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Artif Cells Nanomed Biotechnol. 2018;46(sup1):1102-1113. doi: 10.1080/21691401.2018.1446018. Epub 2018 Feb 28.

Zinc oxide nanoparticles induce murine photoreceptor cell death via mitochondria-related signaling pathway.

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a Clinical Medical College, Jining Medical University , Jining , Shandong Province , China.
b Department of Ophthalmology , The First People's Hospital of Jining , Jining , Shandong Province , China.
c College of Life Sciences , Qingdao Agricultural University , Qingdao , Shandong Province , China.
d Department of Integration of Chinese and Western Medicine , The Affiliated Yantai Yuhuangding Hospital of Qingdao University , Yantai , Shandong Province , China.
e Jiangsu Provincial Key Laboratory for Interventional Medical Devices , Huaiyin Institute of Technology , Huaian , Jiangsu Province , China.
f Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases , Eye Institute of Shandong University of Traditional Chinese Medicine , Jinan , Shandong Province , China.


Zinc oxide (ZnO) nanoparticles can exhibit toxic effect on cells and tissues, which may be involved in the excessive generation of reactive oxygen species (ROS) and the consequent mitochondria-mediated apoptotic pathway. Nevertheless, the detailed mechanism remains unclear. In this study, we explored the effects of ZnO nanoparticles on the expressions of cytochrome c, ATP level, mitochondrial membrane potential, ROS, apoptosis, total antioxidant enzyme activities and apoptotic-related protein levels in murine photoreceptor cells as well as the changes of proteomic profiling. Moreover, we also performed the bioinformatics analysis for the differentially expressed proteins. Our results show that ZnO nanoparticles induce the release of cytochorme c, decrease the intracellular ATP level, collapse the mitochondrial membrane potential, elevate the ROS level, inhibit total antioxidant enzyme activities and increase the Bax and Caspase 3 levels whereas it decrease the Bcl-2 expression, leading to cell death. Proteomic analysis reveals the differentially expressed proteins are involved in cytochrome c oxidase activity and oxidative phosphorylation. Protein-protein interaction analysis confirms the differentially expressed proteins are closely associated with the clusters related to apoptotic signaling pathway and oxidative phosphorylation-associated proteins. Our results indicate that mitochondria play a central role in ZnO nanoparticle-induced murine photoreceptor cell death.


Zinc oxide nanoparticle; apoptosis; mitochondrion; oxidative phosphorylation; proteomics; reactive oxygen species

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