PMID- 28870160
OWN - NLM
STAT- MEDLINE
DCOM- 20180516
LR  - 20181113
IS  - 1471-2253 (Electronic)
IS  - 1471-2253 (Linking)
VI  - 17
IP  - 1
DP  - 2017 Sep 5
TI  - TREK-1 mediates isoflurane-induced cytotoxicity in astrocytes.
PG  - 124
LID - 10.1186/s12871-017-0420-5 [doi]
LID - 124
AB  - BACKGROUND: There are growing concerns that anaesthetic exposure can cause 
      extensive apoptotic degeneration of neurons and the impairment of normal synaptic 
      development and remodelling. However, little attention has been paid to exploring 
      the possible cytotoxicity of inhalation anaesthetics, such as isoflurane, in 
      astrocytes. In this research, we determined that prolonged exposure to an 
      inhalation anaesthetic caused cytotoxicity in astrocytes, and we identified the 
      underlying molecular mechanism responsible for this process. METHODS: Astrocytes 
      were exposed to isoflurane, and astrocytic survival was then measured via LDH 
      release assays, MTT assays, and TUNEL staining. TWIK-related potassium (K(+)) 
      channel-1 (TREK-1) over-expression and knockdown models were also created using 
      lentiviruses. The levels of TREK-1 and brain-derived neurotrophic factor (BDNF) 
      were measured via Western blot and qRT-PCR. RESULTS: Prolonged exposure to 
      isoflurane decreased primary astrocytic viability in a dose- and time-dependent 
      manner. Moreover, with prolonged exposure to isoflurane, the TREK-1 level 
      increased, and the BDNF level was reduced. TREK-1 knockdown promoted the survival 
      of astrocytes and increased BDNF expression following isoflurane exposure. 
      CONCLUSIONS: Overdoses of and prolonged exposure to isoflurane induce 
      cytotoxicity in primary astrocytes. TREK-1 plays an important role in 
      isoflurane-induced cultured astrocytic cytotoxicity by down-regulating the 
      expression of BDNF.
FAU - Guo, Haiyun
AU  - Guo H
AD  - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Peng, Zhengwu
AU  - Peng Z
AD  - Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, 710032, China.
FAU - Yang, Liu
AU  - Yang L
AD  - Department of Neurobiology and Collaborative Innovation Center for Brain Science, 
      Fourth Military Medical University, Xi'an, 710032, China.
FAU - Liu, Xue
AU  - Liu X
AD  - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Xie, Yaning
AU  - Xie Y
AD  - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Cai, Yanhui
AU  - Cai Y
AD  - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Xiong, Lize
AU  - Xiong L
AUID- ORCID: 0000-0002-3087-2569
AD  - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, 710032, China. mzkxlz@126.com.
FAU - Zeng, Yi
AU  - Zeng Y
AD  - Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, 710032, China. zengyi1014@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170905
PL  - England
TA  - BMC Anesthesiol
JT  - BMC anesthesiology
JID - 100968535
RN  - 0 (Anesthetics, Inhalation)
RN  - 0 (Cytotoxins)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - 0 (potassium channel protein TREK-1)
RN  - CYS9AKD70P (Isoflurane)
SB  - IM
MH  - Anesthetics, Inhalation/*toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/*drug effects/*metabolism/pathology
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Cytotoxins/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Isoflurane/*toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/drug effects/metabolism/pathology
MH  - Potassium Channels, Tandem Pore Domain/*physiology
PMC - PMC5584525
OTO - NOTNLM
OT  - Astrocyte
OT  - BDNF
OT  - Cytotoxicity
OT  - Isoflurane
OT  - TREK-1
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The experiments were performed in 
      compliance with the National Institutes of Health Guidelines on the Use of 
      Laboratory Animals and were approved by the Fourth Military Medical University 
      Ethic Committee on Animal Care. CONSENT FOR PUBLICATION: Not applicable. 
      COMPETING INTERESTS: The authors declare that they have no competing interests. 
      PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional 
      claims in published maps and institutional affiliations.
EDAT- 2017/09/06 06:00
MHDA- 2018/05/17 06:00
PMCR- 2017/09/05
CRDT- 2017/09/06 06:00
PHST- 2017/02/19 00:00 [received]
PHST- 2017/08/27 00:00 [accepted]
PHST- 2017/09/06 06:00 [entrez]
PHST- 2017/09/06 06:00 [pubmed]
PHST- 2018/05/17 06:00 [medline]
PHST- 2017/09/05 00:00 [pmc-release]
AID - 10.1186/s12871-017-0420-5 [pii]
AID - 420 [pii]
AID - 10.1186/s12871-017-0420-5 [doi]
PST - epublish
SO  - BMC Anesthesiol. 2017 Sep 5;17(1):124. doi: 10.1186/s12871-017-0420-5.