Figure 8
From: Receptor-interacting protein kinases modulate noise-induced sensory hair cell death
Summary of the molecular cell death pathways in sensory hair cells after traumatic noise exposure. Noise causes both an increase in RIP1 and RIP3 and activation of caspase-8. The activation of caspase-8 leads to apoptotic hair cell death. Inhibition of CC8 by ZVAD blocks apoptotic cell death but stimulates an increase in RIP1 and RIP3. The increase in RIP1 and RIP3 enhances p-AMPK in hair cells and results in necrotic cell death. Inhibition of RIP1 and RIP3 by Nec-1 or siRIP3 diminishes the expression of RIP1 and RIP3, but stimulates activation of caspase-9 and increases EndoG translocation to the OHC nuclei, resulting in apoptotic cell death. Combination treatment of ZVAD and siRIP3 provides synergetic prevention of NIHL and hair cell loss
