Silica nanoparticles induce apoptosis through BCL-2 DNA methylation via the PI3K/AKT/CREB signaling pathway in BEAS-2B cells
With application of nano-sized silica-containing particles (Nano-Si) expanding, the health concerns about their adverse effects on the pulmonary systemare increasing.However, the mechanisms for the pulmonary toxicity of these materials remain unclear.In the present study, we focused on the impacts of silica nanoparticles (SNPs) on dna methylation, a AKT-dependent deacetylase, and investigated whether BCL-2 was involved in SNPs induced apoptosis.The SNPs tended to entered into the human bronchial epithelial cells (BEAS-2B) and released Si2+ inside the cells.SNPs at doses of 5μg/ML for 30 passages inhibited the cell viability.SNPs” produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased the caspase-3activation.The DNA BCL-2 and CREB were hypermethylation ,and the expression of BCL-2 and CREB was markedly down-regulated by the SNPs, accompanied by the influence of AKT.Our results suggest that the repression of BCL-2 and CREB may underlie the SNPs-induced apoptosis via PI3K/Akt/CREB signaling pathway.This knowledge of the impact of SNPs on BCL-2 and CREB may lead to an improved understanding of the toxic mechanisms of Nano-Si and provide a molecular target to antagonize Nano-Si toxicity.
Nanotoxicity Silica nanoparticles Apoptosis DNA methylation
Yang Zou Zhiwei Sun Yanbo Li Caixia Gou Yongbo Yu Junchao Duan Weijia Geng Yumei Yang Yang Yu Yang Li
School of Public Health, Capital Medical University, Beijing, 100069, P.R.China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, P.R.China
国内会议
北京
英文
76-92
2015-06-01（万方平台首次上网日期，不代表论文的发表时间）