PMID- 30626727
OWN - NLM
STAT- MEDLINE
DCOM- 20200128
LR  - 20211204
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 2
DP  - 2019 Feb 28
TI  - Endoplasmic reticulum stress is involved in spiral ganglion neuron apoptosis 
      following chronic kanamycin-induced deafness.
LID - BSR20181749 [pii]
LID - 10.1042/BSR20181749 [doi]
AB  - 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)alpha, activating 
      transcription factor-6alpha, p-PERK, p-eIF2alpha, 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  approximately 50% at the 70th day after kanamycin administration and the ER 
      of most SGCs were dilated. The expression of p-PERK, p-eIF2alpha, p-IRE1alpha, 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.
CI  - (c) 2019 The Author(s).
FAU - Tu, Yaqin
AU  - Tu Y
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Fan, Guorun
AU  - Fan G
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Sun, Haiying
AU  - Sun H
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China.
FAU - Cai, Xiong
AU  - Cai X
AD  - Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430022, China 
      wenly-kong@163.com caixiong@live.com.
FAU - Kong, Wen
AU  - Kong W
AUID- ORCID: 0000-0002-9275-8809
AD  - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China wenly-kong@163.com 
      caixiong@live.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190208
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Ddit3 protein, rat)
RN  - 0 (Ern1 protein, rat)
RN  - 0 (GRP78 protein, rat)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 59-01-8 (Kanamycin)
RN  - EC 2.7.11.1 (PERK kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 3.1.- (Endoribonucleases)
RN  - EC 3.4.22.- (Casp12 protein, rat)
RN  - EC 3.4.22.- (Caspase 12)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Caspase 12/metabolism
MH  - Deafness/chemically induced/*pathology/physiopathology
MH  - *Endoplasmic Reticulum Stress/drug effects
MH  - Endoribonucleases/metabolism
MH  - Heat-Shock Proteins/metabolism
MH  - Kanamycin/*adverse effects
MH  - Male
MH  - Multienzyme Complexes/metabolism
MH  - Neurons/drug effects/metabolism/*pathology
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Rats, Sprague-Dawley
MH  - Spiral Ganglion/drug effects/metabolism/*pathology/ultrastructure
MH  - Transcription Factor CHOP/metabolism
MH  - eIF-2 Kinase/metabolism
PMC - PMC6592474
OTO - NOTNLM
OT  - Apoptosis
OT  - degeneration process
OT  - endoplasmic reticulum stress
OT  - spiral ganglion neurons
COIS- The authors declare that there are no conflicts of interest associated with the 
      manuscript.
EDAT- 2019/01/11 06:00
MHDA- 2020/01/29 06:00
PMCR- 2019/02/08
CRDT- 2019/01/11 06:00
PHST- 2018/09/30 00:00 [received]
PHST- 2018/12/28 00:00 [revised]
PHST- 2019/01/08 00:00 [accepted]
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2020/01/29 06:00 [medline]
PHST- 2019/01/11 06:00 [entrez]
PHST- 2019/02/08 00:00 [pmc-release]
AID - BSR20181749 [pii]
AID - 10.1042/BSR20181749 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Feb 8;39(2):BSR20181749. doi: 10.1042/BSR20181749. Print 2019 
      Feb 28.