Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction
Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction
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DOI：
10.1111/j.1471-4159.2007.04954.x
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发表时间：
2007-12-01
影响因子：
4.7
通讯作者：
Liu, Jiankang
中科院分区：
文献类型：
--
作者：
Liu, Zhongbo;Sun, Lijuan;Liu, Jiankang
羟基酪醇（HTS）是橄榄油中富含的一种天然多酚。越来越多的证据表明高温超导体对人类健康具有有益的作用，可以预防多种疾病。在本研究中，我们研究了HTS对人视网膜色素上皮细胞系ARPE-19（吸烟和年龄相关性黄斑变性的细胞模型）中丙烯醛诱导的毒性的保护作用。丙烯醛是香烟烟雾中的主要成分，也是体内脂质过氧化的产物，在75 μ mol/L下作用24 h可引起细胞活力明显丧失，氧化损伤（氧化剂生成增加和对蛋白质和DNA的氧化损伤，抗氧化剂和抗氧化酶减少，以及Keap 1/Nrf 2途径失活），和线粒体功能障碍（膜电位、线粒体复合物活性、活线粒体、氧消耗和线粒体生物发生因子的降低，以及钙的增加）。HTS剂量依赖性和时间依赖性地保护ARPE-19细胞免受丙烯醛诱导的氧化损伤和线粒体功能障碍。HTS短期预处理（48 h）需要> 75 μ mol/L才能显示保护作用，而长期预处理（7 d）从5 μ mol/L开始显示保护作用。HTS在该模型中的保护作用与已建立的以EPA为靶点的抗氧化营养素一样有效。这些结果表明，HTS也是一种以肾脏为靶点的抗氧化营养素，HTS的饮食给药可能是减少和/或预防香烟烟雾诱导的或年龄相关的视网膜色素上皮变性（如年龄相关性黄斑变性）的有效措施。
Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 mu mol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required > 75 mu mol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 mu mol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration.