PMID- 30504707
OWN - NLM
STAT- MEDLINE
DCOM- 20190121
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 51
IP  - 4
DP  - 2018
TI  - Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose 
      Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling.
PG  - 1852-1862
LID - 10.1159/000495711 [doi]
AB  - BACKGROUND/AIMS: Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) exposure 
      to myocardial cells mimics ischemia-reperfusion injuries. We studied the 
      potential activity of ciliary neurotrophic factor (CNTF) on OGDR-treated 
      myocardial cells. METHODS: CNTF and CNTFR expression were tested by RT-PCR assay 
      and Western blotting assay. Cell viability and death were tested by MTT assay and 
      LDH release assay, respectively. Akt-Nrf2 signalings were tested by Western 
      blotting assay and qPCR assay. RESULTS: CNTF and its receptor CNTFR were 
      functionally expressed in established H9c2 myocardial cells and primary murine 
      myocardiocytes. Pretreatment of CNTF significantly attenuated OGDR-induced 
      viability reduction and death in myocardial cells. Further studies show that in 
      the myocardial cells CNTF activated NF-E2-related factor 2 (Nrf2) signaling to 
      inhibit OGDR-induced reactive oxygen species (ROS) production and programmed 
      necrosis, preventing adenine nucleotide translocator 1 (ANT-1)-p53-cyclophilin D 
      (Cyp-D) mitochondrial association and mitochondrial depolarization. Nrf2 
      silencing or knockout almost abolished CNTF-induced H9c2 cytoprotection against 
      OGDR. CNTF activated Akt in H9c2 cells and primary murine myocardiocytes. 
      Conversely, Akt blockage by the pharmacological inhibitors not only blocked 
      CNTF-induced Nrf2 Ser-40 phosphorylation and activation, but also nullified 
      anti-OGDR actions by CNTF in myocardial cells. CONCLUSION: CNTF activates 
      Akt-Nrf2 signaling to protect myocardial cells from OGDR.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Zheng, Koulong
AU  - Zheng K
FAU - Zhang, Qing
AU  - Zhang Q
FAU - Sheng, Zhenqiang
AU  - Sheng Z
FAU - Li, Yefei
AU  - Li Y
FAU - Lu, Hui-He
AU  - Lu HH
LA  - eng
PT  - Journal Article
DEP - 20181130
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Nfe2l2 protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - Cell Line
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Ciliary Neurotrophic Factor/*metabolism
MH  - Glucose/metabolism
MH  - Mice, Inbred C57BL
MH  - Myocardial Reperfusion Injury/*metabolism/pathology
MH  - Myocytes, Cardiac/cytology/*metabolism/pathology
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Oxidative Stress
MH  - Oxygen/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Akt
OT  - CNTF
OT  - Ischemic heart diseases
OT  - Myocardial cells
OT  - Nrf2
OT  - Oxygen glucose deprivation (OGD)
EDAT- 2018/12/07 06:00
MHDA- 2019/01/22 06:00
CRDT- 2018/12/04 06:00
PHST- 2018/05/17 00:00 [received]
PHST- 2018/11/23 00:00 [accepted]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2019/01/22 06:00 [medline]
PHST- 2018/12/04 06:00 [entrez]
AID - 000495711 [pii]
AID - 10.1159/000495711 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;51(4):1852-1862. doi: 10.1159/000495711. Epub 2018 Nov 
      30.