title: Signaling pathway for apoptosis of vestibular hair cells of mice due to aminoglycosides.
abstract: 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.
authors.affiliation: Department of Otolaryngology--Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Tae Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Fukuichiro
authors.initials: F
authors.lastname: Iguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Endo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kita
authors.forename: Norihiko
authors.initials: N
authors.lastname: Murai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Naito
authors.forename: Sang Heun
authors.initials: SH
authors.lastname: Lee
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D018069:Hair Cells, Vestibular / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008928:Mitochondria / Q000502:physiology; D009355:Neomycin / Q000009:adverse effects*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D020169:Caspases; D009355:Neomycin