果蝇的DHR96核受体结合胆固醇并调节胆固醇稳态。
The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis.
作者信息
Horner Michael A, Pardee Keith, Liu Suya, King-Jones Kirst, Lajoie Gilles, Edwards Aled, Krause Henry M, Thummel Carl S
机构信息
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
出版信息
Genes Dev. 2009 Dec 1;23(23):2711-6. doi: 10.1101/gad.1833609.
Abstract
Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-cholesterol diet. The cholesterol accumulation phenotype can be attributed to misregulation of npc1b, an ortholog of the mammalian Niemann-Pick C1-like 1 gene NPC1L1, which is essential for dietary cholesterol uptake. These studies define DHR96 as a central regulator of cholesterol homeostasis.
摘要
胆固醇稳态是维持正常细胞功能并避免高胆固醇血症有害影响所必需的。我们在此表明，果蝇DHR96核受体结合胆固醇，并且对于受胆固醇调节且参与胆固醇摄取、运输和储存的基因的协调转录反应是必需的。DHR96突变体在低胆固醇水平下生长时会死亡，而在高胆固醇饮食条件下饲养时会积累过量胆固醇。胆固醇积累表型可归因于npc1b的调控异常，npc1b是哺乳动物尼曼-皮克C1样1基因NPC1L1的直系同源基因，对膳食胆固醇摄取至关重要。这些研究将DHR96定义为胆固醇稳态的核心调节因子。
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Cell Metab. 2009 Dec;10(6):481-90. doi: 10.1016/j.cmet.2009.10.010.
2
Cholesterol homeostasis by the intestine: lessons from Niemann-Pick C1 Like 1 [NPC1L1).肠道的胆固醇稳态：来自尼曼-匹克C1样1蛋白（NPC1L1）的启示
Atheroscler Suppl. 2008 Sep;9(2):77-81. doi: 10.1016/j.atherosclerosissup.2008.05.008. Epub 2008 Jun 27.
3
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Cell Metab. 2008 Jun;7(6):508-19. doi: 10.1016/j.cmet.2008.04.001.
4
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Nat Rev Mol Cell Biol. 2008 Feb;9(2):125-38. doi: 10.1038/nrm2336.
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Development. 2007 Oct;134(20):3733-42. doi: 10.1242/dev.004572. Epub 2007 Sep 5.
6
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