Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light.
Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light.
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DOI：
10.1016/j.exer.2016.12.001
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发表时间：
2017-01
影响因子：
3.4
通讯作者：
Duh EJ
中科院分区：
文献类型：
--
作者：
Chen WJ;Wu C;Xu Z;Kuse Y;Hara H;Duh EJ
氧化应激在年龄相关性黄斑变性和遗传性视网膜变性中起关键作用。啮齿类动物的光损伤已被广泛用于模拟氧化应激诱导的光感受器变性，蓝光的光氧化损伤对光感受器的损害尤其严重。保护光感受器免受氧化应激（包括光氧化应激）的内源性因素正在继续阐明。在这项研究中，我们评估了蓝光暴露对光感受器的影响及其与Nrf 2的关系，使用培养的小鼠感光细胞（661 W）。将661 W细胞暴露于2500勒克斯的蓝光。蓝光照射661 W细胞6 ~ 24 h后，细胞内活性氧（ROS）明显增加，细胞死亡率随照射时间的延长而增加。蓝光照射导致Nrf 2的激活，如Nrf 2的核转位增加所示。如定量逆转录PCR（qRT-PCR）所示，这与Nrf 2表达的显著诱导以及一系列Nrf 2靶基因（包括抗氧化基因）相关。为了确定Nrf 2的功能作用，进行了siRNA介导的敲低研究。在661 W细胞中Nrf 2敲低导致蓝光诱导的活性氧水平的显著恶化以及细胞死亡。总之，这些发现表明，Nrf 2是一个重要的内源性保护因子，对感光细胞的氧化应激。这表明靶向Nrf 2的药物可以被认为是AMD和其他视网膜疾病中光感受器的神经保护策略。
Oxidative stress plays a key role in age-related macular degeneration and hereditary retinal degenerations. Light damage in rodents has been used extensively to model oxidative stress-induced photoreceptor degeneration, and photo-oxidative injury from blue light is particularly damaging to photoreceptors. The endogenous factors protecting photoreceptors from oxidative stress, including photo-oxidative stress, are continuing to be elucidated. In this study, we evaluated the effect of blue light exposure on photoreceptors and its relationship to Nrf2 using cultured murine photoreceptor (661W) cells. 661W cells were exposed to blue light at 2500 lux. Exposure to blue light for 6 to 24 hours resulted in a significant increase in intracellular reactive oxygen species (ROS) and death of 661W cells in a time-dependent fashion. Blue light exposure resulted in activation of Nrf2, as indicated by an increase in nuclear translocation of Nrf2. This was associated with a significant induction of expression of Nrf2 as well as an array of Nrf2 target genes, including antioxidant genes, as indicated by quantitative reverse transcription PCR (qRT-PCR). In order to determine the functional role of Nrf2, siRNA-mediated knockdown studies were performed. Nrf2-knockdown in 661W cells resulted in significant exacerbation of blue light-induced reactive oxygen species levels as well as cell death. Taken together, these findings indicate that Nrf2 is an important endogenous protective factor against oxidative stress in photoreceptor cells. This suggests that drugs targeting Nrf2 could be considered as a neuroprotective strategy for photoreceptors in AMD and other retinal conditions.
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DOI：
10.1523/jneurosci.4265-11.2011
发表时间：
2011-12-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Tang PH;Buhusi MC;Ma JX;Crouch RK
通讯作者：
Crouch RK
影响因子：
17.8
作者：
Margrain, TH;Boulton, M;Sliney, DH
通讯作者：
Sliney, DH
影响因子：
4.4
作者：
Pitha-Rowe, Ian;Liby, Karen;Sporn, Michael
通讯作者：
Sporn, Michael
影响因子：
17.8
作者：
Organisciak, Daniel T.;Vaughan, Dana K.
通讯作者：
Vaughan, Dana K.
影响因子：
4.4
作者：
Tan, E;Ding, XQ;Al-Ubaidi, MR
通讯作者：
Al-Ubaidi, MR