A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation

Chang Liu; Dongmei Tang; Zhiwei Zheng; Xiaoling Lu; Wen Li; Liping Zhao; Yingzi He; Huawei Li

Ecotoxicology and Environmental Safety (Sep 2022)

A PRMT5 inhibitor protects against noise-induced hearing loss by alleviating ROS accumulation

Chang Liu,
Dongmei Tang,
Zhiwei Zheng,
Xiaoling Lu,
Wen Li,
Liping Zhao,
Yingzi He,
Huawei Li

Affiliations

Chang Liu: 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
Dongmei Tang: 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
Zhiwei Zheng: 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
Xiaoling Lu: 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
Wen Li: 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
Liping Zhao: 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
Yingzi He: 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; Correspondence to: Department of ENT Institute and Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, PR China.
Huawei Li: 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.

Journal volume & issue: Vol. 243
p. 113992

Abstract

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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.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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