Activator protein asbestos

Zanella, C.L., Posada, J., Tritton, T.R., and Mossman, B.T., Asbestos causes stimulation of the extfacellular signal-regulated kinase 1 mitogen-activated protein kinase cascade after phosphorylation of the epidermal growth factor receptor. Cancer Res., 56, 5334-5338, 1996. 

Flaherty, D.M., Monick, M.M., Carter, A.B., Peterson, M.W., and Elurminghake, G.W., Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages, J. Immunol, 168, 5675-5681, 2002. 

Hamster tracheal epithelial cells exposed to 5.0 jUg crocidolite asbestos/cm showed increases in p65/50 and p50 protein complexes binding to the NFxB-binding consensus DNA sequence (Janssen et al. 1995, Mossman et al. 1997). When N-acetylcysteine, an agent boosting cellular glutathione levels, was added to cells for 18 h, both crocidolite-induced c-fos and c-jun mRNA levels and activator protein-1 to DNA-binding activity were diminished, suggesting that oxidative stress... 

Mineral fibers, particularly asbestos, can activate protein kinase C and increase expression of ornithine decarboxylase, the proto-oncogenes, c-fos, and c-jun (18-20), and the nuclear transcription factor, NF-kB (21). All these events are associated with cell proliferation and, potentially, with neoplastic transformation. Recently, Zanella et al. (22) have shown that asbestos activates the mitosis-associated kinase (MAP) system, apparently through interaction with the epidermal growth factor receptor, probably implying that some of these events are mediated by signal transduction pathways that start on the cell surface, rather than by fiber uptake, although this point needs to be directly examined. 

A major contribution of the free-radical scavenging activity in blood plasma is attributable to the macro-molecular proteins (Wayner et al., 1985) of which albumin is a primary component and trapping agertt (Holt et al., 1984). Serum sulphydryl levels, primarily albumin-related, are decreased in subjects with rheumatoid complicated coalworkers pneumoconiosis, indicative of exacerbated inflammatory R.OM production (Thomas and Evans, 1975). Experimental asbestos inhalation in rats leads to an adaptive but evidendy insufficient response by an increase in endogenous antioxidant enzymes (Janssen etal., 1990). Protection of the vascular endothelium against iron-mediated ROM generation and injury is afforded by the iron sequestiant protein ferritin (Balia et al., 1992). 

Fung H, Kow YW, Van Houten B, et al. 1998. Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. Cancer Res 58 189-194. 

Janssen YMW, Driscoll KE, Howard B, et al. 1997. Asbestos causes translocation of p65 protein and increase NF-KB DNA binding activity in rat lung epithelial and pleural mesothelial cells. Am J Pathol 151 389-401. 

Perderiset M, Marsh JP, Mossman BT. 1991. Activation of protein kinase C by crocidolite asbestos in hamster tracheal epithelial cells. Carcinogenesis 12 1499-1502. 

Fung, H., Kow, Y.W., Van Elouten, B., Taatjes, D.J., Elatahet, Z., Janssen, Y.M., Vacek, P., Faux, S.P., and Mossman, B.T., Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. Cancer Res., 58,189-194,... 

MCP-1 (53). Electron microscopy studies of human pleural mesothelial cells demonstrated that the cells avidly engulfed asbestos fibers including those of amosite, chrysotile, and crocidolite asbestos (54). When pleural mesothelial cells were exposed to asbestos in the presence of interleukin-la or TNF-a, there was enhancement of IL-8 release. Preincubation of the mesothelial cells with E.-l receptor antagonist protein significantly decreased release of IL-8 after stimulation with amosite or crocidolite asbestos. Asbestos is also associated with a large influx of mononuclear cells into the pleural space. Koenig et al. (53) demonstrated the presence of MCP-1 in supernatants of mesothelial cells that were activated by crocidolite asbestos. 

Mechanisms involving inflammatory cells or their products could also account for the dysfunction of surfactant in acute lung injury. Inhaled particles, such as asbestos and silica, stimulate macrophages to release reactive oxygen metabolites (216,217). Activated neutrophils also release proteolytic enzymes, such as elastase and lysozyme (218,219). Activated polymorphonuclear leukocytes impair surfactant function through a process that involves proteolysis of surfactant proteins (148,220). SP-A also has antioxidant properties of its own (220,221). 

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