权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study on bioinorganic chemistry for the mechanism of the development of hapatitis-hepatoma in LEC rats

LEC大鼠肝炎-肝癌发生机制的生物无机化学研究

基本信息

批准号：
06672157
负责人：
SAKURAI Hiromu
金额：
$ 1.41万
依托单位：
Kyoto Pharmaceutical 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：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

We studied on copper-metallothionein (Cu-MT) induced unusually in the liver of LEC (Long-Evans Cinnamon) rats which develop spontaneous hepatic injury associated with severe jaundice and hepatoma, and obtained the following results.(1) We purified the Cu-MT and found that the protein presents in both monomer and polymer as judged by both gel-filtration and electrophoretic methods. In the partially purified protein, nevertheless, two isomers as MT-I and MT-II were detectable and they were subjected to the amino acid sequencing method, the 16 amino acid sequence from the N-terminal being determined.(2) In the partially purified Cu-MT,generation of hydroxyl radicals (・OH) was observed by ESR-spin trapping technique when the protein was reacted with hydrogen peroxide (H_2O_2) which presents in the hepatic cells. The unusual formaiton of ・OH in the Cu-MT of LEC suggests one of the causative factors for the development of the hepatic injury or hepatitis in the LEC rats.(3) To suppress the development of the hepatitis in the LEC rats, we gave a zinc complex by oral administration every day for 6 months to the rats. The data was now analyzing.(4) We analyzed both metal contents and MT levels in human liver cancers. An important finding was obtained, in which Cu-MT is induced as the human hepatoma develops. Thus the great similarity in the hepatic injury of LEC rats and human was found in terms of the induction of Cu-MT.

我们研究了铜金属硫蛋白（Cu-MT）在严重黄疸和肝癌并发自发性肝损伤LEC （Long-Evans Cinnamon）大鼠肝脏中的异常诱导，得到了以下结果。(1)我们纯化了Cu-MT，发现通过凝胶过滤和电泳方法判断，该蛋白以单体和聚合物的形式存在。然而，在部分纯化的蛋白中，可以检测到MT-I和MT-II两个异构体，并对它们进行了氨基酸测序方法，从n端确定了16个氨基酸序列。(2)在部分纯化的Cu-MT中，通过esr -自旋捕获技术观察到，当蛋白质与存在于肝细胞中的过氧化氢（H_2O_2）反应时，羟基自由基（·OH）的产生。在LEC的Cu-MT中异常形成OH提示LEC大鼠肝损伤或肝炎发生的病因之一。(3)为了抑制LEC大鼠肝炎的发展，我们给大鼠每天口服锌复合物，持续6个月。现在正在分析数据。(4)我们分析了人类肝癌中的金属含量和MT水平。获得了一个重要的发现，其中Cu-MT是随着人类肝癌的发展而诱导的。由此可见，在Cu-MT诱导方面，LEC大鼠的肝损伤与人的肝损伤有很大的相似性。