PMID- 32991876
OWN - NLM
STAT- MEDLINE
DCOM- 20211007
LR  - 20211007
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 149
DP  - 2020 Dec
TI  - Glycogen synthase kinase-3beta inhibition alleviates activation of the NLRP3 
      inflammasome in myocardial infarction.
PG  - 82-94
LID - S0022-2828(20)30289-3 [pii]
LID - 10.1016/j.yjmcc.2020.09.009 [doi]
AB  - Inflammasome-promoted sterile inflammation following cardiac damage is critically 
      implicated in heart dysfunction after myocardial infarction (MI). Glycogen 
      synthase kinase-3 (GSK-3beta) is a prominent mediator of the inflammatory response, 
      and high GSK-3 activity is associated with various heart diseases. We 
      investigated the regulatory mechanisms of GSK-3beta in activation of the nod-like 
      receptor family pyrin domain containing 3 (NLRP3) inflammasome in a rat model 
      with successful induction of MI on days 2-28. An in vitro investigation was 
      performed using newborn rat/human cardiomyocytes and fibroblast cultures under 
      typical inflammasome stimulation and hypoxia treatment. GSK-3beta inhibition 
      markedly improved myocardial dysfunction and prevented remodeling, with parallel 
      reduction in the parameters of NLRP3 inflammasome activation after MI. GSK-3beta 
      inhibition reduced NLRP3 inflammasome activation in cardiac fibroblasts, but not 
      in cardiomyocytes. GSK-3beta's interaction with activating signal cointegrator (ASC) 
      as well as GSK-3beta inhibition reduced ASC phosphorylation and oligomerization at 
      the tissues and cellular levels. Taken together, these data show that GSK-3beta 
      directly mediates NLRP3 inflammasome activation, causing cardiac dysfunction in 
      MI.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Wang, Shuhui
AU  - Wang S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Su, Xueling
AU  - Su X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Xu, Lina
AU  - Xu L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Chang, Cheng
AU  - Chang C
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Yao, Yu
AU  - Yao Y
AD  - Undergraduate, Student of Class 2015, Department of Clinical Medicine, Zhengzhou 
      University, Zhengzhou 450052, China.
FAU - Komal, Sumra
AU  - Komal S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Cha, Xuexiang
AU  - Cha X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China.
FAU - Zang, Mingxi
AU  - Zang M
AD  - Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Ouyang, Xinshou
AU  - Ouyang X
AD  - Section of Digestive Diseases, Yale University, New Haven, CT 06520, USA.
FAU - Zhang, Lirong
AU  - Zhang L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China. Electronic address: lrzhang@zzu.edu.cn.
FAU - Han, Shengna
AU  - Han S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou 450001, China. Electronic address: hsn@zzu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200928
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (CARD Signaling Adaptor Proteins)
RN  - 0 (Indoles)
RN  - 0 (Inflammasomes)
RN  - 0 (Maleimides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pycard protein, rat)
RN  - 0 (SB 216763)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Animals
MH  - CARD Signaling Adaptor Proteins/metabolism
MH  - Enzyme Activation/drug effects
MH  - Fibroblasts/drug effects/metabolism
MH  - Glycogen Synthase Kinase 3 beta/*antagonists & inhibitors/metabolism
MH  - Indoles/pharmacology
MH  - Inflammasomes/*metabolism
MH  - Inflammation/pathology
MH  - Male
MH  - Maleimides/pharmacology
MH  - Myocardial Infarction/*metabolism/physiopathology
MH  - Myocardial Ischemia/enzymology/pathology/physiopathology
MH  - Myocytes, Cardiac/drug effects/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Multimerization/drug effects
MH  - Rats, Sprague-Dawley
MH  - Vascular Remodeling/drug effects
OTO - NOTNLM
OT  - ASC
OT  - Cardiac fibroblasts
OT  - Glycogen synthase kinase 3
OT  - Myocardial infarction
OT  - NLRP3 inflammasome
EDAT- 2020/09/30 06:00
MHDA- 2021/10/08 06:00
CRDT- 2020/09/29 20:08
PHST- 2020/07/26 00:00 [received]
PHST- 2020/09/11 00:00 [revised]
PHST- 2020/09/21 00:00 [accepted]
PHST- 2020/09/30 06:00 [pubmed]
PHST- 2021/10/08 06:00 [medline]
PHST- 2020/09/29 20:08 [entrez]
AID - S0022-2828(20)30289-3 [pii]
AID - 10.1016/j.yjmcc.2020.09.009 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2020 Dec;149:82-94. doi: 10.1016/j.yjmcc.2020.09.009. Epub 
      2020 Sep 28.