Concentration-dependent effects of chlorpyrifos oxon on peroxisome proliferator-activated receptor signaling in MCF-7 cells.
Concentration-dependent effects of chlorpyrifos oxon on peroxisome proliferator-activated receptor signaling in MCF-7 cells.
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DOI：
10.1016/j.tiv.2021.105268
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Pope C
中科院分区：
文献类型：
--
作者：
Herriage S;Chen G;Pope C
毒死蜱是有机磷农药毒死蜱的活性代谢产物。CPO是乙酰胆碱酯酶（AChE）和其他丝氨酸水解酶（包括脂肪酸酰胺水解酶（FAAH））的有效抑制剂。AChE在调节胆碱能信号传导中是关键的，而FAAH催化脂肪酸信号传导脂质的失活，所述脂肪酸信号传导脂质包括内源性大麻素（eCB）N-花生四烯酸乙醇胺（anandamide，AEA）和eCB样代谢物（例如，油酰乙醇胺，OEA）。AEA和OEA都是过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPAR）激动剂，其调节参与脂质代谢和能量稳态的众多基因。我们使用MCF-7人乳腺癌细胞系，表达AChE，FAAH和PPAR α和γ亚型，以评估CPO对体外人细胞系统中PPAR相关基因表达的潜在影响。CPO引起了相对相似的浓度依赖性抑制AChE和FAAH。观察到4种选定的PPAR相关基因LXRα、ACOX 1、ABCG 2和AGPAT 2的表达存在显著的浓度和时间依赖性变化。这些结果表明毒死蜱可能通过阻断eCB或eCB样代谢物的降解进而影响PPAR受体的激活来影响脂质代谢。这些结果突出了这种常见杀虫剂代谢物通过破坏过氧化物酶体增殖物激活受体信号传导（包括对脂质代谢、免疫功能和炎症的影响）发挥非胆碱酯酶作用的潜力。
Chlorpyrifos oxon (CPO) is the active metabolite of the organophosphorus pesticide, chlorpyrifos. CPO is a potent inhibitor of acetylcholinesterase (AChE) and other serine hydrolases including fatty acid amide hydrolase (FAAH). AChE is critical in regulating cholinergic signaling while FAAH catalyzes the inactivation of fatty acid signaling lipids including the endocannabinoid (eCB) N-arachidonylethanolamine (anandamide, AEA) and eCB-like metabolites (e.g., oleoylethanolamide, OEA). AEA and OEA are both peroxisome proliferator-activated receptor (PPAR) agonists that regulate numerous genes involved in lipid metabolism and energy homeostasis. We used the MCF-7 human breast cancer cell line, which expresses AChE, FAAH and PPAR alpha and gamma subtypes, to evaluate the potential effects of CPO on PPAR-related gene expression in an in vitro human cell system. CPO elicited relatively similar concentration-dependent inhibition of both AChE and FAAH. Marked concentration- and time-dependent changes in the expression of four selected PPAR-related genes, LXRα, ACOX1, ABCG2 and AGPAT2, were noted. These findings suggest chlorpyrifos may influence lipid metabolism through blocking the degradation of eCBs or eCB-like metabolites and in turn affecting PPAR receptor activation. The results highlight the potential for non-cholinesterase actions of this common insecticide metabolite through disruption of PPAR signaling including effects on lipid metabolism, immune function and inflammation.
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影响因子：
5.8
作者：
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