Alcohol Exposure Causes Overexpression of Heart Development‐Related Genes by Affecting the Histone H3 Acetylation via BMP Signaling Pathway in Cardiomyoblast Cells. (24th November 2016) - Shi, Jin
Abstract : Background: 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. Methods: Cardiomyoblast cells (H9c2 cells) were addicted with alcohol (100 mM) for 24 hours. Dorsomorphin (5 μ M) 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. Results: 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. Conclusions: 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. Abstract : Following alcohol exposure, phosphorylation of SMAD1/5/8 and HATs activities was increased to a significant extent, while histone H3 acetylation and expression of heart development‐related genes were increased accordingly. The said phenomenon was reverted upon dorsomorphin (a specific inhibitor of BMP signaling) treatment. This identified that BMP‐mediated histone H3 acetylation might be one of the cellular mechanisms to control alcohol‐induced overexpression of heart development‐related genes. Dorsomorphin could be a potential way to block congenital heart disease through BMP targeting.