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AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 5 1029-L1035, Copyright © 1997 by American Physiological Society
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L. A. Jimenez, C. Zanella, H. Fung, Y. M. Janssen, P. Vacek, C. Charland, J. Goldberg and B. T. Mossman
Department of Pathology, College of Medicine, University of Vermont, Burlington 05405, USA.
Stimulation of cell signaling cascades by oxidants may be important in the pathogenesis of pulmonary and pleural diseases. Here, we demonstrate in rat pleural mesothelial cells that apoptotic concentrations of crocidolite asbestos and H2O2 induce phosphorylation and activation of extracellular signal-regulated protein kinases (ERK). Activation of c-jun-NH2-terminal protein kinases (JNK)/stress-activated protein kinases was also observed in response to H2O2. In contrast, asbestos caused more protracted activation of ERK without JNK activation. Both H2O2- and asbestos-induced activation of ERK was abolished by catalase. Moreover, chelation of surface iron from crocidolite fibers or addition of N-acetyl-L-cysteine prevented ERK activation and apoptosis by crocidolite, indicating an oxidative mechanism of cell signaling. The MEK1 inhibitor PD-98059 abrogated asbestos-induced apoptosis, confirming a causal relationship between ERK activation and apoptosis. These results suggest that distinct cell-signaling cascades may be important in phenotypic responses elicited by oxidant stresses.
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D. Upadhyay, V. Panduri, and D. W. Kamp Fibroblast Growth Factor-10 Prevents Asbestos-Induced Alveolar Epithelial Cell Apoptosis by a Mitogen-Activated Protein Kinase-Dependent Mechanism Am. J. Respir. Cell Mol. Biol., March 1, 2005; 32(3): 232 - 238. [Abstract] [Full Text] [PDF]
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W. A. Swain, K. J. O'Byrne, and S. P. Faux Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stress Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L859 - L865. [Abstract] [Full Text] [PDF]
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 D. Upadhyay and D. W. Kamp Asbestos-Induced Pulmonary Toxicity: Role of DNA Damage and Apoptosis Experimental Biology and Medicine, June 1, 2003; 228(6): 650 - 659. [Abstract] [Full Text] [PDF]
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S. P. M. Reddy and B. T. Mossman Role and regulation of activator protein-1 in toxicant-induced responses of the lung Am J Physiol Lung Cell Mol Physiol, December 1, 2002; 283(6): L1161 - L1178. [Abstract] [Full Text] [PDF]
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K. M. Lounsbury, M. Stern, D. Taatjes, S. Jaken, and B. T. Mossman Increased Localization and Substrate Activation of Protein Kinase C{delta} in Lung Epithelial Cells following Exposure to Asbestos Am. J. Pathol., June 1, 2002; 160(6): 1991 - 2000. [Abstract] [Full Text] [PDF]
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S. Buder-Hoffmann, C. Palmer, P. Vacek, D. Taatjes, and B. Mossman 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., April 1, 2001; 24(4): 405 - 413. [Abstract] [Full Text]
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A. Shukla, C. R. Timblin, A. K. Hubbard, J. Bravman, and B. T. Mossman Silica-induced Activation of c-Jun-NH2-Terminal Amino Kinases, Protracted Expression of the Activator Protein-1 Proto-Oncogene, fra-1, and S-Phase Alterations Are Mediated via Oxidative Stress Cancer Res., March 1, 2001; 61(5): 1791 - 1795. [Abstract] [Full Text]
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A. Shukla, C. Timblin, K. BeruBe, T. Gordon, W. McKinney, K. Driscoll, P. Vacek, and B. T. Mossman Inhaled Particulate Matter Causes Expression of Nuclear Factor (NF)-kappa B-Related Genes and Oxidant-Dependent NF-kappa B Activation In Vitro Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 182 - 187. [Abstract] [Full Text]
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