Department of Cardiothoracic Surgery, Third Affiliated Hospital of Suzhou University, Changzhou 213003, P.R. China.
Lipids Health Dis. 2011 Nov 4;10:199. doi: 10.1186/1476-511X-10-199.
Apolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317.
Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO901317 together with guggulsterone at different concentrations for 24 hrs. The mRNA levels of ATP-binding cassette transporter A1 (ABCA1), apoA1, apoM, liver receptor homologue-1 (LRH-1) and short heterodimer partner 1 (SHP1) were determined by real-time RT-PCR.
When Caco-2 cell cultured with TO901317 alone, the mRNA levels of ABCA1, apoA1, apoM, LRH-1 and SHP1 were significantly increased with dose-dependent manners (p < 0.05), whereas when the cells cultured with guggulsterone alone, the mRNA levels of apoM, SHP1 and LRH-1 (p < 0.05) were strongly inhibited. Moreover, guggulsterone could abolish the TO901317 enhanced mRNA levels of apoA1 apoM, SHP1 and LRH-1.
The present study demonstrated that LXR agonist TO901317 induced apoM expression in Caco-2 cells might be mediated via the LXR/FXR pathway.
载脂蛋白 M (apoM) 可能具有潜在的抗动脉粥样硬化特性。据报道，apoM 的表达可以受到许多细胞内和细胞外因素的调节。在本研究中，我们进一步研究了肝 X 受体 (LXR) 激动剂 TO901317 刺激 Caco-2 细胞时 apoM 表达的调节。
将 Caco-2 细胞在不同浓度的 TO901317、法尼醇 X 受体 (FXR) 拮抗剂古卡斯特罗或 TO901317 与古卡斯特罗一起培养 24 小时。采用实时 RT-PCR 测定 ATP 结合盒转运蛋白 A1 (ABCA1)、载脂蛋白 A1 (apoA1)、载脂蛋白 M (apoM)、肝受体同系物-1 (LRH-1) 和短异二聚体伴侣 1 (SHP1) 的 mRNA 水平。
当 Caco-2 细胞单独用 TO901317 培养时，ABCA1、apoA1、apoM、LRH-1 和 SHP1 的 mRNA 水平呈剂量依赖性显著增加（p < 0.05），而当细胞单独用古卡斯特罗培养时，apoM、SHP1 和 LRH-1 的 mRNA 水平（p < 0.05）被强烈抑制。此外，古卡斯特罗可以消除 TO901317 增强的 apoA1、apoM、SHP1 和 LRH-1 的 mRNA 水平。
本研究表明，LXR 激动剂 TO901317 诱导 Caco-2 细胞 apoM 表达可能是通过 LXR/FXR 途径介导的。
