Molecular basis for cell-type specific HDL generation by selective LXR modulators

点击翻译按钮获取中文摘要

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.