Department of Cellular and Molecular Biology, Faculty of Advance Science and Technology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
Department of Molecular Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Int J Biol Macromol. 2018 Dec;120(Pt A):1140-1148. doi: 10.1016/j.ijbiomac.2018.08.182. Epub 2018 Sep 1.
The application of nanomaterials in the healthy system may induce some neurodegenerative diseases initiated by tau folding and neuronal cell death. Herein, aluminium oxide nanoparticles (AlO NPs) were synthesized and characterized by XRD, TEM, DLS and zeta potential investigations. Afterwards, the interaction of AlO NPs with tau protein was investigated by fluorescence and CD spectroscopic methods. The molecular docking and molecular dynamic were also run to explore the binding site and conformational changes of tau after interaction with AlO cluster. Moreover, the MTT, LDH, caspase-9/-3 and flow cytometry assays were done to explore the AlO NPs-induced cytotoxicity against SH-SY5Y cells. It was revealed that AlO NPs bind to tau protein and form a static complex and fold the structure of tau toward a more packed structure. Molecular docking and molecular dynamic investigations revealed that NPs bind to the hydrophilic residues of the tau segments and promote some marginal structural folding of tau segment. The cellular assays displayed that AlO NPs can elicit cell mortality through membrane leakage, caspase-9/-3 activations, and induction of both apoptosis and necrosis. This data may indicate that NPs can induce some adverse effects on the biological systems.
纳米材料在健康系统中的应用可能会引发一些由tau 折叠和神经元细胞死亡引发的神经退行性疾病。在此，通过 XRD、TEM、DLS 和 zeta 电位研究合成并表征了氧化铝纳米颗粒 (AlO NPs)。然后，通过荧光和 CD 光谱研究了 AlO NPs 与 tau 蛋白的相互作用。还进行了分子对接和分子动力学模拟，以探索 AlO 簇相互作用后 tau 的结合位点和构象变化。此外，还进行了 MTT、LDH、caspase-9/-3 和流式细胞术测定，以研究 AlO NPs 对 SH-SY5Y 细胞的细胞毒性。结果表明，AlO NPs 与 tau 蛋白结合形成静态复合物，并使 tau 结构折叠成更紧密的结构。分子对接和分子动力学研究表明，纳米颗粒与 tau 片段的亲水性残基结合，并促进 tau 片段的一些边缘结构折叠。细胞实验表明，AlO NPs 可以通过膜渗漏、caspase-9/-3 的激活以及诱导凋亡和坏死来引发细胞死亡。这些数据可能表明纳米颗粒会对生物系统产生一些不良影响。
