Inhibition of Histone H3K9 Acetylation by Anacardic Acid Can Correct the Over-Expression of Gata4 in the Hearts of Fetal Mice Exposed to Alcohol during Pregnancy

Abstract

BackgroundCardiovascular malformations can be caused by abnormalities in Gata4 expression during fetal development. In a previous study, we demonstrated that ethanol exposure could lead to histone hyperacetylation and Gata4 over-expression in fetal mouse hearts. However, the potential mechanisms of histone hyperacetylation and Gata4 over-expression induced by ethanol remain unclear.Methods and ResultsPregnant mice were gavaged with ethanol or saline. Fetal mouse hearts were collected for analysis. The results of ethanol fed groups showed that global HAT activity was unusually high in the hearts of fetal mice while global HDAC activity remained unchanged. Binding of P300, CBP, PCAF, SRC1, but not GCN5, were increased on the Gata4 promoter relative to the saline treated group. Increased acetylation of H3K9 and increased mRNA expression of Gata4, α-MHC, cTnT were observed in these hearts. Treatment with the pan-histone acetylase inhibitor, anacardic acid, reduced the binding of P300, PCAF to the Gata4 promoter and reversed H3K9 hyperacetylation in the presence of ethanol. Interestingly, anacardic acid attenuated over-expression of Gata4, α-MHC and cTnT in fetal mouse hearts exposed to ethanol.ConclusionsOur results suggest that P300 and PCAF may be critical regulatory factors that mediate Gata4 over-expression induced by ethanol exposure. Alternatively, P300, PCAF and Gata4 may coordinate over-expression of cardiac downstream genes in mouse hearts exposed to ethanol. Anacardic acid may thus protect against ethanol-induced Gata4, α-MHC, cTnT over-expression by inhibiting the binding of P300 and PCAF to the promoter region of these genes.

Pulsed glucocorticoids enhance dystrophic muscle performance through epigenetic-metabolic reprogramming

“…Because the H3K27ac patterns were strikingly different between pulsed prednisone-and daily prednisone-treated dystrophic muscle, we queried the role of histone acetylation in this response. The mdx mice were cotreated with the histone acetyltransferase (HAT) inhibitor anacardic acid (28). The mdx mice were treated for 4 weeks with anacardic acid (daily 5 mg/kg i.p.…”

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

“…11 In our previous studies, we demonstrated that alcohol consumption during pregnancy induces hyperacetylation of histone H3K9ac and causes overexpression of cardiomyogenesis genes. 12,13 However, the inhibition of histone H3K9ac hyperacetylation did not completely reverse heart malformation caused by alcohol consumption during pregnancy. Recently, we demonstrated that the interactive control of histone acetylation and methylation is critical for heart development.…”

Pharmacological properties of cashew (Anacardium occidentale)

“…In addition, a reduced acetylation in the promoter region of the GATA4 fetal hearts of mice was also reported. It was also observed that the abortion rates, stillbirths and intestinal timpanismos decreased in mice, thus demonstrating the cardio-protective activity of anacardic acid (Peng et al, 2014).…”