Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
권호 표지

Study on Intracellular Zinc Uptake According to Zinc-ligand

  • Shim, Boo-Im (Department of Biochemistry & Molecular biology, Korea University Mrdical College) ;
  • Kim, Ki-Nam (Department of Biochemistry & Molecular biology, Korea University Mrdical College) ;
  • Kim, Yu-Ri (Department of Biochemistry & Molecular biology, Korea University Mrdical College) ;
  • Lee, Seung-Ho (Department of Biochemistry & Molecular biology, Korea University Mrdical College) ;
  • Lee, Seung-Min (Department of Biochemistry & Molecular biology, Korea University Mrdical College) ;
  • Park, Myung-Gyu (MD BioAlpha Co., Ltd) ;
  • Kim, Meyoung-Kon (Department of Biochemistry & Molecular biology, Korea University Mrdical College)
  • Published : 2007.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Zinc plays indispensable roles in metabolism, including cell growth, apoptosis, proliferation and differentiation. Kidneys are target organs for various regulators of mineral metabolism, and play a key role in zinc balance. To investigate the zinc uptake efficiency, we examined the zinc uptake and accumulation level in vivo and in vitro study. Plasma zinc concentration was peaked out at 1 hr after oral zinc administration. The renal zinc level was peaked out at 12 hr after oral zinc administration, and it was the highest in 40 mg/kg Zn-Asp administrated group in comparison with other groups. In addition, the m-RNA expression level of zinc transporter-1 (ZnT-1), zinc transporter-2 (ZnT-2) and high-affinity L-aspartate transporter (EAAT-3) in Zn-Asp administered group were increased compared with control groups and $ZnSO_4$ group. In order to investigate the intracellular zinc uptake mechanism, we performed the in vitro study by using human embryonic kidney cell line, HEK 293. Intracellular zinc level was peaked out at 3 hr after zinc treatment. In the same way, the mRNA expression level of ZnT-1 and EAAT-3 were increased compared with control group. This study showed that Zn-Asp is effective the zinc uptake into the kidney by increasing the zinc transporter expression.

Keywords

References

  1. Devergnas, S. et al. Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study. Biochem Pharmacol 68:699-709 (2004) https://doi.org/10.1016/j.bcp.2004.05.024
  2. McMahon, R. J. & Cousins, R. J. Regulation of the zinc transporter ZnT-1 by dietary zinc. Proc Natl Acad Sci 95:4841-4846 (1998)
  3. Boonsiri, P. et al. Serum vitamin A and zinc levels of healthy people in northeast Thailand. Clin Chim Acta 373:132-138 (2006) https://doi.org/10.1016/j.cca.2006.05.020
  4. Liuzzi, J. P., Blanchard, R. K. & Cousins, R. J. Differential regulation of zinc transporter 1, 2, and 4 mRNA expression by dietary zinc in rats. J Nutr 131: 46-52 (2001)
  5. Kaler, P. & Prasad, R. Molecular cloning and functional characterization of novel zinc transporter rZip10 (Slc39a10) involved in zinc uptake across rat renal brush-border membrane. Am J Physiol Renal Physiol 292:F217-229 (2007) https://doi.org/10.1152/ajprenal.00014.2006
  6. Prasad, R., Kumar, V., Kumar, R. & Singh, K. P. Thyroid hormones modulate zinc transport activity of rat intestinal and renal brush-border membrane. Am J Physiol 276:E774-782 (1999)
  7. Taylor, K. M. & Nicholson, R. I. The LZT proteins; the LIV-1 subfamily of zinc transporters. Biochim Biophys Acta 1611:16-30 (2003) https://doi.org/10.1016/S0005-2736(03)00048-8
  8. Cousins, R. J. & McMahon, R. J. Integrative aspects of zinc transporters. J Nutr 130(5S Suppl):1384S-1387S (2000)
  9. Kumar, R. & Prasad, R. Functional characterization of purified zinc transporter from renal brush border membrane of rat. Biochim Biophys Acta 1509:429-439 (2000) https://doi.org/10.1016/S0005-2736(00)00325-4
  10. Krebs, N. E. & Hambidge, K. M. Zinc metabolism and homeostasis: the application of tracer techniques to human zinc physiology. Biometals 14:397-412 (2001) https://doi.org/10.1023/A:1012942409274
  11. Iguchi, K. et al. High-level expression of zinc transporter- 2 in the rat lateral and dorsal prostate. J Androl 23:819-824 (2002)
  12. Kambe, T., Yamaguchi-Iwai, Y., Sasaki, R. & Nagao, M. Overview of mammalian zinc transporters. Cell Mol Life Sci 61:49-68 (2004) https://doi.org/10.1007/s00018-003-3148-y
  13. Cousins, R. J. et al. Regulation of zinc metabolism and genomic outcomes. J Nutr 133:1521S-1526S (2006)
  14. Pawan, K. et al. Upregulation of Slc39a10 gene expression in response to thyroid hormones in intestine and kidney. Biochim Biophys Acta 1769:117-123 (2007) https://doi.org/10.1016/j.bbaexp.2006.12.005
  15. François, Verrey. et al Novel renal amino acid transporters. Annu Rev Physiol 67:557-572 (2005) https://doi.org/10.1146/annurev.physiol.67.031103.153949
  16. Franklin, R. B., Zou, J., Yu, Z. & Costello, L. C. EAAC1 is expressed in rat and human prostate epithelial cells; functions as a high-affinity L-aspartate transporter; and is regulated by prolactin and testosterone. BMC Biochem 27:7-10 (2006)
  17. Ranaldi, G. et al. Intracellular distribution of labile Zn(II) and zinc transporter expression in kidney and MDCK cells. Am J Physiol Renal Physiol 283:F1365-1375 (2002) https://doi.org/10.1152/ajpcell.00121.2002
  18. Palmiter, R. D. Protection against zinc toxicity by metallothionein and zinc transporter 1. Proc Natl Acad Sci 101:4918-4923 (2004)