| Title |
Epigenetic histone modifications in a clinically relevant rat model of chronic ethanol-binge-mediated liver injury
|
|---|---|
| Published in |
Hepatology International, June 2014
|
| DOI | 10.1007/s12072-014-9546-4 |
| Pubmed ID | |
| Authors |
Annayya R. Aroor, Ricardo J. Restrepo, Kusum K. Kharbanda, Shivendra D. Shukla |
| Abstract |
Ethanol binge augments liver injury after chronic ethanol consumption in humans, but the mechanism behind the enhanced liver injury by ethanol binge is not known. In this study we used a clinically relevant rat model in which liver injury is amplified by binge after chronic ethanol treatment and investigated the importance of histone modifications. Eight-week-old Sprague-Dawley rats were fed ethanol in a liquid diet for 4 weeks. Control rats were fed an isocaloric liquid diet. This was followed by three binge administrations of ethanol (intragastric 5 g/kg body weight, 12 h apart). In the control, ethanol was replaced by water. Four hours after the last binge administration, liver samples were analyzed for histone modifications and parameters of liver injury. Chronic ethanol administration alone caused an increase in histone H3 ser10 and ser28 (H3S10 or S28) phosphorylation, and binge ethanol reduced their levels. Levels of dually modified phosphoacetylated histone H3 (H3AcK9/PS10) increased after acute binge ethanol and remained same after chronic ethanol binge. In contrast, histone H3 lysine-9 acetylation (H3AcK9) was not increased after chronic ethanol but increased significantly after acute binge and chronic ethanol binge. Increase in histone acetylation was accompanied by increased phospho-ERK1/2 in the nuclear extracts. Increased acetylation after chronic ethanol binge was also accompanied by increased protein levels of GCN5 histone acetyl transferase and a modest increase in HDAC3 in the nucleus. Histone lysine-9 dimethylation was significantly increased after chronic ethanol binge. Chronic ethanol binge also resulted in a decrease in the SAM:SAH ratio with a relative decrease of SAM levels and a corresponding increase in SAH levels. Ethanol binge after chronic ethanol altered the profile of site-specific histone modifications and may underlie the mechanism of augmented liver injury by chronic-ethanol-binge-treated rats. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 50% |
| France | 1 | 25% |
| India | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 18 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 28% |
| Student > Bachelor | 2 | 11% |
| Researcher | 2 | 11% |
| Student > Master | 2 | 11% |
| Lecturer | 1 | 6% |
| Other | 4 | 22% |
| Unknown | 2 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 22% |
| Agricultural and Biological Sciences | 3 | 17% |
| Biochemistry, Genetics and Molecular Biology | 3 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 11% |
| Social Sciences | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 4 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 35. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 July 2015.
All research outputs
#974,679
of 22,765,347 outputs
Outputs from Hepatology International
#8
of 521 outputs
Outputs of similar age
#10,427
of 228,282 outputs
Outputs of similar age from Hepatology International
#1
of 8 outputs
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So far Altmetric has tracked 521 research outputs from this source. They receive a mean Attention Score of 3.7. This one has done particularly well, scoring higher than 98% of its peers.
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