title: Inhibition of histone acetylation by curcumin reduces alcohol-induced expression of heart development-related transcription factors in cardiac progenitor cells.
abstract: Alcohol exposure during pregnancy may cause congenital heart disease (CHD). In our previous studies, we found that alcohol selectively increased acetylation of histone H3 at lysine 9 (H3K9) and enhanced the expression of heart development-related genes in cardiac progenitor cells. The objective of this study is to investigate the protective effects of histone acetyltransferases (HATs) inhibitor, curcumin, on histone hyperacetylation and the over-expression of heart development genes induced by alcohol. Western blot analysis was employed to detect the acetylation levels of histone H3K9 and real-time PCR was applied to measure the expressions of heart development-related transcription factors, GATA4, Mef2c and Tbx5 (GMT). Our results showed that alcohol increased the acetylation of H3K9 by 2.76-fold (P<0.05) and significantly enhanced the expression of GATA4 and Mef2c (P<0.05). When cells were treated with alcohol plus 25 μM curcumin, the hyperacetylation of H3K9 and over-expression of GATA4 and Mef2c by alcohol was reversed. These data indicate that curcumin can correct the over-expression of cardiac genes by reversing the alcohol induced hyperacetylation of histone H3 at lysine 9 in cardiac progenitor cells, suggesting that curcumin is protective against alcohol-induced cardiac gene over-expression that may result in heart malformations.
authors: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
authors: Linyi
authors: L
authors: Wang
authors: Huichao
authors: H
authors: Sun
authors: Bo
authors: B
authors: Pan
authors: Jing
authors: J
authors: Zhu
authors: Guoying
authors: G
authors: Huang
authors: Xupei
authors: X
authors: Huang
authors: Jie
authors: J
authors: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D006657:Histones; D014157:Transcription Factors; D000431:Ethanol; D003474:Curcumin; D008239:Lysine