title: Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis.
abstract: BACKGROUND
  Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development.
  
  
  RESULTS
  Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells.
  
  
  CONCLUSIONS
  These findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy.
authors.affiliation: Department of Cardiology, Heart Centre, The Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Rold, Yu Zhong District, Chongqing, 400014, China.|Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China.|Chongqing Key Laboratory of Pediatrics, Chongqing, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Heart Centre, The Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Rold, Yu Zhong District, Chongqing, 400014, China.|Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.|China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China.|Chongqing Key Laboratory of Pediatrics, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Cardiology, Heart Centre, The Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Rold, Yu Zhong District, Chongqing, 400014, China.
authors.forename: Tiewei
authors.initials: T
authors.lastname: Lv
authors.affiliation: Department of Cardiology, Heart Centre, The Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Rold, Yu Zhong District, Chongqing, 400014, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA. xhuang@health.fau.edu.
authors.forename: Xupei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Heart Centre, The Children's Hospital of Chongqing Medical University, 136 Zhongshan Er Rold, Yu Zhong District, Chongqing, 400014, China. jietian@cqmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005333:Fetus / Q000196:embryology / Q000473:pathology; D006331:Heart Diseases / Q000188:drug therapy / Q000196:embryology / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy
chemical_list: D051017:Apoptosis Regulatory Proteins; D006657:Histones; D003474:Curcumin
keywords: Alcohol; Apoptosis; Caspase; Fetal cardiac development; Histone acetylation