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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Air Pollutants / toxicity
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Cell Cycle / drug effects*
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Cell Line
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Cyclin G
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Cyclin G1
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Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cyclin-Dependent Kinases / metabolism
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Cyclins / metabolism*
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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G1 Phase / drug effects
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Humans
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Particulate Matter / toxicity*
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Pulmonary Alveoli / cytology*
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Pulmonary Alveoli / drug effects*
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Pulmonary Alveoli / metabolism
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RNA, Small Interfering / genetics
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Signal Transduction / drug effects
Substances
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Air Pollutants
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CCNG1 protein, human
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Cyclin G
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Cyclin G1
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Particulate Matter
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RNA, Small Interfering
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Cyclin-Dependent Kinases