TY - JOUR
T1 - Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity
AU - Hoshino, Tomofumi
AU - Tabuchi, Keiji
AU - Nishimura, Bungo
AU - Tanaka, Shuho
AU - Nakayama, Masahiro
AU - Ishii, Tetsuro
AU - Warabi, Eiji
AU - Yanagawa, Toru
AU - Shimizu, Ritsuku
AU - Yamamoto, Masayuki
AU - Hara, Akira
N1 - Funding Information:
This work was supported by a Grant-in-aid for Young Scientists (B) ( 22791567 ) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan .
PY - 2011/11/11
Y1 - 2011/11/11
N2 - 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.
AB - 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.
KW - Age-related hearing loss (AHL)
KW - Cochlea
KW - Gentamicin ototoxicity
KW - NF-E2-related factor (Nrf2)
KW - Reactive oxygen species (ROS)
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U2 - 10.1016/j.bbrc.2011.10.019
DO - 10.1016/j.bbrc.2011.10.019
M3 - Article
C2 - 22020098
AN - SCOPUS:80755188896
SN - 0006-291X
VL - 415
SP - 94
EP - 98
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -