Zhang Jingmei, Ghio Andrew J, Gao Mingxing, Wei Ke, Rosen Glenn D, Upadhyay Daya
Department of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.
FEBS Lett. 2007 Nov 13;581(27):5315-20. doi: 10.1016/j.febslet.2007.10.020. Epub 2007 Oct 23.
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.
我们假设环境空气污染颗粒(颗粒物;PM)可诱导肺泡上皮细胞(AEC)的细胞周期停滞。将PM(25μg/cm²)暴露于AEC后,4小时内可诱导细胞周期停滞于G1期,抑制DNA合成,阻断细胞增殖,并导致细胞周期蛋白E、A、D1及细胞周期蛋白E-细胞周期蛋白依赖性激酶(CDK)-2激酶活性降低。PM可诱导AEC中CDK抑制剂、p21蛋白及p21活性上调。SiRNAp21可阻断PM诱导的细胞周期蛋白下调及AEC G1期停滞。因此,我们提供了证据表明PM通过改变G1期细胞周期蛋白和CDK的调节来诱导AEC G1期停滞。