Endoplasmic reticulum stress-induced necroptosis promotes cochlear inflammation: Implications for age-related hearing loss

In this study, we found that the inflammation, endoplasmic reticulum (ER) stress and necroptosis signalings are activated in the cochlea of aged C57BL/6 mice. ER stress activator tunicamycin (TM) induced necroptosis in cochlear HEI-OC1 cells and cochlear explants, while necroptosis inhibitors protected cochlear cells from ER stress-induced cell death. The antioxidants inhibited necroptosis and protected HEI-OC1 cells from TM insults. Necroptotic HEI-OC1 cells promoted the activation of the co-cultured macrophages via Myd88 signaling. Moreover, necroptosis inhibitor protected from TM-induced hearing loss, and inhibited inflammation in C57BL/6 mice. These findings suggest that ER stress-induced necroptosis promotes cochlear inflammation and hearing loss. Targeting necroptosis serves as a potential approach for the treatment of cochlear inflammation and ARHL.PMID:38490286 | DOI:10.1016/j.exger.2024.112401

Source: Experimental Gerontology - March 15, 2024 Category: Geriatrics Authors: Zhongwu Su Yi Liu Weijian Zhang Wenhui Liang Yuyan Chen Jinyuan Cao Yu Liu Yiqing Zheng Qi Li Source Type: research