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 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 microg/mL significantly upregulated XO activity after 24 h of exposure. Longer exposure (1 week) to a lower concentration of TSC (2 microg/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.
Kayyali
Usamah S
US
Pulmonary and Critical Care Division, Tupper Research Institute, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. ukayyali@tufts-nemc.org
Budhiraja
Rohit
R
Pennella
Corin M
CM
Cooray
Samantha
S
Lanzillo
Joe J
JJ
Chalkley
Roger
R
Hassoun
Paul M
PM
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012906:Smoke / Q000032:analysis; D013997:Time Factors; D015854:Up-Regulation; D014969:Xanthine Oxidase / Q000096:biosynthesis* / Q000187:drug effects; D014026:Nicotiana
D012333:RNA, Messenger; D012906:Smoke; D014969:Xanthine Oxidase