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

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Ami Oguro, Yurino Kaga, Hideaki Sato, Taichi Fujiyama, Shinji Fujimoto, Saki Nagai, Makoto Matsuyama, Masatsugu Miyara, Yasuhiro Ishihara, Takeshi Yamazaki, Susumu Imaoka, Yaichiro Kotake
{"title":"Mice deficient in the phosphatase activity of sEH show decreased levels of the endocannabinoid 2-AG in the olfactory bulb and depressive-like behavior.","authors":"Ami Oguro, Yurino Kaga, Hideaki Sato, Taichi Fujiyama, Shinji Fujimoto, Saki Nagai, Makoto Matsuyama, Masatsugu Miyara, Yasuhiro Ishihara, Takeshi Yamazaki, Susumu Imaoka, Yaichiro Kotake","doi":"10.1002/1873-3468.14984","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.14984","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0

Abstract

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.

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。
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
FEBS Letters
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信