Differential Changes in MAP Kinases, Histone Modifications, and Liver Injury in Rats Acutely Treated With Ethanol

Aroor, Annayya R.; James, Taryn T.; Jackson, Daniel M.; Shukla, Shivendra D.

doi:10.1111/j.1530-0277.2010.01239.x

Cited by 50 publications

(47 citation statements)

References 40 publications

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“…This epigenetic change is associated with the increase of the histone acetyl-transferase activity and with the reduction of histone deacetylase (HDAC) 2 activity (7). In agreement with these observations, H3K9 acetylation has been observed in the liver after alcohol exposure (8). Meng et al have recently shown that epigenetic changes in hepatocytes regulate expression of certain micro-RNAs through methylation of CpG islands in their promoters (9).…”

supporting

confidence: 72%

Age-associated Change of C/EBP Family Proteins Causes Severe Liver Injury and Acceleration of Liver Proliferation after CCl4 Treatments

Hong

Lewis

Iakova

et al. 2014

Journal of Biological Chemistry

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Background: Older patients are more sensitive to drug-mediated development of liver disorders. Results: Age and CCl 4 treatments change expression of C/EBP proteins leading to repression of key regulators of liver biology. Conclusion:The age-associated alterations of C/EBP proteins cause severe liver injury after CCl 4 treatments. Significance: Understanding of mechanisms of age-associated severe liver injury is important for development of therapeutic approaches.

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supporting

confidence: 72%

Age-associated Change of C/EBP Family Proteins Causes Severe Liver Injury and Acceleration of Liver Proliferation after CCl4 Treatments

Hong

Lewis

Iakova

et al. 2014

Journal of Biological Chemistry

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“…We had reported previously that after an acute administration of ethanol histone H3 phosphorylation at Ser10 and Ser28 increased (Aroor et al, 2010). We have now determined the effect of different doses of ethanol on H3 phosphorylation at the 1-h time point.…”

Section: Ethanol Dose and Time Course Of Histone H3 Phosphorylationmentioning

confidence: 98%

“…We have reported that in vivo intraperitoneal acute ethanol promotes histone acetylation at Lys9 and phosphorylation at Ser10 and Ser28 (Aroor et al, 2010). We have now investigated the characteristics of histone H3 phosphorylation (Ser10, Ser28) and phosphoacetylation (K9S10) in vivo and examined their mechanistic relevance to gene expression.…”

Section: Introductionmentioning

confidence: 99%

Histone H3 Phosphorylation (Ser10, Ser28) and Phosphoacetylation (K9S10) Are Differentially Associated with Gene Expression in Liver of Rats Treated In Vivo with Acute Ethanol

James¹,

Aroor²,

Lim³

et al. 2011

J Pharmacol Exp Ther

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The epigenetic histone modification by ethanol is emerging as one of the mechanisms for its deleterious effects in the liver. In this context, we have investigated the role of histone H3 phosphorylation at Ser10 (P-H3-Ser10), and Ser28 (P-H3-Ser28) in liver after acute ethanol treatment in vivo. Ethanol was administered intraperitoneally in male Sprague-Dawley rats. Ethanol dose-response (1-5 g/kg body weight) and time-course (1-4 h) experiments were conducted, and various parameters were monitored. Steatosis and necrosis (serum alanine aminotransferase) of the liver increased in 4 h, suggesting liver injury. There were differences between P-H3-Ser10 and P-H3-Ser28 at 1 h, with the latter being more sensitive to lower ethanol doses. It was noteworthy that phosphorylation of both serines disappeared at the highest dose used (5 g/kg). We also examined phosphoacetylation of histone H3 at K9S10 and observed a dramatic increase. The changes in histone H3 phosphorylation and phosphoacetylation were also accompanied with expression of early response genes (c-fos, c-jun, mitogen-activated protein kinase phosphatase-1). Chromatin immunoprecipitation assays in samples from 1.5 and 4 h of ethanol administration indicated that increased histone H3 phosphorylation at Ser28 was associated with the promoters of c-jun and plasminogen activator inhibitor-1. In conclusion, this study demonstrates for the first time that in vivo exposure of liver to acute ethanol induced phosphorylation and phosphoacetylation of histone H3, and these modifications are differentially involved in the mRNA expression of genes.

