Objective      To investigate whether (-)-epigallo-catechin-3-gallate (EGCG) could regulate the expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) by inhibiting histone deacetylase 1 (HDAC1) in aging mice hearts. Methods      A total of 24 16-month-old C57 BL/6 male aging mice were randomly divided into EGCG group [50 mg/(kg·d) EGCG]

DMSO group and untreated old group (n=8 for each group)

and another 8 3-month-old male mice were assigned as young group. The mice from the EGCG group and DMSO group were treated with EGCG and DMSO by intraperitoneal injection for 8 weeks

respectively. Then all the mice were sacrificed and the heart tissues were harvested from each group. RT-PCR was used to measure the mRNA expression level of Atp2a2 and HDAC1. Meanwhile

the protein level of SERCA2a was detected by Western blotting. The binding levels of HDAC1

acetylated lysine 9 on histone H3 (AcH3K9) and transcription factors GATA4 and Mef2c near the proximal promoter region of Atp2a2 gene were determined by ChIP-Q-PCR. Results      The results of RT-PCR and Western blotting showed a significant decrease of SERCA2a in the aging hearts at both mRNA and protein levels (P0.05)

but the expression of HDAC1 was increased at mRNA level in aging hearts (P0.05). ChIP-Q-PCR demonstrated that the amount of HDAC1 binding to proximal promoter region of Atp2a2 gene was significantly increased

but the binding levels of AcH3K9

GATA4 and Mef2c were reduced in aging hearts (P0.05). After intervention by EGCG for 8 weeks

there were decreases in the expression and binding amount of HDAC1

and rises in AcH3K9

GATA4 and Mef2c binding levels near the proximal promoter region of Atp2a2 gene in aging hearts. EGCG also increased the expression of Atp2a2 gene at both mRNA and protein levels in aging hearts (P0.05). Conclusion     Hypoacetylation of AcH3K9 mediated by HDAC1 may play a critical role in low expression of SERCA2a in aging hearts

and EGCG could inhibit the process and increase the expression of SERCA2a.