Identification, exhaustive analysis, clarification of action mechanism and efficient modification of novel hypolipidemic peptides

我们利用含有胆固醇转运体、肠道ABCA1基因启动子的荧光素酶质粒，阐明了Caco-2细胞中乳抑素抑制肠道胆固醇吸收的分子机制。我们的研究结果表明PPAR/LXR响应元件与Caco-2细胞中乳抑素对胆固醇吸收的抑制有关。研究了一种具有降胆固醇作用的油蛋白，通过肽阵列的详尽分析，阐明了其诱导降胆固醇作用的活性序列。我们发现了两个新的胆汁酸结合肽。与胆汁酸结合肽VAWWMY作为阳性对照相比，两种新型胆汁酸结合肽在体外对胆固醇胶束溶解度有更大的抑制作用。我们发现，在HepG2细胞中，来自大豆β -conglycin α prime亚基的QEK与对照组相比，CYP7A1 mRNA水平显著升高。

We used the luciferase plasmid containing the cholesterol transporter, intestinal ABCA1 gene promoter to clarify the molecular mechanism of the inhibition of intestinal cholesterol absorption by lactostatin in Caco-2 cells. Our results suggested that PPAR/LXR responsive element related to the suppression of cholesterol absorption by lactostatin in Caco-2 cells. An oleosin having a hypocholesterolemic action was investigated to clarify the active sequence of its induced a hypocholesterolemic action by an exhaustive analysis using a peptide array. We found two novel bile acid binding peptides. Two novel bile acid binding peptides exhibited the greater inhibition of micellar solubility of cholesterol in vitro compared with a bile acid binding peptide VAWWMY as a positive control. We found that QEK derived from soybean beta-conglycinin alpha prime subunit exhibited the significant increase in CYP7A1 mRNA levels compared to the control group in HepG2 cells.