title: Ambient particulate matter induces alveolar epithelial cell cycle arrest: role of G1 cyclins.
abstract: We hypothesized that the ambient air pollution particles (particulate matter; PM) induce cell cycle arrest in alveolar epithelial cells (AEC). Exposure of PM (25microg/cm(2)) to AEC induced cells cycle arrest in G1 phase, inhibited DNA synthesis, blocked cell proliferation and caused decrease in cyclin E, A, D1 and Cyclin E- cyclin-dependent kinase (CDK)-2 kinase activity after 4h. PM induced upregulation of CDK inhibitor, p21 protein and p21 activity in AEC. SiRNAp21 blocked PM-induced downregulation of cyclins and AEC G1 arrest. Accordingly, we provide the evidence that PM induces AEC G1 arrest by altered regulation of G1 cyclins and CDKs.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Zhang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: Mingxing
authors.initials: M
authors.lastname: Gao
authors.forename: Ke
authors.initials: K
authors.lastname: Wei
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Rosen
authors.forename: Daya
authors.initials: D
authors.lastname: Upadhyay
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D052638:Particulate Matter / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000393:Air Pollutants; C534702:CCNG1 protein, human; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D052638:Particulate Matter; D034741:RNA, Small Interfering; D018844:Cyclin-Dependent Kinases