Document Detail


Phospholipase A(2)-Modified Low-Density Lipoprotein Activates Liver X Receptor in Human Macrophages.
MedLine Citation:
PMID:  22367754     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Macrophages respond to cholesterol accumulation by increasing cholesterol efflux, which is mediated by activation of the nuclear liver X receptor (LXR) and ATP binding cassette (ABC) transporters. In the present study, we investigated whether foam cell formation induced by phospholipase A(2)-modified low-density lipoprotein (PLA-LDL) influences LXR activity and cholesterol efflux in primary human monocyte-derived macrophages (MDMs). Macrophages were treated with PLA-LDL and expression of the LXR target genes ABCA1 and ABCG1 was analyzed by quantitative PCR and western blot. PLA-LDL time-dependently up-regulated ABCA1 and ABCG1 mRNA and protein. Removal of non-esterified fatty acids from PLA-LDL particles did not influence the induction of ABC transporters. A role of LXR in PLA-LDL-stimulated ABCG1 expression was verified by LXR-knockdown and luciferase reporter assays using a construct containing a LXR response element from the ABCG1 gene. Functionally, cholesterol efflux to apolipoprotein A-I and high-density lipoprotein was higher in PLA-LDL treated cells compared to controls. Together, these results demonstrate that in primary human MDMs PLA-LDL induces ABC transporter expression via LXR activation. A concomitantly increased cholesterol efflux may prevent excessive cholesterol accumulation and thus, attenuate foam cell formation.
Authors:
Daniel Morbitzer; Dmitry Namgaladze; Bernhard Brüne
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-26
Journal Detail:
Title:  Cell biochemistry and biophysics     Volume:  -     ISSN:  1559-0283     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9701934     Medline TA:  Cell Biochem Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Faculty of Medicine, Institute of Biochemistry I/ZAFES, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
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