Calpain activity in the amikacin-damaged rat cochlea.
The principal aim of this study was to investigate the involvement of calpain in the degeneration of hair cells and ganglion neurons in the amikacin-poisoned rat cochlea. An antibody designed against fodrin-breakdown products (FBDP), which result exclusively from cleavage by calpain, was used. In addition, the involvement of both caspases and protein kinase C (PKC) was studied using, respectively, antibodies against activated caspase 3 and PKCgamma. The results demonstrate the accumulation of FBDP in the degenerating hair cells, in some supporting cells such as Deiters cells, and, later, in the affected ganglion neurons that had been deprived of their sensory targets. Activated caspase 3 was evidenced in a few dying hair cells and ganglion neurons. PKCgamma was highly expressed in all ganglion neurons, sometimes after the loss of hair cells. We conclude that calpain plays a role in the degradation of both the sensory cells and neurons after amikacin ototoxicity. In the poisoned hair cells, calpain and caspase 3 may have synergistic effects in the process of apoptosis. In the ganglion neurons deprived of their sensory elements, calpain may have a prominent role in cell degradation. By contrast, in these ganglion neurons PKCgamma may be implicated in a survival process. Finally, we suggest that calpain is involved in the remodeling of Deiters cells during the scarring process that follows hair cell loss.
Institut National de la Santé et de la Recherche Médicale U583 et Université Montpellier I, Laboratoire de Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, 34295 Montpellier, France.
Sabine
S
Ladrech
Matthieu
M
Guitton
Takaomi
T
Saido
Marc
M
Lenoir
D000367:Age Factors; D000583:Amikacin / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D064026:Calbindins; D002154:Calpain / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002470:Cell Survival; D003051:Cochlea / Q000293:injuries* / Q000378:metabolism* / Q000648:ultrastructure; D015834:Cochlear Diseases / Q000139:chemically induced / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000276:immunology / Q000378:metabolism; D008854:Microscopy, Electron / Q000379:methods; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010320:Parvalbumins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013136:Spiral Ganglion / Q000648:ultrastructure; D013997:Time Factors; D013049:Spectrin
D000583:Amikacin; D064026:Calbindins; D002154:Calpain; D002352:Carrier Proteins; D053148:Caspase 3; D020169:Caspases; D008840:Microfilament Proteins; D010320:Parvalbumins; D011493:Protein Kinase C; D064030:S100 Calcium Binding Protein G; D013049:Spectrin; C087857:protein kinase C gamma; C505410:Casp3 protein, rat