Skip to main content
SpringerLink
Log in

Involvement of hydrogen peroxide in asbestos-induced NFAT activation

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by asbestos in mouse embryo fibroblast PW cells. Exposure of cells to asbestos led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of asbestos-induced H2O2 with N-acety-L-cyteine (NAC, a general antioxidant) or catalase (a specific H2O2 inhibitor) resulted in inhibition of NFAT activation. In contrast, an increase in H2O2 generation by the addition of superoxide dismutase (SOD) slightly enhanced asbestos-induced NFAT activation. In addition, pretreatment of cells with sodium formate did not exhibit any inhibition of NFAT activity induced by asbestos. These results demonstrated that H2O2 appeared to play an important role in asbestos-induced NFAT transactivation. Furthermore, it was observed that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) not only resulted in NFAT activation by itself, but also enhanced asbestos-induced NFAT induction. Pretreatment of cells with cyclosporin A (CSA), a pharmacological inhibitor of the phosphatase calcineurin, blocked both asbestos- and TPA plus asbestos-induced NFAT activation. These data suggest that asbestos is able to induce NFAT activation through H2O2-dependent and CSA-sensitive pathways, which may be involved in asbestos-induced carcinogenesis.

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. Mossman BT, Bignon J, Corn M, Seaton A, Gee JB: Asbestos: Scientific developments and implications for public policy. Science 247: 294–301, 1990

    PubMed  Google Scholar 

  2. Mossman BT, Kamp DW, Weitzman SA: Mechanisms of carcinogenesis and clinical features of asbestos-associated careers. Cancer Invest 14: 464–478, 1996

    Google Scholar 

  3. Rom WN, Travis WD, Brody AR: Cellular and molecular basis of asbestos-related diseases. Am Rev Resp Dis 143: 408–422, 1991

    PubMed  Google Scholar 

  4. Kamp DW, Weizman SA: Asbestosis: Clinical spectrum and pathogenic mechanisms. Proc Soc Exp Biol Med 214: 12–226, 1997

    PubMed  Google Scholar 

  5. Kamp DW, Graceffa P, Pryor WA, Weitzman SA: The role of free radicals in asbestos-related diseases. Free Rad Biol Med 157: 1666–1680, 1992

    Google Scholar 

  6. Vallyathan V, Shi X: The role of oxygen free radicals in occupational and environmental lung diseases. Environ Health Perspect 105(suppl 1): 165–177, 1997

    PubMed  Google Scholar 

  7. Janssen YM, Barchowsky A, Treadwell M, Driscoll KE, Mossman BT: Asbestos induces nuclear factor NF-κB DNA binding activity and NF-κB dependent gene expression in tracheal epithelial cells. Proc Natl Acad Sci USA 92: 8458–8462, 1995

    PubMed  Google Scholar 

  8. Ding M, Dong Z, Chen F, Pack D, Ma WY, Ye J, Shi X, Castranova V, Vallyathan V: Asbestos induces activator AP-1 trancactivation in transgenic mice. Cancer Res 59: 1884–1889, 1999

    PubMed  Google Scholar 

  9. Brody AR, Liu JY, Brass D, Corti M: Analyzing the genes and peptide growth factors expressed in lung cells in vivo consequent to asbestos exposure and in vitro. Environ Health Perspect 105(suppl 5): 1165–1171, 1997

    PubMed  Google Scholar 

  10. Mossman BT, Faux S, Janssen Y, Jimenez LA, Timblin C, Zanella C, Goldberg J, Walsh E, Barchowsky A, Driscoll K: Cell signaling pathways elicited by asbestos. Environ Health Perspect 105(suppl 5): 1121–1125, 1997

    PubMed  Google Scholar 

  11. Fung H, Quinlan TR, Janssen YM, Timblin CR, Marsh JP, Heintz NH, Taatjes DJ, Vacek P, Jaken S, Mossman BT: Inhibition of protein kinase C prevents asbestos-induced c-fos abd c-jun proto-oncogenes expression in mesothelial cells. Cancer Res 57: 3101–3105, 1997

    PubMed  Google Scholar 

  12. Durand DB, Shaw JP, Bush MR, Replogle RE, Belageje R, Crabtree GR: Characterization of antigen receptor response elements within the interleukin-2 enhancer. Mol Cell Biol 8: 1715–1724, 1988

