{"title":"在SH-SY5Y人神经母细胞瘤细胞中，gq偶联毒蕈碱乙酰胆碱受体刺激可增强Midnolin基因表达","authors":"Ikuo Norota , Yusuke Zuiki , Ayano Chiba , Mikako Nagashima , Jiro Ogura , Hiroaki Yamaguchi , Kuniaki Ishii , Yutaro Obara","doi":"10.1016/j.jphs.2025.02.006","DOIUrl":null,"url":null,"abstract":"<div><div>We previously demonstrated that the midnolin gene (<em>MIDN</em>) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by <em>MIDN</em> knockout in PC12 cells. Therefore, drugs that upregulate <em>MIDN</em> may have neurotrophic effects. In this study, acetylcholine increased <em>MIDN</em> promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells. These effects were suppressed by atropine and a G<sub>q</sub> inhibitor, YM254890, indicating that muscarinic receptor/G<sub>q</sub> signaling is required for the induction of <em>MIDN</em> by acetylcholine. Our findings suggest that drugs that upregulate <em>MIDN</em> may have therapeutic potential for PD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 4","pages":"Pages 229-232"},"PeriodicalIF":2.9000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Midnolin gene expression is enhanced by Gq-coupled muscarinic acetylcholine receptor stimulation in SH-SY5Y human neuroblastoma cells\",\"authors\":\"Ikuo Norota , Yusuke Zuiki , Ayano Chiba , Mikako Nagashima , Jiro Ogura , Hiroaki Yamaguchi , Kuniaki Ishii , Yutaro Obara\",\"doi\":\"10.1016/j.jphs.2025.02.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>We previously demonstrated that the midnolin gene (<em>MIDN</em>) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by <em>MIDN</em> knockout in PC12 cells. Therefore, drugs that upregulate <em>MIDN</em> may have neurotrophic effects. In this study, acetylcholine increased <em>MIDN</em> promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells. These effects were suppressed by atropine and a G<sub>q</sub> inhibitor, YM254890, indicating that muscarinic receptor/G<sub>q</sub> signaling is required for the induction of <em>MIDN</em> by acetylcholine. Our findings suggest that drugs that upregulate <em>MIDN</em> may have therapeutic potential for PD.</div></div>\",\"PeriodicalId\":16786,\"journal\":{\"name\":\"Journal of pharmacological sciences\",\"volume\":\"157 4\",\"pages\":\"Pages 229-232\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of pharmacological sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1347861325000167\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmacological sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1347861325000167","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/23 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Midnolin gene expression is enhanced by Gq-coupled muscarinic acetylcholine receptor stimulation in SH-SY5Y human neuroblastoma cells
We previously demonstrated that the midnolin gene (MIDN) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by MIDN knockout in PC12 cells. Therefore, drugs that upregulate MIDN may have neurotrophic effects. In this study, acetylcholine increased MIDN promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells. These effects were suppressed by atropine and a Gq inhibitor, YM254890, indicating that muscarinic receptor/Gq signaling is required for the induction of MIDN by acetylcholine. Our findings suggest that drugs that upregulate MIDN may have therapeutic potential for PD.
期刊介绍：
Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.
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