Effects of pyrethroid pesticide cis-bifenthrin on lipogenesis in hepatic cell line
Effects of pyrethroid pesticide cis-bifenthrin on lipogenesis in hepatic cell line
复制标题
拟除虫菊酯类农药顺式联苯菊酯对肝细胞脂肪生成的影响
DOI：
10.1016/j.chemosphere.2018.03.009
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Zhu Guonian
中科院分区：
文献类型：
--
作者：
Xiang D;an;Chu Tianyi;Li Meng;Wang Qiangwei;Zhu Guonian
越来越多的证据表明，接触合成拟除虫菊酯（SP）与肥胖的发生之间存在联系。本研究结果提示，顺式联苯菊酯（cis-BF）可激活人肝癌细胞（HepG 2）中的甾烷X受体（PXR）介导的途径，导致细胞内脂质蓄积。将细胞在对照或不同浓度的cis-BF中孵育24小时。发现1 × 10− 7 M和1 × 10− 6 Mcis-BF暴露可显著诱导细胞甘油三酯（TG）蓄积。油红O染色试验进一步支持了这一现象。cis-BF暴露引起PXR基因和蛋白表达上调。相应地，我们还观察到参与脂质形成的下游基因的表达增加和β-氧化表达的抑制。作为手性农药，cis-BF在脂类代谢中表现出对映体选择性。与1 R-cis-BF相比，1 S-cis-BF孵育的HepG 2细胞显示出显著的TG蓄积。1 S-cis-BF也显示出更高的结合水平，在SPR试验中其KD值为9.184 × 10− 8 M，而1 R-cis-BF为3.463 × 10− 6 M。此外，分子对接模拟分析与SPR测量的KD值相关良好，表明1 S-cis-BF与PXR显示出更好的结合亲和力。本研究的结果还阐明了拟除虫菊酯两种对映体在非靶生物脂质代谢方面的毒性差异。
Mounting evidence suggests there is a link between exposure to synthetic pyrethroids (SPs) and the development of obesity. The information presented in this study suggests thatcis-bifenthrin (cis-BF) could activate pregnane X receptor (PXR) mediated pathway and lead to the lipid accumulation of human hepatoma (HepG2) cells. Cells were incubated in the control or different concentrations ofcis-BF for 24 h. The 1 × 10−7M and 1 × 10−6Mcis-BF exposure were found to induce cellular triglyceride (TG) accumulation significantly. This phenomenon was further supported by Oil Red O Staining assay. Thecis-BF exposure caused upregulation of PXR gene and protein. Correspondingly, we also observed the increased expression of downstream genes involved in lipid formation and the inhibition of the expression of β-oxidation. As chiral pesticide,cis-BF was further conformed to behave enantioselectivity in the lipid metabolism. Rather than 1R-cis-BF, HepG2 cells incubated with 1S-cis-BF exhibited a significant TG accumulation. 1S-cis-BF also showed a higher binding level, of which the KD value was 9.184 × 10−8M in the SPR assay, compared with 1R-cis-BF (3.463 × 10−6M). In addition, the molecular docking simulation analyses correlated well with the KD values measured by the SPR, indicating that 1S-cis-BF showed a better binding affinity with PXR. The results in this study also elucidates the differences between the two enantiomers of pyrethroid-induced toxicity in lipid metabolism of non-target organism.