    PubMed  Google Scholar 

  13. Serfling E, Bsrthelmäs R, Pfeuffer I, Schenk B, Zarius S, Swoboda R, Mercurio F, Karin M: Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes. EMBO J 8: 465–473, 1989

    PubMed  Google Scholar 

  14. Shaw JP, Utz PJ, Durand DB, Toole JJ, Emmel EA, Crabtree GR: Identification of a putative regulator of early T cell activation genes. Science 241: 202–205, 1988

    PubMed  Google Scholar 

  15. Rincon M, Flavell RA: Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells Mol Cell Biol 17: 1522–1534, 1997

    PubMed  Google Scholar 

  16. Rao A, Luo C, Hogan PC: Transcription factors of the NFAT family: Regulation and function. Annu Rev Immunol 15: 707–747, 1997

    Article  PubMed  Google Scholar 

  17. Clipstone NA, Crabtree GR: Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 357: 695–697, 1992

    Article  PubMed  Google Scholar 

  18. Emmel EA, Verweij CL, Durand DB, Higgins KM, Lacy E, Crabtree GR: Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science 246: 1617–1620, 1989

    PubMed  Google Scholar 

  19. Flanagan WF, Corthesy B, Bram RJ, Crabtree GR: Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature 352: 803–807, 1991

    PubMed  Google Scholar 

  20. Jain J, McCaffrey PG, Miner A, Kerppola TK, Lambert JN, Verdine GL, Curram T, Rao A: The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 365: 352–355, 1993

    Article  PubMed  Google Scholar 

  21. O'Keefe SJ, Tamura J, Kincaid RL, Toci MJ, O'Neill EA: FK-506-and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature 357: 692–694, 1992

    PubMed  Google Scholar 

  22. Mattila PS, Ullman KS, Fiering S, Emmel EA, McCutcheon M, Crabtree GR, Herzenberg LA: The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes. EMBO J 9: 4425–4433, 1990

    PubMed  Google Scholar 

  23. Crabtree GR, Clipstone NA: Signal transmission between the plasma membrane and nucleus of T lymphocytes. Annu Rev Biochem 63: 1045–1083, 1994

    Article  PubMed  Google Scholar 

  24. Jain J, Loh C, Rao, A: Transcriptional regulation of the IL-2 gene. Curr Opin Immunol 7: 333–342, 1995

    PubMed  Google Scholar 

  25. Serfling E, Avots A, Neumann M: The architecture of the interleukin-2 promoter: A reflection of T lymphocyte activation. Biochem Biophys Acta 1263: 181–200, 1995

    PubMed  Google Scholar 

  26. McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM, Burgeon E, Lane WS, Lambert JN, Curran T, Verdine GL, Rao A, Hoga PG: Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 262: 750–754, 1993

    PubMed  Google Scholar 

  27. Luo C, Burgeon E, Carew JA, Badalian TM, McCaffrey PG, Lane WS, Hogan PG, Rao A: Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes. Mol Cell Biol 16: 3955–3966, 1996

    PubMed  Google Scholar 

  28. Hoey T, Sun YL, Williamson K, Xu X: Isolation of two new members of the NF-AT gene family and functional characterization of the NFAT proteins. Immunity 2: 461–472, 1995

    Article  PubMed  Google Scholar 

  29. Masuda E, Naito Y, Tokummitsu H, Campbell D, Saito F, Hannum C, Arai KI, Arai N: NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. Mol Cell Biol 15: 2697–2706, 1995

    PubMed  Google Scholar 

  30. Ho SN, Thomas DJ, Timmerman LA, Li X, Francke U, Crabtree GR: NFATc3, a lymphoid-specific NFATc family member that is calciumregulated and exhibits distinct DNA binding specificity. J Biol Chem 270: 19898–19907, 1995

    Article  PubMed  Google Scholar 

  31. Park J, Takeuchi A, Sharma S: Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc. J Biol Chem 34: 29014–29021, 1996

    Google Scholar 

  32. Masuda ES, Imamura R, Amasaki Y, Arai K, Arai N: Signaling into the T-cell nucleus: NFAT regulation. Cell Sig 10: 599–611, 1998

    Article  Google Scholar 

  33. Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR: NF-AT components define a family of transcription factors targeted in T-cell activation. Nature 369: 497–502, 1994

