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Published on: November 26, 2015
Calpain activity in the amikacin-damaged rat cochlea
Sabine Ladrech1, Matthieu Guitton, Takaomi Saido
1Institut 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.
Abstract:
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.
Insights
Calpain contributes to hair cell and neuron degeneration in amikacin-induced hearing loss. This proteinase may work with caspases in hair cells and aid neuron degradation, while PKCgamma might support neuron survival.
Area of Science:
- Ototoxicity research
- Cellular and molecular biology
- Neuroscience
Background:
- Amikacin is an antibiotic known to cause ototoxicity, leading to damage in the cochlea.
- Hair cells and spiral ganglion neurons are critical for hearing and are vulnerable to toxic insults.
- Calpains are calcium-dependent proteases implicated in various cell death pathways.
Purpose of the Study:
- To investigate the role of calpain in hair cell and spiral ganglion neuron degeneration following amikacin exposure in rats.
- To examine the involvement of caspases and protein kinase C (PKC) in this process.
- To elucidate the specific roles of these molecules in different cochlear cell types.
Main Methods:
- Utilized an antibody against fodrin-breakdown products (FBDP) to detect calpain activity.
- Employed antibodies against activated caspase 3 and PKCgamma to assess caspase and PKC activity.
- Examined degenerating hair cells, supporting cells (Deiters cells), and spiral ganglion neurons in amikacin-poisoned rat cochleas.
Main Results:
- FBDP accumulation was observed in degenerating hair cells, Deiters cells, and subsequently in spiral ganglion neurons.
- Activated caspase 3 was detected in a subset of dying hair cells and ganglion neurons.
- PKCgamma showed high expression in ganglion neurons, sometimes appearing after hair cell loss.
Conclusions:
- Calpain plays a significant role in the degradation of both cochlear hair cells and spiral ganglion neurons after amikacin ototoxicity.
- Calpain and caspase 3 may act synergistically in hair cell apoptosis, while calpain is prominent in ganglion neuron degradation.
- PKCgamma may be involved in spiral ganglion neuron survival, and calpain might contribute to Deiters cell remodeling during cochlear scarring.
