NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium.

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Alina Löser, Maria Schwarz, Anna Patricia Kipp
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引用次数: 0

Abstract

Background: Selenium and zinc are essential trace elements known to regulate cellular processes including redox homeostasis. During inflammation, circulating selenium and zinc concentrations are reduced in parallel, but underlying mechanisms are unknown. Accordingly, we modulated the zinc and selenium supply of HepG2 cells to study their relationship.

Methods: HepG2 cells were supplied with selenite in combination with a short- or long-term zinc treatment to investigate intracellular concentrations of selenium and zinc together with biomarkers describing their status. In addition, the activation of the redox-sensitive transcription factor NRF2 was analyzed.

Results: Zinc not only increased the nuclear translocation of NRF2 after 2 to 6 h but also enhanced the intracellular selenium content after 72 h, when the cells were exposed to both trace elements. In parallel, the activity and expression of the selenoprotein thioredoxin reductase 1 (TXNRD1) increased, while the gene expression of other selenoproteins remained unaffected or was even downregulated. The zinc effects on the selenium concentration and TXNRD activity were reduced in cells with stable NRF2 knockdown in comparison to control cells.

Conclusions: This indicates a functional role of NRF2 in mediating the zinc/selenium crosstalk and provides an explanation for the observed unidirectional behavior of selenium and zinc.

NRF2和硫氧化还原酶1是锌和硒相互作用的调节剂
背景:硒和锌是人体必需的微量元素,可调节细胞过程,包括氧化还原平衡。在炎症期间,循环中的硒和锌浓度会同时降低,但其潜在机制尚不清楚。因此,我们调节了 HepG2 细胞的锌和硒供应,以研究它们之间的关系。方法:向 HepG2 细胞提供亚硒酸盐,并结合短期或长期锌处理,以研究细胞内硒和锌的浓度以及描述其状态的生物标志物。此外,还分析了氧化还原敏感转录因子 NRF2 的激活情况:结果:当细胞暴露于锌和硒这两种微量元素时,锌不仅能在 2 至 6 小时后增加 NRF2 的核转位,还能在 72 小时后提高细胞内硒的含量。与此同时,硒蛋白硫氧还蛋白还原酶 1(TXNRD1)的活性和表达也增加了,而其他硒蛋白的基因表达则不受影响,甚至出现下调。与对照细胞相比,稳定敲除NRF2的细胞中锌对硒浓度和TXNRD活性的影响减弱:结论:这表明 NRF2 在介导锌/硒串扰中发挥了功能性作用,并为观察到的硒和锌的单向行为提供了解释。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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