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载脂蛋白 E 蛋白与 LRP1 结合,使 GSK3β 失活,从而减轻二氧化硅纳米颗粒诱导的脑损伤。

Coronal ApoE Protein Combines with LRP1 to Inactivate GSK3β That Mitigates Silica Nanoparticle-Induced Brain Lesion.

机构信息

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Rd, Haidian District, Beijing 100085, China.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Rd, Beibei District, Chongqing 400715, China.

出版信息

ACS Chem Neurosci. 2024 Feb 21;15(4):808-815. doi: 10.1021/acschemneuro.3c00728. Epub 2024 Feb 5.

Abstract

Silica nanoparticles (SiO NPs) are widely used engineered materials that warrant their obvious environmental exposure risk. Our previous study has shown that different routes of SiO NP exposure on the glycogen synthase kinase 3 beta (GSK3β) activity were related to the serum proteins enriched on the surface of SiO NPs, which implied that a particular protein in the serum changed the inherent toxic behavior of SiO NPs and inhibited the activation of GSK3β by SiO NPs. Here, we identified that the SiO NP surface enriched a large amount of apolipoprotein E (ApoE), and the ApoE protein corona bound to the lipoprotein receptor-related protein 1 (LRP1) to inactivate GSK3β, thereby reducing the damage of SiO NPs to the brain. This work presented the first evidence that specific biocorona reduced the toxicity of SiO NPs at the molecular level, which helped to elucidate the role of specific corona components on nanotoxicity.

摘要

硅纳米颗粒 (SiO NPs) 是一种广泛应用的工程材料,具有明显的环境暴露风险。我们之前的研究表明,SiO NPs 暴露于不同途径与表面富含的血清蛋白有关,这表明血清中的特定蛋白改变了 SiO NPs 的固有毒性行为,并抑制了 GSK3β 的激活。在这里,我们发现 SiO NP 表面富含大量载脂蛋白 E (ApoE),ApoE 蛋白冠与脂蛋白受体相关蛋白 1 (LRP1) 结合使 GSK3β失活,从而降低 SiO NPs 对大脑的损伤。这项工作首次证明了特定的生物冠层在分子水平上降低了 SiO NPs 的毒性,有助于阐明特定的冠状成分在纳米毒性中的作用。

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