title: Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells.
abstract: Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death.
authors.affiliation: Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases 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: Daoguang
authors.initials: D
authors.lastname: Wang
authors.forename: Qiuxin
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007477:Ions; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D010316:Particle Size; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D017304:Annexin A5; D007477:Ions; D017382:Reactive Oxygen Species; D011419:Propidium; D053499:Plasma Membrane Calcium-Transporting ATPases; D015034:Zinc Oxide; D002118:Calcium
keywords: Calcium homeostasis; Plasma membrane calcium ATPase; Reactive oxygen species; Retinal ganglion cell; Zinc oxide nanoparticle