缺乏sEH磷酸酶活性的小鼠表现出嗅球中内源性大麻素2-AG水平的降低和类似抑郁的行为。

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2024-07-21 DOI:10.1002/1873-3468.14984

Ami Oguro, Yurino Kaga, Hideaki Sato, Taichi Fujiyama, Shinji Fujimoto, Saki Nagai, Makoto Matsuyama, Masatsugu Miyara, Yasuhiro Ishihara, Takeshi Yamazaki, Susumu Imaoka, Yaichiro Kotake

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引用次数: 0

摘要

可溶性环氧化物水解酶（sEH）是一种具有环氧化物水解酶活性和磷酸酶活性的双功能酶。我们早期的研究发现，溶血磷脂酸是 sEH 体外磷酸酶活性的底物，但其生理功能仍然未知。在此，我们利用CRISPR/Cas9系统和i-GONAD方法产生了缺乏sEH磷酸酶活性的小鼠。在小鼠大脑中，sEH在嗅球中高度表达。缺失sEH磷酸酶活性会导致嗅球中内源性大麻素2-阿achidonoyl甘油（2-AG）的水平下降，而2-AG是2-阿achidonoyl-lysophosphatidic acid的去磷酸化形式。sEH缺陷小鼠表现出类似抑郁的行为。这些结果表明，sEH 可以调节体内 2-AG 的产生和大脑功能。

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Mice deficient in the phosphatase activity of sEH show decreased levels of the endocannabinoid 2-AG in the olfactory bulb and depressive-like behavior.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has epoxide hydrolase activity and phosphatase activity. Our earlier study revealed that lysophosphatidic acids are a substrate of the phosphatase activity of sEH in vitro, but its physiological function remained unknown. Herein, we used the CRISPR/Cas9 system and i-GONAD method to generate mice that are deficient in sEH phosphatase activity. In the mouse brain, sEH was highly expressed in the olfactory bulb. Deletion of the sEH phosphatase activity resulted in decreased levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), which is a dephosphorylated form of 2-arachidonoyl-lysophosphatidic acid in the olfactory bulb. The sEH-deficient mice showed depressive-like behavior. These results indicate that sEH can regulate the production of 2-AG and brain function in vivo.

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.