7-Ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages

Yan Chi, Le Wang, Yuanyuan Liu, Yanhua Ma, Renjun Wang, Xiaofei Han, Hui Qiao, Jiabin Lin, Eiji Matsuura, Shuqian Liu, Qingping Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: ATP binding cassette transporter A1 (ABCA1) is a member of the ATP-binding cassette transporter family. It plays an essential role in mediating the efflux of excess cholesterol. It is known that peroxisome proliferator-activated receptor gamma (PPARγ) promoted ABCA1 expression. We previously found 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) upregulated ABCA1 partially through CD36 mediated signals. In the present study, we intended to test if PPARγ signally is involved in the upregulation mediated by oxLig-1. Methods and results: First, we docked oxLig-1 and the ligand-binding domain (LBD) of PPARγ by using AutoDock 3.05 and subsequently confirmed the binding by ELISA assay. Western blotting analyses showed that oxLig-1 induces liver X receptor alpha (LXRα), PPARγ and consequently ABCA1 expression. Furthermore, oxLig-1 significantly enhanced ApoA-I-mediated cholesterol efflux. Pretreatment with an inhibitor for PPARγ (GW9662) or/and LXRα (GGPP) attenuated oxLig-1-induced ABCA1 expression. Under PPARγ knockdown by using PPARγ-shRNA, oxLig-1-induced ABCA1 expression and cholesterol efflux in THP-1 macrophages was blocked by 62% and 25% respectively. Conclusions: These observations suggest that oxLig-1 is a novel PPARγ agonist, promoting ApoA-I-mediated cholesterol efflux from THP-1 macrophages by increasing ABCA1 expression via induction of PPARγ.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalAtherosclerosis
Volume234
Issue number2
DOIs
Publication statusPublished - Jun 2014

Keywords

  • 7-Ketocholesteryl-9-carboxynonanoate
  • ABCA1
  • Cholesterol efflux
  • LXRα
  • PPARγ

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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