Tu Mengjue, Fan Xingshuo, Shi Jianan, Jing Shengnan, Xu Xiaole, Wang Yuqin
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China.
Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong 226001, China.
Life (Basel). 2022 Mar 11;12(3):406. doi: 10.3390/life12030406.
Fucosylation is one of the most important glycan terminal modifications that affects multiple biological activities of proteins. 2-Fluorofucose (2FF), its specific inhibitor, has recently been reported to reveal numerous biological effects by blocking fucosylation both in vitro and in vivo. The current study aimed to evaluate the effect of 2FF on hydrogen peroxide (HO)-induced oxidative damage in vitro. In our study, treatment with HO increased the level of fucosylation, and 2FF improved the cell viability in HO-treated HepG2 cells. Our study also showed that 2FF significantly decreased the overproduction of reactive oxygen species (ROS) induced by HO and the activities of catalase, glutathione and Mn-superoxide dismutase were remarkably increased by 2FF pretreatment. Furthermore, 2FF attenuated HO-induced early mitochondria dysfunction. The second part of the study revealed that 2FF enhanced antioxidant capacity by affecting Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Being pretreated with 2FF significantly increased the nuclear translocation of Nrf2 and simultaneously promoted the expression of downstream proteins, such as HO-1 and NQO1. Moreover, 2FF remarkably suppressed the expression of inflammation-associated proteins. Taken together, these data suggest that 2FF might have a potential therapeutic effect for oxidative stress.
岩藻糖基化是影响蛋白质多种生物学活性的最重要的聚糖末端修饰之一。其特异性抑制剂2-氟岩藻糖（2FF）最近被报道在体外和体内通过阻断岩藻糖基化揭示了众多生物学效应。本研究旨在评估2FF对体外过氧化氢（H₂O₂）诱导的氧化损伤的影响。在我们的研究中，H₂O₂处理增加了岩藻糖基化水平，而2FF提高了H₂O₂处理的HepG2细胞的活力。我们的研究还表明，2FF显著降低了H₂O₂诱导的活性氧（ROS）的过量产生，并且2FF预处理显著提高了过氧化氢酶、谷胱甘肽和锰超氧化物歧化酶的活性。此外，2FF减轻了H₂O₂诱导的早期线粒体功能障碍。研究的第二部分表明，2FF通过影响HepG2细胞中的Nrf2/keap1和NF-κB信号通路增强了抗氧化能力。用2FF预处理显著增加了Nrf2的核转位，同时促进了下游蛋白如HO-1和NQO1的表达。此外，2FF显著抑制了炎症相关蛋白的表达。综上所述，这些数据表明2FF可能对氧化应激具有潜在的治疗作用。
