NDLI: Salicylate Initiates Apoptosis in the Spiral Ganglion Neuron of Guinea Pig Cochlea by Activating Caspase-3

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Salicylate Initiates Apoptosis in the Spiral Ganglion Neuron of Guinea Pig Cochlea by Activating Caspase-3

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Salicylate Initiates Apoptosis in the Spiral Ganglion Neuron of Guinea Pig Cochlea by Activating Caspase-3

Content Provider	Springer Nature Link
Author	Feng, Hao Yin, Shi Hua Tang, An Zhou Tan, Song Hua
Copyright Year	2011
Abstract	Salicylate-induced ototoxicity leading to sensorineural hearing loss (SNHL) and tinnitus is well documented. However, the exact mechanisms are poorly defined. Caspase-3 is a member of the class of effector caspases and has been activated in nearly every model of apoptosis. To examine its role in salicylate-induced injury, we subjected guinea pigs to treatment with a specific inhibitor zDEVD-FMK via the round window niche (RWN) followed by a systemic injection of salicylate at a dose of 200 mg·kg$^{−1}$·d$^{−1}$ i.p. for 10 consecutive days. For those animals administered with salicylate, immunohistochemical studies revealed that caspase-3 was activated in the spiral ganglion neurons (SGNs) and method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) to identify neuronal apoptosis showed that fragmented nuclei were distributed in Rosenthal’s canal. Topical administration of the zDEVD-FMK at a concentration of 500 mM blocked caspase-3 activation and had an effect in reducing the number of TUNEL-positive auditory neurons. In contrast, the inhibitor at a concentration of 125 or 250 mM caused no variation in the expression of activated caspase-3, or in the ratio of TUNEL-positive neurons. These results indicate that caspase-3 is a crucial mediator of apoptosis induced by salicylate in the primary auditory neuron in vivo, and suggest that the specific inhibitor at a relatively high concentration may be therapeutically beneficial in salicylate-induced apoptosis.
Starting Page	1108
Ending Page	1115
Page Count	8
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	36
Issue Number	6
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2011-03-31
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Salicylate Apoptosis Spiral ganglion neuron Caspase-3 TUNEL Biochemistry Neurosciences Neurology Cell Biology Neurochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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Salicylate Initiates Apoptosis in the Spiral Ganglion Neuron of Guinea Pig Cochlea by Activating Caspase-3