title: Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line.
abstract: Nanoparticles such as nano-SiO(2) are increasingly used in food, cosmetics, diagnosis, imaging and drug delivery. However, toxicological data of nano-SiO(2) on hepatic cells in vitro and their detailed molecular mechanisms still remain unclear. In order to assess toxicity of nano-SiO(2), L-02 cells were exposed to 0.2, 0.4 and 0.6 mg/ml of SiO(2) colloids (21, 48 and 86 nm) for 12, 24, 36 and 48h. Lactate dehydrogenase released from damaged cells were quantified, cellular ultrastructural organization was observed, and the levels of reactive oxygen species (ROS), lipid peroxidation and glutathione were measured. Apoptosis induced by 21 nm SiO(2) was characterized by annexin V-FITC/PI staining and DNA ladder assay. Furthermore, apoptosis related proteins such as p53, Bax and Bcl-2 were analyzed by using western blot analysis. Our data indicated that nano-SiO(2) caused cytotoxicity in size, dose and time dependent manners. Oxidative stress and apoptosis were induced by exposure to 21 nm SiO(2). Moreover, the expression of p53 and Bax was increased in time and dose dependent patterns, whereas the expression of Bcl-2 was not significantly changed. In conclusion, ROS-mediated oxidative stress, the activation of p53 and up-regulation of Bax/Bcl-2 ratio are involved in mechanistic pathways of 21 nm SiO(2) induced apoptosis in L-02 cells.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ye
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Jianhe
authors.initials: J
authors.lastname: Xu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Mingcang
authors.initials: M
authors.lastname: Chen
authors.forename: Minbo
authors.initials: M
authors.lastname: Lan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D012822:Silicon Dioxide; D004247:DNA; D007770:L-Lactate Dehydrogenase; D005978:Glutathione