Objective      To determine the effect of Sirt4 on the activity of GATA-binding protein 4 (GATA4) in neonatal rat cardiomyocytes.       Methods      The AdEasy Vector kit was used to construct an adenoviral vector expressing Sirt4 (Ad-Sirt4) and an adenoviral vector for knockdown of Sirt4 (AdshSirt4). Neonatal rat cardiomyocytes were cultured in DMEM supplemented with 10% FBS

and then infected with the recombinant adenoviruses respectively for 24 h. After that

cardiomyocytes were treated with PBS or 1 μmol/L angiotensin Ⅱ (AngⅡ) for 48 h. The expression of GATA4 at mRNA and protein levels was detected by Real-time PCR and Western blotting respectively. Immunofluorescence assay and nucleus isolation kit were used to examine the nuclear transport of GATA4. The promoter activities of GATA4 downstream molecules

atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)

were detected by dual-luciferase reporter gene assay.       Results      Sirt4 had no effect on the protein and mRNA levels of GATA4 in neonatal rat cardiomyocytes (P0.05). Compared with the control

Sirt4 overexpression significantly increased AngⅡ-induced GATA4 phosphorylation

whereas Sirt4 knockdown reduced the phosphorylation of GATA4. Sirt4 knockdown dramatically inhibited AngⅡ-induced nuclear transport of GATA4. Sirt4 overexpression markedly increased the promoter activities of GATA4 downstream molecules (ANP and BNP

P0.01).       Conclusion      Sirt4 is able to promote AngⅡ-induced GATA4 activation in neonatal rat cardiomyocytes.