SOD2 Alleviates Hearing Loss Induced by Noise and Kanamycin in Mitochondrial DNA4834-deficient Rats by Regulating PI3K/MAPK Signaling
| Autor: | Jun Li, Xiang Dai, Han Xiao, Rong Yang, Zhong-Fang Xia, Xue-Lian He, Shan Huang, Yan Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Hearing loss
SOD2 Biology medicine.disease_cause Biochemistry DNA Mitochondrial Phosphatidylinositol 3-Kinases Kanamycin otorhinolaryngologic diseases Genetics medicine Inner ear skin and connective tissue diseases Hearing Loss Mitogen-Activated Protein Kinase Kinases Mutation Superoxide Dismutase Cell biology Mitochondria medicine.anatomical_structure Gene Expression Regulation Organ of Corti Apoptosis cardiovascular system sense organs Hair cell medicine.symptom Noise medicine.drug Signal Transduction |
| Zdroj: | Current medical science. 41(3) |
| ISSN: | 2523-899X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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