Homoeriodictyol protects human endothelial cells against oxidative insults through activation of Nrf2 and inhibition of mitochondrial dysfunction
Homoeriodictyol protects human endothelial cells against oxidative insults through activation of Nrf2 and inhibition of mitochondrial dysfunction
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高圣草酚通过激活Nrf2和抑制线粒体功能障碍保护人内皮细胞免受氧化损伤
DOI：
10.1016/j.vph.2018.06.007
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发表时间：
2018-10-01
影响因子：
4
通讯作者：
Ren, Dong-Mei
中科院分区：
文献类型：
--
作者：
Shen, Tao;Li, Hai-Zhen;Ren, Dong-Mei
过量的细胞内活性氧（ROS）产生是许多疾病的重要致病因素，例如血管疾病。线粒体是内源性ROS的主要来源，其同时诱导线粒体功能障碍。核因子-红细胞2相关因子2（Nrf 2）是一种重要的细胞内防御系统，可保护细胞免受ROS引起的氧化损伤。因此，具有诱导Nrf 2和防止线粒体功能障碍的能力的分子可以抑制细胞凋亡，因此是用于治疗ROS介导的血管疾病的潜在候选药物。高圣草酚（Homoeriodictyol，HE）是一种Nrf 2的诱导剂。在本研究中，我们研究了其保护ROS诱导的内皮细胞损伤使用H2 O2诱导的人脐静脉EA.hy926细胞氧化损伤模型。我们的研究结果表明，HE激活Nrf 2信号通路，保护细胞免受H2 O2诱导的细胞损伤。HE可减轻H2 O2诱导的线粒体膜电位（MMP）降低，阻断线粒体释放细胞色素C和凋亡诱导因子（AIF），从而抑制H2 O2介导的细胞凋亡。HE还能抑制H_2O_2诱导的凋亡相关蛋白Bcl-2、Bcl-xL、caspase-3、caspase-9和PARP的变化。进一步的研究表明，HE对H2 O2诱导的内皮细胞损伤的保护作用是Nrf 2依赖的。总的来说，我们的观察结果表明，HE能够抵消内皮细胞的氧化损伤，并有可能成为一种治疗剂对ROS介导的血管疾病。
Excess intracellular reactive oxygen species (ROS) production is a significant causative factor of many diseases, exemplified by vascular diseases. Mitochondria are a major source of endogenous ROS, which simultaneously induce mitochondrial dysfunction. Nuclear factor-erythroid 2-related factor 2 (Nrf2) represents an important intracellular defense system that protects cells against oxidative insults caused by ROS. Therefore, molecules with the capacities of inducing Nrf2, and preventing mitochondrial dysfunction can inhibit cell apoptosis, and thus are potential drug candidates for the therapy of ROS-mediated vascular diseases. Homoeriodictyol (HE), previously isolated from Viscun articulatum Burm, has been found to be an Nrf2 inducer. In the present study, we investigated its protection on ROS-induced endothelial cell injury using a H2O2-induced human umbilical vein EA.hy926 cell oxidative insult model. Our results indicated that HE activated Nrf2 signaling pathway and protected cells against H2O2-induced cell damage. HE alleviated H2O2-induced loss of mitochondrial membrane potential (MMP), blocked the releases of cytochrome C and apoptosis inducing factor (AIF) from mitochondria, and thus inhibited mitochondria-mediated cell apoptosis. Furthermore, HE inhibited H2O2-induced changes of apoptosis-related proteins, such as Bcl-2, Bcl-xL, caspases -3, -9 and PARP. Further study demonstrated that the protection of HE against H2O2-induced endothelial cell damage was Nrf2-dependent. Collectively, our observations suggest that HE is capable of counteracting oxidative insults in endothelial cells, and has a potential to be a therapeutic agent against ROS-mediated vascular diseases.