Lack of correlation between ACAT mRNA expression and cholesterol esterification in primary liver cells

被引：16

作者：

Rea, TJ ^{[1
]}

DeMattos, RB ^{[1
]}

Homan, R ^{[1
]}

Newton, RS ^{[1
]}

Pape, ME ^{[1
]}

机构：

[1] WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,DIV THERAPEUT,ATHEROSCLEROSIS RES,ANN ARBOR,MI 48105

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM | 1996年 / 1299卷 / 01期

关键词：

hepatocyte gene regulation; mRNA quantitation; cholesterol; lipoprotein; apolipoprotein; ester;

D O I：

10.1016/0005-2760(95)00190-5

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：

A partial rabbit cDNA clone (14b) for ACAT has been characterized and used to demonstrate that hepatic and aortic ACAT mRNA(14b) abundance increased 2-3-fold in rabbits receiving a high fat/high cholesterol-diet compared to chow fed animals (Pape et al, (1995) J. Lipid Res. 36, 823-838). Because of those data we hypothesized that increased hepatic cholesteryl ester mass and synthesis rates in rabbit liver cells are associated with an increase in ACAT mRNA(14b) levels. To test this hypothesis we altered cellular cholesteryl ester mass and synthesis rates in primary parenchymal and nonparenchymal cells using various extracellular agents and measured the accumulated mass of ACAT mRNA(14b). Parenchymal cells incubated with rabbit beta VLDL or mevalonolactone displayed a 6-10-fold increase in cellular cholesteryl ester mass over a three day treatment with no significant changes in cellular free cholesterol, triacylglycerols, or ACAT mRNA(14b) levels; HMG CoA reductase and LDL receptor mRNA mass decreased initially as a result of cholesteryl ester loading. Treatment of parenchymal cells with CI-976, an ACAT inhibitor, showed a marked reduction in cholesteryl ester synthetic rate compared to beta VLDL controls but displayed no change in ACAT mRNA(14b) levels. A mixed population of rabbit hepatic nonparenchymal cells was incubated with beta VLDL for 24 h in culture which resulted in a 6-fold increase in cellular cholesteryl ester mass; there was no change in ACAT mRNA(14b) levels. In an in vivo study, rabbits consuming a high fat/high cholesterol-diet for three weeks showed a 10-fold increase in hepatic cholesteryl ester with no significant changes in ACAT mRNA(14b) levels. Together these data indicate that rabbit liver cellular cholesteryl ester mass increases of up to 10-fold are not correlated with ACAT mRNA(14b) changes. Thus, hepatic ACAT mRNA(14b) expression and cellular cholesterol esterification do not appear to be coordinately regulated at this level of cholesteryl ester loading.

引用

页码：67 / 74

页数：8

共 40 条

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