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

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. IJCEP