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Hearing vulnerability after noise exposure in a mouse model of reactive oxygen species overproduction
Author(s) -
Morioka Shigefumi,
Sakaguchi Hirofumi,
Yamaguchi Taro,
Ninoyu Yuzuru,
Mohri Hiroaki,
Nakamura Takashi,
Hisa Yasuo,
Ogita Kiyokazu,
Saito Naoaki,
Ueyama Takehiko
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14451
Subject(s) - reactive oxygen species , nadph oxidase , hearing loss , cochlea , ototoxicity , antioxidant , hair cell , microbiology and biotechnology , genetically modified mouse , reactive nitrogen species , oxidative stress , transgene , chemistry , biology , medicine , biochemistry , audiology , anatomy , chemotherapy , gene , cisplatin
Previous studies have convincingly argued that reactive oxygen species ( ROS ) contribute to the development of several major types of sensorineural hearing loss, such as noise‐induced hearing loss ( NIHL ), drug‐induced hearing loss, and age‐related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic ( TG ) mouse line expressing the human NADPH oxidase 4 ( NOX 4, NOX 4‐ TG mice), which is a constitutively active ROS ‐producing enzyme that does not require stimulation or an activator. Overproduction of ROS was detected at the cochlea of the inner ear in NOX 4 ‐ TG mice, but they showed normal hearing function under baseline conditions. However, they demonstrated hearing function vulnerability, especially at high‐frequency sounds, upon exposure to intense noise, which was accompanied by loss of cochlear outer hair cells ( OHC s). The vulnerability to loss of hearing function and OHC s was rescued by treatment with the antioxidant Tempol. Additionally, we found increased protein levels of the heat‐shock protein 47 ( HSP 47) in models using HEK 293 cells, including H 2 O 2 treatment and cells with stable and transient expression of NOX 4. Furthermore, the up‐regulated levels of Hsp47 were observed in both the cochlea and heart of NOX 4 ‐ TG mice. Thus, antioxidant therapy is a promising approach for the treatment of NIHL . Hsp47 may be an endogenous antioxidant factor, compensating for the chronic ROS overexposure in vivo , and counteracting ROS ‐related hearing loss.