Leung Ho Hang, Galano Jean-Marie, Crauste Céline, Durand Thierry, Lee Jetty Chung-Yung
School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
Institut Des Biomolécules Max Mousseron, UMR 5247, CNRS, ENSCM, Université de Montpellier, Montpellier, France.
Neurochem Res. 2020 May;45(5):1007-1019. doi: 10.1007/s11064-020-02994-4. Epub 2020 Feb 22.
Photochemical and oxidative damages in retinal pigment epithelial (RPE) cells are key events in the pathogenesis of age-related macular degeneration. Polyunsaturated fatty acids (PUFA) and carotenoids are rich in retinal cells, and under oxidative stress leads to oxidation and release lipid mediators. We evaluated the impact of carotenoids (lutein, zeaxanthin) and docosahexaenoic acid (DHA) supplementation on RPE cells under oxidative stress. ARPE-19 cells were exposed to HO after pre-treatment with lutein, zeaxanthin, DHA, lutein + zeaxanthin or lutein + zeaxanthin with DHA. The data showed HO reduced cell viability and DHA content, while promoted catalase activity and certain oxidized PUFA products. Treatment with DHA enhanced omega-3 PUFA enzymatic oxidation namely, anti-inflammatory mediators such as hydroxy-DHA, resolvins and neuroprotection compared to control; the effects were not influenced by the carotenoids. Omega-6 PUFA oxidation, namely pro-inflammatory HETE (5-, 9-, 12 and 20-HETE), and isoprostanes (5- and 15-F-IsoP and 4-F-IsoP) were reduced by lutein + zeaxanthin while the addition of DHA did not further reduce these effects. We observed transcriptional regulation of 5-lipoxygenase by DHA and GPx1 and NEFEL2 by the carotenoids that potentially resulted in decreased HETEs and glutathione respectively. 4-HNE was not affected by the treatments but 4-HHE was reduced by lutein + zeaxanthin with and without DHA. To conclude, carotenoids and DHA appeared to regulate inflammatory lipid mediators while the carotenoids also showed benefits in reducing non-enzymatic oxidation of omega-6 PUFA.
视网膜色素上皮（RPE）细胞中的光化学损伤和氧化损伤是年龄相关性黄斑变性发病机制中的关键事件。视网膜细胞富含多不饱和脂肪酸（PUFA）和类胡萝卜素，在氧化应激下会导致氧化并释放脂质介质。我们评估了补充类胡萝卜素（叶黄素、玉米黄质）和二十二碳六烯酸（DHA）对氧化应激下RPE细胞的影响。在用叶黄素、玉米黄质、DHA、叶黄素+玉米黄质或叶黄素+玉米黄质与DHA预处理后，将ARPE-19细胞暴露于过氧化氢（HO）。数据显示，HO降低了细胞活力和DHA含量，同时提高了过氧化氢酶活性和某些氧化的PUFA产物。与对照组相比，DHA处理增强了ω-3 PUFA的酶促氧化，即抗炎介质如羟基-DHA、消退素和神经保护作用；这些作用不受类胡萝卜素的影响。叶黄素+玉米黄质可降低ω-6 PUFA的氧化，即促炎的羟二十碳四烯酸（5-、9-、12-和20-HETE）以及异前列腺素（5-和15-F-异前列腺素以及4-F-异前列腺素），而添加DHA并未进一步降低这些作用。我们观察到DHA对5-脂氧合酶有转录调控作用，类胡萝卜素对谷胱甘肽过氧化物酶1（GPx1）和核因子E2相关因子2（NFE2L2）有转录调控作用，这可能分别导致HETEs和谷胱甘肽减少。4-羟基壬烯醛（4-HNE）不受处理影响，但无论有无DHA，叶黄素+玉米黄质均可降低4-羟基己烯醛（4-HHE）。总之，类胡萝卜素和DHA似乎可调节炎症脂质介质，而类胡萝卜素在减少ω-6 PUFA的非酶促氧化方面也显示出益处。
