Soluble uric acid induces myocardial damage through activating the NLRP3 inflammasome.
Animals
Apoptosis
/ drug effects
Cell Line
Gene Knockdown Techniques
Inflammasomes
/ metabolism
Lysosomes
/ metabolism
Mitochondria, Heart
/ drug effects
Models, Biological
Myocardium
/ metabolism
Myocytes, Cardiac
/ drug effects
NF-kappa B
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Rats
Reactive Oxygen Species
/ metabolism
Signal Transduction
Toll-Like Receptor 6
/ metabolism
Uric Acid
/ blood
Ventricular Remodeling
/ genetics
NLRP3 inflammasome
TLR6/NF-κB signal pathway
UCP2
myocardial damage
soluble uric acid
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
18
10
2019
revised:
25
04
2020
accepted:
24
05
2020
pubmed:
20
6
2020
medline:
14
5
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
Uric acid crystal is known to activate the NLRP3 inflammasome and to cause tissue damages, which can result in many diseases, such as gout, chronic renal injury and myocardial damage. Meanwhile, soluble uric acid (sUA), before forming crystals, is also related to these diseases. This study was carried out to investigate whether sUA could also activate NLRP3 inflammasome in cardiomyocytes and to analyse the mechanisms. The cardiomyocyte activity was monitored, along with the levels of mature IL-1β and caspase-1 from H9c2 cells following sUA stimulus. We found that sUA was able to activate NLRP3 inflammasome, which was responsible for H9c2 cell apoptosis induced by sUA. By elevating TLR6 levels and then activating NF-κB/p65 signal pathway, sUA promoted NLRP3, pro-caspase 1 and pro-IL-1β production and provided the first signal of NLRP3 inflammasome activation. Meanwhile, ROS production regulated by UCP2 levels also contributed to NLRP3 inflammasome assembly and subsequent caspase 1 activation and mature IL-1β secretion. In addition, the tlr6 knockdown rats suffering from hyperuricemia showed the lower level of IL-1β and an ameliorative cardiac function. These findings suggest that sUA activates NLRP3 inflammasome in cardiomyocytes and they may provide one therapeutic strategy for myocardial damage induced by sUA.
Identifiants
pubmed: 32558367
doi: 10.1111/jcmm.15523
pmc: PMC7412683
doi:
Substances chimiques
Inflammasomes
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Reactive Oxygen Species
0
Toll-Like Receptor 6
0
Uric Acid
268B43MJ25
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8849-8861Informations de copyright
2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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