title: ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells.
abstract: We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoAI, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene- 2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet. The detailed mechanism needs further investigation.
authors.affiliation: Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, PR China. ddm502@sohu.com
authors.forename: Dongmei
authors.initials: D
authors.lastname: Di
authors.forename: Zongchun
authors.initials: Z
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Guanghua
authors.initials: G
authors.lastname: Luo
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Shi
authors.forename: Maria
authors.initials: M
authors.lastname: Berggren-Söderlund
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson-Ehle
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics; D000075243:Apolipoproteins M; D001565:Benzoates / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008024:Ligands; D054834:Lipocalins / Q000096:biosynthesis* / Q000235:genetics; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D001565:Benzoates; D001596:Benzylamines; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D054834:Lipocalins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D047490:Retinoid X Receptor alpha; D013449:Sulfonamides; C577836:ABCA1 protein, human; C400523:APOM protein, human; C473027:GW 3965; C082631:NR5A2 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides