Oxidation affects the regulation of hepatic lipid synthesis by chylomicron remnants

被引:23
作者
Napolitano, M
Rivabene, R
Avella, M
Amicone, L
Tripodi, M
Botham, KM
Bravo, E
机构
[1] Univ London Royal Coll Vet Surg, Dept Vet Basic Sci, London NW1 0TU, England
[2] Ist Super Sanita, Lab Metab & Biochim Patol, I-00161 Rome, Italy
[3] Univ La Sapienza, Sez Genet Mol, Dipartimento Biotecnol Cellulare & Ematol, Inst Pasteur Cenci Bolognetti, Rome, Italy
基金
英国惠康基金;
关键词
chylomicron remnants; cholesterol esterification; triacylgylcerol synthesis; phospholipid synthesis; oxidative stress; hepatocytes; free radicals;
D O I
10.1016/S0891-5849(00)00493-7
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
The effects of native and oxidized chylomicron remnants on lipid synthesis in normal and oxidatively stressed liver cells were investigated using MET murine hepatocytes (MMH cells), a nontransformed mouse hepatocyte cell line that maintains a highly differentiated hepatic phenotype in culture. Lipid synthesis was determined by measuring the incorporation of [H-3]oleate into cholesteryl ester, triacylglycerol, and phospholipid by the cells. The formation of cholesteryl ester and phospholipid was decreased by chylomicron remnants in a dose-dependent manner, while triacylglycerol synthesis was increased. Exposure of MMH cells to mild oxidative stress by incubation with CuSO4 (2.5 muM) for 24 h led to significantly increased incorporation of [H-3]oleate into triacylglycerol and phospholipid, but not cholesteryl ester, in the absence of chylomicron remnants. In the presence of the lipoproteins, however, similar effects to those found in untreated cells were observed. Oxidatively modified chylomicron remnants prepared by incubation with CuSO4 (10 muM, 18 h, 37 degreesC) did not influence cholesteryl ester or phospholipid synthesis in MMH cells, but had a similar effect to that found with native remnants on triacylglycerol synthesis. These findings show that hepatic lipid metabolism is altered by exposure to mild oxidative stress and by lipids from the diet delivered to the liver in chylomicron remnants, and these effects may play a role in the development of atherosclerosis, (C) 2001 Elsevier Science Inc.
引用
收藏
页码:506 / 515
页数:10
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