Mechanisms of cell death in the injured auditory system: otoprotective strategies.
Oxidative stress insults such as neurotrophin withdrawal, sound trauma, hypoxia/ischemia, ototoxic antibiotics, and chemotherapeutic agents have been shown to induce apoptosis of both auditory hair cells and neurons. In this paper, we review some components of the apoptotic pathways leading to the death of hair cells and auditory induced by growth factor withdrawal or cisplatin intoxication: (1) reactive oxygen species and free radicals are formed as by-products of several metabolic pathways and these molecules can themselves cause cell damage by reacting with cellular proteins; (2) activation of caspases, and (3) activation of calpain. These mechanisms have several different points at which inhibitors could be targeted to protect cells from programmed cell death, including the prevention of oxidative stress-induced apoptosis and the activation of caspases and calpains.
Lefebvre
Philippe P
PP
Department of Otolaryngology, University of Liège, Belgium.
Malgrange
Brigitte
B
Lallemend
François
F
Staecker
Hinrich
H
Moonen
Gustave
G
Van De Water
Thomas R
TR
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D020932:Nerve Growth Factor / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017382:Reactive Oxygen Species; D020932:Nerve Growth Factor; D002154:Calpain; D020169:Caspases