PMID- 36273620
OWN - NLM
STAT- MEDLINE
DCOM- 20221109
LR  - 20221211
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 731
DP  - 2022 Nov 30
TI  - Kinesin spindle protein inhibitor exacerbates cisplatin-induced hair cell damage.
PG  - 109432
LID - S0003-9861(22)00317-4 [pii]
LID - 10.1016/j.abb.2022.109432 [doi]
AB  - There is emerging evidence indicating that Kinesin family, plays vital roles in 
      influencing the growth of axons, interference with the progression of tumor. 
      However, the function of Kinesin member in the auditory organs remains unknown. 
      SB743921, a kinesin spindle protein (KSP) inhibitor, was applied in mouse organ 
      of Corti and House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line to examine 
      the role of KSP in auditory system with and without cisplatin damage. Cell 
      Counting Kit-8 (CCK-8) and Lactase dehydrogenase (LDH) release assay were 
      conducted to evaluate cell activity and toxicity. Pretreatment with SB743921 
      increased the sensitivity of HEI-OC1 cells to cisplatin ototoxicity through 
      promoting cell apoptosis and deteriorating superoxide generation mediated damage 
      from cisplatin. SB743921 also enhanced cisplatin induced hair cell damage in 
      explants of mouse cochleae in vitro. Furthermore, the combined N-acetylcysteine 
      (NAC) treatment with cisplatin or with cisplatin and SB743921 both completely 
      rescued the reduced number of hair cells impaired by cisplatin, confirming the 
      strengthening function of superoxide accumulation by SB743921 after cisplatin 
      treatment. Inhibition of kinesin spindle protein enhanced the susceptibility of 
      hair cells to cisplatin induced damage in mouse cochlear explants and HEI-OC1 
      cells, indicating that kinesin spindle protein might be an unprecedented target 
      to weaken the ototoxicity of platinum medicaments.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Tang, Dongmei
AU  - Tang D
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State 
      Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Fudan University, NHC Key Laboratory of Hearing Medicine (Fudan 
      University), Shanghai, 200031, China.
FAU - Zheng, Shimei
AU  - Zheng S
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State 
      Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Fudan University, NHC Key Laboratory of Hearing Medicine (Fudan 
      University), Shanghai, 200031, China; Department of Otolaryngology-Head and Neck 
      Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, 241001, China.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Zuo, Na
AU  - Zuo N
AD  - Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan 
      Medical College, Wuhu, Anhui, 241001, China.
FAU - Yan, Renchun
AU  - Yan R
AD  - Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan 
      Medical College, Wuhu, Anhui, 241001, China.
FAU - Wu, Cheng
AU  - Wu C
AD  - Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan 
      Medical College, Wuhu, Anhui, 241001, China.
FAU - Ma, Jun
AU  - Ma J
AD  - Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan 
      Medical College, Wuhu, Anhui, 241001, China.
FAU - Wang, Chuanxi
AU  - Wang C
AD  - Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan 
      Medical College, Wuhu, Anhui, 241001, China.
FAU - Chen, Bing
AU  - Chen B
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State 
      Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Fudan University, NHC Key Laboratory of Hearing Medicine (Fudan 
      University), Shanghai, 200031, China. Electronic address: bingchen@fudan.edu.cn.
FAU - Liu, Shaofeng
AU  - Liu S
AD  - Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan 
      Medical College, Wuhu, Anhui, 241001, China. Electronic address: 
      liusf_cn@163.com.
FAU - He, Yingzi
AU  - He Y
AD  - ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State 
      Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain 
      Science, Fudan University, NHC Key Laboratory of Hearing Medicine (Fudan 
      University), Shanghai, 200031, China. Electronic address: yingzihe09611@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221021
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (SB 743921)
RN  - EC 3.6.4.4 (Kinesins)
RN  - 11062-77-4 (Superoxides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Cisplatin/toxicity
MH  - Kinesins
MH  - *Ototoxicity
MH  - Superoxides
MH  - *Antineoplastic Agents/toxicity
MH  - Reactive Oxygen Species/metabolism
MH  - Cell Survival
MH  - Apoptosis
OTO - NOTNLM
OT  - Apoptosis
OT  - Cisplatin
OT  - Kinesin spindle protein
OT  - Ototoxicity
OT  - Superoxide
COIS- Declaration of competing interest The authors declare that no competing interests 
      exist.
EDAT- 2022/10/24 06:00
MHDA- 2022/11/10 06:00
CRDT- 2022/10/23 19:33
PHST- 2022/06/15 00:00 [received]
PHST- 2022/10/08 00:00 [revised]
PHST- 2022/10/10 00:00 [accepted]
PHST- 2022/10/24 06:00 [pubmed]
PHST- 2022/11/10 06:00 [medline]
PHST- 2022/10/23 19:33 [entrez]
AID - S0003-9861(22)00317-4 [pii]
AID - 10.1016/j.abb.2022.109432 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2022 Nov 30;731:109432. doi: 10.1016/j.abb.2022.109432. 
      Epub 2022 Oct 21.