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麝鼩载脂蛋白B合成缺陷。

Deficiency of apolipoprotein B synthesis in Suncus murinus.

作者信息

Yasuhara M, Ohama T, Matsuki N, Saito H, Matsushima T, Kurokawa K, Teramoto T

机构信息

Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo.

出版信息

J Biochem. 1991 Nov;110(5):751-5. doi: 10.1093/oxfordjournals.jbchem.a123653.

Abstract

We reported previously that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food. In this study, we focused on lipoprotein and apolipoprotein secretion from the liver. The study of lipoproteins from this animal revealed that small amounts of lipoproteins with apolipoprotein (apo) E but without apo B were observed in the fraction of density less than 1.08 g/ml. In order to learn whether apo B is synthesized by the liver or not, isolated suncus livers were perfused with an addition of [35S]methionine. Small amounts of radioactivity were observed in apo E of VLDL, and fairly large amounts in apo E and A-I in the fraction of LDL + HDL, suggesting that VLDL was secreted with apo E but not with apo B from the liver. Northern blot analysis with use of rat apo B cDNA revealed a weak signal of hybridized rat apo B cDNA between 15 kb and 9 kb in the suncus liver and intestinal mucosa; this is almost the same size as rat apo B mRNA. This finding suggests the presence of apo B mRNA in the suncus. In conclusion, apo B is not secreted from the suncus liver, owing to a defect in intracellular post-transcriptional processing or to ineffective transcription. This might be one of the reasons for fatty deposits in the suncus liver. Suncus may be a candidate for an animal model of abetalipoproteinemia as well as fatty liver due to a defect of apo B synthesis.

摘要

我们之前报道过,通过禁食可在一种新型实验动物——麝香鼩鼱(suncus)中轻易诱发脂肪肝。在本研究中,我们聚焦于肝脏中脂蛋白和载脂蛋白的分泌。对该动物脂蛋白的研究表明,在密度小于1.08 g/ml的组分中观察到少量含有载脂蛋白(apo)E但不含apo B的脂蛋白。为了了解肝脏是否合成apo B,向分离出的麝香鼩鼱肝脏灌注添加了[35S]甲硫氨酸。在极低密度脂蛋白(VLDL)的apo E中观察到少量放射性,而在低密度脂蛋白(LDL)+高密度脂蛋白(HDL)组分的apo E和A-I中观察到相当大量的放射性,这表明VLDL是从肝脏中与apo E一起而非与apo B一起分泌的。使用大鼠apo B cDNA进行的Northern印迹分析显示,在麝香鼩鼱肝脏和肠黏膜中,15 kb至9 kb之间存在与大鼠apo B cDNA杂交的微弱信号;这与大鼠apo B mRNA的大小几乎相同。这一发现表明麝香鼩鼱中存在apo B mRNA。总之,由于细胞内转录后加工缺陷或转录无效,apo B并非从麝香鼩鼱肝脏分泌。这可能是麝香鼩鼱肝脏中脂肪沉积的原因之一。由于apo B合成缺陷,麝香鼩鼱可能是无β脂蛋白血症以及脂肪肝动物模型的候选者。

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