The role of apoptosis in MCLR-induced developmental toxicity in zebrafish embryos.
The role of apoptosis in MCLR-induced developmental toxicity in zebrafish embryos.
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DOI：
10.1016/j.aquatox.2014.01.021
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发表时间：
2014-04
影响因子：
4.5
通讯作者：
Cheng Zeng;Hong Sun;P. Xie;Jianghuai Wang;Gui-xian Zhang;Nan Chen;Wei Yan;Guangyu Li
中科院分区：
文献类型：
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作者：
Cheng Zeng;Hong Sun;P. Xie;Jianghuai Wang;Gui-xian Zhang;Nan Chen;Wei Yan;Guangyu Li
我们以前证明，蓝藻衍生的微囊藻毒素-亮氨酸-精氨酸（MPEG4）能够诱导发育毒性，如畸形，生长延迟和斑马鱼胚胎心率下降。然而，在斑马鱼的发展过程中，Mesophila诱导其毒性的分子机制在很大程度上仍然未知。在这里，我们评估细胞凋亡的作用MCLR诱导的发育毒性。将斑马鱼胚胎暴露于不同浓度的蛋氨酸（0、0.2、0.5、2和5.0 mg L−1）96 h，此时在2和5.0 mg L− 1蛋氨酸暴露组中显著诱导了活性氧（ROS）。吖啶橙子（AO）染色和末端脱氧核苷酸转移酶介导的脱氧-UTP缺口末端标记（TUNEL）法显示，MTT法可诱导细胞凋亡。为了测试细胞凋亡途径，分别针对酶活性、基因和蛋白质表达水平检查了几种细胞凋亡相关基因的表达模式。总体结果表明，MIBI诱导ROS，从而引发发育中的斑马鱼胚胎心脏的凋亡。我们的研究结果还表明，p53-Bcl-Bcl-2途径和caspase依赖的凋亡途径在MCLR诱导的发育中的胚胎细胞凋亡中起主要作用。
We previously demonstrated that cyanobacteria-derived microcystin–leucine–arginine (MCLR) is able to induce developing toxicity, such as malformation, growth delay and also decreased heart rates in zebrafish embryos. However, the molecular mechanisms by which MCLR induces its toxicity during the development of zebrafish remain largely unknown. Here, we evaluate the role of apoptosis in MCLR-induced developmental toxicity. Zebrafish embryos were exposed to various concentrations of MCLR (0, 0.2, 0.5, 2, and 5.0 mg L−1) for 96 h, at which time reactive oxygen species (ROS) was significantly induced in the 2 and 5.0 mg L−1MCLR exposure groups. Acridine orange (AO) staining and terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure resulted in cell apoptosis. To test the apoptotic pathway, the expression pattern of several apoptotic-related genes was examined for the level of enzyme activity, gene and protein expression, respectively. The overall results demonstrate that MCLR induced ROS which consequently triggered apoptosis in the heart of developing zebrafish embryos. Our results also indicate that the p53–Bax–Bcl-2 pathway and the caspase-dependent apoptotic pathway play major roles in MCLR-induced apoptosis in the developing embryos.