胡椒酰丁醇诱导了解毒和脂质代谢基因的独特基因表达,并且与营养、微生物群和遗传背景无关

IF 4 1区 农林科学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Luke J. Pfannenstiel, Anastacia E. Dressel, Gabriel A.O. De Guzman, Jeffrey G. Scott , Nicolas Buchon
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引用次数: 0

摘要

胡椒酰丁醇(PBO)是一种常用的杀虫剂增效剂和细胞色素P450 (CYP)抑制剂。虽然PBO在阻断外源代谢中的作用已经得到了很好的证实,但我们在这里发现PBO也会在果蝇中引发一种独特的转录反应。这种反应包括与解毒相关的基因,如Cyps、Gsts和Ugts,以及参与脂质代谢的基因,揭示了一种新的生理程序,将解毒与更广泛的代谢调节结合起来。与其他外源性暴露不同,pbo诱导的转录组不像经典的应激反应。这种转录诱导与遗传背景、饮食组成或微生物群无关,部分由另一种亚甲二氧苯化合物肉豆蔻素再现。精细解剖结合RT-qPCR发现,pbo诱导基因在多个组织中表现出不同的空间表达模式,包括肠道、马氏小管和脂肪体。虽然大多数PBO诱导基因在消化道中表达量最高,但大约有一半主要在消化道中诱导,而其他基因主要在胴体脂肪体中诱导。利用crispr介导的整合盒Gal4报告细胞系,我们可视化了两种pbo诱导的Cyps, Cyp4e2和Cyp28a5的细胞特异性表达,它们在肠道和胴体中表现出互补和区域限制性的激活。我们发现在PBO诱导过程中表达模式得以维持。我们的研究结果表明,PBO对CYP的抑制引发了一种新的、系统性的转录反应,其范围超出了外源解毒,可能反映了代谢稳态的更广泛破坏。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Piperonyl butoxide induces a unique gene expression of both detoxification and lipid metabolism genes and is independent of nutrition, microbiota, and genetic background

Piperonyl butoxide induces a unique gene expression of both detoxification and lipid metabolism genes and is independent of nutrition, microbiota, and genetic background
Piperonyl butoxide (PBO) is a commonly used insecticide synergist and cytochrome P450 (CYP) inhibitor. While its role in blocking xenobiotic metabolism is well established, we show here that PBO also triggers a unique transcriptional response in Drosophila melanogaster. This response includes genes classically associated with detoxification, such as Cyps, Gsts, and Ugts, as well as genes involved in lipid metabolism, revealing a novel physiological program that integrates detoxification with broader metabolic regulation. Unlike other xenobiotic exposures, the PBO-induced transcriptome does not resemble a classical stress response. This transcriptional induction is independent of genetic background, diet composition or microbiota, and is partially recapitulated by myristicin, another methylenedioxyphenyl compound. Fine-scale dissection combined with RT-qPCR reveals that PBO-inducible genes exhibit distinct spatial expression patterns across multiple tissues, including the gut, Malpighian tubules, and fat body. Although most PBO inducible genes show the highest basal expression in the digestive tract, approximately half are primarily induced in the digestive tract, whereas the others are predominantly induced in the fat body of the carcass. Using CRISPR-Mediated Integration Cassette Gal4 reporter lines, we visualized the cell-specific expression of two PBO-induced Cyps, Cyp4e2 and Cyp28a5, which display complementary and regionally restricted activation in the gut and carcass. We find that patterns of expression are maintained during induction by PBO. Our findings suggest that CYP inhibition by PBO triggers a novel, systemic transcriptional response that extends beyond xenobiotic detoxification and may reflect a broader disruption of metabolic homeostasis.
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来源期刊
CiteScore
7.00
自引率
8.50%
发文量
238
审稿时长
4.2 months
期刊介绍: Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance. Research Areas Emphasized Include the Biochemistry and Physiology of: • Comparative toxicity • Mode of action • Pathophysiology • Plant growth regulators • Resistance • Other effects of pesticides on both parasites and hosts.
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