Zinc oxide nanoparticles inhibit expression of manganese superoxide dismutase via amplification of oxidative stress, in murine photoreceptor cells.
OBJECTIVE
As a parenchymal cell, the photoreceptor is more susceptible to alterations in outer micro-environmental conditions than other cells. In the present study, we aimed to investigate inhibitory effects of zinc oxide (ZnO) nanoparticles on expression of manganese superoxide dismutase (MnSOD) in murine photoreceptor-derived cells.


METHODS
We investigated effects of ZnO nanoparticles on murine photoreceptor cell viability and on expression and activity of MnSOD using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, immunofluorescence analysis, flow cytometry, quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA).


RESULTS
ZnO nanoparticles were found to have higher cytotoxic effects in concentration- and time-dependent manners, to elevate intracellular levels of hydrogen peroxide and hydroxyl radicals, and thus to induce overproduction of reactive oxygen species (ROS) and collapse of mitochondrial membrane potential, leading to cell damage. Moreover, ZnO nanoparticles also significantly reduced expression of MnSOD at both the mRNA and protein levels, reduced its activity, and further aggravated oxidative stress-mediated cell damage.


CONCLUSIONS
Overall, ZnO nanoparticle-induced cytotoxicity was associated with elevated levels of oxidative stress due to overproduction of ROS and reduced expression and activity of MnSOD.
Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, 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, China.
Da Dong
da D
Guo
Emergency centre, Yantai Yuhuangding Hospital Affiliated Hospital of Qingdao University Medical College, Yantai, China.
Qin
Q
Li
Shandong University of Traditional Chinese Medicine, Jinan, China.
Hong Ying
HY
Tang
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Jing
J
Su
Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, 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, China.
Hong Sheng
HS
Bi
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010786:Photoreceptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*
D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D015034:Zinc Oxide