Putative receptors and signaling pathways responsible for the biological actions of epoxyeicosatrienoic acids.

IF 4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Chemistry Pub Date : 2025-09-18 DOI:10.1016/j.jbc.2025.110737

Matthew L Edin,Joan P Graves,Darryl C Zeldin

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Abstract

Epoxy fatty acids (EpFAs), including arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), are endogenously produced bioactive signaling molecules with diverse physiological effects, including vasodilation, anti-inflammation, and cardioprotection. EETs are generated by a subset of cytochromes P450 and their biological activity is reduced by hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolases. Inhibition of soluble epoxide hydrolase (sEH) has shown significant therapeutic promise in preclinical models of disease. Despite the profound physiological impact of EETs and the therapeutic potential of sEH inhibitors, the precise signaling mechanisms by which EETs elicit their biological effects remain unknown. Many have sought to identity a high-affinity, EET-activated, G-protein-coupled receptor (GPCR). This review synthesizes current knowledge regarding the evidence supporting the existence of one or more EET-GPCRs and weighs this evidence against alternative or complementary EET signaling pathways. The breadth of these studies highlights the complexities and challenges in fully elucidating the precise molecular mechanisms of EET actions.

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环氧二碳三烯酸生物学作用的推定受体和信号通路。

环氧脂肪酸（EpFAs），包括花生四烯酸（AA）衍生的环氧二碳三烯酸（EETs），是内源性产生的生物活性信号分子，具有多种生理作用，包括血管舒张、抗炎症和心脏保护。eet是由细胞色素P450的一个亚群产生的，它们的生物活性被环氧化物水解酶水解成二羟基二碳三烯酸（DHETs）而降低。可溶性环氧化物水解酶（sEH）的抑制在疾病的临床前模型中显示出显著的治疗前景。尽管eet具有深远的生理影响和sEH抑制剂的治疗潜力，但eet引发其生物学效应的确切信号机制尚不清楚。许多人寻求鉴定一种高亲和力，eet激活的g蛋白偶联受体（GPCR）。本综述综合了目前关于支持一种或多种EET- gpcr存在的证据的知识，并将这些证据与其他或互补的EET信号通路进行了权衡。这些研究的广度突出了充分阐明EET作用的精确分子机制的复杂性和挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry

自引率

4.20%

发文量

1233

期刊介绍： The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.