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蛋白的荧光素酶载体--肠道ABCA1基因启动子，阐明了乳抑素抑制Caco-2细胞对肠道胆固醇吸收的分子机制。我们的结果提示PPAR/LXR反应元件与Lactostatin抑制Caco-2细胞胆固醇吸收有关。对一种具有降胆固醇作用的油球蛋白进行了研究，通过使用多肽阵列进行详尽的分析，阐明了其诱导的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。与胆汁酸结合多肽VAWWMY作为阳性对照相比，两个新的胆汁酸结合多肽在体外对胆固醇的胶束溶解性具有更大的抑制作用。我们发现，在HepG2细胞中，来自大豆β-伴球蛋白α基质亚单位的QEK显示出明显高于对照组的CYP7A1 mRNA水平。

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.