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Abstract #95045 Published in IGR 22-2
Zinc oxide nanoparticle-triggered oxidative stress and autophagy activation in human tenon fibroblasts
Guo D; Wang Z; Guo L; Yin X; Li Z; Zhou M; Li T; Chen C; Bi HEuropean Journal of Pharmacology 2021; 907: 174294
Glaucoma is a leading cause of irreversible blindness worldwide due to elevated intraocular pressure, and filtering surgery can efficiently control intraocular pressure of glaucoma patients. However, failure of filtering surgery commonly results from scarring formation at the surgical site, in which fibroblast proliferation plays an essential role in the scarring process. Our previous study has demonstrated that zinc oxide (ZnO) nanoparticles could efficiently inhibit human tenon fibroblasts (HTFs) proliferation. The present study aimed to explore the underlying mechanism involved in oxidative stress and autophagy signaling in zinc oxide (ZnO) nanoparticles-induced inhibition of HTFs proliferation. In this study, we investigated the effect of ZnO nanoparticles on HTFs proliferation, mitochondrial function, ATP production and nuclear morphology. Moreover, we also explored the interactions between ZnO nanoparticles and HTFs, investigated the influence of ZnO nanoparticles on the autophagosome formation, the expression of autophagy-related 5 (Atg5), Atg12 and Becn1 (Beclin 1), and the level of light chain 3 (LC3). The results suggested that ZnO nanoparticles can efficiently inhibit HTFs proliferation, disrupt the mitochondrial function, attenuate the adenosine triphosphate (ATP) generation, and damage the nuclear morphology of HTFs. Exposure of HTFs to ZnO nanoparticles can also induce the shifted peak, elevate the expression of Atg5, Atg12 and Becn1, enhance the autophagosome formation, and promote the LC3 expression, and thus activate autophagy signaling. Overall, ZnO nanoparticles can apparently trigger oxidative stress and activate autophagy signaling in HTFs, and thus inhibit HTFs proliferation and mediate HTFs apoptosis.
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, 250002, China. Electronic address: dadonggene@163.com.
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