Caspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells.
This review covers the general roles of members of the cysteine protease family of caspases in the process of apoptosis (programmed cell death) looking at their participation in both the "extrinsic" cell death receptor and the "intrinsic" mitochondrial cell death pathways. It defines the difference between initiator and effector caspases and shows the progression of caspase activations that ends up in the apoptotic cell death and elimination of a damaged cell. The review then presents what is currently know about the participation of caspases in the programmed cell death of inner ear sensory cells during the process of normal development and maturation of the inner ear and their importance in this process as illustrated by the results of caspase-3 gene knockout experiments. The participation of specific caspases and the sequence of their activation in the elimination (apoptosis) of damaged sensory cells from adult inner ears after an injury that generates oxidative stress are reviewed. Both the possibility and the potential efficacy of caspase inhibition with a broad-spectrum pancaspase inhibitor as an interventional therapy to treat and rescue oxidative stress-damaged inner ear sensory cells from apoptosis are presented and discussed.
Van De Water
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TR
Department of Otolaryngology, University of Miami Ear Institute, University of Miami School of Medicine, Miami, Florida 33136, USA. tvandewater@med.miami.edu
Lallemend
F
F
Eshraghi
A A
AA
Ahsan
S
S
He
J
J
Guzman
J
J
Polak
M
M
Malgrange
B
B
Lefebvre
P P
PP
Staecker
H
H
Balkany
T J
TJ
D000328:Adult; D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005849:Gerbillinae; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006317:Hearing Loss, Noise-Induced / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D020169:Caspases