Impaired unfolded protein response in the degeneration of cochlea cells in a mouse model of age-related hearing loss.

摘要: Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR) to prevent accumulation of proteins in an aberrant conformation. The UPR can restore homeostasis by upregulating ER chaperones, such as glucose-regulated 78kD (GRP78), refold incorrectly handled protein, and degrading misfolded via ubiquitin-proteasome autophagy-lysosome system. was recently demonstrated be involved pathogenesis age-related diseases. In this study, we measured expression levels GRP78 ubiquitinated cochleae young C57BL/6 mice aged assess capacity UPR. lower increased number observed suggested that impaired cell death pathway activated. We found a markedly ER-related pro-apoptotic factor C/EBP homologous (CHOP) mice, whereas level cleaved caspase-12 did not differ between two groups. addition, cleavage caspase-9, caspase-3 poly [ADP-ribose] polymerase 1 significantly cochleae, suggesting activation apoptosis resulting from cross-talk mitochondria through CHOP. These results indicated may lead is dependent on mitochondrial induced mediated caspase-12.