Responses of CYP450 in the mussel Perna viridis after short-term exposure to the DSP toxins-producing dinoflagellate Prorocentrum lima
Responses of CYP450 in the mussel Perna viridis after short-term exposure to the DSP toxins-producing dinoflagellate Prorocentrum lima
复制标题
短期暴露于产生 DSP 毒素的甲藻原甲藻后，贻贝体内 CYP450 的反应
DOI：
10.1016/j.ecoenv.2019.03.073
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发表时间：
2019
影响因子：
6.8
通讯作者：
Yang Wei Dong
中科院分区：
文献类型：
--
作者：
Wei Xiao Meng;Lu Mi Yu;Duan Guo Fang;Li Hong Ye;Liu Jie Sheng;Yang Wei Dong
腹泻性贝类毒素是引起腹泻、呕吐甚至肿瘤的主要贝类毒素。有趣的是，双壳贝类如翡翠贻贝（Perna viridis）已被报道以物种特异性方式表现出一些抵抗DSP毒素的毒性作用。然而，DSP毒素耐药现象的分子机制，特别是CYP 450的机制作用是缺乏的，尽管它在解毒中的关键作用。在这里，我们暴露了P。结果表明，青原甲藻P.结果表明，暴露于环境中的双壳贝类的CYP 450关键基因的表达具有独特的模式。暴露于P. lima（2 × 105 cells/L）显著调控了CYP 450基因的相对表达。与对照组相比，鳃中CYP 2D 14-like mRNA在6 h时表达显著下调，而消化腺中CYP 3A 4 mRNA在2 h时表达显著上调（p< 0.05），而鳃中CYP 3A 4 mRNA在12 h时表达显著上调。暴露于P.在2 × 106 cells/L浓度下，2 h和12 h时消化腺中CYP 3A 4 mRNA表达显著增加，而6 h时CYP 2D 14-like表达上调。此外，CYP 3L 3和CYP 2C 8也表现出差异表达。这些数据表明，CYP 3A 4，CYP 2D 14-like，甚至CYP 3L 3和CYP 2C 8可能参与DSP毒素代谢。与对照组相比，添加酮康唑后2 h和12 h消化腺中CYP 3A 4含量显著降低，OA含量在2 h和6 h显著降低。这些结果表明，酮康唑可通过抑制CYP 3A 4的活性，从而改变DSP毒素在双壳贝类体内的代谢活性，同时也为研究CYP 3A 4在双壳贝类DSP毒素代谢中的作用机制提供了新的思路。
Diarrhetic shellfish poisoning (DSP) toxins are key shellfish toxins that cause diarrhea, vomiting and even tumor. Interestingly, bivalves such asPerna viridishave been reported to exhibit some resistances to alleviate toxic effects of DSP toxins in a species-specific manner. Nevertheless, the molecular mechanisms underlying the resistance phenomenon to DSP toxins, particularly the mechanistic role of CYP450 is scant despite its crucial role in detoxification. Here, we exposedP. viridistoProrocentrum limaand examined the expression pattern of the CYP450 and our comprehensive analyses revealed thatP. limaexposure resulted in unique expression pattern of key CYP450 genes in bivalves. Exposure toP. lima(2 × 105cells/L) dramatically orchestrated the relative expression of CYP450 genes. CYP2D14-like mRNA was significantly down-regulated at 6 h in gill, but up-regulated at 2 h in digestive gland compared with control counterparts (p< 0.05), while CYP3A4 mRNA was increased at 12 h in gill. After exposure toP. limaat 2 × 106cells/L, the expression of CYP3A4 mRNA was significantly increased in digestive gland at 2 h and 12 h, while CYP2D14-like was up-regulated at 6 h. Besides, CYP3L3 and CYP2C8 also exhibited differential expression. These data suggested that CYP3A4, CYP2D14-like, and even CYP3L3 and CYP2C8 might be involved in DSP toxins metabolism. Besides, provision of ketoconazole resulted in significant decrement of CYP3A4 in digestive gland at 2 h and 12 h, while the OA content significantly decreased at 2 h and 6 h compared to control group without ketoconazole. These findings indicated that ketoconazole could depress CYP3A4 activity in bivalves thereby altering the metabolic activities of DSP toxins in bivalves, and also provided novel insights into the mechanistic role of CYP3A4 on DSP toxins metabolism in bivalves.