References of "Otology & Neurotology"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCaspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells
Van De Water, T. R.; Lallemend, François; Eshraghi, A. A. et al

in Otology & Neurotology (2004), 25(4), 627-632

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 ... [more ▼]

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. [less ▲]

Detailed reference viewed: 58 (2 ULg)
Full Text
Peer Reviewed
See detailArrest of apoptosis in auditory neurons: Implications for sensorineural preservation in cochlear implantation
Scarpidis, U.; Madnani, D.; Shoemaker, C. et al

in Otology & Neurotology (2003), 24(3), 409-417

Hypothesis: The JNK/c-Jun cell death pathway is a major pathway responsible for the loss of oxidative stress-damaged auditory neurons. Background: Implantation of patients with residual hearing ... [more ▼]

Hypothesis: The JNK/c-Jun cell death pathway is a major pathway responsible for the loss of oxidative stress-damaged auditory neurons. Background: Implantation of patients with residual hearing accentuates the need to preserve functioning sensorineural elements. Although some auditory function may survive electrode insertion, the probability of initiating an ongoing loss of auditory neurons and hair cells is unknown. Cochlear implantation can potentially generate oxidative stress, which can initiate the cell death of both auditory neurons and hair cells. Methods: Dissociated cell cultures of P4 rat auditory neurons identified the apoptotic pathway initiated by oxidative stress insults (e.g., loss of trophic factor support) and characterized this pathway by arresting translation of pathway-specific mRNA with antisense oligonucleotide treatment and with the use of pathway specific inhibitors. The presence or absence of apoptosis-specific protein and changes in the level of neuronal survival measured the efficacy of these interventional strategies. Results: These in vitro studies identified the JNK/c-Jun cascade as a major initiator of apoptosis of auditory neurons in response to oxidative stress. Neurons pretreated with c-jun antisense oligonucleotide and exposed to high levels of oxidative stress were rescued from apoptosis, whereas neurons in treatment control cultures died. Treatment of oxidative-stressed cultures with either curcumin, a MAPKKK pathway inhibitor, or PD-098059, a MEK1 inhibitor, blocked loss of neurons via the JNK/c-Jun apoptotic pathway. Conclusion: Blocking the JNK/c-Jun cell death pathway is a feasible approach to treating oxidative stress-induced apoptosis within the cochlea and may have application as an otoprotective strategy during cochlear implantation. [less ▲]

Detailed reference viewed: 13 (1 ULg)