权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

High density lipoprotein receptor gene, its structure and expression.

高密度脂蛋白受体基因、其结构和表达。

基本信息

批准号：
09671087
负责人：
MATSUMOTO Akiyo
金额：
$ 1.92万
依托单位：
National Institute of Health and Nutrition
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671087/
关键词：
HDL HDL receptor HB2 reverse cholesterol transport antiatherogenic

项目摘要

High density lipoprotein (HDL), an antiatherogenic lipoprotein comprises several subclasses differing in composition and metabolic function. This physiological complexity appears to be matched with the growing number of candidate HDL receptors, since several HDL binding proteins have recently been identified in various tissues. It is important to identify their structure and potential role in HDL metabolism. We have cloned a candidate HDL receptor, HB2, which is one of a pair of HDL binding proteins (HBl and HB2) first purified from rat liver. To elucidate the regulation and function of HB2, we studied the effect of cytokines, bile acids and fat-soluble vitamins, which are known to affect gene expression, on the HB2 expression. HB_2, minimally present in monocytic THP-1 cells, is substantially upregulated in phorbol ester (PMA)-differentiated macrophages and appears sensitive to cholesterol loading of these cells. Although Insulin and IGF-1 did not influence HB2 expression, some cytokines, TNF-alpha, IL-6 and M-CSF, strongly reduced expression of HB2 in THP-1 cells. It is known that bile acids up-regulate expression of genes related to cholesterol metabolism. Taurocholate and chenodeoxycholate also increased HB2 expression significantly.- Retinol and 1,25-vitamin D_3 did not change HB2 expression, however, 25-vitamin D_3 increased HB2 mRNA in THP-1 cells. alpha-Tocopherol significantly reduced HB2 mRNA expression in PMA-differentiated THP- 1 macrophages.To elucidate whether an l-IMG-CoA reductase inhibitor affects mRNA levels of HB2 expression, we investigated the effect of simvastatin in rabbits. After three weeks administration of simvastatin, cholesterol contents in liver and lung were decreased. Simvastatin treatment significantly reduced the levels of HB2 mRNA in the liver and lung of rabbits Suppression of HB2 may also be antiatherogenic ; therefore it is an another feature of HMG-CoA reductase inhibitors.

高密度脂蛋白（HDL）是一种抗动脉粥样硬化的脂蛋白，包括在组成和代谢功能上不同的几个亚类。这种生理复杂性似乎与候选HDL受体数量的增加相匹配，因为最近在各种组织中发现了几种HDL结合蛋白。确定它们的结构及其在高密度脂蛋白代谢中的潜在作用是很重要的。我们克隆了一个候选的HDL受体HB2，它是第一次从大鼠肝脏中纯化的一对HDL结合蛋白（hb1和HB2）中的一个。为了阐明HB2的调控和功能，我们研究了已知影响基因表达的细胞因子、胆汁酸和脂溶性维生素对HB2表达的影响。HB_2在单核THP-1细胞中极少存在，但在phorbol ester （PMA）分化的巨噬细胞中显著上调，并对这些细胞的胆固醇负荷敏感。虽然胰岛素和IGF-1不影响HB2的表达，但一些细胞因子，tnf - α， IL-6和M-CSF，在THP-1细胞中强烈降低HB2的表达。已知胆汁酸上调胆固醇代谢相关基因的表达。牛磺胆酸盐和鹅去氧胆酸盐也显著增加HB2的表达。-视黄醇和1,25-维生素D_3不改变HB2的表达，但25-维生素D_3增加了THP-1细胞中HB2 mRNA的表达。-生育酚可显著降低pma分化的THP- 1巨噬细胞中HB2 mRNA的表达。为了阐明l-IMG-CoA还原酶抑制剂是否影响HB2 mRNA表达水平，我们研究了辛伐他汀对家兔的影响。服用辛伐他汀3周后，肝脏和肺部胆固醇含量降低。辛伐他汀治疗显著降低家兔肝脏和肺中HB2 mRNA水平，抑制HB2也可能具有抗动脉粥样硬化作用；因此它是HMG-CoA还原酶抑制剂的另一个特点。