Reactive oxygen species (ROS) and the calcium-(Ca2 ) mediated extrinsic and intrinsic pathways underlying BDE-47-induced apoptosis in rainbow trout (Oncorhynchus mykiss) gonadal cells
Reactive oxygen species (ROS) and the calcium-(Ca2 ) mediated extrinsic and intrinsic pathways underlying BDE-47-induced apoptosis in rainbow trout (Oncorhynchus mykiss) gonadal cells
复制标题
活性氧 (ROS) 和钙 (Ca2+) 介导的 BDE-47 诱导虹鳟 (Oncorhynchus mykiss) 性腺细胞凋亡的内在和外在途径
DOI：
10.1016/j.scitotenv.2018.11.306
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发表时间：
2019
影响因子：
9.8
通讯作者：
You Wang
中科院分区：
文献类型：
--
作者：
Zhongyuan Zhou;Bin Zhou;Hongmei Chen;Xuexi Tang;You Wang
溴化阻燃剂2，2 ′，4，4 ′-四溴二苯醚（BDE-47）对不同的海洋生物具有潜在的负面影响。然而，责任机制仍然未知。以虹鳟鱼性腺细胞系RTG-2为模型，在体外研究了BDE-47（6、12.5和25 μM）诱导细胞凋亡和毒性的机制和途径。RTG-2细胞暴露于BDE-47后出现明显的浓度依赖性凋亡。透射电镜观察线粒体形态学改变。BDE-47暴露降低了细胞线粒体膜电位，增加了细胞色素释放到细胞质中，并提高了Fas蛋白表达。Fas相关死亡结构域蛋白（FADD）、CHOP和GRP 78的mRNA表达也升高，细胞内caspase-8、caspase-12、caspase-9和caspase-3的活性也有类似的升高。这些结果表明，线粒体、内质网和死亡受体途径参与了BDE-47暴露后RTG-2细胞的凋亡。ROS和Ca 2+是造成这些变化的原因，因为它们的过量产生是在细胞凋亡之前检测到的。而加入活性氧清除剂N-乙酰半胱氨酸（NAC）和细胞内钙离子螯合剂（乙酰氧基甲基）-1，2-双-（邻氨基苯氧基）-乙烷-N，N，N′，N′-四乙酸（BAPTA-AM）并不能显著降低细胞凋亡率。本研究的结果表明，BDE-47暴露通过ROS和Ca 2介导的线粒体、内质网和死亡受体凋亡途径诱导RTG-2细胞凋亡。
The brominated flame retardant, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), is well documented to exert potential negative impacts on different marine biota. However, the responsible mechanism remains unknown. The rainbow trout gonadal cell line RTG-2 was used as a model, and the mechanism and pathway underlying BDE-47 (6, 12.5 and 25 μM)-induced apoptosis and toxicity were examined in vitro. Apoptosis occurred in the RTG-2 cells exposed to BDE-47 in a clear concentration-dependent manner. The morphology of the mitochondrial alterations was observed using transmission electron microscopy. BDE-47 exposure decreased the cellular mitochondrial membrane potential, increased the cytochromecreleased into the cytoplasm and elevated Fas protein expression. The mRNA expressions of Fas-associated death domain-containing protein (FADD), CHOP and GRP78 were also elevated, and similar increases were found in the activities of intracellular caspase-8, caspase-12, caspase-9 and caspase-3. These results indicated that the mitochondrial, endoplasmic reticulum and death-receptor pathways were involved in apoptosis in RTG-2 cells following BDE-47 exposure. ROS and Ca2+were responsible for these changes because their overproduction was detected prior to apoptosis. However, the addition of the ROS scavengerN-acetyl-l-cysteine (NAC) and the intracellular calcium chelator (acetoxymethyl)-1,2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) did not significantly alleviate the apoptosis rate. The results of the present study show that BDE-47 exposure induced apoptosis in RTG-2 cells via ROS- and Ca2-mediated mitochondrial, endoplasmic reticulum and death-receptor apoptotic pathways.