首页> 外文期刊>The Journal of Nutritional Biochemistry >Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells.
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Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells.

机译:羟基酪醇通过同时激活视网膜色素上皮细胞中的线粒体生物发生和II期解毒酶系统来防止氧化损伤。

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摘要

Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1 alpha) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including gamma-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1 alpha led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress.
机译:该实验室的研究先前表明,羟基酪醇是橄榄中的主要抗氧化剂多酚,可保护ARPE-19人视网膜色素上皮细胞免受丙烯醛(一种环境毒素和脂质氧化的内源性终产物)诱导的氧化损伤,而丙烯醛水平升高。老年性黄斑变性病变。为此提出的机制是通过同时激活两个至关重要的途径,即诱导II期解毒酶和刺激线粒体生物发生,来赋予羟基酪醇抵抗氧化应激的保护作用。用羟基酪醇预处理培养的ARPE-19细胞,并用丙烯醛攻击。考察了羟基酪醇对线粒体生物发生和Ⅱ期解毒酶系统关键因子的保护作用。羟基酪醇处理可同时防止丙烯醛对ARPE-19细胞中核因子E2相关因子2(Nrf2)和过氧化物酶体增殖物激活受体共激活因子1 alpha(PPARGC1 alpha)的抑制作用。 Nrf2的激活导致II期解毒酶的激活,包括γ-谷氨酰基-半胱氨酸-连接酶,NADPH(烟酰胺腺嘌呤二核苷酸磷酸)-醌氧化还原酶1,血红素加氧酶-1,超氧化物歧化酶,过氧化物酶和硫氧还蛋白其他抗氧化酶,而PPARGC1 alpha的激活导致线粒体转录因子A,蛋白2和线粒体复合物的蛋白表达增加。这些结果表明,羟基酪醇是II期解毒酶的有效诱导剂和线粒体生物发生的增强剂。饮食中的羟基酪醇可以通过防止氧化应激诱导的视网膜色素上皮细胞变性来促进眼睛健康。

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