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ToxSci Advance Access published online on September 11, 2003

Toxicological Sciences, doi:10.1093/toxsci/kfg221
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received June 6, 2003; accepted August 11, 2003
© 2003 Society of Toxicology

Environmental Toxicology

Gaseous Nitrogen Oxides Stimulate Cell Cycle Progression by Rb Phosphorylation via Activation of Cyclins/Cdks

Jing-Hsien Chen 1, Tsui-Hwa Tseng 2, Yung-Chyan Ho 2, Hui-Hsuan Lin 1, Wea-Lung Lin 3, and Chau-Jong Wang 1*

1 Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan
2 Department of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan
3 Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan

* To whom correspondence should be addressed. E-mail: wcj{at}csmu.edu.tw.


   Abstract

Nitrogen oxides (NOx) are important indoor and outdoor air pollutants. Many studies have indicated that NOx gas causes lung tissue damage by its oxidation properties and its free-radicals. In a previous study we demonstrated that NOx gas induced proliferation of human lung fibroblast MRC-5 cells. In this study we show that NOx gas stimulates MRC-5 cell proliferation by Rb phosphorylation via activation of cyclin-cdk complexes. Western blot and immunoprecipitation data showed that NOx gas increased the expressions of cyclinA/cdk2, cyclinD1/cdk4 and cyclinE/cdk2 complexes in the cells 9 h after treatment. The levels of phospho-Rb were also increased and cdk inhibitors (CKIs) p27 and p16 were apparently decreased. These data suggested that NOx gas stimulates cell cycle progression by Rb phosphorylation via activation of cyclin-cdk complexes and inhibition of CKIs. In conclusion, the NOx gas induced lung fibroblast cell proliferation by stimulation of cell cycle progression may contribute to lung fibrosis by NOx pollutants.

Key Words: Gaseous nitrogen oxides, proliferation, cdk inhibitor(CKI), Rb phosphorylation, cell cycle progression .


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J.-H. Chen, H.-H. Lin, T.-A. Chiang, J.-D. Hsu, H.-H. Ho, Y.-C. Lee, and C.-J. Wang
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[Abstract] [Full Text] [PDF]



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