Document Detail


Selective regulation of UGT1A1 and SREBP-1c mRNA expression by docosahexaenoic, eicosapentaenoic, and arachidonic acids.
MedLine Citation:
PMID:  20648548     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluated, in human cell line HepG2, the action of individual dietary polyunsaturated fatty acids (PUFAs) on the expression of several lipid metabolism genes. The effects of docosahexaenoic acid, 22:6, n-3 (DHA), eicosapentaenoic acid, 20:5, n-3 (EPA), and arachidonic acid, 20:4, n-6 (AA) were studied alone and with vitamin E (Vit.E). DHA, EPA, and AA down-regulated mRNAs and encoded proteins of stearoyl-CoA desaturase (SCD) and sterol regulatory element binding protein (SREBP-1c), two major factors involved in unsaturated fatty acids synthesis. DHA affected SREBP-1c mRNA less markedly than EPA and AA. Vit.E did not affect these products, both when individually added or together with fatty acids. The expression of UDP-glucuronosyl transferase 1A1 (UGT1A1) mRNA, an enzyme of phase II drug metabolism with relevant actions within lipid metabolism, resulted also differentially regulated. DHA did not essentially reduce UGT1A1 mRNA expression while EPA and AA produced a considerable decrease. Nevertheless, when these PUFAs were combined with Vit.E, which by itself did not produce any effect, the result was a reduction of UGT1A1 mRNA with DHA, an increase reverting to basal level with EPA and no variation with AA. Observed regulations did not result to be mediated by peroxisome proliferator-activated receptor (PPAR). Our data indicate that major dietary PUFAs and Vit.E are differentially and selectively able to affect the expression of genes involved in lipid metabolism. The different actions of these slightly different molecules could be associated with their physiological role as relevant nutrient molecules.
Authors:
Mariella Caputo; Hylde Zirpoli; Gaetano Torino; Mario Felice Tecce
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-10-27     Completed Date:  2010-12-06     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  187-93     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acid / pharmacology*
Cell Line, Tumor
Cell Survival
Docosahexaenoic Acids / pharmacology*
Dose-Response Relationship, Drug
Eicosapentaenoic Acid / pharmacology*
Gene Expression Regulation / drug effects
Glucuronosyltransferase / genetics,  metabolism*
Humans
PPAR alpha / genetics,  metabolism
RNA, Messenger / genetics,  metabolism
Stearoyl-CoA Desaturase / metabolism
Sterol Regulatory Element Binding Protein 1 / genetics,  metabolism*
Vitamin E / pharmacology*
Chemical
Reg. No./Substance:
0/PPAR alpha; 0/RNA, Messenger; 0/Sterol Regulatory Element Binding Protein 1; 1406-18-4/Vitamin E; 25167-62-8/Docosahexaenoic Acids; 27YG812J1I/Arachidonic Acid; AAN7QOV9EA/Eicosapentaenoic Acid; EC 1.14.19.1/Stearoyl-CoA Desaturase; EC 2.4.1.-/UGT1A1 enzyme; EC 2.4.1.17/Glucuronosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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