title: Zinc oxide nanoparticles induce rat retinal ganglion cell damage through bcl-2, caspase-9 and caspase-12 pathways.
abstract: Nanomaterials, including zinc oxide (ZnO) nanoparticles, are being developed for a variety of commercial products. Recent reports showed that cells exposed to ZnO nanoparticles produced severe cytotoxicity accompanied by oxidative stress and genotoxicity. To understand the possible mechanism underlying oxidative stress of ZnO nanoparticles, the present investigation focused on the direct bioactivity of ZnO nanoparticles using a rat retinal ganglion cell (RGC-5) culture. At concentrations relevant to those used in vitro exposure of RGC-5 cells to ZnO nanoparticles, it was found that ZnO nanoparticles could inhibit cell proliferation in time- and concentration-dependent manners. Meanwhile, cell cycle arrest of S and G2/M phases occurred in RGC-5 cells induced by ZnO nanoparticles. Moreover, our results also demonstrated that the overproduction of reactive oxygen species (ROS) and elevated level of caspase-12 as well as decreased levels of bcl-2 and caspase-9 occurred after treatment with different concentrations of ZnO nanoparticles when compared to those in untreated cells. In summary, our findings suggest that ZnO nanoparticles could lead to the over generations of ROS and caspase-12 as well as decreased levels of bcl-2 and caspase-9. These results indicate that bcl-2, caspase-9 and caspase-12 may play significant roles in ZnO nanoparticle-induced RGC-5 cell damage.
authors.affiliation: Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
authors.forename: Dadong
authors.initials: D
authors.lastname: Guo
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Bi
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; D017209:Apoptosis; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D020552:Comet Assay; D005434:Flow Cytometry; D015870:Gene Expression; D053768:Metal Nanoparticles / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015034:Zinc Oxide / Q000737:chemistry*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D053454:Caspase 12; D053453:Caspase 9; D015034:Zinc Oxide