Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity

Neomycin ototoxicity and electrode insertion trauma both involve activation of the mitogen activated protein kinase (MAPK)/c-Jun-N-terminal kinase (JNK) cell death signal cascade. This article discusses mechanisms of cell death on a cell biology level (e.g. necrosis and apoptosis) and proposes the b...

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Bibliographic Details
Published in:Hearing research 2007-04, Vol.226 (1), p.168-177
Main Authors: Eshraghi, Adrien A., Wang, Jing, Adil, Eelam, He, Jiao, Zine, Azel, Bublik, Michael, Bonny, Christophe, Puel, Jean-Luc, Balkany, Thomas J., Van De Water, Thomas R.
Format: Article
Language:English
Subjects:
Aminoglycoside ototoxicity
Animals
Anti-Bacterial Agents
Anti-Bacterial Agents - toxicity
Apoptosis
Apoptosis - drug effects
Biological and medical sciences
Caspases
Caspases - metabolism
D-JNKI-1 peptide (AM-111)
Drug toxicity and drugs side effects treatment
Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology
Electrode insertion trauma
Electrodes
Electrodes - adverse effects
Free Radicals
Free Radicals - metabolism
Guinea Pigs
Hair cells
Hearing Loss
Hearing Loss - chemically induced
Hearing Loss - enzymology
Hearing Loss - etiology
Hearing Loss - prevention & control
JNK Mitogen-Activated Protein Kinases
JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors
JNK signaling
Life Sciences
MAP Kinase Signaling System
MAP Kinase Signaling System - drug effects
Medical sciences
Neomycin
Neomycin - toxicity
Neurons and Cognition
Non tumoral diseases
Otoprotection
Otorhinolaryngology. Stomatology
Peptides
Peptides - pharmacology
Pharmacology. Drug treatments
Signal Transduction
Signal Transduction - drug effects
Toxicity: respiratory system, ent, stomatology
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Summary:Neomycin ototoxicity and electrode insertion trauma both involve activation of the mitogen activated protein kinase (MAPK)/c-Jun-N-terminal kinase (JNK) cell death signal cascade. This article discusses mechanisms of cell death on a cell biology level (e.g. necrosis and apoptosis) and proposes the blocking of JNK signaling as a therapeutic approach for preventing the development of a permanent hearing loss that can be initiated by either neomycin ototoxicity or electrode insertion trauma. Blocking of JNK molecules incorporates the use of a peptide inhibitor (i.e. D-JNKI-1), which is specific for all three isoforms of JNK and has been demonstrated to prevent loss of hearing following either electrode insertion trauma or loss of both hearing and hair cells following exposure to an ototoxic level of neomycin. We present previously unpublished results that control for the effect of perfusate washout of aminoglycoside antibiotic by perfusion of the scala tympani with an inactive form of D-JNKI-1 peptide, i.e. JNKI-1 mut peptide, which was not presented in the original J. Neurosci. article that tested locally delivered D-JNKI-1 peptide against both noise- and neomycin-induced hearing loss (i.e. Wang, J., Van De Water, T.R., Bonny, C., de Ribaupierre, F., Puel, J.L., Zine, A. 2003a. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J. Neurosci. 23, 8596–8607). D-JNKI-1 is a cell permeable peptide that blocks JNK signaling at the level of the three JNK molecular isoforms, which when blocked prevents the increases in hearing thresholds and the loss of auditory hair cells. This unique therapeutic approach may have clinical application for preventing: (1) hearing loss caused by neomycin ototoxicity; and (2) the progressive component of electrode insertion trauma-induced hearing loss.
ISSN:0378-5955
1878-5891
DOI:10.1016/j.heares.2006.09.008