Nucleolin protects macrophages from oxLDL-induced foam cell formation through up-regulating ABCA1 expression.
Biochem Biophys Res Commun
; 486(2): 364-371, 2017 04 29.
Article
em En
| MEDLINE
| ID: mdl-28315324
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
RNA Mensageiro
/
Proteínas de Ligação a RNA
/
Aterosclerose
/
Transportador 1 de Cassete de Ligação de ATP
/
Hiperlipidemias
/
Lipoproteínas LDL
Tipo de estudo:
Etiology_studies
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article