A protective mechanism against antibiotic-induced ototoxicity: role of prestin

Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains uncle...

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Bibliographic Details
Published in:PloS one 2011-02, Vol.6 (2), p.e17322
Main Authors: Yu, Li, Jiang, Xiao Hua, Zhou, Zhen, Tsang, Lai Ling, Yu, Mei Kuen, Chung, Yiu Wa, Zhang, Xiao Hu, Wang, Ai Mei, Tang, Hao, Chan, Hsiao Chang
Format: Article
Language:English
Subjects:
Aminoglycosides
Analysis
Animals
Anti-Bacterial Agents - adverse effects
Antibiotics
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Apoptosis - physiology
Biology
Cell growth
Cell Line
Chloride
CHO Cells
Cochlea
Cricetinae
Cricetulus
Cytoprotection - drug effects
Cytoprotection - genetics
Developing countries
Ear Diseases - chemically induced
Ear Diseases - genetics
Ear Diseases - metabolism
Hair cells
Hair Cells, Auditory - drug effects
Hair Cells, Auditory - metabolism
Hair Cells, Auditory - pathology
Hearing loss
Hearing Loss - chemically induced
Hearing Loss - genetics
Hearing Loss - metabolism
Kanamycin - adverse effects
Kinases
LDCs
Male
Medicine
Mice
Mice, Inbred BALB C
Molecular Motor Proteins - genetics
Molecular Motor Proteins - metabolism
Molecular Motor Proteins - physiology
mRNA
Ototoxicity
Outer hair cells
Physiology
Proteins
Regulation
Rodents
Sensors
Side effects
Sound amplification
Studies
Tuberculosis
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Summary:Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains unclear. In the present study, we test the possibility that prestin, the motor protein specifically expressed in the basolateral membrane of outer hair cells (OHCs) in the cochlea with electromotility responsible for sound amplification, may be involved in the process of AG-induced apoptosis in OHCs. Our results from both mice model and cultured cell line indicate a previously unexpected role of prestin, in mediating antibiotic-induced apoptosis, the effect of which is associated with its anion-transporting capacity. The observed downregulation of prestin mRNA prior to detectable apoptosis in OHCs and hearing loss in the antibiotic-treated mice is interesting, which may serve as a protective mechanism against hearing loss induced by AGs in the early stage.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0017322