Curcumin Ameliorates The H3K9 Hyperacetylation And Heart Development-Related Genes Over-Expression Induced By Alcohol In Cardiac Progenitor Cells

BackgroundAlcohol exposure during pregnancy may cause congenital heart disease(CHD), however, the underlying mechanism is still not clear. In our preliminary research, we found that alcohol selectively increased acetylation of histone H3 at lysine 9 (H3K9) and augmented the expression of heart development- related genes in cardiac progenitor cells. This may be a mechanism by which the alcohol alters the gene expression in occurrence of CHD.ObjectiveTherefore, the objective of this study is to further explore the possible potential pathway by intervening the regulation of alcohol with curcumin, and to detect that whether curcumin ameliorates the H3K9 hyperacetylation and related genes over-expression induced by alcohol. Materials and MethodsCardiac progenitor cells were treated with alcohol at 200mM and curcumin was dissolved in the 200mM alcohol at 5,15,25μM, respectively. Mitochondrial activity (MTT) assay was used to assess the viability of cardiac progenitor cells. Western blot analysis was employed to detect the acetylation of histone H3K9 to select the effective concentration of curcumin. Real-time PCR was applied to measure the expressions of heart development-related genes GATA4, Mef2c and Tbx5.ResultsAlcohol at 200mM reduced cell viability by 28%; curcumin that was dissolved in 200mM alcohol respectively at 5,15,25,35μM reduced cell viability by 30%,33%,37%,52%;curcumin that was dissolved in DMSO at 25μM reduced cell viability by 26%. 200mM Alcohol group increased the acetylation of H3K9 by 2.76-fold(P<0.05) and significantly augmented the expression of GATA4 and Mef2c(P<0.05) compared to control group. 5μM,15μM,25μM curcumin group decrease 20%(P>0.05),43%(P<0.05), 63%(P<0.05)acetylation of H3K9 compared with alcohol group. 5, 15μM curcumin group increased the acetylation of H3K9 by 2.22- and 1.58-fold, respectively(P<0.05).There are no significant difference of the H3K9 acetylation and the expression of GATA4,Mef2c and Tbx5 at 25μM curcumin group compared to the control group(P>0.05).ConclusionsThese data indicated that: curcumin can ameliorate the hyeracetylation of histone H3 at lysine 9 and the over-expression of heart development- related genes induced by alcohol in the cardiac progenitor cells, which may be one of the pathogenesis that alcohol leads to CHD.