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实验性肾病中载脂蛋白基因表达及血浆高密度脂蛋白组成的调控

Regulation of apolipoprotein gene expression and plasma high-density lipoprotein composition in experimental nephrosis.

作者信息

Marshall J F, Apostolopoulos J J, Brack C M, Howlett G J

机构信息

Russell Grimwade School of Biochemistry, University of Melbourne, Parkville, Australia.

出版信息

Biochim Biophys Acta. 1990 Feb 23;1042(3):271-9. doi: 10.1016/0005-2760(90)90153-o.

DOI:10.1016/0005-2760(90)90153-o
PMID:2306478
Abstract

Hepatic and intestinal RNA levels were measured in rats made nephrotic by injection of puromycin aminonucleoside (PAN). The following increases in hepatic RNA levels, relative to controls, were measured: poly A+ (1.2), ribosomal (1.2), mRNA levels for transferrin (1.8), albumin (3.8) apolipoprotein (apo)E (2.3), apoB (2.5), apoA-II (1.9) and apoA-I (6.1). Increases of 1.5- to 2.2-fold in hepatic mRNA levels for albumin, apoA-II, apoB and apoE were measured in pre-nephrotic animals killed before the onset of proteinuria. Intestinal RNA levels in pre-nephrotic and nephrotic animals were not significantly different from control values. Transcription of the hepatic apoA-I gene increased 1.8-fold in nephrotic animals compared to controls. Immunological detection of apolipoproteins in high-density lipoproteins (HDL) separated by gradient gel electrophoresis indicated an increase in apoA-I and a decrease in apoA-IV and apoE containing HDL particles in nephrosis. To simulate the effects of increased apoA-I gene expression, human apoA-I was added to rat plasma in vivo and in vitro. ApoE was displaced from HDL by increased concentration of apoA-I. The results indicate that relatively small changes in apoA-I levels in the serum lead to significant changes in the apolipoprotein composition of HDL.

摘要

通过注射嘌呤霉素氨基核苷(PAN)使大鼠产生肾病,然后测定其肝脏和肠道的RNA水平。相对于对照组,测得肝脏RNA水平有以下升高:多聚腺苷酸(poly A+)升高1.2倍,核糖体RNA升高1.2倍,转铁蛋白的mRNA水平升高1.8倍,白蛋白升高3.8倍,载脂蛋白(apo)E升高2.3倍,apoB升高2.5倍,apoA-II升高1.9倍,apoA-I升高6.1倍。在蛋白尿出现前处死的肾病前期动物中,测得白蛋白、apoA-II、apoB和apoE的肝脏mRNA水平升高了1.5至2.2倍。肾病前期和肾病动物的肠道RNA水平与对照值无显著差异。与对照组相比,肾病动物肝脏apoA-I基因的转录增加了1.8倍。通过梯度凝胶电泳分离的高密度脂蛋白(HDL)中载脂蛋白的免疫检测表明,肾病时含apoA-I的HDL颗粒增加,含apoA-IV和apoE的HDL颗粒减少。为了模拟apoA-I基因表达增加的影响,在体内和体外将人apoA-I添加到大鼠血浆中。apoA-I浓度的增加使apoE从HDL中被置换出来。结果表明,血清中apoA-I水平相对较小的变化会导致HDL载脂蛋白组成发生显著变化。

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Regulation of apolipoprotein gene expression and plasma high-density lipoprotein composition in experimental nephrosis.实验性肾病中载脂蛋白基因表达及血浆高密度脂蛋白组成的调控
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引用本文的文献

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2
Graded effects of proteinuria on HDL structure in nephrotic rats.蛋白尿对肾病大鼠高密度脂蛋白结构的分级影响。
J Am Soc Nephrol. 2005 May;16(5):1309-19. doi: 10.1681/ASN.2004080644. Epub 2005 Mar 23.
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The full induction of human apoprotein A-I gene expression by the experimental nephrotic syndrome in transgenic mice depends on cis-acting elements in the proximal 256 base-pair promoter region and the trans-acting factor early growth response factor 1.
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Inflammation. 1993 Apr;17(2):153-66. doi: 10.1007/BF00916102.