Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice

doi:10.1016/j.ymthe.2024.02.029

科研成果详情

题名	Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice
作者	Liu, Ziyi 1; Zhang, Hanbing 3; Hong, Guodong 1; Bi, Xiuli 1; Hu, Jun 2; Zhang, Tiancheng2; An, Yachun 5; Guo, Na 1; Dong, Fengyue 5; Xiao, Yu 5; Li, Wen 1; Zhao, Xiaoxu 1; Chu, Bo 10; Guo, Siwei 5; Zhang, Xiaohan 1; Chai, Renjie 2,4,6,7,8,9; Fu, Xiaolong 1
发表日期	2024-02-27
发表期刊	Molecular therapy : the journal of the American Society of Gene Therapy 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Fsp1 Gpx4 cisplatin-induced ototoxicity ferroptosis luteolin transferrin
摘要	Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss
资助项目	National Key R&D Program of China[2019YFA0111400,2020YFA0112503,2021YFA1101300,2021YFA1101800];National Natural Science Foundation of China[82330033,82201294,92149304,82030029,82201296,82001204,82271175,82301305,82192863];Natural Science Foundation of Shandong Province[ZR2022QH338,ZR2021QH269,ZR2022QH205];Shenzhen Science and Technology Program[JCYJ20210324125608022,JCYJ20190814093401920];Open Project Fund of Guangdong Academy of Medical Sciences[YKY-KF202201];Science and Technology Department of Sichuan Province[2021YFS0371];
出版者	Cell Press
ISSN	1525-0016
EISSN	1525-0024
卷号	32 期号:5 页码:1387-1406
DOI	10.1016/j.ymthe.2024.02.029
收录类别	PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	38414247
Scopus记录号	2-s2.0-85187991021
通讯作者地址	[Chai, Renjie]Southeast University,Nanjing,China ; [Fu, Xiaolong]Medical Science and Technology Innovation Center,Shandong First Medical University & Shandong Academy of Medical Sciences,Shandong,Jinan,250117,China
scopus学科分类	Molecular Medicine;Molecular Biology;Genetics;Pharmacology;Drug Discovery
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210160
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_硕士
通讯作者	Chai, Renjie; Fu, Xiaolong
作者单位	1.Medical Science and Technology Innovation Center,Institute of Brain Science and Brain-inspired Research,Shandong Provincial Hospital,Shandong First Medical University & Shandong Academy of Medical Sciences,Shandong,Jinan,250117,China; 2.Otolaryngology-Head and Neck Surgery,First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.Department of Otorhinolaryngology,Qilu Hospital of Shandong University,NHC Key Laboratory of Otorhinolaryngology (Shandong University),Shandong,Jinan,250012,China; 4.State Key Laboratory of Digital Medical Engineering,Department of Otolaryngology Head and Neck Surgery,Zhongda Hospital,School of Life Sciences and Technology,School of Medicine,Advanced Institute for Life and Health,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,Southeast University,Jiangsu,Nanjing,210096,China; 5.School of Life Science,Shandong University,Shandong,Qingdao,266237,China; 6.Co-Innovation Center of Neuroregeneration,Nantong University,Jiangsu,Nantong,226001,China; 7.Department of Neurology,Aerospace Center Hospital,School of Life Science,Beijing Institute of Technology,Beijing,100081,China; 8.Department of Otolaryngology Head and Neck Surgery,Sichuan Provincial People's Hospital,School of Medicine,University of Electronic Science and Technology of China,Sichuan,Chengdu,610072,China; 9.Southeast University Shenzhen Research Institute,Guangdong,Shenzhen,518063,China; 10.Department of Cell Biology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Shandong,Jinan,250102,China
推荐引用方式 GB/T 7714	Liu, Ziyi,Zhang, Hanbing,Hong, Guodong,et al. Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice[J]. Molecular therapy : the journal of the American Society of Gene Therapy,2024,32(5):1387-1406.
APA	Liu, Ziyi., Zhang, Hanbing., Hong, Guodong., Bi, Xiuli., Hu, Jun., ... & Fu, Xiaolong. (2024). Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice. Molecular therapy : the journal of the American Society of Gene Therapy, 32(5), 1387-1406.
MLA	Liu, Ziyi,et al."Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice".Molecular therapy : the journal of the American Society of Gene Therapy 32.5(2024):1387-1406.