Browsing by Subject "Transcription factor FOXO3"

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    Inhibiting NLPR3 inflammasome by FOXO3-mediated activation of SIRT2 alleviates myocardial injury in rats
    (2026) Guligena Sawuer; Cheng Liang; Lu Lu; Gang Wu; Xinbin Wang; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Background. Myocardial ischemia/ reperfusion (MI/R) injury may cause serious arrhythmia and even sudden death. Sirtuin 2 (SIRT2) belongs to NAD (+) dependent class III histone deacetylase. The present study explored the potential mechanism of SIRT2 in MI/R injury. Methods. A rat model with MI/R injury was established. Differentially expressed genes in myocardial tissues of MI/R-treated rats and sham-operated rats were analyzed by microarray. The AAV9-encapsulated SIRT2 overexpression vector was injected into rats to evaluate the effect of SIRT2 on MI/R injury. Oxygen glucose deprivation/reoxygenation (OGD/R) treatment was used to simulate MI/R injury at a cellular level. SIRT2 over expression vector was transfected into cardiomyocytes. The expression of forkhead box O3 (FOXO3), a potential transcription factor predicted to bind to SIRT2, was detected in myocardial tissues of modeled rats and OGD/R-treated cardiomyocytes. The effect of FOXO3 on OGD/R-treated cardiomyocytes was confirmed by functional rescue experiments. The expressions of NLRP3 and caspase1 were detected. Results. SIRT2 was downregulated in myocardial tissues of MI/R-treated rats. Overexpression of SIRT2 alleviated MI/R injury in modeled rats and enhanced viability of OGD/R-treated cardiomyocytes. FOXO3 activated SIRT2 transcription and expression. FOXO3 was downregulated in the myocardial tissues of MI/R treated rats and OGD/R-treated cardiomyocytes. Knockdown of FOXO3 weakened the effects of SIRT2 on MI/R injury. SIRT2 reduced MI/R injury by inhibiting NLPR3/caspase1 inflammasome signaling. Conclusion. FOXO3 activates SIRT2 expression and inhibits NLPR3 inflammasome signaling pathway, thus alleviating MI/R injury. This study may offer a novel molecular target for the management of MI/R injury.