Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV
Activation of Nrf2 by Ginsenoside Rh3 protects retinal pigment epithelium cells and retinal ganglion cells from UV
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人参皂苷 Rh3 激活 Nrf2 可保护视网膜色素上皮细胞和视网膜神经节细胞免受紫外线侵害
DOI：
10.1016/j.freeradbiomed.2018.02.001
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发表时间：
2018-03-01
影响因子：
7.4
通讯作者：
Cao, Cong
中科院分区：
文献类型：
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作者：
Tang, Chun-zhou;Li, Ke-Ran;Cao, Cong
过度的紫外线 (UV) 辐射会对常驻视网膜色素上皮 (RPE) 细胞 (RPE) 和视网膜神经节细胞 (RGC) 造成损害。在这里，我们测试了人参皂苷 Rh3（“Rh3”）对该过程的潜在活性。在培养的人类 RPE 和 RGC 中，Rh3 预处理可抑制紫外线诱导的活性氧 (ROS) 产生以及凋亡/非凋亡细胞死亡。视网膜细胞中的 Rh3 处理诱导核因子 E2 相关因子 2 (Nrf2) 激活，Nrf2 蛋白稳定化及其核转位以及抗氧化反应元件 (ARE) 依赖性基因（HO1、NOQ1 和 GCLC）的转录证明了这一点。通过靶向shRNA敲低Nrf2几乎消除了Rh3诱导的视网膜细胞对紫外线的保护。进一步的研究发现，Rh3 诱导 microRNA-141（“miR-141”）表达，导致 RPE 和 RGC 中其靶基因 Keap1 下调。另一方面，Rh3 诱导的 Nrf2 激活和视网膜细胞保护在很大程度上被 miR-141 的抑制剂 antagomiR-141 减弱。在体内，玻璃体内注射 Rh3 可抑制小鼠光损伤引起的视网膜功能障碍。 Rh3 玻璃体内注射还诱导小鼠视网膜中 miR-141 表达、Keap1 下调和 Nrf2 激活。我们得出结论，Rh3 通过激活 Nrf2 信号传导来保护视网膜细胞免受紫外线侵害。
Excessive Ultra-violet (UV) radiation shall induce damages to resident retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs). Here we tested the potential activity of Ginsenoside Rh3 ("Rh3") against the process. In cultured human RPEs and RGCs, pretreatment with Rh3 inhibited UV-induced reactive oxygen species (ROS) production and following apoptotic/non-apoptotic cell death. Rh3 treatment in retinal cells induced nuclear-factor-E2-related factor 2 (Nrf2) activation, which was evidenced by Nrf2 protein stabilization and its nuclear translocation, along with transcription of antioxidant responsive element (ARE)-dependent genes (HO1, NOQ1 and GCLC). Nrf2 knockdown by targeted-shRNA almost abolished Rh3-induced retinal cell protection against UV. Further studies found that Rh3 induced microRNA-141 ("miR-141") expression, causing downregulation of its targeted gene Keap1 in RPEs and RGCs. On the other hand, Rh3-induced Nrf2 activation and retinal cell protection were largely attenuated by the miR-141's inhibitor, antagomiR-141. In vivo, intravitreal injection of Rh3 inhibited retinal dysfunction by light damage in mice. Rh3 intravitreal injection also induced miR-141 expression, Keap1 downregulation and Nrf2 activation in mouse retinas. We conclude that Rh3 protects retinal cells from UV via activating Nrf2 signaling.