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Epigenetic effects of ethanol on the liver and gastrointestinal system.

Shukla SD, Lim RW - Alcohol Res (2013)

Bottom Line: The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs.Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses.Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver-GI axis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA.

ABSTRACT
The widening web of epigenetic regulatory mechanisms also encompasses ethanol-induced changes in the gastrointestinal (GI)-hepatic system. In the past few years, increasing evidence has firmly established that alcohol modifies several epigenetic parameters in the GI tract and liver. The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses. Furthermore, ethanol-induced fatty liver (i.e., steatohepatitis) and progression of liver cancer (i.e., hepatic carcinoma) may be consequences of the altered epigenetics. Modification of gene and/or protein expression via epigenetic changes also may contribute to the cross-talk among the GI tract and the liver as well as to systemic changes involving other organs. Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver-GI axis.

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Related in: MedlinePlus

Ethanol-induced epigenetic alterations and cross-organ talk through the gastrointestinal–liver axis.
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f3-arcr-35-1-47: Ethanol-induced epigenetic alterations and cross-organ talk through the gastrointestinal–liver axis.

Mentions: The response of the liver to ethanol and endotoxin is a complex process involving macrophage-like Kupffer cells, hepatocytes, and stellate cells. Alcohol’s effects on the activities of these cells may lead to liver injury and ultimately carcinoma. Ethanol causes epigenetic alterations in these cells that could result in changes in expression of genes associated with modified histones, including genes coding for various cytokines. Increases in the expression of these cytokines may occur in the liver, resulting in increased cytokine levels that then are circulated through the blood to other organs (e.g., heart or kidney) and in turn affect the functions of these organs. Thus, alcohol-induced epigenetic effects in the liver eventually may influence the cross-talk among these organs (see figure 3). This will be a fruitful topic for future studies to fully comprehend the role of ethanol-induced epigenetic alterations in the GI–hepatic system and its link to the responses of other organs.


Epigenetic effects of ethanol on the liver and gastrointestinal system.

Shukla SD, Lim RW - Alcohol Res (2013)

Ethanol-induced epigenetic alterations and cross-organ talk through the gastrointestinal–liver axis.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860425&req=5

f3-arcr-35-1-47: Ethanol-induced epigenetic alterations and cross-organ talk through the gastrointestinal–liver axis.
Mentions: The response of the liver to ethanol and endotoxin is a complex process involving macrophage-like Kupffer cells, hepatocytes, and stellate cells. Alcohol’s effects on the activities of these cells may lead to liver injury and ultimately carcinoma. Ethanol causes epigenetic alterations in these cells that could result in changes in expression of genes associated with modified histones, including genes coding for various cytokines. Increases in the expression of these cytokines may occur in the liver, resulting in increased cytokine levels that then are circulated through the blood to other organs (e.g., heart or kidney) and in turn affect the functions of these organs. Thus, alcohol-induced epigenetic effects in the liver eventually may influence the cross-talk among these organs (see figure 3). This will be a fruitful topic for future studies to fully comprehend the role of ethanol-induced epigenetic alterations in the GI–hepatic system and its link to the responses of other organs.

Bottom Line: The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs.Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses.Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver-GI axis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA.

ABSTRACT
The widening web of epigenetic regulatory mechanisms also encompasses ethanol-induced changes in the gastrointestinal (GI)-hepatic system. In the past few years, increasing evidence has firmly established that alcohol modifies several epigenetic parameters in the GI tract and liver. The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses. Furthermore, ethanol-induced fatty liver (i.e., steatohepatitis) and progression of liver cancer (i.e., hepatic carcinoma) may be consequences of the altered epigenetics. Modification of gene and/or protein expression via epigenetic changes also may contribute to the cross-talk among the GI tract and the liver as well as to systemic changes involving other organs. Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver-GI axis.

Show MeSH
Related in: MedlinePlus