PMID- 30820888
OWN - NLM
STAT- MEDLINE
DCOM- 20190523
LR  - 20200225
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 35
IP  - 4
DP  - 2019 May
TI  - Salicylate-Induced Ototoxicity of Spiral Ganglion Neurons: Ca(2+)/CaMKII-Mediated 
      Interaction Between NMDA Receptor and GABA(A) Receptor.
PG  - 838-847
LID - 10.1007/s12640-019-0006-8 [doi]
AB  - Sodium salicylate (SS) is one of the nonsteroidal anti-inflammatory drugs and 
      widely used in clinical practice. Therefore, we aimed to investigate the 
      potential ototoxicity mechanism of sodium salicylate: the influence of 
      Ca(2+)/calmodulin-dependent protein kinase II (Ca(2+)/CaMKII) in interaction 
      between NMDA receptors (NMDAR) and GABA(A) receptors (GABA(A)R) in rat cochlear 
      spiral ganglion neurons (SGNs). After treatment with SS, NMDA, and an NMDAR 
      inhibitor (APV), the changes of GABA(A)R beta3 (GABR beta3) mRNA, surface and total 
      protein, and GABA(A)R currents in SGNs were assessed by quantitative PCR, Western 
      blot, and whole-cell patch clamp. Mechanistically, SS and/or NMDA increased the 
      GABR beta3 mRNA expression, while decreased GABR beta3 surface protein levels and 
      GABA(A)R-mediated currents. Moreover, application of SS and/or NMDA showed 
      promotion in phosphorylation levels at S383 of GABR beta3. Collectively, Ca(2+) 
      chelator (BAPTA) or Ca(2+)/CaMKII inhibitor (KN-93) reversed the effects of SS 
      and/or NMDA on GABA(A)R. Therefore, we hypothesize that the interaction between 
      NMDAR and GABA(A)R is involved in the SGNs damage induced by SS. In addition, the 
      underlying molecular mechanism is related to Ca(2+)/CaMKII-mediated signaling 
      pathway, which suggests that the interaction between calcium signal-regulated 
      receptors mediates SS ototoxicity.
FAU - Qin, Danxue
AU  - Qin D
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
FAU - Liu, Peiqiang
AU  - Liu P
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
FAU - Chen, Huiying
AU  - Chen H
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
FAU - Huang, Xi
AU  - Huang X
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
AD  - Department of Otolaryngology-Head and Neck Surgery, Wuhan No.1 Hospital, Wuhan, 
      430022, Hubei, China.
FAU - Ye, Wenhua
AU  - Ye W
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
FAU - Lin, Xiaoyu
AU  - Lin X
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
FAU - Wei, Fangyu
AU  - Wei F
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China.
FAU - Su, Jiping
AU  - Su J
AD  - Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of 
      Guangxi Medical University, Nanning, 530021, Guangxi, China. ymsu2@126.com.
LA  - eng
GR  - 81360157/National Natural Science Foundation of China/
GR  - 81560174/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190228
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - WIQ1H85SYP (Sodium Salicylate)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*toxicity
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Sodium Salicylate/*toxicity
MH  - Spiral Ganglion/*drug effects/metabolism
OTO - NOTNLM
OT  - Ca2+/CaMKII
OT  - GABAAR
OT  - NMDAR
OT  - Neurotoxicity
OT  - Spiral ganglion neurons
EDAT- 2019/03/02 06:00
MHDA- 2019/05/24 06:00
CRDT- 2019/03/02 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2019/01/24 00:00 [accepted]
PHST- 2019/01/21 00:00 [revised]
PHST- 2019/03/02 06:00 [pubmed]
PHST- 2019/05/24 06:00 [medline]
PHST- 2019/03/02 06:00 [entrez]
AID - 10.1007/s12640-019-0006-8 [pii]
AID - 10.1007/s12640-019-0006-8 [doi]
PST - ppublish
SO  - Neurotox Res. 2019 May;35(4):838-847. doi: 10.1007/s12640-019-0006-8. Epub 2019 
      Feb 28.