English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/124847
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

C-Raf deficiency leads to hearing loss and increased noise susceptibility

AuthorsIriarte, Rocío de ; Magariños, Marta ; Pfeiffer, Verena; Rapp, Ulf R.; Varela-Nieto, Isabel
KeywordsOtic
Programmed cell death
NIHL
Inflammation
FoxG1
ERK
Issue Date2015
PublisherSpringer
CitationCellular and Molecular Life Sciences 72(20): 3983-3998 (2015)
AbstractThe family of RAF kinases transduces extracellular information to the nucleus, and their activation is crucial for cellular regulation on many levels, ranging from embryonic development to carcinogenesis. B-RAF and C-RAF modulate neurogenesis and neuritogenesis during chicken inner ear development. C-RAF deficiency in humans is associated with deafness in the rare genetic insulin-like growth factor 1 (IGF-1), Noonan and Leopard syndromes. In this study, we show that RAF kinases are expressed in the developing inner ear and in adult mouse cochlea. A homozygous C-Raf deletion in mice caused profound deafness with no evident cellular aberrations except for a remarkable reduction of the K+ channel Kir4.1 expression, a trait that suffices as a cause of deafness. To explore the role of C-Raf in cellular protection and repair, heterozygous C-Raf +/− mice were exposed to noise. A reduced C-RAF level negatively affected hearing preservation in response to noise through mechanisms involving the activation of JNK and an exacerbated apoptotic response. Taken together, these results strongly support a role for C-RAF in hearing protection.
DescriptionThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Publisher version (URL)http://dx.doi.org/10.1007/s00018-015-1919-x
URIhttp://hdl.handle.net/10261/124847
DOI10.1007/s00018-015-1919-x
Identifiersdoi: 10.1007/s00018-015-1919-x
issn: 1420-682X
e-issn: 1420-9071
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
C-Raf.pdf5,6 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.