Document Detail


Cocoa flavanol metabolites activate HNF-3β, Sp1, and NFY-mediated transcription of apolipoprotein AI in human cells.
MedLine Citation:
PMID:  23293065     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
SCOPE: To identify the mechanisms by which cocoa induces HDL levels and since apolipoprotein AI (ApoAI) is the major protein in HDLs, we analyzed, upon incubation with cocoa metabolites, ApoAI mRNA levels, its transcriptional regulation, and the levels of the transcription factors involved in this process. METHODS AND RESULTS: Epicatechin and cocoa metabolites caused an increase in ApoAI expression in HepG2 cells. Electrophoretic mobility shift assays revealed the involvement of Sites A and B of the ApoAI promoter in the induction of ApoAI mRNA upon incubation with cocoa metabolites. Using supershift assays, we demonstrated the binding of HNF-3β, HNF-4, ER-α, and RXR-α to Site A and the binding of HNF-3β, NFY, and Sp1 to Site B. Luciferase assays performed with a construct containing Site B confirmed its role in the upregulation of ApoAI by cocoa metabolites. Incubation with 3-methyl-epicatechin led to an increase in HNF-3β mRNA, HNF-3β, ER-α, Sp1, and NFY protein levels and the activation of ApoAI transcription mediated by NFY, Sp1, and ER-α. CONCLUSION: The activation of ApoAI transcription through Site B by cocoa flavanol metabolites is mainly mediated by an increase in HNF-3β, with a significant contribution of Sp1 and NFY, as a mechanism for the protective role of these compounds in cardiovascular diseases.
Authors:
Carlota Oleaga; Carlos J Ciudad; Maria Izquierdo-Pulido; Véronique Noé
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  -     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Barcelona, Spain.
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