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.

journal_name

Life Sci

journal_title

Life sciences

authors

Huang Z,Li W,Wang R,Zhang F,Chi Y,Wang D,Liu Z,Zhang Y,Matsuura E,Liu Q

doi

10.1016/j.lfs.2010.09.028

subject

Has Abstract

pub_date

2010-11-20 00:00:00

pages

651-7

issue

19-22

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(10)00416-9

journal_volume

87

pub_type

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