang, H. Yu, J. E. Taggart, and W.-Q. Ding, “Zinc at cytotoxic concentrations affects posttranscriptional events of gene expression in cancer cells,” Cellular Physiology and Biochemistry, vol. 29, no. 1-2, pp. 181–188, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. B. Adams, A. Kasinski, and F. Slack, “Aberrant regulation and function of microRNAs in cancer,” Current Biology, vol. 24, no. 16, pp. R762–R776, 2014. View at Publisher · View at Google Scholar
  42. M. Haneklaus, M. Gerlic, L. A. J. O'Neill, and S. L. Masters, “MiR-223: infection, inflammation and cancer,” Journal of Internal Medicine, vol. 274, no. 3, pp. 215–226, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Xiong, L. Jiang, Y. Zhou et al., “The miR-200 family regulates TGF-β1-induced renal tubular epithelial to mesenchymal transition through smad pathway by targeting ZEB1 and ZEB2 expression,” The American Journal of Physiology—Renal Physiology, vol. 302, no. 3, pp. F369–F379, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Kurashige, H. Kamohara, M. Watanabe et al., “MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma,” Annals of Surgical Oncology, vol. 19, no. 3, supplement, pp. S656–S664, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. C. Urani, P. Melchioretto, and L. Gribaldo, “Regulation of metallothioneins and ZnT-1 transporter expression in human hepatoma cells HepG2 exposed to zinc and cadmium,” Toxicology in Vitro, vol. 24, no. 2, pp. 370–374, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Choi and A. J. Bird, “Zinc'ing sensibly: controlling zinc homeostasis at the transcriptional level,” Metallomics, vol. 6, no. 7, pp. 1198–1215, 2014. View at Publisher · View at Google Scholar