PMID- 30283292
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 12
DP  - 2018
TI  - Melatonin Protects Against Neuronal Apoptosis via Suppression of the ATF6/CHOP 
      Pathway in a Rat Model of Intracerebral Hemorrhage.
PG  - 638
LID - 10.3389/fnins.2018.00638 [doi]
LID - 638
AB  - Neuronal apoptosis is an important factor accounting for the poor outcomes of 
      intracerebral hemorrhage (ICH). This study first showed that inhibition of 
      activating transcription factor 6 (ATF6) could alleviate secondary brain injury 
      through anti-apoptosis after ICH in rats. Melatonin, ATF6 and 
      CCAAT/enhancer-binding protein homologous protein (CHOP) siRNAs were applied in 
      this study. Brain edema, neurological functions, blood-brain barrier (BBB) 
      integrity were evaluated at 24 h after ICH. Western blot analysis was used to 
      evaluate the protein level of target proteins (ATF6, CHOP, Bip, Bcl-2, Bax, and 
      cleaved caspase-3). Reverse transcription-polymerase chain reaction (RT-PCR) was 
      used to assess the mRNA level of ATF6, CHOP and cleaved caspase-3. Terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and 
      caspase-3 immunofluorescence staining were applied to evaluate the neuronal cell 
      death. The results suggested that the levels of ATF6 and its downstream protein, 
      CHOP, were upregulated and reached the peak at 24 h after ICH. ATF6 was highly 
      expressed in neurons. The administration of melatonin significantly decreased the 
      mRNA and protein levels of ATF6, and its downstream targets, CHOP and cleaved 
      caspase-3, but increased the Bcl-2/Bax ratio, which ameliorated the neurological 
      functions. The CHOP siRNA significantly reversed the pro-apoptotic effect induced 
      by the increased ATF6 level after ICH. Melatonin could protect against neuronal 
      apoptosis via suppression of ATF6/CHOP arm of ER-stress-response pathway.
FAU - Xu, Weilin
AU  - Xu W
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Lu, Xiaoyang
AU  - Lu X
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Zheng, Jingwei
AU  - Zheng J
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Li, Tao
AU  - Li T
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Gao, Liansheng
AU  - Gao L
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Lenahan, Cameron
AU  - Lenahan C
AD  - Burrell College of Osteopathic Medicine, New Mexico State University, Las Cruces, 
      NM, United States.
FAU - Shao, Anwen
AU  - Shao A
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
FAU - Zhang, Jianmin
AU  - Zhang J
AD  - Department of Neurosurgery, 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 - Yu, Jun
AU  - Yu J
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20180919
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC6156428
OTO - NOTNLM
OT  - CCAAT/enhancer-binding protein homologous protein (CHOP)
OT  - apoptosis
OT  - intracerebral hemorrhage
OT  - mesencephalic astrocyte-derived neurotrophic factor (ATF6)
OT  - secondary brain injury
EDAT- 2018/10/05 06:00
MHDA- 2018/10/05 06:01
PMCR- 2018/01/01
CRDT- 2018/10/05 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/08/27 00:00 [accepted]
PHST- 2018/10/05 06:00 [entrez]
PHST- 2018/10/05 06:00 [pubmed]
PHST- 2018/10/05 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2018.00638 [doi]
PST - epublish
SO  - Front Neurosci. 2018 Sep 19;12:638. doi: 10.3389/fnins.2018.00638. eCollection 
      2018.