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The analysis of the mechanism of the anti-atherogenic action of polyphenol utilizing new evaluation technology

利用新评价技术分析多酚抗动脉粥样硬化作用机制

基本信息

批准号：
12660114
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

As the structure of the isoflavonoids is similar to that of estrogen and isoflavonoids has a estrogenic activity, the beneficial effects of dietary soy isoflavonoids on atherosclerosis, cancer, osteoporosis has been extensively reported. As it is reported that the serum level of the antiatherogenic factor, apolipoprotein A-I (ApoA-I) changes by hormone such as estrogen, isoflavonoids is expected to have its effects. There is few reports that the effects of isoflavonoids on the ApoA-I gene expression. Thus, in the present study, we investigate that the effects of soy isoflavonoids, genistein on the level of ApoA-I and its mRNA, the mechanism of genistein action on the ApoA-I gene expression. The secreted ApoA-I level is significantly increased by genistein compared to control in HepG2 cells. The mRNA level of ApoA-I is significantly increased by genistein compared to control in HepG2 cells. In estrogen receptor a tranfected HepG2 cells, the ApoA-I gene transcription is significantly increased by genistein compared to control. The transfection of both estrogen receptor α and the ApoA-I mutated promoter CAT plasmids (-264〜-191 deleted CAT plasmid and -80-40 deleted CAT plasmid) into HepG2 cells, the ApoA-I gene transcription is unchanged by genistein compared to control.We found for the first time that genistein increased ApoA-I and its mRNA levels, and transactivated the ApoA-I gene expression through estrogen receptor α and -264〜-191 and -80〜-40 in the ApoA-I gene promoter.

由于大豆黄酮的结构与雌激素的结构相似，且大豆黄酮具有雌激素活性，因此膳食大豆黄酮对动脉粥样硬化、癌症、骨质疏松症的有益作用已被广泛报道。据报道，抗动脉粥样硬化因子载脂蛋白A-I（ApoA-I）的血清水平会因雌激素等激素而发生变化，因此，预计雌二醇具有其作用。关于黄芪对ApoA-I基因表达的影响，国内外报道较少。因此，本研究探讨大豆异黄酮、染料木黄酮对ApoA-I及其mRNA水平的影响，探讨染料木黄酮对ApoA-I基因表达的作用机制。在HepG 2细胞中，与对照相比，染料木黄酮显著增加了分泌的ApoA-I水平。在HepG 2细胞中，与对照相比，染料木黄酮显著增加ApoA-I的mRNA水平。在雌激素受体a转染的HepG 2细胞中，与对照相比，染料木素显著增加ApoA-I基因转录。雌激素受体α和ApoA-I突变启动子CAT质粒的转染（-264-191缺失CAT质粒和-80-40缺失CAT质粒）转染HepG 2细胞后，与对照组相比，金雀异黄素对ApoA-I基因转录无影响。通过雌激素受体α和ApoA-I基因启动子区的-264-191和-80-40反式激活ApoA-I基因的表达。