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Inhibition of Gpx4-mediated Ferroptosis Alleviates Cisplatin-Induced Hearing Loss in C57BL/6 mice

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收录情况： ◇ SCIE

作者：
Liu Ziyi[1] * ; Zhang Hanbing[3] * ; Hong Guodong[1] * ; Bi Xiuli[1] ; Hu Jun[2] ; Zhang Tiancheng[2] ; 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[4,2,6,7,8,9] ; Fu Xiaolong[1] ;
机构： [1]Medical Science and Technology Innovation Center, Institute of Brain Science and Brain7 inspired Research, Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China [2]Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China [3]Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, 250012, Shandong, [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, Nanjing, 210096, Jiangsu, China. [5]School of Life Science, Shandong University, Qingdao, 266237, Shandong, China [6]Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, 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,Chengdu, 610072, Sichuan, China. [9]Southeast University Shenzhen Research Institute, Shenzhen, 518063, Guangdong, China. [10]Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250102, Shandong, China.
出处：
DOI： 10.1016/j.ymthe.2024.02.029
ISSN：

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-Seq, 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 OHC loss and progressive damage of synapses in IHC 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.Copyright © 2024. Published by Elsevier Inc.

基金：
National Key R&D Program of China (No. 2019YFA0111400, 2021YFA1101300, 2021YFA1101800, 2020YFA0112503), the National Natural Science Foundation of China (No. 82271175, 82192863, 82001204, 82201294, 82201296, 82301305, 82330033, 82030029, 92149304), the Natural Science Foundation from Shandong Province (No. ZR2022QH338, ZR2021QH269, ZR2022QH205), Science and Technology Department of Sichuan Province (No. 2021YFS0371), Shenzhen Science and Technology Program (JCYJ20190814093401920, JCYJ20210324125608022), 2022 722 Open Project Fund of Guangdong Academy of Medical Sciences (YKY-KF202201).
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外文
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出版当年[2024]版：
无
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 生物工程与应用微生物 1 区 遗传学 1 区 医学：研究与实验
JCR分区：
出版当年[2024]版：
无
最新[2023]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2023版]

第一作者：
第一作者机构： [1]Medical Science and Technology Innovation Center, Institute of Brain Science and Brain7 inspired Research, Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China
共同第一作者：
通讯作者：
通讯机构： [2]Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, 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, Nanjing, 210096, Jiangsu, China. [6]Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, 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,Chengdu, 610072, Sichuan, China. [9]Southeast University Shenzhen Research Institute, Shenzhen, 518063, Guangdong, 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.doi:10.1016/j.ymthe.2024.02.029.
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)
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

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