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Liver X receptor agonist downregulates hepatic apoM expression in vivo and in vitro

In English

Författare

Summary, in English

It has been demonstrated that apolipoprotein M (apoM), a recently discovered HDL apolipoprotein, has antiatherosclerotic properties, which may be mediated by the enhancement of reversed cholesterol transportation and/or hepatic cholesterol catabolism. The detailed mechanisms are unknown yet. Liver X receptor (LXR) belongs to the nuclear receptor superfamily and is a ligand-activated transcription factor involved in the regulation of lipid metabolism and inflammation. Activation of LXR in the cell cultures results in an enhancement of cholesterol efflux to apoAl. In the present study, we investigated effects of the LXR agonist, T0901317 on hepatic apoM expression in vivo and in vitro. Serum apoM levels in mice given T0901317 at 10 mg or 100 mg/kg for 7 days were reduced by 12-17% (P < 0.05). In HepG2 cell cultures, apoM mRNA levels were significantly lower in presence of 25 mu M T0901317 (37.1%) than in control cells (P < 0.001). A similar reduction was found by the addition of 9-cis retinoic acid (RA). Twenty-five micromolar T0901317 together with 100 nM RA decreased apoM mRNA expression by 65% (P < 0.001). Thus, the LXR agonist T0901317 significantly downregulates apoM mRNA expression in vivo and in vitro, which indicates that apoM is another novel target gene regulated by the LXR. The combination of RA and T0901317 showed additive effects, which suggests that apoM expression can be modulated by LXR/RXR pathway.

Publiceringsår

2008

Språk

Engelska

Sidor

114-117

Publikation/Tidskrift/Serie

Biochemical and Biophysical Research Communications

Volym

371

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Biological Sciences

Nyckelord

  • t0901317
  • apolipoprotein M
  • liver X receptor
  • 9-cis retinoic acid

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1090-2104