Nrf2 affects DNA damage repair and cell apoptosis through regulating HR and the intrinsic Caspase-dependent apoptosis pathway in TK6 cells exposed to hydroquinone

IF 2.6 3区医学 Q3 TOXICOLOGY Toxicology in Vitro Pub Date : 2024-07-18 DOI:10.1016/j.tiv.2024.105901

Lin Chen , Pu Guo , Lu Zhai, Lingxue Yu, Delong Zhu, Xiaoyi Hu, Zhuanzhuan Li, Yuting Chen, Qian Sun, Lei Sun, Hao Luo, Huanwen Tang

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Abstract

Hydroquinone (HQ) is one of benzene metabolites that can cause oxidative stress damage and Homologous recombination repair (HR). A good deal of reactive oxygen species (ROS) generated by oxidative stress can trigger apoptotic signaling pathways. The nuclear factor erythroid 2-related factor 2 (Nrf2) can regulate the cell response to oxidative stress damage. The aim of this study was to explore whether Nrf2 participate in HQ-induced apoptosis and its mechanism. The findings displayed that HQ triggered HR, promoted Nrf2 transfer into the cell nucleus and induced cell apoptosis, while Nrf2 deficient elevated cell apoptosis, attenuated the expression of PARP1 and RAD51. We also observed that Nrf2 deficient triggered Caspase-9. Thus, we speculated that Nrf2 might participate in HQ-induced cell apoptosis through Caspase-9 dependent pathways. Meanwhile, Nrf2 participated in HQ-induced DNA damage repair by regulating the level of PARP1 and RAD51.

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在暴露于氢醌的TK6细胞中，Nrf2通过调节HR和依赖于Caspase的内在凋亡途径影响DNA损伤修复和细胞凋亡。

对苯二酚（HQ）是苯的代谢产物之一，可导致氧化应激损伤和同源重组修复（HR）。氧化应激产生的大量活性氧（ROS）可触发细胞凋亡信号通路。核因子红细胞2相关因子2（Nrf2）可以调节细胞对氧化应激损伤的反应。本研究旨在探讨Nrf2是否参与了HQ诱导的细胞凋亡及其机制。研究结果表明，HQ诱导HR，促进Nrf2转移到细胞核内，诱导细胞凋亡，而Nrf2缺乏会增加细胞凋亡，减少PARP1和RAD51的表达。我们还观察到，缺乏 Nrf2 会触发 Caspase-9。因此，我们推测 Nrf2 可能通过 Caspase-9 依赖性途径参与 HQ 诱导的细胞凋亡。同时，Nrf2通过调节PARP1和RAD51的水平参与了HQ诱导的DNA损伤修复。

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

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.