title: Alcohol exposure increases the expression of cardiac transcription factors through ERK1/2-mediated histone3 hyperacetylation in H9c2 cells.
abstract: Alcohol abuse during pregnancy may cause fetal cardiac developmental abnormalities. Our previous studies showed that alcohol could induce histone hyperacetylation and over-expression of cardiac transcription factors both in vivo and in vitro. The objective of the present study was to investigate the role of ERK1/2 signaling pathway in alcohol-induced histone hyperacetylation and up-regulation of cardiac transcription factors in H9c2 cells. The Cardiac cell line H9c2 was cultured with alcohol. U0126, a specific inhibitor of ERK1/2 pathway was employed to block the ERK1/2 signaling pathway. Western blotting analysis showed that alcohol significantly enhanced the levels of phosphorylated ERK1/2 and induced hyperacetylation of histone3, which were both effectively prevented with U0126. Real-time PCR showed that U0126 treatment significantly decreased alcohol-induced over-expression of GATA4 and MEF2c, and the basal expression level of GATA4, but did not affect MEF2c. ChIP assay showed that U0126 treatment significantly decreased alcohol-induced hyperacetylation of histone3 near the promoter regions of GATA4 and MEF2c. The basal acetylation level of histone3 near the promoter region of GATA4 was affected by U0126 as well, but not that near the promoter region of MEF2c. These data indicated that ERK1/2 signaling played an important role in mediating alcohol induced over-expression of GATA4 and MEF2c, which is possibly through the up-regulation of acetylation of histone3 near the gene promoters that affects the expression of GATA4 and MEF2c in H9c2 cells. ERK1/2 pathway might be a potential target for the intervention of alcohol induced congenital heart diseases.
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Wenqun
authors.initials: W
authors.lastname: Gao
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, PR China; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing, PR China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: Xupei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Division of Cardiovascular Diseases, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address: jietian@cqmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000209:etiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002070:Butadienes; D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D006657:Histones; D064326:MEF2 Transcription Factors; C578042:MEF2C protein, rat; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; C113580:U 0126; D000431:Ethanol
keywords: Alcohol; ERK1/2 signaling pathway; GATA4; Histone3 acetylation; MEF2c; U0126