Effects of cigarette smoke on the activation of oxidative stress-related transcription factors in female A/J mouse lung

Job C. Tharappel, Jill Cholewa, Parvaneh Espandiari, Brett T. Spear, C. Gary Gairola, Howard P. Glauert

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Cigarette smoke contains a high concentration of free radicals and induces oxidative stress in the lung and other tissues. Several transcription factors are known to be activated by oxidative stress, including nuclear factor-B (NF-κB), activator protein-1 (AP-1), and hypoxia-inducible factor (HIF). Studies were therefore undertaken to examine whether cigarette smoke could activate these transcription factors, as well as other transcription factors that may be important in lung carcinogenesis. Female A/J mice were exposed to cigarette smoke for 2, 5, 10, 15, 20, 42, or 56 d (6 hr/d, 5 d/wk). Cigarette smoke did not increase NF-κB activation at any of these times, but NF-κB DNA binding activity was lower after 15 d and 56 d of smoke exposure. The DNA binding activity of AP-1 was lower after 10 d and 56 d but was not changed after 42 d of smoke exposure. The DNA binding activity of HIF was quantitatively increased after 42 d of smoke exposure but decreased after 56 d. Whether the activation of other transcription factors in the lung could be altered after exposure to cigarette smoke was subsequently examined. The DNA binding activities of FoxF2, myc-CF1, RORE, and p53 were examined after 10 d of smoke exposure. The DNA binding activities of FoxF2 and p53 were quantitatively increased, but those of myc-CF1 and RORE were unaffected. These studies show that cigarette smoke exposure leads to quantitative increases in DNA binding activities of FoxF2 and p53, while the activations of NF-κB, AP-1, and HIF are largely unaffected or reduced.

Original languageEnglish
Pages (from-to)1288-1297
Number of pages10
JournalJournal of Toxicology and Environmental Health - Part A: Current Issues
Volume73
Issue number19
DOIs
StatePublished - 2010

Bibliographical note

Funding Information:
Received 18 Decembver 2009; accepted 9 March 2010. These studies were supported by the Kentucky Lung Cancer Research Program. Jill Cholewa was supported by a training grant from the National Institutes of Health (DK07778). Address correspondence to Howard P. Glauert, PhD, Graduate Center for Nutritional Sciences, University of Kentucky, 222 Funkhouser Building, Lexington, KY 40506-0054, USA. E-mail: hglauert@uky.edu

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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