Document Detail


Hepatocyte growth factor protects auditory hair cells from aminoglycosides.
MedLine Citation:
PMID:  19688848     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES/HYPOTHESIS: To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms. STUDY DESIGN: Experimental study. METHODS: We quantitatively assessed protective effects of HGF on mouse cochlear hair cells against neomycin toxicity using explant culture systems. To understand mechanisms of hair cell protection by HGF, we examined the expression of c-Met, HGF receptor, and 4-hydroxynonenal (a lipid peroxidation marker) in the cochlea by means of immunohistochemistry and Western blotting. RESULTS: The application of HGF to cochlear explant cultures significantly reduced the hair cell loss induced by neomycin. Immunohistochemistry showed c-Met expression in normal auditory hair cells, and its increase in response to neomycin-induced damage. Immunostaining for 4-hydroxynonenal suggested that HGF acted by attenuating the lipid peroxidation of auditory epithelia induced by neomycin. CONCLUSIONS: These findings demonstrate that a functional HGF/c-Met coupling is present in the cochlea, and HGF application exerts protective effects on hair cells, indicating the potential of HGF as a therapeutic agent for sensorineural hearing loss.
Authors:
Yayoi S Kikkawa; Takayuki Nakagawa; Hirohito Tsubouchi; Akio Ido; Takatoshi Inaoka; Kazuya Ono; Juichi Ito
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Laryngoscope     Volume:  119     ISSN:  1531-4995     ISO Abbreviation:  Laryngoscope     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-28     Completed Date:  2009-10-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8607378     Medline TA:  Laryngoscope     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2027-31     Citation Subset:  IM    
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, Kyoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Hair Cells, Auditory / drug effects*,  metabolism
Hearing Loss, Sensorineural / drug therapy
Hepatocyte Growth Factor / metabolism,  pharmacology*
Immunohistochemistry
Lipid Peroxidation / drug effects
Mice
Mice, Inbred ICR
Neomycin / adverse effects*
Oxidative Stress / drug effects
Protein Synthesis Inhibitors / adverse effects*
Proto-Oncogene Proteins c-met / metabolism
Chemical
Reg. No./Substance:
0/Protein Synthesis Inhibitors; 1404-04-2/Neomycin; 67256-21-7/Hepatocyte Growth Factor; EC 2.7.10.1/Proto-Oncogene Proteins c-met

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