Role of Hsp90/Akt pathway in the pathogenesis of gentamicin-induced hearing loss

Ruosha Lai1, Wei Li1, Peng Hu1

  • 1Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University Changsha, Hunan, P. R. China.

Insights

Gentamicin ototoxicity may involve the Hsp90/Akt pathway. This study found reduced Hsp90 and pAkt levels in hair cells after gentamicin treatment, suggesting this pathway

Area of Science:

  • Ototoxicity and molecular signaling pathways.
  • Auditory neuroscience and drug-induced hearing loss.

Background:

  • Gentamicin is a known ototoxic antibiotic.
  • The Hsp90/Akt signaling pathway is implicated in gentamicin-induced hair cell apoptosis.
  • The precise role of this pathway in gentamicin ototoxicity requires further elucidation.

Purpose of the Study:

  • To investigate Heat Shock Protein 90 (Hsp90) expression in gentamicin-treated cochleae.
  • To explore the involvement of the Hsp90/Akt signaling pathway in gentamicin-induced ototoxicity.

Main Methods:

  • In vitro organotypic cultures of the organ of Corti were treated with gentamicin.
  • In vivo experiments involved gentamicin injection in CBA/J mice to induce hearing loss.
  • Immunochemistry and western blot analyses were used to examine protein expression and complex formation.

Main Results:

  • Gentamicin treatment led to decreased Hsp90 expression in cochlear hair cells.
  • Phosphorylated Akt (pAkt) protein levels were significantly reduced post-gentamicin exposure.
  • The levels of the Hsp90-Akt complex were diminished in gentamicin-treated subjects.

Conclusions:

  • The Hsp90/Akt signaling pathway plays a significant role in gentamicin-induced ototoxicity.
  • Reduced Hsp90 and pAkt expression are key indicators of gentamicin's harmful effects on auditory hair cells.

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