Ambient particulate matter induces alveolar epithelial cell cycle arrest: role of G1 cyclins |
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| Authors: | Zhang Jingmei Ghio Andrew J Gao Mingxing Wei Ke Rosen Glenn D Upadhyay Daya |
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| Affiliation: | Department of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA. |
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| 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. |
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| Keywords: | AEC, alveolar epithelial cells CDK, cyclin-dependent kinases PM, particulate matter ROS, reactive oxygen species |
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