Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells
Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells
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DOI：
10.1021/acs.jafc.7b01929
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发表时间：
2017-07-26
影响因子：
6.1
通讯作者：
Baldermann, Susanne
中科院分区：
文献类型：
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作者：
Frede, Katja;Ebert, Franziska;Baldermann, Susanne
由氧化损伤引起的视网膜色素上皮变性是年龄相关性黄斑变性（AMD）的发展阶段。类胡萝卜素叶黄素是一种主要的黄斑色素，可以减少 AMD 的发生和进展，但其潜在机制目前尚不完全清楚。已知类胡萝卜素是直接抗氧化剂。然而，类胡萝卜素还可以激活细胞途径，从而产生间接的抗氧化作用。在这里，我们使用负载叶黄素的 Tween40 胶束研究叶黄素对人视网膜色素上皮细胞（ARPE-19 细胞）中核因子红细胞 2 相关因子 2 (Nrf2) 靶基因激活的影响。这些胶束被认为是合适的递送系统，因为它们在 APRE-19 细胞中最高可达 0.04% Tween40 是无毒的，并且在 24 小时后导致细胞叶黄素积累为 62 muM +/- 14 muM。 4小时后，与未负载的胶束相比，叶黄素显着增强Nrf2向细胞核的易位1.5+/-0.4倍。此外，叶黄素处理24小时使NAD(P)H:醌氧化还原酶1 (NQO1)的转录物显着增加1.7 +/- 0.1倍，谷氨酸半胱氨酸连接酶调节亚基(GCLm)的转录物显着增加1.4 +/- 0.1倍，血红素加氧酶-1 (HO-1)的转录物显着增加1.8 +/- 0.3倍。此外，我们观察到 NQO1 活性显着增强 1.2 +/- 0.1 倍。总的来说，这项研究表明叶黄素不仅可以作为直接抗氧化剂，还可以激活 ARPE-19 细胞中的 Nrf 2。
The degeneration of the retinal pigment epithelium caused by oxidative damage is a stage of development in age related macular degeneration (AMD). The carotenoid lutein is a major macular pigment that may reduce the incidence and progression of AMD, but the underlying mechanism is currently not fully understood. Carotenoids are known to be direct antioxidants. However, carotenoids can also activate cellular pathways resulting in indirect antioxidant effects. Here, we investigate the influence of lutein on the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes in human retinal pigment epithelial cells (ARPE-19 cells) using lutein-loaded Tween40 micelles. The micelles were identified as a suitable delivery system since they were nontoxic in APRE-19 cells up to 0.04% Tween40 and led to a cellular lutein accumulation of 62 mu M +/- 14 mu M after 24 h. Lutein significantly enhanced Nrf2 translocation to the nucleus 1.5 +/- 0.4-fold compared to that of unloaded micelles after 4 h. Furthermore, lutein treatment for 24 h significantly increased the transcripts of NAD(P)H:quinone oxidoreductase 1 (NQO1) by 1.7 +/- 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 +/- 0.1-fold, and heme oxygenase-1 (HO-1) by 1.8 +/- 0.3-fold. Moreover, we observed a significant enhancement of NQO1 activity by 1.2 +/- 0.1-fold. Collectively, this study indicates that lutein not only serves as a direct antioxidant but also activates Nrf 2 in ARPE-19 cells.