    PubMed  Google Scholar 

  34. Huang C, Mattjus P, Ma WY, Rincon M, Chen NY, Brown RE, Dong Z: Involvement of nuclear factor of activated T cells activation in UV response. Evidence from cell culture and transgenic mice. J Biol Chem 275: 9143–9149, 2000

    Article  PubMed  Google Scholar 

  35. Singh RK, Gutman M, Reich R, Bar-Eli M: Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8. Cancer Res 55: 3669–3674, 1995

    PubMed  Google Scholar 

  36. Jiang H, Yamamoto S, Nishikawa K, Kato R: Anti-tumor-promoting action of FK506, a potent immunosuppressive agent. Carcinogenesis 14: 67–71, 1993

    PubMed  Google Scholar 

  37. Huang C, Ding M, Li J, Leonard SS, Rojanasakul Y, Castranova V, Vallyathan V, Ju G, Shi X: Vanadium-induced nuclear factor of activated T cells activation through hydrogen peroxide. J Biol Chem 276: 22397–22403, 2001

    PubMed  Google Scholar 

  38. Huang C, Ma WY, Dawson MI, Rincon M, Flavell RA, Dong Z: Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci USA 94: 5826–5830, 1997

    PubMed  Google Scholar 

  39. Hardy JA, Aust AE: Iron in asbestos chemistry and carcinogenicity. Chem Rev 95: 97–118, 1995

    Article  Google Scholar 

  40. Vallyathan V, Mega JF, Shi X, Dalal NS: Enhanced generation of free radicals from phagocytes induced by mineral dusts. Am J Resp Cell Mol Biol 6: 404–413, 1992

    Google Scholar 

  41. Churg A: The uptake of mineral particles by pulmonary epithelial cells. Am J Resp Crit Care Med 154: 1124–1140, 1996

    PubMed  Google Scholar 

  42. Mossman BT, Churg A: Mechanisms of the pathogenesis of asbestos and silicosis. Am J Respir Crit Care Med 157: 1666–1680, 1998

    PubMed  Google Scholar 

  43. Bradley MO, Erikson LC: Comparison of effects of hydrogen peroxide and x-ray irradiation on toxicity, mutation and DNA damage/repair in mammalian cells. Biochem Biophys Acta 654: 125–141, 1981

    Google Scholar 

  44. Broaddus VC, Yang L, Scavo LM, Ernst JD, Boylan AM: Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species. J Clin Invest 98: 2050–2059, 1996

    PubMed  Google Scholar 

  45. Leevers SJ, Marshall CJ: Activation of extracellular signal regulated kinase, ERK2 by p21 ras oncoprotein. EMBO 11: 569–574, 1992

    Google Scholar 

  46. Cerutti P, Shah G, Peskin A, Amstad P: Oxidant carcinogenesis and antioxidant defense. Ann NY Acad Sci 663: 158–166, 1992

    PubMed  Google Scholar 

  47. Fernando M, Cristina LR, Anjana R: Partners in transcription: NFAT and AP-1. Oncogene 20: 2476–2489, 2001

    PubMed  Google Scholar 

  48. Jain JP, McCaffrey PG, Valge-Archer VE, Rao A: Nuclear factor of activated T cells contains Fos and Jun. Nature 356: 801–804, 1992

    PubMed  Google Scholar 

  49. Shibasaki F, Price ER, Milan D, McKeon F: Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4 Nature 382: 370–373, 1996

    PubMed  Google Scholar 

  50. Chow CW, Rincon M, Cavanaugh J, Dickens M, Davis RJ: Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. Science 278: 1638–1641, 1997

    PubMed  Google Scholar 

  51. Tsatsanis C, Patriotis C, Tsichlis PN: Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-kappaB. Oncogene 17: 2609–2618, 1998

    PubMed  Google Scholar 

  52. Zamzami N, Marchetti P, Castedo M, Hirsch T, Susin SA, Masse B, Kroemer G: Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. FEBS Lett 384: 53–57, 1996

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY, 10987, USA

    Jingxia Li, Bihui Huang & Chuanshu Huang

  2. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA

    Xianglin Shi, Vincent Castranova & Val Vallyathan

Authors
  1. Jingxia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bihui Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xianglin Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vincent Castranova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Val Vallyathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chuanshu Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, J., Huang, B., Shi, X. et al. Involvement of hydrogen peroxide in asbestos-induced NFAT activation. Mol Cell Biochem 234, 161–168 (2002). https://doi.org/10.1023/A:1015962916195

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015962916195

Search

Navigation