Document Detail

Triglyceride accumulation in macrophages upregulates paraoxonase 2 (PON2) expression via ROS-mediated JNK/c-Jun signaling pathway activation.
MedLine Citation:
PMID:  23047827     Owner:  NLM     Status:  Publisher    
The aim of this study was to analyze the effect and mechanism of action of macrophage triglyceride accumulation on cellular PON2 expression. Incubation of J774A.1 (murine macrophages) with VLDL (0-75 μg protein/mL) significantly and dose-dependently increased cellular triglyceride mass, and reactive oxygen species (ROS) formation, by up to 3.3- or 1.8-fold, respectively. PON2 expression (mRNA, protein, activity) in cells treated with VLDL (50 μg protein/mL) was higher by 2- to 3-fold, as compared with control cells. Similar effects were noted upon using THP-1 (human macrophages). Incubation of macrophages with synthetic triglyceride or triglyceride fraction from carotid lesion resulted in similar effects, as shown for VLDL. Upon using specific inhibitors of MEK1/2 (UO126, 10 μM), p38 (SB203580, 10 μM), or JNK (SP600125, 20 μM), we demonstrated that MEK, as well as JNK, but not p38, are involved in VLDL-induced macrophage PON2 upregulation. VLDL activated JNK (but not ERK), which resulted in c-Jun phosphorylation. This signaling pathway is probably activated by ROS, since the antioxidant reduced glutathione (GSH), significantly decreased VLDL-induced macrophage ROS formation, c-Jun phosphorylation and PON2 overexpression. We conclude that macrophage triglyceride accumulation upregulates PON2 expression via MEK/ JNK/c-Jun pathway, and these effects could be related, at least in part, to cellular triglycerides-induced ROS formation. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Mira Rosenblat; Nina Volkova; Nicole Paland; Michael Aviram
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  BioFactors (Oxford, England)     Volume:  -     ISSN:  1872-8081     ISO Abbreviation:  Biofactors     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8807441     Medline TA:  Biofactors     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.
The Lipid Research Laboratory, Technion Faculty of Medicine, the Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel.
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