Enhancing mitophagy by ligustilide through BNIP3-LC3 interaction attenuates oxidative stress-induced neuronal apoptosis in spinal cord injury.

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
International Journal of Biological Sciences Pub Date : 2024-08-12 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.98051
Hui Yao, Chaoyang Cai, Weijun Huang, Caizhen Zhong, Tianlun Zhao, Jiawei Di, Juliang Tang, Depeng Wu, Mao Pang, Lei He, Limin Rong, Bin Liu
{"title":"Enhancing mitophagy by ligustilide through BNIP3-LC3 interaction attenuates oxidative stress-induced neuronal apoptosis in spinal cord injury.","authors":"Hui Yao, Chaoyang Cai, Weijun Huang, Caizhen Zhong, Tianlun Zhao, Jiawei Di, Juliang Tang, Depeng Wu, Mao Pang, Lei He, Limin Rong, Bin Liu","doi":"10.7150/ijbs.98051","DOIUrl":null,"url":null,"abstract":"<p><p>Mitophagy selectively eliminates damaged or dysfunctional mitochondria, playing a crucial role in maintaining mitochondrial quality control. However, it remains unclear whether mitophagy can be fully activated and how it evolves after SCI. Our RNA-seq analysis of animal samples from sham and 1, 3, 5, and 7 days post-SCI indicated that mitophagy was indeed inhibited during the acute and subacute early stages. <i>In vitro</i> experiments showed that this inhibition was closely related to excessive production of reactive oxygen species (ROS) and the downregulation of BNIP3. Excessive ROS led to the blockage of mitophagy flux, accompanied by further mitochondrial dysfunction and increased neuronal apoptosis. Fortunately, ligustilide (LIG) was found to have the ability to reverse the oxidative stress-induced downregulation of BNIP3 and enhance mitophagy through BNIP3-LC3 interaction, alleviating mitochondrial dysfunction and ultimately reducing neuronal apoptosis. Further animal experiments demonstrated that LIG alleviated oxidative stress and mitophagy inhibition, rescued neuronal apoptosis, and promoted tissue repair, ultimately leading to improved motor function. In summary, this study elucidated the state of mitophagy inhibition following SCI and its potential mechanisms, and confirmed the effects of LIG-enhanced mitophagy through BNIP3-LC3, providing new therapeutic targets and strategies for repairing SCI.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379069/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7150/ijbs.98051","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Mitophagy selectively eliminates damaged or dysfunctional mitochondria, playing a crucial role in maintaining mitochondrial quality control. However, it remains unclear whether mitophagy can be fully activated and how it evolves after SCI. Our RNA-seq analysis of animal samples from sham and 1, 3, 5, and 7 days post-SCI indicated that mitophagy was indeed inhibited during the acute and subacute early stages. In vitro experiments showed that this inhibition was closely related to excessive production of reactive oxygen species (ROS) and the downregulation of BNIP3. Excessive ROS led to the blockage of mitophagy flux, accompanied by further mitochondrial dysfunction and increased neuronal apoptosis. Fortunately, ligustilide (LIG) was found to have the ability to reverse the oxidative stress-induced downregulation of BNIP3 and enhance mitophagy through BNIP3-LC3 interaction, alleviating mitochondrial dysfunction and ultimately reducing neuronal apoptosis. Further animal experiments demonstrated that LIG alleviated oxidative stress and mitophagy inhibition, rescued neuronal apoptosis, and promoted tissue repair, ultimately leading to improved motor function. In summary, this study elucidated the state of mitophagy inhibition following SCI and its potential mechanisms, and confirmed the effects of LIG-enhanced mitophagy through BNIP3-LC3, providing new therapeutic targets and strategies for repairing SCI.

利格列奈通过 BNIP3-LC3 相互作用增强有丝分裂,可减轻氧化应激诱导的脊髓损伤神经细胞凋亡。
有丝分裂可选择性地消除受损或功能障碍的线粒体,在维持线粒体质量控制方面发挥着至关重要的作用。然而,目前仍不清楚有丝分裂是否能被完全激活以及它在 SCI 后是如何演变的。我们对假性 SCI 和 SCI 后 1、3、5 和 7 天的动物样本进行的 RNA-seq 分析表明,在急性和亚急性早期阶段,有丝分裂确实受到了抑制。体外实验表明,这种抑制与活性氧(ROS)的过度产生和 BNIP3 的下调密切相关。过量的 ROS 导致有丝分裂通量受阻,并进一步导致线粒体功能障碍和神经元凋亡增加。幸运的是,研究发现藁本内酯(LIG)能够逆转氧化应激诱导的 BNIP3 下调,并通过 BNIP3-LC3 相互作用增强有丝分裂,缓解线粒体功能障碍,最终减少神经元凋亡。进一步的动物实验表明,LIG 可缓解氧化应激和有丝分裂抑制,挽救神经元凋亡,促进组织修复,最终改善运动功能。总之,本研究阐明了 SCI 后有丝分裂抑制的状态及其潜在机制,并证实了 LIG 通过 BNIP3-LC3 增强有丝分裂的作用,为修复 SCI 提供了新的治疗靶点和策略。
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
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
×
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