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“…p38 MAPK is a multifunctional protein kinase and its biological role is both beneficial and harmful (Cuenda and Rousseau, 2007). The function of p38 MAPK in the liver has not been fully unveiled, but it was reported that p38 MAPK seemed to be involved in hepatotoxicity induced by some hepatotoxicants (Aroor et al, 2010;Zhang et al, 2010;Iida et al, 2009). In addition, inhibition of p38 MAPK is known to attenuate hepatic injury (Lv et al, 2012;Wang et al, 2009;Wu and Cederbaum, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Although the roles of p38 MAPK in the liver have not been completely clarified, some reports indicated that p38 MAPK is involved in hepatotoxicant-induced hepatotoxicity. For example, ethanol administration elicited rapid p38 MAPK activation before hepatic necrosis occurred (Aroor et al, 2010). Likewise, activated p38 MAPK was noted after administration of lipopolysaccharide/D-galactosamine (Zhang et al, 2010) or carbon tetrachloride (Iida et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Decreased hepatic phosphorylated p38 mitogen-activated protein kinase contributes to attenuation of thioacetamide-induced hepatic necrosis in diet-induced obese mice

et al. 2016

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-We previously reported that thioacetamide (TA)-induced hepatocellular necrosis was attenuated in mice fed a high-fat diet (HFD mice) compared with mice fed a normal rodent diet (ND mice). In this study, we investigated whether p38 mitogen-activated protein kinase (p38 MAPK) was involved in this attenuation. Western blot analysis revealed that hepatic phosphorylated p38 MAPK protein decreased at 8 and 24 hours (hr) after TA dosing in the HFD mice, while it decreased only at 24 hr in the ND mice in comparison to the time-and diet-matched, vehicle-treated mice. p38 MAPK regulates various biological functions including inflammation, therefore, hepatic metabolomics analysis focusing on pro-inflammatory lipid mediators was performed. At 24 hr after TA dosing, only one pro-inflammatory mediator, 12-hydroxyeicosatetraenoic acid (HETE), was higher in the HFD mice. On the other hand, in addition to 12-HETE, 15-HETE and 12-hydroxyeicosapentaenoic acid (HEPE) were higher and omega-3/ omega-6 polyunsaturated fatty acids ratios were lower in the ND mice at 24 hr. These results of metabolomics indicated that less pro-inflammatory state was seen in HFD mice than in ND mice at 24 hr. Finally, to confirm whether the observed decrease in phosphorylated p38 MAPK could attenuate TA-induced hepatocellular necrosis, we showed that SB203580 hydrochloride, an inhibitor of p38 MAPK, partially attenuated TA-induced hepatic necrosis in ND mice. Collectively, these results suggest that a prompt decrease in phosphorylation of p38 MAPK after TA administration is one of the factors that attenuate TAinduced hepatic necrosis in HFD mice.

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Differential Changes in MAP Kinases, Histone Modifications, and Liver Injury in Rats Acutely Treated With Ethanol

Cited by 50 publications

References 40 publications

Age-associated Change of C/EBP Family Proteins Causes Severe Liver Injury and Acceleration of Liver Proliferation after CCl4 Treatments

Age-associated Change of C/EBP Family Proteins Causes Severe Liver Injury and Acceleration of Liver Proliferation after CCl4 Treatments

Histone H3 Phosphorylation (Ser10, Ser28) and Phosphoacetylation (K9S10) Are Differentially Associated with Gene Expression in Liver of Rats Treated In Vivo with Acute Ethanol

Decreased hepatic phosphorylated p38 mitogen-activated protein kinase contributes to attenuation of thioacetamide-induced hepatic necrosis in diet-induced obese mice

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