Skip to main content
SpringerLink
Log in

Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

To clarify the effect of a phytochemical, methyl gallate (MG) on a heavy metal (cadmium)-induced renal toxicity, cytotoxicity and the change of heme oxygenase-1 (HO-1) gene expression was studied using cultured mouse renal glomerular mesangial cells (MMC). By employing RT-PCR and Western blotting analysis, we have examined the HO-1 induction in MMCs that were treated with Cd2+ and/or MG. Using MTT assay we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of Cd2+. In MMCs exposed to Cd2+ and MG, expression of HO-1 (mRNA and protein) was increased in a concentration- and time-dependent manner. The increments of HO-1 mRNA and protein expressions by Cd2+ and MG were inhibited by the treatment of the cells with actinomycin D, an inhibitor of transcription. The decreased viability of the cells by Cd2+ was partially recovered by the treatment of MG and this recovery by the MG was reduced by the treatment of zinc protoporphyrin IX (a HO-1 inhibitor). From these results, methyl gallate might have cytoprotective effect on Cd2+-induced cytotoxicity that is related with heme oxygenase-1 induction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jarup, L. Hazards of heavy metal contamination. Br Med Bull 68:167–182 (2003).

    Article  PubMed  Google Scholar 

  2. Sethi, P. K. & Khandelwal, D. Cadmium exposure: health hazards of silver cottage industry in developing countries. J Med Toxicol 2:14–15 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Singh, B. R. & McLaughlin M. J. Cadmium in soils and plants. In: Developments in Plant and Soil Sciences, edited by McLaughlin MJ and Singh BR. Dordrecht, The Netherlands: Kluwer, 257–268 (1999).

    Google Scholar 

  4. Nomiyama, K. & Nomiyama, H. Cadmium-induced renal dysfunction: new mechanism, treatment and prevention. J Trace Elem Exper Med 11:275–288 (1998).

    Article  CAS  Google Scholar 

  5. Tsukahara, T. et al. Rice as the most influential source of cadmium intake among general Japanese population. Sci Total Environ 305:41–51 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Goering, P. L., Waalkes, M. P. & Klaassen, C. D. Toxicology of cadmium, Toxicology of metals. In Handbook of experimental pharmacology, pp. 189–214. Berlin: Springer-Verlag (1996).

    Google Scholar 

  7. Templeton, D. M. & Chaitu, N. Effects of divalent metals on the isolated rat glomerulus. Toxicology 61:119–133 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Dorian, C., Gattone II, V. H. & Klaasen, C. D. Renal cadmium deposition and injury as a result of accumulation of cadmium-metallothionein (CdMT) by the proximal convoluted tubules — a light microscopic autoradiography study with 109CdMT. Toxicol Appl Pharmacol 114:173–181 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Schöcklmann, H. O., Lang, S. & Sterzel, R. B. Regulation of mesangial cell proliferation. Kidney Int 56:1199–1207 (1999).

    Article  PubMed  Google Scholar 

  10. Liu, Y. & Templeton, D. M. Cadmium activates CaMK-II and initiates CaMK-II dependent apoptosis in mesangial cells. FEBS Lett 581:1481–1486 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Apostolova, M. D., Christova, T. & Templeton, D. M. Involvement of gelsolin in cadmium-induced disruption of the mesangial cell cytoskeleton. Toxicol Sci 89:465–474 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Nogué, S., Sanz-Gallén, P., Torras, A. & Boluda F. Chronic overexposure to cadmium fumes associated with IgA mesangial glomerulonephritis. Occup Med (Lond) 54:265–267 (2004).

    Google Scholar 

  13. Badisa, V. L. et al. Cytotoxicity and stress gene microarray analysis in cadmium-exposed CRL-1439 normal rat liver cells. Int J Mol Med 22:213–219 (2008).

    CAS  PubMed  Google Scholar 

  14. Kusakabe, T. et al. Changes of heavy metal, metallothionein and heat shock proteins in Sertoli cells induced by cadmium exposure. Toxicol In Vitro 22:1469–1475 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. Tenhuen, R., Marver, H. S. & Schmid, R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 68:748–755 (1968).

    Article  Google Scholar 

  16. Ottterbein, L. O. & Choi, A. M. K. Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol 279:L1029–L1037 (2000).

    Google Scholar 

  17. Srisook, K. et al. Heme oxygenase-1-mediated partial cytoprotective effect by NO on cadmium-induced cytotoxicity in C6 rat glioma cells. Toxicol In Vitro 19:31–39 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Sue, Y. M. et al. Antioxidation and anti-inflammation by haem oxygenase-1 contribute to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells. Nephrol Dial Transplant 24:769–777 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Wang, D., Zhong, X. P., Qiao, Z. X. & Gui, J. F. Inductive transcription and protective role of fish heme oxygenase-1 under hypoxic stress. J Exp Biol 211:2700–2706 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Yu, J. B. & Yao, S. L. Protective effects of hemin pretreatment combined with ulinastatin on septic shock in rats. Chin Med J (Engl) 121:49–55 (2008).

    Google Scholar 

  21. Hassoun, E. A. & Stohs, S. Cadmium-induced production of superoxide anion and nitric oxide, DNA single strand breaks and lactate dehydrogenase leakage in J774.1 cell cultures. Toxicology 112:219–226 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Hwang, D. F. & Wang, L. C. Effect of taurine on toxicity of cadmium in rats. Toxicology 167:173–180 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Nigam, D., Shukla, G. S. & Agarwal, A. K. Glutathione depletion and oxidative damage in mitochondria following exposure to cadmium in rat liver and kidney. Toxicology Letters 106:151–157 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Robinson, M. K., Barfuss, D. W. & Zalups, R. K. Cadmium transport and toxicity in isolated perfused segments of the renal proximal tubule. Toxicol Appl Pharmacol 121:103–111 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Thijssen, S., Maringwa, J., Faes, C., Lambrichts, I. & Van Kerkhove, E. Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels. Toxicology 229:145–156 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Kozyraki, R. et al. Megalindependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc Natl Acad Sci USA 98:12491–12496 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Wang, S. H., Shih, Y. L., Ko, W. C., Wei, Y. H. & Shih C. M. Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway. Cell Mol Life Sci 65:3640–3652 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Yang, L. Y., Wu, K. H., Chiu, W. T., Wang, S. H. & Shih, C. M. The cadmium-induced death of mesangial cells results in nephrotoxicity. Autophagy 5:571–572 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Hartsfield, C. L., Alam, J. & Choi, A. M. K. Transcriptional regulation of the heme oxygenase 1 gene by pyrrolidone dithiocarbamate. FASEB Journal 12:1675–1682 (1998).

    CAS  PubMed  Google Scholar 

  30. Zhang, W. L., Tsuneishi, S. & Nakamura, H. Induction of heat shock proteins and its effects on glial differentiation in rat C6 glioblastoma cells. Kobe Journal of Medical Science 47:77–95 (2001).

    CAS  Google Scholar 

  31. Bagchi, D., Bagchi, M., Tang, L. & Stohs, S. J. Comparative in vitro and in vivo protein kinase C activation by selected pesticides and transition metal salts. Toxicology Letters 91:31–37 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Huang, H. C., Nguyen, T. & Pickett, C. B. Regulation of the antioxidant response element by protein kinase-C mediated phosphorylation of NF-E2-related factor 2. Proceedings of the National Academy of Sciences of the United States of America 97:12475–12480 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. He, C. H. et al. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein: implication for heme oxygenase-1 gene regulation. J Biol Chem 276:20858–20865 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Choi, B. M. et al. Piperine protects cisplatin-induced apoptosis via heme oxygenase-1 induction in auditory cells. J Nutr Biochem 18:615–622 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Lee, H. J. et al. Rosmarinic acid protects human dopaminergic neuronal cells against hydrogen peroxideinduced apoptosis. Toxicology 250:109–115 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Yang, C., Zhang, X., Fan, H. & Liu, Y. Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 1282:133–141 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Cho, E. J. et al. Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1,1-diphenyl-2-picrylhydrazyl radical. Phytomedicine 10:544–551 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Hsieh, T. et al. Protective effect of methyl gallate from Toona sinensis (Meliaceae) against hydrogen peroxideinduced oxidative stress and DNA damage in MDCK cells. Food Chem Toxicol 42:843–850 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Lim, M. Y., Park, Y. H., Son, D. J., Kim, M. K. & Lee, H. S. Antiplatelet activity of gallic acid and methyl gallate. Food Sci Biot 13:806–809 (2004).

    CAS  Google Scholar 

  40. Cho, E. J., Yokozawa, T., Kim, H. Y., Shibahara, N. & Park, J. C. Rosa rugosa attenuates diabetic oxidative stress in rats with streptozotocin-induced diabetes. Am J Chinese Med 32:487–496 (2004).

    Article  Google Scholar 

  41. Kang, M. S., Oh, J. S., Kang, I. C., Hong, S. J. & Choi, C. H. Inhibitory effect of methyl gallate and gallic acid on oral bacteria. J Microbiol 46:744–750 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Stocker, R., Yamamoto, Y., Mcdonagh, A. F., Glazer, A. N. & Ames, B. N. Biliribin is an antioxidant of possible physiological importance. Science 235:1043–1046 (1987).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Biotechnology, College of Medicine, Inha University, Incheon, 400-712, Korea

    Seok Ho Cha

  2. Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, 400-712, Korea

    Chang Kook Suh

  3. Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University, Incheon, 400-712, Korea

    Seok Ho Cha & Chang Kook Suh

Authors
  1. Seok Ho Cha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chang Kook Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chang Kook Suh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cha, S.H., Suh, C.K. Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells. Mol. Cell. Toxicol. 6, 127–133 (2010). https://doi.org/10.1007/s13273-010-0019-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-010-0019-0

Keywords

Search

Navigation