当前位置： SCI文献检索 > ATHEROSCLEROSIS期刊下所有文献 > Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters.

Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters.

Abstract：

:Administration of ursodeoxycholic acid (UDCA) has been shown to decrease serum total and low density lipoprotein (LDL) cholesterol in hypercholesterolemic patients with primary biliary cirrhosis. Results of previous studies prompted us to postulate that the cholesterol-lowering effect of UDCA may be due, at least in part, to a direct increment in hepatic LDL receptor binding [Bouscarel et al., Biochem J, 1991;280:589; Bouscarel et al., Lipids 1995;30:607]. The aim of the present investigation was to determine the ability of UDCA to enhance hepatocellular LDL receptor recruitment, as determined by its effect in vivo on LDL uptake, and its effect in vitro on LDL binding, under conditions of moderately elevated serum cholesterol. Study groups consisted of male golden Syrian hamsters fed either a standard chow diet (control), a 0.15% cholesterol-containing diet, or a 0.15% cholesterol-containing diet supplemented with either 0.1% UDCA, or 0.1% chenodeoxycholic acid (CDCA). Cholesterol feeding increased (P<0.01) total serum cholesterol by 44%, and was associated with a 10-fold accumulation of cholesteryl esters in the liver (P<0.01). In vivo, hepatic uptake of [U-(14)C]sucrose-labeled hamster LDL was increased (P<0.05) to a level of 454+/-101 microl in animals fed a cholesterol-containing diet supplemented with UDCA, compared to that either without UDCA (337+/-56 microl), or with CDCA (240+/-49 microl). The hepatic uptake of [U-(14)C]sucrose-labeled methylated human LDL, a marker of LDL receptor-independent LDL uptake, was unaffected by bile acid feeding. In vitro, specific binding of [125I]hamster LDL to isolated hepatocytes was determined at 4 degrees C, in presence and absence of 700 micromol/l UDCA. The K(D) ranged from 25 to 31 microg/ml, and was not affected by either cholesterol feeding or UDCA. In the presence of UDCA, the B(max) was increased by 19% (P<0.05) in cells isolated from control animals and by 29% (P<0.01) in cells isolated from hamsters fed a cholesterol-supplemented diet. In conclusion, in dietary hypercholesterolemic hamsters, both chronic in-vivo and acute in-vitro treatments with UDCA resulted in restoration of hepatic LDL binding and uptake to levels observed in control hamsters.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Ceryak S,Bouscarel B,Malavolti M,Robins SJ,Caslow KL,Fromm H

doi

10.1016/s0021-9150(00)00396-8

keywords:

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

59-67

issue

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(00)00396-8

journal_volume

153

pub_type

杂志文章

在线工具

Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters.