Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.
Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.
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大鼠模型和威尔逊病患者中铜与脱辅基铜蓝蛋白的结合有缺陷。
DOI：
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
M. Esumi
中科院分区：
文献类型：
--
作者：
N. Kojimahara;H. Nakabayashi;T. Shikata;M. Esumi
为了研究Long-Evans Cinnamon（LEC）大鼠（Wilson病的一种拟议模型）血清铜蓝蛋白（Cp）降低的机制，我们分析了转录和翻译阶段的Cp产物。北方印迹分析和免疫印迹分析表明，LEC大鼠Cp mRNA和蛋白的水平和分子大小与对照Long-Evans-Agouti（莱亚）大鼠相似。而LEC大鼠的Cp铁氧化酶活性明显降低。我们用pH调节的非变性聚丙烯酰胺凝胶电泳将血清Cp分为两种形式：一种是具有铜和铁氧化酶活性的holo-Cp，另一种是不含铜的失活apo-Cp。在莱亚大鼠和正常人中，Holo-Cp是主要形式，而在LEC大鼠和Wilson病患者中，apo-Cp是主要形式。采用回交大鼠分析LEC大鼠中apo-Cp优势与疾病的共分离。Apo-Cp在11只患病子代中占优势的有8只，而在19只正常子代中无一只占优势。这些结果表明，铜结合apo-Cp的遗传障碍可能与LEC大鼠的发病机制密切相关，并可能在威尔逊病。
To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.
DOI：
10.1006/bbrc.1993.2471
发表时间：
1993-11-30
影响因子：
3.1
作者：
YAMAGUCHI, Y;HEINY, ME;GITLIN, JD
通讯作者：
GITLIN, JD
大鼠铜蓝蛋白的一级结构和发育过程中组织特异性基因表达的分析。
DOI：
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发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fleming,RE;Gitlin,JD
通讯作者：
Gitlin,JD