Mechanisms for biological control of metals and participation of metal-binding proteins : disordered copper metabolism in LEC rats.

金属生物控制机制和金属结合蛋白的参与:LEC 大鼠铜代谢紊乱。

基本信息

  • 批准号:
    05454576
  • 负责人:
  • 金额:
    $ 4.35万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
  • 财政年份:
    1993
  • 资助国家:
    日本
  • 起止时间:
    1993 至 1994
  • 项目状态:
    已结题

项目摘要

Our approach can be described under several subheadings as following : (i) Process of normal accumulation of copper in LEC rats leading to and following acute hepatitis, (ii) Selective transfer of copper from metallothionein to copper-binding enzymes in LEC rats, (iii) Selective removal of copper bound to metallothionein by tetrathiomolybdate and recovery from acute hepatitis, and (iv) Enhanced induction of metallothionein synthesis in the liver of LEC rats.Our experiments revealed that copper accumulates in the liver of LEC rats in a form bound to metallothionein up to the limits of liver's capacity to synthesize this protein. Then copper not bound to metallothionein starts to appear in free form in liver cells and signs of acute hepatitis (jaundice) begin to appear. Copper liberated from the copper-metallothionein in liver is detected in the blood stream and is sequestered by the kidney. Although, this copper is not incorporated in ceruloplasmin (a specific copper-dependent protein) and apo-ceruloplasmin appears in the serum of LEC rats, the metal can be utilized by the copper, zinc-superoxide dismutase. The phenomenon can be explained by a direct and selective transfer of copper from metallothionein to apo-superoxide dismutase. Copper present in liver, bound to metallothionein was removed selectively by tetrathiomolybdate and the mechanisms, including the formation of molybdenum-copper-sulfur complexes, were proposed. LEC rats can be cured from the acute hepatitis by treatment with tetrathiomolybdate.Abnormal accumulation of copper in LEC rats is now explained by the lack of copper-binding liver ATPase, which cause the efflux of copper from this organ, However, our results suggest that metallothionein synthesis is enhanced even in the hepatocytes derived from the LEC rats after removing copper and lowering the metallothionein mRNA levels to normal values, indicating that metallothionein is overexpressed in LEC rats selectively by copper.
我们的方法可以在以下几个小标题下描述:(I)导致和紧随急性肝炎的LEC大鼠的铜的正常积累过程,(Ii)LEC大鼠的铜从金属硫蛋白选择性地转移到铜结合酶中,(Iii)通过四硫钼酸盐选择性地去除与金属硫蛋白结合的铜并从急性肝炎中恢复,以及(Iv)增强诱导LEC大鼠肝脏中金属硫蛋白的合成。我们的实验表明,LEC大鼠的肝脏中铜以与金属硫蛋白结合的形式积累,达到肝脏合成该蛋白质的能力极限。然后,未与金属硫蛋白结合的铜开始以游离形式出现在肝细胞中,急性肝炎(黄疸)的迹象开始出现。从肝脏中的铜金属硫蛋白中释放出来的铜在血液中被检测到,并被肾脏隔离。虽然铜蓝蛋白(一种特定的铜依赖蛋白)不结合铜,而脱铜蛋白在LEC大鼠的血清中出现,但铜锌超氧化物歧化酶可以利用铜锌超氧化物歧化酶。这一现象可以通过铜从金属硫蛋白直接和选择性地转移到脱脂超氧化物歧化酶来解释。用四硫代钼酸盐选择性地去除肝脏中与金属硫蛋白结合的铜,并提出了钼-铜-硫络合物的形成机理。用四硫代钼酸盐治疗可以治愈LEC大鼠的急性肝炎。LEC大鼠铜的异常蓄积现在解释为缺乏铜结合的肝脏ATPase,导致铜从这个器官外流。然而,我们的结果表明,即使在LEC大鼠的肝细胞中,在去除铜并将金属硫蛋白mRNA水平降低到正常值后,金属硫蛋白的合成也被增强,这表明铜选择性地在LEC大鼠肝细胞中过表达金属硫蛋白。

