ALTERNATIVE REGULATION BETWEEN THE Ya AND Yc SUBUNIT OF LIVER GLUTATHIONE S-TRANSFERASES IN HEPATITIS AND CANCEROUS RATS

肝炎和癌症大鼠肝脏谷胱甘肽 S 转移酶 Ya 和 Yc 亚基之间的替代调节

基本信息

批准号：
61580038
负责人：
MATSUMOTO Kozo
金额：
$ 1.28万
依托单位：
University of Tokushima School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Spontaneously hepatitis in rats are similar in certain respects to human acute hepatitis and liver cancer. The hepatitis in rats occur at the age of approximately 4 months old and most rats with severe jaundice were died within one week. It was known that the hepatitis was identified as a recessive mutation of mendelian fashion. We have postulated that the mechanism of the hepatitis in rat may be due to enzyme alterations or lack in the liver. Recently. we confirmed that the rats which were breeding for over one year had liver tumors. It is well known that glutathione S-transferases are major metabolic enzyme in liver and very good marker of hepatoma.-Namely, expression of this enzyme reflects circumstances of liver.In order to investigate the mechanism of hepatitis and then hepatoma, glutathione S-transferases were purified from hepatitis rats and normal rats by -s-hexylglutathione-linked agarose column, chromatofocusing. Seven major glutathione s-transferases were isolated. We found that glutathione S-transferase 1-1 was markedly decrease, and conversely glutathione S-transferase 2-2 was markedly increase. It is known that the genes are very similar but different genes. So it seems that the gene expression alters in hepatitis rat liver. Glutathione S-transferase 4-4 also increased.We have produced a monoclonal antibody specific for glutathione S-transferase 2-2 and rabbit anti glutathione S-transferase 4-4. We determined the enzyme localization on the liver section which had neoplastic nodules by immunohistochemical method using the antibodies. The expression of glutathione S-transferase 2-2 and 4-4 seemed to be out of the neoplastic nodules.It is obvious that the gene expression alters in hepatitis rats as compared with in normal rats. It is not clear whether such a alteration is due to a clinical phenomenon, or genetical factor. Genetic analysis is now in progress.

大鼠自发性肝炎在某些方面与人类急性肝炎和肝癌相似。大鼠肝炎发生在4月龄左右，大部分黄疸严重的大鼠在1周内死亡。据了解，肝炎被鉴定为孟德尔时尚的隐性突变。我们推测大鼠肝炎的机制可能是由于肝脏中酶的改变或缺乏所致。最近。我们证实饲养一年以上的大鼠患有肝脏肿瘤。众所周知，谷胱甘肽S-转移酶是肝脏中的主要代谢酶，也是肝癌的良好标志物。即该酶的表达反映了肝脏的情况。为了研究肝炎进而肝癌的发生机制，谷胱甘肽S-转移酶从肝炎大鼠和正常大鼠中通过β-己基谷胱甘肽连接的琼脂糖柱、层析聚焦纯化。分离出七种主要的谷胱甘肽 s-转移酶。我们发现谷胱甘肽S-转移酶1-1显着降低，相反谷胱甘肽S-转移酶2-2显着升高。众所周知，这些基因非常相似但又不同。因此，肝炎大鼠肝脏中的基因表达似乎发生了变化。谷胱甘肽S-转移酶4-4也增加。我们生产了谷胱甘肽S-转移酶2-2特异性单克隆抗体和兔抗谷胱甘肽S-转移酶4-4。我们使用抗体通过免疫组织化学方法确定了具有肿瘤结节的肝脏切片上的酶定位。谷胱甘肽S-转移酶2-2和4-4的表达似乎不在肿瘤结节之外。与正常大鼠相比，肝炎大鼠的基因表达发生了明显的变化。目前尚不清楚这种改变是由于临床现象还是遗传因素。遗传分析正在进行中。