A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss.

Détails

ID Serval
serval:BIB_F89371D729F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss.
Périodique
Journal of Neuroscience
Auteur(s)
Wang J., Van De Water T.R., Bonny C., de Ribaupierre F., Puel J.L., Zine A.
ISSN
1529-2401[electronic]
Statut éditorial
Publié
Date de publication
2003
Volume
23
Numéro
24
Pages
8596-8607
Langue
anglais
Résumé
Hearing loss can be caused by a variety of insults, including acoustic trauma and exposure to ototoxins, that principally effect the viability of sensory hair cells via the MAP kinase (MAPK) cell death signaling pathway that incorporates c-Jun N-terminal kinase (JNK). We evaluated the otoprotective efficacy of D-JNKI-1, a cell permeable peptide that blocks the MAPK-JNK signal pathway. The experimental studies included organ cultures of neonatal mouse cochlea exposed to an ototoxic drug and cochleae of adult guinea pigs that were exposed to either an ototoxic drug or acoustic trauma. Results obtained from the organ of Corti explants demonstrated that the MAPK-JNK signal pathway is associated with injury and that blocking of this signal pathway prevented apoptosis in areas of aminoglycoside damage. Treatment of the neomycin-exposed organ of Corti explants with D-JNKI-1 completely prevented hair cell death initiated by this ototoxin. Results from in vivo studies showed that direct application of D-JNKI-1 into the scala tympani of the guinea pig cochlea prevented nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity. Local delivery of D-JNKI-1 also prevented acoustic trauma-induced permanent hearing loss in a dose-dependent manner. These results indicate that the MAPK-JNK signal pathway is involved in both ototoxicity and acoustic trauma-induced hair cell loss and permanent hearing loss. Blocking this signal pathway with D-JNKI-1 is of potential therapeutic value for long-term protection of both the morphological integrity and physiological function of the organ of Corti during times of oxidative stress.
Mots-clé
Acoustic Stimulation, Aminoglycosides, Animals, Cell Death, Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Administration Routes, Drug Evaluation, Preclinical, Enzyme Inhibitors, Guinea Pigs, Hair Cells, Auditory, Hearing Loss, Hearing Loss, Noise-Induced, Hearing Tests, JNK Mitogen-Activated Protein Kinases, Ligands, Mice, Mitogen-Activated Protein Kinases, Neuroprotective Agents, Organ of Corti, Peptides, Proto-Oncogene Proteins c-fos, Signal Transduction
Pubmed
Web of science
Création de la notice
25/01/2008 15:16
Dernière modification de la notice
03/03/2018 22:52
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