Liver X receptor agonist downregulates hepatic apoM expression in vivo and in vitro.
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 apoAI. 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 microM 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.
Zhang
Xiaoying
X
Comprehensive Laboratory, The Third Affiliated Hospital of Suzhou University, Changzhou 213003, China.
Zhu
Zhaojin
Z
Luo
Guanghua
G
Zheng
Lu
L
Nilsson-Ehle
Peter
P
Xu
Ning
N
D000818:Animals; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000075243:Apolipoproteins M; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000819:agonists*; D015536:Down-Regulation; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013449:Sulfonamides / Q000008:administration & dosage*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D001053:Apolipoproteins; D001055:Apolipoproteins B; D000075243:Apolipoproteins M; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D000960:Hypolipidemic Agents; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C501623:ApoM protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides