Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress
Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress
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七叶皂苷激活 AKT-Nrf2 信号传导以保护视网膜色素上皮细胞免受氧化应激
DOI：
10.1016/j.bbrc.2015.10.117
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发表时间：
2015-12-25
影响因子：
3.1
通讯作者：
Chen, Min
中科院分区：
文献类型：
--
作者：
Wang, Kaijun;Jiang, Yiqian;Chen, Min
在这里，我们探讨了七叶皂苷，一种天然的三萜皂苷，对过氧化氢（H2 O2）在视网膜色素上皮（RPE）细胞的抗氧化和细胞保护潜力。我们发现，七叶皂苷显着衰减H2 O2诱导的死亡和细胞凋亡的建立（ARPE-19）和原代小鼠RPE细胞。同时，七叶皂苷显著抑制H2 O2引起的ROS生成和脂质过氧化反应。在RPE细胞中的七叶皂苷处理导致NF-E2相关因子2（Nrf 2）信号传导激活，这通过抗氧化反应元件（ARE）调节基因（包括HO-1、NQO-1和SRXN-1）的转录来证明。通过靶向shRNA/siRNA敲低Nrf 2可减轻七叶皂苷介导的ARE基因转录，并几乎消除七叶皂苷介导的抗氧化活性和RPE对H2 O2的细胞保护作用。因此，七叶皂苷对Nrf 2过表达的ARPE-19细胞中的H2 O2损伤更有效。进一步的研究表明，七叶皂苷诱导的RPE细胞中的Nrf 2激活需要ART信号。ART抑制剂（LY 294002和perifosine）阻断了七叶皂苷诱导的ART激活，并显着抑制Nrf 2磷酸化，其在RPE细胞中的胞浆积累和核转位。AKT抑制剂也能减轻EclO诱导的RPE对H2 O2的细胞保护作用。总之，这些结果表明，七叶皂苷可能通过激活AKT-Nrf 2信号传导保护RPE细胞免受氧化应激。(C)2015爱思唯尔公司All rights reserved.
Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H2O2) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H2O2-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H2O2 were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H2O2. Reversely, escin was more potent against H2O2 damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required ART signaling. ART inhibitors (LY294002 and perifosine) blocked escin-induced ART activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H2O2 was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling. (C) 2015 Elsevier Inc. All rights reserved.