RRC ID |
43453
|
著者 |
Nishimaki-Mogami T, Tamehiro N, Sato Y, Okuhira K, Sai K, Kagechika H, Shudo K, Abe-Dohmae S, Yokoyama S, Ohno Y, Inoue K, Sawada J.
|
タイトル |
The RXR agonists PA024 and HX630 have different abilities to activate LXR/RXR and to induce ABCA1 expression in macrophage cell lines.
|
ジャーナル |
Biochem Pharmacol
|
Abstract |
Release of cellular cholesterol by ATP-binding cassette transporter (ABC)A1 and apolipoproteins is a major source of plasma high-density lipoprotein (HDL). Expression of ABC transporter A1 (ABCA1) is directly stimulated by liver X receptor (LXR)/retinoid X receptor (RXR) activation. We evaluated the abilities of two RXR agonists, PA024 and HX630, to increase ABCA1 expression. In differentiated THP-1 cells, the two agonists efficiently enhanced ABCA1 mRNA expression and apoA-I-dependent cellular cholesterol release. However, in RAW264 cells and undifferentiated THP-1 cells, PA024 was highly effective while HX630 was inactive in increasing ABCA1 mRNA. In parallel, the two agonists had different abilities to activate ABCA1 promoter in an LXR-responsive-element (LXRE)-dependent manner and to directly stimulate LXRalpha/RXR transactivation. The ability of HX630 to enhance ABCA1 expression was correlated closely with the cellular PPARgamma mRNA level. Moreover, HX630 was able to activate PPARgamma/RXR. Transfection of PPARgamma in RAW264 cells induced HX630-mediated activation of LXRE-dependent transcription and ABCA1 promoter, suggesting the ability of HX630 to activate PPARgamma-LXR-ABCA1 pathway. We conclude that RXR agonist PA024 and HX630 have different abilities to activate LXR/RXR, and that the cell-type-dependent effect of HX630 on ABCA1 expression and HDL generation is closely associated with this defect.
|
巻・号 |
76(8)
|
ページ |
1006-13
|
公開日 |
2008-10-15
|
DOI |
10.1016/j.bcp.2008.08.005
|
PII |
S0006-2952(08)00534-0
|
PMID |
18761326
|
MeSH |
ATP Binding Cassette Transporter 1
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters / drug effects
ATP-Binding Cassette Transporters / genetics*
ATP-Binding Cassette Transporters / metabolism
ATP-Binding Cassette Transporters / physiology
Animals
Cell Differentiation / drug effects
Cell Line
DNA-Binding Proteins / physiology*
Humans
Liver X Receptors
Macrophages / cytology
Macrophages / drug effects
Macrophages / physiology*
Mice
Monocytes / drug effects
Monocytes / physiology*
Orphan Nuclear Receptors
PPAR gamma / genetics
PPAR gamma / physiology
RNA, Messenger / genetics
RNA, Ribosomal, 18S / genetics
Receptors, Cytoplasmic and Nuclear / physiology*
Receptors, Retinoic Acid / agonists
Receptors, Retinoic Acid / physiology*
Tetradecanoylphorbol Acetate / pharmacology
Transfection
|
IF |
4.96
|
引用数 |
30
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |