Nucleolin protects macrophages from oxLDL-induced foam cell formation through up-regulating ABCA1 expression

Autor: Yanjuan Liu, Xuanyou Liu, Qinglan Lv, Meidong Liu, Xianzhong Xiao, Pengfei Liang, Yuting Tang, Yuanbin Li, Bimei Jiang, Zhongyi Tong
Rok vydání: 2017
Předmět:
0301 basic medicine
CD36 Antigens
Male
CD36
RNA Stability
Biophysics
Hyperlipidemias
Diet
High-Fat
Biochemistry
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Mice
Apolipoproteins E
Gene expression
Oil Red O
Animals
RNA
Messenger
Scavenger receptor
Molecular Biology
Foam cell
ATP Binding Cassette Transporter
Subfamily G
Member 1
Mice
Knockout
biology
Dose-Response Relationship
Drug
Macrophages
RNA-Binding Proteins
Scavenger Receptors
Class A
Biological Transport
Cell Differentiation
Cell Biology
Scavenger Receptors
Class B
Atherosclerosis
Phosphoproteins
Molecular biology
Lipoproteins
LDL
030104 developmental biology
Cholesterol
chemistry
ABCG1
Gene Expression Regulation
ABCA1
biology.protein
lipids (amino acids
peptides
and proteins)
Nucleolin
ATP Binding Cassette Transporter 1
Foam Cells
Signal Transduction
Zdroj: Biochemical and biophysical research communications. 486(2)
ISSN: 1090-2104
Popis: Our recent studies have indicated that nucleolin, as a multifunctional RNA-binding protein, exerts protective effects in the myocardial cells and endothelial cells under the condition of oxidative stress. However, the function of nucleolin and its potential mechanism in macrophage-derived foam cell formation remain largely unexplored. ApoE-/- mice were fed with a high-fat diet (HFD) for 10-24 weeks. Protein expression was measured by western blotting or immunofluorescence, and gene expression at the mRNA level was detected by qRT-PCR. The level of lipid in macrophages was examined by Oil Red O staining, high-performance liquid chromatography (HPLC) and NBD-cholesterol. Actinomycin D (Act D) was used to determine the stability of ABCA1 mRNA in macrophages. The interaction of nucleolin with ABCA1 mRNA was assessed using co-immunoprecipitation (co-IP). The aortas advanced plaques demonstrated significantly lower levels of nucleolin protein compared with early plaques in ApoE-/- mice, in which the macrophage foam cells occupied main body. Nucleolin expression at the mRNA and protein levels in RAW264.7 macrophages was significantly reduced by oxidized low-density lipoprotein (oxLDL) in a dose- and time-dependent manner. Furthermore, nucleolin overexpression markedly attenuated lipid accumulation in oxLDL-challenged macrophages through increasing cholesterol efflux. In addition, nucleolin overexpression significantly increased the expression of ATP-binding cassette transporter A1 (ABCA1) at the mRNA and protein levels without affecting expressions of scavenger receptors (SR)-A, SR-B1, CD36 and ATP-binding cassette transporter G1 (ABCG1) at the mRNA level. Moreover, nucleolin overexpression increased the stability of ABCA1 mRNA in macrophages, whereas nucleolin ablation abrogated the oxLDL-induced up-regulation of ABCA1. The up-regulation of ABCA1 by nucleolin resulted from its protein-RNA interaction. Our data suggested that nucleolin inhibited foam cell formation through enhancing stability of ABCA1 mRNA and subsequently increasing cholesterol efflux.
Databáze: OpenAIRE
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