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Nur77对脂多糖诱导的小胶质细胞活化作用的蛋白质组学分析。

Proteomic analysis of the effects of Nur77 on lipopolysaccharide-induced microglial activation.

作者信息

Chen Yan, Jin Yuexinzi, Zhan Hui, Chen Jian, Chen Yanting, Meng Hailan, Jin Jiali, Yu Linjie, Cao Xiang, Xu Yun

机构信息

Department of Neurology, Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.

Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210008, China.

出版信息

Neurosci Lett. 2017 Oct 17;659:33-43. doi: 10.1016/j.neulet.2017.07.022. Epub 2017 Jul 17.

Abstract

Microglia are critical components of the immune response in the central nervous system. Our study aims to explore potential role of Nur77 in lipopolysaccharide (LPS)-induced microglial activation. Primary wild-type and Nur77 microglia were stimulated with LPS and protein extracts were detected via mass spectrometry. Q-PCR and western blotting were performed to validate candidate proteins. A total of 2004 proteins were identified, with 749 and 677 significantly differentially expressed proteins in wild-type and Nur77 microglia in resting and activated states, respectively. Signaling pathway analysis showed that significantly differentially expressed proteins in LPS-treated Nur77 microglia were present in important signaling pathways of microglial activation, including the Toll-like receptor signaling pathway, the MAPK signaling pathway, FcγR-mediated phagocytosis, and chemokine signaling pathways. Furthermore, we found that Nur77 could be the upstream protein of the vav1 and ERK1/2 signaling pathway. This study provided new insights into the understanding the mechanisms of the effects of Nur77 on LPS-activated microglia.

摘要

小胶质细胞是中枢神经系统免疫反应的关键组成部分。我们的研究旨在探讨Nur77在脂多糖(LPS)诱导的小胶质细胞激活中的潜在作用。用LPS刺激原代野生型和Nur77小胶质细胞,并通过质谱检测蛋白质提取物。进行Q-PCR和蛋白质印迹以验证候选蛋白质。共鉴定出2004种蛋白质,其中分别有749种和677种在静息和激活状态下的野生型和Nur77小胶质细胞中显著差异表达的蛋白质。信号通路分析表明,LPS处理的Nur77小胶质细胞中显著差异表达的蛋白质存在于小胶质细胞激活的重要信号通路中,包括Toll样受体信号通路、MAPK信号通路、FcγR介导的吞噬作用和趋化因子信号通路。此外,我们发现Nur77可能是vav1和ERK1/2信号通路的上游蛋白。本研究为理解Nur77对LPS激活的小胶质细胞作用机制提供了新的见解。

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