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Role of mitogen-activated protein kinases (MAPK) in cell injury and proliferation by environmental particulates

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Abstract

Cell signaling pathways may be initiated by environmental particulates by indirect mechanisms such as elaboration of reactive oxygen or nitrogen species (ROS/RNS) or directly upon contact of particulates with the plasma membrane and uptake by epithelial or mesothelial cells. Research in the last few years has mainly addressed cell signaling cascades leading to activation of the redox-sensitive transcription factors, nuclear factor kappa-B (NF-κB), and activator protein-1 (AP-1). The activation of these transcription factors may be linked to increases in gene expression controlling cell injury or apoptosis, proliferation and /or cell survival, and inflammatory cytokines. Here, we provide an overview of the MAPK signaling pathways and their activation by asbestos, specifically the role of ROS, receptor-dependent and independent activation via the epidermal growth factor receptor (EGFR), and strategies for proving causal relationships between these pathways and changes in epithelial cell phenotype linked to disease causation.

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References

  1. Shi X, Ding M, Yucesoy B, Mossman B, Vallyathan V: Diseases caused by silica: Mechanisms of injury and disease development. Int Immunopharmacol, 2002 (in press)

  2. Manning C, Vallyathan V, Mossman B: Diseases caused by asbestos: Mechanisms of injury and disease development. Int Immunopharmacology, 2002 (in press)

  3. Schaeffer H, MJ W: Mitogen-activated protein kinases: Specific messages from ubiquitous messengers. Mol Cell Biol 19: 2435–2444, 1999

    PubMed  Google Scholar 

  4. Rincon M, Flavell R, Davis R: The JNK and p38 MAP kinase signaling pathways in T-cell mediated immune responses. Free Radic Biol Med 28: 1328–1337, 2000

    PubMed  Google Scholar 

  5. Zanella C, Posada J, Tritton T, Mossman B: Asbestos causes stimulation of the ERK-1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res 56: 5334–5338, 1996

    PubMed  Google Scholar 

  6. Jimenez L, Zanella C, Fung H, Janssen Y, Vacek P, Charland C, Goldberg J, Mossman B: Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2. Am J Physiol (Lung Cell Mol Physiol) 273: L1029–L1035, 1997

    Google Scholar 

  7. Robledo R, Buder-Hoffmann S, Cummins A, Walsh E, Taatjes D, Mossman B: Increased phosphorylated ERK immunoreactivity associated with proliferative and morphologic lung alterations following chrysotile asbestos inhalation in mice. Am J Pathol 156: 1307–1316, 2000

    PubMed  Google Scholar 

  8. Abe M, Kuo W-L, MB H, Rosner M: Extracellular signal-regulated kinase 7 (ERK7), a novel ERK with a c-terminal domain that regulates its activity, its cellular location, and cell growth. Mol Cell Biol 19: 1301–1312, 1999

    PubMed  Google Scholar 

  9. Gille H, Sharrocks A, Shaw P: Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at cfos promoter. Nature 358: 414–417, 1992

    PubMed  Google Scholar 

  10. Marais R, Wynne J, Treisman R: The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell 73: 381–393, 1993

    Article  PubMed  Google Scholar 

  11. Kyriakis J, Banerjee P, Nikolakaki E, Dai T, Rubie E, Ahmad M, Avruch J, Woodgett J: The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369: 156–160, 1994

    Article  PubMed  Google Scholar 

  12. Derijard B, Hibi M, Wu I, Barrett T, Su B, Deng T, Karin M, Davis R: JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76: 1025–1037, 1994

    Article  PubMed  Google Scholar 

  13. Gupta S, Barrett T, Whitmarsh A, Cavanagh J, Sluss H, Derijard B, Davis R: Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15: 2760–2770, 1996

    PubMed  Google Scholar 

  14. Whitmarsh A, Davis R: Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 74: 589–607, 1996

    Article  PubMed  Google Scholar 

  15. Yang D, Kuan C, Whitmarsh A, Rincon M, Zheng T, Davis R, Rakic P, Flavell R: Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389: 865–870, 1997a

    Article  PubMed  Google Scholar 

  16. Yang D, Tournier C, Wysk M, Lu H, Xu J, Davis R, Flavell R: Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity. Proc Natl Acad Sci USA 94: 3004–3009, 1997b

    PubMed  Google Scholar 

  17. Ip Y, Davis R: Signal transduction by the c-Jun T-terminal kinase (JNK) - from inflammation to development. Curr Opin Cell Biol 10: 205–219, 1998

