JOURNAL ARTICLE

Ethanol and its metabolites induce histone lysine 9 acetylation and an alteration of the expression of heart development-related genes in cardiac progenitor cells

Lilin Zhong, Jing Zhu, Tiewei Lv, Guozhen Chen, Huichao Sun, Xuefang Yang, Xupei Huang, Jie Tian
Cardiovascular Toxicology 2010, 10 (4): 268-74
20811785
Alcohol exposure during pregnancy may cause congenital heart disease (CHD), but the underlying mechanisms are not clear. Recent evidence suggests that ethanol and its metabolites can selectively increase histone H3 acetylation at lysine 9 (H3AcK9) residue in rat hepatocytes. This may be a mechanism by which ethanol alters gene expression. The goal of current study is to investigate the effect of ethanol and its metabolites on H3AcK9 acetylation and the mRNA expression of heart development-related genes (GATA4, Mef2c, and Tbx5) in cardiac progenitor cells. We used mitochondrial activity (MTT) assay to assess the viability of cardiac progenitor cells. Western blotting and real-time PCR were employed to determine H3AcK9 acetylation and gene expression. Low levels of ethanol (50 mM), acetaldehyde (4 mM), and acetate (4 mM) had no effect on cell proliferation. However, high concentrations of ethanol (200 mM), acetaldehyde (12 mM), and acetate (16 mM) reduced cell viability by 30%, respectively (P < 0.05). Low levels of ethanol and acetate increased the acetylation of H3 lysine 9 by 2.4- and 2.2-fold, respectively (P < 0.05), but did not significantly change the expression of the heart development-related genes. High concentrations of ethanol and acetate increased H3 lysine 9 acetylation by 5.3- and 5.6-fold, respectively (P < 0.05). Moreover, high levels of ethanol and acetate significantly augmented the expression of GATA4 and Mef2c. Conversely, acetaldehyde (4 or 12 mM) had little effect on H3 lysine 9 acetylation or the expression of the heart development-related genes. Our studies demonstrate that high levels of ethanol or its metabolites induce H3AcK9 acetylation and impair cardiac progenitor cells. The altered histone H3 acetylation at lysine 9 has an important impact on the expression of the heart development-related genes, which may be one of the mechanisms underlying the alcohol-induced CHD.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
20811785
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"