論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 38 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |