Ambient particulate matter induces alveolar epithelial cell cycle arrest: role of G1 cyclins.
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.
Zhang
Jingmei
J
Department of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.
Ghio
Andrew J
AJ
Gao
Mingxing
M
Wei
Ke
K
Rosen
Glenn D
GD
Upadhyay
Daya
D
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
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