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Purified human paraoxonase-1 interacts with plasma membrane lipid rafts and mediates cholesterol efflux from macrophages.
MedLine Citation:
PMID:  22336243     Owner:  NLM     Status:  Publisher    
Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme thought to make a major contribution to the antioxidant and anti-inflammatory capacities of HDLs. However, the role of PON1 in the modulation of cholesterol efflux is poorly understood. The aim of our study was to investigate the involvement of PON1 in the regulation of cholesterol efflux, especially the mechanism by which it modulates HDL-mediated cholesterol transport. The enrichment of HDL(3) with human PON1 enhanced, in a dose-dependent manner, cholesterol efflux from THP-1 macrophage-like cells and ABCA1-enriched J774 macrophages. Moreover, an additive effect was observed when ABCA1-enriched J774 macrophages were incubated with both PON1 and apo-AI. Interestingly, PON1 alone was able to mediate cholesterol efflux from J774 macrophages and to upregulate ABCA1 expression on J774 macrophages. Immunofluorescence measurement showed an increase in PON1 levels in the cytoplasm of J774 macrophages overexpressing ABCA1. PON1 used an apo-AI-like mechanism to modulate cholesterol efflux from rapid and slow efflux pools derived from the lipid raft and nonraft domains of the plasma membrane, respectively. This was supported by the fact that ABCA1 protein was incrementally expressed by J774 macrophages within the first few hours of incubation with cholesterol-loaded J774 macrophages and that cyclodextrin significantly inhibited the capacity of PON1 to modulate cholesterol efflux from macrophages. This finding suggested that PON1 plays an important role in the antiatherogenic properties of HDLs and may exert its protective function outside the lipoprotein environment.
Hicham Berrougui; Soumaya Loued; Abdelouahed Khalil
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-1
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Research Center on Aging, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Canada QC J1H 4C4; Department of Medicine, Geriatrics Service, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Canada QC J1H 4C4.
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