title: Alcohol Exposure Causes Overexpression of Heart Development-Related Genes by Affecting the Histone H3 Acetylation via BMP Signaling Pathway in Cardiomyoblast Cells.
abstract: Abusive alcohol utilization of pregnant woman may cause congenital heart disease (CHD) of fetus, where alcohol ignites histone H3 hyperacetylation leading to abnormal development of heart morphogenesis and associated genes. Knowledge about the regularized upstream genes is little, but bone morphogenetic protein (BMP) signaling may actively and prominently take part in alteration in acetylation of histone H3. The supreme objective of this study was to unearth the involvement of BMP signaling pathway in alcohol-driven hyperacetylation of histone H3 in cardiomyoblast cells.
  
  
  
  Cardiomyoblast cells (H9c2 cells) were addicted with alcohol (100 mM) for 24 hours. Dorsomorphin (5 μM) was used for the inhibition of BMP signaling pathway. We detected the phosphorylation activity of SMAD1/5/8, mRNA expression, histone acetyltransferases (HAT)/histone deacetylase (HDAC) activity, and acetylation of histone H3.
  
  
  
  Following alcohol exposure, phosphorylation of SMAD1/5/8 and HAT activities was increased to a significant extent, while histone H3 acetylation and expression of heart development-related genes were also increased. The said phenomenon influenced by alcohol was reverted upon dorsomorphin treatment to the cells without effecting HDAC activity.
  
  
  
  The data clearly identified that BMP-mediated histone H3 acetylation of heart development-related genes might be one of the possible cellular mechanisms to control alcohol-induced expression of heart development-related genes. Dorsomorphin, on the other hand, may modulate alcohol-induced hyperacetylation of histone H3 through BMP targeting, which could be a potential way to block CHD.
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.|Key Laboratory of Developmental Disease in Childhood, Ministry of Education, Chongqing Medical University, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.|Key Laboratory of Developmental Disease in Childhood, Ministry of Education, Chongqing Medical University, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Si
authors.affiliation: Key Laboratory of Developmental Disease in Childhood, Ministry of Education, Chongqing Medical University, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Developmental Disease in Childhood, Ministry of Education, Chongqing Medical University, Chongqing, China.|Key Laboratory of Pediatrics in Chongqing, Chongqing, China.|Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Lingjuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D006657:Histones; D000431:Ethanol
keywords: Alcohol; BMP Signaling Pathway; Dorsomorphin; Heart Development-Related Genes; Histone H3 Acetylation