Document Detail

Signaling pathway for apoptosis of vestibular hair cells of mice due to aminoglycosides.
MedLine Citation:
PMID:  15078083     Owner:  NLM     Status:  MEDLINE    
Previous studies on regeneration of mammalian vestibular hair cells have indicated the potential for self-repair of damaged hair cells. The rescue of damaged hair cells from cell death may therefore increase regenerated hair cells in affected vestibular epithelia. The role of apoptosis in the degradation of vestibular hair cells following aminoglycoside treatment has been elucidated. To seek a method of protecting vestibular hair cells from aminoglycoside toxicity, we examined the apoptosis signaling pathway of vestibular hair cells due to aminoglycoside toxicity. Induction of apoptosis in hair cells of mouse ampullar cristae damaged by local application of neomycin was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method and transmission electron microscopy (TEM). Immunohistochemistry for apoptosis-related proteins was employed to determine the signaling pathway of apoptosis of hair cells. The occurrence of apoptosis in hair cells was demonstrated by TUNEL staining and TEM. In apoptotic hair cells, activation of caspase-3 and -9, and redistribution of cytochrome c was identified, while there was no expression of activated caspase-8 or apoptosis-inducing factor. In conclusion, these findings indicate that the mitochondria-mediated pathway of apoptosis may play a role in inducing the apoptosis of vestibular hair cells due to aminoglycoside toxicity. Stabilization of the mitochondrial membrane may therefore rescue vestibular hair cells from apoptosis, leading to an increase in self-repaired hair cells in affected vestibular epithelia.
Ji Eun Lee; Takayuki Nakagawa; Tae Soo Kim; Fukuichiro Iguchi; Tsuyoshi Endo; Tomoko Kita; Norihiko Murai; Yasushi Naito; Sang Heun Lee; Juichi Ito
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta oto-laryngologica. Supplementum     Volume:  -     ISSN:  0365-5237     ISO Abbreviation:  Acta Otolaryngol Suppl     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-04-13     Completed Date:  2004-08-31     Revised Date:  2008-02-13    
Medline Journal Info:
Nlm Unique ID:  0370355     Medline TA:  Acta Otolaryngol Suppl     Country:  Norway    
Other Details:
Languages:  eng     Pagination:  69-74     Citation Subset:  IM    
Department of Otolaryngology--Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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MeSH Terms
Anti-Bacterial Agents / adverse effects*
Apoptosis / drug effects*
Caspases / metabolism
Hair Cells, Vestibular / cytology,  drug effects*,  ultrastructure
In Situ Nick-End Labeling
Mice, Inbred C57BL
Microscopy, Electron
Mitochondria / physiology
Neomycin / adverse effects*
Signal Transduction / physiology*
Reg. No./Substance:
0/Anti-Bacterial Agents; 1404-04-2/Neomycin; EC 3.4.22.-/Caspases

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