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SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling

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Summary

Superoxide dismutase 2 (SOD2)-mediated gene therapy has significant protective effects against kanamycin-induced hearing loss and hair cell loss in the inner ear, but the underlying mechanisms are still unclear. Herein, an in vivo aging model of mitochondrial DNA (mtDNA)4834 deletion mutation was established using D-galactose, and the effects of noise or kanamycin on inner ear injury was investigated. Rats subjected to mtDNA4834 mutation via D-galactose administration showed hearing loss characterized by the disruption of inner ear structure (abnormal cell morphology, hair cell lysis, and the absence of the organ of Corti), increased SOD2 promoter methylation, and an increase in the degree of apoptosis. Exposure to noise or kanamycin further contributed to the effects of D-galactose. SOD2 overexpression induced by viral injection accordingly counteracted the effects of noise and kanamycin and ameliorated the symptoms of hearing loss, suggesting the critical involvement of SOD2 in preventing deafness and hearing-related conditions. The PI3K and MAPK signaling pathways were also regulated by noise/kanamycin exposure and/or SOD2 overexpression, indicating that they may be involved in the therapeutic effect of SOD2 against age-related hearing loss.

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Author notes

  1. The authors contributed equally to this work.

Authors and Affiliations

  1. Department of Otorhinolaryngology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Yan Zhang, Shan Huang, Zhong-fang Xia & Jun Li

  2. Reproductive Laboratory, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Xiang Dai

  3. Biological Sample Bank, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Han Xiao

  4. Central Laboratory, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Xue-lian He

  5. Health Care Department, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Rong Yang

Authors
  1. Yan Zhang
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Correspondence to Jun Li.

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This work was supported by Hubei Provincial Natural Science Foundation of China (No. 2014CKB511).

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Zhang, Y., Huang, S., Dai, X. et al. SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling. CURR MED SCI 41, 587–596 (2021). https://doi.org/10.1007/s11596-021-2376-4

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  • DOI: https://doi.org/10.1007/s11596-021-2376-4

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