DESIALIZED LOW-DENSITY LIPOPROTEIN REGULATES CHOLESTEROL-METABOLISM IN RECEPTOR-DEFICIENT FIBROBLASTS

被引:16
作者
FILIPOVIC, I
BUDDECKE, E
机构
[1] Institut Für Physiologische Chemie, Westfälischen Wilhelms-Universität Münster, Münster, D-4400
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1979年 / 101卷 / 01期
关键词
D O I
10.1111/j.1432-1033.1979.tb04223.x
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
Binding of homologous low density lipoproteins (LDL) to specific cell‐membrane receptors initiates regulation of cholesterol metabolism in normal human fibroblasts, but minor regulatory effects are observed in receptor‐deficient cells. After enzymic removal of sialic acid residues, however, the desialized LDL aquires the ability to regulate cholesterol biosynthesis and cholesterol esterification in receptor‐deficient cells as effective as native LDL in normal cells. This is indicated by a suppression of hydroxymethylglutaryl‐CoA reductase activity, by a reduced incorporation of [14C]acetate into cholesterol and by a stimulation of the [3H]oleate incorporation into cholesterol esters in both normal and receptor deficient cells. Competitive binding and internalisation experiments revealed that the action of desialized LDL in normal and receptor‐deficient cells is receptor‐specific. The results suggest that desialisation of LDL facilitates its binding to cell membrane receptors, its internalisation and subsequent regulation of cellular cholesterol metabolism, this effect becoming significant in fibroblasts with reduced number of LDL receptors. Copyright © 1979, Wiley Blackwell. All rights reserved
引用
收藏
页码:119 / 122
页数:4
相关论文
共 23 条
[1]   LOCALIZATION OF LOW-DENSITY LIPOPROTEIN RECEPTORS ON PLASMA-MEMBRANE OF NORMAL HUMAN FIBROBLASTS AND THEIR ABSENCE IN CELLS FROM A FAMILIAL HYPERCHOLESTEROLEMIA HOMOZYGOTE [J].
ANDERSON, RGW ;
GOLDSTEIN, JL ;
BROWN, MS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (07) :2434-2438
[2]   DEGRADATION OF CATIONIZED LOW-DENSITY LIPOPROTEIN AND REGULATION OF CHOLESTEROL-METABOLISM IN HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA FIBROBLASTS [J].
BASU, SK ;
GOLDSTEIN, JL ;
ANDERSON, RGW ;
BROWN, MS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (09) :3178-3182
[3]   HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - POSSIBLE BIOCHEMICAL EXPLANATION OF CLINICAL HETEROGENEITY [J].
BRESLOW, JL ;
SPAULDING, DR ;
LUX, SE ;
LEVY, RI ;
LEES, RS .
NEW ENGLAND JOURNAL OF MEDICINE, 1975, 293 (18) :900-903
[4]   FAMILIAL HYPERCHOLESTEROLEMIA - DEFECTIVE BINDING OF LIPOPROTEINS TO CULTURED FIBROBLASTS ASSOCIATED WITH IMPAIRED REGULATION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE-ACTIVITY [J].
BROWN, MS ;
GOLDSTEIN, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1974, 71 (03) :788-792
[5]   RECEPTOR-MEDIATED CONTROL OF CHOLESTEROL-METABOLISM [J].
BROWN, MS ;
GOLDSTEIN, JL .
SCIENCE, 1976, 191 (4223) :150-154
[6]  
BROWN MS, 1976, NEW ENGL J MED, V294, P1386
[7]   RECEPTOR-DEPENDENT HYDROLYSIS OF CHOLESTERYL ESTERS CONTAINED IN PLASMA LOW-DENSITY LIPOPROTEIN [J].
BROWN, MS ;
DANA, SE ;
GOLDSTEIN, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1975, 72 (08) :2925-2929
[8]  
CORNWELL DG, 1961, J LIPID RES, V2, P110
[9]   ROLE OF NET CHARGE OF LOW-DENSITY LIPOPROTEINS IN HIGH-AFFINITY BINDING AND UPTAKE BY CULTURED-CELLS [J].
FILIPOVIC, I ;
BUDDECKE, E .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1979, 88 (02) :485-490
[10]   SIALIC-ACID CONTENT OF LOW-DENSITY LIPOPROTEINS CONTROLS THEIR BINDING AND UPTAKE BY CULTURED-CELLS [J].
FILIPOVIC, I ;
SCHWARZMANN, G ;
MRAZ, W ;
WIEGANDT, H ;
BUDDECKE, E .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1979, 93 (01) :51-55