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NF-kappaB-dependent apoptotic hair cell death in the auditory system


Nagy, I; Caelers, A; Monge, A; Bonabi, S; Huber, A M; Bodmer, D (2007). NF-kappaB-dependent apoptotic hair cell death in the auditory system. Audiology and Neurotology, 12(4):209-220.

Abstract

Hair cells are the most vulnerable elements in the inner ear and their degeneration is the most common cause of hearing loss. In the last few years progress has been made in uncovering the molecular mechanisms involved in hair cell damage and death. However, little is known about factors important for hair cell survival. Recently, it has been demonstrated that the transcription factor NF-kappaB is required for survival of immature auditory hair cells in vitro. Here we used DNA microarray technology to explore NF-kappaB downstream events in organ of Corti explants of postnatal day-5 Sprague-Dawley rats which were exposed to a cell-permeable NF-kappaB-inhibitory peptide. Gene expression was analyzed using DNA microarray technology. Genes were selected on the basis of comparative analysis, which reliably distinguished the NF-kappaB inhibitor-treated samples from control samples. Interestingly, among the up-regulated genes was the gene coding for the regulatory subunit of phosphatidylinositol 3-kinase. Moreover, inhibition of the phosphatidylinositol 3-kinase signaling pathway in organ of Corti explants exposed to the NF-kappaB inhibitor reduced caspase-3 activation. These data link NF-kappaB-dependent hair cell death to phosphatidylinositol 3-kinase signaling.

Hair cells are the most vulnerable elements in the inner ear and their degeneration is the most common cause of hearing loss. In the last few years progress has been made in uncovering the molecular mechanisms involved in hair cell damage and death. However, little is known about factors important for hair cell survival. Recently, it has been demonstrated that the transcription factor NF-kappaB is required for survival of immature auditory hair cells in vitro. Here we used DNA microarray technology to explore NF-kappaB downstream events in organ of Corti explants of postnatal day-5 Sprague-Dawley rats which were exposed to a cell-permeable NF-kappaB-inhibitory peptide. Gene expression was analyzed using DNA microarray technology. Genes were selected on the basis of comparative analysis, which reliably distinguished the NF-kappaB inhibitor-treated samples from control samples. Interestingly, among the up-regulated genes was the gene coding for the regulatory subunit of phosphatidylinositol 3-kinase. Moreover, inhibition of the phosphatidylinositol 3-kinase signaling pathway in organ of Corti explants exposed to the NF-kappaB inhibitor reduced caspase-3 activation. These data link NF-kappaB-dependent hair cell death to phosphatidylinositol 3-kinase signaling.

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15 citations in Web of Science®
16 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Otorhinolaryngology
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2007
Deposited On:22 Mar 2009 17:44
Last Modified:04 Aug 2016 07:40
Publisher:Karger
ISSN:1420-3030
Publisher DOI:https://doi.org/10.1159/000101328
PubMed ID:17389787
Permanent URL: https://doi.org/10.5167/uzh-15991

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