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Fascin2缺失会增加小鼠对顺铂诱导的听力损伤及耳蜗细胞凋亡的易感性。

Loss of Fascin2 increases susceptibility to cisplatin-induced hearing impairment and cochlear cell apoptosis in mice.

作者信息

Wang Yan, Liu Yingying, Xie Yi, Luan Jun, Liu Rongrong, Zhu Yongjia, Ma Ying, Fan Yi, Sun Yan, Shang Wenjing, Han Fengchan

机构信息

Department of Biochemistry and Molecular Biology, and Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, Shandong, PR China.

Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, PR China.

出版信息

J Otol. 2024 Jul;19(3):133-139. doi: 10.1016/j.joto.2024.07.001. Epub 2024 Oct 19.

DOI:10.1016/j.joto.2024.07.001
PMID:39735238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11681795/
Abstract

OBJECTIVES

Deletion of gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of on cisplatin-induced hearing impairment in mice and to explore the possible mechanism.

METHODS

Two-week-old mice and mice were treated with two doses of cisplatin, with a 3-day recovery period in between. ABR (auditory evoked brain stem response) thresholds were measured and cochlear pathology was observed at 3 weeks of age.

RESULTS

Both and mice showed hearing loss under the effect of cisplatin, but the impairment was more severe in mice. Further experiments showed that the percentages of outer hair cell (OHC) and spiral ganglion neuron (SGN) loss were significantly higher in cisplatin-treated mice compared to mice. Additionally, knockdown of in HEI-OC1 cells worsened cisplatin-induced cell apoptosis.

CONCLUSION

FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis.

摘要

目的

小鼠体内某基因的缺失与进行性听力丧失及耳蜗细胞变性有关。顺铂是一种抗肿瘤药物，可引起包括耳毒性在内的各种副作用。本研究的目的是探讨该基因对顺铂诱导的小鼠听力损伤的影响，并探索其可能的机制。

方法

对两周龄的该基因敲除小鼠和野生型小鼠给予两剂顺铂治疗，中间间隔3天恢复期。在3周龄时测量听觉脑干反应（ABR）阈值并观察耳蜗病理情况。

结果

在顺铂作用下，基因敲除小鼠和野生型小鼠均出现听力损失，但基因敲除小鼠的损伤更严重。进一步实验表明，与野生型小鼠相比，顺铂处理的基因敲除小鼠中外毛细胞（OHC）和螺旋神经节神经元（SGN）损失的百分比显著更高。此外，在HEI-OC1细胞中敲低该基因会加重顺铂诱导的细胞凋亡。

结论

FSCN2通过抑制细胞凋亡介导顺铂诱导的耳毒性降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/21835535a551/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/6d6d0784359d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/1ba97136f671/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/150f83e2d539/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/134004cf36aa/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/8af1f00d17b3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/21835535a551/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/6d6d0784359d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/1ba97136f671/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/150f83e2d539/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/134004cf36aa/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/8af1f00d17b3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e41c/11681795/21835535a551/gr6.jpg

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本文引用的文献

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Cell Death Discov. 2024 Feb 19;10(1):89. doi: 10.1038/s41420-024-01851-5.
2
CD44+ and CD133+ Non-Small Cell Lung Cancer Cells Exhibit DNA Damage Response Pathways and Dormant Polyploid Giant Cancer Cell Enrichment Relating to Their p53 Status.CD44+ 和 CD133+ 非小细胞肺癌细胞表现出与 p53 状态相关的 DNA 损伤反应途径和休眠多倍体巨癌细胞富集。
Int J Mol Sci. 2022 Apr 28;23(9):4922. doi: 10.3390/ijms23094922.
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Nrf2 activation protects auditory hair cells from cisplatin-induced ototoxicity independent on mitochondrial ROS production.
Nrf2 激活可保护听觉毛细胞免受顺铂诱导的耳毒性，而不依赖于线粒体 ROS 的产生。
Toxicol Lett. 2020 Oct 1;331:1-10. doi: 10.1016/j.toxlet.2020.04.005. Epub 2020 May 16.
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ALA protects against ERS-mediated apoptosis in a cochlear cell model with low citrate synthase expression.ALA 可防止低柠檬酸合酶表达的耳蜗细胞模型中 ERS 介导的细胞凋亡。
Arch Biochem Biophys. 2020 Jul 30;688:108402. doi: 10.1016/j.abb.2020.108402. Epub 2020 May 11.
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GSTA4 mediates reduction of cisplatin ototoxicity in female mice.GSTA4 介导雌性小鼠顺铂耳毒性的降低。
Nat Commun. 2019 Sep 12;10(1):4150. doi: 10.1038/s41467-019-12073-0.
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Advances in Toxicological Research of the Anticancer Drug Cisplatin.顺铂抗癌药物毒理学研究进展。
Chem Res Toxicol. 2019 Aug 19;32(8):1469-1486. doi: 10.1021/acs.chemrestox.9b00204. Epub 2019 Aug 5.
7
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