title: Zerumbone, A Natural Cyclic Sesquiterpene, Promotes ABCA1-Dependent Cholesterol Efflux from Human THP-1 Macrophages.
abstract: This study was conducted to explore the effect of zerumbone, isolated from Zingiberzerumbet Smith, on apolipoprotein A-I (apoA-I)-mediated cholesterol efflux from THP-1 macrophages. THP-1 macrophages were treated with different concentrations (10-100 μmol/l) of zerumbone and cholesterol efflux was measured. The involvement of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 and ERK1/2 signaling was checked. Notably, zerumbone caused a concentration-dependent induction of ABCA1 but not ABCG1, coupled with enhanced phosphorylation of ERK1/2. Pre-treatment with PD98059 (a potent ERK1/2 inhibitor) significantly blocked the upregulation of ABCA1 by zerumbone. Small interfering RNA-mediated downregulation of ABCA1 but not ABCG1 significantly impaired the promotion of apoA-I-mediated cholesterol efflux by zerumbone. Taken together, zerumbone has the capacity to facilitate apoA-I-mediated cholesterol efflux from macrophages through the activation of ERK1/2 signaling and upregulation of ABCA1.
authors.affiliation: Cadre Ward, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Shenshen
authors.initials: S
authors.lastname: Zhu
authors.forename: Jin-Hua
authors.initials: JH
authors.lastname: Liu
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D012333:RNA, Messenger; D012717:Sesquiterpenes; C403304:zerumbone; D002784:Cholesterol