Cadmium-induced oxidative stress promotes apoptosis and necrosis through the regulation of the miR-216a-PI3K/AKT axis in common carp lymphocytes and antagonized by selenium
Cadmium-induced oxidative stress promotes apoptosis and necrosis through the regulation of the miR-216a-PI3K/AKT axis in common carp lymphocytes and antagonized by selenium
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DOI：
10.1016/j.chemosphere.2020.127341
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发表时间：
2020-11-01
期刊：
影响因子：
8.8
通讯作者：
Xu, Shiwen
中科院分区：
文献类型：
--
作者：
Zhang, Jiaqi;Zheng, Shufang;Xu, Shiwen
镉（Cd）是导致水生动物免疫功能障碍的主要环境污染物。 MicroRNA (miRNA) 在免疫器官的程序性坏死和凋亡中发挥关键作用。硒(Se)作为一种重要元素，可以拮抗鸟类体内的镉毒性，但硒对鲤鱼(Cyprinus carpio)的影响尚未见报道。为了探讨Se拮抗miR-216a介导的鲤鱼脾脏淋巴细胞中Cd诱导的免疫毒性机制，我们从脾脏中提取淋巴细胞并分为对照组、Se组（10(-6)mol/L Na2SeO3）、Se+Cd组和Cd组（4×10(-5)mol/L CdCl2）。孵育6小时后，进行AO/EB染色、流式细胞术、qPCR和Western blot。结果表明，镉暴露引起淋巴细胞凋亡（BAX、Bcl-2、Caspase 3、Caspase 9）和程序性坏死（RIP、RIP3、MLKL），增加CYP酶、糖代谢相关酶的表达和ROS的产生，同时刺激氧化应激（MDA、SOD、CAT和GSH-PX），上调miR-216a的表达，减弱 PI3K 的水平。然而，这些变化在 Se + Cd 组中明显减轻。总之，我们证明Cd会激活氧化应激和miR-216a-PI3K/AKT轴紊乱，从而促进淋巴细胞凋亡和坏死。此外，Se还可以拮抗Cd引发的淋巴细胞凋亡和坏死。 (C) 2020 Elsevier Ltd. 保留所有权利。
Cadmium (Cd) is a primary environmental pollutant which causes the immune dysfunction of aquatic animals. MicroRNAs (miRNAs) play a key role in programmed necrosis and apoptosis of immune organs. Selenium (Se), known as an important element, can antagonize Cd toxicity in birds, but the impact of Se on common carps (Cyprinus carpio) has not been reported. To investigate the Cd-induced immunotoxicity mechanism mediated by miR-216a in splenic lymphocytes of common carp and antagonized by Se, we extracted lymphocytes from the spleen and divided them into control group, Se group (10(-6) mol/L of Na2SeO3), Se + Cd group and Cd group (4 x 10(-5) mol/L of CdCl2). After 6 h of incubation, AO/EB staining, Flow cytometry, qPCR and Western blot were performed. The results showed that Cd exposure caused the apoptosis (BAX, Bcl-2, Caspase 3, Caspase 9) and programmed necrosis (RIP, RIP3, MLKL) in lymphocytes, increased the expression of CYP enzymes, glycometabolism-related enzymes and production of ROS, while irritated the oxidative stress (MDA, SOD, CAT and GSH-PX), upregulated the expression of miR-216a which attenuated the levels of PI3K. However, those variations were apparently mitigated in the Se + Cd group. In short, we have proven that Cd activates oxidative stress and miR-216a-PI3K/AKT axis disorder, thus promoting apoptosis and necrosis in lymphocytes. Moreover, Se can antagonize Cd-triggered apoptosis and necrosis in lymphocytes. (C) 2020 Elsevier Ltd. All rights reserved.