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

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences Pub Date : 2025-02-23 DOI:10.1016/j.jphs.2025.02.006

Ikuo Norota , Yusuke Zuiki , Ayano Chiba , Mikako Nagashima , Jiro Ogura , Hiroaki Yamaguchi , Kuniaki Ishii , Yutaro Obara

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引用次数: 0

摘要

我们之前在Yamagata和British队列中证明midnolin基因（MIDN）是帕金森病（PD）的一个危险因素，并且PC12细胞中的MIDN敲除会消除神经突的生长。因此，上调MIDN的药物可能具有神经营养作用。在本研究中，乙酰胆碱在SH-SY5Y细胞中以浓度依赖性的方式增加MIDN启动子活性和基因表达。这些作用被阿托品和Gq抑制剂YM254890抑制，表明乙酰胆碱诱导MIDN需要毒蕈碱受体/Gq信号。我们的研究结果表明，上调MIDN的药物可能具有治疗PD的潜力。

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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 G_q inhibitor, YM254890, indicating that muscarinic receptor/G_q signaling is required for the induction of MIDN by acetylcholine. Our findings suggest that drugs that upregulate MIDN may have therapeutic potential for PD.

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

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.