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D-青霉胺对小鼠肝细胞中金属硫蛋白mRNA水平及铜分布的影响。

The effect of D-penicillamine on metallothionein mRNA levels and copper distribution in mouse hepatocytes.

作者信息

McArdle H J, Kyriakou P, Grimes A, Mercer J F, Danks D M

机构信息

Department of Child Health, Ninewells Hospital and Medical School, Dundee, Scotland.

出版信息

Chem Biol Interact. 1990;75(3):315-24. doi: 10.1016/0009-2797(90)90074-w.

DOI:10.1016/0009-2797(90)90074-w
PMID:2379260
Abstract

Penicillamine increases the levels of metallothionein (MT) mRNA in a time and concentration dependent manner without altering either the rate of copper uptake or the amount of copper within the cell. The effect is dependent on the presence of intracellular copper, however, since depletion of copper by chelators blocks the effect, and does not alter the ability of dexamethasone to stimulate mRNA production. Penicillamine did not alter the distribution of 64Cu in the hepatocytes, as measured by fast protein liquid chromatography (FPLC), although the pattern may be affected by the amount of MT present. The data indicates that penicillamine removes copper from some intermediary ligand, thereby making it available to induce metallothionein. It is possible that this is part of the therapeutic action of the chelator in the treatment of Wilson's disease.

摘要

青霉胺能以时间和浓度依赖的方式增加金属硫蛋白(MT)mRNA的水平,而不会改变细胞内铜的摄取速率或铜的含量。然而,这种作用依赖于细胞内铜的存在,因为螯合剂耗尽铜会阻断这种作用,且不会改变地塞米松刺激mRNA产生的能力。通过快速蛋白质液相色谱法(FPLC)测量,青霉胺不会改变肝细胞中64Cu的分布,尽管这种模式可能会受到MT含量的影响。数据表明,青霉胺从某些中间配体中去除铜,从而使其可用于诱导金属硫蛋白。这可能是螯合剂在治疗威尔逊病中的部分治疗作用。

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2
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引用本文的文献

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Metallothionein induction in cultured fibroblasts and liver of a marine flatfish, the turbot,Scophthalmus maximus.诱导培养的鱼类成纤维细胞和肝脏中海鲡金属硫蛋白的表达
Fish Physiol Biochem. 1992 May;10(1):43-54. doi: 10.1007/BF00004653.
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Advance in the pathogenesis and treatment of Wilson disease.
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Transl Neurodegener. 2012 Nov 27;1(1):23. doi: 10.1186/2047-9158-1-23.
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Biochem J. 1993 Jun 15;292 ( Pt 3)(Pt 3):673-6. doi: 10.1042/bj2920673.
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