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. 1997 Sep;105(Suppl 5):1121–1125. doi: 10.1289/ehp.97105s51121

Cell signaling pathways elicited by asbestos.

B T Mossman 1, S Faux 1, Y Janssen 1, L A Jimenez 1, C Timblin 1, C Zanella 1, J Goldberg 1, E Walsh 1, A Barchowsky 1, K Driscoll 1
PMCID: PMC1470124  PMID: 9400710

Abstract

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angel P., Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. doi: 10.1016/0304-419x(91)90011-9. [DOI] [PubMed] [Google Scholar]
  2. Barchowsky A., Dudek E. J., Treadwell M. D., Wetterhahn K. E. Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells. Free Radic Biol Med. 1996;21(6):783–790. doi: 10.1016/0891-5849(96)00174-8. [DOI] [PubMed] [Google Scholar]
  3. BéruBé K. A., Quinlan T. R., Fung H., Magae J., Vacek P., Taatjes D. J., Mossman B. T. Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos. Am J Respir Cell Mol Biol. 1996 Jul;15(1):141–147. doi: 10.1165/ajrcmb.15.1.8679218. [DOI] [PubMed] [Google Scholar]
  4. BéruBé K. A., Quinlan T. R., Moulton G., Hemenway D., O'Shaughnessy P., Vacek P., Mossman B. T. Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos. Toxicol Appl Pharmacol. 1996 Mar;137(1):67–74. doi: 10.1006/taap.1996.0058. [DOI] [PubMed] [Google Scholar]
  5. Chao C. C., Park S. H., Aust A. E. Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells. Arch Biochem Biophys. 1996 Feb 1;326(1):152–157. doi: 10.1006/abbi.1996.0059. [DOI] [PubMed] [Google Scholar]
  6. Chen Q., Marsh J., Ames B., Mossman B. Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos. Carcinogenesis. 1996 Nov;17(11):2525–2527. doi: 10.1093/carcin/17.11.2525. [DOI] [PubMed] [Google Scholar]
  7. Driscoll K. E., Carter J. M., Iype P. T., Kumari H. L., Crosby L. L., Aardema M. J., Isfort R. J., Cody D., Chestnut M. H., Burns J. L. Establishment of immortalized alveolar type II epithelial cell lines from adult rats. In Vitro Cell Dev Biol Anim. 1995 Jul-Aug;31(7):516–527. doi: 10.1007/BF02634029. [DOI] [PubMed] [Google Scholar]
  8. Dérijard B., Hibi M., Wu I. H., Barrett T., Su B., Deng T., Karin M., Davis R. J. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994 Mar 25;76(6):1025–1037. doi: 10.1016/0092-8674(94)90380-8. [DOI] [PubMed] [Google Scholar]
  9. Grune T., Siems W. G., Zollner H., Esterbauer H. Metabolism of 4-hydroxynonenal, a cytotoxic lipid peroxidation product, in Ehrlich mouse ascites cells at different proliferation stages. Cancer Res. 1994 Oct 1;54(19):5231–5235. [PubMed] [Google Scholar]
  10. Guyton K. Z., Liu Y., Gorospe M., Xu Q., Holbrook N. J. Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem. 1996 Feb 23;271(8):4138–4142. doi: 10.1074/jbc.271.8.4138. [DOI] [PubMed] [Google Scholar]
  11. Heintz N. H., Janssen Y. M., Mossman B. T. Persistent induction of c-fos and c-jun expression by asbestos. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3299–3303. doi: 10.1073/pnas.90.8.3299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hesterberg T. W., Barrett J. C. Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis. Carcinogenesis. 1985 Mar;6(3):473–475. doi: 10.1093/carcin/6.3.473. [DOI] [PubMed] [Google Scholar]
  13. Hibi M., Lin A., Smeal T., Minden A., Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993 Nov;7(11):2135–2148. doi: 10.1101/gad.7.11.2135. [DOI] [PubMed] [Google Scholar]
  14. Huang R. P., Wu J. X., Fan Y., Adamson E. D. UV activates growth factor receptors via reactive oxygen intermediates. J Cell Biol. 1996 Apr;133(1):211–220. doi: 10.1083/jcb.133.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Janssen Y. M., Barchowsky A., Treadwell M., Driscoll K. E., Mossman B. T. Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8458–8462. doi: 10.1073/pnas.92.18.8458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Janssen Y. M., Heintz N. H., Marsh J. P., Borm P. J., Mossman B. T. Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers. Am J Respir Cell Mol Biol. 1994 Nov;11(5):522–530. doi: 10.1165/ajrcmb.11.5.7946382. [DOI] [PubMed] [Google Scholar]
  17. Janssen Y. M., Heintz N. H., Mossman B. T. Induction of c-fos and c-jun proto-oncogene expression by asbestos is ameliorated by N-acetyl-L-cysteine in mesothelial cells. Cancer Res. 1995 May 15;55(10):2085–2089. [PubMed] [Google Scholar]
  18. Kim G., Yurkow E. J. Chromium induces a persistent activation of mitogen-activated protein kinases by a redox-sensitive mechanism in H4 rat hepatoma cells. Cancer Res. 1996 May 1;56(9):2045–2051. [PubMed] [Google Scholar]
