Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.

Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.
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DOI:
10.1016/j.tem.2021.07.009
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发表时间:
2021-10
期刊:
Trends in endocrinology and metabolism: TEM
影响因子:
--
通讯作者:
Anakk S
Anakk S
中科院分区:
其他
文献类型:
--
作者:
Sen A;Anakk S

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核受体(NR)是调节基因网络和生理反应的配体结合转录因子。通常氧化应激先于肝脏疾病的发生,而 Nrf2 是抗氧化途径的关键调节因子。 NR 与 Nrf2 相互干扰,因为 NR 激活可以通过调节还原细胞过程来影响氧化环境。饮食和外源物质也调节 NR 表达和活性,这表明存在反馈循环。根据组织环境和线索,NR 会增加或减少毒性和氧化损伤。 FDA 批准的许多药物都以 NR 为靶点,并且有可能重新利用它们来改善活性氧。在这里,我们讨论了几种 NR 如何调节饮食、有机污染物和药物引起的肝脏损伤后的氧化应激。
Nuclear receptors (NRs) are ligand-binding transcription factors that regulate gene networks and physiological responses. Often oxidative stress precedes the onset of liver diseases and Nrf2 is a key regulator of antioxidant pathways. NRs crosstalk with Nrf2 since NR activation can influence the oxidative milieu by modulating the reductive cellular processes. Diet and xenobiotics also regulate NR expression and activity, suggesting a feedback loop. Depending on the tissue contexts and cues, NRs either increase or decrease toxicity and oxidative damage. Many of the FDA-approved drugs target NRs, and one could potentially repurpose them to ameliorate reactive oxygen species. Here, we discuss how several NRs modulate oxidative stress subsequent to the diet, organic pollutants, and drug-induced injury to the liver.
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