Nrf2 for cardiac protection: pharmacological options against oxidative stress.
Nrf2 for cardiac protection: pharmacological options against oxidative stress.
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Nrf2用于心脏保护：对抗氧化应激的药理学选择
DOI：
10.1016/j.tips.2021.06.005
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发表时间：
2021-09
影响因子：
13.8
通讯作者：
Chen QM
中科院分区：
文献类型：
--
作者：
Chen QM
心肌缺血或再灌注会增加受损线粒体、NADPH氧化酶、黄嘌呤氧化酶以及炎症反应所产生的活性氧（ROS）。ROS可被八种内源性抗氧化和氧化还原系统清除，其中许多成分在活化的Nrf2转录因子的影响下表达。转录组分析、Nrf2结合DNA的测序以及Nrf2基因敲除研究揭示了Nrf2的作用超出了抗氧化和解毒反应，包括从组织恢复、修复和重塑、线粒体更新、代谢重编程到抑制促炎细胞因子等方面。Nrf2蛋白水平或活性的多方面调节机制已被定位到其功能域Nrf2 - ECH同源结构域（Neh）1 - 7。氧化应激通过核转位、从头蛋白质翻译以及由于去除了类Kelch的ECH相关蛋白1（Keap1）检查点、β - 转导素重复包含蛋白（β - TrCP）失活或Hmg - CoA还原酶降解蛋白1（Hrd1）而增加的蛋白质稳定性来激活Nrf2。本文讨论了来自天然产物或其衍生物的小分子Nrf2诱导剂的前景。提供了实验证据以支持Nrf2作为药物开发的主要靶点，以进一步改善心肌梗死（MI）的治疗效果。
Myocardial ischemia or reperfusion increases the generation of reactive oxygen species (ROS) from damaged mitochondria, NADPH oxidases, xanthine oxidase, and inflammation. ROS can be removed by eight endogenous antioxidant and redox systems, many components of which are expressed under the influence of the activated Nrf2 transcription factor. Transcriptomic profiling, sequencing of Nrf2-bound DNA, and Nrf2 gene knockout studies have revealed the power of Nrf2 beyond the antioxidant and detoxification response, from tissue recovery, repair, and remodeling, mitochondrial turnover, and metabolic reprogramming to the suppression of proinflammatory cytokines. Multifaceted regulatory mechanisms for Nrf2 protein levels or activity have been mapped to its functional domains, Nrf2-ECH homology (Neh)1–7. Oxidative stress activates Nrf2 via nuclear translocation, de novo protein translation, and increased protein stability due to removal of the Kelch-like ECH-associated protein 1 (Keap1) checkpoint, or the inactivation of β-transducin repeat-containing protein (β-TrCP), or Hmg-CoA reductase degradation protein 1 (Hrd1). The promise of small-molecule Nrf2 inducers from natural products or derivatives is discussed here. Experimental evidence is presented to support Nrf2 as a lead target for drug development to further improve the treatment outcome for myocardial infarction (MI).
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影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
DOI：
10.1056/nejmoa1306033
发表时间：
2013-12-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
de Zeeuw D;Akizawa T;Audhya P;Bakris GL;Chin M;Christ-Schmidt H;Goldsberry A;Houser M;Krauth M;Lambers Heerspink HJ;McMurray JJ;Meyer CJ;Parving HH;Remuzzi G;Toto RD;Vaziri ND;Wanner C;Wittes J;Wrolstad D;Chertow GM;BEACON Trial Investigators
通讯作者：
BEACON Trial Investigators
影响因子：
7.4
作者：
Erkens, Ralf;Kramer, Christian M.;Cortese-Krott, Miriam M.
通讯作者：
Cortese-Krott, Miriam M.
影响因子：
8
作者：
Chowdhry, S.;Zhang, Y.;McMahon, M.;Sutherland, C.;Cuadrado, A.;Hayes, J. D.
通讯作者：
Hayes, J. D.
影响因子：
158.5
作者：
Cannon, CP;Braunwald, E;Skene, AM
通讯作者：
Skene, AM