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氧化锌纳米颗粒通过阻断钾通道和抑制钠/钾-ATP酶对小鼠感光细胞的细胞毒性作用。

Cytotoxic effect of zinc oxide nanoparticles on murine photoreceptor cells via potassium channel block and Na /K -ATPase inhibition.

作者信息

Chen Chao, Bu Wenjuan, Ding Hongyan, Li Qin, Wang Dabo, Bi Hongsheng, Guo Dadong

机构信息

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

Department of Ophthalmology, The First People's Hospital of Jining, Jining, Shandong Province, China.

出版信息

Cell Prolif. 2017 Jun;50(3). doi: 10.1111/cpr.12339. Epub 2017 Feb 19.

Abstract

OBJECTIVE

Zinc oxide (ZnO) nanoparticles can exhibit toxicity towards organisms and oxidative stress is often hypothesized to be one of the most important factors. Nevertheless, the detailed mechanism of toxicity-induced by ZnO nanoparticles has not been completely addressed. The present study aimed to investigate the toxic effects of ZnO nanoparticles on the expression and activity of Na /K -ATPase and on potassium channel block.

MATERIALS AND METHODS

In the present study, we explored the cytotoxic effect of ZnO nanoparticles on murine photoreceptor cells using lactate dehydrogenase (LDH) release assay, reactive oxygen species (ROS) determination, mitochondrial membrane potential (Δφm) measurement, delayed rectifier potassium current recordings and Na /K -ATPase expression and activity monitoring.

RESULTS

The results indicated that ZnO nanoparticles could increase the LDH release in medium, aggravate the ROS level within cells, collapse the Δφm, block the delayed rectifier potassium current, and attenuate the expressions of Na /K -ATPase at both mRNA and protein levels and its activity, and thus exert cytotoxic effects on murine photoreceptor cells, finally damaging target cells.

CONCLUSION

Our findings will facilitate the understanding of the mechanism involved in ZnO nanoparticle-induced cytotoxicity in murine photoreceptor cells via potassium channel block and Na /K -ATPase inhibition.

摘要

目的

氧化锌(ZnO)纳米颗粒可对生物体表现出毒性,氧化应激常被认为是最重要的因素之一。然而,ZnO纳米颗粒诱导毒性的详细机制尚未完全阐明。本研究旨在探讨ZnO纳米颗粒对Na /K -ATP酶表达和活性以及对钾通道阻滞的毒性作用。

材料与方法

在本研究中,我们使用乳酸脱氢酶(LDH)释放试验、活性氧(ROS)测定、线粒体膜电位(Δφm)测量、延迟整流钾电流记录以及Na /K -ATP酶表达和活性监测,探究了ZnO纳米颗粒对小鼠感光细胞的细胞毒性作用。

结果

结果表明,ZnO纳米颗粒可增加培养基中LDH的释放,加重细胞内ROS水平,使Δφm崩溃,阻滞延迟整流钾电流,并在mRNA和蛋白质水平以及活性上减弱Na /K -ATP酶的表达,从而对小鼠感光细胞产生细胞毒性作用,最终损害靶细胞。

结论

我们的研究结果将有助于理解ZnO纳米颗粒通过钾通道阻滞和Na /K -ATP酶抑制在小鼠感光细胞中诱导细胞毒性的机制。

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