gms | German Medical Science

80th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

20.05. - 24.05.2009, Rostock

Geldanamycin induces heat shock protein 70 (HSP70) production in the organ of Corti and protects against gentamicin ototoxicity

Meeting Abstract

  • corresponding author Agnes Szczepek - Charité University Hospital, Berlin, Germany
  • Heidemarie Haupt - Charité University Hospital, Berlin, Germany
  • Timo Stöver - MHH, Hannover, Germany
  • Birgit Mazurek - Charité University Hospital, Berlin, Germany

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. 80th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Rostock, 20.-24.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09hno032

DOI: 10.3205/09hno032, URN: urn:nbn:de:0183-09hno0329

Published: July 22, 2009

© 2009 Szczepek et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

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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