Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal.
Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal.
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DOI：
10.1016/j.yexcr.2016.09.002
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发表时间：
2016-10
影响因子：
3.7
通讯作者：
Xue Zhu;Ke Wang;Kai Zhang;Fanfan Zhou;Ling Zhu
中科院分区：
文献类型：
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作者：
Xue Zhu;Ke Wang;Kai Zhang;Fanfan Zhou;Ling Zhu
据估计，游离型全反式视网膜（atRAL）清除延迟是年龄相关性黄斑变性（AMD）等视网膜病变发病过程中视网膜色素上皮（RPE）细胞损伤的关键原因，然而，其潜在的分子机制尚不清楚。在本研究中，我们研究了 atRAL 对人视网膜色素上皮 ARPE-19 细胞的细胞毒性作用及其潜在分子机制。结果表明，atRAL 可通过诱导 ARPE-19 细胞氧化和亚硝化应激而导致细胞功能障碍。 atRAL 诱导的氧化应激是通过上调活性氧 (ROS) 生成、激活线粒体依赖性和 MAPK 信号通路介导的，最终导致 ARPE-19 细胞凋亡。 NADPH 氧化酶抑制剂 apocynin 可以部分减弱 ROS 的产生，表明 NADPH 氧化酶活性参与 atRAL 诱导的 ARPE-19 细胞氧化应激。 atRAL诱导的亚硝化应激主要体现在增加一氧化氮（NO）产生，增强iNOS、ICAM-1和VCAM-1表达，促进单核细胞粘附。此外，使用核因子κB（NF-κB）抑制剂SN50可以显着阻断上述效应，表明atRAL诱导的氧化和亚硝化应激是由NF-κB介导的。这些结果有助于更好地了解 atRAL 诱导的人类 RPE 细胞毒性。
Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells.