Cordycepin Ameliorates Kainic Acid-Induced HT22 Cell Neurotoxicity by Activating GPR120-Mediated Mitophagy

IF 2.7 4区 医学 Q2 DEVELOPMENTAL BIOLOGY
Yongzhi San, Minghua Wang
{"title":"Cordycepin Ameliorates Kainic Acid-Induced HT22 Cell Neurotoxicity by Activating GPR120-Mediated Mitophagy","authors":"Yongzhi San,&nbsp;Minghua Wang","doi":"10.1002/dneu.22961","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Mitophagy is important for normal neural activity. Epilepsy is intimately linked to neurotoxicity due to mitochondrial dysfunction. Cordycepin (Cor) has been shown to exert neuroprotective effects. This study aims to investigate whether Cor could mitigate neurotoxicity in epilepsy by modulating mitophagy.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In vitro, kainic acid (KA) was utilized to induce cytotoxicity in HT22 cell. Cell viability was assessed using the CCK-8 assay, while cell damage was evaluated through an LDH kit. Flow cytometry was used to assess apoptosis. The expressions of G protein-coupled receptor 120 (GPR120), apoptosis, and mitophagy-related proteins were analyzed by western blot. Inflammatory factors and oxidative stress levels were examined by kits. DCFH-DA staining was applied to observe cellular reactive oxygen species (ROS) levels. The three-dimensional coordinates of GPR120 were retrieved from the PDB database, and molecular docking was performed using AutoDock. Immunofluorescence staining was used to observe mitophagy level.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Cor significantly attenuated KA-induced HT22 cell viability injury and inflammation, while suppressing ROS and oxidative stress levels. Notably, Cor ameliorated the decrease of mitophagy level observed in HT22 cells treated with KA. GPR120 expression was upregulated following KA treatment and further elevated after adding Cor. Cor could bind to GPR120. Interference with GPR120 reversed the ameliorative effects of Cor on KA-induced mitophagy and cytotoxicity in HT22 cells.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Overall, Cor significantly alleviated KA-induced HT22 cell neurotoxic damage and oxidative stress. This protective effect may be mediated through GPR120-regulated mitophagy.</p>\n </section>\n </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/dneu.22961","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Mitophagy is important for normal neural activity. Epilepsy is intimately linked to neurotoxicity due to mitochondrial dysfunction. Cordycepin (Cor) has been shown to exert neuroprotective effects. This study aims to investigate whether Cor could mitigate neurotoxicity in epilepsy by modulating mitophagy.

Methods

In vitro, kainic acid (KA) was utilized to induce cytotoxicity in HT22 cell. Cell viability was assessed using the CCK-8 assay, while cell damage was evaluated through an LDH kit. Flow cytometry was used to assess apoptosis. The expressions of G protein-coupled receptor 120 (GPR120), apoptosis, and mitophagy-related proteins were analyzed by western blot. Inflammatory factors and oxidative stress levels were examined by kits. DCFH-DA staining was applied to observe cellular reactive oxygen species (ROS) levels. The three-dimensional coordinates of GPR120 were retrieved from the PDB database, and molecular docking was performed using AutoDock. Immunofluorescence staining was used to observe mitophagy level.

Results

Cor significantly attenuated KA-induced HT22 cell viability injury and inflammation, while suppressing ROS and oxidative stress levels. Notably, Cor ameliorated the decrease of mitophagy level observed in HT22 cells treated with KA. GPR120 expression was upregulated following KA treatment and further elevated after adding Cor. Cor could bind to GPR120. Interference with GPR120 reversed the ameliorative effects of Cor on KA-induced mitophagy and cytotoxicity in HT22 cells.

Conclusion

Overall, Cor significantly alleviated KA-induced HT22 cell neurotoxic damage and oxidative stress. This protective effect may be mediated through GPR120-regulated mitophagy.

虫草素通过激活gpr120介导的线粒体自噬改善Kainic酸诱导的HT22细胞神经毒性
线粒体自噬对正常的神经活动很重要。由于线粒体功能障碍,癫痫与神经毒性密切相关。虫草素(Cor)已被证明具有神经保护作用。本研究旨在探讨甘草是否能通过调节线粒体自噬来减轻癫痫的神经毒性。方法采用kainic acid (KA)体外诱导HT22细胞毒性。使用CCK-8法评估细胞活力,通过LDH试剂盒评估细胞损伤。流式细胞术检测细胞凋亡。western blot检测G蛋白偶联受体120 (GPR120)、凋亡、有丝分裂相关蛋白的表达。用试剂盒检测炎症因子和氧化应激水平。DCFH-DA染色观察细胞活性氧(ROS)水平。从PDB数据库中检索GPR120的三维坐标,使用AutoDock软件进行分子对接。免疫荧光染色法观察细胞自噬水平。结果Cor可显著减轻ka诱导的HT22细胞活力损伤和炎症,同时抑制ROS和氧化应激水平。值得注意的是,Cor改善了KA处理HT22细胞中线粒体自噬水平的下降。KA处理后GPR120表达上调,加入Cor后表达进一步升高,Cor可与GPR120结合。干扰GPR120逆转了Cor对ka诱导的HT22细胞有丝分裂和细胞毒性的改善作用。结论总的来说,Cor可显著减轻ka诱导的HT22细胞神经毒性损伤和氧化应激。这种保护作用可能是通过gpr120调控的线粒体自噬介导的。
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
Developmental Neurobiology
Developmental Neurobiology 生物-发育生物学
CiteScore
6.50
自引率
0.00%
发文量
45
审稿时长
4-8 weeks
期刊介绍: Developmental Neurobiology (previously the Journal of Neurobiology ) publishes original research articles on development, regeneration, repair and plasticity of the nervous system and on the ontogeny of behavior. High quality contributions in these areas are solicited, with an emphasis on experimental as opposed to purely descriptive work. The Journal also will consider manuscripts reporting novel approaches and techniques for the study of the development of the nervous system as well as occasional special issues on topics of significant current interest. We welcome suggestions on possible topics from our readers.
×
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