Hearing vulnerability after noise exposure in a mouse model of reactive oxygen species overproduction

Autor: Kiyokazu Ogita, Hirofumi Sakaguchi, Hiroaki Mohri, Yuzuru Ninoyu, Shigefumi Morioka, Yasuo Hisa, Takashi Nakamura, Taro Yamaguchi, Takehiko Ueyama, Naoaki Saito
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
antioxidant
Stimulation
Biochemistry
Mass Spectrometry
Mice
0302 clinical medicine
chemistry.chemical_classification
NADPH oxidase
biology
NOX4
ROS
Cochlea
Cell biology
medicine.anatomical_structure
NADPH Oxidase 4
Sensorineural hearing loss
medicine.symptom
Hearing loss
Mice
Transgenic
Transfection
03 medical and health sciences
Cellular and Molecular Neuroscience
Evoked Potentials
Auditory
Brain Stem
otorhinolaryngologic diseases
medicine
Animals
Humans
Immunoprecipitation
Inner ear
ATP Binding Cassette Transporter
Subfamily B
Member 1
HSP47 Heat-Shock Proteins
hearing loss
Aldehydes
Reactive oxygen species
business.industry
Hsp47
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
HEK293 Cells
030104 developmental biology
transgenic mouse model
Gene Expression Regulation
Hearing Loss
Noise-Induced
chemistry
Mutation
biology.protein
Reactive Oxygen Species
business
030217 neurology & neurosurgery
Zdroj: Journal of Neurochemistry. 146(4):459-473
ISSN: 0022-3042
Popis: 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 (NOX4, NOX4-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 NOX4-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 (OHCs). The vulnerability to loss of hearing function and OHCs was rescued by treatment with the antioxidant Tempol. Additionally, we found increased protein levels of the heat-shock protein 47 (HSP47) in models using HEK293 cells, including H2 O2 treatment and cells with stable and transient expression of NOX4. Furthermore, the up-regulated levels of Hsp47 were observed in both the cochlea and heart of NOX4-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.
Databáze: OpenAIRE
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