gms | German Medical Science

GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery

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

ISSN 1865-1038

Alteration of Activator Protein 1 DNA Binding Activity in Gentamicin Induced Hair Cell Degeneration.

Poster

  • corresponding author Andrea Albinger - ORL Klinik Zürich, ORL-Klinik, UniversitätsSpital Zürich, Zürich, Switzerland
  • Ivan Hegyi - ORL Klinik Zürich, ORL-Klinik, UniversitätsSpital Zürich, Zürich, Switzerland
  • Daniel Bodmer - ORL Klinik Zürich, ORL-Klinik, UniversitätsSpital Zürich, Zürich, Switzerland
  • Stephan Schmid - ORL Klinik Zürich, ORL-Klinik, UniversitätsSpital Zürich, Zürich, Switzerland
  • Ivana Nagy - ORL Klinik Zürich, ORL-Klinik, UniversitätsSpital Zürich, Zürich, Switzerland
  • Morana Bodmer - ORL Klinik Zürich, ORL-Klinik, UniversitätsSpital Zürich, Zürich, Switzerland

GMS Curr Posters Otorhinolaryngol Head Neck Surg 2005;1:Doc104

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/journals/cpo/2005-1/cpo000104.shtml

Published: December 6, 2005

© 2005 Albinger 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

Abstract

Sensorineural hearing loss (SNHL) is associated with damage of cochlear hair cells (HCs) and/or of the neurons of the auditory pathway. This damage can result from a variety of causes, e.g. genetic disorders, aging, exposure to certain drugs such as aminoglycosides, infectious disease and intense sound overexposure. Intracellular events that mediate aspects of aminoglycoside mediated damage to HCs have been partially unraveled. Several independent research groups have demonstrated a crucial role of mitogen activated protein kinase (MAPK) signaling in aminoglycoside induced ototoxicity.

MAPKs are important mediators of signal transduction from the cell surface to the nucleus. Jun N-terminal kinases (JNK), members of the MAPK family, are strongly activated in cell culture conditions by stress-inducing stimuli. In HCs, the JNK signaling pathway was shown to be activated by aminoglycoside treatment. Activation of JNK leads to phosphorylation and thereby activation of transcription factors and consequently to altered gene expression.

One of the downstream targets of JNK is the transcription factor activating protein -1 (AP-1). AP-1 is a dimeric complex composed of members of the Fos and Jun proteins. Induction of AP-1 is thought to play a central role in reprogramming gene expression in response to external stimuli.

In this study we have analyzed the effect of gentamicin treatment on the downstream targets of JNK. Our results demonstrate that gentamicin treatment of explants of Organ of Corti (OC) results in increased AP-1 binding activity. The main component of these AP-1 complexes is the c-Fos protein. Moreover, we show that the AP-1 induction is transient and occurs exclusively in HCs of OC explants.