Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
Cell Signal. 2013 Mar;25(3):615-29. doi: 10.1016/j.cellsig.2012.11.025. Epub 2012 Dec 5.
Previous studies have demonstrated that Notch signaling pathway plays a regulatory role in cellular oxidative stress injury (OSI). In this study, our aim was to explore the role of the Notch signaling pathway in hydrogen peroxide (H(2)O(2))-induced OSI and the protective effect of curcumin during (H(2)O(2))-induced injury in human umbilical vein endothelial cells (HUVECs). DAPT, a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to study Notch activity. Further, HUVECs were exposed to H(2)O(2) in the absence or presence of curcumin. DAPT and Notch1 siRNA significantly inhibited OSI and the expression of Notch1 and Hes1. Curcumin conferred a protective effect on the HUVECs against H(2)O(2), which was evidenced by improved cell viability, adhesive ability and migratory ability and a decreased apoptotic index, decreased production of reactive oxygen species (ROS) and a reduction in several biochemical parameters. Immunofluorescence and Western blotting analyses demonstrated that H(2)O(2) treatment upregulated the expression of Notch1, Hes1, Caspase3, Bax and cytochrome c downregulated the expression of Bcl2, and treatment with curcumin reversed these effects. We demonstrated for the first time that the inhibition of Notch signaling pathway imparts a protective effect against endothelial OSI. The protective effects of curcumin against OSI are at least in part dependent on Notch1 inhibition.
先前的研究表明，Notch 信号通路在细胞氧化应激损伤（OSI）中发挥调节作用。在这项研究中，我们的目的是探索 Notch 信号通路在过氧化氢（H₂O₂）诱导的 OSI 中的作用，以及姜黄素在（H₂O₂）诱导的人脐静脉内皮细胞（HUVEC）损伤中的保护作用。Notch 信号通路的特异性抑制剂 DAPT 和 Notch1 siRNA 用于研究 Notch 活性。进一步，将 HUVEC 暴露于 H₂O₂ 中，同时存在或不存在姜黄素。DAPT 和 Notch1 siRNA 显著抑制 OSI 和 Notch1 和 Hes1 的表达。姜黄素对 HUVEC 对抗 H₂O₂ 具有保护作用，这表现在细胞活力、黏附能力和迁移能力提高，凋亡指数降低，活性氧（ROS）产生减少以及几种生化参数降低。免疫荧光和 Western blot 分析表明，H₂O₂处理上调 Notch1、Hes1、Caspase3、Bax 和细胞色素 c 的表达，下调 Bcl2 的表达，而姜黄素处理则逆转了这些效应。我们首次证明，抑制 Notch 信号通路对内皮 OSI 具有保护作用。姜黄素对 OSI 的保护作用至少部分依赖于 Notch1 抑制。
