苏尔福拉重新连接中央新陈代谢以支持抗氧化反应并实现葡萄糖平衡
Federico Bernuzzi1, Andre Maertens2, Shikha Saha1
1Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom.
Redox biology
|September 13, 2023
概括
在西兰花中发现的硫福拉 (SF) 通过激活NRF2通路来增强葡萄糖代谢并减少氧化应激. 这项研究证明了SF.
科学领域:
- 生物化学 生物化学
- 代谢学 代谢学 代谢学
- 细胞生物学 细胞生物学
背景情况:
- 像西兰花一样的十字花蔬菜与降低癌症,心血管疾病和2型糖尿病的风险有关.
- 花的代谢物硫福拉 (SF) 是一种关键的生物活性化合物,也是转录因子NRF2的强有力的激活剂,它是抗氧化反应的主调节者.
- SF在葡萄糖平衡中的特定作用及其潜在机制在很大程度上仍未被阐明.
研究的目的:
- 调查SF调节葡萄糖代谢并通过NRF2激活人类肝细胞 (HepG2) 缓解葡萄糖过载引起的氧化应激的假设.
- 在葡萄糖代谢和氧化应激的背景下,阐明受SF影响的代谢途径.
主要方法:
- 用不同的葡萄糖度 (基础和高) 和生理SF度对待HepG2细胞.
- 使用标记的葡萄糖和谷氨酸进行了代谢流量分析.
- 对使用CRISPR-Cas9基因组编辑创建的NRF2-knockdown (KD) HepG2细胞进行了转录和向代谢学 (LC-MS) 分析.
主要成果:
- SF显著增加了谷氨 (GSH) 水平和高调的GSH生物合成基因.
- SF改变了代谢流动,增加了甘氨酸和谷氨酸的利用率,并增加了氨酸的进口,同时将葡萄糖从甘氨酸分解转向酸 (PPP) 途径和1C代谢.
- 通过CRISPR-Cas9介导的NRF2中断证实,SF的代谢作用依赖于NRF2.
结论:
- SF调节葡萄糖代谢,并通过NRF2激活增强肝细胞中的抗氧化能力.
- 这些发现将十字植物饮食的代谢益处与由SF和NRF2介导的抗氧化特性联系起来.
- SF在调节葡萄糖稳态和氧化应激方面的作用为富含十字花蔬菜的饮食所带来的健康益处提供了分子基础.
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