title: 7-ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages.
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.
  
  
  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.
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Renjun
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.affiliation: Biomedical Engineering Department, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3107, USA. Electronic address: sliu@northwestern.edu.
authors.forename: Shuqian
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Dalian, Liaoning 116622, China. Electronic address: qingpingliu40@126.com.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Liu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection
chemical_list: C457499:2-chloro-5-nitrobenzanilide; C510905:7-ketocholesteryl-9-carboxynonanoate; C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000813:Anilides; D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008024:Ligands; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma
keywords: 7-Ketocholesteryl-9-carboxynonanoate; ABCA1; Cholesterol efflux; LXRα; PPARγ