cochlea; peripheral nervous system; PKC; neuroprotection; signal transduction; neuritogenesis
Abstract :
[en] In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKC beta I was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKC beta I. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKC beta I activation represents a key factor for the protection of the integrity of neural elements in the cochlea.
Research center :
Giga-Neurosciences - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Lallemend, François
Hadjab, Saida
Hans, Grégory ; Université de Liège - ULiège > Anesthésie et réanimation
Moonen, Gustave ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine
Lefèbvre, Philippe ; Université de Liège - ULiège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie
Malgrange, Brigitte ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Language :
English
Title :
Activation of protein kinase CbetaI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons
Publication date :
2005
Journal title :
Journal of Cell Science
ISSN :
0021-9533
eISSN :
1477-9137
Publisher :
Company Of Biologists Ltd, Cambridge, United Kingdom
Volume :
118
Issue :
19
Pages :
4511-4525
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Fonds Léon Fredericq [BE]
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