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Mechanism of action of new hypocholesterolemic pentapeptidei

新型降胆固醇五肽的作用机制

基本信息

批准号：
14560095
负责人：
NAGAOKA Satoshi
金额：
$ 2.3万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14560095/
关键词：
cholesterol β-lactoglobulin mouse CYP7A1 HMG-CoAreductase HepG2 bile acid milk 遺伝子コレステロール輸送担体

项目摘要

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.

一般来说，与植物蛋白相比，酪蛋白等动物蛋白被认为是导致动脉粥样硬化的原因。然而，我们发现作为动物蛋白的牛乳乳清蛋白及其主要成分蛋白β-乳球蛋白和β-乳球蛋白胰酶水解物比酪蛋白及其胰酶水解物降低血清胆固醇水平。此外，我们通过Caco-2细胞筛选和动物实验鉴定了从LTH中提取的新的降胆固醇多肽。这是包括IIAEK(Ile-Ile-Ala-Glu-Lys)在内的四种多肽。在这份报告中，我们研究了一种新的从(3-乳球蛋白)衍生的低胆固醇多肽IIAEK在体内和体外的作用。目前在小鼠体内的研究表明，IIAEK有降低肝脏胆固醇水平和胆固醇储备的趋势，并对肝脏的基因表达有影响。胆汁酸生物合成限速酶CyP7A1的表达显著下调，胆固醇生物合成限速酶或低密度脂蛋白受体HMG-CoA还原酶的表达也显著下调。然而，IIAEK显著上调了HepG2细胞中CYP7A1的mRNA水平。此外，荧光素酶活性测定显示，IIAEK可激活细胞色素P7A1基因转录。我们推测IIAEK加速了HepG2细胞中胆固醇的降解。