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

Adrien Eshraghi, Jing Wang, Eelam Adil, Jiao He, Azel Zine, Michael Bublik, Christophe Bonny, Jean Luc Puel, Thomas J. Balkany, Thomas R Van De Water

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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 We present previously unpublished results that control for the effect of perfusate washout of aminoglycoside antibiotic by perfusion of the scala tympani with an inactive form of D-JNKI-1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-1mut 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.

Original languageEnglish
Pages (from-to)168-177
Number of pages10
JournalHearing Research
Volume226
Issue number1-2
DOIs
StatePublished - Apr 1 2007

Fingerprint

Neomycin
JNK Mitogen-Activated Protein Kinases
Hearing Loss
Electrodes
Wounds and Injuries
Peptides
Auditory Hair Cells
Noise-Induced Hearing Loss
Cell Death
Aminoglycosides
Protein Isoforms
Scala Tympani
Alopecia
Mitogen-Activated Protein Kinases
Cell Biology
Necrosis
Perfusion
Apoptosis
Anti-Bacterial Agents
D-JNKI-1

Keywords

  • Aminoglycoside ototoxicity
  • Apoptosis
  • D-JNKI-1 peptide (AM-111)
  • Electrode insertion trauma
  • Hair cells
  • Hearing loss
  • JNK signaling
  • Otoprotection

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity. / Eshraghi, Adrien; Wang, Jing; Adil, Eelam; He, Jiao; Zine, Azel; Bublik, Michael; Bonny, Christophe; Puel, Jean Luc; Balkany, Thomas J.; Van De Water, Thomas R.

In: Hearing Research, Vol. 226, No. 1-2, 01.04.2007, p. 168-177.

Research output: Contribution to journalArticle

Eshraghi, A, Wang, J, Adil, E, He, J, Zine, A, Bublik, M, Bonny, C, Puel, JL, Balkany, TJ & Van De Water, TR 2007, 'Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity', Hearing Research, vol. 226, no. 1-2, pp. 168-177. https://doi.org/10.1016/j.heares.2006.09.008
Eshraghi, Adrien ; Wang, Jing ; Adil, Eelam ; He, Jiao ; Zine, Azel ; Bublik, Michael ; Bonny, Christophe ; Puel, Jean Luc ; Balkany, Thomas J. ; Van De Water, Thomas R. / Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity. In: Hearing Research. 2007 ; Vol. 226, No. 1-2. pp. 168-177.
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