title: Reactive oxygen species-induced cytotoxic effects of zinc oxide nanoparticles in rat retinal ganglion cells.
abstract: Recent studies have proved that zinc oxide (ZnO) nanoparticles can cause toxicity in different cell lines, oxidative stress is often hypothesized to be an important factor in cytotoxicity of ZnO nanoparticles. However, the mechanisms are incompletely understood. The present study aimed to investigate the role of oxidative stress in toxicity and possible involvement of mitochondria in the production of reactive oxygen species (ROS) upon exposure of retinal ganglion cells (RGC-5) to ZnO nanoparticles. In this study, the effects of ZnO nanoparticles on mitochondrial membrane potential and ROS levels involved in hydrogen peroxide and hydroxyl radical production were investigated via inverted fluorescence microscope and hydrogen peroxide and hydroxyl radical assay kits, respectively. Furthermore, the mRNA of caspase-12 and the protein secreted into culture supernatant were also determined by means of real-time quantitative PCR and ELISA techniques. Our studies indicate that ZnO nanoparticles could apparently decrease the mitochondrial membrane potential, increase the production of ROS and lead to the overexpression of caspase-12 in RGC-5 cells, suggesting that ZnO nanoparticle-induced toxicity via ROS overproduction will trigger endoplasmic reticulum stress, lead to the RGC-5 cell damage and finally induce apoptosis/necrosis, the overexpression of caspase-12 may be involved in cell death in RGC-5 cells.
authors.affiliation: Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Jinan 250002, China.
authors.forename: Dadong
authors.initials: D
authors.lastname: Guo
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Bi
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Qiuxin
authors.initials: Q
authors.lastname: Wu
authors.forename: Daoguang
authors.initials: D
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000818:Animals; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D010718:Phosphatidylserines / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D010718:Phosphatidylserines; D012333:RNA, Messenger; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D053454:Caspase 12; D015034:Zinc Oxide