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.
Keywords: Apoptosis; Cochlea; Endoplasmic reticulum stress; Glucocorticoid-induced leucine zipper; Noise-induced hearing loss.