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Updated: Dec 30, 2025

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
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.
Abstract:
Studies have suggested that gentamicin may induce hair cell apoptosis through the Hsp90/Akt signaling pathway. Nevertheless, the exact mechanisms remain unclear. The following study investigated Hsp90 expression in gentamicin-treated cochleae (in vitro and in vivo) and explored whether the Hsp90/Akt signaling pathway has a role in gentamicin ototoxicity. For in vitro experiments, organotypic cultures from post-natal organ of Corti, collected from post-natal day 2 or 3 (p2-3) CBA/J explants were treated with 0.2 mM gentamicin for 24 h; for the in vivo experiments, 6-week-old male CBA/J mice were injected with gentamicin (150 mg/kg) to induce hearing loss. P-Akt and AKT proteins expression and the levels of Hsp90-Akt complex were examined using immunochemistry and western blot. Our data suggested that Hsp90 expression decreased in the hair ear cells after treatment. In addition, the pAkt and Hsp90/AKT levels significantly decreased in treated mice compared to the control group. To conclude, these results support the idea that the Hsp90/Akt signaling pathway may have an important role in the ototoxic effects of gentamicin.
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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