Involvement of ras activation in toxic hair cell damage of the mammalian cochlea

Battaglia, A. and Pak, K. and Brors, D. and Bodmer, D. and Frangos, J. A. and Ryan, A. F.. (2003) Involvement of ras activation in toxic hair cell damage of the mammalian cochlea. Neuroscience, Vol. 122, H. 4. pp. 1025-1035.

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Official URL: http://edoc.unibas.ch/dok/A5252069

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To identify possible intracellular mediators of hair cell (HC) death due to ototoxins, we treated basal-turn, neonatal, rat HCs in vitro with several intracellular signaling inhibitors, prior to and during gentamicin exposure. The general guanine nucleotide-binding protein (G-protein) inhibitor, GDP-betaS (1 mM), provided potent HC protection, suggesting involvement of G-proteins in the intracellular pathway linking gentamicin exposure to HC death. ADP-betaS had minimal effect, indicating that the protection is specific to guanosine diphosphate (GDP)-binding, rather than a general reaction to nucleotides. Azido-GTP(32) photolabeling and gel electrophoresis indicated activation of an approximately 21 kDa G-protein in HCs after exposure to gentamicin. Spectroscopic analysis of peptide fragments from this band matched its sequence with H-Ras. The Ras inhibitors B581 (50 microM) and FTI-277 (10 microM) provided potent protection against damage and reduced c-Jun activation in HC nuclei, suggesting that activation of Ras is functionally involved in damage to these cells due to gentamicin.
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
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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