    PubMed  Google Scholar 

  18. Han J, Lee J, Bibbs L, Ulevitch R: A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265: 808–811, 1994

    PubMed  Google Scholar 

  19. Fuchs S, Dolan L, Davis R, Ronai Z: Phosphorylation-dependent targeting of c-Jun ubiquitination by Jun N-kinase. Oncogene 13: 1531–1535, 1996

    PubMed  Google Scholar 

  20. Musti A, Treier M, Bohmann D: Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases. Science 275: 400–402, 1997

    PubMed  Google Scholar 

  21. Cowley S, Paterson H, Kemp P, Marshall C: Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 77: 841–852, 1994

    PubMed  Google Scholar 

  22. Mansour S, Matten W, Hermann A, Candia J, Rong S, Fukasawa K, Vande Woude G, Ahn N: Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 265: 966–970, 1994

    PubMed  Google Scholar 

  23. Watts R, Huang C, Young M, Li J, Dong Z, Pennie W, Colburn N: Expression of dominant negative ERK2 inhibits AP-1 transactivation and neoplastic transformation. Oncogene 17: 3493–3498, 1998

    Article  PubMed  Google Scholar 

  24. Huang C, Ma W, Dong Z: The extracellular signal-regulated protein kinases (ERKs) are required for UV-induced AP-1 activation in JB6 cells. Oncogene 18: 2828–2835, 1999

    PubMed  Google Scholar 

  25. Bennett A, Tonks N: Regulation of distinct stages of skeletal muscle differentiation by mitogen-activated protein kinases. Science 278: 1288–1291, 1997

    PubMed  Google Scholar 

  26. Whalen A, Galasinski S, Shapiro P, Nahreini T, Ahn N: Megakaryocytic differentiation induced by constitutive activation of mitogenactivated protein kinase kinase. Mol Cell Biol 17: 1947–1958, 1997

    PubMed  Google Scholar 

  27. Chin B, Choi M, Burdick M, Strieter R, Risby T, Choi A: Induction of apoptosis by particulate matter: role of TNF-α and MAPK. Am J Physiol (Lung Cell Mol Physiol) 275: L942–L949, 1998

    Google Scholar 

  28. Bhat N, Zhang P: Hydrogen peroxide activation of multiple mitogenactivated protein kinases in an oligodendrocyte cell line: Role of extracellular signal-regulated kinase in hydrogen peroxide-induced cell death. J Neurochem 72: 112–119, 1999

    Article  PubMed  Google Scholar 

  29. Zanella C, Timblin C, Cummins A, Jung M, Goldberg J, Raabe R, Tritton T, Mossman B: Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos expression and apoptosis. Am J Physiol (Lung Cell Mol Physiol) 277: L684–L693, 1999

    Google Scholar 

  30. Sebolt-Leopold J, Dudley D, Herrera R, Van Becelaere K, Wiland A, Gowan R, Tecle H, Barrett S, Bridges A, Przybranowski S, Leopold W, Saltiel A: Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nature Med 5: 810–816, 1999

    Article  PubMed  Google Scholar 

  31. Xia Z, Dickens M, Raingeaud J, Davis R, Greenberg M: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326–1331, 1995

    PubMed  Google Scholar 

  32. Karin M, Liu Z, Zandi E: AP-1 function and regulation. Curr Opin Cell Biol 9: 240–246, 1997

    Article  PubMed  Google Scholar 

  33. Smeal T, Hibi M, Karin M: Altering the specificity of signal transduction cascades: positive regulation of c-Jun transcriptional activity by protein kinase A. EMBO J 13: 6006–6010, 1994

    PubMed  Google Scholar 

  34. Janknecht R, Cahill M, Nordheim A: Signal integration at the c-fos promoter. Carcinogenesis 16: 443–450, 1995

    PubMed  Google Scholar 

  35. Whitmarsh A, Yang S-H, Su M, Sharrocks A, Davis R: Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors. Mol Cell Biol 17: 2360–2371, 1997

    PubMed  Google Scholar 

  36. Karin M: The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270: 16483–16486, 1995

    PubMed  Google Scholar 

  37. Bergers G, Graninger P, Braselmann S, Wrighton C, Busslinger M: Transcriptional activation of the fra-1 gene by AP-1 is mediated by regulatory sequences in the first intron. Mol Cell Biol 15: 3748–3758, 1995

    PubMed  Google Scholar 

  38. Cohen D, Ferreira P, Gentz R, Franza BJ, Curran T: The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: Transciption factor AP-1 is comprised of multiple protein complexes. Genes Dev 3: 173–184, 1989

