PMID- 29512699
OWN - NLM
STAT- MEDLINE
DCOM- 20180913
LR  - 20211122
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 5
DP  - 2018 May
TI  - High expression of active ATF6 aggravates endoplasmic reticulum stress‑induced 
      vascular endothelial cell apoptosis through the mitochondrial apoptotic pathway.
PG  - 6483-6489
LID - 10.3892/mmr.2018.8658 [doi]
AB  - Activating transcription factor 6 (ATF6), one of three sensor proteins in the 
      endoplasmic reticulum (ER), is an important regulatory factor in the ER 
      stress‑induced apoptosis pathway. Although recent studies have made some progress 
      in elucidating the regulation mechanism of ATF6, the specific regulatory 
      mechanism of ER stress‑induced vascular endothelial cell (VEC) apoptosis is still 
      unclear. The present study was designed to investigate the role of ATF6 in VECs 
      under thapsigargin (TG)‑induced ER stress. ATF6 (1‑366aa; ATF6 high‑expressed 
      plasmid) and ATF6 (151‑366aa; plasmid without transcriptional activity) were 
      transfected into VECs to yield an ATF6 high‑expression model and a positive 
      control model, respectively. High expression of ATF6 decreased viability and 
      aggravated ER stress‑induced apoptosis in VECs. Increased expression of 
      apoptosis‑related genes, including those encoding caspase‑3, caspase‑9, C/EBP 
      homologous protein (CHOP), cytochrome c and B‑cell lymphoma‑associated protein X 
      (Bax)/B‑cell lymphoma (Bcl‑)2, was detected by polymerase chain reaction and 
      western blotting in the ATF6 (1‑366aa) + TG group. No significant effect of TG 
      treatment and high ATF6 expression was indicated on the expression of death 
      receptor‑related genes, including those encoding caspase‑8 and Fas. The results 
      demonstrated that high expression of activated ATF6 aggravates ER stress‑induced 
      VEC apoptosis through the mitochondrial apoptotic pathway. Furthermore, in 
      response to ER stress, ATF6 upregulates the expression of caspase‑3, caspase‑9, 
      CHOP, cytochrome c and Bax/Bcl‑2.
FAU - Huang, Jingyong
AU  - Huang J
AD  - Department of Vascular Surgery, The Second Affiliated Hospital of Soochow 
      University, Soochow, Jiangsu 215000, P.R. China.
FAU - Wan, Li
AU  - Wan L
AD  - Department of Pathology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, P.R. China.
FAU - Lu, Heping
AU  - Lu H
AD  - Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, P.R. China.
FAU - Li, Xiaoqiang
AU  - Li X
AD  - Department of Vascular Surgery, The Second Affiliated Hospital of Soochow 
      University, Soochow, Jiangsu 215000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180301
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (ATF6 protein, human)
RN  - 0 (Activating Transcription Factor 6)
RN  - 0 (Apoptosis Regulatory Proteins)
SB  - IM
MH  - Activating Transcription Factor 6/*biosynthesis/genetics
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins/*biosynthesis
MH  - Human Umbilical Vein Endothelial Cells/cytology/*metabolism
MH  - Humans
MH  - Mitochondria/genetics/*metabolism
MH  - *Models, Biological
MH  - *Up-Regulation
PMC - PMC5928631
OTO - NOTNLM
OT  - endoplasmic reticulum stress
OT  - vascular endothelial cells
OT  - activating transcription factor 6
OT  - apoptosis pathway
EDAT- 2018/03/08 06:00
MHDA- 2018/09/14 06:00
PMCR- 2018/03/01
CRDT- 2018/03/08 06:00
PHST- 2017/03/23 00:00 [received]
PHST- 2017/11/21 00:00 [accepted]
PHST- 2018/03/08 06:00 [pubmed]
PHST- 2018/09/14 06:00 [medline]
PHST- 2018/03/08 06:00 [entrez]
PHST- 2018/03/01 00:00 [pmc-release]
AID - mmr-17-05-6483 [pii]
AID - 10.3892/mmr.2018.8658 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 May;17(5):6483-6489. doi: 10.3892/mmr.2018.8658. Epub 2018 Mar 
      1.