Oxidative stress initiates a cascade of reactions leading to cell death via one or more sequences of molecular events

Oxidative stress initiates a cascade of reactions leading to cell death via one or more sequences of molecular events. First, calcium-dependant calcineurin/calpain activation can initiate downstream events including dephosphorylation of NFAT and activation of BAD, release of cytochrome c, activation of caspases 9 and 3, and cell death. Second, a caspase-2 dependant pathway to cell death can be triggered by DNA damage. Third, caspase-independent pathways to cell death include release of AIF and EndoG from the mitochondria. Translocation to the cell nucleus results in chromatin condensation and high-molecular mass-chromatin fragments. Fourth, receptor-mediated cell death begins with ligation of death receptors, death inducible signaling complex is formed, which activates pro-caspase-8. Caspase-8 can activate caspase-3, leading to cell death, or cleave Bid, which results in translocation and insertion of Bax and/or Bak into the mitrochondrial membrane and release of cytochrome c, activation of caspases 9 and 3, and cell death. The caspase-2 dependent pathway differs from the caspase-8 and caspase-9 dependent pathways in that pro-caspase-2 is activated by DNA damage. Different cell types vary in the extent to which apoptotic cell death depends on the activation of caspase-2 (; ), and a specific role for caspase-2 in apoptotic cell death in the inner ear has not been described to date.

Publication

Mechanisms of Noise-Induced Hearing Loss Indicate Multiple Methods of Prevention. () Colleen G. Le Prell, et al. Hear Res. ;226(1-2):22-43. Figure: F7. All organisms Homo sapiens Drosophila melanogaster Danio rerio

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