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首页> 外文会议>World Association for Laser Therapy >Agonists of Orphan Nuclear Receptors:Relationships between Induction ofApo E Synthesis in Cultured Cells andHDL Levels in Animal Models
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Agonists of Orphan Nuclear Receptors:Relationships between Induction ofApo E Synthesis in Cultured Cells andHDL Levels in Animal Models

机译：孤儿核受体的激动剂：动物模型中培养细胞和HDL水平的诱导eAPO e合成之间的关系

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摘要

ApoE is a well conserved protein throughout species and synthesized by most tissues including liver and macrophages. By affecting lipoprotein metabolism and cholesterol turnover in mammals, ApoE plays an important role in tissue and total body cholesterol homeostasis. The pharmaceutical modulation of ApoE synthesis and secretion has not been investigated thoroughly as potential target for the treatment of atherosclerosis. It has been shown recently that the orphan nuclear receptor LXRa regulates the transcription of the ApoE gene and of other genes involved in lipogenesis and HDL metabolism (i.e. SREBP-lc, lipoprotein lipase, CETP).. The close analogue of LXRa, FXR, has also been shown to up regulate PLTP and ApoCII which are involved in plasma HDL metabolism. For these reasons, we investigated the activity of selective synthetic agonists of LXRa (TO901317) and FXR (GW4064) on ApoE mRNA expression in monocyte-macrophage (THP-1) and in hepatocytes (HepG2). Both the LXRa and FXR agonists increased ApoE mRNA and protein secretion in liver cells, whereas in macrophages only the LXRa agonist was found to be active.
机译：Apoe在整个物种中是一种良好的蛋白质，并且由大多数组织合成，包括肝脏和巨噬细胞。通过影响哺乳动物的脂蛋白代谢和胆固醇周转，Apoe在组织和全身胆固醇稳态中起重要作用。 ApoE合成和分泌的药物调制尚未彻底研究作为治疗动脉粥样硬化的潜在靶标。最近已经表明，孤儿核受体LXRA调节APOE基因的转录和参与脂肪生成的其他基因和HDL代谢（即Srebp-LC，脂蛋白脂肪酶，CETP）.. LXRA，FXR的紧密类似物，具有还被证明调节调节PLTP和APOCII，其参与血浆HDL代谢。由于这些原因，我们研究了在单核细胞 - 巨噬细胞（THP-1）和肝细胞（HepG2）中的Apoe mRNA表达上LXRA（TO901317）和FXR（GW4064）的选择性合成激动剂的活性。 LXRA和FXR激动剂均增加肝细胞中的ApoE mRNA和蛋白质分泌，而在巨噬细胞中，发现LXRA激动剂被发现活性。

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