Article
Geldanamycin induces heat shock protein 70 (HSP70) production in the organ of Corti and protects against gentamicin ototoxicity
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Published: | July 22, 2009 |
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Introduction: Induction of HSP70 in inner ear protects against various ototoxic conditions. Here, we tested the ability of geldanamycin and resveratrol to induce HSP70 in the organ of Corti (OC). Furthermore, we determined the protective effect of pahrmacologically induced HSP70 against ototoxicity of gentamicin, common cause of hearing loss.
Methods: We used the in vitro explant cultures of the organ of Corti (OC) isolated from p3-p5 Wistar rats. Resveratrol (phytoalexin) and geldanamycin (benzoquinone ansamycin antibiotic) were added to OC cultures at various concentrations. The time course of Hsp70 mRNA expression was tested with qRT-PCR, whereas HSP70 protein concentration was determined using ELISA.. For the the ototoxicity experiments, gentamicin was used at 0.5 mM concentration and geldanamycin at 0.02M. After 24h incubation, the hair cells were stained with phalloidin and counted under the fluorescent microscope.
Results: We have shown that geldanamycin is a reliable inducer of HSP70 in OC, whereas resveratrol has no effect. Geldanamycin induced the transcription of HSP70 4h after addition to OC and HSP70 translation 8h after addition to OC. The HSP70 was strongly expressed in the outer and inner hair cells. Importantly, simultaneous application of geldanamycin and gentamycin inhibited the ototoxicity.
Conclusions: Induction of HSP70 by geldanamycin protects against gentamicin-mediated ototoxicity. Geldanamycin and geldanamycin-induced mechanisms of HSP70 production has a promising therapeutic potential in treatment and prevention of gentamicin-induced ototoxicity.
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