7-ketocholesteryl-9-carboxynonanoate induced nuclear factor-kappa B activation in J774A.1 macrophages.

Abstract

AIMS:

7-Ketocholesteryl-9-carboxynonanoate (oxLig-1), a lipid moiety of oxidized low-density lipoprotein (oxLDL), has been reported to be a crucial ligand of beta2-glycoprotein I (β(2)-GPI), and plays a potential role in the development of atherosclerosis (AS), however, the role of the sole oxLig-1 in the development of AS remains unclear.

MAIN METHODS:

Expression and phosphorylation levels of several proteins, such as nuclear factor-kappaB (NF-κB), protein kinase C (PKC), IκBα and inter-cellular adhesion molecule 1 (ICAM-1) were determined by Western blot; nuclear localization of NF-κB was studied by immunocytochemistry; NF-κB activation was assayed by electrophoretic mobility shift assay (EMSA); and expressions of genes associated with AS process were investigated by Mouse Atherosclerosis RT(2) Profiler PCR Array assay.

KEY FINDINGS:

The present work indicated that oxLig-1 induced IκBα phosphorylation and results in the nuclear translocation of NF-κB in J774A.1 macrophages. Moreover, oxLig-1-induced NF-κB DNA binding activity was detected by EMSA. Indeed, oxLig-1 led to the activation of PKC prior to activating NF-κB. The treatment of oxLig-1 in J774A.1 macrophages up-regulates the expression of NF-κB target genes including ICAM-1.

SIGNIFICANCE:

OxLig-1 on the oxLDL plays an important role in AS process, as evidenced by the NF-κB activation and up-regulation of genes involved in AS development in oxLig-1 challenged J774A.1 macrophages.

• Authors: Zhenyu Huang, Wenzhe Li, Renjun Wang, Fan Zhang, Yan Chi, Dan Wang, Zhe Liu, Yingbiao Zhang, Eiji Matsuura, Qingping Liu
• Journal: Life sciences (Life Sci) Vol. 87 Issue 19-22 Pg. 651-7 (Nov 20 2010) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 20932850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• 7-ketocholesteryl-9-carboxynonanoate
• Cholesterol Esters
• I-kappa B Proteins
• Lipoproteins, LDL
• NF-kappa B
• Nfkbia protein, mouse
• oxidized low density lipoprotein
• Intercellular Adhesion Molecule-1
• NF-KappaB Inhibitor alpha

Topics

• Animals
• Atherosclerosis (physiopathology)
• Blotting, Western
• Cell Line
• Cholesterol Esters (metabolism)
• I-kappa B Proteins (metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Lipoproteins, LDL (metabolism)
• Macrophages (metabolism)
• Mice
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Phosphorylation
• Polymerase Chain Reaction
• Up-Regulation