Effects of cigarette smoke on the activation of oxidative stress-related transcription factors in female A/J mouse lung.
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-kappaB (NF-kappaB), 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-kappaB activation at any of these times, but NF-kappaB 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-kappaB, AP-1, and HIF are largely unaffected or reduced.
Tharappel
Job C
JC
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40506-0054, USA.
Cholewa
Jill
J
Espandiari
Parvaneh
P
Spear
Brett T
BT
Gairola
C Gary
CG
Glauert
Howard P
HP
D000818:Animals; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D016328:NF-kappa B / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000235:genetics*; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis
D051793:Hypoxia-Inducible Factor 1; D016328:NF-kappa B; D014028:Tobacco Smoke Pollution; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA