The Protective effect of the endoplasmic reticulum stress-related factors BiP/GRP78 and CHOP/Gadd153 on noise-induced hearing loss in guinea pigs

Qiuhong Xue, Caihong Li, Jia Chen, Hongmei Guo, Dongqing Li, Xianglei Wu

Noise and Health 2016 18(84):247-255

Context: The audiological features and cochlear morphology of individuals with noise-induced hearing loss (NIHL) are well characterized. However, the molecular processes in the cochlea are not well understood. Aims: To explore the role of the endoplasmic reticulum stress (ERS) response in the guinea pig model of cochlear damage induced by exposure to intense noise. Settings and Design: A pilot case–control study. Subjects and Methods: Forty-eight guinea pigs were divided into four equal groups. At 1, 4, or 14 days (d) post-exposure, the auditory brainstem responses (ABRs) were tested before sacrificing the subjects. The expression levels of the binding immunoglobulin protein/glucose-regulated protein 78 (BiP/GRP78) and C/EBP-homologous protein/growth arrest and DNA damage-inducible gene 153 (CHOP/Gadd153) proteins were evaluated using immunohistochemistry and Western blotting. The number of cochlear hair cells with altered nuclei was counted using confocal fluorescence microscopy. Statistical analysis used: One-way analysis of variance (ANOVA) and the least squares difference (LSD) test. Results: The outer hair cells (OHCs) showed changes of apoptosis, necrosis, and loss after noise exposure. In the 1- and 4-d groups, more apoptotic cells were found than necrotic cells (P < 0.01). The level of BiP/GRP78 was significantly higher in all three experimental groups compared to the control group (P < 0.01). The level of CHOP/Gadd153 was increased at 1 d post-exposure, achieving a peak that was maintained until 4 d, after which it returned to baseline levels by 14 d post-exposure. Conclusions: ERS response was activated by inducing the expression of BiP/GRP78 to lessen the extent of the resulting cellular damage and activating the CHOP/Gadd153 pathway to eliminate the most severely damaged cells.

from #Audiology via xlomafota13 on Inoreader http://ift.tt/2eqLehv
via IFTTT