2010 Fiscal Year Final Research Report
Molecular basis for cell-type specific HDL generation by selective LXR modulators
| Project/Area Number |
20590116
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
MOGAMI Tomoko National Institute of Health Sciences, 機能生化学部, 室長 (90174333)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 核内受容体 / LXR / HDL / 選択的モジュレーター / ABCA1 / PPARγ / RXR |
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| Research Abstract |
Nuclear receptor LXR stimulates HDL-generating ABC transporter A1 (ABCA1) expression. However, because LXR also enhances lipogenesis, cell-type or gene-selective LXR modulates may be promising strategies. We previously identified Riccardin C as a LXRα agonist/LXRβ antagonist that functions as a cell-type selective modulator. In this study, we investigated molecular basis of selective LXR/RXR modulators and showed the followings. Helix 3-7 of LXRα and Ala327 in this region play critical roles in Riccardin C-induced LXRα transactivation. The RXR agonists PA024, HX630, and tributyltin have different abilities to activate LXR/RXR, resulting in cell-type specific inductions of ABCA1 expression and HDL generation.
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[Journal Article] The RXR agonists PA024 and HX630 have different abilities to activate LXR/RXR and to induce ABCA1 expression in macrophage cell lines.2008
Author(s)
Nishimaki-Mogami T, Tamehiro N, Sato Y, Okuhira K, Sai K, Kagechika H, Shudo K, Abe-Dohmae S, Yokoyama S, Inoue K, Sawada J
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Journal Title
Biochem Pharmacol 76
Pages: 1006-1013
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