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Nrf2/Keap1信号通路在无机汞诱导大黄鱼肝脏氧化应激中的作用

The role of Nrf2/Keap1 signaling in inorganic mercury induced oxidative stress in the liver of large yellow croaker Pseudosciaena crocea.

作者信息

Zeng Lin, Zheng Jia-Lang, Wang Yong-Hong, Xu Mei-Ying, Zhu Ai-Yi, Wu Chang-Wen

机构信息

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022, PR China.

National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022, PR China.

出版信息

Ecotoxicol Environ Saf. 2016 Oct;132:345-52. doi: 10.1016/j.ecoenv.2016.05.002. Epub 2016 Jun 28.

DOI:10.1016/j.ecoenv.2016.05.002
PMID:27362492
Abstract

The aim of the present study was to evaluate the effects of acute inorganic Hg exposure (0, 32 and 64μgHgL(-1)) on lipid peroxidation, activities and gene expression of antioxidant enzymes (Cu/Zn-SOD, CAT, GPx, GR and GST), and mRNA levels of the Keap1-Nrf2 signaling molecules at different exposure times (6h, 12h, 24h, 48h, and 96h) in the liver of large yellow croaker Pseudosciaena crocea. The results showed that lipid peroxidation was sharply reduced by 32μg Hg L(-1) during 6-12h before returning to control levels. Similarly, lipid peroxidation was significantly reduced during 6-12h followed by a sharp increase towards the end of the exposure in the 64μgHgL(-1) group. There was a negative relationship between lipid peroxidation and antioxidant enzyme activities, and positive relationship between activities and gene expression of antioxidant enzymes, suggesting that the changes at a molecular level may underlie enzymatic level and accordingly affect hepatic lipid peroxidation. Obtained results also showed a coordinated transcriptional regulation of antioxidant genes, suggesting that Nrf2 is required for the protracted induction of these genes. Furthermore, a negative relationship between the mRNA levels of Nrf2 and Keap1 indicated that Keap1 may play an important role in switching off the Nrf2 response. In conclusion, this is the first study to elucidate effects of waterborne Hg on antioxidant system in large yellow croaker through the Keap1-Nrf2 pathway, which will aid our understanding of the molecular mechanisms of waterborne heavy metal on antioxidant responses in fish.

摘要

本研究旨在评估急性无机汞暴露(0、32和64μgHgL(-1))对大黄鱼(Pseudosciaena crocea)肝脏在不同暴露时间(6小时、12小时、24小时、48小时和96小时)的脂质过氧化、抗氧化酶(铜/锌超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽S-转移酶)活性及基因表达,以及Keap1-Nrf2信号分子mRNA水平的影响。结果表明,在6至12小时期间,32μg Hg L(-1)使脂质过氧化急剧降低,随后恢复到对照水平。同样,在64μgHgL(-1)组中,脂质过氧化在6至12小时期间显著降低,随后在暴露末期急剧增加。脂质过氧化与抗氧化酶活性呈负相关,抗氧化酶活性与基因表达呈正相关,这表明分子水平的变化可能是酶水平变化的基础,并相应影响肝脏脂质过氧化。所得结果还表明抗氧化基因存在协同转录调控,这表明Nrf2是这些基因长期诱导所必需的。此外,Nrf2和Keap1的mRNA水平呈负相关,表明Keap1可能在关闭Nrf2反应中起重要作用。总之,这是首次通过Keap1-Nrf2途径阐明水体汞对大黄鱼抗氧化系统影响的研究,这将有助于我们理解水体重金属对鱼类抗氧化反应的分子机制。

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