title: The Protective effect of the endoplasmic reticulum stress-related factors BiP/GRP78 and CHOP/Gadd153 on noise-induced hearing loss in guinea pigs.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  A pilot case-control study.
  
  
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Otorhinolaryngology, Tianyou Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery of Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Tianyou Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, Tianyou Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery of Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China; Laboratory of Immunology, Faculty of Medicine, University of Lorraine, Vandoeuvre-Les-Nancy, Nancy, France.
authors.forename: Xianglei
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000473:pathology*; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009336:Necrosis; D051742:Transcription Factor CHOP / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP