PMID- 29804533
OWN - NLM
STAT- MEDLINE
DCOM- 20190506
LR  - 20190506
IS  - 1875-5739 (Electronic)
IS  - 1567-2026 (Linking)
VI  - 15
IP  - 2
DP  - 2018
TI  - Bradykinin B2 receptors play a neuroprotective role in Hypoxia/reoxygenation 
      injury related to pyroptosis pathway.
PG  - 138-144
LID - 10.2174/1567202615666180528073141 [doi]
AB  - BACKGROUND: Kinins are pro-inflammatory peptides that mediate numerous vascular 
      and pain responses in tissue injury. Kinins exert their biological functions via 
      two G-protein-coupled receptors: Bradykinin 1 Receptor (B1R) and Bradykinin 2 
      Receptor (B2R). We previously demonstrated the up-regulation of B2R after 
      Hypoxia/Reoxygenation (H/R) injury in primary cultured cortical neurons. However, 
      the role of B2R in inflammasome-induced pyroptosis remains unknown. METHODS: We 
      induced H/R neuronal injury in primary cultured cortical neurons harvested from 
      embryonic day 17 brains. Next, we examined the neuroprotective function of B2R in 
      H/R-induced neuronal apoptosis or necrosis using an annexin V FITC/Propidium 
      Iodide (PI) double-staining technique. The pyroptosis signaling cascade, 
      including caspase-1, IL-1beta and IL-18 levels and Cleaved Gasdermin D (GSDMD) 
      expression was examined by real-time quantitative reverse transcription 
      polymerase chain reaction (RT-qPCR) and western blotting to explore the 
      underlying molecular mechanism. RESULTS: H/R injury significantly increased B2R 
      protein expression (P<0.05) as well as the percentage of early apoptotic and 
      necrotic or late apoptotic neurons as verified by the annexin V FITC/PI flow 
      cytometric analysis. Bradykinin (BK), a specific B2R agonist, caused a 
      significant decrease in apoptotic neuronal death after H/R injury, while HOE140, 
      a specific B2R antagonist, markedly reduced the neuroprotective effect of B2R. 
      Following H/R injury, BK downregulated the caspase-1, IL-1beta and IL-18 levels 
      (P<0.01). In contrast, pretreatment with HOE140 significantly increased 
      caspase-1, IL-1beta, and IL-18 levels (P<0.01). Further analysis revealed that 
      GSDMD, a key executioner of pyroptosis, is a target for B2R-mediated inhibition 
      of neuronal pyroptosis. Cleaved GSDMD expression was significantly inhibited by 
      BK pretreatment and significantly enhanced by HOE140 pretreatment (P<0.01). 
      CONCLUSION: These results indicate that activation of B2R plays an important role 
      in pyroptosis mediated by H/R injury.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Tang, Min
AU  - Tang M
AD  - Department of Neurology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, 
      China.
FAU - Li, Xia
AU  - Li X
AD  - Department of Neurology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, 
      China.
FAU - Liu, Ping
AU  - Liu P
AD  - Department of Neurology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, 
      China.
FAU - Wang, Jianwen
AU  - Wang J
AD  - Department of Neurology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, 
      China.
FAU - He, Fangping
AU  - He F
AD  - Department of Neurology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, 
      China.
FAU - Zhu, Xiongchao
AU  - Zhu X
AD  - Department of Neurology, The First Affiliated Hospital, College of Medicine, 
      Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Neurovasc Res
JT  - Current neurovascular research
JID - 101208439
RN  - 0 (Bradykinin B2 Receptor Antagonists)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Bradykinin B2)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7PG89G35Q7 (icatibant)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Bradykinin/analogs & derivatives/pharmacology
MH  - Bradykinin B2 Receptor Antagonists/pharmacology
MH  - Caspase 1/metabolism
MH  - Cell Hypoxia/*drug effects/*physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Embryo, Mammalian
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Mice
MH  - Neurons
MH  - Nitric Oxide/metabolism
MH  - Pyroptosis/drug effects/*physiology
MH  - RNA, Messenger/metabolism
MH  - Receptor, Bradykinin B2/genetics/*metabolism
MH  - Signal Transduction/drug effects/*physiology
OTO - NOTNLM
OT  - Bradykinin B2 receptor
OT  - GSDMD
OT  - hypoxia/reoxygenation
OT  - inflammatory responses
OT  - ischemic stroke
OT  - pyroptosis.
EDAT- 2018/05/29 06:00
MHDA- 2019/05/07 06:00
CRDT- 2018/05/29 06:00
PHST- 2018/04/02 00:00 [received]
PHST- 2018/04/14 00:00 [revised]
PHST- 2018/04/16 00:00 [accepted]
PHST- 2018/05/29 06:00 [pubmed]
PHST- 2019/05/07 06:00 [medline]
PHST- 2018/05/29 06:00 [entrez]
AID - CNR-EPUB-90699 [pii]
AID - 10.2174/1567202615666180528073141 [doi]
PST - ppublish
SO  - Curr Neurovasc Res. 2018;15(2):138-144. doi: 10.2174/1567202615666180528073141.