项目成果

期刊论文数量(60)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
K.T.Suzuki, K.Yamamoto, S.Kanno, Y.Aoki and N.Takeichi: "Selective removal of copper bound to metallothionein in the liver of LEC rats by tetrathiomolybdate." Toxicology. 83. 149-158 (1993)
K.T.Suzuki、K.Yamamoto、S.Kanno、Y.Aoki 和 N.Takeichi:“通过四硫代钼酸盐选择性去除 LEC 大鼠肝脏中与金属硫蛋白结合的铜。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
S.Kanno, Y.Aoki, J.S.Suzuki, N.Takeichi, S.Misawa and K.T.Suzuki: "Enhanced synthesis of metallothionein as a possible cause of abnormal copper accumulation in LEC rats." J.Inorg.Biochem.56. 117-125 (1994)
S.Kanno、Y.Aoki、J.S.Suzuki、N.Takeichi、S.Misawa 和 K.T.Suzuki:“金属硫蛋白合成增强可能是 LEC 大鼠异常铜积累的原因。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
K.T.Suzuki,et al.: "Direct transfer of copper from metallothionein to superoxide dismutase:A possible mechanism for differential supply of Cu to SOD and ceruloplasmin in LEC rats." Res.Commun.Mol.Pathol.Pharmacol.86. 15-23 (1994)
K.T.Suzuki 等人:“铜从金属硫蛋白直接转移到超氧化物歧化酶:LEC 大鼠中铜向 SOD 和铜蓝蛋白差异供应的可能机制。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
K.T.Suzuki et al.: "Metal Ions in Biology and Medicine" Ph.Collery,L.A.Poirier,N.A.Littlefield and J.C.Etienne(Eds),John Libbey Eurotext., (1994)
K.T.Suzuki 等人:“生物学和医学中的金属离子”Ph.Collery、L.A.Poirier、N.A.Littlefield 和 J.C.Etienne(编辑)、John Libbey Eurotext.,(1994)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
K.T.Suzuki: "Metal Ions in Medicine and Biology" B.Sarker ed,Marcel Dekker,Inc., (1995)
K.T.Suzuki:“医学和生物学中的金属离子”B.Saker ed,Marcel Dekker, Inc.,(1995)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

SUZUKI Kazuo t.其他文献

SUZUKI Kazuo t.的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('SUZUKI Kazuo t.', 18)}}的其他基金

Mechanism underlying the selective removal of copper accumulating in the liver of LEC rats and development of the therapy for Wilson disease
选择性清除LEC大鼠肝脏铜积累的机制及威尔逊病治疗的进展
  • 批准号:
    09470511
  • 财政年份:
    1997
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

相似国自然基金

金属硫蛋白(METALLOTHIONEIN)与重金属肝、肾毒性
  • 批准号:
    39270597
  • 批准年份:
    1992
  • 资助金额:
    5.0 万元
  • 项目类别:
    面上项目

相似海外基金

Elucidation of the relationship between life span and carnitine biosynthetic capacity in metallothionein knockout mice.
阐明金属硫蛋白基因敲除小鼠的寿命与肉碱生物合成能力之间的关系。
  • 批准号:
    23K10907
  • 财政年份:
    2023
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Role of Metallothionein 1 E in the protection of cystic fibrosis-related diabetes
金属硫蛋白 1 E 在保护囊性纤维化相关糖尿病中的作用
  • 批准号:
    10714873
  • 财政年份:
    2023
  • 资助金额:
    $ 4.35万
  • 项目类别:
Tumor suppressor vulnerability conferred by aneuploid loss of haploinsufficient metallothionein genes
单倍体金属硫蛋白基因的非整倍体缺失导致肿瘤抑制脆弱性
  • 批准号:
    10469891
  • 财政年份:
    2022
  • 资助金额:
    $ 4.35万
  • 项目类别:
The Effect of Aging on Protein Control of Metallation Pathways in Human Liver Metallothionein
衰老对人肝脏金属硫蛋白金属化途径蛋白质控制的影响
  • 批准号:
    548029-2020
  • 财政年份:
    2022
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The Effect of Aging on Protein Control of Metallation Pathways in Human Liver Metallothionein
衰老对人肝脏金属硫蛋白金属化途径蛋白质控制的影响
  • 批准号:
    548029-2020
  • 财政年份:
    2021
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
The Effect of Aging on Protein Control of Metallation Pathways in Human Liver Metallothionein
衰老对人肝脏金属硫蛋白金属化途径蛋白质控制的影响
  • 批准号:
    548029-2020
  • 财政年份:
    2020
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Preventive strategy against Alzheimer's disease by metallothionein induction
通过金属硫蛋白诱导预防阿尔茨海默氏病
  • 批准号:
    19H03374
  • 财政年份:
    2019
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and Survival
金属硫蛋白 1E 作为人胰腺 β 细胞功能和存活的中央调节剂
  • 批准号:
    10220173
  • 财政年份:
    2019
  • 资助金额:
    $ 4.35万
  • 项目类别:
Elucidation of Aging Regulatory Mechanisms in Mesenchymal Tissues of Metallothionein Knockout mice.
阐明金属硫蛋白基因敲除小鼠间充质组织的衰老调节机制。
  • 批准号:
    19K11732
  • 财政年份:
    2019
  • 资助金额:
    $ 4.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Metallothionein 1E as a Central Regulator of Human Pancreatic Beta Cell Function and Survival
金属硫蛋白 1E 作为人胰腺 β 细胞功能和存活的中央调节剂
  • 批准号:
    10190924
  • 财政年份:
    2019
  • 资助金额:
    $ 4.35万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了