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硅纳米颗粒诱导神经母细胞瘤细胞系中 tau 蛋白构象改变、氧化应激和细胞凋亡。

Silica nanoparticles induce conformational changes of tau protein and oxidative stress and apoptosis in neuroblastoma cell line.

机构信息

Department of Cellular and Molecular Biology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.

Department of Biology, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran.

出版信息

Int J Biol Macromol. 2019 Mar 1;124:1312-1320. doi: 10.1016/j.ijbiomac.2018.09.118. Epub 2018 Sep 21.

Abstract

The adverse effects of SiO NPs on the biological systems like nervous system have not been well explored. This study aimed to evaluate the toxicity of SiO NPs on the nervous system in vitro. Therefore, human tau protein and neuroblastoma cell line (SH-SY5Y) were used as targets. In this study we examined the side effects of SiO NPs on tau protein structure using several techniques including CD, ANS fluorescence, UV-vis (360 nm), Congo red absorbance, TEM, and molecular dynamic. Also, the cytotoxicity effects of SiO NPs against SH-SY5Y cell line were evaluated using MTT, ROS and apoptotic assays. Spectroscopic and molecular dynamic investigations indicated that natively unfolded structure of tau in the presence of SiO NPs experienced a partially folded and amorphous aggregated structure. Cellular assay demonstrated that SiO NPs exerted cytotoxic effect on SH-SY5Y cells through ROS accumulation and induction of apoptosis. Overall, these findings proved that SiO NPs could induce adverse effects on tau structure and SH-SY5Y cell integrity. Moreover, further studies are required to elucidate the molecular mechanism of SiO NPs-induced side effects in vivo.

摘要

SiO NPs 对神经系统等生物系统的不良影响尚未得到充分探索。本研究旨在评估 SiO NPs 对体外神经系统的毒性。因此,使用人 tau 蛋白和神经母细胞瘤细胞系 (SH-SY5Y) 作为靶标。在这项研究中,我们使用包括 CD、ANS 荧光、UV-vis(360nm)、刚果红吸收、TEM 和分子动力学在内的几种技术来检查 SiO NPs 对 tau 蛋白结构的副作用。此外,还使用 MTT、ROS 和凋亡测定法评估了 SiO NPs 对 SH-SY5Y 细胞系的细胞毒性作用。光谱和分子动力学研究表明,在 SiO NPs 存在下,tau 的天然无规卷曲结构经历了部分折叠和无定形聚集结构。细胞试验表明,SiO NPs 通过 ROS 积累和诱导细胞凋亡对 SH-SY5Y 细胞发挥细胞毒性作用。总的来说,这些发现证明了 SiO NPs 可能会对 tau 结构和 SH-SY5Y 细胞完整性产生不良影响。此外,需要进一步的研究来阐明 SiO NPs 诱导的体内副作用的分子机制。

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