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MicroRNA-based regulatory mechanisms underlying the synergistic antioxidant action of quercetin and catechin in H2O2-stimulated HepG2 cells: Roles of BACH1 in Nrf2-dependent pathways.
Free Radical Biology and Medicine ( IF 7.1 ) Pub Date : 2020-04-25 , DOI: 10.1016/j.freeradbiomed.2020.04.018
Dan Wang 1 , Yang Jiang 2 , Dong-Xiao Sun-Waterhouse 3 , Hao Zhai 4 , Hui Guan 2 , Xue Rong 2 , Feng Li 2 , Jia-Cheng Yu 2 , Da-Peng Li 2
Affiliation  

The microRNA-based mechanisms underlying the antioxidant action(s) of co-existing flavonoids in response to oxidative stress are of high interest. This study aimed to extend the existing knowledge and provide insights into the potential regulatory network in response to oxidative stress and the co-presence of quercetin and catechin antioxidants, via a preclinical approach using H2O2-stimulated HepG2 cells. It was confirmed that BACH1 serves as an essential and direct negative regulator of the Keap1-Nrf2 signaling pathway and the antioxidant synergism between quercetin and catechin. BACH1 promoted reactive oxygen species (ROS) accumulation while inhibiting cell growth, which could be reversed by the synergistic action of let-7a-5p and miR-25-3p in the co-presence of quercetin and catechin. Both let-7a-5p and miR-25-3p could directly regulate the expression and function of BACH1 (e.g. upregulation of the two miRNAs could rescue largely overexpression of BACH1). Although these molecular interactions likely represented only some aspects of the overall regulatory network, this research confirms the feasibility of the combined uses of dietary flavonoids with chemopreventive properties in synergy during multiple-target interactions and multiple-pathway regulation.

中文翻译:

槲皮素和儿茶素在 H2O2 刺激的 HepG2 细胞中协同抗氧化作用的基于 MicroRNA 的调节机制:BACH1 在 Nrf2 依赖性途径中的作用。

共存类黄酮响应氧化应激的抗氧化作用的基于 microRNA 的机制引起了人们的高度关注。本研究旨在通过使用 H2O2 刺激的 HepG2 细胞的临床前方法,扩展现有知识并深入了解潜在的调节网络以应对氧化应激以及槲皮素和儿茶素抗氧化剂的共存。已证实 BACH1 是 Keap1-Nrf2 信号通路以及槲皮素和儿茶素之间的抗氧化协同作用的必需和直接负调节剂。BACH1 在抑制细胞生长的同时促进活性氧 (ROS) 的积累,这可以通过 let-7a-5p 和 miR-25-3p 在槲皮素和儿茶素的共同存在下的协同作用来逆转。let-7a-5p 和 miR-25-3p 都可以直接调节 BACH1 的表达和功能(例如,两种 miRNA 的上调可以很大程度上挽救 BACH1 的过表达)。尽管这些分子相互作用可能只代表了整个调控网络的某些方面,但这项研究证实了在多靶点相互作用和多途径调控过程中,膳食类黄酮与化学预防特性联合使用的可行性。
更新日期:2020-04-25
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