title: Gaseous nitrogen oxides stimulate cell cycle progression by retinoblastoma phosphorylation via activation of cyclins/Cdks [correction].
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 retinoblastoma (Rb) phosphorylation via activation of cyclin-cell division protein kinase (cdk) complexes [correction]. Western blot and immunoprecipitation data showed that NOx gas increased the expressions of cyclinA/cdk2, cyclinD1/cdk4, and cyclinE/cdk2 complexes in the cells at 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 that induced lung fibroblast cell proliferation by stimulation of cell-cycle progression may contribute to lung fibrosis by NOx pollutants.
authors.affiliation: Institute of Biochemistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Jing-Hsien
authors.initials: JH
authors.lastname: Chen
authors.forename: Tsui-Hwa
authors.initials: TH
authors.lastname: Tseng
authors.forename: Yung-Chyan
authors.initials: YC
authors.lastname: Ho
authors.forename: Hui-Hsuan
authors.initials: HH
authors.lastname: Lin
authors.forename: Wea-Lung
authors.initials: WL
authors.lastname: Lin
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D005740:Gases / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000166:cytology; D009589:Nitrogen Oxides / Q000633:toxicity*; D010766:Phosphorylation; D012413:Rubidium / Q000494:pharmacology
chemical_list: D016213:Cyclins; D005740:Gases; D009589:Nitrogen Oxides; D018844:Cyclin-Dependent Kinases; D012413:Rubidium