Proteomic analysis of brain proteins of rats exposed to high fluoride and low iodine

Abstract

Epidemiological investigations reveal that high fluoride and low iodine have strong adverse effects on the intelligence quotient (IQ) of children. Studies also report that in some high fluoride areas, iodine deficiency also exists, especially in China. Here, with the proteomic techniques, we first report on the proteomic changes in brain proteins in offspring rats at postnatal day 20 exposed to high fluoride and/or low iodine. To investigate molecular mechanisms of central neural system injury induced by the above two elements, proteins were isolated and profiled by two-dimensional gel electrophoresis (2DE). By the analysis of Image-Master 2D Elite software, 71 protein spots in 2DE gels of treatment groups were gained and up- or down-regulated by two folds, and 5 proteins were regulated by five folds, with the comparison to the control group. The proteins changed by five folds were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The identified proteins are mainly related with cellular signaling, energy metabolism, and protein metabolism and provide a valuable clue to explore the mechanism underlining the neurotoxicity of high fluoride and low iodine. Moreover, these results could provide potential biomarkers for hazards caused by excessive fluoride and low iodine.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Baumann EJ, Metzger N (1949) Behavior of the thyroid towards elements of the seventh periodic group. Proc Soc Exp Biol Med 70:536–540

    CAS  PubMed  Google Scholar 

  2. Bhatnagar M, Rao P, Saxena A, Bhatnagar R, Meena P, Barbar S, Chouhan A, Vimal S (2006) Biochemical changes in brain and other tissues of young adult female mice from fluoride in their drinking water. Fluoride 39:280–284

    CAS  Google Scholar 

  3. Chapman ER (2002) Synaptotagmin: a Ca (2+) sensor that triggers exocytosis? Nat Rev Mol Cell Biol 3:498–508

    CAS  Article  PubMed  Google Scholar 

  4. Chapman ER (2008) How does synaptotagmin trigger neurotransmitter release? Annu Rev Biochem 77:615–641

    CAS  Article  PubMed  Google Scholar 

  5. Chen J, Chen XM, Yang KD, Xia T, Xie H (2002) Studies on DNA damage and apoptosis in rat brain induced by fluoride. Chin J Prev Med 36:222–224 (in Chinese)

    CAS  Google Scholar 

  6. Chirumari K, Reddy PK (2007) Dose-dependent effects of fluoride on neurochemical milieu in the hippocampus and neocortex of rat brain. Fluoride 40:101–110

    CAS  Google Scholar 

  7. Dong J, Yin HB, Liu WY (2005) Congenital iodine deficiency and hypothyroidism impair LTP and decrease c-fos and c-jun expression in rat hippocampus. Neurotoxicology 26:417–426

    CAS  Article  PubMed  Google Scholar 

  8. Doull J, Boekelheide K, Farishian BG, Isaacson RL, Klotz JB, Kumar JV, Limeback H, Poole C, Puzas JE, Reed N-MR et al (2006) Fluoride in drinking water: a scientific review of EPA’s standards. National Academies, Washington, pp 205–223

    Google Scholar 

  9. Firth JD, Ebert BL, Ratcliffe PJ (1995) Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem 270:21021–21027

    CAS  Article  PubMed  Google Scholar 

  10. Ge YM, Ning HM, Wang SL, Wang JD (2005a) Comet assay of DNA damage in brain cells of adult rats exposed to high fluoride and low iodine. Fluoride 38:209–214

    CAS  Google Scholar 

  11. Ge YM, Ning HM, Wang SL, Wang JD (2005b) DNA damage in thyroid gland cells of rats exposed to long-term intake of high fluoride and low iodine. Fluoride 38:318–323

    CAS  Google Scholar 

  12. Ge YM, Ning HM, Feng CP, Wang HW, Yan XY, Wang SL, Wang JD (2006) Apoptosis in brain cells of offspring rats exposed to high fluoride and low iodine. Fluoride 39:173–178

    CAS  Google Scholar 

  13. Goodsell DS (2003) The molecular perspective: ubiquitin and the proteosome. Stem Cells 21:509–510

    CAS  Article  PubMed  Google Scholar 

  14. Harris NO, Hayes RL (1955) A tracer study of the effect of acute and chronic exposure to sodium fluoride on the thyroid iodine metabolism of rats. J Dent Res 34:470–477

    CAS  Article  PubMed  Google Scholar 

  15. Hoff H, Zhang H, Sell C (2004) Protein degradation via the proteosome. Methods Mol Biol 285:79–92

    CAS  PubMed  Google Scholar 

  16. Koh TW, Bellen HJ (2003) Synaptotagmin I, a Ca2+ sensor for neurotransmitter release. Trends Neurosci 26:413–422

    CAS  Article  PubMed  Google Scholar 

  17. Kuo WL, Duke CJ, Abe MK, Kaplan EL, Gomes S, Rosner MR (2004) ERK7 expression and kinase activity is regulated by the ubiquitin-proteosome pathway. J Biol Chem 279:23073–23081

    CAS  Article  PubMed  Google Scholar 

  18. Lin FF, Aihaiti ZHX, Lin J, Jiang JY, Ma L, Maimaiti Aiken, Geng B (1991) High fluoride and low iodine environment and subclinical cretinism in Xinjiang. Endem Dis Bull 6:62–68 (in Chinese)

    Google Scholar 

  19. Maas RP, Patch SC, Christian AM, Coplan MJ (2007) Effects of fluoridation and disinfection agent combinations on lead leaching from leaded-brass parts. Neurotoxicology 28:1023–1031

    CAS  Article  PubMed  Google Scholar 

  20. McLaren JR (1976) Possible effects of fluorides on the thyroid. Fluoride 9:105–116

    CAS  Google Scholar 

  21. Refsnes M, Schwarze PE, Holme JA, Låg M (2003) Fluoride-induced apoptosis in human epithelial lung cells (A549 cells): role of different G protein-linked signal systems. Hum Exp Toxicol 22:111–123

    CAS  Article  PubMed  Google Scholar 

  22. Robishaw JD, Berlot CH (2004) Translating G protein subunit diversity into functional specificity. Curr Opin Cell Biol 16:206–209

    CAS  Article  PubMed  Google Scholar 

  23. Rocha-Amador D, Navarro ME, Carrizales L, Morales R, Calderón J (2007) Decreased intelligence in children and exposure to fluoride and arsenic in drinking water. Cad Saude Publica 23(Suppl 4):S579–S587

    PubMed  Google Scholar 

  24. Rosenbaum DM, Rasmussen SG, Kobilka BK (2009) The structure and function of G-protein-coupled receptors. Nature 459:356–363

    CAS  Article  PubMed  Google Scholar 

  25. Semenza GL (2007) Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405:1–9

    CAS  PubMed  Google Scholar 

  26. Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, Giallongo A (1996) Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271:32529–32537

    CAS  Article  PubMed  Google Scholar 

  27. Sesikeran B, Rao SH, Krishnamurti D, Reddy DR (1994) Studies on sural nerve biopsies in endemic skeletal fluorosis. Fluoride 27:189–193

    Google Scholar 

  28. Shashi A (1988) Biochemical effects of fluoride on thyroid gland during experimental fluorosis. Fluoride 21:127–130

    CAS  Google Scholar 

  29. Thrane EV, Refsnes M, Thoresen GH, Låg M, Schwarze PE (2001) Fluoride-induced apoptosis in epithelial lung cells involves activation of MAP kinases p38 and possibly JNK. Toxicol Sci 61:83–91

    CAS  Article  PubMed  Google Scholar 

  30. Tokuoka H, Goda Y (2003) Synaptotagmin in Ca2+ -dependent exocytosis: dynamic action in a flash. Neuron 38:521–524

    CAS  Article  PubMed  Google Scholar 

  31. Trabelsi M, Guermazi F, Zeghal N (2001) Effect of fluoride on thyroid function and cerebellar development in mice. Fluoride 34:165–173

    CAS  Google Scholar 

  32. Trivedi MH, Verma RJ, Chinoy NJ, Patel RS, Sathawara NG (2007) Effect of high fluoride water on intelligence of school children in India. Fluoride 40:178–183

    Google Scholar 

  33. Wang JP, Li J, Aihaiti LinQ, Yang Y, Zhang L, Wang SL (1997) Investigation and analysis of fluorosis and IDD co-existing in areas of Xinjiang. Endem Dis Bull 12:57–59 (in Chinese)

    Google Scholar 

  34. Wang JD, Ge YM, Ning HM, Wang SL (2004a) Effect of high fluoride and low iodine on oxidative stress and antioxidant defense of the brain in offspring rats. Fluoride 37:264–270

    CAS  Google Scholar 

  35. Wang JD, Ge YM, Ning HM, Wang SL (2004b) Effects of high fluoride and low iodine on biochemical indexes of the brain and learning-memory of offspring rats. Fluoride 37:201–208

    CAS  Google Scholar 

  36. Wang SX, Wang ZH, Cheng XT, Li J, Sang ZP, Zhang XD, Han LL, Qiao XY, Wu ZW, Wang ZQ (2007) Arsenic and fluoride exposure in drinking water: children’s IQ and growth in Shanyin county, Shanxi province, China. Environ Health Perspect 115:643–647

    CAS  Article  PubMed  Google Scholar 

  37. Wang Y, Hou Y, Dong J, Xu H, Gong J, Chen J (2010) Developmental iodine deficiency and hypothyroidism reduce phosphorylation of calcium/calmodulin-dependent kinase II in the rat entorhinal cortex. Biol Trace Elem Res doi:10.1007/s12011-009-8591-7

  38. Wilkie TM, Yokoyama S (1994) Evolution of the G protein alpha subunit multigene family. Soc Gen Physiol Ser 49:249–270

    CAS  PubMed  Google Scholar 

  39. Wong LJ, O’Brien WE (1995) Characterization of the cDNA and the gene encoding murine adenylosuccinate lyase. Genomics 28:341–343

    CAS  Article  PubMed  Google Scholar 

  40. Wu CX, Gu XL, Ge YM, Zhang JH, Wang JD (2006) Effects of high fluoride and arsenic on brain biochemical indexes and learning-memory in rats. Fluoride 39:274–279

    CAS  Google Scholar 

Download references

Acknowledgments

This research was sponsored by the China National Natural Science Foundation (Grant No. 30871899 and 30671545), the Program for Ministry of Agriculture (Grant No. 2009-Z47), the Shanxi Province Science and Technology Bureau Program (Grant No. 20090311036), and the Shanxi Province Natural Science Foundation (Grant No. 2009021035-1).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jundong Wang.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ge, Y., Niu, R., Zhang, J. et al. Proteomic analysis of brain proteins of rats exposed to high fluoride and low iodine. Arch Toxicol 85, 27–33 (2011). https://doi.org/10.1007/s00204-010-0537-5

Download citation

Keywords

  • Brain protein
  • Fluoride
  • Iodine deficiency
  • Two-dimensional electrophoresis
  • Mass spectrometry
  • Proteomic