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

• Published in: Noise & health Vol. 18; no. 84; pp. 247 - 255
• Main Authors: Xue, Qiuhong, Li, Caihong, Chen, Jia, Guo, Hongmei, Li, Dongqing, Wu, Xianglei
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.09.2016; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Animals; Apoptosis; Blotting, Western; Cochlea; Conflicts of interest; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Evoked Potentials, Auditory, Brain Stem; Exposure; Fluorescence microscopy; Gene expression; Guinea Pigs; Hair; Hair Cells, Auditory - pathology; Hair Cells, Auditory, Outer - pathology; Hearing loss; Hearing Loss, Noise-Induced - metabolism; Hearing Loss, Noise-Induced - pathology; Hearing Loss, Noise-Induced - physiopathology; Hearing protection; Heat-Shock Proteins - metabolism; Immunohistochemistry; Kinases; Male; Necrosis; Noise; Noise induced hearing loss; Occupational diseases; Original; Proteins; Risk factors; Statistical analysis; Swine; Transcription Factor CHOP - metabolism; Transcription factors; Variance analysis; Cochlea; noise-induced hearing loss; endoplasmic reticulum stress
• ISSN: 1463-1741; 1998-4030
• DOI: 10.4103/1463-1741.192481

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.