TY - JOUR T1 - Endoplasmic reticulum stress is involved in spiral ganglion neuron apoptosis following chronic kanamycin-induced deafness JF - Bioscience Reports JO - Biosci Rep DO - 10.1042/BSR20181749 VL - 39 IS - 2 SP - BSR20181749 AU - Tu, Yaqin AU - Fan, Guorun AU - Sun, Haiying AU - Cai, Xiong AU - Kong, Wen Y1 - 2019/02/28 UR - http://www.bioscirep.org/content/39/2/BSR20181749.abstract N2 - Accepted Manuscript online January 9, 2019.Aminoglycoside antibiotics-induced hearing loss is a common sensorineural impairment. Spiral ganglion neurons (SGNs) are first-order neurons of the auditory pathway and are critical for the maintenance of normal hearing. In the present study, we investigated the time-course of morphological changes and the degeneration process of spiral ganglion cells (SGCs) following chronic kanamycin-induced deafness and determined whether the endoplasmic reticulum (ER) stress was involved in the degeneration of SGNs. We detected density changes in SGCs and the expressions of Bip, inositol requirement 1 (IRE1)α, activating transcription factor-6α, p-PERK, p-eIF2α, CHOP, and caspase-12 at each time point after kanamycin treatment. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was also performed. The number of SGC deletions reached ∼50% at the 70th day after kanamycin administration and the ER of most SGCs were dilated. The expression of p-PERK, p-eIF2α, p-IRE1α, Bip, caspase-12, and Chop was significantly unregulated after kanamycin treatment. The number of SGCs that were positive for both TUNEL and caspase-12 increased from day 7 to 28. Taken together, these data demonstrate that ER stress was involved in kanamycin-induced apoptosis of SGNs. Kanamycin-induced SGN apoptosis is mediated, at least in part, by ER stress-induced upregulation of CHOP and caspase-12.ABRs, evoked auditory brain stem responses; ASK1, apoptosis signal regulating kinase 1; ATF6, activating transcription factor 6; CDK1, cyclin dependent kinase 1; CHOP, C/EBP Homologous Protein; dUTP, 2′-deoxyuridine 5′-triphosphate; ER, endoplasmic reticulum; ERAD, Endoplasmic Reticulum Associated Degradation; IRE1, inositol requirement 1; JNK, c-Jun N-terminal kinase; LSD, Least significant difference; PERK, interferon-induced double stranded RNA-activated protein kinase (PRKR) -like endoplasmic reticulum kinase; ROS, reactive oxygen species; SGCs, spiral ganglion cells; SGN, spiral ganglion neuron; SNHL, severe sensorineural hearing loss; SPL, sound pressure level; TEM, transmission electron microscopy; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; UPR, unfolded protein response. ER -