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Binge alcohol alters PNPLA3 levels in liver through epigenetic mechanism involving histone H3 acetylation.
- Source :
-
Alcohol (Fayetteville, N.Y.) [Alcohol] 2017 May; Vol. 60, pp. 77-82. Date of Electronic Publication: 2017 Mar 12. - Publication Year :
- 2017
-
Abstract
- The human PNPLA3 (patatin-like phospholipase domain-containing 3) gene codes for a protein which is highly expressed in adipose tissue and liver, and is implicated in lipid homeostasis. While PNPLA3 protein contains regions homologous to functional lipolytic proteins, the regulation of its tissue expression is reflective of lipogenic genes. A naturally occurring genetic variant of PNPLA3 in humans has been linked to increased susceptibility to alcoholic liver disease. We have examined the modulatory effect of alcohol on PNPLA3 protein and mRNA expression as well as the association of its gene promoter with acetylated histone H3K9 by chromatin immunoprecipitation (ChIP) assay in rat hepatocytes in vitro, and in vivo in mouse and rat models of acute binge, chronic, and chronic followed by acute binge ethanol administration. Protein expression of PNPLA3 was significantly increased by alcohol in all three models used. PNPLA3 mRNA also increased, albeit to a varying degree. ChIP assay using H3AcK9 antibody showed increased association with the promoter of PNPLA3 in hepatocytes and in mouse liver. This was less evident in rat livers in vivo except under chronic treatment. It is concluded for the first time that histone acetylation plays a role in the modulation of PNPLA3 levels in the liver exposed to binge ethanol both in vitro and in vivo.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Acetylation
Animals
Binge Drinking enzymology
Binge Drinking pathology
Cells, Cultured
Disease Models, Animal
Enzyme Induction
Liver enzymology
Liver pathology
Male
Membrane Proteins biosynthesis
Mice, Inbred C57BL
Phospholipases A2 biosynthesis
Phospholipases A2, Calcium-Independent biosynthesis
Promoter Regions, Genetic
Protein Processing, Post-Translational
RNA, Messenger biosynthesis
RNA, Messenger genetics
Rats, Sprague-Dawley
Binge Drinking genetics
Epigenesis, Genetic drug effects
Ethanol toxicity
Histones metabolism
Liver drug effects
Membrane Proteins genetics
Phospholipases A2 genetics
Phospholipases A2, Calcium-Independent genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6823
- Volume :
- 60
- Database :
- MEDLINE
- Journal :
- Alcohol (Fayetteville, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 28433418
- Full Text :
- https://doi.org/10.1016/j.alcohol.2017.01.009