PMID- 27712936
OWN - NLM
STAT- MEDLINE
DCOM- 20170529
LR  - 20181001
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 480
IP  - 3
DP  - 2016 Nov 18
TI  - GSK621 activates AMPK signaling to inhibit LPS-induced TNFalpha production.
PG  - 289-295
LID - S0006-291X(16)31656-4 [pii]
LID - 10.1016/j.bbrc.2016.10.001 [doi]
AB  - LPS stimulation in macrophages/monocytes induces TNFalpha production. We here tested 
      the potential effect of GSK621, a novel AMP-activated protein kinase (AMPK) 
      activator, against the process. In RAW264.7 macrophages, murine bone 
      marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease 
      (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFalpha 
      protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPKalpha shRNA 
      knockdown or dominant negative mutation (T172A), almost abolished GSK621's 
      suppression on TNFalpha in RAW264.7 cells. Reversely, forced-expression of a 
      constitutively-active AMPKalpha (T172D) mimicked GSK621 actions and reduced 
      LPS-induced TNFalpha production. Molecularly, GSK621 suppressed LPS-induced reactive 
      oxygen species (ROS) production and nuclear factor kappa B (NFkappaB) activation. 
      In vivo, GSK621 oral administration inhibited LPS-induced TNFalpha production and 
      endotoxin shock in mice. In summary, GSK621 activates AMPK signaling to inhibit 
      LPS-induced TNFalpha production in macrophages/monocytes.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Wu, Yong-Hong
AU  - Wu YH
AD  - Department of Medical Technology, Xi'an Medical University, China.
FAU - Li, Quan
AU  - Li Q
AD  - Center of Stomatology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, China.
FAU - Li, Ping
AU  - Li P
AD  - Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong 
      University, Xi'an, China. Electronic address: drlipingxamu@163.com.
FAU - Liu, Bei
AU  - Liu B
AD  - Department of Medical Technology, Xi'an Medical University, China. Electronic 
      address: liubeixamu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20161003
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (GSK621)
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyrimidinones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects/immunology
MH  - Enzyme Activation/drug effects/immunology
MH  - Imidazoles/*administration & dosage
MH  - Leukocytes, Mononuclear/drug effects/*immunology
MH  - Lipopolysaccharides/*administration & dosage
MH  - Mice
MH  - Pulmonary Disease, Chronic Obstructive/*immunology
MH  - Pyrimidinones/*administration & dosage
MH  - RAW 264.7 Cells
MH  - Tumor Necrosis Factor-alpha/*immunology
OTO - NOTNLM
OT  - AMPK
OT  - GSK621
OT  - LPS
OT  - ROS and NFkappaB
OT  - TNFalpha
EDAT- 2016/10/30 06:00
MHDA- 2017/05/30 06:00
CRDT- 2016/11/06 06:00
PHST- 2016/09/21 00:00 [received]
PHST- 2016/10/01 00:00 [accepted]
PHST- 2016/11/06 06:00 [entrez]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/05/30 06:00 [medline]
AID - S0006-291X(16)31656-4 [pii]
AID - 10.1016/j.bbrc.2016.10.001 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Nov 18;480(3):289-295. doi: 
      10.1016/j.bbrc.2016.10.001. Epub 2016 Oct 3.