Ogt-mediated O-GlcNAcylation inhibits astrocytes activation through modulating NF-κB signaling pathway.
Ogt-mediated O-GlcNAcylation inhibits astrocytes activation through modulating NF-κB signaling pathway.
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Ogt介导的O-GlcNAc化通过调节NF-κB信号通路抑制星形胶质细胞活化。
DOI：
10.1186/s12974-023-02824-8
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发表时间：
2023-06-22
影响因子：
9.3
通讯作者：
Li, Xuekun
中科院分区：
文献类型：
--
作者：
Dong, Xiaoxue;Shu, Liqi;Zhang, Jinyu;Yang, Xu;Cheng, Xuejun;Zhao, Xingsen;Qu, Wenzheng;Zhu, Qiang;Shou, Yikai;Peng, Guoping;Sun, Binggui;Yi, Wen;Shu, Qiang;Li, Xuekun
先前的研究表明，Ogt介导的O-GlcNAc酰化对于神经元的发育和功能是必不可少的。然而，O-GlcNAc转移酶（Ogt）和O-GlcNAc酰化在星形胶质细胞中的功能仍很不清楚。在这里，我们表明，Ogt缺乏诱导体内和体外星形胶质细胞的炎症激活，并损害小鼠的认知功能。通过补充GlcNAc恢复O-GlcNAc酰化抑制星形胶质细胞的活化、炎症并改善Ogt缺陷小鼠受损的认知功能。在机制上，Ogt与NF-κB p65相互作用并催化星形胶质细胞中NF-κB p65的O-GlcNAc酰化。Ogt缺乏通过促进Gsk 3 β结合而激活NF-κB信号通路。此外，Ogt耗竭诱导源自人诱导多能干细胞的星形胶质细胞的活化。O-GlcNAc化的恢复在体内外均能抑制AD小鼠星形胶质细胞的活化、炎症反应和减少Aβ斑块。总之，我们的研究揭示了Ogt介导的O-GlcNAc化通过调节NF-κB信号通路在星形胶质细胞中的重要作用。在线版本包含补充材料，可通过10.1186/s12974-023-02824-8获得。
Previous studies have shown that Ogt-mediated O-GlcNAcylation is essential for neuronal development and function. However, the function of O-GlcNAc transferase (Ogt) and O-GlcNAcylation in astrocytes remains largely unknown. Here we show that Ogt deficiency induces inflammatory activation of astrocytes in vivo and in vitro, and impairs cognitive function of mice. The restoration of O-GlcNAcylation via GlcNAc supplementation inhibits the activation of astrocytes, inflammation and improves the impaired cognitive function of Ogt deficient mice. Mechanistically, Ogt interacts with NF-κB p65 and catalyzes the O-GlcNAcylation of NF-κB p65 in astrocytes. Ogt deficiency induces the activation of NF-κB signaling pathway by promoting Gsk3β binding. Moreover, Ogt depletion induces the activation of astrocytes derived from human induced pluripotent stem cells. The restoration of O-GlcNAcylation inhibits the activation of astrocytes, inflammation and reduces Aβ plaque of AD mice in vitro and in vivo. Collectively, our study reveals a critical function of Ogt-mediated O-GlcNAcylation in astrocytes through regulating NF-κB signaling pathway. The online version contains supplementary material available at 10.1186/s12974-023-02824-8.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
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Schwartz, Michal
影响因子：
4.3
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影响因子：
15.3
作者：
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通讯作者：
Bethea, JR
影响因子：
5.1
作者：
Dela Justina, Vanessa;Goncalves, Jessica S.;Giachini, Fernanda R.
通讯作者：
Giachini, Fernanda R.
DOI：
10.1073/pnas.1300065110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Howerton, Christopher L.;Morgan, Christopher P.;Bale, Tracy L.
通讯作者：
Bale, Tracy L.