A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation
The aim of this study was to investigate the effect of LLY-283, a selective inhibitor of protein arginine methyltransferase 5 (PRMT5), on a noise-induced hearing loss (NIHL) mouse model and to identify a potential target for a therapeutic intervention against NIHL. Eight-week-old male C57BL/6 mice w...
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| Format: | Article |
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Elsevier
2022-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322008326 |
| _version_ | 1798004606832214016 |
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| author | Chang Liu Dongmei Tang Zhiwei Zheng Xiaoling Lu Wen Li Liping Zhao Yingzi He Huawei Li |
| author_facet | Chang Liu Dongmei Tang Zhiwei Zheng Xiaoling Lu Wen Li Liping Zhao Yingzi He Huawei Li |
| author_sort | Chang Liu |
| collection | DOAJ |
| description | The aim of this study was to investigate the effect of LLY-283, a selective inhibitor of protein arginine methyltransferase 5 (PRMT5), on a noise-induced hearing loss (NIHL) mouse model and to identify a potential target for a therapeutic intervention against NIHL. Eight-week-old male C57BL/6 mice were used. The auditory brainstem response was measured 2 days after noise exposure. The apoptosis of hair cells (HCs) was detected by caspase-3/7 staining, whereas the accumulation of reactive oxygen species (ROS) was measured by 4-HNE staining. We demonstrated that the death of HCs and loss of cochlear synaptic ribbons induced by noise exposure could be significantly reduced by the presence of LLY-283. LLY-283 pretreatment before noise exposure notably decreased 4-HNE and caspase-3/7 levels in the cochlear HCs. We also noticed that the number of spiral ganglion neurons (SGNs) was notably increased after LLY-283 pretreatment. Furthermore, we showed that LLY-283 could increase the expression level of p-AKT in the SGNs. The underlying mechanism involves alleviation of ROS accumulation and activation of the PI3K/AKT pathway, indicating that LLY-283 might be a potential candidate for therapeutic intervention against NIHL. |
| first_indexed | 2024-04-11T12:26:17Z |
| format | Article |
| id | doaj.art-e03ee47f81a74404853045e56a90e0ce |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T12:26:17Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-e03ee47f81a74404853045e56a90e0ce2022-12-22T04:23:56ZengElsevierEcotoxicology and Environmental Safety0147-65132022-09-01243113992A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulationChang Liu0Dongmei Tang1Zhiwei Zheng2Xiaoling Lu3Wen Li4Liping Zhao5Yingzi He6Huawei Li7ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR ChinaENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR ChinaENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR ChinaENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR ChinaENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR ChinaENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR ChinaENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR China; Correspondence to: Department of ENT Institute and Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, PR China.ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, PR China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, PR China; Correspondence to: Department of ENT Institute and Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, PR China.The aim of this study was to investigate the effect of LLY-283, a selective inhibitor of protein arginine methyltransferase 5 (PRMT5), on a noise-induced hearing loss (NIHL) mouse model and to identify a potential target for a therapeutic intervention against NIHL. Eight-week-old male C57BL/6 mice were used. The auditory brainstem response was measured 2 days after noise exposure. The apoptosis of hair cells (HCs) was detected by caspase-3/7 staining, whereas the accumulation of reactive oxygen species (ROS) was measured by 4-HNE staining. We demonstrated that the death of HCs and loss of cochlear synaptic ribbons induced by noise exposure could be significantly reduced by the presence of LLY-283. LLY-283 pretreatment before noise exposure notably decreased 4-HNE and caspase-3/7 levels in the cochlear HCs. We also noticed that the number of spiral ganglion neurons (SGNs) was notably increased after LLY-283 pretreatment. Furthermore, we showed that LLY-283 could increase the expression level of p-AKT in the SGNs. The underlying mechanism involves alleviation of ROS accumulation and activation of the PI3K/AKT pathway, indicating that LLY-283 might be a potential candidate for therapeutic intervention against NIHL.http://www.sciencedirect.com/science/article/pii/S0147651322008326PRMT5NIHLHair cellSpiral ganglion neuronsReactive oxygen species |
| spellingShingle | Chang Liu Dongmei Tang Zhiwei Zheng Xiaoling Lu Wen Li Liping Zhao Yingzi He Huawei Li A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation Ecotoxicology and Environmental Safety PRMT5 NIHL Hair cell Spiral ganglion neurons Reactive oxygen species |
| title | A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation |
| title_full | A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation |
| title_fullStr | A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation |
| title_full_unstemmed | A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation |
| title_short | A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation |
| title_sort | prmt5 inhibitor protects against noise induced hearing loss by alleviating ros accumulation |
| topic | PRMT5 NIHL Hair cell Spiral ganglion neurons Reactive oxygen species |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322008326 |
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