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Nrf2/Keap1 信号通路在暴露于环境相关浓度阿司匹林的艾氏拟腹吸鳅(M. abei)中的反应。

Responses of the Nrf2/Keap1 signaling pathway in Mugilogobius abei (M. abei) exposed to environmentally relevant concentration aspirin.

机构信息

Department of Ecology, Jinan University, Guangzhou, 510632, China.

Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, Jinan University, Guangzhou, 510632, China.

出版信息

Environ Sci Pollut Res Int. 2020 May;27(13):15663-15673. doi: 10.1007/s11356-020-07912-3. Epub 2020 Feb 20.

DOI:10.1007/s11356-020-07912-3
PMID:32080815
Abstract

Aspirin (ASA) is a widely used non-steroidal anti-inflammatory drug. Its high detection frequency in various waterborne and environmental residues has drawn wide attention. Limited information were provided for the effects of aspirin exposure on oxidative stress signaling pathway in fish, which is closely related to pathological and immunological process of fish. In this study, a small fish - Mugilogobius abei (M. abei) distributing widely in aquatic ecosystems in southern China, was employed as testing organism and the key genes of the detoxification metabolism were cloned for the first time. The responses of Nrf2/Keap1 signaling pathway were investigated under the environmentally relevant concentration aspirin exposure (0.5 μg L, 5 μg L, and 50 μg L) for 24 h, 72 h, and 168 h then. The transcriptional expression of the key genes (Nrf2, Keap1, GCLC, GPx, GST, SOD, CAT, Trx2, and TrxR) as well as the changes of the related enzymatic activities (GPx, GST, SOD, and CAT) and GSH and MDA content were also determined. Results showed that Nrf2 and Keap1 gene expression displayed a negative correlation to some extent under ASA exposure, the transcriptional expressions of the downstream related genes (GCLC, GST, SOD, CAT, Trx2, and TrxR) in Nrf2/Keap1 signaling pathway showed inhibition at 24 h but induction at 72 h and 168 h. At the protein level, ASA exposure can improve the antioxidant capacity by increasing GSH synthesis and enzymatic activity of GPx, GST, SOD, and CAT to reduce the degree of lipid peroxidation. We proposed that ASA exposure may interfere with the redox balance in M. abei at an early stage but sub-chronic ASA exposure can activate the Nrf2 signaling pathway to improve the antioxidant capacity of M. abei.

摘要

阿司匹林(ASA)是一种广泛使用的非甾体抗炎药。其在各种水载和环境残留中的高检测频率引起了广泛关注。然而,关于暴露于阿司匹林对鱼类氧化应激信号通路的影响的信息有限,而该通路与鱼类的病理和免疫过程密切相关。在这项研究中,我们选择了广泛分布在中国南方水生生态系统中的小鱼——纹缟虾虎鱼(Mugilogobius abei)作为测试生物,并首次克隆了其解毒代谢的关键基因。我们研究了在环境相关浓度的阿司匹林暴露(0.5μg/L、5μg/L 和 50μg/L)下,Nrf2/Keap1 信号通路在 24h、72h 和 168h 时的响应。测定了关键基因(Nrf2、Keap1、GCLC、GPx、GST、SOD、CAT、Trx2 和 TrxR)的转录表达以及相关酶活性(GPx、GST、SOD 和 CAT)和 GSH 和 MDA 含量的变化。结果表明,在 ASA 暴露下,Nrf2 和 Keap1 基因表达在某种程度上呈负相关,Nrf2/Keap1 信号通路下游相关基因(GCLC、GST、SOD、CAT、Trx2 和 TrxR)的转录表达在 24h 时受到抑制,但在 72h 和 168h 时被诱导。在蛋白质水平上,ASA 暴露可以通过增加 GSH 的合成和 GPx、GST、SOD 和 CAT 的酶活性来提高抗氧化能力,从而降低脂质过氧化程度。我们提出,ASA 暴露可能会在早期干扰纹缟虾虎鱼的氧化还原平衡,但亚慢性 ASA 暴露可以激活 Nrf2 信号通路,提高纹缟虾虎鱼的抗氧化能力。

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