Asbestos-induced activation of cell signaling pathways in human bronchial epithelial cells.
Using respiratory epithelial cells transfected with either superoxide dismutase (SOD) or catalase, the authors tested the hypothesis that the activation of the epidermal growth factor (EGF) receptor signal pathway after asbestos exposure involves an oxidative stress. Western blotting using phospho-specific antibodies demonstrated that the EGF receptor kinase inhibitor PD153035 decreased both the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and its upstream signal pathway, including mitogen-activate protein kinase/ERK kinase (MEK)1/2. Similarly, the MEK1/2 kinase inhibitor PD98059 also demonstrated the ability to decrease phosphorylation of ERK1/2. Crocidolite-induced phosphorylation of EGF receptor, ERK1/2, and MEK1/2 was reduced by transfection of BEAS-2B cells with a catalase vector, supporting a participation of oxidative stress in this pathway. These results show that crocidolite can activate the phosphorylation of EGF receptor and its downstream cell signal pathway in BEAS-2B cells and this is associated with the oxidative stress presented by the fibers.
Wang
Xinchao
X
National Health Effects and Environmental Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Samet
James M
JM
Ghio
Andrew J
AJ
D017638:Asbestos, Crocidolite / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D002274:Carcinogens, Environmental; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011799:Quinazolines; D017638:Asbestos, Crocidolite; D002374:Catalase; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline