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. Wang, Thomas R Van De Water, C. Bonny, F. De Ribaupierre, J. L. Puel, Azel Zine

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8596-8607
Number of pages12
JournalJournal of Neuroscience
Volume23
Issue number24
StatePublished - Sep 17 2003

Fingerprint

Auditory Hair Cells
Noise-Induced Hearing Loss
JNK Mitogen-Activated Protein Kinases
Aminoglycosides
Hearing Loss
Signal Transduction
Cell Death
Organ of Corti
Cochlea
Phosphotransferases
Peptides
Neomycin
Guinea Pigs
Scala Tympani
Organ Culture Techniques
Alopecia
Pharmaceutical Preparations
Oxidative Stress
D-JNKI-1
Apoptosis

Keywords

  • Acoustic trauma
  • Apoptosis of hair cells
  • c-Jun N-terminal kinase (JNK)
  • JNK inhibition
  • Neomycin
  • Noise-induced hearing loss
  • Organ of Corti
  • Ototoxicity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. / Wang, J.; Van De Water, Thomas R; Bonny, C.; De Ribaupierre, F.; Puel, J. L.; Zine, Azel.

In: Journal of Neuroscience, Vol. 23, No. 24, 17.09.2003, p. 8596-8607.

Research output: Contribution to journalArticle

Wang, J, Van De Water, TR, Bonny, C, De Ribaupierre, F, Puel, JL & Zine, A 2003, 'A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss', Journal of Neuroscience, vol. 23, no. 24, pp. 8596-8607.
Wang, J. ; Van De Water, Thomas R ; Bonny, C. ; De Ribaupierre, F. ; Puel, J. L. ; Zine, Azel. / A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 24. pp. 8596-8607.
@article{cb8e7d003246491a9af29e803f55919f,
title = "A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss",
abstract = "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.",
keywords = "Acoustic trauma, Apoptosis of hair cells, c-Jun N-terminal kinase (JNK), JNK inhibition, Neomycin, Noise-induced hearing loss, Organ of Corti, Ototoxicity",
author = "J. Wang and {Van De Water}, {Thomas R} and C. Bonny and {De Ribaupierre}, F. and Puel, {J. L.} and Azel Zine",
year = "2003",
month = "9",
day = "17",
language = "English",
volume = "23",
pages = "8596--8607",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "24",

}

TY - JOUR

T1 - A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss

AU - Wang, J.

AU - Van De Water, Thomas R

AU - Bonny, C.

AU - De Ribaupierre, F.

AU - Puel, J. L.

AU - Zine, Azel

PY - 2003/9/17

Y1 - 2003/9/17

N2 - 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.

AB - 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.

KW - Acoustic trauma

KW - Apoptosis of hair cells

KW - c-Jun N-terminal kinase (JNK)

KW - JNK inhibition

KW - Neomycin

KW - Noise-induced hearing loss

KW - Organ of Corti

KW - Ototoxicity

UR - http://www.scopus.com/inward/record.url?scp=0141457877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141457877&partnerID=8YFLogxK

M3 - Article

C2 - 13679429

AN - SCOPUS:0141457877

VL - 23

SP - 8596

EP - 8607

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 24

ER -