Document Detail


CYP2E1 enhances ethanol-induced lipid accumulation but impairs autophagy in HepG2 E47 cells.
MedLine Citation:
PMID:  20932821     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The regulation and function of autophagy and lipid metabolism have recently been reported to be reciprocally related. Macroautophagy mediates the breakdown of lipids stored in lipid droplets. An inhibition of autophagy leads to the development of a fatty liver. We evaluated the ability of CYP2E1 to modulate the effects of ethanol on lipid accumulation and autophagy in vitro. The E47 HepG2 cell which expresses CYP2E1 was treated with ethanol at 50, 100 and 150mM for 4 or 5days. Ethanol-induced lipid accumulation and an increase of triglycerides (TG) in E47 cells to a greater extent than in control C34 cells which do not express CYP2E1. In contrast, autophagy (LC3 II/LC3 I ratio) was significantly induced by ethanol in C34 cells to a greater extent than in E47 cells. P62 was significantly increased in E47 cells after ethanol treatment. Thus, there is a reciprocal relationship between the effects of ethanol on lipid accumulation and autophagy in the CYP2E1-expressing cells. Inhibition of autophagy by 3-methyladenine (3MA), increased lipid accumulation and TG levels in C34 cells which display elevated autophagy, but enhanced lipid accumulation and TG level to a lesser extent in E47 cells which displayed lower autophagy. Ethanol induced CYP2E1 activity and oxidative stress in E47 cells compared with C34 cells. These experiments suggest that the expression of CYP2E1 may impair autophagy formation which contributes to lipid accumulation in the liver. We hypothesize that CYP2E1-induced oxidative stress promotes the accumulation of lipid droplets by ethanol and this may be responsible for the suppression of autophagy in the liver.
Authors:
Defeng Wu; Xiaodong Wang; Richard Zhou; Arthur Cederbaum
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-12
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  402     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-03     Completed Date:  2010-12-08     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  116-22     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pharmacology & Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029,USA.
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MeSH Terms
Descriptor/Qualifier:
Autophagy*
Cytochrome P-450 CYP2E1 / metabolism*
Ethanol / pharmacology*
Fatty Liver / chemically induced*,  enzymology,  pathology
Hep G2 Cells
Humans
Lipid Metabolism / drug effects*
Liver / drug effects*,  enzymology,  pathology
Oxidative Stress
Grant Support
ID/Acronym/Agency:
AA017425/AA/NIAAA NIH HHS; AA018790/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
64-17-5/Ethanol; EC 1.14.14.1/Cytochrome P-450 CYP2E1
Comments/Corrections

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