PMID- 32905819
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20211025
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1748
DP  - 2020 Dec 1
TI  - The ligand-gated ion channel P2X7 receptor mediates NLRP3/caspase-1-mediated 
      pyroptosis in cerebral cortical neurons of juvenile rats with sepsis.
PG  - 147109
LID - S0006-8993(20)30467-4 [pii]
LID - 10.1016/j.brainres.2020.147109 [doi]
AB  - Sepsis-associated encephalopathy (SAE) is a common complication of severe sepsis. 
      Some studies have suggested that P2X7 receptors, a ligand-gated ion channel 
      receptor subgroup activated by extracellular ATP, plays an important role in cell 
      pyroptosis. However, the role of P2X7 receptors in the development of SAE with 
      pyroptosis and its pathways are still unclear. In this study, we established a 
      juvenile rat model of sepsis by cecal ligation and perforation, and showed that 
      there was a significant increase in P2X7 receptor expression in the cortex of 
      juvenile rats with sepsis. When the P2X7 receptor antagonist was administrated, 
      the pyroptosis and extracellular-signal-regulated kinase (ERK) 1/2 signaling 
      pathway were inhibited, and when the P2X7 receptor agonist was administrated, the 
      pyroptosis and ERK1/2 signaling pathway were further activated. In addition, we 
      also found that the administration of ERK1/2 signaling pathway inhibitor not only 
      weakened downstream pyroptosis, but also caused the inhibition of upstream P2X7 
      receptor expression. In conclusion, our findings illustrated that the 
      ligand-gated ion channel P2X7 receptor mediates NLRP3/caspase-1-related 
      pyroptosis in cerebral cortex of juvenile rats with sepsis through ERK1/2 
      signaling pathway and plays a neuroprotective role.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Sun, Xuemei
AU  - Sun X
AD  - Department of Pediatrics, West China Second University Hospital, Sichuan 
      University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related 
      Diseases of Women and Children (Sichuan University), Ministry of Education, 
      Chengdu 610041, China.
FAU - Zhou, Ruixi
AU  - Zhou R
AD  - Department of Pediatrics, West China Second University Hospital, Sichuan 
      University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related 
      Diseases of Women and Children (Sichuan University), Ministry of Education, 
      Chengdu 610041, China.
FAU - Lei, Yupeng
AU  - Lei Y
AD  - Department of Pediatrics, West China Second University Hospital, Sichuan 
      University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related 
      Diseases of Women and Children (Sichuan University), Ministry of Education, 
      Chengdu 610041, China.
FAU - Hu, Juan
AU  - Hu J
AD  - Department of Pediatrics, West China Second University Hospital, Sichuan 
      University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related 
      Diseases of Women and Children (Sichuan University), Ministry of Education, 
      Chengdu 610041, China. Electronic address: hujuan5@163.com.
FAU - Li, Xihong
AU  - Li X
AD  - Department of Pediatrics, West China Second University Hospital, Sichuan 
      University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related 
      Diseases of Women and Children (Sichuan University), Ministry of Education, 
      Chengdu 610041, China. Electronic address: hxlixihong@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200906
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Purinergic P2X Receptor Agonists)
RN  - 0 (Purinergic P2X Receptor Antagonists)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Caspase 1/metabolism
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Disease Models, Animal
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Neurons/drug effects/*metabolism
MH  - Purinergic P2X Receptor Agonists/pharmacology
MH  - Purinergic P2X Receptor Antagonists/pharmacology
MH  - Pyroptosis/drug effects/*physiology
MH  - Rats
MH  - Receptors, Purinergic P2X7/*metabolism
MH  - Sepsis/*metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Brain injury
OT  - ERK1/2 signaling pathway
OT  - Juvenile
OT  - P2X7 receptor
OT  - Pyroptosis
OT  - Sepsis
EDAT- 2020/09/10 06:00
MHDA- 2021/10/26 06:00
CRDT- 2020/09/09 20:08
PHST- 2020/05/11 00:00 [received]
PHST- 2020/08/29 00:00 [revised]
PHST- 2020/09/01 00:00 [accepted]
PHST- 2020/09/10 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2020/09/09 20:08 [entrez]
AID - S0006-8993(20)30467-4 [pii]
AID - 10.1016/j.brainres.2020.147109 [doi]
PST - ppublish
SO  - Brain Res. 2020 Dec 1;1748:147109. doi: 10.1016/j.brainres.2020.147109. Epub 2020 
      Sep 6.