Zhang Li, Fei Maoxin, Peng Yaonan, Li Tao, Ji Xiangjun, Gao Jinqi, Tian Mi
Department of Neurosurgery, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, P.R. China.
Department of Anesthesiology, Surgery and pain management, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, P.R. China.
Neurochem Res. 2025 Aug 13;50(4):260. doi: 10.1007/s11064-025-04519-3.
O-linked-N-acetylglucosaminylation (O-GlcNAcylation), a distinctive post-translational modification (PTM), is ubiquitously present in numerous nuclear and mitochondrial proteins. The emerging role of O-GlcNAcylation is increasingly recognized for its involvement in various diseases. However, its role in traumatic brain injury (TBI) has not been explored. This study was aimed to explore the neuroprotection of O-GlcNAcylation in both in vivo and in vitro TBI models. Our results revealed that the levels of O-GlcNAcylation were increased after TBI. Up-regulation of O-GlcNAcylation by Thiamet G (TMG) provided neuroprotection after TBI. Moreover, TMG inhibited TBI-triggered blood-brain barrier (BBB) damage. Furthermore, TMG alleviated apoptosis and ferroptosis caused by TBI. Besides, TMG activated mitophagy after TBI, and the neuroprotection of TMG was attenuated when mitophagy was inhibited. Importantly, TMG also attenuated cell death, decreased apoptosis and ferroptosis, and activated mitophagy after TBI in vitro. Taken together, our data provided the first evidence that O-GlcNAcylation played a crucial role in TBI by activation of mitophagy.
O-连接的N-乙酰葡糖胺化修饰（O-GlcNAcylation）是一种独特的翻译后修饰（PTM），广泛存在于众多核蛋白和线粒体蛋白中。O-GlcNAcylation修饰在各种疾病中的作用日益受到关注。然而，其在创伤性脑损伤（TBI）中的作用尚未得到研究。本研究旨在探讨O-GlcNAcylation修饰在体内和体外TBI模型中的神经保护作用。我们的结果显示，TBI后O-GlcNAcylation修饰水平升高。噻美尼定（TMG）上调O-GlcNAcylation修饰可在TBI后提供神经保护作用。此外，TMG可抑制TBI引发的血脑屏障（BBB）损伤。此外，TMG可减轻TBI引起的细胞凋亡和铁死亡。此外，TMG可在TBI后激活线粒体自噬，而抑制线粒体自噬会减弱TMG的神经保护作用。重要的是，TMG在体外也可减轻TBI后的细胞死亡、减少细胞凋亡和铁死亡，并激活线粒体自噬。综上所述，我们的数据首次证明O-GlcNAcylation修饰通过激活线粒体自噬在TBI中发挥关键作用。
