Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response.
Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response.
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DOI：
10.1016/j.chemosphere.2016.05.038
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发表时间：
2016-08
期刊：
影响因子：
8.8
通讯作者：
M. Qi;Yao Dang;Qinglong Xu;Liqin Yu;Chunsheng Liu;Yongchao Yuan;Jianghuai Wang
中科院分区：
文献类型：
--
作者：
M. Qi;Yao Dang;Qinglong Xu;Liqin Yu;Chunsheng Liu;Yongchao Yuan;Jianghuai Wang
近年来的研究表明，蓝藻源微囊藻毒素-LR（MC-LR）对斑马鱼（Danio rerio）幼鱼具有发育毒性和诱导凋亡的作用，但其机制尚不清楚。在这项研究中，我们检验了MC-LR诱导发育毒性的机制是通过激活内质网（ER）应激的假设。MC-LR（4.0 μM）可引起斑马鱼幼体畸形、生长延迟和心率减慢等严重的发育毒性，雌激素受体阻断剂牛磺熊去氧胆酸（TUDCA，20 μM）可抑制MC-LR对斑马鱼幼体的发育毒性。同时，叮啶橙子（AO）染色显示TUDCA可以挽救MC-LR暴露引起的斑马鱼幼虫心脏区细胞凋亡。实时荧光定量PCR分析结果表明，MC-LR可诱导内质网应激激活，从而引发斑马鱼幼鱼的凋亡。Western blot检测蛋白表达结果表明，MC-LR可激活斑马鱼仔鱼的MAPK 8/Bcl-2/Bax通路和caspase依赖的凋亡通路，抑制内质网应激可减轻MC-LR的激活作用。总之，本研究中观察到的结果表明，ER应激在MC-LR暴露的斑马鱼胚胎发育毒性和凋亡中起着关键作用。
Recent studies have demonstrated that cyanobacteria-derived Microcystin-LR (MC-LR) can cause developmental toxicity and trigger apoptosis in zebrafish (Danio rerio) larvae, but the underlying mechanisms remain largely unknown. In this study, we tested the hypothesis that the mechanism by which MC-LR induces developmental toxicity is through activation of endoplasmic reticulum (ER) stress. MC-LR (4.0 μM) exposure through submersion caused serious developmental toxicity, such as malformation, growth delay and decreased heart rates in zebrafish larvae, which could be inhibited by ER stress blocker, tauroursodeoxycholic acid (TUDCA, 20 μM). Meanwhile, acridine orange (AO) staining showed TUDCA could rescue cell apoptosis in heart area in zebrafish larvae resulted by MC-LR exposure. Real-time polymerase chain reaction (real-time PCR) analysis demonstrated that MC-LR induced activation of ER stress which consequently triggered apoptosis in zebrafish larvae. Protein expression examined by western blot indicated that MC-LR could activate MAPK8/Bcl-2/Bax pathway and caspase-dependent apoptotic pathway in zebrafish larva and the effects were mitigated by inhibition of ER stress. Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR.