title: Tertiary-butylhydroquinone upregulates expression of ATP-binding cassette transporter A1 via nuclear factor E2-related factor 2/heme oxygenase-1 signaling in THP-1 macrophage-derived foam cells.
abstract: BACKGROUND
  Tert-butylhydroquinone (tBHQ), a synthetic phenolic antioxidant, is commonly used as a food preservative because of its potent antilipid peroxidation activity. Several lines of evidence have demonstrated that dietary supplementation with antioxidants has an antiatherogenic function through reducing cholesterol uptake or promoting reverse cholesterol transport. In this study, we investigated whether tBHQ affects expression of ATP-binding cassette transporter A1 (ABCA1) and the potential subsequent effect on cellular cholesterol homeostasis.
  
  
  RESULTS
  tBHQ increased ABCA1 protein levels and markedly enhanced cholesterol efflux from THP-1 macrophage-derived foam cells. Furthermore, tBHQ reduced calpain-mediated ABCA1 proteolysis via activation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Inhibition of HO-1 with a pharmacological inhibitor or siRNA and knockdown of Nrf2 suppressed the stimulatory effects of tBHQ on ABCA1 expression and calpain activity.
  
  
  CONCLUSIONS
  Nrf2/HO-1 signaling is required for the regulation by tBHQ of ABCA1 expression and cholesterol efflux in macrophage-derived foam cells and an antiatherogenic role of tBHQ is suggested.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Shi-Lin
authors.initials: SL
authors.lastname: Tang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhao
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ouyang
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Chen
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Yin
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis*; D000975:Antioxidants / Q000494:pharmacology*; D002154:Calpain; D045744:Cell Line, Tumor; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000975:Antioxidants; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C018855:2-tert-butylhydroquinone; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D002154:Calpain