Artemisinin protects human retinal pigment epithelial cells from hydrogen peroxide-induced oxidative damage through activation of ERK/CREB signaling.
Artemisinin protects human retinal pigment epithelial cells from hydrogen peroxide-induced oxidative damage through activation of ERK/CREB signaling.
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青蒿素通过激活 ERK/CREB 信号传导保护人视网膜色素上皮细胞免受过氧化氢诱导的氧化损伤
DOI：
10.1016/j.redox.2016.06.002
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发表时间：
2016-10
期刊：
影响因子：
11.4
通讯作者：
Zheng W
中科院分区：
文献类型：
--
作者：
Chong CM;Zheng W
视网膜色素上皮 (RPE) 中活性氧 (ROS) 水平的病理性增加与年龄相关性黄斑变性 (AMD) 的发展有关。需要发现有效保护 RPE 细胞免受氧化损伤的候选药物，以解决 AMD 的病理问题并改变其进程。在这项研究中，FDA 批准的抗疟疾药物青蒿素被发现可以抑制过氧化氢 (H2O2) 诱导的人 RPE 细胞 D407 细胞的细胞死亡。进一步的研究表明，青蒿素通过恢复核形态、细胞内ROS、线粒体膜电位和凋亡生物标志物的异常变化，显着抑制H2O2−诱导的D407细胞死亡。蛋白质印迹分析表明，青蒿素能够激活细胞外调节的 ERK/CREB 存活信号。此外，在 ERK 抑制剂 PD98059 存在的情况下，青蒿素无法抑制 H2O2 诱导的细胞毒性和 caspase 3/7 活性的增加。综上所述，这些结果表明青蒿素是一种潜在的保护剂，通过激活 ERK/CREB 途径，具有抗 H2O2 损伤的促生存作用。青蒿素调节 △ψm 和 caspase 3 凋亡途径。青蒿素诱导 ERK/CREB 信号通路。青蒿素可保护 RPE 细胞免受 H2O2 诱导的氧化应激。青蒿素抑制 H2O2 诱导的 RPE 细胞中 ROS 的增加。
The pathological increase in the levels of reactive oxygen species (ROS) in the retinal pigment epithelium (RPE), is implicated in the development of age-related macular degeneration (AMD). The discovery of drug candidates to effectively protect RPE cells from oxidative damage is required to resolve the pathological aspects and modify the process of AMD. In this study, a FDA-approved anti-malaria drug, Artemisinin was found to suppress hydrogen peroxide (H2O2)-induced cell death in human RPE cell-D407 cells. Further study showed that Artemisinin significantly suppressed H2O2− induced D407 cell death by restoring abnormal changes in nuclear morphology, intracellular ROS, mitochondrial membrane potential and apoptotic biomarkers. Western blotting analysis showed that Artemisinin was able to activate extracellular regulated ERK/CREB survival signaling. Furthermore, Artemisinin failed to suppress H2O2-induced cytotoxicity and the increase of caspase 3/7 activity in the presence of the ERK inhibitor PD98059. Taken together, these results suggest that Artemisinin is a potential protectant with the pro-survival effects against H2O2 insult through activation of the ERK/CREB pathway. Artemisinin modulates △ψm and caspase 3 apoptotic pathways. Artemisinin induces ERK/CREB signaling pathway. Artemisinin protects RPE cells against H2O2-induced oxidative stress. Artemisinin suppresses H2O2-induced the increase of ROS in RPE cells.