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

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...

Full description

Saved in:

Bibliographic Details
Published in:	FEBS letters Vol. 487; no. 2; pp. 293 - 297
Main Authors:	Kramer, Werner, Glombik, Heiner, Petry, Stephan, Heuer, Hubert, Schäfer, Hans-Ludwig, Wendler, Wolfgang, Corsiero, Daniel, Girbig, Frank, Weyland, Claudia
Format:	Journal Article
Language:	English
Published:	England Elsevier B.V 29-12-2000
Subjects:	2-Azetidinone Animals Anticholesteremic Agents - pharmacology Azetidines - pharmacology Bile Acids and Salts - pharmacology Carrier Proteins - metabolism Cephalexin - pharmacology Cholesterol - analogs & derivatives Cholesterol - pharmacokinetics Cholesterol transport inhibitor Cholesterol transporter Drug Design Ezetimibe Fatty Acids - pharmacology Glucose - pharmacology Intestinal Absorption - drug effects Intestinal cholesterol absorption Intestinal Mucosa - physiology Intestine, Small - physiology Male Membrane Proteins - metabolism Mice Mice, Inbred Strains Microvilli - physiology Photoaffinity labeling Rabbits Small intestine Structure-Activity Relationship Transport protein Photoaffinity labeling 2-Azetidinone Transport protein Cholesterol transport inhibitor Small intestine Intestinal cholesterol absorption Cholesterol transporter
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-5793 1873-3468
DOI:	10.1016/S0014-5793(00)02372-3