Atherogenic diet increases cholesteryl ester transfer protein messenger RNA levels in rabbit liver.

Atherogenic diet increases cholesteryl ester transfer protein messenger RNA levels in rabbit liver.
复制标题

致动脉粥样硬化饮食会增加兔肝脏中胆固醇酯转移蛋白信使 RNA 的水平。

DOI:
10.1172/jci114446
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发表时间:
1990
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Tall,AR
Tall,AR
中科院分区:
--
文献类型:
--
作者:
Quinet,EM;Agellon,LB;Kroon,PA;Marcel,YL;Lee,YC;Whitlock,ME;Tall,AR

文献摘要

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胆固醇喂养兔血浆中胆固醇酯转移活性增加。为了研究导致活性变化的机制,我们在对照组(n = 8)和胆固醇喂养的家兔(n = 10)中通过RIA测量胆固醇酯转移蛋白(CETP)质量,并通过北方和狭缝印迹分析使用人CETP cDNA探针测量CETP mRNA丰度。与对照组(3.86 +/- 0.38 μ g/ml)相比,胆固醇喂养(食物加0.5%胆固醇,10%玉米油)30天使胆固醇喂养兔血浆中CETP质量增加3.2倍(12.45 +/- 0.82 μ g/ml)。在高胆固醇血症兔中,肝脏CETP mRNA水平增加了2.8倍对照mRNA水平。肌动蛋白、载脂蛋白E、卵磷脂-胆固醇酰基转移酶和白蛋白mRNA丰度无变化。与人类中广泛的组织分布相反,在对照组或胆固醇喂养动物的肝外组织中未检测到CETP mRNA。使用敏感的RNase保护试验,在开始高胆固醇饮食的3天内可检测到肝脏CETP mRNA的增加。因此,响应于致动脉粥样硬化饮食,肝脏CETP mRNA早期增加,可能导致CETP合成和分泌增加,以及血浆CETP增加。结果表明CETP基因可能受到饮食诱导的脂质代谢变化的调节。图片
Cholesteryl ester transfer activity is increased in plasma of cholesterol-fed rabbits. To investigate the mechanisms leading to changes in activity, we measured cholesteryl ester transfer protein (CETP) mass by RIA and CETP mRNA abundance by Northern and slot blot analysis using a human CETP cDNA probe in control (n = 8) and cholesterol-fed rabbits (n = 10). Cholesterol feeding (chow plus 0.5% cholesterol, 10% corn oil) for 30 d increased CETP mass in plasma 3.2-fold in the cholesterol-fed rabbits (12.45 +/- 0.82 micrograms/ml) compared with controls (3.86 +/- 0.38 micrograms/ml). In the hypercholesterolemic rabbit, liver CETP mRNA levels were increased 2.8 times control mRNA levels. Actin, apo E, lecithin-cholesterol acyltransferase, and albumin mRNA abundances were unchanged. In contrast to the widespread tissue distribution in humans, CETP mRNA was not detected in extrahepatic tissues of either control or cholesterol-fed animals. Using a sensitive RNase protection assay, the increase in liver CETP mRNA was detectable within 3 d of beginning the high cholesterol diet. Thus, in response to the atherogenic diet there is an early increase in liver CETP mRNA, probably causing increased CETP synthesis and secretion, and increased plasma CETP. The results indicate that the CETP gene may be regulated by diet-induced changes in lipid metabolism.Images