title: Apolipoprotein A-1 binding protein promotes macrophage cholesterol efflux by facilitating apolipoprotein A-1 binding to ABCA1 and preventing ABCA1 degradation.
abstract: BACKGROUND
  Previous studies have shown that apolipoprotein-1 (apoA-1) binding protein (AIBP) is highly associated with the regulation of apoA-1 metabolism, suggesting its role in the treatment of atherosclerosis. However, how AIBP regulates foam cell formation remains largely unexplored.
  
  
  OBJECTIVE
  To investigate the mechanisms underlying AIBP inhibition of foam cell formation from macrophages.
  
  
  RESULTS
  THP-1-derived macrophages were incubated without or with apoA-1 and AIBP, followed by assessing the formation of foam cells and the potential mechanisms. Our results showed that AIBP and apoA-1 enhanced cholesterol efflux, altered the levels of cellular free cholesterol and cholesterol ester and prevented lipid accumulation so as to reduce the formation of foam cells. Meanwhile, lack of AIBP 115-123 amino acids resulted in the loss of AIBP binding to apoA-1. Moreover, our chemiluminescent analysis showed that AIBP promoted biotin-labeled apoA-1 binding to macrophages. Besides with AIBP, more apoA-1 bound to ABCA1, a key transporter responsible for cholesterol efflux to apoA-1, as indicated by our co-immunoprecipitation assay. Our results also showed that AIBP did not regulate ABCA1 mRNA expression, but stabilized its protein from CSN2-mediated degradation.
  
  
  CONCLUSIONS
  AIBP promotes apoA-1 binding to ABCA1 on the cell membrane of macrophages and prevents ABCA1 protein from CSN2-mediated degradation so as to prevent foam cell formation. AIBP 115-123 amino acids is at least partially responsible for its binding to apoA-1.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Xia
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Meng-Ya
authors.initials: MY
authors.lastname: Zeng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Cheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China.
authors.forename: Zhen-Wang
authors.initials: ZW
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan, 421001, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism; D001692:Biological Transport; D001710:Biotin / Q000737:chemistry; D000075686:COP9 Signalosome Complex; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005487:Foam Cells / Q000166:cytology; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; C402762:COPS2 protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D012097:Repressor Proteins; D001710:Biotin; D002784:Cholesterol; D000075686:COP9 Signalosome Complex
keywords: ABCA1; AIBP; ApoA-1; Atherosclerosis; CSN2; Cholesterol efflux; Foam cell; Ubiquitination