PMID- 29891453
OWN - NLM
STAT- MEDLINE
DCOM- 20190204
LR  - 20220325
IS  - 1673-4254 (Print)
IS  - 2663-0842 (Electronic)
IS  - 1673-4254 (Linking)
VI  - 38
IP  - 5
DP  - 2018 May 20
TI  - [Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat 
      hippocampal neurons].
PG  - 567-571
AB  - OBJECTIVE: To investigate the role of caspase-1 activation in bilirubin-induced 
      neuronal injury and the protective effect of VX-765 against bilirubin-induced 
      neurotoxicity in cultured primary rat hippocampal neurons. METHODS: Cultured 
      primary rat hippocampal neurons were exposed to DMSO (control group), 50 micromol/L 
      bilirubin, or 50 micromol/L bilirubin 1 h after 50 micromol/L VX-765 treatment. The 
      expressions of NLRP3 and caspase-1 in the neurons were detected by Western 
      blotting, and the relative cell survival and death rates were assessed with a 
      modified MTT assay, lactate dehydrogenase assay and Typan blue staining. 
      Interleukin-18 (IL-18) concentration in the culture supernatant was measured 
      using enzyme-linked immunosorbent assay (ELISA). RESULTS: In cultured primary rat 
      hippocampal neurons, bilirubin exposure for 3 and 6 h caused significant 
      increases in the expressions of NLRP3 and activated caspase-1 compared with those 
      in the control group (P<0.05). Pretreatment of the cells with VX-765 obviously 
      suppressed bilirubin-induced activation of caspase-1 (P<0.05). The relative 
      survival rate of the neurons was (84.02-/+2.31)% in VX-765 intervention group, 
      significantly higher than that in bilirubin group (P<0.05) but lower than that in 
      the control group (P<0.05); LDH release rate in VX-765 intervention group was 
      (10.78-/+1.58)%, significantly lower than that in bilirubin group (P<0.05) but 
      higher than that in the control group (P<0.05). The cell death rate in VX-765 
      intervention group was (5.58-/+1.23)%, significantly lower than that in bilirubin 
      group (P<0.05) but higher than that in the control group (P<0.05). CONCLUSION: In 
      cultured primary rat hippocampal neurons, caspase-1 activation plays a role in 
      bilirubin-induced neurotoxicity, and VX-765 treatment provides protection against 
      bilirubin-induced neuronal injury by inhibiting caspase-1 activation.
FAU - Wei, Qian
AU  - Wei Q
AD  - Department of Neonatology, Children's Hospital of Chongqing Medical University, 
      Ministry of Education Key Laboratory of Child Development and Disorders, China 
      International Science and Technology Cooperation Base of Child Development and 
      Critical Disorders, Chongqing Key Laboratory of Translational Medical Research in 
      Cognitive Development and Learning and Memory Disorders, Chongqing 400014, 
      China.E-mail: 1476595281@qq.com.
FAU - Feng, Jie
AU  - Feng J
FAU - He, Chun-Mei
AU  - He CM
FAU - Hua, Zi-Yu
AU  - Hua ZY
LA  - chi
PT  - Journal Article
PL  - China
TA  - Nan Fang Yi Ke Da Xue Xue Bao
JT  - Nan fang yi ke da xue xue bao = Journal of Southern Medical University
JID - 101266132
RN  - 0 (Dipeptides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (para-Aminobenzoates)
RN  - 00OLE78529 (belnacasan)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - RFM9X3LJ49 (Bilirubin)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bilirubin/antagonists & inhibitors/pharmacology
MH  - Caspase 1/*metabolism
MH  - Caspase 3/metabolism
MH  - Caspases/metabolism
MH  - Cell Death
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Dimethyl Sulfoxide
MH  - Dipeptides/pharmacology
MH  - Enzyme Activation/physiology
MH  - *Hippocampus
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Neurons/cytology/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - para-Aminobenzoates/pharmacology
PMC - PMC6743908
EDAT- 2018/06/13 06:00
MHDA- 2019/02/05 06:00
PMCR- 2018/05/20
CRDT- 2018/06/13 06:00
PHST- 2018/06/13 06:00 [entrez]
PHST- 2018/06/13 06:00 [pubmed]
PHST- 2019/02/05 06:00 [medline]
PHST- 2018/05/20 00:00 [pmc-release]
AID - nfykdxxb-38-5-567 [pii]
AID - 10.3969/j.issn.1673-4254.2018.05.10 [doi]
PST - ppublish
SO  - Nan Fang Yi Ke Da Xue Xue Bao. 2018 May 20;38(5):567-571. doi: 
      10.3969/j.issn.1673-4254.2018.05.10.