The role of PKCzeta in amikacin-induced apoptosis in the cochlea: prevention by aspirin.

Details

Serval ID
serval:BIB_B3E1E953507A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The role of PKCzeta in amikacin-induced apoptosis in the cochlea: prevention by aspirin.
Journal
Apoptosis : An International Journal On Programmed Cell Death
Author(s)
Lecain E., Omri B., Behar-Cohen F., Tran Ba Huy P., Crisanti P.
ISSN
1360-8185 (Print)
ISSN-L
1360-8185
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
12
Number
2
Pages
333-342
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Aminoglycoside antibiotics are ototoxic, inducing irreversible sensorineural hearing loss mediated by oxidative and excitotoxic stresses. The NF-kappaB pathway is involved in the response to aminoglycoside damage in the cochlea. However, the molecular mechanisms of this ototoxicity remain unclear. We investigated the expression of PKCzeta, a key regulator of NF-kappaB activation, in response to aminoglycoside treatment. Amikacin induced PKCzeta cleavage and nuclear translocation. These events were concomitant with chromatin condensation and paralleled the decrease in NF-kappaB (p65) levels in the nucleus. Amikacin also induced the nuclear translocation of apoptotic inducing factor (AIF). Prior treatment with aspirin prevented PKCzeta cleavage and nuclear translocation. Thus, aspirin counteracts the early effects of amikacin, thereby protecting hair cells and spiral ganglion neurons. These results demonstrate that PKCzeta acts as sentinel connecting specific survival pathways to mediate cellular responses to amikacin ototoxicity.
Keywords
Amikacin/pharmacology, Animals, Anti-Bacterial Agents/pharmacology, Anti-Inflammatory Agents, Non-Steroidal/pharmacology, Apoptosis/drug effects, Apoptosis Inducing Factor/metabolism, Aspirin/pharmacology, Audiometry, Evoked Response, Cell Nucleus/drug effects, Cell Nucleus/metabolism, Cochlea/cytology, Cochlea/enzymology, Male, Protein Kinase C/metabolism, Protein Transport/drug effects, Rats, Rats, Inbred Lew, Spiral Ganglion/cytology, Spiral Ganglion/drug effects, Subcellular Fractions/drug effects, Subcellular Fractions/enzymology, Transcription Factor RelA/metabolism
Pubmed
Web of science
Create date
29/08/2013 14:59
Last modification date
20/08/2019 15:22
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