Glucocorticoid-induced leucine zipper protects noise-induced apoptosis in cochlear cells by inhibiting endoplasmic reticulum stress in rats

  • Hongguang Jia
  • Zhan Yu
  • Xiaohui Ge
  • Zhiting Chen
  • Xiaobing Huang
  • Yongxiang WeiEmail author
Original Paper


Endoplasmic reticulum (ER) stress-mediated apoptosis has been reported to be involved in the noise-induced hearing loss (NIHL). Glucocorticoid-induced leucine zipper (GILZ) protein has been reported to have different regulatory effects on apoptosis according to cell types. However, whether GILZ regulates apoptosis in cochlear cells is unclear. Our study aimed to investigate the mechanism by which GILZ protected ER stress-mediated cochlear apoptosis induced by noise exposure. In our trials, forty-eight male Spraque–Dawley rats were randomized into the noise, OE-GILZ-rLV + noise (ON), shRNA-GILZ-rLV + noise (SN), and control group. Rats in noise and control groups were pre-treated by administration of Blank-rLV. Before and on days 1, 4, 14 after noise exposure, auditory brainstem response (ABR) and cochlear apoptosis were detected. Changes in GILZ, GRP78, CHOP, Bcl-xL, Bax, and cleaved caspase-3 levels were investigated. Noise exposure increased ABR threshold shifts and cochlear apoptosis in parallel with downregulation of Bcl-xL and upregulation of GRP78, CHOP, Bax and cleaved caspase-3. GILZ overexpression significantly reduced ABR threshold shifts and apoptotic cochlear cells owing to noise exposure. GILZ overexpression in the cochlea further increased GRP78 elevation, decreased expression of CHOP, Bax and cleaved caspase-3, and increased expression of Bcl-xL. GILZ silencing demonstrated the opposite effect on these effects. GILZ protects cochlea from ER stress-mediated apoptosis induced by noise exposure through reduction of CHOP and regulation of ER stress-associated apoptotic proteins.


Glucocorticoid-induced leucine zipper Cochlea Noise-induced hearing loss Endoplasmic reticulum stress Apoptosis 



This research was funded by Project of development funds of Beijing traditional Chinese medicine science and technology under Grant JJ2015-07.

Compliance with ethical standards

Conflict of interest

This manuscript has not been submitted for publication nor has it been published in whole or in part elsewhere. The study has not been supported by any pharmaceutical company. The author(s) participating in this study declare that there is no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2019

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen HospitalCapital Medical UniversityBeijingChina

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