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.

[1]  M. Seidman,et al.  Pharmacologic Manipulation of the Labyrinth with Novel and Traditional Agents Delivered to the Inner Ear , 2003, Ear, nose, & throat journal.

[2]  G. Cohen,et al.  Caspase Activation Involves the Formation of the Aposome, a Large (∼700 kDa) Caspase-activating Complex* , 1999, The Journal of Biological Chemistry.

[3]  J. I. Matsui,et al.  Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death , 2002, The Journal of Neuroscience.

[4]  T. Takizawa,et al.  Caspase-3-deficiency induces hyperplasia of supporting cells and degeneration of sensory cells resulting in the hearing loss , 2001, Brain Research.

[5]  Raouf Fetni,et al.  The Neuronal Apoptosis Inhibitory Protein Is a Direct Inhibitor of Caspases 3 and 7 , 2002, The Journal of Neuroscience.

[6]  D. Fekete,et al.  Involvement of programmed cell death in morphogenesis of the vertebrate inner ear. , 1997, Development.

[7]  K. Schulze-Osthoff,et al.  Many cuts to ruin: a comprehensive update of caspase substrates , 2003, Cell Death and Differentiation.

[8]  G. Cohen,et al.  Caspase activation involves the formation of the aposome, a large (approximately 700 kDa) caspase-activating complex. , 1999, The Journal of biological chemistry.

[9]  J B Schulz,et al.  Caspases as treatment targets in stroke and neurodegenerative diseases , 1999, Annals of neurology.

[10]  N. Segil,et al.  Deafness due to degeneration of cochlear neurons in caspase-3-deficient mice. , 2001, Biochemical and biophysical research communications.

[11]  D. Vaux,et al.  The molecular biology of apoptosis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Tomonori Takasaka,et al.  The Expression of Apoptosis‐Related Proteins in the Aged Cochlea of Mongolian Gerbils , 2001, The Laryngoscope.

[13]  O. Alonso,et al.  Apoptotic and Antiapoptotic Mechanisms after Traumatic Brain Injury , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  Colin Adrain,et al.  Executioner Caspase-3, -6, and -7 Perform Distinct, Non-redundant Roles during the Demolition Phase of Apoptosis* , 2001, The Journal of Biological Chemistry.

[15]  B. Malgrange,et al.  Caspase inhibitors prevent cisplatin‐induced apoptosis of auditory sensory cells , 1998, Neuroreport.

[16]  T. Nicotera,et al.  Involvement of apoptosis in progression of cochlear lesion following exposure to intense noise 1 1 Presented in part at the Midwinter Meeting of the Association for Research in Otolaryngology, 2001, St. Petersburg Beach, FL, USA. , 2002, Hearing Research.

[17]  G. Moonen,et al.  Mechanisms of Cell Death in the Injured Auditory System: Otoprotective Strategies , 2002, Audiology and Neurotology.

[18]  J. Harlan,et al.  The caspase inhibitor z-VAD is more effective than CD18 adhesion blockade in reducing muscle ischemia-reperfusion injury: implication for clinical trials. , 2002, Blood.

[19]  M. Lutter,et al.  Biochemical pathways of caspase activation during apoptosis. , 1999, Annual review of cell and developmental biology.

[20]  R. Liddington,et al.  Dimer formation drives the activation of the cell death protease caspase 9 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Ken-ichi Watanabe,et al.  Detection of apoptotic change in the lipopolysaccharide (LPS)-treated cochlea of guinea pigs , 2001, Hearing Research.

[22]  Jun Chen,et al.  Cloning and Characterization of Rat Caspase-9: Implications for a Role in Mediating Caspase-3 Activation and Hippocampal Cell Death after Transient Cerebral Ischemia , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  E. J. de la Rosa,et al.  Programmed cell death in the developing inner ear is balanced by nerve growth factor and insulin-like growth factor I , 2003, Journal of Cell Science.

[24]  T. Nicotera,et al.  The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea , 2003, Journal of the Association for Research in Otolaryngology.

[25]  L. Martin,et al.  Immature and Mature Cortical Neurons Engage Different Apoptotic Mechanisms Involving Caspase-3 and the Mitogen-Activated Protein Kinase Pathway , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  Edwin W Rubel,et al.  Caspase Activation in Hair Cells of the Mouse Utricle Exposed to Neomycin , 2002, The Journal of Neuroscience.

[27]  Xiaodong Wang,et al.  Exogenous Smac Induces Competence and Permits Caspase Activation in Sympathetic Neurons , 2002, The Journal of Neuroscience.

[28]  Edwin W Rubel,et al.  Hair Cell Death in the Avian Basilar Papilla: Characterization of the in vitro Model and Caspase Activation , 2003, Journal of the Association for Research in Otolaryngology.

[29]  A. Forge,et al.  Apoptotic death of hair cells in mammalian vestibular sensory epithelia , 2000, Hearing Research.