    PubMed  Google Scholar 

  39. Vallone D, Battista S, Pierantoni G, Fedele M, Casalino L, Santoro M, Viglietto G, Fusco A, Verde P: Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product. EMBO J 16: 5310–5321, 1997

    Article  PubMed  Google Scholar 

  40. Gruda M, Kovary K, Metz R, Bravo R: Regulation of Fra-1 and Fra-2 phosphorylation differs during the cell cycle of fibroblasts and phosphorylation in vitro by MAP kinase affects DNA binding activity. Oncogene 9: 2537–2547, 1994

    PubMed  Google Scholar 

  41. Berube K, Quinlan T, Fung H, Magae J, Vacek P, Taatjes D, Mossman B: Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos. Am J Respir Cell Mol Biol 15: 141–147, 1996

    PubMed  Google Scholar 

  42. Goldberg J, Zanella C, Janssen Y, Timblin C, Jimenez L, Vacek P, Taatjes D, Mossman B: Novel cell imaging approaches show induction of apoptosis and proliferation in mesothelial cells by asbestos. Am J Respir Cell Mol Biol 17: 265–271, 1997

    PubMed  Google Scholar 

  43. Pache J, Janssen Y, Walsh E, Quinlan T, Zanella C, Low R, Taatjes D, Mossman B: Increased epidermal growth factor-receptor (EGF-R) protein in a human mesothelial cell line in response to long asbestos fibers. Am J Pathol 152: 333–340, 1998

    PubMed  Google Scholar 

  44. Buder-Hoffmann S, Palmer C, Vacek P, Taatjes D, Mossman B: Different accumulation of activated extracellular signal-regulated kinases (ERK 1/2) and role in cell-cycle alterations by epidermal growth factor, hydrogen peroxide, or asbestos in pulmonary epithelial cells. Am J Respir Cell Mol Biol 24: 405–413, 2001

    PubMed  Google Scholar 

  45. Malkinson A, Dwyer-Nield L, Rice P, Dinsdale D: Mouse lung epithelial cell lines - tools for the study of differentiation and the neoplastic phenotype. Toxicology 123: 53–100, 1997

    PubMed  Google Scholar 

  46. Janssen Y, Barchowsky A, Treadwell M, Driscoll K, Mossman B: Asbestos induces nuclear factor κB (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 

  47. Janssen Y, Driscoll K, Howard B, Quinlan T, Treadwell M, Barchowsky A, Mossman B: Asbestos causes translocation of p65 protein and increases NF-κB DNA binding activity in rat lung epithelial and pleural mesothelial cells. Am J Pathol 151: 389–401, 1997

    PubMed  Google Scholar 

  48. Laveck M, Somers A, Moore L, Gerwin B, Lechner J: Dissimilar peptide growth factors can induce normal human mesothelial cell multiplication. In Vitro Cell Dev Biol 24: 1077–1084, 1988

    PubMed  Google Scholar 

  49. Mossman B, Gruenert D: SV40, growth factors, and mesothelioma - another piece of the puzzle. Am J Respir Cell Mol Biol 26: 167–170, 2002

    PubMed  Google Scholar 

  50. Prenzel N, Fischer O, Streit S, Hart S, Ullrich A: The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Rel Cancer 8: 11–31, 2001

    Article  Google Scholar 

  51. Hubbard A, Timblin C, Shukla A, Rincon M, Mossman B: Activation of NF-κB-dependent gene expression by silica. Am J Physiol (Lung Cell Mol Physiol), 2002 (in press)

  52. Hubbard A, Timblin C, Rincon M, Mossman B: Use of transgenic luciferase reporter mice to determine activation of transcription factors and gene expression of fibrogenic particles. Chest 120: 24S–25S, 2001

    Article  PubMed  Google Scholar 

  53. Taatjes D, Palmer C, Pantano C, Buder-Hoffmann S, Cummins A, Mossman B: Laser-based microscopic approaches: Application to cell signaling in environmental lung disease. Biotechniques 31: 880–894, 2001

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Vermont College of Medicine, Burlington, VT, 05405, USA

    Maria E. Ramos-Nino, Astrid Haegens, Arti Shukla & Brooke T. Mossman

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  1. Maria E. Ramos-Nino
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  2. Astrid Haegens
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  3. Arti Shukla
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  4. Brooke T. Mossman
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Ramos-Nino, M.E., Haegens, A., Shukla, A. et al. Role of mitogen-activated protein kinases (MAPK) in cell injury and proliferation by environmental particulates. Mol Cell Biochem 234, 111–118 (2002). https://doi.org/10.1023/A:1015924413043

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