論文 - 詳細
| RRC ID | 1296 |
|---|---|
| 著者 | Suzuki S, Nishimaki-Mogami T, Tamehiro N, Inoue K, Arakawa R, Abe-Dohmae S, Tanaka AR, Ueda K, Yokoyama S. |
| タイトル | Verapamil increases the apolipoprotein-mediated release of cellular cholesterol by induction of ABCA1 expression via Liver X receptor-independent mechanism. |
| ジャーナル | Arterioscler Thromb Vasc Biol |
| Abstract |
OBJECTIVE:Release of cellular cholesterol and phospholipid mediated by helical apolipoprotein and ATP-binding cassette transporter (ABC) A1 is a major source of plasma HDL. We investigated the effect of calcium channel blockers on this reaction. METHODS AND RESULTS:Expression of ABCA1, apoA-I-mediated cellular lipid release, and HDL production were enhanced in cAMP analogue-treated RAW264 cells by verapamil, and similar effects were also observed with other calcium channel blockers. The verapamil treatment resulted in rapid increase in ABCA1 protein and its mRNA, but not the ABCG1 mRNA, another target gene product of the nuclear receptor liver X receptor (LXR). By using the cells transfected with a mouse ABCA1 promoter-luciferase construct (-1238 to +57bp), verapamil was shown to enhance the transcriptional activity. However, it did not increase transcription of LXR response element-driven luciferase vector. CONCLUSIONS:The data demonstrated that verapamil increases ABCA1 expression through LXR-independent mechanism and thereby increases apoA-I-mediated cellular lipid release and production of HDL. |
| 巻・号 | 24(3) |
| ページ | 519-25 |
| 公開日 | 2004-3-1 |
| DOI | 10.1161/01.ATV.0000117178.94087.ba |
| PII | 01.ATV.0000117178.94087.ba |
| PMID | 14726413 |
| MeSH | 2-Hydroxypropyl-beta-cyclodextrin ATP Binding Cassette Transporter 1 ATP Binding Cassette Transporter, Subfamily G, Member 1 ATP-Binding Cassette Transporters / biosynthesis* ATP-Binding Cassette Transporters / genetics Animals Apolipoprotein A-I / physiology Bucladesine / pharmacology Calcium Channel Blockers / chemistry Calcium Channel Blockers / pharmacology* Cell Line / drug effects Cell Line / metabolism Cholesterol / metabolism* DNA-Binding Proteins Gene Expression Regulation / drug effects Genes, Reporter Humans Hydroxycholesterols / pharmacology Lipoproteins / genetics Lipoproteins, HDL / biosynthesis Lipoproteins, HDL / genetics Liver X Receptors Lovastatin / analogs & derivatives* Lovastatin / pharmacology Macrophages / drug effects Macrophages / metabolism Mice Nicardipine / pharmacology Nifedipine / pharmacology Orphan Nuclear Receptors Phospholipids / metabolism RNA, Messenger / biosynthesis Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors Stereoisomerism Transfection Verapamil / chemistry Verapamil / pharmacology* beta-Cyclodextrins / pharmacology |
| IF | 6.604 |
| 引用数 | 40 |
| WOS 分野 | HEMATOLOGY PERIPHERAL VASCULAR DISEASE |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |