Identification of binding proteins for cholesterol absorption inhibitors as components of the intestinal cholesterol transporter

被引：44

作者：

Kramer, W ^{[1
]}

Glombik, H ^{[1
]}

Petry, S ^{[1
]}

Heuer, H ^{[1
]}

Schäfer, HL ^{[1
]}

Wendler, W ^{[1
]}

Corsiero, D ^{[1
]}

Girbig, F ^{[1
]}

Weyland, C ^{[1
]}

机构：

[1] Aventis Pharma Deutschland GMBH, Dis Grp Metab Dis, D-65926 Frankfurt, Germany

来源：

FEBS LETTERS | 2000年 / 487卷 / 02期

关键词：

intestinal cholesterol absorption; cholesterol transporter; 2-azetidinone; transport protein; cholesterol transport inhibitor; photoaffinity labeling; small intestine;

D O I：

10.1016/S0014-5793(00)02372-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To identify protein components of the intestinal cholesterol transporter, rabbit small intestinal brush border membrane vesicles were submitted to photoaffinity labeling using photoreactive derivatives of 2-azetidinone cholesterol absorption inhibitors. An integral membrane protein of M-r 145.3 +/- 7.5 kDa was specifically labeled in brush border membrane vesicles from rabbit jejunum and ileum. Its labeling was concentration-dependently inhibited by the presence of cholesterol absorption inhibitors whereas bile acids, D-glucose, fatty acids or cephalexin had no effect. The inhibitory potency of 2-azetidinones to inhibit photolabeling of the 145 kDa protein correlated with their in vivo activity to inhibit intestinal cholesterol absorption. These results suggest that an integral membrane protein of M-r, 145 kDa is (a component of) the cholesterol absorption system in the brush border membrane of small intestinal enterocytes. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：293 / 297

页数：5