Ethanol and Its Metabolites Induce Histone Lysine 9 Acetylation and an Alteration of the Expression of Heart Development-Related Genes in Cardiac Progenitor Cells

Zhong, Ling; Zhu, Jing; Lv, Tiewei; Chen, Guozhen; Sun, Huichao; Yang, Xiyan; Huang, Xupei; Tian, Jie

doi:10.1007/s12012-010-9081-z

Cited by 46 publications

(36 citation statements)

References 25 publications

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“…The cells were divided into five groups: alcohol; curcumin; alcohol + curcumin; DMSO; and control. From our previous studies [14, 18], we found that 200 mM alcohol was an effective concentration resulting in hyperacetylation of cardiac progenitor cells, and 25 μM curcumin could completely reversed the hyperacetylation induced by alcohol (200 mM). So we used 200 mM alcohol and 25 μM curcumin (SIGMA, USA) to intervene our cells for 24 h.…”

Section: Methodsmentioning

confidence: 99%

“…Acetylation of histone generated by histone acetyltransferases (HATs) can neutralize the positive charges between histone and DNA allowing the binding of transcription factors to DNA, and consequently advances gene transcription [13, 14]. In addition, studies have also revealed that alcohol exposure can lead to hyperacetylation of histone H3K9 [15–17], an event believed to be associated with abnormal heart development [14, 18–21]. H3K9 plays a critical role in cell cycle progression and apoptosis [22, 23].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis

Yan

Pan

et al. 2017

J Biomed Sci

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BackgroundPrenatal 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.Methods and resultsQ-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.ConclusionsThese 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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis

Yan

Pan

et al. 2017

J Biomed Sci

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“…Both genetics and epigenetics play a part in regulating the expression of Gata4 and alterations that lead to uncontrolled expression of Gata4 could affect normal development of the heart. We have demonstrated that high consumption of alcohol or its metabolites can induce histone hyperacetylation that leads to over-expression of Gata4 [12], [13]. However, it is not clear whether alcohol exposure increases myocardial histone acetylation or Gata4 over-expression in developing hearts.…”

Section: Introductionmentioning

confidence: 93%

Inhibition of Histone H3K9 Acetylation by Anacardic Acid Can Correct the Over-Expression of Gata4 in the Hearts of Fetal Mice Exposed to Alcohol during Pregnancy

et al. 2014

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BackgroundCardiovascular malformations can be caused by abnormalities in Gata4 expression during fetal development. In a previous study, we demonstrated that ethanol exposure could lead to histone hyperacetylation and Gata4 over-expression in fetal mouse hearts. However, the potential mechanisms of histone hyperacetylation and Gata4 over-expression induced by ethanol remain unclear.Methods and ResultsPregnant mice were gavaged with ethanol or saline. Fetal mouse hearts were collected for analysis. The results of ethanol fed groups showed that global HAT activity was unusually high in the hearts of fetal mice while global HDAC activity remained unchanged. Binding of P300, CBP, PCAF, SRC1, but not GCN5, were increased on the Gata4 promoter relative to the saline treated group. Increased acetylation of H3K9 and increased mRNA expression of Gata4, α-MHC, cTnT were observed in these hearts. Treatment with the pan-histone acetylase inhibitor, anacardic acid, reduced the binding of P300, PCAF to the Gata4 promoter and reversed H3K9 hyperacetylation in the presence of ethanol. Interestingly, anacardic acid attenuated over-expression of Gata4, α-MHC and cTnT in fetal mouse hearts exposed to ethanol.ConclusionsOur results suggest that P300 and PCAF may be critical regulatory factors that mediate Gata4 over-expression induced by ethanol exposure. Alternatively, P300, PCAF and Gata4 may coordinate over-expression of cardiac downstream genes in mouse hearts exposed to ethanol. Anacardic acid may thus protect against ethanol-induced Gata4, α-MHC, cTnT over-expression by inhibiting the binding of P300 and PCAF to the promoter region of these genes.

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“…Under ethanol exposure, it was found that heart development was significantly affected, and H3 acetylation ensued. The effect was dose dependent, leading to greater gene expression changes in higher ethanol doses (Zhong et al, 2010). In fetal neuronal stem cell neurospheres, ethanol was observed to remove histone methylation marks from promoters (either H3K4me3 and H3K27me3, or both) across 20 candidate genes playing roles in processes such as the regulation of neural stem cell biology, and neural patterning (Veazey et al, 2013).…”

Section: Fetal Alcohol Exposure Causes Epigenetic Changes Critical Tomentioning

confidence: 99%

Fetal alcohol spectrum disorders and their transmission through genetic and epigenetic mechanisms

Mead

Sarkar

2014

Front. Genet.

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Fetal alcohol spectrum disorders (FASD) are a group of related conditions that arise from prenatal exposure to maternal consumption of the teratogen, ethanol. It has been estimated that roughly 1% of children in the US suffer from FASD (Sampson etal., 1997), though in some world populations, such as inhabitants of some poorer regions of South Africa, the rate can climb to as high as 20% (May etal., 2013). FASD are the largest cause of mental retardation in U.S. neonates, and ironically, are entirely preventable. FASD have been linked to major changes in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in lifelong impairments through mental disorders, retardation, and sensitivity to stress. FASD are linked to an impaired immune system which consequently leads to an elevated risk of cancer and other diseases. FASD arise from a complex interplay of genetic and epigenetic factors. Here, we review current literature on the topic to tease apart what is known in these areas particularly emphasizing HPA axis dysfunction and how this ties into new studies of transgenerational inheritance in FASD.

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Ethanol and Its Metabolites Induce Histone Lysine 9 Acetylation and an Alteration of the Expression of Heart Development-Related Genes in Cardiac Progenitor Cells

Cited by 46 publications

References 25 publications

Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis

Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis

Inhibition of Histone H3K9 Acetylation by Anacardic Acid Can Correct the Over-Expression of Gata4 in the Hearts of Fetal Mice Exposed to Alcohol during Pregnancy

Fetal alcohol spectrum disorders and their transmission through genetic and epigenetic mechanisms

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