  19. Kyriakis J. M., Banerjee P., Nikolakaki E., Dai T., Rubie E. A., Ahmad M. F., Avruch J., Woodgett J. R. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994 May 12;369(6476):156–160. doi: 10.1038/369156a0. [DOI] [PubMed] [Google Scholar]
  20. Liu Y., Guyton K. Z., Gorospe M., Xu Q., Lee J. C., Holbrook N. J. Differential activation of ERK, JNK/SAPK and P38/CSBP/RK map kinase family members during the cellular response to arsenite. Free Radic Biol Med. 1996;21(6):771–781. doi: 10.1016/0891-5849(96)00176-1. [DOI] [PubMed] [Google Scholar]
  21. Luo W., Sharif T. R., Sharif M. Substance P-induced mitogenesis in human astrocytoma cells correlates with activation of the mitogen-activated protein kinase signaling pathway. Cancer Res. 1996 Nov 1;56(21):4983–4991. [PubMed] [Google Scholar]
  22. Marsh J. P., Mossman B. T. Mechanisms of induction of ornithine decarboxylase activity in tracheal epithelial cells by asbestiform minerals. Cancer Res. 1988 Feb 1;48(3):709–714. [PubMed] [Google Scholar]
  23. Mossman B. T., Bignon J., Corn M., Seaton A., Gee J. B. Asbestos: scientific developments and implications for public policy. Science. 1990 Jan 19;247(4940):294–301. doi: 10.1126/science.2153315. [DOI] [PubMed] [Google Scholar]
  24. Mossman B. T. Carcinogenesis and related cell and tissue responses to asbestos: a review. Ann Occup Hyg. 1994 Aug;38(4):617-24, 423. doi: 10.1093/annhyg/38.4.617. [DOI] [PubMed] [Google Scholar]
  25. Mossman B. T., Gee J. B. Asbestos-related diseases. N Engl J Med. 1989 Jun 29;320(26):1721–1730. doi: 10.1056/NEJM198906293202604. [DOI] [PubMed] [Google Scholar]
  26. Mossman B. T., Kamp D. W., Weitzman S. A. Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. Cancer Invest. 1996;14(5):466–480. doi: 10.3109/07357909609018904. [DOI] [PubMed] [Google Scholar]
  27. Ng L., Forrest D., Curran T. Differential roles for Fos and Jun in DNA-binding: redox-dependent and independent functions. Nucleic Acids Res. 1993 Dec 25;21(25):5831–5837. doi: 10.1093/nar/21.25.5831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pandey S., Wang E. Cells en route to apoptosis are characterized by the upregulation of c-fos, c-myc, c-jun, cdc2, and RB phosphorylation, resembling events of early cell-cycle traverse. J Cell Biochem. 1995 Jun;58(2):135–150. doi: 10.1002/jcb.240580203. [DOI] [PubMed] [Google Scholar]
  29. Staal F. J., Anderson M. T., Staal G. E., Herzenberg L. A., Gitler C., Herzenberg L. A. Redox regulation of signal transduction: tyrosine phosphorylation and calcium influx. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3619–3622. doi: 10.1073/pnas.91.9.3619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Takeuchi T., Morimoto K. Crocidolite asbestos increased 8-hydroxydeoxyguanosine levels in cellular DNA of a human promyelocytic leukemia cell line, HL60. Carcinogenesis. 1994 Apr;15(4):635–639. doi: 10.1093/carcin/15.4.635. [DOI] [PubMed] [Google Scholar]
  31. Thanos D., Maniatis T. NF-kappa B: a lesson in family values. Cell. 1995 Feb 24;80(4):529–532. doi: 10.1016/0092-8674(95)90506-5. [DOI] [PubMed] [Google Scholar]
  32. Timblin C. R., Janssen Y. W., Mossman B. T. Transcriptional activation of the proto-oncogene c-jun by asbestos and H2O2 is directly related to increased proliferation and transformation of tracheal epithelial cells. Cancer Res. 1995 Jul 1;55(13):2723–2726. [PubMed] [Google Scholar]
  33. Vallyathan V., Shi X. L., Dalal N. S., Irr W., Castranova V. Generation of free radicals from freshly fractured silica dust. Potential role in acute silica-induced lung injury. Am Rev Respir Dis. 1988 Nov;138(5):1213–1219. doi: 10.1164/ajrccm/138.5.1213. [DOI] [PubMed] [Google Scholar]
  34. Whitmarsh A. J., Shore P., Sharrocks A. D., Davis R. J. Integration of MAP kinase signal transduction pathways at the serum response element. Science. 1995 Jul 21;269(5222):403–407. doi: 10.1126/science.7618106. [DOI] [PubMed] [Google Scholar]
  35. Xia Z., Dickens M., Raingeaud J., Davis R. J., Greenberg M. E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995 Nov 24;270(5240):1326–1331. doi: 10.1126/science.270.5240.1326. [DOI] [PubMed] [Google Scholar]
  36. Zanella C. L., Posada J., Tritton T. R., Mossman B. T. Asbestos causes stimulation of the extracellular signal-regulated kinase 1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res. 1996 Dec 1;56(23):5334–5338. [PubMed] [Google Scholar]

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