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

Usamah S. Kayyali, Rohit Budhiraja, Corin M. Pennella, Samantha Cooray, Joe J. Lanzillo, Roger Chalkley, Paul M. Hassoun

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-68
Number of pages10
JournalToxicology and Applied Pharmacology
Volume188
Issue number1
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Keywords

  • Cigarette
  • Lung disease
  • Oxidant
  • Reactive oxygen

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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