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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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Published in: | PloS one 2011-02, Vol.6 (2), p.e17322 |
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description | 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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0017322</identifier><identifier>PMID: 21364896</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2011-02, Vol.6 (2), p.e17322</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Yu et al. 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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. 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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 |
title | A protective mechanism against antibiotic-induced ototoxicity: role of prestin |
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