ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells

Biochem Biophys Res Commun. 2012 Apr 27;421(1):152-6. doi: 10.1016/j.bbrc.2012.04.022. Epub 2012 Apr 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism*
  • Apolipoproteins / biosynthesis*
  • Apolipoproteins / genetics
  • Apolipoproteins M
  • Benzoates / pharmacology
  • Benzylamines / pharmacology
  • Hep G2 Cells
  • Humans
  • Hydrocarbons, Fluorinated / pharmacology
  • Ligands
  • Lipocalins / biosynthesis*
  • Lipocalins / genetics
  • Liver X Receptors
  • Orphan Nuclear Receptors / agonists
  • Orphan Nuclear Receptors / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Retinoid X Receptor alpha / metabolism*
  • Sulfonamides / pharmacology
  • Up-Regulation


  • ABCA1 protein, human
  • APOM protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Apolipoproteins
  • Apolipoproteins M
  • Benzoates
  • Benzylamines
  • GW 3965
  • Hydrocarbons, Fluorinated
  • Ligands
  • Lipocalins
  • Liver X Receptors
  • NR5A2 protein, human
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Retinoid X Receptor alpha
  • Sulfonamides
  • TO-901317
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid