Gene expression modifications in the liver caused by binge drinking and S-adenosylmethionine feeding. The role of epigenetic changes

Li, Jun; Bardag‐Gorce, Fawzia; Oliva, Joan; Dedes, Jennifer; French, Barbara A.; French, Samuel W.

doi:10.1007/s12263-009-0158-x

Cited by 23 publications

(20 citation statements)

References 10 publications

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“…As shown in Figure 5B, the SAM/SAH ratios negatively correlated with the expression levels of TGF-βR1 and TGF-βR2 ( p <0.05). This result corresponds with previous experimental studies [45], which suggest that our approach was feasible in examining the role of hypomethylation in regulating the expression of anti-inflammatory cytokines, and that DNA methylation status in cells can determine the functional status of TGF-β signaling [47]. Notably, the tissue expression of the two subunits of IL-35, IL-12a, and EBI3, were increased as the tissue SAM/SAH ratios were decreased ( p = 0.16 or 0.06).…”

Section: Resultssupporting

confidence: 93%

IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

Li¹,

Mai²,

Virtue³

et al. 2012

PLoS ONE

208

197

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Interleukin‐35 (IL‐35), a recently discovered heterodimeric cytokine with anti‐inflammatory/immunosuppressive properties, has a central role in limiting the immune response in various disease models including colitis, arthritis and asthma. However, it remains unknown whether IL‐35 is different from other anti‐inflammatory cytokines such as IL‐10 and transforming growth factor (TGF)‐β in terms of inhibition of inflammation initiation or suppression of full‐blown inflammation. In this study, we examined the tissue expression profiles and regulatory mechanisms of IL‐35 in comparison to other anti‐inflammatory cytokines. Our results suggest that in contrast to TGF‐β, IL‐35 is not constitutively expressed in human tissues but is inducible in response to inflammatory stimuli. We also provide structural evidence suggesting that AU‐rich element (ARE) binding proteins and microRNAs target IL‐35 subunit transcripts, which are responsible for quick degradation of IL‐35. Furthermore, we propose a new system to categorize anti‐inflammatory cytokines into two groups: (1) the housekeeping cytokines, such as TGF‐β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL‐35 suppress inflammation in full‐blown stage. Our in‐depth analysis of molecular events that regulate the production of IL‐35 and new categorization system of anti‐inflammatory cytokines are important for the design of new strategies of immune intervention. This work was partially supported by the National Institutes of Health Grants HL094451 and HL108910 (XFY), HL67033, HL82774 and HL77288 (HW).

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Section: Resultssupporting

confidence: 93%

IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

Li¹,

Mai²,

Virtue³

et al. 2012

PLoS ONE

208

197

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“…The livers used were from the previously published study (Li et al, 2009). Three or 4 rats per group were fed an acute bolus.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies showed that an acute bolus of alcohol consumption affects global gene expression (Li et al, 2009). 3h post ethanol bolus caused a marked change in gene expression compared to the 12h post bolus, and the genes that were affected differed.…”

Section: Introductionmentioning

confidence: 99%

“…In the blood alcohol level cycling model of ethanol metabolism during chronic ethanol intragastric feeding, it was shown that there were a large number of changes in gene expression at high blood ethanol levels (peak), when compared to low blood ethanol levels (trough) and to the controls (Bardag-Gorce et al, 2006, French et al, 2005). When SAMe was added to the diet with ethanol feeding, the blood alcohol levels were decreased and the up regulation of gene expression was down regulated (Li et al, 2009). The question, then, is: by what mechanism did SAMe affect the metabolism of ethanol in the acute alcohol bolus model.…”

Section: Introductionmentioning

confidence: 99%

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S-adenosylmethionine decreases the peak blood alcohol levels 3h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver

Bardag‐Gorce

Oliva

Wong

et al. 2010

Experimental and Molecular Pathology

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Introduction An alcohol bolus causes the blood alcohol level (BAL) to peak at 1-2 hours post ingestion. The ethanol elimination rate is regulated by alcohol metabolizing enzymes, primarily alcohol dehydrogenase (ADH1), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 (CYP2E1). Recently, S-adenosylmethionine (SAMe) was found to reduce acute BALs 3h after an alcohol bolus. The question, then, was: what is the mechanism involved in this reduction of BAL by feeding SAMe? To answer this question, we investigated the changes in ethanol metabolizing enzymes and the epigenetic changes that regulate the expression of these enzymes during acute binge drinking and chronic drinking. Methods Rats were fed a bolus of ethanol with or without SAMe, and were sacrificed at 3h or 12 h after the bolus. Results RT-PCR and Western blot analyses showed that SAMe significantly induced ADH1 levels in the 3h liver samples. However, SAMe did not affect the changes in ADH1 protein levels 12h post bolus. Since SAMe is a methyl donor, it was postulated that the ADH1 gene expression up regulation at 3h was due to a histone modification induced by methylation from methyl transferases. Dimethylated histone 3 lysine 4 (H3K4me2), a modification responsible for gene expression activation, was found to be significantly increased by SAMe at 3h post bolus. Conclusion These results correlated with the low BAL found at 3h post bolus, and support the concept that SAMe increased the gene expression to increase the elimination rate of ethanol in binge drinking by increasing H3K4me2.

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“…Moreover, ethanol was shown to promote transcription of dopamine β-hydroxylase (DBH) mRNA [13]. Later high bolus dose of ethanol (6g per kg of body weight) was shown to change the expression of 646 genes in rat liver cells at 3 hours after admission [22]. In general, ethanol may participate in hydrophobic interactions with amino acid residues due to the presence of CH3-CH2-group and in polar interactions due to the presence of -OH group.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico

Vladimirovich¹,

Khrustalev²,

Victorovich³

et al. 2013

AJMBR

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The influence of ethanol on enzymatic activities of muscle and liver pyruvate kinases has been studied in rats in series of in vivo and in vitro experiments accompanied by in silico study. Activity of muscle pyruvate kinase significantly decreased in experiments on acute alcohol intoxication (5.0g/kg of body weight), during chronic alcohol consumption (3.5g/kg of body weight 2 times a day for 14 and 28 days) and during the abstinence after the period of alcohol consumption (5.0g/kg of body weight 2 times a day for 5 days). Activity of liver pyruvate kinase was not decreased in rats after the period of alcohol consumption (5.0g/kg of body weight 2 times a day for 5 days) and during chronic alcohol consumption (3.5g/kg of body weight 2 times a day for 28 days). It even became significantly higher during the chronic alcohol consumption (3.5g/kg of body weight 2 times a day) lasting for 14 days. Inhibitory effect of alcohol bolus on activities of both pyruvate kinases should be linked with certain indirect mechanisms, since direct inhibitory effect was seen in vitro only after the addition of 500 mM ethanol to the rat muscle and liver supernatants. Since lactate dehydrogenase is used in a coupled assay for pyruvate kinase activity estimation we approved that 500mM ethanol did not inhibit lactate dehydrogenase activity in human plasma. Direct inhibition of pyruvate kinases activities should be due to the ability of ethanol to bind amino acid residues from the known allosteric site for alanine binding on muscle and liver pyruvate kinases shown by us with the help of molecular docking. Indirect activation of liver pyruvate kinase can be explained by the increase of glucose blood levels in rats during alcohol consumption promoting dephosphorylation of the enzyme as well as expression of the gene coding for it, and the decrease of alanine concentration in liver.

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Gene expression modifications in the liver caused by binge drinking and S-adenosylmethionine feeding. The role of epigenetic changes

Abstract: Chronic ethanol ingestion, achieved by feeding ethanol at a constant rate using intragastric

Cited by 23 publications

References 10 publications

IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines

S-adenosylmethionine decreases the peak blood alcohol levels 3h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico

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