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, Shu Qian Liu, Qingping Liu*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 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 (US)
Pages (from-to)461-468
Number of pages8
JournalAtherosclerosis
Volume234
Issue number2
DOIs
StatePublished - Jan 1 2014

Fingerprint

ATP-Binding Cassette Transporters
PPAR gamma
Macrophages
Cholesterol
Apolipoprotein A-I
7-ketocholesteryl-9-carboxynonanoate
Small Interfering RNA
Up-Regulation
Western Blotting
Enzyme-Linked Immunosorbent Assay
Ligands

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Chi, Yan ; Wang, Le ; Liu, Yuanyuan ; Ma, Yanhua ; Wang, Renjun ; Han, Xiaofei ; Qiao, Hui ; Lin, Jiabin ; Matsuura, Eiji ; Liu, Shu Qian ; Liu, Qingping. / 7-Ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages. In: Atherosclerosis. 2014 ; Vol. 234, No. 2. pp. 461-468.
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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.",
keywords = "7-Ketocholesteryl-9-carboxynonanoate, ABCA1, Cholesterol efflux, LXRα, PPARγ",
author = "Yan Chi and Le Wang and Yuanyuan Liu and Yanhua Ma and Renjun Wang and Xiaofei Han and Hui Qiao and Jiabin Lin and Eiji Matsuura and Liu, {Shu Qian} and Qingping Liu",
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7-Ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages. / Chi, Yan; Wang, Le; Liu, Yuanyuan; Ma, Yanhua; Wang, Renjun; Han, Xiaofei; Qiao, Hui; Lin, Jiabin; Matsuura, Eiji; Liu, Shu Qian; Liu, Qingping.

In: Atherosclerosis, Vol. 234, No. 2, 01.01.2014, p. 461-468.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 7-Ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages

AU - Chi, Yan

AU - Wang, Le

AU - Liu, Yuanyuan

AU - Ma, Yanhua

AU - Wang, Renjun

AU - Han, Xiaofei

AU - Qiao, Hui

AU - Lin, Jiabin

AU - Matsuura, Eiji

AU - Liu, Shu Qian

AU - Liu, Qingping

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - 7-Ketocholesteryl-9-carboxynonanoate

KW - ABCA1

KW - Cholesterol efflux

KW - LXRα

KW - PPARγ

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