Acetylation of FOXO1 activates Bim expression involved in CVB3 induced cardiomyocyte apoptosis.
Apoptosis
; 29(7-8): 1271-1287, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38127284
ABSTRACT
Viral myocarditis (VMC) is the major reason for sudden cardiac death among both children and young adults. Of these, coxsackievirus B3 (CVB3) is the most common causative agent of myocarditis. Recently, the role of signaling pathways in the pathogenesis of VMC has been evaluated in several studies, which has provided a new perspective on identifying potential therapeutic targets for this hitherto incurable disease. In the present study, in vivo and in vitro experiments showed that CVB3 infection leads to increased Bim expression and triggers apoptosis. In addition, by knocking down Bim using RNAi, we further confirmed the biological function of Bim in apoptosis induced by CVB3 infection. We additionally found that Bim and forkhead box O1 class (FOXO1) inhibition significantly increased the viability of CVB3-infected cells while blocking viral replication and viral release. Moreover, CVB3-induced Bim expression was directly dependent on FOXO1 acetylation, which is catalyzed by the co-regulation of CBP and SirTs. Furthermore, the acetylation of FOXO1 was an important step in Bim activation and apoptosis induced by CVB3 infection. The findings of this study suggest that CVB3 infection induces apoptosis through the FOXO1 acetylation-Bim pathway, thus providing new insights for developing potential therapeutic targets for enteroviral myocarditis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Enterovirus Humano B
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Infecções por Coxsackievirus
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Miócitos Cardíacos
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Proteína 11 Semelhante a Bcl-2
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Proteína Forkhead Box O1
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Miocardite
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article