NF-kappaB inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats.
Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-kappaB) in this process. Exposure of rats to 80 mg/m(3) tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-kappaB activity, noted by suppression of inhibitor of kappaB (IkappaB) kinase (IKK), accumulation of IkappaBalpha, decrease of NF-kappaB DNA binding activity, and downregulation of NF-kappaB-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-kappaB pathway in tobacco smoke-induced apoptosis.
Zhong
Cai-Yun
CY
Center for Health and the Environment, University of California, Davis, CA 95616, USA.
Zhou
Ya Mei
YM
Pinkerton
Kent E
KE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D008168:Lung / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; D007202:Indicators and Reagents; D016328:NF-kappa B; D009687:Nuclear Proteins; D012906:Smoke; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D020169:Caspases