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Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration

Albinger-Hegyi, A. and Hegyi, I. and Nagy, I. and Bodmer, M. and Schmid, S. and Bodmer, D.. (2006) Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration. Neuroscience, Vol. 137, H. 3. pp. 971-980.

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Official URL: http://edoc.unibas.ch/dok/A5252062

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Abstract

Sensorineural hearing loss is often associated with damage of cochlear hair cells 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 hair cells have been partially unraveled. Several independent research groups have demonstrated a crucial role of mitogen-activated protein kinase signaling in aminoglycoside-induced ototoxicity. Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus. Jun N-terminal kinases, members of the mitogen-activated protein kinase family, are strongly activated in cell culture conditions by stress inducing stimuli, including ultraviolet light, heat shock and tumor necrosis factor; therefore they are also referred to as stress-activated protein kinases. In hair cells aminoglycoside treatment was shown to activate the Jun N-terminal kinase signaling pathway. Activation of Jun N-terminal kinase leads to phosphorylation and thereby activation of transcription factors and consequently to altered gene expression. There are many nuclear Jun N-terminal kinase substrates including c-Jun, ATF-2, and Elk-1 proteins. One of the downstream targets of Jun N-terminal kinase is the transcription factor activating protein-1. Activating protein-1 is a dimeric complex composed of members of the Fos and Jun proteins. A variety of different stimuli is known to induce activating protein-1 activity. Induction of activating protein-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 Jun N-terminal kinase. Our results demonstrate that gentamicin treatment of explants of organ of Corti results in increased
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialf├Ącher (Klinik) > Otorhinolaryngologie > Oto-Rhino-Laryngologie (Bodmer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialf├Ącher (Klinik) > Otorhinolaryngologie > Oto-Rhino-Laryngologie (Bodmer)
UniBasel Contributors:Bodmer, Daniel K
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0306-4522
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:36

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