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

Zhang, Xiaoying; Zhu, Zhaojin; Luo, Guanghua; Zheng, Lu; Nilsson-Ehle, Peter LU and Xu, Ning LU (2008) In Biochemical and Biophysical Research Communications 371(1). p.114-117
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
t0901317, apolipoprotein M, liver X receptor, 9-cis retinoic acid
in
Biochemical and Biophysical Research Communications
volume
371
issue
1
pages
114 - 117
publisher
Elsevier
external identifiers
  • wos:000255923900023
  • scopus:46349106551
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.04.017
language
English
LU publication?
yes
id
9c3b6c20-fc13-4d5b-99b0-c598ddb273aa (old id 1203534)
date added to LUP
2008-09-17 09:28:48
date last changed
2017-04-16 03:44:39
@article{9c3b6c20-fc13-4d5b-99b0-c598ddb273aa,
  abstract     = {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 &lt; 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 &lt; 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 &lt; 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.},
  author       = {Zhang, Xiaoying and Zhu, Zhaojin and Luo, Guanghua and Zheng, Lu and Nilsson-Ehle, Peter and Xu, Ning},
  issn         = {1090-2104},
  keyword      = {t0901317,apolipoprotein M,liver X receptor,9-cis retinoic acid},
  language     = {eng},
  number       = {1},
  pages        = {114--117},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Liver X receptor agonist downregulates hepatic apoM expression in vivo and in vitro},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2008.04.017},
  volume       = {371},
  year         = {2008},
}