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Biological Trace Element Research

, Volume 159, Issue 1–3, pp 425–433 | Cite as

Zinc Chloride Inhibits Human Lens Epithelial Cell Migration and Proliferation Involved in TGF-β1 and TNF-α Signaling Pathways in HLE B-3 Cells

  • Yuxiang Du
  • Dadong Guo
  • Qiuxin Wu
  • Dongmei Liu
  • Hongsheng BiEmail author
Article

Abstract

Zinc is one of the most abundant essential elements in the human body, which is an essential, coenzyme-like component of many enzymes, and is indispensable to their functions. However, high levels of zinc ions can lead to cell damage. In the present study, we explored the effects of high concentrations of zinc chloride (ZnCl2) on lens epithelial cell proliferation and migration and further investigated the effects of different concentrations of ZnCl2 on caspase-9 and caspase-12, transforming growth factor-beta 1 (TGF-β1), and tumor necrosis factor-alpha (TNF-α). We found that ZnCl2 could inhibit human lens epithelial (HLE) B-3 cell migration and induce apoptosis/necrosis. In addition, ZnCl2 can efficiently decrease the expressions of caspase-9 and caspase-12, increase the expression of TNF-α at both gene and protein levels, and thus induces cell death. Taken together, our results indicate that ZnCl2 can inhibit HLE B-3 cell migration and proliferation by decreasing the expression of TGF-β1 and increasing the expression of TNF-α and finally lead to HLE B-3 cell death.

Keywords

Zinc ion Lens epithelial cell Caspase Transforming growth factor Tumor necrosis factor 

Notes

Acknowledgments

This work was supported by the Natural Science Foundation of Shandong province (ZR2010HM032).

Conflict of Interest

The authors declare that they have no competing interests.

References

  1. 1.
    Vallee BL (1988) Zinc: biochemistry, physiology, toxicology and clinical pathology. Biofactors 1:31–36PubMedGoogle Scholar
  2. 2.
    Feng P, Li TL, Guan ZX et al (2002) Direct effect of zinc on mitochondrial apoptogenesis in prostate cells. Prostate 52:311–318PubMedCrossRefGoogle Scholar
  3. 3.
    Morris DR, Levenson CW (2012) Ion channels and zinc: mechanisms of neurotoxicity and neurodegeneration. J Toxicol 2012:785647PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Chang I, Cho N, Koh JY et al (2003) Pyruvate inhibits zinc-mediated pancreatic islet cell death and diabetes. Diabetologia 46:1220–1227PubMedCrossRefGoogle Scholar
  5. 5.
    Strasser A, O’Connor L, Dixit VM (2000) Apoptosis signaling. Annu Rev Biochem 69:217–245PubMedCrossRefGoogle Scholar
  6. 6.
    Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312PubMedCrossRefGoogle Scholar
  7. 7.
    Heyninck K, Beyaert R (2001) Crosstalk between NF-kappaBactivating and apoptosis-inducing proteins of the TNF-receptor complex. Mol Cell Biol Res Commun 4:259–265PubMedCrossRefGoogle Scholar
  8. 8.
    Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371PubMedCrossRefGoogle Scholar
  9. 9.
    Chang KL, Hung TC, Hsieh BS et al (2006) Zinc at pharmacologic concentrations affects cytokine expression and induces apoptosis of human peripheralblood mononuclear cells. Nutrition 22:465–474PubMedCrossRefGoogle Scholar
  10. 10.
    Argun M, Tök L, Uğuz AC et al (2012) Melatonin and amfenac modulate calcium entry, apoptosis, and oxidative stress in ARPE-19 cell culture exposed to blue light irradiation (405 nm). Eye (Lond). doi: 10.1038/eye.2014.50 Google Scholar
  11. 11.
    Nazıroğlu M, Yoldaş N, Uzgur EN et al (2013) Role of contrast media on oxidative stress, Ca(2+) signaling and apoptosis in kidney. J Membr Biol 246:91–100PubMedCrossRefGoogle Scholar
  12. 12.
    Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381–389PubMedCrossRefGoogle Scholar
  13. 13.
    Denault JB, Eckelman BP, Shin H et al (2007) Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated inhibition of caspase 9. Biochem J 405:11–19PubMedCentralPubMedGoogle Scholar
  14. 14.
    Radisky DC, Kenny PA, Bissell MJ (2007) Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 101:830–839PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Kalluri R, Neilson EG (2003) Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 112:1776–1784PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454PubMedCrossRefGoogle Scholar
  17. 17.
    Wormstone IM (2002) Posterior capsule opacification: a cell biological perspective. Exp Eye Res 74:337–347PubMedCrossRefGoogle Scholar
  18. 18.
    Nelson CM, VanDuijn MM, Inman JL et al (2006) Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science 314:298–300PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Taylor MA, Parvani JG, Schiemann WP (2010) The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-β in normal and malignant mammary epithelial cells. J Mammary Gland Biol Neoplasia 15:169–190PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Awasthi N, Guo S, Wagner BJ (2009) Posterior capsular opacification: a problem reduced but not yet eradicated. Arch Ophthalmol 127:555–562PubMedCrossRefGoogle Scholar
  21. 21.
    Liu J, Hales AM, Chamberlain CG et al (1994) Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor /3. Invest Ophthalmol Us Sci 35:388–401Google Scholar
  22. 22.
    Taibi A, Mandavawala KP, Noel J et al (2013) Zebrafish churchill regulates developmental gene expression and cell migration. Dev Dyn 242:614–621PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Grahn BH, Paterson PG, Gottschall-Pass KT et al (2001) Zinc and the eye. J Am Coll Nutr 20:106–118PubMedCrossRefGoogle Scholar
  24. 24.
    Guo DD, Bi HS, Wang DG et al (2013) Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells. Int J Biochem Cell B 45:1849–1859CrossRefGoogle Scholar
  25. 25.
    Jansen S, Arning J, Beyersmann D (2003) Effects of the Ca ionophore a23187 on zinc-induced apoptosis in C6 glioma cells. Biol Trace Elem Res 96:133–142PubMedCrossRefGoogle Scholar
  26. 26.
    Uguz AC, Cig B, Espino J et al (2012) Melatonin potentiates chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor cells. J Pineal Res 53:91–98PubMedCrossRefGoogle Scholar
  27. 27.
    Kim SJ, Eum HA, Billiar TR et al (2013) Role of heme oxygenase 1 in TNF/TNF receptor-mediated apoptosis after hepatic ischemia/reperfusion in rats. Shock 39:380–388PubMedCrossRefGoogle Scholar
  28. 28.
    Truong-Tran AQ, Carter J, Ruffin RE et al (2001) The role of zinc in caspase activation and apoptotic cell death. Biometals 14:315–330PubMedCrossRefGoogle Scholar
  29. 29.
    Maret W, Jacob C, Vallee BL et al (1999) Inhibitory sites in enzymes: zinc removal and reactivation by thionein. Proc Natl Acad Sci USA 96:1936–1940PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Kown MH, Van Der Steenhoven T, Blankenberg FG et al (2000) Zinc-mediated reduction of apoptosis in cardiac allografts. Circulation 102:228–232CrossRefGoogle Scholar
  31. 31.
    Sakurai M, Takahashi G, Abe K et al (2005) Endoplasmic reticulum stress induced in motor neurons by transient spinal cord ischemia in rabbits. J Thorac Cardiovasc Surg 130:640–645PubMedCrossRefGoogle Scholar
  32. 32.
    Palsamy P, Bidasee KR, Shinohara T (2014) Valproic acid suppresses Nrf2/Keap1 dependent antioxidant protection through induction of endoplasmic reticulum stress and Keap1 promoter DNA demethylation in human lens epithelial cells. Exp Eye Res 121C:26–34CrossRefGoogle Scholar
  33. 33.
    Bian Q, Fernandes AF, Taylor A et al (2008) Expression of K6W-ubiquitin in lens epithelial cells leads to upregulation of a broad spectrum of molecular chaperones. Mol Vis 14:403–412PubMedCentralPubMedGoogle Scholar
  34. 34.
    Huber KL, Hardy JA (2012) Mechanism of zinc-mediated inhibition of caspase-9. Protein Sci 21:1056–1065PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Rudolf E, Cervinka M (2006) Cytoskeletal changes in non-apoptotic cell death. Acta Medica (Hradec Kralove) 49:123–128Google Scholar
  36. 36.
    Sensi SL, Ton-That D, Sullivan PG et al (2003) Modulation of mitochondrial function by endogenous Zn2+ pools. Proc Natl Acad Sci USA 100:6157–6162PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Kondoh M, Tasaki E, Araragi S et al (2002) Requirement of caspase and p38MAPK activation in zinc-induced apoptosis in human leukemia HL-60 cells. Eur J Biochem 269:6204–6211PubMedCrossRefGoogle Scholar
  38. 38.
    Mann JJ, Fraker PJ (2005) Zinc pyrithione induces apoptosis and increases expression of Bim. Apoptosis 10:369–379PubMedCrossRefGoogle Scholar
  39. 39.
    Wilson MR, Foucaud L, Barlow PG et al (2007) Nanoparticle interactions with zinc and iron: implications for toxicology and inflammation. Toxicol Appl Pharmacol 225:80–89PubMedCrossRefGoogle Scholar
  40. 40.
    Kou X, Jing Y, Deng W et al (2013) Tumor necrosis factor-alpha attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells. BMC Cancer 13:438PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Zhou P, Lu Y, Sun XH (2012) Effects of a novel DNA methyltransferase inhibitor Zebularine on human lens epithelial cells. Mol Vis 18:22–28PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yuxiang Du
    • 1
  • Dadong Guo
    • 2
  • Qiuxin Wu
    • 3
  • Dongmei Liu
    • 2
  • Hongsheng Bi
    • 2
    • 3
    Email author
  1. 1.Shandong University of Traditional Chinese MedicineJinanChina
  2. 2.Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases of Shandong province; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong; Eye Institute of Shandong University of Traditional Chinese MedicineJinanChina
  3. 3.Affiliated Eye Hospital of Shandong University of Traditional Chinese MedicineJinanChina

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