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内质网应激诱导的自噬和凋亡在两种吉富罗非鱼(Carassius gibelio)品系中对急性水镉暴露的差异调节。

Differential regulation of endoplasmic reticulum stress-induced autophagy and apoptosis in two strains of gibel carp (Carassius gibelio) exposed to acute waterborne cadmium.

机构信息

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

出版信息

Aquat Toxicol. 2021 Feb;231:105721. doi: 10.1016/j.aquatox.2020.105721. Epub 2020 Dec 9.

Abstract

Previous studies illustrated that gibel carp F strain displays better lipid mobilization and antioxidant ability and compared to the A strain. We therefore hypothesized that the F strain would exhibit superior defense to cadmium exposure. Comparative studies were conducted between A and F strains using plasma stress biomarkers, histological observations, and analysis of hepatic molecular events to examine exposure to waterborne Cd (11.9 mg L) for 48 h and 96 h. Waterborne Cd exposure stimulated stress response and hepatic metallothionein mRNA induction in both gibel carp strains confirming exposure. Antioxidant responses were stimulated to counteract Cd toxicity, suggested by the upregulation of mRNA levels of genes associated with nuclear factor erythroid 2-related factor 2 (nrf2) signaling. Cd exposure induced endoplasmic reticulum (ER) stress, meanwhile, branches of genes in unfolded protein response (UPR) were activated. Slight time-dependent effects were implied by greater ER stress, UPR, and apoptosis signals with the duration of Cd exposure. Genotype-specific effects were identified, revealing that the F strain showed greater stress at 96 h exposure and higher antioxidant response compared to the A strain, as indicated by the mRNA levels of genes in nrf2 signaling. ER stress and UPR were also stronger in the F strain after Cd exposure. In contrast, the A strain showed higher autophagy and apoptosis response compared to the F strain. Collectively, combined autophagy and apoptosis were triggered under ER stress, which might serve as defense strategies in both gibel carp strains. The F strain showed greater antioxidant detoxification response and UPR to mitigate Cd toxicity, whereas excessive ER stress contributed to higher autophagy and apoptosis in the A strain. The present study uncovered the differential regulation and defense strategies in fish strains exposed to metal exposure.

摘要

先前的研究表明,异育银鲫 F 系显示出更好的脂质动员和抗氧化能力,与 A 系相比。因此,我们假设 F 系将表现出对镉暴露的更好防御。使用血浆应激生物标志物、组织学观察和肝分子事件分析,在水培 Cd(11.9 mg/L)暴露 48 小时和 96 小时的情况下,对 A 和 F 系进行了比较研究。水培 Cd 暴露刺激了两种异育银鲫的应激反应和肝金属硫蛋白 mRNA 的诱导,证实了暴露的存在。抗氧化反应被刺激以抵消 Cd 毒性,这表明与核因子红细胞 2 相关因子 2(nrf2)信号相关的基因的 mRNA 水平上调。Cd 暴露诱导内质网(ER)应激,同时激活未折叠蛋白反应(UPR)的基因分支。随着 Cd 暴露时间的延长,暗示 ER 应激、UPR 和细胞凋亡信号出现了轻微的时间依赖性效应。鉴定出了基因型特异性效应,表明与 A 系相比,F 系在 96 小时暴露时表现出更大的应激和更高的抗氧化反应,这表明 nrf2 信号中基因的 mRNA 水平更高。在 Cd 暴露后,F 系的 ER 应激和 UPR 也更强。相比之下,A 系表现出比 F 系更高的自噬和细胞凋亡反应。总的来说,在 ER 应激下,联合自噬和细胞凋亡被触发,这可能是两种异育银鲫在受到金属暴露时的防御策略。F 系表现出更强的抗氧化解毒反应和 UPR 来减轻 Cd 毒性,而 A 系过度的 ER 应激导致更高的自噬和细胞凋亡。本研究揭示了在鱼类品系暴露于金属时的差异调节和防御策略。

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