title: NiO nanoparticles induce apoptosis through repressing SIRT1 in human bronchial epithelial cells.
abstract: With application of nano-sized nickel-containing particles (Nano-Ni) expanding, the health concerns about their adverse effects on the pulmonary system are increasing. However, the mechanisms for the pulmonary toxicity of these materials remain unclear. In the present study, we focused on the impacts of NiO nanoparticles (NiONPs) on sirtuin1 (SIRT1), a NAD-dependent deacetylase, and investigated whether SIRT1 was involved in NiONPs-induced apoptosis. Although the NiONPs tended to agglomerate in fluid medium, they still entered into the human bronchial epithelial cells (BEAS-2B) and released Ni(2+) inside the cells. NiONPs at doses of 5, 10, and 20μg/cm(2) inhibited the cell viability. NiONPs' produced cytotoxicity was demonstrated through an apoptotic process, indicated by increased numbers of Annexin V positive cells and caspase-3 activation. The expression of SIRT1 was markedly down-regulated by the NiONPs, accompanied by the hyperacetylation of p53 (tumor protein 53) and overexpression of Bax (Bcl-2-associated X protein). However, overexpression of SIRT1 through resveratrol treatment or transfection clearly attenuated the NiONPs-induced apoptosis and activation of p53 and Bax. Our results suggest that the repression of SIRT1 may underlie the NiONPs-induced apoptosis via p53 hyperacetylation and subsequent Bax activation. Because SIRT1 participates in multiple biologic processes by deacetylation of dozens of substrates, this knowledge of the impact of NiONPs on SIRT1 may lead to an improved understanding of the toxic mechanisms of Nano-Ni and provide a molecular target to antagonize Nano-Ni toxicity.
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Duan
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Min-Di
authors.initials: MD
authors.lastname: He
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Qian
authors.affiliation: Institute of Hepatobiliary Surgery, XinQiao Hospital, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Hui-Feng
authors.initials: HF
authors.lastname: Pi
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Chun-Hai
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Lu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Zheng-Wang
authors.initials: ZW
authors.lastname: Cao
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Yu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China. Electronic address: lunazhou00@163.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053758:Nanoparticles / Q000378:metabolism / Q000633:toxicity*; D009532:Nickel / Q000378:metabolism / Q000633:toxicity*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D009532:Nickel; C028007:nickel monoxide; D053148:Caspase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Apoptosis; BEAS-2B; Bax; NiO nanoparticles; SIRT1; p53 acetylation