Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D01931 (TiO2)
 11,320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asbestos causes asbestosis and malignancies by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) injury by iron-induced reactive oxygen species (ROS) is one important mechanism. To determine whether asbestos causes apoptosis in AECs, we exposed WI-26 (human type I-like cells), A549 (human type II-like cells), and rat alveolar type II cells to amosite asbestos and assessed apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labeling (TUNEL) staining, nuclear morphology, annexin V staining, DNA nucleosome formation, and caspase 3 activation. In contrast to control medium and TiO2, amosite asbestos and H2O2 each caused AEC apoptosis. A role for iron-catalyzed ROS was suggested by the finding that asbestos-induced AEC apoptosis and caspase 3 activation were each attenuated by either an iron chelator (phytic acid and deferoxamine) or a.OH scavenger (dimethyl-thiourea, salicylate, and sodium benzoate) but not by iron-loaded phytic acid. To determine whether asbestos causes apoptosis in vivo, rats received a single intratracheal instillation of amosite (5 mg) or normal saline solution, and apoptosis in epithelial cells in the bronchoalveolar duct regions was assessed by TUNEL staining. One week after exposure, amosite asbestos caused a 3-fold increase in the percentage of apoptotic cells in the bronchoalveolar duct regions as compared with control (control, 2.1% +/- 0.35%; asbestos, 7.61% +/- 0.15%; n = 3). However, by 4 weeks the number of apoptotic cells was similar to control. We conclude that asbestos-induced pulmonary toxicity may partly be caused by apoptosis in the lung epithelium that is mediated by iron-catalyzed ROS and caspase 3 activation.
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PMID:Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals. 1132 27

Asbestos has been implicated in the pathogenesis of interstitial lung diseases including asbestosis. Tissue factor (TF) initiates blood coagulation in vivo contributing to inflammation and tissue remodeling via extravascular fibrin deposition and signaling for profibrogenic mediators. We hypothesized that asbestos could induce TF expression by lung epithelial cells. We found that TF mRNA and TF-dependent procoagulant activity were induced in asbestos-treated Beas-2B human airway epithelial cells, which we used as a model system. The effect was increased by crocidolite and chrysotile versus control particulates, including titanium dioxide (TiO2) and Wollastonite (W). Transcription factors that bind the TF gene promoter, including NF-kappaB, AP1 and Sp1, were induced by asbestos while TF mRNA was unstable. TF mRNA was inhibited by mithramycin in asbestos-treated as well as control cells suggesting that Sp1 contributes to TF maintenance in Beas-2B cells. Sp1 knockdown with specific siRNA decreased TF antigen, which is consistent with Sp1-mediated control of TF in Beas-2B cells. The results demonstrate that asbestos induces TF expression in lung epithelial cells in vitro, representing a newly recognized potential mechanism by which asbestos may modulate epithelial cell responses germane to lung remodeling. The mechanism involves alterations in steady-state TF mRNA that do not involve posttranscriptional regulation, implicating control of TF gene expression at the transcriptional level through Sp1 or other transcription factors.
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PMID:Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro. 1563 97