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Biological function of iron, copper and metallothionein in the onset of hepatitis and liver cancer : Significance of these parameters in LEC rats with hereditary hereditary hepatitis and liver cancer

铁、铜和金属硫蛋白在肝炎和肝癌发病中的生物学功能：这些参数在患有遗传性遗传性肝炎和肝癌的LEC大鼠中的意义

基本信息

批准号：
05670358
负责人：
SUGAWARA Naoki
金额：
$ 1.28万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
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

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670358/
关键词：
Copper metabolism Metallothionein LEC rat Hepatitis Liver cancer Free radicals

项目摘要

1.Mechanism of Cu accumulation in the liver.It seems likely that a gross deposit of hepatic Cu is due to a lack of biliary excretion of Cu. The lack is partly dependent on the dysfunction of lysosmes. The increased-Cu induces metallothionein (MT) synthesis, resulting in sequestration of Cu in the MT.Finally, the vicious cycle of Cu stimulates the Cu deposition in the LEC rat liver.2.Biliary excretion of Cu and metallothionein (MT).When Cd was qiven LEC rats at a low level, there was no difference of hepatic Cd concentration between LEC and Fischer rats. Accordingly, the abnormal metabolism found in LEC rats is specific for Cu. Biliary excretion of Cu-MT was significantly higher in LEC rats than in Fischer rats. However, its excretion was not responded to the gross accumulation of hepati MT.3.Relation between deposition of Cu and MT,and onset of hepatitis.MT in the LEC liver showed a preventive action against the lipidperoxidation stimulated by Fe-NTA.Accordingly, until the onset of hepatits, MT plays as a scavenger, When LEC rats were fed a Cu deficient diet, hepatitis was not occured at around 120 days after birth. Accordingly, the onset of hepatitis is related closely to the Cu level in food.4.Therapy of hepatitis, and liver cancer.Chelator, tetrathiomolybdate (TTM) was effective for the therapy of hepatitis. Now, survived rats from hepatitis by the treatment are maintained for the further occurance of liver cancer.

1.铜在肝脏中的蓄积机制：肝脏铜的大量沉积可能是由于胆汁中铜排泄不足所致。这种缺乏在一定程度上依赖于溶酶的功能障碍。铜的增加诱导金属硫蛋白(MT)的合成，导致铜在金属硫蛋白中的滞留，最终铜的恶性循环刺激铜在LEC大鼠肝脏中沉积。2.铜和金属硫蛋白(MT)的胆汁排泄。因此，在LEC大鼠体内发现的异常代谢是铜所特有的。LEC大鼠胆汁中铜-MT排泄量显著高于Fischer大鼠。3.铜和MT在LEC肝脏中的沉积与肝炎发病的关系。MT在LEC肝脏中对Fe-NTA刺激的脂质过氧化具有预防作用。因此，在肝炎发生之前，MT是一种清除剂，当LEC大鼠饲喂铜缺乏饲料时，出生后120天左右不会发生肝炎。因此，肝炎的发生与食物中铜的水平密切相关。4.治疗肝炎和肝癌。现在，通过治疗从肝炎中存活下来的大鼠是为了进一步发生肝癌而维持的。