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Tea polyphenols direct Bmal1-driven ameliorating of the redox imbalance and mitochondrial dysfunction in hepatocytes
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-10-11 , DOI: 10.1016/j.fct.2018.10.031
Guoyuan Qi 1 , Wanqiang Wu 1 , Yashi Mi 1 , Renjie Shi 1 , Keyu Sun 1 , Runnan Li 1 , Xiao Liu 1 , Xuebo Liu 1
Affiliation  

Circadian rhythms are intimately linked to cellular redox status homeostasis via the regulation of mitochondrial function. Tea polyphenols (TP) are nutraceuticals that possess powerful antioxidant properties, especially ameliorating oxidative stress. The objective of this study was to investigate whether circadian clock is involved in the protection effect of TP on oxidative stress cell models. TP ameliorate H2O2-triggered relatively shallow daily oscillations and phase shift of circadian clock genes transcription and protein expression. Meanwhile, TP attenuate H2O2-stimulated excessive secretions of reactive oxygen species (ROS) and restore the depletions of mitochondrial function in a Bmal1-dependent manner. Furthermore, TP treatment accelerates nuclear translocation of Nrf2 and modulates the downstream expressions of antioxidant enzymes. Intriguingly, knockdown of Bmal1 notably blocked Nrf2/ARE/HO-1 redox-sensitive transcription pathway. Our study revealed that TP, as a Bmal1-enhancing natural compound, alleviated redox imbalance via strengthening Keap1/Nrf2 antioxidant defense pathway and ameliorating mitochondrial dysfunction in a Bmal1-dependent manner.



中文翻译:


茶多酚直接改善 Bmal1 驱动的肝细胞氧化还原失衡和线粒体功能障碍



昼夜节律通过线粒体功能的调节与细胞氧化还原状态稳态密切相关。茶多酚 (TP) 是一种营养保健品,具有强大的抗氧化特性,尤其是改善氧化应激。本研究的目的是探讨生物钟是否参与TP对氧化应激细胞模型的保护作用。 TP 改善 H 2 O 2 - 触发昼夜节律时钟基因转录和蛋白质表达的相对较浅的每日振荡和相移。同时,TP 可减弱 H 2 O 2刺激的活性氧 (ROS) 的过度分泌,并以 Bmal1 依赖性方式恢复线粒体功能的损耗。此外,TP 处理加速 Nrf2 的核转位并调节抗氧化酶的下游表达。有趣的是,Bmal1 的敲低显着阻断了 Nrf2/ARE/HO-1 氧化还原敏感转录途径。我们的研究表明,TP 作为一种增强 Bmal1 的天然化合物,可以通过增强 Keap1/Nrf2 抗氧化防御途径并以 Bmal1 依赖性方式改善线粒体功能障碍来缓解氧化还原失衡。

更新日期:2018-10-11
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