title: DNA Hypermethylation of CREB3L1 and Bcl-2 Associated with the Mitochondrial-Mediated Apoptosis via PI3K/Akt Pathway in Human BEAS-2B Cells Exposure to Silica Nanoparticles.
abstract: The toxic effects of silica nanoparticles (SiNPs) are raising concerns due to its widely applications in biomedicine. However, current information about the epigenetic toxicity of SiNPs is insufficient. In this study, the epigenetic regulation of low-dose exposure to SiNPs was evaluated in human bronchial epithelial BEAS-2B cells over 30 passages. Cell viability was decreased in a dose- and passage-dependent manner. The apoptotic rate, the expression of caspase-9 and caspase-3, were significantly increased induced by SiNPs. HumanMethylation450 BeadChip analysis identified that the PI3K/Akt as the primary apoptosis-related pathway among the 25 significant altered processes. The differentially methylated sites of PI3K/Akt pathway involved 32 differential genes promoters, in which the CREB3L1 and Bcl-2 were significant hypermethylated. The methyltransferase inhibitor, 5-aza, further verified that the DNA hypermethylation status of CREB3L1 and Bcl-2 were associated with downregulation of their mRNA levels. In addition, mitochondrial-mediated apoptosis was triggered by SiNPs via the downregulation of PI3K/Akt/CREB/Bcl-2 signaling pathway. Our findings suggest that long-term low-dose exposure to SiNPs could lead to epigenetic alterations.
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Caixia
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Junchao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Toxicology and Sanitary Chemistry, 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.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D019175:DNA Methylation; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D019254:Genes, bcl-2; D006801:Humans; D008422:Materials Testing; D008928:Mitochondria / Q000502:physiology; D053758:Nanoparticles / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012822:Silicon Dioxide / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: C485618:CREB3L1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012822:Silicon Dioxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt