Copper exposure induces toxicity to the antioxidant system via the destruction of Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle: Amelioration by myo-inositol
Copper exposure induces toxicity to the antioxidant system via the destruction of Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle: Amelioration by myo-inositol
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铜暴露会通过破坏鱼肌肉中的 Nrf2/ARE 信号传导和 caspase-3 调节的 DNA 损伤来诱导抗氧化系统的毒性：肌醇的改善
DOI：
10.1016/j.aquatox.2014.12.020
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发表时间：
2015-02-01
影响因子：
4.5
通讯作者：
Zhou, Xiao-Qiu
中科院分区：
文献类型：
--
作者：
Jiang, Wei-Dan;Liu, Yang;Zhou, Xiao-Qiu
肌肉是人类食用的鱼类的主要部分。铜（Cu）可引起鱼类肌肉的氧化损伤。然而，铜暴露对肌肉抗氧化系统和分子模式的影响以及针对这些影响的预防措施仍不清楚。本研究分析了铜暴露和肌醇预处理后鱼肌肉中ROS的产生、抗氧化酶和NF-E2相关因子2（Nrf 2）信号相关分子的酶和mRNA水平、抗氧化反应元件（ARE）结合能力、DNA片段化和caspase-3活性。结果表明，由于铜暴露的污染引起的ROS的产生增加约3倍，诱导脂质过氧化和蛋白质氧化，并导致谷胱甘肽（GSH）含量的鱼肌肉的耗尽。此外，铜暴露导致总超氧化物歧化酶（T-SOD），CuZnSOD，谷胱甘肽过氧化物酶（GPx）的活性下降，伴随着CuZnSOD，GPx 1a，GPx 1b和信号因子蛋白激酶C δ mRNA水平的下降。抗氧化酶基因mRNA水平的降低被证实部分是由于核Nrf 2蛋白水平降低，ARE结合能力差和caspase-3信号调节的DNA片段在鱼肌肉中增加。有趣的是，MI预处理主要通过增加GSH含量，提高CuZnSOD和GPx活性以及相应的mRNA水平和ARE结合能力来防止Cu诱导的鱼类肌肉氧化损伤。综上所述，我们的研究结果首次表明，铜暴露通过下调与Nrf 2/ARE信号传导中断相关的基因的表达来降低抗氧化酶活性，从而对肌肉造成氧化损伤，并且这种下调部分由caspase-3调节的DNA片段化引起。最后，MI保护鱼类免受Cu毒性。(C)2014爱思唯尔有限公司版权所有。
The muscle is the main portion of fish that is consumed by humans. Copper (Cu) can induce oxidative damage in fish muscle. However, the effects of Cu exposure on the muscle antioxidant system and molecular patterns and preventive measures against these effects remain unclear. In this study, ROS production, enzymatic and mRNA levels of antioxidant enzymes and NF-E2-related factor 2 (Nrf2) signaling-related molecules, antioxidant response element (ARE) binding ability, DNA fragmentation and caspase-3 activities were analyzed in fish muscle following Cu exposure or myo-inositol (MI) pre-administration. The results indicated that contamination due to copper exposure caused an approximately three-fold increase in ROS production, induced lipid peroxidation and protein oxidation, and resulted in depletion of the glutathione (GSH) content of fish muscle. Moreover, Cu exposure caused decreases in the activities of total superoxide dismutase (T-SOD), CuZnSOD, and glutathione peroxidase (GPx) that were accompanied by decreases in CuZnSOD, GPx1a, GPx1b and signaling factor protein kinase C delta mRNA levels. The decreases in the antioxidant enzyme gene mRNA levels were confirmed to be partly due to the reduced nuclear Nrf2 protein levels, poor ARE binding ability and increased caspase-3 signaling-modulated DNA fragmentation in the fish muscle. Interestingly, MI pre-treatment prevented fish muscle from Cu-induced oxidative damages mainly through increasing the GSH content, and increasing the CuZnSOD and GPx activities and corresponding mRNA levels and ARE binding ability. Taken together, our results show for the first time that Cu exposure caused oxidative damage to the muscle by decreasing the antioxidant enzyme activities via the down-regulation of the expression of genes related to the disruption of the Nrf2/ARE signaling, and this down-regulation was partially caused by caspase-3-regulated DNA fragmentation. Finally, MI protects fish against Cu toxicity. (C) 2014 Elsevier B.V. All rights reserved.