Calayir Emine, Becker Tatjana M, Kratzer Adelheid, Ebner Birgit, Panzenböck Ute, Stefujl Jasminka, Kostner Gerhard M
Institute of Molecular Biology and Biochemistry, Ctr. for Molecular Medicine, Medical University of Graz, Austria.
Curr Pharm Biotechnol. 2008 Dec;9(6):516-21. doi: 10.2174/138920108786786376.
Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human intestinal Caco-2 cells in vitro. The expression of apoM was analyzed by quantitative real time PCR, and compared to well-established LXR target genes. Mice fed with TO901317 for six days showed a downregulation of apoM and apoAI in the liver to 40 % and 60 % respectively and an upregulation of Cyp7A1 to 280 %. In the small intestine, however, apoM and apoAI were upregulated by 30-60 % and ABCA1 by 250-430 %. In Caco-2 cells TO901317 caused a 60 % upregulation and the natural LXR agonist 22-hydroxycholesterol a 40 % upregulation of apoM. Possible causes for the differential effects in liver and intestine are discussed.
载脂蛋白M（apoM）被认为在胆固醇逆向转运中发挥作用。在此，我们研究了肝脏X受体（LXR）激动剂对apoM转录调控的影响。研究在小鼠肝脏和肠道黏膜细胞中进行了体内实验，并在人肠道Caco-2细胞中进行了体外实验。通过定量实时PCR分析apoM的表达，并与已明确的LXR靶基因进行比较。用TO901317喂养6天的小鼠肝脏中apoM和apoAI分别下调至40%和60%，而Cyp7A1上调至280%。然而，在小肠中，apoM和apoAI上调30 - 60%，ABCA1上调250 - 430%。在Caco-2细胞中，TO901317使apoM上调60%，天然LXR激动剂22-羟基胆固醇使apoM上调40%。本文讨论了肝脏和肠道中出现不同效应的可能原因。
