The structural and functional analysis of copper transporting P-type ATPase in inborn error of copper metabolism

先天性铜代谢缺陷中铜转运P型ATP酶的结构和功能分析

基本信息

  • 批准号:
    08670919
  • 负责人:
  • 金额:
    $ 1.47万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1996
  • 资助国家:
    日本
  • 起止时间:
    1996 至 1997
  • 项目状态:
    已结题

项目摘要

1.The intracellular localization of Menkes disease gene (ATP-7A) protein and Wilson disease gene (ATP-7B) proteinBoth of the proteins synthesized from ATP-7A and 7B were localized in the trans-Golgi network under steady conditions. An increase in the intracellular copper concentration resulted in the rapid movement of these proteins to a cytoplasmic vesicular compartment. This copper-specific cellular redistribution of ATP-7A and 7B protein is a reversible process that occurs independent of new protein (small vesicles of copper transport).2.The corelationship between genotype and clinical features in Wilson diseaseThe most of mutations of ATP-7B in hepatic type (including fulminant type) of Wilson disease were one point dilutions that make frame shift. Truncated proteins must be synthesized from these mutated genes. And these proteins may have no any function as a Copper transporter. The patients who have neurologic symptom revealed missense mutation and exon skipping. These mutated protein can be leave some part of function. These results suggest that difference of phenotypes of Wilson disease depend on functional levels of Wilson disease protein. And protein function is regulated by types of gene mutations (genotype). The sever impairment of ATP-7B,such one base deletion would remove function, leads to sever liver dysfunction, such as fulminant type of Wilson disease.
1.门克斯病基因(ATP-7A)蛋白和威尔逊病基因(ATP-7B)蛋白的细胞内定位由ATP-7A和7B合成的蛋白在稳定条件下均定位于跨高尔基体网络。细胞内铜浓度的增加导致这些蛋白质快速移动到细胞质囊泡区室。 ATP-7A 和 7B 蛋白的这种铜特异性细胞重新分布是一个可逆过程,其发生独立于新蛋白(铜转运小囊泡)。2.威尔逊病基因型与临床特征之间的相关性大多数 ATP-7B 突变在肝型(包括暴发型)威尔逊病中,进行一点稀释,导致移码。截短的蛋白质必须由这些突变基因合成。这些蛋白质可能没有任何铜转运蛋白的功能。有神经系统症状的患者表现出错义突变和外显子跳跃。这些突变的蛋白质可以保留部分功能。这些结果表明威尔逊病表型的差异取决于威尔逊病蛋白的功能水平。蛋白质功能受基因突变类型(基因型)的调节。 ATP-7B的严重损伤,如一个碱基缺失就会导致功能丧失,导致严重的肝功能障碍,如暴发型威尔逊病。

项目成果

期刊论文数量(33)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Shimizu N,Nagayama T,Nakazono H,Fujioka Y,Miki J,Hiyamuta S,Aoki T: A trial study for neonatal screening system of Wilson's disease in Japan using dried filter papers. Neonatal and Perinatal Screening : The Asian Pacific Perspectives, Stephen TS Lam, MD,F
Shimizu N,Nagayama T,Nakazono H,Fujioka Y,Miki J,Hiyamuta S,Aoki T:日本使用干燥滤纸进行威尔逊病新生儿筛查系统的试验研究。
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    0
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  • 通讯作者:
Yamaguchi Y,Suzuki M,Shimizu N,Gitlin JD,Aoki T: "Intracellular localization of P-Type ATPase relating copper transporters.19Gc07 : Biomed Res Trace Elements" 7. 141-142 (1996)
Yamaguchi Y、Suzuki M、Shimizu N、Gitlin JD、Aoki T:“与铜转运蛋白相关的 P 型 ATP 酶的细胞内定位。19Gc07:Biomed Res 微量元素”7. 141-142 (1996)
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    0
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  • 通讯作者:
Nakazone H,Fujii H,Kawase C,Yamaguchi Y,Fujioka Y,Shimizu N,Aoki T,Hiyamuta S: "A study of copper metabolism in patients with fuluminant type of Wilson disease." Biomed Res Trace Elements. 7. 139-140 (1996)
Nakazone H、Fujii H、Kawase C、Yamaguchi Y、Fujioka Y、Shimizu N、Aoki T、Hiyamuta S:“烟酸型威尔逊病患者铜代谢的研究。”
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  • 影响因子:
    0
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Shimizu N, Yamaguci Y, et al: "Age-related copper,zinc,and iron metabolism in Long-Evans Cinnamon rats and copper-eliminating effects of D-penicillamine and trienthine-2HCl" J Trace Elem Exp Med. 10. 49-59 (1997)
Shimizu N、Yamaguci Y 等人:“Long-Evans Cinnamon 大鼠中与年龄相关的铜、锌和铁代谢以及 D-青霉胺和 trienthine-2HCl 的铜消除作用”J Trace Elem Exp Med。
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  • 影响因子:
    0
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  • 通讯作者:
Shimizu N: "Molecular diagnosis of Wilson's disease" Lancet. 349. 1811-1812 (1997)
Shimizu N:“威尔逊氏病的分子诊断”《柳叶刀》。
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    0
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SHIMIZU Norikazu其他文献

Microfossils from Siliceous Rock Pebbles Contained in the Lower Cretaceous Ishido Formation of the Sanchu Group, Central Japan
日本中部三洲群下白垩统石户组硅质岩卵石微化石
  • DOI:
    10.5026/jgeography.130.311
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    OZEKI Masanori;SHIMIZU Norikazu;AGEMATSU Sachiko;SASHIDA Katsuo
  • 通讯作者:
    SASHIDA Katsuo

SHIMIZU Norikazu的其他文献

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{{ truncateString('SHIMIZU Norikazu', 18)}}的其他基金

IMPROVEMENTS OF ACCURACY OF DISPLACEMENT MEASUREMENTS USING GPS FOR MONITORING THE STABILITY OF SLOPES
提高使用 GPS 监测斜坡稳定性的位移测量精度
  • 批准号:
    17560445
  • 财政年份:
    2005
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Research for Early Imperial Steel Works YAWATA
早期帝国制钢所八幡研究
  • 批准号:
    16330066
  • 财政年份:
    2004
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Strategy of ATP7B gene analysis for Japanese patients with Wilson disease, using ARMS method. ..................................
使用 ARMS 方法对日本威尔逊病患者进行 ATP7B 基因分析策略。
  • 批准号:
    10670764
  • 财政年份:
    1998
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on stress redistribution around a rock chamber based on field measurements with progressive excavations
基于渐进开挖现场测量的岩室周围应力重新分布研究
  • 批准号:
    04805064
  • 财政年份:
    1992
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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