Affordable Access

deepdyve-link
Publisher Website

Effects of NB-598, a potent squalene epoxidase inhibitor, on the apical membrane uptake of cholesterol and basolateral membrane secretion of lipids in Caco-2 cells

Authors
  • Horie, Masahiro
  • Iwasawa, Yoshikazu
  • Satoh, Toshihiko
  • Shimizu, Akiko
  • Nagata, Yasufumi
  • Kamei, Toshio
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 1993
Accepted Date
Mar 10, 1993
Volume
46
Issue
2
Pages
297–305
Identifiers
DOI: 10.1016/0006-2952(93)90418-V
Source
Elsevier
Keywords
License
Unknown

Abstract

Caco-2 cells grown on membrane filters were used as a model to study the effects of NB-598, an inhibitor of squalene epoxidase, on cholesterol absorption from the intestinal epithelia. NB-598 (10 μM) inhibited the synthesis of sterol and sterol ester from [ 14C]acetate without affecting the synthesis of other lipids such as phospholipids (PL), free fatty acids (FFA) and triacylglycerol (TG). When labeled lipid was apically loaded as a micellar lipid solution into Caco-2 cell cultures, NB-598 reduced basolaterally secreted radioactivity in cholesterol, cholesterol ester, PL and TG. Furthermore, NB-598 suppressed the basolateral secretion of apolipoprotein (apo) B. When microsomes prepared from control Caco-2 cells were incubated with 10 μM NB-598, acyl CoA:cholesterol acyltransferase (ACAT) activity was inhibited slightly. After incubating Caco-2 cells with 10 μM NB-598, a slight reduction in cellular ACAT activity was also observed. These results suggest that suppression of the secretion of particles containing apo B and reduction of cellular ACAT activity in the intestinal epithelia are part of the mechanism of the cholesterol-lowering effect of NB-598.

Report this publication

Statistics

Seen <100 times