Aldehyde dehydrogenase 2 inhibited oxidized LDL-induced NLRP3 inflammasome priming and activation via attenuating oxidative stress.
Biochem Biophys Res Commun
; 529(4): 998-1004, 2020 09 03.
Article
em En
| MEDLINE
| ID: mdl-32819611
ABSTRACT
Oxidized low-density lipoprotein (ox-LDL)-mediated NLRP3 inflammasome activation is crucial in atherosclerosis (AS) initiation and progression. Aldehyde dehydrogenase 2 (ALDH2) has been reported to display protective effects during AS development; however, the underlying mechanisms are largely unknown. Here we investigate the role of ALDH2 in ox-LDL-induced NLRP3 inflammasome priming and activation. We treated RAW264.7 murine macrophages with ox-LDL with or without ALDH2 activator Alda-1 and measured NLRP3 inflammasome priming and activation, ALDH2 protein expression and enzyme activity, IL-1ß release, and DNA damage. It was found that ox-LDL impaired ALDH2 activity and induced NLRP3 inflammasome priming and activation. Alda-1 inhibited both of the priming and activation steps of NLRP3 inflammasome as well as subsequent cell pyroptosis and attenuated ROS and 4-HNE levels in ox-LDL-treated macrophages. Taken together, ALDH2 activation inhibits priming and activation of NLRP3 inflammasome via reducing oxidative stress, which suggests that ALDH2 may be a potential target for anti-inflammatory therapies in AS treatment.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Benzodioxóis
/
Inflamassomos
/
Aldeído-Desidrogenase Mitocondrial
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
/
Lipoproteínas LDL
/
Anti-Inflamatórios
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article