欧类固醇通过FOXO/NF-κB/亡信号通路诱导神经毒性
Jianwen Chen1, Yuheng Wang1, Zhengxu Cai1
1Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Brain research bulletin
|November 14, 2024
概括
欧类固醇通过激活FOXO,NF-κB和亡途径引起神经毒性. 了解这些机制是其安全治疗用途的关键.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 欧类固醇是一种来自Euphorbia lathyris L.的化合物,显示出抗瘤和多药耐药性逆转效应.
- 欧类固醇的潜在神经毒性阻碍了其临床应用.
- 这项研究调查了euphorbiasteroid的神经毒性作用和潜在机制.
研究的目的:
- 为了研究euphorbiasteroid在神经和质细胞中的神经毒性作用.
- 阐明分子机制,包括信号通路和蛋白质相互作用,参与euphorbiasteroid诱导的神经毒性.
- 评估叉头盒O (FOXO) 途径在euphorbiasteroid神经毒性的作用.
主要方法:
- 通过PC12细胞和初级星体细胞的细胞活力和乳酸脱酶 (LDH) 测定来评估神经毒性.
- 转录基因分析预测了FOXO,核因子-kappa B (NF-κB) 和亡途径的参与.
- 细胞亡标记物,信号蛋白和FOXO3A相互作用通过TUNEL染色,西部斑点和分子对接进行了分析.
主要成果:
- 欧类固醇诱导PC12细胞和星球细胞显著的细胞毒性,激活FOXO,NF-κB和亡途径.
- 通过增加Bax/Bcl-2比率和割裂caspase3,减少-FOXO3A和增强NF-κBp65酸化,证实了亡.
- 分子对接显示euphorbiasteroid与FOXO3A结合,FOXO3A敲击显著降低了神经毒性.
结论:
- 欧类固醇通过激活FOXO/NF-κB/亡信号级联来诱导神经毒性.
- 这些发现揭示了对euphorbiasteroid神经毒性机制的新见解.
- 了解这些途径对于开发策略来缓解euphorbiasteroid治疗用途的不良影响至关重要.
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