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Stress and survival pathways in the mammalian cochlea

Antje Caelers1, Vesna Radojevic, Jens Traenkle

  • 1Department of Biomedicine, University Hospital Basel and Klinik für Ohren-, Nasen-, Halskrankheiten, University Hospital Basel, Basel, Switzerland.

Audiology & Neuro-Otology
|February 5, 2010
PubMed

Insights

This study reveals how signaling pathways in the cochlear organs of Corti (OC) affect hair cell survival. High-throughput protein microarrays effectively measured key molecular changes after gentamicin or NF-kappaB inhibitor exposure.

Area of Science:

  • Molecular Otology
  • Cellular Signaling Pathways
  • Hair Cell Biology

Background:

  • Signaling pathways in the cochlear organs of Corti (OC) are crucial for hair cell survival and death.
  • Understanding these pathways is vital for molecular otology, especially under stress conditions like ototoxicity and noise exposure.

Purpose of the Study:

  • To characterize signaling pathways in normal and stressed OC.
  • To evaluate high-performance reverse protein microarray technology for assessing signaling pathway activation.

Main Methods:

  • Utilized high-performance reverse protein microarray technology with phospho-specific antibodies.
  • Examined microdissected OC explants from postnatal rats over time.
  • Assessed activation status of molecules involved in apoptotic and prosurvival signaling.

Main Results:

  • Gentamicin and an NF-kappaB inhibitor increased the phospho-c-Jun/c-Jun ratio in OC explants.
  • NF-kappaB inhibition led to an early decrease in the phospho-Akt/Akt ratio.
  • NF-kappaB inhibition caused a consistent decrease in phospho-p38/p38 ratio, while gentamicin caused a transient decrease.

Conclusions:

  • Reverse protein microarrays are effective for high-throughput assessment of signaling in OC explants.
  • Specific signaling molecules (c-Jun, Akt, p38) show altered activation patterns in response to ototoxic stress and NF-kappaB inhibition.
  • Findings contribute to understanding molecular mechanisms of hair cell survival and death in the inner ear.

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