A liver X receptor and retinoid X receptor heterodimer mediates apolipoprotein E expression, secretion and cholesterol homeostasis in astrocytes

• DOI: 10.1111/j.1471-4159.2004.02183.x
• Publication Date: 2005-07-28T14:30:33Z
• Authors: Yu Liang; Suizhen Lin; Thomas P. Beyer; Youyan Zhang; Xin Wu; Kelly R. Bales; Ronald B. DeMattos; Patrick C. May; Shuyu Dan Li; Xian‐Cheng Jiang; Patrick I. Eacho; Guoqing Cao; Steven M. Paul
• Keywords: Liver X receptor; Retinoid X receptor; Apolipoprotein E

Abstract Apolipoprotein E (apoE) is an important protein involved in lipoprotein clearance and cholesterol redistribution. ApoE abundantly expressed astrocytes the brain closely linked to pathogenesis of Alzheimer's disease (AD). We report here that small molecule ligands activate either liver X receptors (LXR) or retinoid receptor (RXR) lead a dramatic increase apoE mRNA expression as well secretion human astrocytoma cell line (CCF‐STTG1 cells). Examination primary mouse also revealed significant induction mRNA, following incubation with LXR/RXR agonists. Moreover, treatment mice specific synthetic LXR agonist T0901317 resulted up‐regulation both hippocampus cerebral cortex, indicating can be up‐regulated by agonists vivo . Along ABCA1 transporter expression, these effectively mediate efflux CCF‐STTG1 cells presence absence apolipoprotein AI (apoAI). Our studies provide strong evidence synthesis homeostasis astrocytes. may have impact on multiple neurological diseases, including AD.