PMID- 32848609
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 14
DP  - 2020
TI  - HIF-1alpha Mediates TRAIL-Induced Neuronal Apoptosis via Regulating DcR1 Expression 
      Following Traumatic Brain Injury.
PG  - 192
LID - 10.3389/fncel.2020.00192 [doi]
LID - 192
AB  - Background: Neuronal apoptosis involved in secondary injury following traumatic 
      brain injury (TBI) significantly contributes to the poor outcomes of patients 
      with TBI. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can 
      selectively induce apoptosis of tumor cells. Hypoxia factor (HIF) 1alpha is a 
      controversial factor that mediates the neuronal apoptotic pathway. Herein, we 
      hypothesize that HIF-1alpha may mediate the TRAIL-induced neuronal apoptosis after 
      TBI. Methods: We used Western blots and immunofluorescence to study the 
      expression and cell localization of TRAIL and death receptor 5 (DR5) after TBI in 
      rats. Soluble DR5 (sDR5) administration was used to block the TRAIL-induced 
      neuronal death and neural deficits. HIF-1alpha inhibitor 2ME and agonist DMOG were 
      used to study the role of HIF-1alpha in TRAIL-induced neuronal death. Meanwhile, 
      HIF-1alpha siRNA was used to investigate the role of HIF-1alpha in TRAIL-induced neuronal 
      death in vitro. Results: The expressions of microglia-located TRAIL and 
      neuron-located DR5 were significantly upregulated after TBI. sDR5 significantly 
      attenuated TRAIL-induced neuronal apoptosis and neurological deficits. 2ME 
      decreased neuronal apoptosis, lesion area, and brain edema and improved 
      neurological function via increased expression of TRAIL decoy receptor 1 (DcR1), 
      which inhibited TRAIL-induced apoptosis after TBI. The administration of DMOG 
      produced the opposite effect than did 2ME. Similarly, HIF-1alpha siRNA attenuated 
      TRAIL-induced neuronal death via increased DcR1 expression in vitro. Conclusion: 
      Our findings suggested that the TRAIL/DR5 signaling pathway plays an important 
      role after neuronal apoptosis after TBI. HIF-1alpha mediates TRAIL-induced neuronal 
      apoptosis by regulating DcR1 expression following TBI.
CI  - Copyright (c) 2020 Fang, Lu, Wang, Wu, Mei, Zheng, Xu, Lenahan, Chen, Zhang and 
      Hong.
FAU - Fang, Yuanjian
AU  - Fang Y
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Lu, Jianan
AU  - Lu J
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Wang, Xiaoyu
AU  - Wang X
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Wu, Haijian
AU  - Wu H
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Mei, Shuhao
AU  - Mei S
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Zheng, Jingwei
AU  - Zheng J
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Xu, Shenbin
AU  - Xu S
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Lenahan, Cameron
AU  - Lenahan C
AD  - Center for Neuroscience Research, Loma Linda University School of Medicine, Loma 
      Linda, CA, United States.
AD  - Burrell College of Osteopathic Medicine, Las Cruces, NM, United States.
FAU - Chen, Sheng
AU  - Chen S
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Zhang, Jianmin
AU  - Zhang J
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
AD  - Brain Research Institute, Zhejiang University, Hangzhou, China.
AD  - Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, 
      China.
FAU - Hong, Yuan
AU  - Hong Y
AD  - Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20200803
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC7416670
OTO - NOTNLM
OT  - death receptor 5
OT  - decoy receptor
OT  - hypoxia-induced factor-1alpha
OT  - traumatic brain injury
OT  - tumor necrosis factor-related apoptosis-inducing ligand
EDAT- 2020/08/28 06:00
MHDA- 2020/08/28 06:01
PMCR- 2020/01/01
CRDT- 2020/08/28 06:00
PHST- 2020/02/16 00:00 [received]
PHST- 2020/06/02 00:00 [accepted]
PHST- 2020/08/28 06:00 [entrez]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2020/08/28 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2020.00192 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2020 Aug 3;14:192. doi: 10.3389/fncel.2020.00192. 
      eCollection 2020.