神经蛋白-3激活了Akt-依赖的Nrf2级联,以保护骨质母细胞免受氧化应激的影响
Jian-Bo Fan1, Kun Yuan1, Xin-Hui Zhu1
1Department of Orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong, China.
Free radical biology & medicine
|September 29, 2023
概括
神经原蛋白-3 (NLGN3) 通过激活Akt依赖的Nrf2通路来保护骨质母细胞免受氧化应激. 这一发现为骨质疏松症和相关骨疾病提供了潜在的治疗点.
科学领域:
- 骨生物学 骨生物学 骨生物学
- 细胞应激反应的应激反应
- 骨质疏松症的分子机制
背景情况:
- 骨质疏松症的特征是由于过度的氧化应激导致的骨质细胞损伤.
- 神经原蛋白-3 (NLGN3),一种细胞粘附蛋白,存在于骨组织中.
- 对于NLGN3在骨质母细胞中抗氧化损伤的保护作用,至今仍在很大程度上未被探索.
研究的目的:
- 研究NLGN3在保护骨质母细胞免受过氧化 (H2O2) 诱导的氧化损伤方面的潜力.
- 阐明涉及NLGN3介导细胞保护的分子通路.
主要方法:
- 主要的小鼠和人类骨质细胞被培养并用NLGN3和H2O2.2处理.
- 评估了信号通路 (Akt, Erk1/2, S6K, Nrf2) 的激活.
- 测量了活性氧物种 (ROS) 生产,细胞毒性和基因表达 (HO1,GCLC,NQO1).
- 包括shRNA和淘汰赛模型在内的基因操纵被用于确认途径的参与.
- 使用德甲和化的骨质细胞损伤模型被使用.
主要成果:
- NLGN3刺激激活了Akt,Erk1/2和S6K通路,这种方式取决于剂量.
- NLGN3预处理显著降低了H2O2诱导的细胞毒性,细胞死亡和ROS产生.
- NLGN3激活了Nrf2信号级联,导致Nrf2稳定和核转位,并增加了抗氧化剂基因表达.
- 通过NLGN3介导的保护依赖于Nrf2的激活,因为Nrf2的敲击取消了保护作用.
- 该Akt通路对于NLGN3诱导的Nrf2激活和随后的细胞保护至关重要.
- 发现NLGN3表达在接受德克萨米他治疗的患者的骨髓性骨组织中受到下调.
结论:
- 通过激活Akt依赖的Nrf2信号级联,NLGN3为骨质母细胞提供了对氧化应激的细胞保护.
- NLGN3代表了治疗骨质疏松症和其他与氧化压力相关的骨疾病的潜在治疗标.
- 这些发现凸显了NLGN3在压力条件下维持骨质母细胞健康的关键作用.
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