| First Author | Hoshino T | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 415 |
| Issue | 1 | Pages | 94-8 |
| PubMed ID | 22020098 | Mgi Jnum | J:178706 |
| Mgi Id | MGI:5299967 | Doi | 10.1016/j.bbrc.2011.10.019 |
| Citation | Hoshino T, et al. (2011) Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity. Biochem Biophys Res Commun 415(1):94-8 |
| abstractText | Expression of antioxidant enzymes is regulated by transcription factor NF-E2-related factor (Nrf2) and induced by oxidative stress. Reactive oxygen species contribute to the formation of several types of cochlear injuries, including age-related hearing loss and gentamicin ototoxicity. In this study, we examined the roles of Nrf2 in age-related hearing loss and gentamicin ototoxicity by measuring auditory brainstem response thresholds in Nrf2-knockout mice. Although Nrf2-knockout mice maintained normal auditory thresholds at 3 months of age, their hearing ability was significantly more impaired than that of age-matched wild-type mice at 6 and 11 months of age. Additionally, the numbers of hair cells and spiral ganglion cells were remarkably reduced in Nrf2-knockout mice at 11 months of age. To examine the importance of Nrf2 in protecting against gentamicin-induced ototoxicity, 3-day-old mouse organ of Corti explants were cultured with gentamicin. Hair cell loss caused by gentamicin treatment was enhanced in the Nrf2-deficient tissues. Furthermore, the expressions of some Nrf2-target genes were activated by gentamicin treatment in wild-type mice but not in Nrf2-knockout mice. The present findings indicate that Nrf2 protects the inner ear against age-related hearing injuries and gentamicin ototoxicity by up-regulating antioxidant enzymes and detoxifying proteins. |
