Upregulation of xanthine oxidase by tobacco smoke condensate in pulmonary endothelial cells

Tobacco smoking has been causally linked to the development of chronic obstructive pulmonary disease. It has been reported that the reactive oxygen species (ROS)- generating enzyme xanthine dehydrogenase/oxidase (XO) is increased in smoking-related stomach ulcers and that gastric mucosal damage caus...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2003-04, Vol.188 (1), p.59-68
Main Authors: Kayyali, Usamah S, Budhiraja, Rohit, Pennella, Corin M, Cooray, Samantha, Lanzillo, Joe J, Chalkley, Roger, Hassoun, Paul M
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Hypoxia - drug effects
Cells, Cultured
Cigarette
Endothelium, Vascular - cytology
Endothelium, Vascular - enzymology
Enzyme Activation
Gene Expression Regulation, Enzymologic - drug effects
Lung - drug effects
Lung - enzymology
Lung disease
Medical sciences
Oxidant
Phosphorylation - drug effects
Promoter Regions, Genetic - genetics
Rats
Reactive oxygen
RNA, Messenger - analysis
Smoke - analysis
Time Factors
Tobacco Products
Tobacco, tobacco smoking
Toxicology
Up-Regulation
Xanthine Oxidase - biosynthesis
Xanthine Oxidase - drug effects
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Summary:Tobacco smoking has been causally linked to the development of chronic obstructive pulmonary disease. It has been reported that the reactive oxygen species (ROS)- generating enzyme xanthine dehydrogenase/oxidase (XO) is increased in smoking-related stomach ulcers and that gastric mucosal damage caused by tobacco smoke can be blocked by the XO inhibitor allopurinol. In order to test the hypothesis that tobacco may cause the upregulation of XO in the lung, cultured rat pulmonary microvascular endothelial cells were exposed to tobacco smoke condensate (TSC). TSC at a concentration of 20 μg/mL significantly upregulated XO activity after 24 h of exposure. Longer exposure (1 week) to a lower concentration of TSC (2 μg/mL) also caused an increase in XO activity. Unlike hypoxia, TSC treatment did not alter the phosphorylation of XO. However, TSC treatment increased XO mRNA expression and the XO gene promoter activity. Furthermore, actinomycin D blocked the activation of XO by TSC. In conclusion, our results indicate that tobacco smoke condensate causes upregulation of XO transcription and activity.
ISSN:0041-008X
1096-0333
DOI:10.1016/S0041-008X(02)00076-5