孕烷X受体(PXR)是一种核激素受体,在调节各种配体的基因表达中起关键作用。特别是外源性物质。在这种情况下,这项研究的目的是阐明在海洋贻贝Mytilusgalloprovincialis中鉴定的四种NR1J1旁系同源物的配体亲和力和功能,采用双荧光素酶报告基因测定。为了实现这一点,这些旁系同源物响应各种毒素的激活模式,包括淡水氰毒素(Anatoxin-a,圆柱精子素,和微囊藻毒素-LR,-RR,和-YR)和海洋藻类毒素(Nodularin,毒素,和河豚毒素),与天然化合物(圣约翰草,熊果酸,和8-甲氧基补骨脂素)和微藻提取物(Tetraselmis,等速疗法,LEGE95046和LEGE11351提取物),被研究过。调查揭示了旁白反应模式的细微差别,突出了MgaNR1J1γ和MgaNR1J1δ旁系同源物对几种毒素的显着敏感性。总之,这项研究揭示了复杂的异源生物代谢和解毒机制,特别关注海洋贻贝NR1J1在响应多种化合物中的作用。此外,与人类PXR的比较分析揭示了解毒机制中潜在的物种特异性适应,暗示进化的含义。这些发现加深了我们对PXR介导的代谢机制的理解,提供对环境监测和进化生物学研究的见解。
The pregnane X receptor (PXR) is a nuclear hormone receptor that plays a pivotal role in regulating gene expression in response to various ligands, particularly xenobiotics. In this context, the aim of this study was to shed light on the ligand affinity and functions of four NR1J1 paralogs identified in the marine mussel Mytilus galloprovincialis, employing a dual-luciferase reporter assay. To achieve this, the activation patterns of these paralogs in response to various
toxins, including freshwater cyanotoxins (Anatoxin-a, Cylindrospermopsin, and Microcystin-LR, -RR, and -YR) and marine algal
toxins (Nodularin, Saxitoxin, and Tetrodotoxin), alongside natural compounds (Saint John\'s Wort, Ursolic Acid, and 8-Methoxypsoralene) and microalgal extracts (Tetraselmis, Isochrysis, LEGE 95046, and LEGE 91351 extracts), were studied. The investigation revealed nuanced differences in paralog response patterns, highlighting the remarkable sensitivity of MgaNR1J1γ and MgaNR1J1δ paralogs to several
toxins. In conclusion, this study sheds light on the intricate mechanisms of xenobiotic metabolism and detoxification, particularly focusing on the role of marine mussel NR1J1 in responding to a diverse array of compounds. Furthermore, comparative analysis with human PXR revealed potential species-specific adaptations in detoxification mechanisms, suggesting evolutionary implications. These findings deepen our understanding of PXR-mediated metabolism mechanisms, offering insights into environmental monitoring and evolutionary biology research.