Phospholipid Transfer Protein Is Regulated by Liver X Receptors in Vivo

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作者：

G Cao，TP Beyer，XP Yang，RJ Schmidt，Y Zhang，WR Bensch，RF Kauffman，H Gao，TP Ryan，Y Liang

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摘要：

Liver X receptors (LXR) belong to the nuclear receptor superfamily that can regulate important lipid metabolic pathways. The plasma phospholipid transfer protein (PLTP) is known to mediate transfer of phospholipids from triglyceride-rich lipoproteins to high density lipoprotein (HDL) and plays a critical role in HDL metabolism. We report here that a specific LXR agonist, T0901317, elevated HDL cholesterol and phospholipid in C57/BL6 mice and generated enlarged HDL particles that were enriched in cholesterol, ApoAI, ApoE, and phospholipid. The appearance of these HDL particles upon oral dosing of T0901317 in C57/BL6 mice was closely correlated with the increased plasma PLTP activity and liver PLTP mRNA levels. Nuclear run-on assay indicated that the effect of LXR agonist on PLTP expression was at the transcriptional level. In mouse peritoneal macrophage cells, PLTP expression was also up-regulated by the LXR/RXR (retinoid X receptor) heterodimer. However, cholesterol efflux in mouse peritoneal macrophage cells from PLTP-deficient mice (PLTP0) was not significantly different from wild type animals. Although in PLTP-deficient mice, the induction of HDL cholesterol as well as HDL particle size increase persisted, the extent of the induction was greatly attenuated. We conclude that is a direct target gene of LXRs and plays an important role in LXR agonist-mediated HDL cholesterol and size increase in mice.

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关键词：

hygrolidin cell cycle p21 V-ATPase tumor growth

DOI：

10.1074/jbc.M207187200

被引量：

711

年份：

2002