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

FEBS Letters

Kramer, Werner¹  Weyland, Claudia¹  Heuer, Hubert¹  Wendler, Wolfgang¹  Glombik, Heiner¹  Schäfer, Hans-Ludwig¹  Girbig, Frank¹  Petry, Stephan¹  Corsiero, Daniel¹ 

[1] Aventis Pharma Deutschland GmbH, Disease Group Metabolic Diseases, D-65926 Frankfurt am Main, Germany

关键词: Intestinal cholesterol absorption;    Cholesterol transporter;    2-Azetidinone;    Transport protein;    Cholesterol transport inhibitor;    Photoaffinity labeling;    Small intestine;   

DOI  :  10.1016/S0014-5793(00)02372-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown