Mechanism of action of new hypocholesterolemic pentapeptidei

通常，与植物蛋白相比，被称为酪蛋白等的动物蛋白被认为是导致动脉粥样硬化的原因。然而，我们已经表明，与酪蛋白及其胰蛋白酶水解物相比，牛乳乳清蛋白是动物蛋白，其主要成分蛋白质β-乳球蛋白和β-乳球蛋白胰蛋白酶水解物（LTH）降低血清胆固醇水平。此外，我们确定了新的降胆固醇肽来源于LTH筛选使用Caco-2细胞和动物实验。这是包括IIAEK（Ile-Ile-Ala-Glu-Lys）在内的四种肽。在这份报告中，我们研究了一种新的降胆固醇肽IIAEK衍生自β-乳球蛋白在体内或体外的行动。目前在小鼠中的研究表明，IIAEK倾向于降低肝脏胆固醇水平和胆固醇池，并且对肝脏中的基因表达有影响。被称为胆汁酸生物合成的限速酶的CYP 7A 1的表达显著下调，并且被称为胆固醇生物合成的限速酶或LDL受体的HMG CoA还原酶的表达也下调。IIAEK能显著提高HepG 2细胞中CYP 7A 1 mRNA的表达水平。此外，IIAEK激活HepG 2细胞中的CYP 7A 1基因转录通过荧光素酶测定。我们推测，IIAEK加速胆固醇降解HepG 2细胞。

Generally, animal proteins known as casein and else are considered to cause atherosclerosis in comparison with vegetable proteins. However, we have shown bovine milk whey protein which is animal protein and its major constituent protein β-lactoglobulin and β-lactoglobulin tryptic hydrolysate (LTH) reduce the serum cholesterol level compared with casein and its tryptic hydrolysate. Moreover, we identified the novel hypocholesterolemic peptides derived from LTH by screening using Caco-2 cells and animal studies. These are four kinds of peptides including IIAEK (Ile-Ile-Ala-Glu-Lys). In this report, we investigate the actions of a novel hypocholesterolemic peptide IIAEK derived from (3 -lactoglobulin in vivo or in vitro. The present study in mice suggests that IIAEK tends to decrease liver cholesterol level and cholesterol pool, and has influence to gene expression in liver The expression of the CYP7A1 known as rate-limiting enzyme of bile acids biosynthesis is dramatically down-regulated And expression of the HMG-CoA reductase known as rate-limiting enzyme of cholesterol biosynthesis or LDL-receptor is also down-regulated However, CYP7A1 mRNA level was significantly increased by IIAEK in HepG2 cells. Moreover, IIAEK activated CYP7A1 gene transcription measured by luciferase assay in HepG2 cells. We speculate that IIAEK accelerates cholesterol degradation in HepG2 cells.